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13th EMERGENCY & CRITICAL CAREUK ANNUAL CONGRESSLECTURE NOTES10th & 11th November 2016

Speakers at CongressSpeakers at CongressSophie graduated from Liverpool University in 1999; completed an internship in anaesthesia at the University of Bristol followed by a rotating small animal internship at the Animal Health Trust and received her Certificate in Veterinary Anaesthesia. After completing her residency at the Royal Veterinary College, Sophie received her Diploma in Emergency & Critical Care in 2005, and now works as an ECC Clinician at Langford Veterinary Services, University of Bristol.Sophie AdamantosBVSc CertVA DACVECC DipECVECC MRCVS FHEA RCVS Specialist in Emergency & Critical CareKaren graduated from Oxford University Medical School in 2002, gaining Membership of the Royal College of Physicians in 2005 and her Fellowship of the College of Emergency Medicine in 2011. After achieving her MSc in Sports & Exercise Medicine, she spent a further two years gaining Sports Medicine specialist training. Karen currently works as a Consultant in Emergency Medicine at University Hospital in Coventry, a regional Major Trauma Centre.Karen JonesBM BCh (Oxon) MA MSc SEM PG Dip Medical Ultrasound FRCEM MRCP MFSEMJennifer KinnsBSc VetMB DipECVDI DACVR MRCVS RCVS Specialist in Diagnostic ImagingLouise gained her Diploma in Advanced Veterinary Nursing (Surgical) in 2004, followed by her Diploma in Advanced Veterinary Nursing (Medical) in 2007, her Veterinary Technician Specialist (Emergency and Critical Care) in 2011 and her Veterinary Technician Specialist (Anesthesia) in 2014. After 15 years at PetMedics in Manchester, firstly as Head Nurse and latterly as Clinical Director, Louise moved to Vets Now in October 2015 to take up the position of Clinical Support Manager. Louise O’DwyerMBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVNNick SteeleBSc (Hons) CIPD Cert L&DNick joined Zoetis in 1997 and is now their national consulting manager. He has more than ten years’ experience in learning and development management roles, which he now applies to help develop veterinary practice teams to enable them to deliver business results now and for the future. He is part of a global team identifying and developing business solutions for veterinary practices. In 2011, Nick completed his CIPD certificate in learning & development. He is also an accredited coach and practitioner in personality profiling.Kenichiro YagiBS RVT VTS (ECC SAIM)Kenichiro practices at Adobe Animal Hospital in California as an ICU and Blood Bank Manager. He serves on the board for the Veterinary Emergency and Critical Care Society, Academy of Veterinary Emergency and Critical Care Technicians, and the Veterinary Innovation Council, and as the NAVTA State Representative Chairperson. Jennifer graduated from the University of Cambridge in 2002, before completing an internship and time in mixed practice. She undertook a radiology residency at the University of Pennsylvania gaining a diploma from both the European College of Veterinary Diagnostic Imaging and the American College of Veterinary Radiology in 2007. For three years Jennifer was Assistant Professor at Michigan State University and since returning to the UK has worked as a radiology consultant and team lead for Idexx telemedicine. Greg received his DVM degree from Cornell University in 1991. After completing a rotating internship in small animal medicine and surgery and a residency in ECC in 2008, he became a Diplomate of the American College of Veterinary Emergency and Critical Care in 2009. Greg is also a Diplomate of the American Board of Veterinary Practitioners (Companion Animal). He is currently CEO of FASTVet.com and co-owner of Hill Country Veterinary Specialists in San Antonio, Texas.Greg LisciandroDVM Dipl ABVP DACVECCSøren Boysen DVM DACVECCSøren graduated from the Western College of Veterinary Medicine, Canada in 1996. He completed an internship at the Atlantic Veterinary College, Canada, followed by a Residency in Small Animal ECC at Tufts University in Massachusetts, before becoming a Diplomate of the American College of Veterinary Emergency and Critical Care in 2003. Søren worked at the University of Montreal until 2009, when he moved to the University of Calgary as a Full Professor in Small Animal Emergency and Critical Care.Jennifer is a graduate of the Ontario Veterinary College, University of Guelph. After completing an internship and ECC residency in Milwaukee, WI, she became a Diplomate of the American College of Veterinary Emergency & Critical Care in 1996. Previously director of emergency and intensive care services at a number of large private referral practices in Canada and the United States, Jennifer is currently consulting and working across North America as an ECC specialist.Jennifer Devey DVM DACVECC

Tutor PageThursday 10th NovemberLecture stream 1Emergency cage-side AFAST ultrasound and critically ill and unstable cases Boysen & Lisciandro 1Emergency cage-side TFAST ultrasound for collapse and respiratory distress cases Boysen & Lisciandro 17Clinical discussion forum 31Sepsis: what have we learnt from human medicine over the last 15 years Adamantos 33Identification and management of the septic patient Adamantos 39Lecture stream 2Immune mediated haemolytic anaemia Yagi 41Anaemia: it’s not only about bleeding! Yagi 47The air our cells breathe: arterial blood gases Yagi 55To clot or not to clot? Haemostatic disorders Yagi 61Getting the best and most appropriate radiographic images first time Kinns 69ECC certification for RVNs (advance your learning) 73Lecture stream 3EMS presentations 75The role of front of house: before and after the consultation Steele 77Handling dicult client situations Steele 81Flexible leadership and managing team performance Steele 85Friday 11th November Lecture stream 1Hyperosmolar/hyperglycaemic states in cats and dogs Boysen 89Professional dilemmas discussion forum 99Acute lung injury/acute respiratory distress syndrome Boysen 101Radiology of the patient with acute dyspnoea. Where is the problem? Kinns 107Do I need to cut this now? Radiology of the acute abdomen Kinns 111Angiostrongylus vasorum- an update Adamantos 117Biomarkers of acute kidney injury Adamantos 121Lecture stream 2Bloody truths: transfusion medicine, myths and facts Yagi 127B-harmony: are you the right type for me? Yagi 135RVN clinical discussion forum 143Myth busters: using evidence to guide critical care nursing Yagi 145Prior planning prevents poor performance O’Dwyer 153Anaesthesia monitoring parameters O’Dwyer 159Lecture stream 3Point of care lung ultrasound: canine cases with respiratory distress Lisciandro 165Point of care lung ultrasound: feline cases with respiratory distress Lisciandro 177Applying global fast to small animal cases: monitoring, CPR and advanced life support Lisciandro 189Comparative medicine: point of care ultrasound in human emergency medicine Jones 203Papers that have made me think Adamantos 207Abstract session 211Autotransfusion and xenotransfusion Yagi 219Index 227ContentsContents

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 1 of 226 EMERGENCY CAGESIDE AFAST ULTRASOUND AND CRITICALLY ILL AND UNSTABLE CASES FROM THE TRENCHES Søren Boysena and Greg Lisciandrob a University of Calgary, Faculty of Veterinary Medicine srboysen@ucalgary.ca bHill Country Veterinary Specialists & FASTVet.com San Antonio, Texas FastSavesLives@gmail.com Cell 210-260-5576 INTRODUCTION Focused emergency cageside sonography is expanding rapidly and with ultrasound machines becoming common place, they have become an integral part of the early evaluation and triage of small animal patients that present to the emergency service or that are hospitalized in the ICU. In fact, these formats, AFAST, TFAST and Vet BLUE, should be considered an extension of the physical exam for any patient critical or stable. These exams require minimal ultrasound experience to perform, can be done at the cageside concurrent with other resuscitative efforts, are non-invasive, safe, relatively inexpensive, repeatable, and can be completed in under 10 minutes. Multiple studies in the human and veterinary profession have shown that focused emergency sonography can identify potentially life threatening conditions and help direct therapeutic options. Although new applications of focused emergency cageside sonography are continually being developed and applied in veterinary patients, to date there are 3 main areas of emergency cage side sonography that have been investigated in small animal patients; 1) Assessment of the chest and lungs (thoracic focused assessment with sonographyfor trauma/triage/tracking and the Vet BLUE exam),2) Assessment of the abdomen (abdominal focused assessment with sonography fortrauma/triage/tracking), and3) Estimation of intravascular volume status via assessment of the caudal vena cava.Important factors to consider when applying focused emergency cageside sonography to small animal veterinary patients:  Perform the obvious first. i) Obtain IV access, ii) commence fluid therapy, iii) controlobvious hemorrhage, iv) ensure adequate airway and breathing, etc. prior to performingthe sonographic examination.Emergency cage-side AFAST ultrasound and critically ill and unstable cases

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 2 of 226  The ultrasound machine should be brought to the resuscitation area for unstable patients; do not move an unstable patient for the purposes of emergency sonographic evaluation!  These exams do not assess all organs of the body and are not a replacement for formal or complete abdominal and echocardiographic sonographic exams.  Focused emergency cageside sonography should be considered an extension of the physical exam, and not a substitute for, the triage exam or a complete physical exam; triage exams identify unstable patients while emergency cageside sonography is one tool that can help rapidly identify the underlying cause and direct therapy that is often lifesaving.  When free fluid is detected, and is safely accessible, in the peritoneal, retroperitoneal, pleural, and pericardial spaces, then the pursuit of ultrasound-guided therapeutic and diagnostic centesis (pericardial, abdominal and thoracocentesis) is expedited potentially improving patient care and better directing diagnostic testing. Although originally developed to assess blunt and penetrating trauma, these exams are now becoming standard of care for all emergent/critical care situations in which an underlying cause is not readily apparent, particularly if the patient is unstable. A recent veterinary study applied to unstable, non-traumatized dogs and cats, demonstrated that AFAST and TFAST combined, detected free fluid in the peritoneal, pleural, and/or pericardial spaces in approximately 75% of these cases presenting to the ER (See Algorithm 1). ABDOMINAL FOCUSED ASSESSMENT WITH SONOGRAPHY FOR TRAUMA (AFAST) Important points to consider  The subxiphoid (DH) view of the AFAST exam is a shared view with the TFAST exam, and can therefore detect pericardial and pleural fluid in addition to free intra-abdominal fluid (see TFAST).  Detection of free fluid is often instrumental in the management of critically ill patients; it helps to narrow differential diagnoses, directs diagnostic steps, and guides therapeutic options.  Identification of gallbladder wall edema (called the halo sign) has been documented to be a marker for canine anaphylaxis and is easily detected at the subxiphoid (DH) view; however, in collapsed or weak dogs, pericardial effusion and right-sided CHF and generalized systolic dysfunction (dilated cardiomyopathy), also lead to hepatic venous

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 3 of 226 congestion and a gallbladder halo sign making the use of AFAST and TFAST combined a better strategy make an accurate diagnosis. INDICATIONS  Any patient with blunt trauma. Blunt trauma patients, particularly those that are critical and/or unstable, that have a total solids of less than 60 g/L and/or a decreased PCV, or an elevated serum alanine transaminase (ALT), or a pneumothorax, or pelvic fractures have a high probability of being AFAST-positive (See Algorithm 4).  Any patient with penetrating trauma  Any patient in which intra-abdominal free fluid is suspected  Any collapsed and/or unstable patient (i.e. elevated shock index, hyperlactatemia, unexplained hypotension, tachycardia, or decreased mentation) regardless of trauma, particularly if the underlying cause is uncertain (See Algorithm 1).  Any patient with acute abdomen/abdominal pain (See Algorithm 5)  Any patient with anemia  Any patient with a fever  Post-surgical patients that become unstable or in whom there is a concern for bleeding or risk of dehiscence/peritonitis. Avoid being confounded by lavage fluid which can last several days in the abdominal cavity, dry the abdominal cavity prior to closure.  Serial AFAST exams are warranted to: 1) monitor progression/resolution of intra-abdominal fluid in AFAST positive patients, and 2) to re-assess AFAST negative patients, particularly those that are unstable, and/or have received significant quantities of intravascular fluids 3) may be used to calculate urinary bladder volume measured in centimetres the formula length x width x height x 0.625 gives you an estimation in millilitres. CONTRAINDICATIONS  None. AFAST exams are rapid, non-invasive, do not require sedation or anesthesia, and do not compromise patient stability with special positioning or restraint.  Patients that struggle with gentle positioning in lateral recumbency can be assessed in the standing or sternal position (standing AFAST exams negate the abdominal fluid score – see below)  Dorsal recumbency should not be used due to the risk of decompensating hemodynamically and respiratory fragile patients by compromising venous return and ventilation through the weight of the abdominal organs on the caudal vena cava and

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 4 of 226 diaphragm, respectively. MATERIALS  Ultrasound machine capable of B-mode (ideally portable or permanently located in the triage area of the clinic).  A curvilinear probe (also called microconvex) with a 5 MHz setting for larger patients (> 20kg) and 7.5MHz setting for smaller patients (≤ 20 kg) and a maximum capable depth of 10-20 cm is used for the abdomen, thorax and lung.  Alcohol and/or ultrasound conducting gel or alcohol-based hand sanitizer.  Clippers (optional). Anesthesia, analgesia, sedation  Patients generally tolerate the procedure well without the need for sedation or anesthesia.  Patients presenting with evidence of pain (trauma, acute abdomen, etc.) should be managed with analgesia. TECHNIQUE/PROCEDURE  The fur does not need to be clipped although shaving a small 5 x 5 cm area may improve image quality in some patients (i.e. patients with thick undercoats).  The probe location sites are soaked with alcohol after parting the fur keeping in mind the best image will be obtained with the probe head directly in contact with skin.  Some images are improved with the addition of ultrasound gel as well as alcohol.  Left or right lateral recumbency can be used depending on operator preference, or patient’s presenting position.  Transducer depth is generally set between 5-10cm depending on the size of the patient and the organs to be identified.  At each site, the ultrasound probe is initially placed longitudinally to the underlying organs and fanned through an angle of 45° and moved 2.5 cm in cranial, caudal, left, and right directions.  Fanning and moving the probe increases likelihood that abdominal fluid is detected and that target organs are properly identified.  The AFAST scan can be done in any order, although developing a systematic approach is recommended to standardize and help ensure important structures are not overlooked. The authors suggest starting at the subxiphoid (DH) view and then imaging the least gravity-dependent (SR or HR view depending on what lateral positioning) before going to

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 5 of 226 the CC view ending at the most gravity-dependent view (HR or SR depending on what lateral positioning). The advantage is that gain may be set when imaging the gallbladder as normal bile is purely anechoic (black) and ending at the most gravity-dependent site completes AFAST and is generally a favorable safe site for abdominocentesis.  The ultrasound probe is placed at 4 focal regions of the abdomen in a consistent systematic manner. At the minimum the probe is fanned toward and away from the table top and then rocked toward the head of the patient at each of the 4 views (See Fig. 4): 1) Subxiphoid or Diaphragmatico-hepatic (DH) site: the probe is tucked into the “v” formed by the ribs where they join the xiphoid. Direct the probe cranially and towards the spinal column under the xiphoid process. Allows visualization of the diaphragm, liver lobes, and gallbladder (gentle pressure to slide the probe just under the xiphoid may be required). Tilting and fanning the probe to the right of midline at the subxiphoid site identifies the gallbladder. Adjust the gain until the fluid-filled gallbladder appears anechoic. This sets the gain to identify anechoic free peritoneal fluid (black triangulations) elsewhere in the abdomen. After fanning toward and away from the exam table top, rock the probe toward the sternum to pick up the “cardiac bump” where the apex of the heart is against the diaphragm for detecting or ruling out pericardial effusion (helpful in dogs, not easy to see in cats). 2) Left paralumbar or spleno-renal (SR) site: the probe is placed on the left lateral side of the animal at the pocket formed where the ribs and paralumbar muscles come into contact. Allows visualization of the spleen and left kidney. Fan through the left kidney in both directions in a sagittal (or longitudinal plane mean the same thing) and then rock the probe toward the head to image the head of the spleen where it is attached to the stomach by its short gastric vascular branches. 3) Off midline over the bladder or cysto-colic (CC) site: the probe is placed on the upward side of the patient and directed lateral to medial towards the table top keeping in mind that free fluid is gravity-dependent. The ultrasound beam passes through the bladder, allowing visualization of the bladder apex and gravity dependent caudal region of the peritoneum referred to as the CC pouch. Fan through the urinary bladder prior to imaging the CC pouch one final time. 4a) Right paralumbar or hepato-renal (HR) site: the probe is placed on the right lateral side of the animal at the pocket formed where the ribs and paralumbar muscles come into contact. Allows visualization of the liver and right kidney. This site is difficult to find with patients in right lateral recumbency. In dogs it may be necessary to direct the probe cranially under the ribs to find the right kidney, which blends into the liver because it is cupped in the liver’s renal fossa.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 6 of 226 4b) A variation, which can be done in addition to or in place of the gravity-dependent paralumbar view, is to place the probe at the umbilicus and direct it laterally towards the table top. This allows the abdomen to be quickly "flashed" for the presence of fluid at the most gravity-dependent view of your patient’s abdominal cavity, where large volumes of fluid are most likely to accumulate because of gravity. However, without the right paralumbar (HR) view’s target organs, detailed assessment of the right kidney and associated liver is missed.  If results are positive for the detection of free fluid in the longitudinal orientation, the probe is moved to the next site.  If the results are negative or equivocal with the probe placed longitudinally, then a transverse view of the organs should be obtained with fanning and movement of the probe repeated at that site. Figure 4: To perform an AFAST exam the patient can be placed in right or left lateral recumbency. Left lateral recumbency is shown in this figure. The 4 sites to be evaluated include the subxiphoid or diaphragmatico-hepatic (DH) site (1), the right paralumbar or hepato-renal (HR) site (2), off midline over the bladder or cysto-colic (CC) site (3) and the left paralumbar or spleno-renal (SR) site (4). A variation of the technique whereby a "flash" scan in place of the gravity-dependent view (site 4 with the dog in left lateral recumbency or site 3 with the dog in right lateral recumbency) can be substituted if the objective is to identify free fluid and right kidney and its associated liver assessment is not vital. At each site, the ultrasound probe is initially placed longitudinally to the underlying organs and fanned through an angle of 45° and moved 2.5 cm in cranial, caudal, left, and right directions. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 7 of 226 INTERPRETATION  Free fluid is hypoechoic to anechoic (black), often forming triangles or sharp angles between organs.  Fluid identified on AFAST may be blood, urine, ascites, septic, or inflammatory; ultrasound guided fluid aspiration is necessary, when fluid is safely accessible, to confirm the type of fluid present.  An Abdominal Fluid Score (AFS) specific to trauma has been applied to dogs. AFS is determined by recording the number of AFAST sites at which free abdominal fluid is detected.  AFS 1 is positive for free fluid at one site;  AFS 2: positive at any 2 sites;  AFS 3: positive at any 3 sites;  AFS 4: positive in all 4 sites.  The AFS has only been validated in lateral positions.  An increase in the AFS suggests ongoing intra-abdominal hemorrhage; further patient evaluation and serial monitoring of the AFS is warranted – blood transfusion may be required based on clinical assessment of the patient.  A decrease in the AFS indicates resolving hemorrhage.  Patients with an AFS of 1 or 2 following major trauma are not expected to become anemic, particularly if the AFS remains at 1 or 2 on serial exam (unless the patient is bleeding elsewhere or had pre-existing anemia).  AFS of 3 or 4 following major trauma are considered large volume bleeders. Dogs beginning or progressing to an AFS 3 or 4, following trauma, will become anemic with 20-25% requiring blood transfusion. *Cats generally do not survive large volume bleeds so cats surviving initial trauma with large volume effusions (AFS 3, 4) are more likely to have uroabdomen in contrast to dogs that are far more likely to have hemoabdomen.  Not all trauma-induced abdominal injury and peritoneal diseases produce free fluid; the absence of free fluid (negative AFAST) does not imply the absence of pathology and importantly only provides indirect evidence.  AFAST scans are not good at detecting intrapelvic injury and it is not known how reliable AFAST scans are for detecting retroperitoneal free fluid.  AFAST scans detect the presence of fluid and help collect samples, but do not locate the source/origin of the free fluid in many cases. However, it is important to record both fluid score and location, particularly in patients that may require subsequent surgery or other interventional procedures.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 8 of 226  AFAST scans omit large areas of the abdomen and can easily miss localized organ injury.  Adjusting the depth and focus at each location enhances the organs of interest and decreases the chance of missing small free fluid accumulations.  Certain normal anatomic features within the abdomen may be mistaken for free fluid (i.e. gallbladder, hepatic veins, vena cava, GI contents, etc.). Using the transverse view in addition to the longitudinal view helps decrease false positives. Linear anechoic stripes are generally not free fluid and typically either small intestine or vessels.  AFAST scans that are initially negative for fluid may become positive over time; serial AFAST scans are recommended to decrease false negatives and detect dynamic intra-abdominal pathology.  Hemorrhage behaves differently between blunt and penetrating trauma. In blunt trauma cavitary bleeding rapidly defibrinates and is free fluid readily recognized acutely. In contrast, in penetrating trauma blood often clots, and clotted blood looks like adjacent soft tissue, thus serial exams are integral for penetrating trauma cases that may be surgical because in time clotted blood defibrinates and becomes free fluid recognized on ultrasound.  Hemorrhaging blunt trauma patients uncommonly need exploratory surgery, think transfusion first; penetrating trauma cases with positive AFAST scans should be explored.  Post-intervention cases (percutaneous liver/other organ biopsy, post splenectomy surgery, laparoscopy, etc.) with hemoabdomen and an AFS of 1 or 2 may be serially followed (every 4-hours provided the patient remains stable) and monitored, however, bleeding post-intervention cases that progress to AFS 3 or 4 are unlikely to cease hemorrhaging without surgical ligation of bleeding vessel(s). Further reading: 1. Lisciandro GR. Chapter 2: The Abdominal (AFAST) Exam. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014 2. Boysen SR, Lisciandro GR. The use of Ultrasound in the Emergency Room (AFAST and TFAST). Vet Clin North Am Small Anim Pract 2013;43(4):773-97. 3. Boysen SR. Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 9 of 226 RAPID SONOGRAPHIC ESTIMATION OF VOLUME STATUS VIA THE CAUDAL VENA CAVA IN THE CRITICALLY ILL PATIENT Emergency and critical care patients are often at risk to develop hypo- and hypervolemia. Unfortunately, predicting which patient is suffering from either state is not always easy. Although further research is required, evaluating the caudal vena cava (CVC) shows promise in estimating the intravascular volume status, particularly in dogs. By placing the probe longitudinally, at the subxiphoid site of the FAST exam and fanning just to the right of midline, the CVC can be detected as it crosses the diaphragm. At this location the caudal vena cava diameter and its change in diameter, between the expiratory and inspiratory phases of respiration, can then be used to estimate the patient's volume status. In healthy euvolemic human patients the CVC has a larger diameter at the end of expiration than it does at the end of inspiration. The changes between expiration vary but are generally in the neighbourhood of 20-60%. Similar changes in the CVC diameter during the respiratory cycle are likely in healthy dogs as well. In hypovolemic patients the CVC becomes “flatter” than normal and may show greater collapse at the end of inspiration. For example, the CVC diameter between expiration and inspiration will likely vary by >60% in the face of hypovolemia. The opposite is true in hypervolemic patients, or patients with increased right atrial pressures (i.e. pericardial effusion, right sided heart failure, etc.), where the CVC becomes "fatter" than normal, hardly changing (<20%) between expiration and inspiration. If the hepatic veins are visualized (often seen at the site they enter the CVC just caudal to the diaphragm) they are often distended as well in cases with increased right atrial pressures and/or hypervolemia (See Fig. 5). Using M mode will sometimes allow the difference in diameter of the CVC during expiration and inspiration to be more objectively assessed although the eyeball approach or fat (high CVP, hypervolemia), flat (low CVP, hypo-volemia) or having a bounce (somewhere in the ballpark of normal) is often reliable (see Image Fig 6). A)

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 10 of 226 B) C) Figure 5 A,B,C: Place the probe longitudinally at the subxiphoid location and gently fan the probe to the right of midline until the gall bladder is visible – continue gently fanning from this location, keeping a close eye on the diaphragm until the CVC is visible crossing it. A) With hypovolemic patients the CVC becomes “flatter” than normal and may collapse at the end of inspiration. Hypovolemic patients also have wide changes in CVC diameter between expiration and inspiration (>60%). B) In euvolemic patients the CVC width will vary between inspiration and expiration by roughly 20-60%. C) The CVC becomes fat, not changing much (<20%) between inspiration and expiration in hypervolemic patients and in patients with increased right atrial pressures. If the hepatic veins are visualized (often seen at the site they enter the CVC just caudal to the diaphragm) they are often distended as well. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 11 of 226 Fig 6: An M mode image is shown with the ultrasound beam (dotted white within the image field) crossing the caudal vena cava (CVC) at the level of the diaphragm. At this site a more objective measurement of the change in diameter between expiration (small arrow in the lower part of the image) and inspiration (larger arrows in the lower part of the image) can be performed. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”. Further reading: 1. Ferrada P, Evans D, Wolfe L, et al. Findings of a randomized controlled trial using limited transthoracic echocardiogram (LTTE) as a hemodynamic monitoring tool in the trauma bay. J Trauma Acute Care Surg 2013; 76 (1): 31-28. 2, Ferrada P, Vanguri P, Anand RJ, et al. Flat Inferior Vena Cava: Indicator of Poor Prognosis in Trauma and Acute Care Surgery Patients. Am Surg. 2012;78(12):1396-8.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 12 of 226 Algorithms for interpretation of focused emergency cage side sonography in small animal veterinary patients. Centesis if free fluid noted present Fluid analysis and cytology TFAST Septic Bile, urine Blood Emergency surgery End points of resuscitation reached Continual monitoring, further work up for underlying cause Delayed surgery Emergency surgery Hemodynamically unstable despite resuscitation or recurrence of shock End points of resuscitation reached Continual monitoring, further work up for underlying cause VET BLUE B lines Predominantly caudo-dorsal: rule out non-cardiogenic pulmonary edema Consider various causes of interstitial alveolar syndromes in light of other clinical findings; pulmonary contusions, aspiration pneumonia, ARDS, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, etc. Pleural effusion Diagnostic/ therapeutic thoracocentesis Absence of glide sign, lung point noted Pneumothorax Cardiac tamponade Pericardiocentesis Fluid analysis not supportive of surgical condition Further diagnostic tests Delayed surgery vs medical management Further diagnostic tests AFAST NOTE: Dashed lines denote pericardial or pleural fluid detected via the subxiphoid view of the AFAST exam Algorithm 1: Focused Assessment with Sonography in the Cardiovascularly and/or Respiratory Unstable Dog Presenting with Acute Collapse. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 13 of 226 TFAST Pulmonary Contusions Pleural effusion Absence of glide sign, lung point noted B lines / ultrasound lung rockets Rules out pneumothorax Algorithm 2: Thoracic Focused Assessment with Sonography for Cats and Dogs with Thoracic Trauma Marked respiratory distress, decreased breath sounds ≤ 1 per site, at only 1-2 sites Multiple per site Normal finding Pneumothorax Traumatic Cardiac Tamponade Medical management Hemodynamically Stable Monitor continually, Serial TFAST Hemodynamically Unstable Oxygen therapy and anti-anxiolytics as needed Confirm with chest radiographs when stable Therapeutic thoracocentesis (if not tapped prior to TFAST) Confirm with radiographs when stable Mild dyspnea only Confirm with radiographs Transfusion Hemothorax Marked dyspnea Thoracocentesis: until dyspnea improves: control bleeding Hemodynamically Unstable Hemodynamically Stable Emergency Surgery Hemodynamically Unstable Emergency surgery Thoracic Trauma Penetrating Trauma Blunt Trauma

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 14 of 226 TFAST Pulmonary Contusions Pleural effusion Absence of glide sign, lung point noted B lines / ultrasound lung rockets Rules out pneumothorax Algorithm 3: Thoracic Focused Assessment with Sonography for Cats and Dogs with Thoracic Trauma Marked respiratory distress, decreased breath sounds ≤ 1 per site, at only 1-2 sites Multiple per site Normal finding Pneumothorax Traumatic Cardiac Tamponade Medical management Hemodynamically Stable Monitor continually, Serial TFAST Hemodynamically Unstable Oxygen therapy and anti-anxiolytics as needed Confirm with chest radiographs when stable Therapeutic thoracocentesis (if not tapped prior to TFAST) Confirm with radiographs when stable Mild dyspnea only Confirm with radiographs Transfusion Hemothorax Marked dyspnea Thoracocentesis: until dyspnea improves: control bleeding Hemodynamically Unstable Hemodynamically Stable Emergency Surgery Hemodynamically Unstable Emergency surgery Thoracic Trauma Penetrating Trauma Blunt Trauma

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 15 of 226 AFASTAFASTNegativeAbdominocentesiswithfluidanalysisandcytologyBLUNTABDOMINALTRAUMASeptic,bile,urineBloodMedicalmanagementExploratorySurgeryAFSscorestableordecreasingHemodynamicallyunstableHemodynamicallystableContinualmonitoringHemodynamicallyUnstableAFASTpositiveRecordAFSscoreSerialAFASTAlgorithm4:AbdominalFocusedAssessmentwithSonographyforCatsandDogswithBluntAbdominalTraumaLookforothersourceofbleeding,i.e.fracturesites,retroperitoneum,,TFASTforpleural&pericardialeffusionAFASTNegativeAFASTpositiveRecordAFSscoreAFSscoreincreasingHemodynamicallyunstableHemodynamicallyunstabledespitemedicalmanagement

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 16 of 226 Centesis if free fluid noted present Fluid analysis and cytology Septic Bile, urine Blood Emergency surgery End points of resuscitation reached Continual monitoring, further work up for underlying cause Delayed surgery Emergency surgery Hemodynamically unstable despite resuscitation or recurrence of shock End points of resuscitation reached Continual monitoring, further work up for underlying cause Fluid analysis not supportive of surgical condition Further diagnostic tests Delayed surgery vs medical management Algorithm 5: Abdominal Focused Assessment with Sonography for Cats and Dogs with Acute Abdomen AFAST

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 17 of 226 EMERGENCY CAGESIDE TFAST ULTRASOUND FOR COLLAPSE AND RESPIRATORY DISTRESS: CASE-BASED DISCUSSIONS Søren Boysena and Greg Lisciandrob a University of Calgary, Faculty of Veterinary Medicine srboysen@ucalgary.ca bHill Country Veterinary Specialists & FASTVet.com San Antonio, Texas FastSavesLives@gmail.com Cell 210-260-5576 INTRODUCTION Focused emergency cageside sonography is expanding rapidly and with ultrasound machines becoming common place, they have become an integral part of the early evaluation and triage of small animal patients that present to the emergency service or that are hospitalized in the ICU. These exams require proper training of veterinarians with minimal ultrasound experience to perform, can be done at the cageside concurrent with other resuscitative efforts, are non-invasive, safe, relatively inexpensive, repeatable, and can be completed in under 10 minutes. Multiple studies in the human and veterinary profession have shown focused emergency sonography can identify potentially life-threatening conditions and help direct therapeutic options. Although new applications of focused emergency cageside sonography are continually being developed and applied in veterinary patients, to date there are 3 main areas of emergency cageside sonography that have been investigated in small animal patients; 1) Assessment of the thorax and lungs (thoracic focused assessment with sonography for trauma/triage/tracking (TFAST) and the Vet BLUE exam), 2) Assessment of the abdomen (abdominal focused assessment with sonography for trauma/triage/tracking (AFAST)), and 3) Estimation of intravascular volume status via assessment of the caudal vena cava. Important factors to consider when applying focused emergency cageside sonography to small animal veterinary patients:  Perform the obvious first. i) Obtain IV access, ii) commence fluid therapy, iii) control obvious hemorrhage, iv) ensure adequate airway and breathing, etc. prior to performing the sonographic examination.  The ultrasound machine should be brought to the resuscitation area for unstable patients; do not move an unstable patient for the purposes of emergency sonographic evaluation! Emergency cage-side TFAST ultrasound for collapse and respiratory distress cases

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 18 of 226  These exams do not assess all organs of the body and are not a replacement for formal or complete abdominal or echocardiographic sonographic exams.  Focused emergency cage side sonography should be considered an extension of your physical exam, immediately after the triage exam or your complete physical exam.  When free fluid is detected, and is safely accessible, in the peritoneal, retroperitoneal, pleural, and pericardial spaces, then the pursuit of ultrasound-guided therapeutic and diagnostic centesis (pericardial, abdominal and thoracocentesis) is expedited potentially improving patient care and better directing diagnostic testing.  Ultrasound cannot characterize the type of free fluid. Thus, when free fluid is safely accessible for sampling via centesis, characterization through biochemical analysis, cytology, and culture leads to more rapidly gained evidence-based diagnosis over traditional means without the use of FAST ultrasound.  Although originally developed to assess blunt and penetrating trauma, these exams are now becoming standard of care for all emergent/critical care situations in which an underlying cause is not readily apparent, particularly if the patient is unstable. A recent veterinary study applied to unstable, non-traumatized dogs and cats, demonstrated that AFAST and TFAST combined, detected free fluid in the peritoneal, pleural, and/or pericardial spaces in approximately 75% of these cases presenting to the ER (See Algorithm 1). THORACIC FOCUSED ASSESSMENT WITH SONOGRAPHY FOR TRAUMA (TFAST) AND EMERGENCY CAGESIDE LUNG ULTRASOUND (VET BLUE) Important points to consider  The two protocols used most widely in small animal emergency medicine at this time are probably TFAST and Vet BLUE. The two are really complementary and overlap each other, to some degree, with regards to identifying underlying thoracic pathology.  TFAST has been validated for detection of pleural space disease (pleural effusion and pneumothorax) as well as pericardial effusion in dogs.  Vet BLUE is an extension of TFAST and focuses more specifically on lung pathology, particularly interstitial/alveolar conditions through the identification of B-lines and their distribution using a regionally-based approach.  B-lines (often referred to as lung rockets, comet tail artefact, or ring down artefact) are hyperechoic vertical lines extending from the pleural line to the edge of the far field image (See Image Fig. 2B).  B-lines move in a to-and-fro fashion with inspiration and expiration, synchronous with

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 19 of 226 the glide sign.  Pneumothorax poses challenges for rapidly, shallow breathing or panting dogs and cats; however, through the use of some probe manoeuvres that scatter or oblique the ultrasound beam (one-eyed gator, and fanning the probe) and use of the lung point concept, help improve its diagnosis.  Cardiac performance, including volume and contractility, right- and left-sided problems, can be assessed with these TFAST and Vet BLUE protocols but requires proper training and generally more experience to master. INDICATIONS  Any small animal trauma patient (See Algorithm 2).  Any small animal patient presenting for dyspnea, particularly if the underlying cause is uncertain: perform after/concurrent to providing oxygen +/- anxiolytics, IV access, lifesaving intubation, etc. (See Algorithm 3)  Any patient suspected to have pneumothorax (dyspnea with decreased breath sounds dorsally).  Any patient in which pericardial effusion is suspected (pulses paradoxis, muffled heart sounds, electrical alternans), or detection of an overly distended caudal vena cava, hepatic veins and/or gallbladder wall edema (the halo sign) at the FAST DH view.  Any patient suspected to have pleural effusion (dyspnea with decreased breath sounds ventrally). CONTRAINDICATIONS  None. TFAST and Vet BLUE exams are rapid, non-invasive, do not require sedation or anesthesia, and do not compromise patient stability with special positioning or restraint.  Dyspneic patients can be assessed in sternal recumbency or the standing position concurrent with oxygen therapy +/- sedation.  Dorsal recumbency should not be used due to the risk of decompensating hemodynamically and respiratory fragile patients by compromising venous return and ventilation through the weight of the abdominal organs on the caudal vena cava and diaphragm, respectively. MATERIALS  An ultrasound machine capable of B-mode (ideally portable or permanently located in the triage area of the clinic).  A curvilinear (also called microconvex) probe within a range 5-7.5MHz setting and a

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 20 of 226 maximum capable depth of 10-20 cm is used for the abdomen, thorax and lung  Linear array probes may be used to identify the glide sign but are not required.  Phase-array probes may be used for cardiac evaluation but are not required.  Alcohol and/or ultrasound conducting gel or alcohol-based hand sanitizer.  Clippers (optional). Anaesthesia, analgesia, sedation  Patients tolerate the procedure well without the need for sedation or anesthesia.  Patients presenting with evidence of pain (trauma, acute abdomen etc.,) should be managed with analgesia. TECHNIQUE/PROCEDURE: TFAST EXAM  Fur does not require clipping, although shaving a small 5 x 5 cm area may improve image quality in some patients (i.e. patients with thick undercoats).  The probe location sites are soaked with alcohol after parting the fur keeping in mind the best image will be obtained with the probe head directly in contact with skin.  Some images are improved with the addition of ultrasound gel as well as alcohol (if a good image is not obtained with alcohol, try adding gel on top of the alcohol - if this still fails to provide a good image try clipping the fur and using gel).  Patients that are not dyspneic can be scanned in lateral recumbency as an extension of the AFAST exam.  The subxiphoid site, non-gravity dependent chest tube site (CTS), and pericardial site (PCS) are obtained following the AFAST exam with the animal in right or left lateral recumbency. The animal is rolled into sternal recumbency to obtain the contra-lateral CTS and PCS sites.  Alternatively, all 5 sites can be obtained with the patient standing or in sternal recumbency, particularly if the patient demonstrates signs of respiratory distress.  Transducer depth is generally set between 10-20 cm for the subxiphoid view, 5-15 cm for the PCS views, and 2-6 cm for the CTS views, depending on the patient size and body condition score. The ultrasound probe is placed at 5 focal regions of the chest in a consistent systematic manner; 1) Subxiphoid (DH) site: the probe is placed just caudal to the xiphoid and the depth adjusted to allow visualization of the pleural and pericardial spaces via the liver and diaphragm (liver and diaphragm remain visible in the near field). It helps to angle the probe

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 21 of 226 cranially at this site (direct the probe almost parallel to the spine with the head of the probe just tucked under the xiphoid process), and it may be necessary to gently but firmly push the probe under the xiphoid process in larger dogs, particularly deep-chested breeds. The probe is moved 2.5 cm in several directions and rocked or fanned at this site to improve the chances of finding free pericardial and/or pleural fluid. The targets of the subxiphoid (DH view) are the liver, gallbladder, diaphragm, heart against the diaphragm (difficult in cats), pleural and pericardial spaces, and the caudal vena cava as it traverses the diaphragm. The subxiphoid (DH view) should look almost identical whether performed in lateral recumbency or in sternal or standing positioning. 2) Left and right chest tube site (CTS): the probe is placed at the 7th-9th intercostal spaces on the dorsolateral thoracic wall (closer to vertebrae). The “classic” view, referred to as the gator sign, involves holding the probe perpendicular to the long-axis of the ribs, at the intercostal space (See Fig. 1). It is important to hold the probe static at this site through several respiratory cycles, as iatrogenic movement of the probe can create the illusion of a false glide sign. Fanning the probe slightly off perpendicular such that the ultrasound beam passes through the pleural line at an angle, referred to as obliquing the echoes, often enhances visualization of the glide sign. Another technique is called the one-eyed gator by placing the rib head in the centre of the image to scatter the echoes. An intercostal view with the probe held parallel to the long-axis of the ribs can also be used and may facilitate identification of the lung point, although the land marks associated with the rib are lost with this orientation (the lung point is the site where the lung begins to come in contact with the parietal surfaces when pneumothorax is present). 3) Left and right pericardial sites (PCS): These sites are used to detect pleural and pericardial effusions, to evaluate volume and contractility, and to screen for right- and left-sided heart conditions. The probe is placed to visualize the heart, pericardial sac, and pleural spaces. The probe is placed over the heart at the level of 5th-6th intercostal space on the ventrolateral thoracic wall (closer to the sternum). The probe is moved 2.5 cm in several directions (may need to move between rib spaces) and is rocked and fanned at this site to improve the chances of finding free pericardial and/or pleural fluid. Increasing the ultrasound depth to include the entire heart within the image field, particularly in the short-axis view, improves the likelihood of differentiating pericardial from pleural fluid and not mistaking a heart chamber for either. Also comparing the PCS view and the subxiphoid view helps in differentiating pericardial from pleural fluid.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 22 of 226 Figure 1: Sites to be examined during the TFAST exam include placement of the probe perpendicular to the ribs at the left and right chest tube site (CTS) (probe labelled 1), the left and right pericardial sites with the probe in both longitudinal and transverse orientation to the heart (PCS) (probe labelled 2), and the subxiphoid site with the probe initially placed in a longitudinal orientation (probe labelled 3). In this figure the dog is in sternal recumbency with the hind end shifted into a more right lateral position. This allows both side of the chest to be evaluated while still leaving access to the subxiphoid site. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”. INTERPRETATION: TFAST EXAM  Free fluid is hypoechoic (black) and may be located in the pleural and/or pericardial spaces.  Fluids identified on TFAST may be blood, septic, chylous, or other; ultrasound guided fluid aspiration is recommended with fluid cytology and analysis to confirm the type of fluid present.  In cases of pneumothorax, air in the pleural space obliterates the normally present glide sign. Healthy patients have their visceral and parietal linings in contact with each other. Together these linings sonographically form a single visible white line referred to as the pulmonary-pleural line. The pulmonary-pleural line is located between two adjacent ribs when the ultrasound probe is placed in the “classic” CTS orientation referred to as the gator sign (See Image Fig. 2A).  As the visceral and parietal pleura slide back and forth across each other during inspiration and expiration, they form a dynamic pulmonary-pleural interface. This dynamic process creates a continuous speckling along the white pleural line referred to as the glide sign.  With pneumothorax, the glide sign is absent even during inspiration and expiration. The

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 23 of 226 loss of the glide sign during respirations implies the presence of air in the pleural space. The loss of the glide sign occurs because air separates the parietal from the visceral lining and prevents the gliding or sliding from being seen during the dynamic phases of respiration. Note: a white pleural line is still sonographically visible when pneumothorax is present (composed of only the parietal lining); the pleural line is indistinguishable between healthy patients and those with pneumothorax, except the pleural linings no longer move back and forth against each other (absent glide sign) in cases of pneumothorax (See Image Fig. 2A). Figure 2 A: Sonographic image obtained when the ultrasound probe is placed perpendicular to the ribs at the chest tube site (CTS) referred to as the gator sign with the rib heads the two eyes, and the line in between the bridge of its nose, likened to a partially submerged alligator looking at you. The ribs appear as the curvilinear white lines to either side of the image with rib shadowing (RS). The first white line that appears distal to the rib, connecting the two ribs, is the pleural line (identified by the long white arrow). This is the area that is assessed for the back and forth shimmering or glide sign. The reverberation artefact that causes the pleural line to be repeated in the far field of the image are known as A-lines (short arrows). Note that the pleural line and A -lines are both present in patients with normal peripheral lung and patients with pneumothorax. It is the back and forth motion, the glide sign, along the pleural line that differentiates normal peripheral lung (glide sign present) from patients with a pneumothorax (glide sign absent). From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”.  The CTS sites can also allow detection of B-lines; reverberation artefacts originating from the pulmonary-pleural line extending to the edge of the far field image that move to-

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 24 of 226 and-fro with inspiration and expiration (See Image Fig. 2B). B-lines serve two purposes: 1) their presence definitively rules out the possibility of pneumothorax, and 2) if they are increased in number they represent a variety of interstitial-alveolar pathology.  A single B-line at a single probe site can be normal in healthy dogs and cats. Numerous to converging B-lines indicate significant interstitial-alveolar pathology is present. With a history of trauma B-lines most likely indicate pulmonary contusion. The number of B-lines semi-quantitates the severity of lung contusions by the larger the number, the more severe the contusions. Figure 2 B: Sonographic image obtained when the ultrasound probe is placed perpendicular to the ribs at the chest tube site (CTS) in a patient in respiratory distress with crackles noted on auscultation. The ribs appear as the curvilinear white lines to either side of the image with rib shadowing (RS). The first white line that appears distal to the rib, connecting the two ribs, is the pulmonary-pleural line (long white arrow). In patients with interstitial/alveolar disease (e.g. pulmonary edema, contusions, etc.) vertical white lines known as B-lines (B) may be noted. These originate at the pulmonary-pleural line, extend to the far field of the image, obliterating A-lines, and will move back and forth with respirations similarly to the glide sign. From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”. TECHNIQUE/PROCEDURE: VET BLUE EXAM The Vet BLUE protocol involves examination of the thorax at 4 bilateral sites; caudo-dorsal, peri-hilar, middle, and cranio-ventral lung regions (See Fig. 3). It is often done in conjunction with the TFAST exam because it’s an extension from the TFAST Chest Tube site for more information regarding the lung. Depth is set between 4 (smaller)-6cm (larger) for most dogs and cats. It is important to avoid diagnosing pleural and pericardial effusion during Vet BLUE because depth is too shallow, and it is easy to confuse heart chambers for either.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 25 of 226 TFAST PCS and subxiphoid (DH) views with increased depth avoid this mistake. The four sites evaluated with the Vet BLUE exam on each hemothorax (8 sites total) include: 1) Upper third of the thorax at the 8th-9th intercostal space called the dorsal caudo-dorsal (Cd) lung region (this is the CTS of the TFAST exam) 2) 6th-7th intercostal space in the middle third of the thorax called the perihilar (Ph) region 3) Lower third of the thorax near the costochondral junction at the 4th-5th intercostal space called the middle (Md) lung region 4) The lower third of the thorax near the costochondral junction at the 2nd-3rd intercostal space called the cranial (Cr) lung region. The probe is placed at each site and initially moved 1-2 rib spaces cranially and caudally to rapidly look for B-lines and other described lung ultrasound signs (shred sign, tissue sign, nodule sign, and wedge sign [PTE])- not covered here. In larger dogs, the probe can also be moved 1-2 cm dorsally and ventrally. If B-lines are visualized, the probe is held stationary and the number of B-lines is recorded, over the most representative view, at that Vet BLUE location. If no B-lines are found, the probe is held stationary and the presence/absence of a glide sign is evaluated. At the middle lung site (3), the probe is initially placed over the 4th-5th intercostal space just above the level of the costochondral junction; if the heart obscures the field of view and prevents visualization of the lung field, the probe is moved 1-2 rib spaces caudally or dorsally, just enough until the heart is out of view or is no longer visible and the lung can be evaluated. At the cranial lung site (4), the probe is placed over the 2nd -3rd intercostal space. The heart may be used as a landmark so that when the heart is visible, the probe is then moved cranially one rib space at a time until the heart is no longer visible and the lung can be evaluated. In the cranial direction, the thoracic inlet may be used as a landmark and the probe moved caudally counting to the 2nd and 3rd intercostal space. The patient’s forelimb often needs to be pulled cranially to facilitate probe positioning at this site. Once pneumothorax is ruled out, record the presence or absence and number of B-lines other described lung ultrasound signs (shred sign, tissue sign, nodule sign, and wedge sign [PTE]) at each site. Numbers of B-lines directly correlate with the degree of alveolar-interstitial edema. The counting system over the most representative intercostal space at each Vet BLUE view that has been published is 1, 2, 3, >3 (more than 3 but still split into individual B-lines) and infinity B pattern (confluent having so many that no B-lines can be recognized individually).

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 26 of 226 Figure 3: Four sites are evaluated on each hemithorax: upper third of the thorax at the 8-9th intercostal space, or caudo-dorsal (Cd) lung region (1), 6-7th intercostal space in the middle third of the thorax or perihilar (Ph) lung region (2), lower third of the thorax near the costochondral junction at the 4th to 5th intercostal space or middle (Md) lung region (3), and the lower third of the thorax near the costochondral junction at the 2nd to 3rd intercostal space or crania (Cr)l lung region (4). From Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada; with permission”. The probe is placed at each site and initially moved 1-2 rib spaces cranially and caudally to rapidly look for B-lines. In larger dogs, the probe can also be moved 1-2 cm dorsally and ventrally. At the middle lung site (3), the probe is initially placed over the 4th-5th intercostal space just above the level of the costochondral junction; if the heart obscures the field of view and prevents visualization of the lung field, the probe is moved either caudally 1-2 rib spaces until the heart is no longer visible and the lung can be evaluated, or if abdominal contents are immediately caudal to the heart, then move dorsally just enough until the heart is out of view. At the cranial lung site (4), the probe is initially placed over the 2nd to 3rd

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 27 of 226 intercostal space 1-3 cm (depending on the size of the patient) near the costochondral junction. If the heart is visible, the probe is then moved cranially, one rib space at a time, until the heart is no longer visible and the lung can be evaluated. In the cranial direction, the thoracic inlet may be used as a landmark and the probe moved caudally counting to the 2nd and 3rd intercostal space. The patient’s forelimb often needs to be pulled cranially to facilitate probe positioning at this site. INTERPRETATION: VET BLUE EXAM  The VET BLUE protocol detects pulmonary pathology in cats and dogs, and the presence or absence of a glide sign (see TFAST).  Pulmonary pathology (most often interstitial/alveolar edema) is identified on Vet BLUE via the identification of B-lines, defined as artefacts (most commonly created by fluid next to air) originating from the pulmonary line extending to the edge of the far field image that move to-and-fro with inspiration and expiration (See Image Fig. 2B).  A single B-line at a single Vet BLUE site may be a normal finding in dogs and cats without respiratory disease.  A B-line or the glide sign effectively rules out pneumothorax at that specific site along the thoracic wall.  Multiple B-lines (>3) that are visible within the same image field, or that coalesce (infinity) may indicate different underlying pathology, depending on their distribution (See Algorithm 3). o A preponderance of B-lines present in the upper caudo-dorsal and peri-hilar regions support left-sided congestive heart failure and forms of non-cardiogenic pulmonary edema. Left-sided congestive heart failure often involves 3 or more views bilaterally. o A preponderance of B lines present in the middle and cranial lung regions supports bacterial and aspiration pneumonia. The use of the shred sign (an air bronchogram on radiographs) gives more credence to pneumonia. o By using the basic lung ultrasound signs of consolidation and infiltration, described as the shred sign, tissue sign, nodule sign and wedge sign, a better working diagnosis may be established during Vet BLUE.  When B-lines are numerous they create what is called a B-pattern, which is indicative of advanced interstitial-alveolar disease. Importantly, B-lines are non-specific and may represent different types of fluid, e.g., water (CHF), blood (contusions, coagulopathy), pus (pneumonia) immediately adjacent to air, thus the regionally-

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 28 of 226 based Vet BLUE approach and its basic lung ultrasound signs help better interpret findings during lung ultrasound. IMPORTANT CONSIDERATIONS  Patients that have a negative initial TFAST and/or Vet BLUE scan that fail to stabilize or have persistent clinical signs often benefit from serial exams.  A negative TFAST or Vet BLUE scan does not exclude internal injury or pathology. Pathology located more than a few mm within the lung that does not extend to the lung periphery is unlikely to be seen during lung sonography making thoracic radiography and other advanced imaging important once the patent is stable.  Vet BLUE can help better interpret radiographical findings because lung ultrasound is very sensitive for detecting lung surface pathology  Patients that are panting or have rapid shallow respirations can be difficult to assess for a glide sign if B-lines are not present. As this can also be opioid-induced, titration of the opioid IV or administering a lower dose of the selected drug IM helps avoid this phenomenon.  The glide sign is only visible during the dynamic phases of inspiration and expiration and thus cannot be observed between breaths (static phases of respiration and during periods of apnea).  Movement of your hand, the probe, or the patient may cause a false positive glide sign; keep your hand, the patient, and the ultrasound probe still when looking for the glide sign.  Scattering the echoes by placing the rib head in the centre of the image (one-eyed gator), or by obliquing the echoes by directing the probe at an angle to the pulmonary-pleural line are helpful tricks to more effectively and rapidly observe for the glide sign.  A linear array probe and changing the angle of the probe from perpendicular may help identify the glide sign. Further reading: 1. Lisciandro GR. Chapter 9: TFAST in Focused Ultrasound Techniques for the Small Animal Practitioner, Ed. Lisciandro GR, Wiley 2014. 2. Lisciandro GR. Chapter 10: Vet BLUE lung Scan in Focused Ultrasound Techniques for the Small Animal Practitioner, Ed. Lisciandro GR, Wiley 2014. 3. DeFrancesco TC. Chapter 11: Focused Echo in Focused Ultrasound Techniques for the Small Animal Practitioner, Ed. Lisciandro GR, Wiley 2014.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 29 of 226 4. Lisciandro GR and Armenise AA. Chapter 16: Global FAST and FAST ABCDE for Cardiopulmonary Resuscitation in Focused Ultrasound Techniques for the Small Animal Practitioner, Ed. Lisciandro GR, Wiley 2014. 5. Boysen SR. Chapter 17: Ultrasound Guided Procedures in Focused Ultrasound Techniques for the Small Animal Practitioner, Ed. Lisciandro GR, Wiley 2014. 6. Boysen SR. Veterinary Emergency and Critical Care, 3rd ed. Mathews, 2016, Lifelearn, Guelph, Ontario, Canada.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 31 of 226 CLINICAL DISCUSSION FORUM Ava Firth BS DVM MVS MANZVSc DACVECC MRCVS with panellists including Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA, Dan Lewis VetMB MA CertVA DACVECC MRCVS and Louise O’Dwyer MBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVN Clinical case discussion We all see cases that challenge our thinking and where we struggle to know if we are doing the right thing. Come along and join us for this panel discussion and hear some of our speakers discuss cases from their past that caused them to think twice. Expect some lively debate! Clinical discussion forum

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 33 of 226 SEPSIS: WHAT HAVE WE LEARNT FROM HUMAN MEDICINE OVER THE LAST 15 YEARS Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA Langford Veterinary Services, University of Bristol Sophie.adamantos@bristol.ac.uk Sepsis is an extremely important cause of morbidity and mortality in human medicine. Current estimates are that sepsis affects more people on an annual basis than heart attack and that it causes more deaths than many forms of cancer. The cost of sepsis in the US likely runs in excess of $20 billion/year. However, as a global health concern there is significantly less awareness within the population with fewer than 50% of people having heard of it. With excellent care the prognosis is reasonable for survival, however many people will have long-term health problems associated with the condition. Interestingly despite improvements in health care and new therapies and interventions being described there has been little improvement in the prognosis for people receiving excellent health care. The Surviving Sepsis Campaign was set up in 2001 to reduce mortality from sepsis by 25% by creating a plan. One of their first actions was to create definitions for sepsis and since then they have been involved in the creation and review of guidelines. In early 2016 they reviewed the definitions for sepsis resulting in significant changes to management and guidance. Over the last 15 years there has been a huge amount of research into a variety of treatments for sepsis. This talk will highlight some of the more important papers including those that have impacted significantly on management. Goal Directed Therapy Goal directed approaches had been discussed for some time prior to the publication of the landmark study by Rivers et al in NEJM in 2001. This study used guidelines presented by the American College of Chest Physicians and SCCM aimed at optimising haemodynamic variables in people with severe sepsis and septic shock. This study identified people presenting to an emergency room with severe sepsis or septic shock and randomised them to 6 hours of standard therapy or early goal- directed therapy. The study enrolled 263 patients. There were no differences in base-line characteristics. Sepsis: what have we learnt from human medicine over the last 15 years

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 34 of 226 Mortality in the standard therapy group was 46.5% and that in the EGDT group 30.5% which were statistically different. As a result of this study EGDT was adopted into the surviving sepsis guidelines around the world and many people assumed that this represented gold-standard therapy for sepsis. However, things have changed. In 2014 two studies and one study in 2015 were published that failed to reproduce the results found in the Rivers study. The ProCESS study was a multi-centre study carried out in the US and compared protocol-based EGDT vs protocol-based standard care vs usual care. This was a larger study with 1341 patients enrolled. The results were that there were no significant differences in 90 day mortality between the three groups. The ARISE study was another multicentre study that took place in Australia and New Zealand comparing EGDT to standard care. Again this was a larger study with 1600 patients enrolled. Again no significant difference was noted between the groups. The final trial, ProMISe was carried out in the UK with a similar number of patients and randomised them to EGDT or usual care. Again no difference in outcome was noted between the two groups, however people in the EGDT group had increased intensity of treatment which was associated with more severe organ failure score and longer time spent in the ICU. Of note the mortality rates in two of these studies were lower than the Rivers study (ProCESS 21% vs 18.2% vs 18.9% ad ARISE 18.6% vs 18.8%, ProMISe 29.5% vs 29.2%). Critics of these subsequent studies have tried to argue that standard care has improved significantly, and this is possible. Earlier identification may mean that treatment nowadays is more effective, however these studies do highlight now that EGDT probably performs no better than standard care when care is good and is associated with administration of less fluids, blood and fewer central lines. Blood pressure management In the early 2000s dopamine was most commonly used for management of hypotension associated with sepsis particularly with the expansion of protocol driven management. There was limited evidence to support the use of dopamine and some evidence of harm associated with its use. In 2007 a large randomised study published in the Lancet examined the use of noradrenalin plus dobutamine vs adrenalin. There was no difference identified between the two groups in the primary outcome of 28 day mortality. In a search for alternatives and with the recent increased use of vasopressin there were a number of studies published examining the use of this drug, most of which failed to show benefit over standard of care. More recently the practice of targeting blood pressure has been questioned, and if we are to target blood pressure what pressure to target. In 2014 the SEPSISPAM investigators

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 35 of 226 published a study to try and identify what blood pressure we should target. This multicentre study randomised patients to undergo resuscitation to a MAP of either 80-85mmHg (High-target group) vs 65-70mmHg (low target group). At 28 days there was no difference in mortality or adverse events. Perhaps highlighting that high blood pressure targets are not necessary. Fluid therapy Fluid therapy has becoming increasingly controversial and over the last 5 years’ significant associations have been identified between the use of hydroxyethyl starches and mortality in critically ill patients, which resulted in the removal of these fluids from use in Europe and the U.K except for a few specific indications. At this stage no association has been identified in dogs and cats between the use of colloids and AKI, however the population of patients is different, and increases in renal biomarkers have been found following use of HES in dogs. In people the SAFE study published in 2004 examined the use of albumin vs saline for resuscitation. This was a huge study (nearly 7000 patients) from Australia and New Zealand, which failed to show a difference in outcome at 28 days. Most interestingly in the last few years are those studies that have been performed and those that are ongoing in areas with limited resource including the FEAST trial. This study examined the use of fluid bolus in African children with severe infection. This is again a huge multi-centre study which has much to be admired. This study showed a small but significant increase in mortality associated with the use of fluid bolus in these children. Interpreting these results where there is high quality care is challenging, applying them to animals even more so. However, these studies indicate that while fluid therapy is important in management of sepsis careful consideration as to the type and amount should be given, and in many cases keeping it simple and having a light touch may impact on survival. Steroids In the early part of the 2000s there was much discussion as to the role of the HPA axis in sepsis and survival. The landmark study by Annane et al in 2002 included 300 patients in 19 different centres and identified a mortality benefit associated with the use of corticosteroids (including fludrocortisone) in people with septic shock. A later study performed by the CORTICUS study group published in 2008 had conflicting results. There is no evidence that using an ACTH stimulation test to identify at risk patients is useful and the effects of hydrocortisone infusion are thought to be independent of this. Routine use of steroids is not

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 36 of 226 indicated in septic shock; however, many people will still use them in patients at high risk of death that are failing to respond to vasopressors. Research is ongoing in this area. Antibiotics Most of the research examining use of antimicrobials in sepsis has concentrated on timing and there is now good evidence to suggest that early antimicrobials are of benefit in these patients. However, there have been contradictory findings over time. In 2006 Kimar et al published a landmark paper which was a retrospective study that showed that there was a strong correlation between delay in effective antimicrobial initiation and persistent hypotension and in-hospital mortality. In addition, it identified that only 50% of patients received effective antimicrobials within 6 hours of documented hypotension. This recommendation has been adopted into the surviving sepsis guidelines and remains a strong message. Fever Fever control is controversial with many thinking that this evolutionary response should not be meddled with! There are a few studies examining the control of fever in the ICU. One of the challenges that people have had with examining this in a controlled manner in sepsis is the lower than expected incidence of fever in these patients. There is no evidence that fever is associated with mortality in septic patients, although interestingly fever is independently associated with death in non-septic patients. Furthermore, there is an association between the administration of NSAIDs and paracetamol in people with sepsis. These findings are difficult to interpret. However, it is likely that fever is not a bad thing in sepsis and control is probably not required. Watch this space. Conclusions Reviewing the last 15 of the literature on sepsis, it is startling to find the number of recommendations that have been overturned through enquiry and repeated multi-centre studies. It is as if the complexity of ICU medicine is being broken down to “good care”. This includes rapid identification of sepsis, appropriate source management and stabilisation. Not pushing physiology beyond what is normal and perhaps tolerating some abnormality. There is some evidence that these abnormalities are driven by mitochondrial dysfunction and may be normal. I have certainly changed my practice significantly over the last 5 years. The challenge we have in veterinary practice is knowing whether this makes a difference. We need large multi-centre research groups to lead research and to move things forward.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 37 of 226 References/further reading: ARISE investigators (2014) Goal-directed resuscitation for patients in early septic shock. NEJM 371(16) 1496-506 Annane et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288(7): 862-71 Asfar et al (2014) High versus low blood-pressure target in patients with septic shock. NEJM 370(17): 1583-93 Finfer et al (SAFE study investigators) (2004) A comparison of albumin and saline for fluid resuscitation in the intensive care unit. NEJM 350(22): 2247-56 Kumar et al (2006) Duration of hypotension before initiation of effective antimicrobial therapy is a critical determinant of survival in human septic patients. Critical care medicine 34(6); 1589-96 Maitland et al (FEAST collaborators) (2011) Mortality after fluid bolus in African children with severe infection. NEJM 364(26): 2483-95 Mouncey et al (SEPSISPAM) (2015) Trial of early, goal-directed resuscitation for septic shock. NEJM 372: 1301-11 Perner et al (2012) Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. NEJM 367(2): 124-34 ProCESS investigators (2014) A randomized trial of protocol-based care for early septic shock. NEJM 370(18) 1683-93 Rivers E et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine 245 (19); 1368-77 Sprung et al (CORTICUS study group) (2008) Hydrocortisone therapy for patients with septic shock. NEJM 358(2): 111-24

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 39 of 226 IDENTIFICATION AND MANAGEMENT OF THE SEPTIC PATIENT Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA Langford Veterinary Services, University of Bristol Sophie.adamantos@bristol.ac.uk Rapid identification of sepsis and appropriate management is vital for success in these patients. This lecture will use a case based approach to highlight key features of sepsis and investigative strategies. Key therapeutic strategies including fluid resuscitation, management of blood pressure and the appropriate use of antimicrobials will be discussed. Identification and management of the septic patient

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 41 of 226 IMMUNE MEDIATED HAEMOLYTIC ANAEMIA: LEAVING THE PATH OF SELF-DESTRUCTION Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com ABSTRACT Anaemia, the reduction of functional circulating red blood cells (RBC) supplying enough oxygen carrying capacity to achieve oxygen delivery meeting oxygen consumption demands, is a common ailment in veterinary medicine. One form of anaemia is the destruction of RBCs by the body’s immune system, or immune-mediated hemolytic anaemia (IMHA). Various causes, methods in diagnosis, therapy, and nursing care for patients with IMHA will be discussed. INTRODUCTION Anaemia, the reduction of functional circulating red blood cells (RBC) supplying enough oxygen carrying capacity to achieve oxygen delivery meeting oxygen consumption demands, is a common ailment in veterinary medicine. Anaemia can result from RBC loss (hemorrhaging), RBC destruction (haemolysis), or reduced RBC production (non-regenerative anaemia). In any of these situations, circulating hemoglobin levels are reduced, causing a decrease in arterial oxygen content, leading to inadequate oxygen delivery (DO2) and hypoxia. Body systems cannot efficiently produce energy in the form of ATP without oxygen, and experience shock. Various defects in RBCs can cause increased rates of destruction leading to anaemia, and may be inherited or acquired. Causes of acquired defects include toxins contained in food (onion, garlic, propylene glycol), drugs (acetaminophen, vitamin K1 and K3, benzocaine), and chemicals (copper, naphthalene, skunk musk, zinc). Mechanical damage from altered blood flow (cardiac disease, heartworm infestation, hemangiosarcoma, patent ductus arteriosus), nutritional deficiencies (hypophosphatemia, folate deficiency, Vitamin B12 deficiency, cobalt deficiency), and immune-mediated haemolysis are other causes. Anaemia due to haemolysis results in lowered red cell mass and subsequent reduction in oxygen carrying capacity without significant changes in plasma volume. Haemolysis can be intravascular (destruction of RBC within the blood stream), extravascular (phagocytosis by macrophages in the spleen, liver, bone marrow, and lymph nodes), or both. Intravascular haemolysis will result in the presence of free hemoglobin in the plasma, leading to hemoglobinemia and hemoglobinuria (when renal threshold is exceeded). Hemoglobinuria Immune mediated haemolytic anaemia

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 42 of 226 leads to tubular necrosis resulting in acute kidney injury in humans, posing similar concerns in veterinary medicine. Icterus may be seen in patients with RBC destruction rate exceeding the liver’s ability to process bilirubin. In addition, the presence of red blood cell fragments may trigger disseminated intravascular coagulopathy. Extravascular haemolysis can lead to splenic enlargement, though other intravascular signs of hemoglobinemia, hemoglobinuria, and jaundice are not seen. Hemolytic anaemia is usually regenerative. PATHOPHYSIOLOGY IMHA results from an antibody-mediated RBC destruction and is a common disease in dogs, causing a significant degree of morbidity and mortality. IMHA may be primary (idiopathic), with dysregulation of the immune system leading to antibody production against unaltered RBCs, without an identifiable cause to the immune response. Secondary IMHA can occur with infectious diseases, neoplasia, or drug administration induces changes to RBC surface antigens leading to an antibody response and haemolysis. While the exact mechanisms leading to a loss of immunologic tolerance to self RBCs are unknown, autoreactive T-lymphocytes are implicated in the process. Immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies binding to RBC antigens opsonize the RBC, leading to complete or partial phagocytosis. Phagocytic loss of RBC membranes reduces the surface area of the RBC, leading to formation of spherocytes (RBCs that have lost the biconcave structure). Gross agglutination of red cells may also be seen. RBCs that are bound by IgG typically are eliminated extravascularly, while IgM mediated haemolysis may be intravascular or extravascular. The haemolysis eventually leads to a clinical level of anaemia. Immunologic response is not always limited to RBCs, and can involve platelets, leading to immune-mediated thrombocytopenia (IMT) and hemorrhaging. Concurrent IMHA and IMT is called Evan’s syndrome. The systemic inflammatory response incited by the acute hemolytic reaction also contributes to the disease process, causing the blood stream to be more likely to create clots, or a hypercoagulable state. The hypercoagulable state results from increased levels of triggers (tissue factor) and building blocks (fibrinogen) of clots, as well as increasing platelet reactivity. Reduction in anticoagulant forces (antithrombosis and fibrinolysis) through inhibition of production and activity of antithrombotic and fibrinolytic proteins (antithrombin, thrombomodulin, protein C, plasminogen, and plasminogen activators). A common complication seen in patients with IMHA is thromboembolic disease, related to the hypercoagulable state. Pulmonary thromboembolism (PTE), or lodging of a clot in a major vessel leading to the blood gas barrier, results in sudden and severe respiratory distress. Disseminated intravascular coagulation (DIC) can also occur, leading to microvascular

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 43 of 226 ischemia in major organs such as the spleen, lungs, kidneys, liver, heart, pituitary gland, stomach, skin, and lymph nodes, then a subsequent consumptive coagulopathy. CLINICAL SIGNS Clinical signs of IMHA vary depending on the severity, and are associated with signs of anaemia. Patients may present being lethargic, depressed, weak, or with a lack of appetite, sometimes accompanied with vomiting, diarrhea, polydipsia, or eating soil (pica). In severe situations, they may have collapsed. Physical examination will typically reveal tachycardia, tachypnea, hemic murmurs (caused by increased blood velocity and turbulence), pale mucous membranes, and prolonged capillary refill time. Signs of intravascular haemolysis such as hemoglobinuria and extravascular haemolysis such as icterus, splenomegaly, and hepatomegaly may also be noticed. If the patient has concurrent thrombocytopenia, signs of bleeding such as epistaxis, petechiae, melena, and other surface bleeding may be seen. American Cocker Spaniels, while any canine breed can develop primary IMHA, seem to have a higher prevalence (11-33%) and a higher chance (3.3-12.2 times) of developing IMHA. American Cocker Spaniels with IMHA are more often negative in DEA 7 (a red cell antigen) expression, but DEA 7 status seems to be a breed predisposition rather than a linked cause. The Miniature Schnauzer, Collie, English Springer Spaniel, Poodle, Bichon Frise, Miniature Pinscher, Finnish Spitz, and Old English Sheepdog also are reported breeds at higher risk of IMHA. IMHA seems to occur more often in animals middle-aged and older (greater than 4 years old). Prevalence of IMHA is higher in females and neutered individuals of both genders, potentially indicating the protective effects androgens may have against IMHA. Seasonal trends have also been reported, possibly from regional tendencies in vaccine schedule, antiparasitic agent administration, prevalence of infectious diseases, and even exposure to the cold. While definite connections have not yet been made, vaccinations are thought to increase chances of IMHA through formation of antibodies against red cell antigens or non-specific immune system stimulation. DIAGNOSIS Diagnosis of IMHA starts with a CBC and blood film evaluation. Regenerative changes, spherocytosis, and autoagglutination are seen with patients with IMHA. A concurrent decreased leukocyte and platelet count may be seen in the case of non-specific immune response to cell components. Not all listed features need to be fulfilled when IMHA is present. Patients with IMHA present with a low hematocrit (HCT) of 13-21%. A corrected

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 44 of 226 reticulocyte count of >1% or absolute reticulocyte count of >60,000 cells/µL will be seen if sufficient time (approximately 4 days) has elapsed from the onset of anaemia, stimulating a regenerative response. A reduced PCV and a normal TP is consistent in hemolytic disorders. Marked leukocytosis is often seen, possibly from an inflammatory response incited by immune response, or possibly from response to tissue necrosis from hypoxia related to anaemia (though the latter is debatable as it is not observed in other types of anaemia). Thrombocytopenia occurs in 25-70% of patients with IMHA, though bleeding in patients suspected of IMHA should not be assumed to be IMT since DIC is another possibility. Increased serum bilirubin is often seen (60-86% of IMHA cases), assumed to be majorly from extravascular haemolysis, though increased ALP and ALT suggest hepatic damage from hypoxia and drug administration. Hypophosphatemia can be seen, but is often artefactual due to the hyperbilirubinemia. Hemoglobinemia and hemoglobinuria is another sign haemolysis is occurring. Presence of an immune response may be determined by testing for autoagglutination and anti-erythrocyte antibodies. A saline agglutination test performed by mixing a drop of normal saline and equal volume of EDTA-anticoagulated blood and observing for macroscopic or microscopic agglutination, persisting beyond the dilution, can be performed to detect autoagglutination. Autoagglutination is suggestive of the presence of anti-erythrocyte antibodies, and should be differentiated from rouleaux formation. If clumping cannot be confidently differentiated between agglutination and rouleaux, further dilution is warranted. A direct antiglobulin test (DAT), or Coombs’ test is a laboratory test testing for presence of anti-erythrocyte antibodies, if autoagglutination is not observed, but IMHA is suspected. A DAT utilizes antisera containing antibodies against antibodies bound to RBCs, in the case of IMHA, and observe for agglutination caused by the antisera. A positive result indicates IMHA, though acute and delayed hemolytic transfusion reaction, intra-erythrocytic parasites, toxin induced hemolytic anaemia, neonatal isoerythrolysis, and lymphoproliferative disorders may also return positive results. A negative DAT result does not necessarily rule out IMHA since various factors contribute to a false-negative. Detection of anti-erythrocyte antibodies may be accomplished by flow cytometry, and may be more specific than determining IMHA through blood film changes or DAT. Causes of haemolysis aside from IMHA should also be ruled out, such as toxin ingestion (zinc, for example) and neoplasia. This may require radiography or ultrasonography. These imaging studies may also confirm hepatomegaly or splenomegaly. Pleural and peritoneal effusions may be seen if IMHA is leading to thromboembolism or increased vascular

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 45 of 226 permeability from inflammatory response. Testing for blood borne pathogens and systemic autoimmune diseases should be considered if history warrants. TREATMENT Initial treatment should be directed at supporting oxygen delivery, if severity is leading to tissue hypoxia. Fluid administration aimed at replacing any fluid deficits and providing for intravascular volume in optimizing cardiac output is warranted. A reduction in HCT from hemodilution is often a concern preventing fluid administration, but should not deprive a patient of appropriate volume load to circulate the remaining RBCs through the body adequately. If oxygen carrying capacity from a reduced RBC mass is leading to tissue hypoxia (most cases of IMHA), supplementation through RBC transfusions or hemoglobin-based oxygen carrier solution (HBOCS) is warranted. Storage lesions, or biochemical changes in blood solutions during storage, is thought to have negative effects in patients with IMHA, possibly increasing morbidity and mortality, and is an area of ongoing investigation. The least antigenic blood type is ideal for transfusion (negative for as many testable red cell antigens as possible), and repeat transfusions are not expected to cause immunologic reactions if within 4 days of the first transfusion. Blood type matching can be performed by immunochromatographic blood typing kits and cross matching is recommended if no autoagglutination is seen. With immediate life-threatening anaemia treated to the best of our abilities, immunosuppressive therapy is warranted. Any current medication that is not life sustaining should be discontinued to eliminate potential immunologic stimulation. Glucocorticoids such as prednisone and dexamethasone are used for immunosuppression, though beneficial effects may be of a delayed and long term nature, and various side effects can be seen (polyuria, polydipsia, gastric ulceration, iatrogenic hyperadrenocorticism, thromboembolic disorders, etc.). Additional immunosuppressive agents such as azathioprine, inhibiting lymphocyte proliferation through disruption of RNA, DNA, and protein synthesis, are used to minimize the glucocorticoid use. Cyclosporine, suppressing activation and proliferation of T-lymphocytes, is also used. Luflunomide and mycophenolate suppress lymphocyte and antibody production by inhibiting DNA synthesis. Liposomal clodronate is thought to reduce macrophage population by inducing apoptosis, though not all forms of IMHA benefit from reduced macrophages. The efficacy of luflunomide, mycophenolate, and clodronate use is currently under investigation. Thromboprophylaxis, or administration of antithrombotic agents to prevent thromboembolic disorders, has been attempted. Anticoagulants have been used in the hope to create this

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 46 of 226 effect. Unfractionated heparin inhibits coagulation factor Xa activity, and is observed to improve survival time in IMHA. Aspirin inhibits cyclooxygenase-mediated production of thromboxane A2, a procoagulant, but its effect in reducing incidence of thromboembolism has not been substantiated. Clopidogrel, an antiplatelet agent, has been observed to be as effective as using aspirin. Long term management of the disease involves monitoring through periodic evaluation of CBC and blood film for HCT, regenerative changes, and autoagglutination as immunosuppressive therapy is continued. Improvements in clinical signs should be judged from owner feedback. Relapse in disease often occurs as immunosuppressive therapy is altered or discontinued after resolution of IMHA, and requires reinstitution to control the immune response. Studies evaluating the rate of survival to discharge from an IMHA crisis observe 50-88%, and patients are prone to repeated relapses leading to death or euthanasia within a few months, though life span after an IMHA crisis is highly variable. SUGGESTED READING Day MJ. Immune-mediated haemolytic anaemia. In: Day MJ, Kohn B. BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine. British Small Animal Veterinary Association, Gloucester, 2012;59-66. Garcia J, South-Bodiford R. Hematology, In: Merrill L. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Wiley-Blackwell, Ames, 2012: 171-174. Mitchell K, Kruth, S. Immune-Mediated Hemolytic Anaemia and Other Regenerative Anaemias. In: Ettinger SJ, Feldman EC. Textbook of Veterinary Internal Medicine. Saunders Elsevier, St. Louis 2010; 761-772.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 47 of 226 ANAEMIA: IT IS NOT ONLY ABOUT BLEEDING! Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com Anaemia, most accurately described, is a deficiency in the blood’s oxygen carrying capacity due to a reduction in the circulating red cell mass. Measurement of total red cell mass requires specialized testing and is difficult to accomplish in clinical practice. Measurement of PCV, HCT, hemoglobin (Hgb), and RBC count are more common methods in the assessment of erythrocyte content of blood. Thus, anaemia is commonly defined as a reduction in these values, and occurs when the rate of red blood cell loss or destruction exceeds the rate of production. Anaemia is caused by various diseases, many of them resulting in the patient requiring immediate attention. Functional Role of Red Blood Cells Erythrocytes or red blood cells (RBCs) exist mainly to transport oxygen, obtained through the lungs, to body tissues. The cell’s functions are devoted to optimizing oxygen delivery, with all of its potential energy directed towards maintenance of enzymatic and hemoglobin function, as well as cell integrity. The general structure of RBCs involves cells with no nuclei or organelles and no ability to produce proteins. Therefore, a mature red blood cell must have its full set of proteins to function appropriately. The RBC’s oxygen carrying capacity is very much dependent on hemoglobin, an iron-porphyrin-protein complex. Hemoglobin is synthesized during the erythrocyte’s development to its mature form. The molecule is a tetramer of heme groups working in cooperation to load and unload oxygen molecules. The percentage of heme groups bound to oxygen molecules is characterized by the oxygen-hemoglobin dissociation curve, visualizing the relationship between partial pressure of oxygen in the blood vessel and oxygen binding. Affinity of hemoglobin to oxygen can be affected by various factors, such as temperature, presence of hydrogen ions (pH), and presence of 2,3 diphosphoglycerate (2,3 DPG), altering the ability for transfused RBCs to deliver oxygen in specific conditions. Erythropoiesis RBCs are produced through a process called erythropoiesis. Hematopoietic stem cells are progressively differentiated into numerous precursors, eventually expelling their nuclei and developing into reticulocytes, which develop into erythrocytes in 3-4 days. This process is regulated by a hormone called erythropoietin (EPO), which signals the production of new Anaemia: it’s not only about bleeding!

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 48 of 226 RBCs. EPO is a glycoprotein produced mainly by the peritubular interstitial fibroblasts in the kidney, though the liver contributes to a small amount of production in anaemia. Autocrine production of EPO by erythroid progenitor cells has also been observed. There is a normal amount of erythropoiesis, or basal erythropoiesis, which replace RBCs living out their life span, maintaining the total red cell mass in a normal range. Upregulated erythropoiesis, in response to an increased EPO production stimulated by inadequate oxygen carrying capacity and resultant hypoxemia and hypoxia (leading up to a 1000-fold increase in severe hypoxia), is called stress erythropoiesis. Any cause for anaemia, such as hemorrhaging or haemolysis, can trigger EPO production, with a noticeable increase in serum EPO level observed within minutes. Reticulocytes are seen within 3-5 days after EPO level is increased, and take another 3-4 days to mature into erythrocytes. Patients seen within 3 days after the blood loss are said to be in the “pre-regenerative” state with no increase in reticulocyte count. If the blood sample of an anemic patient is showing increased reticulocyte count, the patient has a “regenerative” anaemia. Patients without an increase in reticulocyte count after 5 days of ongoing anaemia may have “non-regenerative” anaemia. Normal RBC Lifespan Canine RBCs have a normal life span of 100-115 days, while feline RBCs normally live 73 days. RBCs are taken out of circulation as age-related damage occurs. Age-related damage includes compromise in rheological properties due to membrane deformability loss, immunologic removal through IgG binding and opsonization, reduction in antioxidant defences leading to denaturing of hemoglobin, and compromise to membrane structure through peroxidation of the phospholipid bilayer (oxidative damage). These damaged cells are removed by the macrophages of the mononuclear phagocyte system, involving the spleen, liver and bone marrow. TYPES OF ANAEMIA RBC Loss One of the most common causes of anaemia is an increased rate of RBC loss. Blood can be lost through internal or external hemorrhaging. Internal hemorrhage can involve blood loss into the internal spaces, such as peritoneal, retroperitoneal, pleural, pericardial, and gastrointestinal spaces. There are numerous causes of internal and external hemorrhage. Trauma, surgical accidents, and ruptured neoplasms can cause physical damage to vessels resulting in acute or gradual hemorrhaging. Coagulation factor deficiencies, thrombocytopenia, and thrombocytopathia may render a patient unable to prevent bleeding

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 49 of 226 from normal damage to the vasculature. Parasitism can lead to external hemorrhage (fleas, ticks, lice) or internal hemorrhage (Ancylostoma, Uncinaria). Gastrointestinal ulcers and hemorrhagic gastroenteritis are GI specific sources of hemorrhage. Anaemia due to hemorrhaging is usually regenerative. RBCs lost internally may be placed back into circulation through the lymphatic system, or removed from circulation by macrophages, and their components are recycled. Plasma, RBCs, and their iron content cannot be recovered with external hemorrhaging. Hemorrhage leads to a reduction in red cell mass as well as a compromise in perfusion, leading to reduced oxygen delivery. Dogs have a total blood volume of 78-88ml/kg, while cats have a total blood volume of 62-66ml/kg. Blood loss exceeding 20% leads to significant hypotension, and a loss exceeding 30% will lead to hypovolemic shock and possible death. Treatment of RBC loss through hemorrhaging is directed at maintaining oxygen delivery through providing adequate perfusion and oxygen carrying capacity. Fluid therapy to address hypovolemia is warranted to ensure perfusion to vital organs. Restoration of a normal blood volume will not be possible without addressing the source of the hemorrhage. Locating the source of the blood loss may be more obvious in the case of external hemorrhaging, but may prove to be a challenge if internal. Hemorrhaging from trauma, surgical accidents, and ruptured neoplasms are often stopped through surgical intervention. Coagulation factor deficiencies warrant replacement through appropriate plasma products. The cause of thrombocytopenia and thrombocytopathia should be addressed with appropriate therapy, and platelet transfusions administered if the hemorrhaging is life threatening. Correction of hemostatic disorders should ideally be accomplished before surgical intervention, if warranted. Ectoparasite and endoparasite infestations will require the appropriate anti-parasitic. Gastrointestinal ulcers will require removal of causes and supportive care. If the patient is showing a rapid decline in lab values related to red cell mass (PCV, HCT, or Hgb) or showing clinical signs of hypoxia due to the anaemia, a red blood cell transfusion is warranted. Clinical signs of anaemia may vary slightly due to the cause of anaemia. In general, any form of anaemia is associated with paleness. Patients who have compromised delivery of oxygen will exhibit signs of weakness, exercise intolerance, lethargy, fatigue, and sometimes collapse. Their mentation may be dulled due to brain hypoxia. In acute anaemia, a prolonged capillary refill time (CRT) due to peripheral vasoconstriction, to shunt blood to vital organs, may be seen (Patients with chronic anaemia will show a normal CRT).

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 50 of 226 Tachycardia, tachypnea, and bounding pulses without other explanations also point towards compromised oxygen delivery. RBC Destruction Various types of defects in RBCs can cause an increased rate of destruction leading to anaemia. Anaemia due to haemolysis results in lowered red cell mass and subsequent reduction in oxygen carrying capacity without significant changes in plasma volume. Haemolysis can be intravascular (destruction of RBC within the blood stream), extravascular (phagocytosis by macrophages in the spleen, liver, bone marrow, and lymph nodes) or both. Intravascular haemolysis will result in the presence of free hemoglobin in the plasma, leading to hemoglobinemia and hemoglobinuria (when renal threshold is exceeded). Hemoglobinuria leads to tubular necrosis resulting in acute kidney injury in humans, and poses similar concerns in veterinary medicine. Jaundice may be seen in patients with RBC destruction rate exceeding the liver’s ability to process bilirubin. In addition, the presence of red blood cell fragments may trigger disseminated intravascular coagulopathy. Extravascular haemolysis can lead to splenic enlargement, though other intravascular signs of hemoglobinemia, hemoglobinuria, and jaundice are not seen. Hemolytic anaemia is usually regenerative. Genetic defects of red blood cells, though rare, can cause hemolytic anaemia. Elliptocytes, stomatocytes, and pyruvate kinase defect lead to reduced life span due to abnormalities in RBC membrane and shape. Spectrin deficiency and phosphofructokinase defect lead to reduced life span by increasing the fragility of RBCs. Haemolysis is most commonly caused by acquired RBC defects, resulting in direct membrane injury or osmotic lysis. Exposure to chemicals and drugs that cause Heinz body formation will lead to removal of these red cells from circulation through the phagocytic system or cause direct lysis. Causes of Heinz body formation include toxins contained in food (onion, garlic, propylene glycol), drugs (acetaminophen, vitamin K1 and K3, benzocaine), and chemicals (copper, naphthalene, skunk musk, zinc). Cats are more prone to Heinz body formation, but are also more forgiving towards red cells containing Heinz bodies, allowing for a longer survival time. Because of this, feline RBCs may show Heinz bodies without anaemia. Cats can develop Heinz bodies when exposed to propylene glycol, and are more prone if inflicted with diabetes mellitus, lymphoma, or hyperthyroidism. Cats with diabetes mellitus or hepatic lipidosis can develop hypophosphatemia which also can cause haemolysis. Phosphate supplementation is recommended if a phosphate level below

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 51 of 226 0.5mmol/L is seen. Intraerythrocytic parasites such as Babesia canis and Cytauxzoon felis, can lead to hemolytic anaemia as well. Haemolysis may be caused by antibody or complement response to the surface antigens of red blood cells by the patient’s own immune system, termed immune-mediated hemolytic anaemia (IMHA). Extravascular haemolysis can result from an immunoglobulin G (IgG) mediated type II hypersensitivity (cytotoxic) reaction. Phagocytic loss of RBC membranes reduces the surface area of the RBC, leading to formation of spherocytes (RBCs that have lost the biconcave structure). Gross agglutination of red cells may also be seen. If the immune response is initiated by factors such as cancer, drug administration, or infection, the hemolytic anaemia is considered to be secondary IMHA. Passive acquirement of anti-red cell antibodies through blood transfusions and colostrum can cause an IMHA as well. The latter results in a phenomenon called neonatal isoerythrolysis, where anti-red cell antibody is passively acquired by a nursing neonate, resulting in the destruction of red cells. When no causative agents can be identified, the hemolytic anaemia is considered to be primary IMHA, or auto-immune hemolytic anaemia (AIHA). Changes in rheology and passage of RBCs through narrow vessels can cause mechanical and shearing damage to the membranes. Hemoglobinemia and hemoglobinuria result as this is a form of intravascular haemolysis. Fragmented schistocytes and keratocytes are seen on blood smears as an indication of mechanical damage. Patients with cardiac disease, severe heartworm infection, hemangiosarcoma, patent ductus arteriosus, and any other causes of altered blood flow and microangiopathy may show signs of fragmentation of RBCs. DIC can be a cause of fragmentation, and at the same time precipitate DIC. Efforts in treatment of hemolytic anaemia are directed towards removing the cause of the haemolysis, and supporting oxygen carrying capacity as needed. Genetic disorders typically cannot be completely resolved, though patients with disorders leading to haemolysis through the mononuclear phagocytic system may benefit from a splenectomy. Exposure to chemicals, inducing Heinz body related haemolysis, should have the source removed (change in diet, surgical removal of the ingested copper or zinc material). Some toxins may have antidotes such as acetylcysteine in acetaminophen toxicity. Therapy for mechanical injury induced haemolysis is directed at the underlying cause. IMHA is treated with immunosuppressive agents such as glucocorticoids, cyclosporine, mycophenolate, azathioprine, and intravenous immunoglobulin.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 52 of 226 Regardless of the cause of the haemolysis, when the anaemia leads to clinical signs of hypoxia, oxygen carrying capacity is supplemented. Packed RBC (pRBC) transfusions are typically the ideal choice as hemolytic anaemia does not cause blood volume loss. pRBC will provide oxygen carrying capacity while minimizing the volume of transfused product, reducing the chances of fluid volume overload. In the case of IMHA where finding compatible blood or simply judging compatibility may be difficult, hemoglobin-based oxygen carrier solution (HBOCS) administration may be beneficial. Decreased Production Anaemia can result from a reduced production of red cells as well. One cause for reduced red cell production is a decreased level of EPO, leading to reduced erythropoiesis. Patients with chronic renal disease often become anemic as EPO production by the kidneys are diminished. Other factors such as uremic toxins leading to a lowered red cell half-life, hemorrhagic loss due to GI ulcers, increased bleeding tendencies due to platelet dysfunction, inhibition of iron store release, suppression of erythropoiesis by the parathyroid, and reduced nutrient intake may also contribute. Suppression of response to EPO is another cause of reduced production. In the presence of chronic inflammatory disease such as chronic infections, chronic immune conditions, and malignant cancers, or in acute inflammatory diseases, red cell production is reduced. This is attributed to an increased production of hepcidin by hepatocytes during inflammatory disease, which inhibit the iron exporting action of ferroportin in macrophages and enterocytes. This reduces the iron available for erythropoiesis. In addition, inflammatory mediators (tumor necrosis factor-α and interleukin-1) released from leukocytes reduce surface EPO receptors on erythroid stem cells, leading to suppression of erythropoiesis. Dysfunction of the bone marrow may be another cause for reduced RBC production. Irradiation, toxicities, viral or bacterial infections, and administration of certain drugs can result in marrow aplasia, leading to a lack of marrow stem cells. Myelopthisis, or marrow suppression secondary to marrow infiltration by tumors can displace or inhibit production of hematopoietic cells. Both of these situations result in a pancytopenia. In FeLV infections in cats or immune-mediated erythroid stem cell destruction in dogs, erythrocyte precursor cells are specifically reduced in number, leading to red cell aplasia. When nutrients required for producing the signaling system for erythropoiesis and functional erythrocytes are deficient, anaemia will occur. Folic acid, vitamin B12, cobalt and intrinsic factor (a glycoprotein aiding in absorption of vitamin B12) deficiency can result in a

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 53 of 226 dysfunction of DNA and RNA synthesis, leading to production of erythrocytes of abnormal shape and size. These abnormal cells are destroyed in the bone marrow, thus never making it into circulation. Administration of drugs that antagonize folate (methotrexate for malignant tumors), inhibit folate metabolism (sulfonamides), and deplete folate concentrations (phenobarbital) are potential causes of malformed erythrocytes. A genetic disorder in Giant Schnauzers, Beagles, and Border Collies involving selective malabsorption of vitamin B12 has been reported and lead to a non-regenerative anaemia. A deficiency in iron results in production of erythrocytes with a reduced concentration of Hgb, or lead to delay in red cell production resulting in anaemia. Treatment for non-regenerative anaemia consists of supportive care while the underlying disease process is treated. Infectious and toxic causes may be alleviated over time, yet neoplastic and genetic causes typically have no complete resolutions. Ineffective erythropoiesis due to nutrient deficiency can be alleviated through supplementation. In the case of decreased EPO levels, such as chronic kidney disease, EPO may be administered to promote erythropoiesis. If the anaemia reaches a point of clinical signs of hypoxia, administration of red cell products or HBOC solution may be beneficial.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 54 of 226 Notes page

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 55 of 226 THE AIR OUR CELLS BREATHE: ARTERIAL BLOOD GASES Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com Evaluation of the respiratory status of the patient can be evaluated in numerous ways. One of the most accessible method is visual assessment of respiratory effort and respiratory rate, as well as auditory evaluation through auscultation of the chest cavity. Both of these methods allows one to detect a patient who is having difficulty breathing, as well as giving some hints to the type of respiratory disorder. When evaluating the severity of respiratory compromise, visual assessment and auscultation is not always sufficient. A more objective look at respiratory status can be made through more sophisticated, and sometimes invasive methods to determine the patient’s blood gas values. There are many gases dissolved and carried by the blood in various forms. Two which are of the most interest for respiratory function are oxygen and carbon dioxide. Oxygen is required for efficient energy production through oxidative phosphorylation through aerobic respiration, and CO2 level is controlled by the body in order to maintain a normal pH value suitable for life. Oxygenation The importance of maintaining adequate delivery of oxygen (DO2) lies in the difference of the amount of adenosine triphosphate (ATP) produced in the presence and absence of oxygen. ATP is considered the “currency of cellular energy”, providing energy for cellular processes required to maintain life, as phosphate groups are cleaved off resulting in energy release and formation of adenosine diphosphate (ADP) or adenosine monophosphate (AMP). ATP is involved in cellular signalling, DNA and RNA synthesis, muscle contraction, cytoskeletal maintenance, active transporting, and many other cellular functions. There is a finite amount of ATP available within a body, and a constant recycling of ADP and AMP into ATP is required to keep up with energy demands. In the presence of oxygen, 38 ATP molecules are generated from metabolism of a single glucose molecule undergoing oxidative phosphorylation, occurring in the mitochondria. In contrast, a single glucose molecule yields two ATP molecules through anaerobic metabolism. The presence of oxygen is imperative in efficient energy generation. Provided there is adequate intravascular volume and tissue perfusion, DO2 is dependent on the oxygen level contained in the blood (arterial oxygen content, CaO2) and how quickly the body can circulate the blood to the tissues (cardiac output, CO). The resulting mathematical expression of DO2 is: DO2 = CaO2 x CO. Oxygen contained within blood exists in two forms; The air our cells breathe: arterial blood gases

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 56 of 226 dissolved in the plasma and bound to hemoglobin. The amount of oxygen dissolved in plasma depends on the partial pressure of oxygen (PaO2), with 1 mmHg creating enough tension to result in 0.0031mL of dissolved O2 per dL of plasma. Each gram of hemoglobin is able to theoretically carry 1.39mL of O2 when fully bound with oxygen, making up a significant portion of oxygen content of blood. In reality, there are portions of dysfunctional hemoglobin lowering this to approximately 1.34mL. In addition, not every hemoglobin molecule will be fully bound to oxygen in every situation (SaO2, or arterial oxyhemoglobin saturation) adding some variability. With all of these considerations in mind, the resultant formula to quantify DO2 is the following, expressing the impact lowered hemoglobin concentration and saturation of the hemoglobin will have on overall delivery of oxygen: DO2 = [(1.34 x Hgb x SaO2) + (0.0031 x PaO2)] x CO. The respiratory system is responsible for providing SaO2 and PaO2. The respiratory system ensures adequate oxygenation of the blood, to provide sufficient DO2 to meet the body’s oxygen consumption, by bringing air with oxygen (~21% in the atmosphere) to the blood-gas barrier and allowing diffusion of O2 into the plasma. The diffused oxygen is then taken up by hemoglobin in the red cells, and carried to the rest of the body. Oxygenation can be decreased by reduced oxygen content of breathed in air (high altitudes or rebreathing of expired air), increased thickness of the blood-gas barrier (pulmonary edema, pneumonia, pulmonary fibrosis), reduction of the amount of air moved in and out of the lungs (hypoventilation caused by pleural space disease, respiratory muscle dysfunction, respiratory suppression), ventilation of alveoli without proper perfusion (dead space ventilation caused by pulmonary thromboembolism, pulmonary vascular injury or hypotension), and areas of the lungs with dysfunction in ventilation even though receiving proper perfusion (shunting such as in pulmonary edema, pneumonia, acute respiratory distress syndrome, atelectasis, and airway obstruction). A physical sign seen in patients with severe hypoxemia is cyanosis, or a blue color to the mucous membranes. Cyanosis becomes apparent when there is more than 5 g/dL of deoxyhemoglobin present in the blood. An average hemoglobin level in dogs is approximately 13-17 g/dL, and in cats is approximately 10-14 g/dL. This means the oxygen saturation of hemoglobin will be a significantly decreased level on average of 61-70% for dogs and 50-64% for a cat before cyanosis is seen. Patients presenting with cyanosis are severely compromised in their DO2 and require immediate attention. Oxygenation can be better gauged through measurement of PaO2, serving as an indicator of pulmonary function. PaO2 can be measured through blood gas analysis of arterial blood,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 57 of 226 requiring arterial blood sampling and a blood gas analyzer. A patient with normal respiratory function, breathing room air will have a PaO2 of 80-100mmHg. PaO2 of less than 80mmHg qualifies as hypoxemia, and 60mmHg is considered severe hypoxemia. Pulse oximetry allows non-invasive measurements of the percentage of oxygenated functional hemoglobin in the arterial bloodstream, utilizing the concept of light absorption. The saturation of oxygen measured by pulse oximetry (SpO2) closely reflects SaO2 and can be used to estimate the PaO2 level. The oxygen-hemoglobin dissociation curve expresses the relationship between SaO2 and PaO2. A SaO2 of 95-98% corresponds to a PaO2 of 80-100mmHg. A SaO2 below 90% indicates a PaO2 of less than 60mmHg. Pulse oximetry has its limitations, including false reading in the presence of significant levels of dysfunctional hemoglobin species (methemoglobin, carboxyhemoglobin), inconsistent readings with movement, poor perfusion, anemia, and pigmented skin. Interpretation of oxygenation and pulmonary function based on hemoglobin saturation is especially difficult when the patient is provided inspired oxygen level (FiO2) higher than that of room air (21%, or 0.21). Simplistically speaking, the PaO2 can be expected to be about 4-5x the FiO2 expressed as a percentage in patients with normal pulmonary function. Patients on room air (FiO2 21%) will be expected to have a PaO2 of 80-100mmHg, with 95-98% oxygen saturation of hemoglobin. Patients on oxygen therapy receiving 40%, 60%, 80%, and 100% for example, will be expected to have a PaO2 of 160-200mmHg, 240-300mmHg, 320-400mmHg, and 400-500mmHg, respectively. Oxygen saturation of hemoglobin with PaO2 above 100mmHg will consistently read 98-100%, and therefor will not allow for estimation of PaO2 beyond 100mmHg. Because of this limitation, an actual PaO2 measurement through blood gas analysis is necessary in order to gauge the efficiency of gas exchange. By determination of PaO2, a value called PaO2:FiO2 Ratio (PF ratio) can be calculated. For example, a patient breathing air that is 21% oxygen and having a PaO2 of 100mmHg has a PF ratio of 100 divided by 0.21 (decimal expression of 21%), which equals 476. A PF ratio of 400-500 indicates normal pulmonary function, 200-300 indicates a degree of pulmonary dysfunction seen with acute lung injury, and anything less than 200 indicate severe pulmonary dysfunction often seen with acute respiratory distress syndrome. The PF ratio is important in making patient progress, in recovery from their pulmonary dysfunction, quantifiable. A patient with a PaO2 of 200mmHg on 80% FiO2 on day 1, having a PaO2 of 140mmHg on 40% FiO2 on day 2, has increased the PF ratio from 250 to 350, indicating improved pulmonary function between the two measurements, even though the PaO2 has decreased in value. In long term oxygen therapy, delivering oxygen supplementation,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 58 of 226 allowing the PaO2 to be between 80-100mmHg for any given pulmonary function, is most effective in providing adequate DO2 and minimizing effects of oxidative damage (which is more likely to occur with higher oxygen concentration). Another calculated value called the A-a or alveolar-arterial gradient, is the difference between alveolar and arterial concentration of O2 indicating the efficiency of gas exchange. At room air, the A-a gradient is normally around 10-15mmHg, but can be larger with lung pathology causing more significant ventilation/perfusion mismatching. Carbon Dioxide Control CO2 is produced by tissues as a metabolic by-product of energy production. The body normally maintains control of CO2 levels in order to control the pH level of the body. An accumulation of CO2 causes an increase in levels of carbonic acid, leading to higher levels of dissociated hydrogen ions, leading to a more acidic environment (lower pH). A reduction in CO2 level will lead to a decrease in hydrogen ions, leading to a more basic environment. This effect is called respiratory acidosis and respiratory alkalosis, respectively. Maintenance of the pH in a normal range of 7.35-7.45 is important as there are various negative effects caused by abnormal pH. Acidosis (pH < 7.35) for example, can cause cardiovascular effects (decreased contractility, arrhythmias), central nervous system dysfunction (CNS depression, increased intracranial pressure), respiratory dysfunction (decreased oxygen uptake by hemoglobin), and enzyme dysfunction. Alkalosis (pH >7.45) can cause similar cardiovascular effects, decreased cerebral blood flow, decreased oxygen unloading by hemoglobin and enzyme dysfunction. The amount of CO2 eliminated by the body largely depends on the movement of air in and out of the alveoli, to perform gas exchange or ventilation. Room air contains about 0.04% CO2 (0.3mmHg) and the replacement of gas within the alveoli with fresh room air will promote diffusion of CO2 out of the blood stream into the gas within the alveoli, which in turn gets expired out of the lungs and airway. A normal CO2 level within the blood is approximately 35-45mmHg in dogs, and 30-40mmHg in cats, and can be measured by blood gas analysis (PaCO2 if arterial or PvCO2 if venous). The difference in PCO2 in the pulmonary capillaries and alveoli creates a pressure gradient required for gas exchange (high to low; high in the capillary, low in the alveoli). PCO2 is largely influenced by the amount of air that can be moved in and out of the alveoli, or alveolar ventilation. The value will increase with hypoventilation leading to hypercapnia (>45mmHg) in cases of respiratory depression (suppression of respiration due to drugs,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 59 of 226 neuromuscular disease, CNS disease), inability to expand the lungs (pleural space disease, compromise to chest walls), or increased resistance to breathing (narrowed airway). Hyperventilation and subsequent hypocapnia (low PaCO2) can be seen in patients with increased RR due to anemia and hypoxia. When the patient experiences metabolic acidosis, compensatory increase in respiratory effort and hyperventilation is often seen, countering the metabolic acidosis effect with respiratory alkalosis. This occurs because the presence of hydrogen ions will stimulate the respiratory centre of the brain to increase respiratory efforts. Table 1. Arterial Blood Gas Values and Ranges Human Dog Cat pH 7.35-7.45 7.35-7.46 7.31-7.46 PaCO2 (mmHg) 35-45 32-43 26-36 Base Deficit (mmol/L) -2 to +2 +1 to -5 -2 to -8 HCO3 (mmol/L) 22-26 18-26 14-22 PaO2 (mmHg), sea level 80-105 80-105 95-115 Source: Silverstein DC, Hopper K. Small Animal Critical Care Medicine, 2e The PaCO2 can be estimated by measurement of End-tidal CO2 (ETCO2). The CO2 content in the gas present at the probe at the end of expiration is measured to obtain this value. The ETCO2 in normal cardiovascular and respiratory situation, is within 5mmHg of the PaCO2. The ETCO2 is most easily measured when an endotracheal tube is placed in a patient (anesthetic procedure or mechanically ventilated patients, for example). There are nasal tubes and masks available allowing for less invasive ETCO2 measurement. Arterial Blood Gas Analysis Arterial blood samples need to be collected in order to perform blood gas analysis for respiratory assessment. Sampling can be performed periodically through a syringe and needle, with common sampling sites including the dorsal pedal and femoral arteries. Radial, auricular, and lingual arteries are less common, but are good alternatives when access to dorsal and femoral arteries are limited or have been attempted and exhausted. Proper knowledge of anatomy and experience with palpation of each vessel is required to

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 60 of 226 accurately puncture the artery. Successful sampling with minimal trauma and stimulation to the vessel is recommended, since stimulation will cause constriction of the artery and make sampling more difficult. If frequent or repeated sampling is needed, an arterial catheter becomes more desirable and useful, especially with patients on mechanical ventilation and severe respiratory compromise. The placement of an arterial catheter also gives the ability to measure direct arterial pressure, being beneficial in many critical care patients. Complications of arterial catheters include thrombophlebitis and embolism. The collected sample should be analysed immediately to prevent mixing with room air, resulting in inaccurate results. Prolonged exposure to room air will result in a reduced PaCO2 and inaccurate PaO2 (direction depends on what the sample contains, heading towards 150mmHg). Even if the sample is kept from being exposed to air, delay in analysis will allow metabolic processes of RBCs to alter blood gas results. Because of this, placing the sample on ice to maintain at 4°C is recommended, if the sample needs to wait for analysis, keeping the sample results stable for up to 6 hours. Heparin used beyond 10% of the sample volume will result in significantly diluted results. Coating of the syringe with heparin, by pulling heparin into the syringe and then expelling it, is recommended to minimize the dilution effect. Self-venting arterial sampling syringe sets are commercially available which are preloaded with dry heparin pellets, minimizing dilution and facilitating sampling as well. There is a controversy that exists in blood gas analysis involving temperature correction of the values. The sample is analysed at 37°C in the analyser. The patient’s body temperature may be different from 37°C, which changes the blood gas values. The body temperature can also affect the affinity for oxygen with hemoglobin, and alter metabolic rates and gas solubility. Because all of the effects of hypothermia and hyperthermia are not completely understood, whether temperature correction in calculated blood gas values is necessary is also unknown. The importance of temperature correction in clinical practice lies in making sure whether it is applied, it is done consistently between samples. Arterial blood gas analysis, while requiring extensive training and comfort in sampling techniques, is a very valuable tool in evaluating the patient’s respiratory status. Both oxygenation and ventilation status, as well as pulmonary function is most accurately assessed through blood gas analysis, providing a better idea of patient progress through treatment. While blood gas analysis is a powerful tool, a veterinary technician utilizing a combination of low-tech patient assessment skills relying on honed senses and high-tech assessment tools to grasp the entire picture of the patient’s respiratory status.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 61 of 226 TO CLOT OR NOT TO CLOT? HAEMOSTATIC DISORDERS Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com To clot, or not to clot? That is the question. The haemostatic system is a complex protective mechanism sealing off avenues of blood loss through the vascular system upon damage. While cessation of blood loss is vital in preventing subsequent anemia and eventual death, coagulation of the blood is normally controlled, limiting it within the intravascular space to maintain normal blood flow and minimizing chances of thrombosis. This delicate balance and interaction of procoagulant and anticoagulant mechanisms is essential in the proper function of the haemostatic system. In emergency and critical care, dysfunctions of the haemostatic system lead to life-threatening situations through a variety of mechanisms. Haemostasis The coagulation mechanism has been described traditionally by dividing the process into two phases of coagulation, consisting of primary haemostasis (platelet plug formation) and secondary haemostasis (coagulation cascade), followed by the fibrinolytic phase. In addition, newer knowledge incorporates the roles of tissue factor (TF) bearing cells and platelets in less distinct, overlapping phases called the “cell based model” of coagulation. The cell based model consists of the initiation, amplification, and propagation phases. (Note: For the rest of the document, coagulation factors will be referred to with an “F” for “factor”, followed by its number, and with or without an “a” to indicate inactive and active form, respectively). Initiation: TF expressed by cells located outside of the vasculature serves as the initiator for coagulation. The localization of TF in the extravascular compartment prevents the activation of coagulation in normal circumstances where the endothelium is intact. TF is also expressed by some cells in circulation but is kept in an inactivated form. Injury of the endothelium exposes the TF, leading to the binding of FVIIa, which in turn activates more TF-FVII complexes. The complex activation leads to generation of FIXa, FXa, and FVa. FXa and FVa form the prothrombinase complex, leading to small amounts of thrombin generation through cleaving of prothrombin. Amplification: Platelets are activated by the generated thrombin as they leave the intravascular space through the injured endothelium. Through changes in membrane surfaces, incited by thrombin binding to receptors, platelets degranulate to release fibronectin, platelet factor, von Willebrand’s factor (vWF), calcium, and other procoagulants. To clot or not to clot? Haemostatic disorders

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 62 of 226 These factors further activate platelets and promote binding of coagulation factors to the membrane surface. Thrombin then activates FXIa and FVa on the platelet surface, and cleaves vWF off FVIII, releasing vWF and activating FVIII to FVIIIa. This phase is considered to have amplified the small signalling for coagulation through thrombin generation in the initiation phase. Propagation: The effect of degranulation includes the expression of platelet surface ligands, which results in platelet aggregation. FIXa (generated during initiation and amplification) and FVIIIa (generated during amplification) form the tenase complex on the platelet surface. Tenase then rapidly generates FXa on the platelet surface, binds to FVa (generated in the amplification phase), and cleaves prothrombin into thrombin. Thrombin is the protease responsible for fibrin formation. When there is a significant amount of thrombin generated, they serve to convert fibrinogen to fibrin, allowing for clotting. Thrombin further promotes coagulation by activating FVII, FXI, FVIII, and FV, activating platelets, and activation of FXIII (a transglutaminase responsible for crosslinking fibrin fibrils). In a healthy animal, coagulation is inhibited to maintain good blood flow and prevent thromboembolism. Decreased thrombin levels or activity, entailing the body’s normal antithrombotic mechanism, involve several events. These events include tissue factor pathway inhibitor (TFPI) inhibiting TF-FVIIa and FXa, C1-inhibitor inhibiting FXIIa, and FXIa, antithrombin inhibiting thrombin, protein C inactivating FVa and FVIIIa, thrombomodulin modifying thrombin to decrease its ability to convert fibrinogen to fibrin, and protein S aiding in protein C’s ability to inactivate factors as well as TFPI’s inhibition of FXa. Fibrin clots seal the damage in vasculature to prevent intravascular fluid loss. Once the damage is repaired through healing mechanisms, removal of the clot is required to re-establish unimpeded blood flow. Fibrinolysis is the process of breaking down of the fibrin clot. Fibrin degradation is performed by an enzyme called plasmin. Plasmin is formed by the cleaving of plasminogen by plasminogen activators such as tissue-type plasminogen activator (tPA, active when fibrin is present) and urokinase plasminogen activator (uPA, active extravascularly and independent of fibrin presence). Fibrinolysis is normally inhibited by inhibitors of plasmin activity (thrombin activatable fibrinolysis inhibitor), plasminogen activation (α2-antiplasmin), or plasminogen activator inhibitors (plasminogen activator inhibitor 1). The haemostatic system is a complex system involving elements controlling thrombosis, antithrombosis, fibrinolysis, and antifibrinolysis. These processes interact with each other

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 63 of 226 through complicated feedback systems to form clots where appropriate to maintain the vascular system. Disorders of Haemostasis Consequences of haemostatic dysfunction can be divided into two categories: hypercoagulation (thrombosis), or hypocoagulation (haemorrhagic coagulopathy). Thrombosis occurs from the development of a hypercoagulable state, and can be further divided into macrovascular thrombosis (leading to clinical manifestations of aortic thromboembolism and pulmonary thromboembolism or PTE), and microvascular thrombosis (leading to microvascular ischemia and coagulation factor depletion and resultant DIC). Haemorrhagic coagulopathies can arise from dysfunctions in the coagulation, occurring due to platelet depletion or dysfunction, as well as the coagulation factor inhibition or depletion. Thrombosis Thrombosis, or formation of matrices of platelets, fibrin, and cellular debris, occurs within the intravascular space potentially leading to thromboembolism due to three factors (described by Virchow’s triad): hypercoagulability, blood stasis, and endothelial injury. Hypercoagulability can result from platelet hyper-reactivity, excessive coagulation factor activation, natural anticoagulant deficiency, hypofibrinolysis, or a combination of any of these causes. Platelet hyper-reactivity can result from increases in platelet activators. This includes direct stimulation by inflammatory cytokines, release of other platelet agonists, and hypoalbuminemia-mediated increase in thromboxane A2 (a prothrombotic). Endothelial damage leading to decreased availability of platelet inhibitors (prostacyclin, nitrous oxide, and ADPase) or administration of antiplatelet drugs can lead to a reduced inhibition. Excessive coagulation factor activation occurs when increased expression of TF by endothelial cells, macrophages, and cell-derived microparticles is induced by endotoxins or inflammatory mediators. An increased exposure of already existing TF can also occur due to endothelial damage. Deficiencies in natural anticoagulants may be genetic or acquired in origin (we will focus on acquired origins as they are more prevalent in animals). Antithrombin (AT) deficiencies can arise from hepatic failure, protein-losing nephropathies, consumption due to a pathologic increase in thrombin (DIC or massive thromboembolism), or suppression from drugs. Protein C deficiencies can develop due to sepsis, malignancy, pancreatitis, DIC, and hepatic or cardiac failure. Tissue factor pathway inhibitor (TFPI) deficiencies are seen in hypercholesterolemia, seen as a risk factor for thromboembolism. Hypofibrinolysis has not been very well defined in veterinary medicine, but is thought to occur with an increased level of plasminogen activator inhibitor (PAI-1) and/or α2-antiplasmin. Hypoplasminogenemia has

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 64 of 226 been reported in traumatized dogs and horses with strangulating obstructions. Areas of impaired blood flow can lead to varying degrees of blood stasis. Changes in cardiovascular anatomy and cardiovascular function can cause abnormal or reduced flow, being risk factors of thrombosis. Left atrial dilation causing an aberrant blood flow is a well-known cause of FATE. Other conditions associated with altered blood flow include hypovolemia, hyperviscosity disorders, neoplasia, vascular and cardiac abnormalities. Protein-losing nephropathy: Glomerular disease leading to protein loss through the urine is known to cause a hypercoagulable state, associated with venous and arterial thromboembolism in dogs. AT loss in the urine is the primary factor in thrombosis for these patients. Because AT and albumin have similar molecular sizes, hypoalbuminemia (< 2.0g/dL) can be thought of as a decreased AT level and increased risk of thromboembolism as well. As mentioned earlier, hypoalbuminemia in itself leads to increased risk of thrombosis due to increased thromboxane A2. Glomerular nephropathies are also associated with hyperfibrinogenemia, hypercholesterolemia, increased FVIII, increased PAI-1 (causing hypofibrinolysis), all contributing to hypercoagulability. Thrombin activation is thought to increase even with only a very modest amount of protein loss in the urine. Neoplasia: An association between neoplasia and thrombosis is now well accepted, with some types to have a higher degree of association than others. Thrombosis is observed to be associated with lymphoma, acute leukemia, and other solid tumors. Occurrences of hypercoagulable states have been determined by thromboelastography (TEG) in significant percentages of patients with malignant neoplasia (45-66%) studies, supporting this connection. Patients with malignancies with metastasis show higher fibrinogen and D-dimer concentration compared to those with local neoplasia. The mechanism behind neoplasia associated hypercoagulability includes a multitude of factors. Malignant cells release procoagulant material and inflammatory cytokines leading to platelet activation, and can directly interact with endothelial cells, platelets, and monocytes. Malignant cells may also express TF, and release cancer procoagulants. Malignancy may also lead to activated protein C resistance and deficiencies in anticoagulants. Neoplasia can indirectly contribute to hypercoagulability by causing vascular invasion and anomalies, immobility, or prompt venous catheterization, corticosteroid therapy, surgery and chemotherapy. Immune-mediated Haemolytic Anemia: Thromboembolism is commonly associated in patients with IMHA, leading to significant mortality. Evidence of thromboembolism is seen on necropsy findings in 30-80% of IMHA patients. Other laboratory findings such as hyperfibrinogenemia, high D-dimer levels, thrombocytopenia, hypoalbuminemia,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 65 of 226 hyperbilirubinemia, and low AT level are also seen, which supports a hypercoagulable state. The mechanism behind the state is not fully understood, but is thought to involve an increased circulating level of activated platelets, a haemolysis mediated hyper-reactivity of the platelets to platelet agonists, and antiphospholipid antibodies. Acute Pancreatic Necrosis: Pancreatitis is associated with venous and arterial thromboembolism in dogs, and venous thromboembolism in cats. Damaged pancreatic tissues release TF and inflammatory cytokines. There is also an increase in phospholipase A2, leading to increased platelet activating factor and cytokine synthesis. Both of these events trigger platelet activation and increase platelet hyper-reactivity. Platelet reactivity is further enhanced through inhibition of prostacyclin production and increased thromboxane A2 release, resulting from high plasma free fatty acid and hypoalbuminemia, respectively. In addition, an increased level of PAI-1 and decreased activity of tPA lead to hypofibrinolysis. Hypercortisolism: Pulmonary thromboembolism, portal vein, and splenic vein thrombosis are known complications encountered by dogs with hyperadrenocorticism. A high cortisol level is thought to be involved in the development of a hypercoagulable state, indicated by similar effects seen with corticosteroid therapy, though a relationship between dosage and duration of therapy is not well defined. An increase in several coagulation factors (II, V, VII, IX, X, XII, fibrinogen), reduction in AT levels, and TEG changes consistent with a hypercoagulable state support the connection. Dogs with pituitary-dependent hyperadrenocorticism were found to have increased clot strength, rate of clot formation, and possibly platelet reactivity, with trilostane therapy significantly decreasing clot strength. Sepsis and DIC: Microvascular thrombosis and DIC are known to be triggered by sepsis and systemic inflammatory response syndrome (SIRS). An increase in proinflammatory cytokines induce TF expression on the monocytes and endothelial cells, leading to initiation of coagulation. In addition, several events contribute to a loss of anticoagulation. First, TFPI is broken down by granulocytic elastases. Second, TFPI expression is suppressed by cytokines. Lastly, TFPI is overwhelmed by the number of TF-FVIIa. As thrombin level increases through amplification, anticoagulation through upregulation of antithrombin and protein C becomes insufficient and leads to a hypercoagulable state. While factors normally leading to an increase in fibrinolysis (increased release of tissue plasminogen activator and inflammation related activation of contact pathway) are present, fibrinolysis is inadequate due to increase in plasminogen activator inhibitors and activation of thrombin-activatable fibrinolysis inhibitor. As anticoagulant factors are overwhelmed and thrombin activates more platelets, diffuse microvascular fibrin thrombi are generated. The perpetuation of coagulation

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 66 of 226 in DIC contributes to consumption of coagulation factors. Eventual haemodynamic changes which decrease tissue perfusion, in addition to secondary acidosis which inhibit platelet function and coagulation factor activity, lead to a haemorrhagic coagulopathy. Coagulopathies Haemorrhaging occurs when an individual’s haemostatic efforts are unable to keep up with the blood loss resulting from compromised vascular integrity. The loss of vascular integrity may occur from direct physical trauma leading to gross physical compromise in the vasculature. In some cases, a coagulopathy related to inability for the individual to properly form a fibrin plug leads to the haemorrhaging. Individuals can acquire these coagulopathies through a delay in clot formation, prevention of clot formation, or increased rate of fibrinolysis. Synthetic Failure: Many procoagulants, coagulation factors, and anticoagulant proteins are synthesized by the liver (FII, FV, FVII, FIX, FX, FXI, FXII, FXIII, protein S, protein C). While production of these proteins is affected in a variable manner in hepatic failure, which leads to decreased level of both procoagulants and anticoagulants, hepatic failure typically results in clinical manifestation of haemorrhaging. Coagulation factors with the shortest plasma half-lives (FVII, with half-life of 6hr, for example) will be depleted first. In some cases, hepatic dysfunction may produce dysfunctional proteins, as seen in defective fibrin formation from production of dysfunctional fibrinogen. Activation Defects: The activation of coagulation factors II, VII, IX, and X is accomplished through the addition of gamma-carboxyglutamic acid, allowing the factors to interact with calcium, bind to membrane surfaces, and form active enzyme complexes. Vitamin K is essential in the activation of these factors, aiding the carboxylation through oxidation from vitamin K hydroquinone (KH2) to vitamin K epoxide (KO). A commonly seen coagulopathy in emergency and critical care is anticoagulant rodenticide toxicity, caused by the toxic component (coumarins) inhibiting the activity of vitamin K epoxide reductase. Vitamin K epoxide reductase converts KO to KH2. The inhibition of this enzyme results in the depletion of KH2 and subsequent depletion of functional vitamin K dependent coagulation factors. Factor Consumption and Dilutional Coagulopathies: A significant demand on coagulation factors as seen in DIC will lead to a consumptive coagulopathy, with liver synthesis unable to meet the demands. Snake envenomation can cause coagulation factor depletion and defibrination through proteases contained within the venom activating clotting factors or directly degrading available fibrinogen. In cases of high volume fluid resuscitation or massive

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 67 of 226 transfusions, a dilutional coagulopathy can manifest. The coagulopathy arises from diluted concentration of the procoagulants, as the intravascular space is filled with fluid without coagulation factors. Dilution results from fluid shift from the intracellular and interstitial space into the intravascular space, in response to change in hydrostatic pressure during hypovolemia, and additional intravenous administration of crystalloids, synthetic colloids, or red blood cell products. In the case of breach in endothelial integrity (e.g. trauma), activation of coagulation and consumption of coagulation factors and platelets contributes to a reduction in available procoagulants. If blood products are used, hypocalcemia from citrate and hypothermia can lead to further exacerbation. Simultaneous administration of fresh frozen plasma and platelets, along with RBCs, in massive transfusions have been observed to increase survival in humans, presumably due to replacement of coagulation factors and platelets leading to a less severe dilutional effect. Coagulation Inhibitors: Presence of coagulation inhibitors can act in several ways to cause a coagulopathy. Antibodies can develop due to sensitization to coagulation factors after transfusion. In haemophilia A and B dogs, alloimmunization against FVIII (haemophilia A) and FIX (haemophilia B) were seen as a result of transfusion. Alloimmunization against other coagulation factors has been observed post transfusion leading to an acquired coagulation factor defect (most commonly FVIII), termed “acquired haemophilia”. Other forms of coagulation inhibitors include medications such as hirudin (anticoagulant found in salivary glands of leeches) causing delays in expression of coagulation factors, and heparin compounds which aid antithrombin function. In addition, increased levels of fibrin degradation products from fibrinolysis may inhibit coagulation (most commonly seen in DIC). Fibrinolysis Defect: When fibrin clots undergo fibrinolysis at a rate faster than the amount of time vascular repair is completed, haemorrhaging can result. Increased fibrinolysis is associated with increased plasminogen activators, decreased plasminogen inhibitors, or both occurring at the same time. Hyperfibrinolysis may arise with neoplasia due to increased secretion of plasminogen activators by tumor cells. DIC enhances fibrinolysis due to increased tPA. An increased bleeding tendency is seen in dogs with ascites due to right-sided congestive heart failure, possibly to be due to hyperfibrinolysis. Because the tissues of the prostate and uterus contain a high concentration of tPA and uPA, surgeries involving these organs will have an increased risk of haemorrhagic complications due to local hyperfibrinolysis. Platelet Dysfunction: Platelets are the first line in responding to exposed TF, serving a vital role in the initiation of coagulation. There are several disorders involving platelets, leading to

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 68 of 226 a coagulopathy. Coagulopathies involving platelet dysfunction typically manifest as surface haemorrhaging such as petechiae, ecchymosis, epistaxis, gastrointestinal haemorrhage, oral bleeding, and the like. Platelet destruction can occur through an autoimmune response to platelet and megakaryocyte antigens, or non-immune mediated destruction (infection, drugs, neoplasia). Platelet loss can occur due to acute haemorrhaging (trauma) and consumption (DIC, thrombocytopenic thrombotic purpura, haemolytic uremic syndrome). Dysfunction in platelet production is uncommon, and includes immune-mediated amegakaryocytic thrombocytopenia, megakaryocytic hypoplasia (drugs, neoplasia), irradiation, myelonecrosis, and hereditary. Haemostasis is a complex system involving proper coagulation, anticoagulation, fibrinolysis, and antifibrinolysis occurring in a finely balanced manner. Many causes of disruption in these forces result in the formation of thrombi leading to thromboembolism or a coagulopathy leading to haemorrhagic disorders. As a veterinary technician, having thorough knowledge of risk factors and progression of haemostatic disorders will allow us to aid our ability to minimize potential for a pathological consequence. With potential clinical manifestations in mind, the improved ability to recognize consequences of haemostatic dysfunction will allow for a swift and appropriate action.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 69 of 226 GETTING THE BEST AND MOST APPROPRIATE RADIOGRAPHIC IMAGES FIRST TIME Jennifer Kinns VetMB DipECVDI DACVR MRCVS IDEXX Telemedicine A radiographic interpretation can only be as good as the radiographs obtained. A poor quality study can lead to missed diagnosis or over-interpretation. In emergency medicine the ability to obtain a perfect study may be limited by the status of the patient as well as extrinsic factors such as budget, equipment and staff availability. This lecture looks at real cases and the best ways to obtain a diagnostic study in those patients. General technical factors Radiographic exposure factors should be optimal for the case in question. Over or under exposure can limit interpretation. With digital systems there is much more latitude in the exposure technique which can be used to obtain a diagnostic study, but over-exposure can still cause misdiagnosis of pneumothorax or a missed lesion of the ventral abdomen. When the dyspnoeic patient is on the table this is not the time to be revising your radiographic technique! Technique charts should be established and adjusted before emergency use to avoid unnecessary repeat exposures in a potentially unstable patient. When sedation is not possible due to patient stability or owner request, judicious use of positioning devices such as troughs and sandbags can aid patient positioning to produce a diagnostic study. Trauma radiographs An ideal study will comprise perfectly positioned orthogonal radiographs collimated to and centred on the region of concern. In emergency polytrauma patients this is rarely possible. Clinical localization can be challenging, and the presence of concurrent thoracic, abdominal, skeletal and spinal trauma complicates evaluation. Once the patient is sufficiently stable survey radiographs can be obtained with the aim of regional evaluation. It is likely that further imaging may be necessary once the immediate clinical concerns are addressed. Sedation and pain relief are often necessary to obtain a diagnostic study. Either may compromise the muscular protection of spinal injury, and any patient with potential spinal injury should be handled with caution. Orthogonal (craniocaudal / dorsopalmar and lateral) radiographs are necessary for complete evaluation of skeletal structures. A single view can miss significant trauma including joint luxation and fracture. Where ligamentous instability is suspected stressed radiographs may be appropriate. Flexed lateral views can expose the caudal aspect of a joint and assess for Getting the best and most appropriate radiographic images first time

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 70 of 226 instability in the palmar / plantar supporting structures. Stressed dorsopalmar and dorsoplantar views can be used to assess for collateral instability and may reveal intercarpal or intertarsal instability. Oblique projections can also be used to assess for non-displaced trauma that may not be evident on a standard study. Spinal studies in non-trauma patients must be straight to avoid artefactual narrowing of the intervertebral disc spaces. Use of a trough for ventrodorsal views and positioning wedges for lateral spinal images can improve straightness and diagnostic quality. Collimated radiographs of the spinal region of concern can reduce artefact as compared to whole body or whole spine images. Additional advanced imaging is often required in this cases for more definitive diagnosis. Radiographs of the acute abdomen Radiographs of the abdomen should include the entire abdomen, from the diaphragmatic margin to the pelvic inlet. This may require additional views in larger patients. A lateral and ventrodorsal view are recommended. Most clinics obtain a right lateral view as standard. In vomiting patients, a left lateral view can be extremely useful. With the patient in left lateral recumbency the right sided pylorus is uppermost and will be gas filled, as will the descending duodenum. Pyloric or duodenal foreign material is therefore surrounded by gas and can be seen, whereas soft tissue opacity material will efface with the surrounding fluid on a right lateral view and can be missed. A left lateral and ventrodorsal view may be the study of choice in a vomiting patient. Potential gastric dilatation volvulus (GDV) cases are the one instance when a single right lateral view is appropriate. The characteristic appearance of the stomach on a right lateral view is often diagnostic for the condition, and the ventrodorsal image can be confusing. In most other acute abdominal cases two views are necessary for complete evaluation. Mechanical obstruction is characterized by segmental distension of small intestine which can be missed on a single projection. A foreign body or splenic mass may only be seen on one view, and two views are necessary to localize a potential lesion. Upper GI contrast study An upper GI contrast study may be indicated to help differentiate the surgical from non-surgical acute abdomen. It is important that enough contrast is administered to obtain a diagnostic study.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 71 of 226 Method For canine patients 5-10ml/kg of 30% weight per volume of micropulverised liquid barium should be administered by either orogastric tube (ideal) or oral syringe. If necessary confirmation of the position of the tube can be obtained with a lateral radiograph. The larger dose would be recommended in smaller animals. For feline patients 12-20ml/kg of contrast is necessary for a diagnostic study. A lesser volume can markedly increase gastric emptying time and lead to a false diagnosis of delay and limited gastric evaluation. Contrast should never be mixed with food for this study. This will also lead to delayed gastric emptying and there will be an irregular appearance to the contrast which can confound interpretation. Immediately after contrast administration initial radiographs should be obtained. A lateral and ventrodorsal view is necessary as a minimum. If there is any concern for a gastric lesion, dorsoventral and opposite lateral views will also be necessary, as a filling defect associated with a lesion of the wall may only be visible on one view. Follow up lateral and ventrodorsal views are ideally recommended at 30 min, 1 hr, 2 hrs and until contrast has filled the colon and gastric emptying has occurred. Follow up radiographs obtained at 12 hours can help to confirm that all the contrast reaches the colon. If this sequence is not followed a partially obstructive surgical lesion or focal intestinal abnormality could be missed. In cat’s gastrointestinal transit is more rapid and images should also be obtained at 15min. Other contrast agents can be used. Iodinated contrast is typically recommended if gastrointestinal perforation is suspected. However, this does not provide an ideal study. Ionic iodinated contrast is hyperosmolar and will draw water in to the intestines leading to gradual decreased opacification and intestinal dilation which can confuse interpretation. Non-ionic agents are better, but are very expensive for this purpose. Imaging the acutely dyspnoeic patient Thoracic radiographs should include the entire thorax, from the thoracic inlet to the caudodorsal thoracic margin. In larger dogs this may require additional images. Obliquity can limit evaluation and straighter lateral views may be obtained by placing a wedge under the ventral thorax. Two or three views are always recommended. In lateral recumbency the ‘down’ lung is compressed and is not evaluated. A right lateral view will therefore only provide assessment of the left pulmonary parenchyma. Where aspiration pneumonia is a consideration evaluation of the most commonly affected right middle lung lobe is indicated, and inclusion of a left lateral view in addition to a ventrodorsal view can provide better evaluation of this region. Use of a single lateral view is not recommended in any patient as significant disease could be missed.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 72 of 226 The acutely dyspnoeic patient presents a thoracic imaging challenge. The ideal thoracic radiograph is obtained during inspiration, but this is often impossible when presented with a tachypnoeic terrier. Radiographic interpretation must therefore take into account the artefactual effects of an often expiratory study. Two or three view thoracic radiographs are of course ideal, but if patient stability is compromised by positioning, a dorsoventral radiograph may be possible when a ventrodorsal image is not, and lateral recumbency may initially only be possible on one side or not at all. Flow by oxygen may help to reduce distress and ease positioning in dyspnoeic pets. Radiographs of the neck can also be extremely valuable to exclude upper airway aetiologies for the acute presentation. When initially reviewing the acquired study it should be noted that pleural effusion or pneumothorax can impact the exposure technique necessary to obtain a diagnostic study. In both cases follow up radiographs obtained after thoracocentesis can often provide more information than the original study. Recommended reading 1. BSAVA Manual of Canine and Feline Radiography and Radiology (2013). McConnell F and Holloway A. 2. The handbook of veterinary contrast radiology. Seth T. Wallack. 2003. Published by the author, San Diego Veterinary Imaging Inc., 361 North Sierra Avenue, Solana Beach, CA 92075

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 73 of 226 EMERGENCY & CRITICAL CARE CERTIFICATION FOR RVNS (ADVANCE YOUR LEARNING) & CERTVNECC AWARDS CEREMONY Advancing your learning: why study for a Certificate or an advanced qualification? What is out there? What is the CertVNECC? Is there funding available to support my learning? Come and join us for presentations from Wendy Busby, Louise O’Dwyer and Rebecca Hubbard from VN Times, and join us in celebrating our most recent CertVNECC certificate holders – with a celebratory glass of prosecco! ECC certification for RVNs (advance your learning)

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 75 of 226 EMS PRESENTATIONS Vets Now run a national EMS programme placing fourth and final year vet students in emergency practice. In this session, a shortlist of vet students will present cases they found particularly rewarding from either a diagnostic or treatment perspective during their placement with Vets Now. In its second year, this is an interesting case discussion session from a student’s perspective. The judging panel will consist of Aoife O Sullivan, Sophie Adamantos, Rebecca Pope and Malishia Connolly. EMS presentations

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 77 of 226 THE ROLE OF FRONT OF HOUSE: BEFORE AND AFTER THE CONSULTATION Nick Steele BSc (Hons), CIPD Cert. Learning & Development National Consulting Manager Zoetis UK Limited nick.steele@zoetis.com Being qualified veterinary healthcare professions and working together as an effective team to deliver an excellent clinical service is the minimum expected by your clients, especially in an emergency setting. Your clients expect you to have the necessary skills, knowledge and training and to have all the necessary equipment at your disposal. Many practices think these are the areas where they can differentiate themselves and in some, like additional services and specialisms you can, but these aspects are essentially the qualifiers to being considered a potential provider of veterinary healthcare. The experience choosing you and engaging with your practice is the real factor that will differentiate you from potential alternatives and competitors. Understanding what this needs to look like and providing this clarity to your team will give you the opportunity to enhance your client experience and differentiate you from other practices and providers. In essence, this client experience is the combination of clinical care being delivered with the right level of client care for your practice. At Zoetis, we describe this as the medical value you offer. It is your key differentiator, all team members have a role to play in delivering it and your front-of-house professionals are central to its delivery. But medical value is one of three drivers that inter-play within the operations of your business; the other two are communicating a promise to your clients and potential clients and setting a culture within your practice in terms of how things are done. You can see that these three are closely connected and all three need to be present within your operation to ensure the best chance of success. So why is client experience so important; surely clients simply want a good service from their vet practice whether it’s a general practice or an emergency centre? Veterinary practices are not like medical GP practices where we have a limited choice as users based on geography and population density; rather, pet owners are “chooser-users” making veterinary healthcare providers service-centred businesses. This is undeniably the case for general veterinary practices and also true for emergency providers, as choice is always available to pet owners. If pet owners are dissatisfied with the service, it means they did not receive The role of front of house: before and after the consultation

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 78 of 226 value in return for the cost of engaging with you. Given that they expect the right clinical care to be delivered, this lack of value must surely come from the service and experience they received from you and they will seek an alternative where this balance is offered to them. How do you know what the right level of client experience is for your practice? One method to determine this is to examine the relationship between the level of service (clinical and client) you want to offer and the price/cost you ask in return for it. You must first think about your market – what level of service do the people who live around you want and expect; there’s no point offering a high-end service to a population who are seeking a ‘value’ experience? The relationship to the price or cost is that increasing levels of service must be associated with increasing price or cost; you can’t deliver a ‘value’ service and charge high prices as clients will quickly become dissatisfied and go elsewhere. Likewise, offering a high level of service with low price or cost isn’t sustainable from a business perspective; developing higher levels of service requires investment in your team and practice, so gaining a return on this investment through revenue and profit is essential. This process is about understanding your position in your marketplace – your value proposition. This is essential for a general practice to define and increasingly for emergency practices to consider, as alternative providers and substitute services develop in this space. Knowing this and communicating it clearly to the team is central to defining what the client experience needs to be within your practice. Word-of-mouth, be it between pet owners in the park or via social media, is the second biggest driver of clients to your services and extensive research in other service-centred business illustrates the impact client experience. These businesses recognise the importance of defining a client experience congruent with their value proposition and take time to clearly communicate this to their teams and develop their skill and knowledge to give them the best chance to consistently deliver that experience to their customers. How does a veterinary practice go about achieving this? As well as knowing you value proposition and communicating it clearly to your team, it’s important to map the client journey the pet owner takes engaging with you. This client journey should look at all aspects from choosing you, contacting you, coming to you and being in the practice, to lapsing or leaving you. Knowing this will enable you to identify the metrics to assess your performance at each stage and begin the process of helping the team

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 79 of 226 understand the role they play and how they need to deliver the client experience to support your practice value proposition. Delivering a service is a combination of what you need to do and how you need to do it. Practices are often very good at defining what needs to be done, clinical protocols for example, but don’t often go as far as defining protocols for client service. Is there a specific way the telephone calls should be handled and managed? Have you defined the consistent way you want the pet owner and patient to be invited into the consult room? Small things, but you can see how getting these wrong can have a major impact on the perceptions clients have of you and your reputation. Visiting a veterinary practice is stressful for pet owners as the health and wellness of their pet is so important to them; this is even more so in the emergency setting. Your front-of-house professional play a pivotal role here are they are the first voice and face clients will encounter. Likewise, they will be the last team member a pet owner engages with as they pay and leave the practice; and once on their journey home, they immediately start to reflect on their experience and make decisions about choosing you in the future. How can we define the ‘what’ and ‘how’ of these phases of the client journey to make them congruent with our value proposition? This requires the creation of client service behaviours. Why behaviours? Performance can be assessed by looking at results, but performance can only be changed when we look at behaviours. Creating these client service behaviours involves identifying the key client touch points along the client journey, deciding what the experience at that point needs to be and defining how it should be delivered. A simple way to approach this is to consider what an observer would see and hear. Building these behaviours along the client journey has several benefits: they make it tangible for the front-of-house team; they enable the team to be developed; they enable the smooth induction of new team members; and they enable managers to give constructive feedback on performance. Ultimately, creating these tools to define and support the delivery of your client experience means you have given your team and practice the best chance at leveraging your key differentiator – the client experience you deliver.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 81 of 226 HANDLING DIFFICULT CLIENT SITUATIONS Nick Steele BSc (Hons), CIPD Cert. Learning & Development National Consulting Manager Zoetis UK Limited nick.steele@zoetis.com We’re comfortable in a veterinary practice because it’s familiar and we understand the environment, but it causes varying levels of stress for our clients when they visit us. Even when it’s just for the routine annual health check and booster, there will be a level of stress – “what if they find something wrong?”, “what if they judge me for being a bad owner?” Imagine the stress levels when pet owners have made the decision to bring their pet to an emergency clinic. Whatever their concern and whatever the level of stress, it will have an effect on the way people behave and react to situations. In many ways, a visit to the vet practice causes people to change from normal, rational behaviour into an irrational state. Being in this irrational state is often why we see difficult situations and reactions emerge in our clients and the higher the levels of stress the greater the chance of a difficult situation occurring. In essence, we need to be ready to deal with people and situations. So how can we recognise this and have strategies in place to deal with different people and situations? We can’t hold multiple scenarios in our mind, so what are some over-arching principles that we can draw upon when the need arises? Any principle we have to deal with people and situations needs to achieve some specific aims. They must allow you to deal with people and situations in a positive way that is delivered in an assertive and consistent manner. Central to this is the client experience we want our team and practice to deliver; a challenging situation can be converted into a positive result. We can also see that our skills in communication will be important to support the principles. One such over-arching principle is the LEARN model. It can be used flexibly to handle any difficult client situation and aims to put responsiveness, empathy and good communication at the centre of the interaction. Handling dicult client situations

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 82 of 226 The LEARN model consists of the following components:  Listen  Empathise  Apologise  Respond  Notify Listening involves giving the client your complete undivided attention in order to fully understand the problem. Often we are tempted to jump-in and start providing solutions or defend our position, but it’s important to first fully understand the person and the situation before we can decide how to proceed. The key here is about demonstrating empathetic listening and doing this in a genuine way that doesn’t appear patronising. Developing understanding is achieved through relevant questions and the use of paraphrasing and summarising techniques to demonstrate you are listening and understand the problem. It’s important to refrain from making any judgement during this phase; wait until you have formed a complete picture. Also refrain from offering any opinion; neither should you agree or disagree – just show you are listening and understand. If the client is angry, then let them vent their frustration until they calm down. How do we show the customer we are really listening? This is where our communication skills come into play. Think about both verbal and non-verbal communication: affirmative words, nodding, matching of body language, taking notes and staying in rapport. Empathy means showing the client that you really do care and it can help if you demonstrate you have placed yourself in the customer shoes. How may they be feeling about this? Useful phrases include: “If I were in your shoes I would possibly feel exactly the same” ‘I can see this has caused difficulties for you” At this point we really need the client to believe we fully understand how this problem has affected them. Importantly, we are not agreeing or disagreeing, nor are we expressing an opinion; we are simply empathising with them. It’s also important not to disagree or dismiss how they are feeling; perception is powerful and is reality for that person. Disagreeing with them now would mean you’ve challenged their values and beliefs and that’s very dangerous territory if you want to achieve a positive outcome.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 83 of 226 Apologising in the LEARN model doesn’t mean we are accepting blame or saying that something has gone wrong; it is simply apologising for the fact that the client feels the way that they do. So it’s important that we do this with sincerity and show the client that this is being taken seriously and you will do what you can to resolve the situation to everyone’s satisfaction. It is also a good point to actually thank the client for raising the problem with you to give you a further opportunity to deliver the client service you desire. In the case of a client complaining about price, we are not apologising for the price, we are apologising for the fact that the client feels this way. Where a person is very aggressive or frustrated their mind-set is often in an irrational state and is certainly lacking logic and objectivity. Therefore, in this situation arguing back will only inflame the situation further. Individuals in this state are often looking for an argument and are expecting a response to reflect this. Welcoming the complaint is very unexpected by the individual and can often shock them into calming down instantly, especially when supported with empathy. This is because it is unexpected and suddenly the person is feeling listened to and their complaints are being taken seriously. This takes the individual from a more irrational state to a more neutral one. By adding in the value step, the theory is that the individual will be taken to a more logical mind-set, calmer state. Responding involves sharing with the client how this can be resolved now that you fully understand their perspective. It doesn’t mean sharing the solution as further steps might be required to build a full picture; the perspective of others, or evidence may need to be gathered. This is also an opportunity to ensure the client is able to offer their own thoughts at this point to enable them to feel part of the process or solution, further building towards a positive outcome. Next, notify anyone else within the practice as to what the agreed actions are and what the process or solution will be. Also notify the client as to what has been done to resolve this and keep them updated. So the LEARN model is providing us with some principles to apply to any difficult situation and can be adapted so that you can flexible respond to different scenarios. It includes good principles of communication and client service and supports you to achieve a mutually beneficial result protecting your reputation.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 85 of 226 FLEXIBLE LEADERSHIP AND MANAGING TEAM PERFORMANCE Nick Steele BSc (Hons), CIPD Cert. Learning & Development National Consulting Manager Zoetis UK Limited nick.steele@zoetis.com A few years ago, Zoetis conducted the first piece of research seeking to understand the model of employee engagement within veterinary practices. Over 5000 of you contributed to the research and it enabled us to provide veterinary practices with a mechanism to understand the level of their team’s engagement and solutions to make it better. So why is employee engagement important? Engagement isn’t about levels of motivation; that’s part of it, but in pure terms it’s measuring the clarity your team have on the practice goals and their individual contribution towards achieving them. The research revealed that the three drivers that contribute the most to overall team engagement are: 1. Being an effective leader 2. Executing an effective performance management process 3. Enabling effective team working So leadership is vital, but it needs to be supported by the practice running an effective performance management process. What does effective leadership look like and how do you apply different leadership strategies to different performance situations? Firstly, we need to define leadership and contrast it to management. Covey put it very well when he said: “Management is efficiency in climbing the ladder of success; leadership determines whether the ladder is leaning against the right wall.” In a veterinary practice of any type, the role of the leader is to understand the situation of the practice and set the course for the future, identifying the right strategies to take to achieve success. The role of managers with the organisation is to ensure the strategy is delivered through execution of the right tactics, all the while being supported by the leader. Flexible leadership and managing team performance

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 86 of 226 It’s important to recognise that leaders can be found at all levels and roles within practice; leaders are not just those who own the practice. To be effective teams we all need to demonstrate leadership. Of course, in the reality of practice life, we are both leaders and managers; have we taken a step back to understand our natural preference towards leadership or management and are we aware of this in our role? This is all very well, but leadership can appear quite nebulous, so it would be useful to have a model of leadership to compare ourselves to and understand our strengths and potential development areas. One such model has been created by Kouzes and Posner. They were interested in how ordinary people in an organisation achieved extraordinary things. They believed these people could demonstrate that leadership was accessible to everyone. Their book ‘The Leadership Challenge: How to Keep Getting Extraordinary Things done in Organisations (Jossey-Bass, San Francisco, 1995) was based on the results of a questionnaire completed by hundreds of people within organisations. Each person was asked to select a project or event that represented their ‘personal best’ leadership experience. Despite the differences in people’s stories the personal-best leadership experiences revealed similar patterns of action. They found that when leaders were at their personal best they were doing the following things: Challenging the Process Leaders search for opportunities to change the status quo. They look for innovative ways to improve the organisation. In doing so, they experiment and take risks. And because leaders know that risk taking involves mistakes and failures they accept the inevitable disappointments as learning opportunities. Inspiring a Shared Vision Leaders believe that they can make a difference. They envision the future, creating an ideal and unique image of what the organisation can become. Through effective communication and providing clarity on their vision, leaders align their team to the vision. They bring their visions to life and get people to see exciting possibilities for the future.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 87 of 226 Enabling Others to Act Leaders foster collaboration and build effective teams. They actively involve others. Leaders understand that mutual respect is what sustainable performance; they strive to create an atmosphere of trust and respect. They empower others, making each person feel capable and powerful. Modelling the Way Leaders establish principles concerning the way people should be treated and the way goals should be pursued. They create standards of excellence and then set an example for others. Because the prospect of complex change can overwhelm people and stifle action, they set interim goals so that people can achieve small wins as they work toward larger objectives. They unravel bureaucracy when it impedes action, they put up signposts when people are unsure of where to go or how to get there; and they create opportunities for success. Encouraging the Heart Accomplishing extraordinary things in organisations is hard work. To keep hope and determination alive, leaders recognise contributions that individuals make. In every winning team the members need to share in the rewards of their efforts so leaders celebrate accomplishments. They understand the importance of reward and recognition. As well as having a model of leadership to be guided by, we also need to recognise that we each will have a personal style of leadership and research suggests there are five: 1. Controlling 2. Influencing 3. Conferring 4. Involving 5. Delegating Controlling leaders like to be responsible for making decisions and can find it difficult to delegate. They ensure that members of staff receive clear instructions and detailed plans as to the way in which they work. They believe that it is important to monitor the progress of staff on a regular basis to ensure that they keep to an agreed schedule. Influencing leaders use their powers of persuasion to achieve results and to win their staff over to their way of thinking. They often offer incentives and rewards to staff for behaving in a particular way. They are strong negotiators and are prepared to change their own

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 88 of 226 behaviour in order to obtain desired outcomes. They are flexible when it comes to rule following and are able to use their awareness of internal politics to achieve results. Conferring leaders like to gain input from staff at different stages of the decision-making process and are interested to hear their opinions and views on how projects/ tasks should be approached. They will give full consideration to staff input, but take control of the final analysis and prefer to keep control of final decisions. Ultimate choices will reflect the leader’s final analysis and may be in direct conflict with staff opinion. Involving leaders believe in the importance of including all staff in decision-making. These leaders are friendly and caring and take particular care over the well-being of their staff. Each staff member’s opinion is valued and they are encouraged to contribute at each stage of the decision-making process. Involving leaders prefer to make decisions that are the result of group discussion and are prepared to take extra time over decisions to ensure that all staff members have their say. Delegating leaders like to allow staff to take responsibility for planning their own work and making their own decisions with regards to the way in which tasks should be approached. Delegating leaders are happy to pass on ‘ownership’ of tasks to their staff with relatively little instruction and are comfortable leaving staff to work independently on assigned tasks. They have little involvement in the day-to-day concerns of staff and prefer to leave staff to their own devices. You will appreciate that an effective leader will be a person who knows their own style, but can be flexible to adopt a different style as the situation requires. A way to understand what these different scenarios are, is to consider the competency ladder where team members move from unconscious incompetence through to unconscious competence; each step of the ladder requires a different leadership strategy. Knowing what leadership is, what your natural style is and how to flex to other leadership styles, when the situation requires, combine to make you an effective leader and enable team performance.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 89 of 226 HYPEROSMOLAR HYPERGLYCAEMIC STATES IN DOGS AND CATS Søren Boysen, DVM, DACVECC University of Calgary, Faculty of Veterinary Medicine srboysen@ucalgary.ca There are two major complications of diabetes mellitus: diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndromes (HHS). Both conditions are very complex and often have entire books devoted to them. These proceedings will emphasize the key points regarding pathophysiology, treatment considerations and potential complications in the management of HHS. KEY POINTS:  In diabetic patients, an underlying condition causing decreased GFR that prevents glucose excretion can result in HHS  In patients with HHS, it is very important to identify this underlying disease process  Patients with HHS tend to be very ill, requiring 24-hour hospital care and intravenous catheterization with repeat/serial blood sampling  In patients with HHS, start fluid therapy immediately and delay insulin administration for several hours, only start insulin therapy after euvolemia is achieved and good renal perfusion is established PATHOPHYSIOLOGY The metabolic derangements HHS arise from two major issues: 1) a relative or absolute insulin deficiency, combined with 2) a decreased glomerular filtration rate (GFR) and increased concentrations of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). In uncomplicated diabetes mellitus with hyperglycemia that exceeds the renal threshold for glucose clearance, glucosuria and osmotic diuresis occur. HHS can develop in diabetic patients with a concurrent or underlying disease that causes decreased GFR. The reduction in GFR may be pre-renal (dehydration or hypovolemia), renal, or post-renal in origin. A decreased GFR results in decreased glucose clearance by the kidneys, which exacerbates the severity of hyperglycemia. In diabetic humans with HHS, an inverse relationship between GFR and blood glucose concentration has been demonstrated (blood glucose rises as GFR decreases). Hyperosmolar/hyperglycaemic states in cats and dogs

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 90 of 226 Common underlying diseases that contribute to decreased GFR in cases of HHS include shock, renal failure, and heart failure. These diseases should be considered and ruled out in patients that develop HHS. Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, and sympathomimetic agents, have also been reported to precipitate HHS, even in patients receiving insulin therapy and in patients that have had no prior history of diabetes. Although not well established, it is believed that ketone formation is minimal in cases of HHS, due to the presence of low levels of insulin, which are sufficient to effectively inhibit lipolysis but insufficient to control blood glucose concentrations. Ketones are often absent in HHS patients, although this is not a requirement for diagnosis. Some cases with HHS may have some degree of ketoacidosis present and some DKA patients may also meet the criteria of HHS. It may be necessary to treat both conditions simultaneously. *** In summary, decreased GFR (from any disease state), combined with insulin deficiency and increased counter regulatory hormones in diabetic patients, results in decreased renal clearance of glucose with subsequent increases in blood glucose concentration. DIAGNOSIS Criteria for the diagnosis of HHS include: 1) glucose concentration > 30 mmol/L, 2) calculated total serum osmolality > 350 mOsm, and 3) usually an absence of ketones in the urine. Effective serum osmolarity can be calculated from the biochemistry panel using the following equation: Effective serum osmolality (mOsm) = 2x[serum sodium concentration (mmol/L)] + [serum glucose concentration (mmol/L)] Some clinicians add potassium to the equation so that serum osmolality = 2x[sodium + potassium] + [glucose]. However, the potassium concentration cannot increase significantly without killing the patient so other clinicians choose to ignore potassium. Although urea does contribute to serum osmolality, urea freely crosses the cell membranes so it cannot contribute to fluid osmosis and is therefore not included in the calculation of “effective” osmolality.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 91 of 226 PROGNOSIS The prognosis in cases of HHS varies depending on the severity of concurrent diseases. Underlying diseases have been identified in 69 - 92% of patients with either DKA or HHS, including infection, neoplasia, heart failure, renal failure, pancreatitis, gastrointestinal tract disease, hyperadrenocorticism, hepatic disease, dermatitis, and uterine disease. Patients with HSS should be given a guarded prognosis (but that’s why we love critical care – to fix cases that have a guarded prognosis). ASSOCIATED COMPLICATIONS Acid-base imbalance Acidosis can be a serious complication in dogs and cats with HHS, particularly in cases with concurrent DKA. The cause of acidosis is multifactorial. Ketosis can contribute to the development of acidosis. Patients with ketosis have excess of acetoacetic and beta-hydroxybutyric acid (organic acids). Acetoacetic acid is the initial ketone produced by the liver, which may then be reduced to beta-hydroxybutyric acid or non-enzymatically decarboxylated to acetone (chemically neutral). At physiologic pH, acetoacetic and beta-hydroxybutyric acid dissociate completely, resulting in the production of hydrogen ions and ketoanions. The hydrogen ions are buffered by bicarbonate, resulting in acidosis when bicarbonate is depleted. Lactic acidosis can also contribute to acidosis. In patients with HHS, lactic acidosis commonly results from hypoperfusion or hypovolemia secondary to fluid loss in the urinary and GI tracts. Renal failure is often identified in cats with HHS, which may be associated with significant renal azotemia that contributes to the development of acidosis. Finally, hyperchloremic metabolic acidosis may also occur in HHS patients, as a result of chloride retention when ketoanions (negatively charged) are secreted with sodium or potassium (positively charged) in place of the chloride anion. The use of chloride rich fluids (such as 0.9% saline) during fluid therapy may also contribute to hyperchloremic metabolic acidosis. This acidosis is usually self-limiting and of minimal clinical significance as it tends to resolve within 24-48 hours following initiation of fluid therapy due to enhanced renal acid excretion.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 92 of 226 Fluid balance: Multiple factors contribute to fluid losses in patients with HHS. Each patient must be assessed individually to estimate initial losses and re-evaluated regularly to account for ongoing losses. Hyperglycaemia, and to a lesser extent ketosis, induce osmotic diuresis which results in fluid loss, which can be severe in patients with HHS. Vomiting and diarrhea, frequently reported clinical signs in patients with HHS, can also contribute to fluid losses. Concurrent diseases (such as renal failure, vasculitis, liver failure, and hyperadrenocorticism) can also affect fluid losses and need to be considered when assessing the patient's fluid therapy regime. Electrolyte imbalances: Sodium: Patients with HHS can have low, normal or high plasma sodium concentration, however most studies show hyponatremia at the time of presentation (based on the uncorrected sodium concentration). Hyponatremia is often a consequence of hyperglycaemia; as elevated blood glucose concentrations cause an osmotic shift of fluid into the vascular space which dilutes the sodium concentration. In patients with HHS, it has therefore been recommended that a corrected sodium concentration be calculated relative to the degree of hyperglycaemia by adding 1 mmol/L to the measured sodium concentration for every 3.5 mmol/L increase in glucose above normal, to more accurately reflect the true intracellular hydration status of the patient. Potassium and phosphorus: Patients with HHS often have profound depletion of total body potassium and phosphorus, despite some animals presenting with normal to elevated plasma concentrations of these electrolytes (remember that the plasma concentration does not accurately reflect total body concentration, especially for electrolytes that are predominantly intracellular). Extracellular potassium and phosphorus are lost via the kidneys through osmotic diuresis and insulin deficiency. Osmotic diuresis increases delivery of fluid to the distal nephron and dilutes electrolyte concentrations within the tubular lumen, resulting in decreased renal re-absorption of these electrolytes (intraluminal ion concentration plays an important role in the re-absorption of many electrolytes and diluting their concentration decreases their absorption). Insulin is required for normal sodium, chloride, potassium, and phosphorus absorption in tubular epithelial cells. Further depletion of electrolytes occurs due to anorexia, vomiting and diarrhea.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 93 of 226 TREATMENT The primary treatment objectives in patients with HHS include: 1) restore intravascular volume 2) correct dehydration 3) correct electrolyte and acid base disturbances 4) decrease glucose concentrations 5) identify and address any underlying diseases HHS is considered a life-threatening emergency, so therapy should always involve 24-hour hospitalization of the patient. Fluids The first priority in patients with HHS is to restore intravascular volume through the administration of fluids. If the patient presents in shock, priority is given to achieving cardiovascular stability and reversing the state of shock. If the patient is cardiovascularly stable, fluid therapy will vary according to the degree of dehydration and clinical signs of the patient. If the patient is alert, eating, drinking, and does not show significant systemic signs of illness, aggressive fluid therapy is unnecessary. However, the vast majority of patients with HHS will present with moderate to severe fluid and electrolyte imbalances and systemic signs of illness that necessitate aggressive fluid resuscitation. It is very important to initiate fluid administration before starting insulin therapy. Fluid losses are a major contributing factor to the development of severe hyperglycaemia, so priority must be given to restoring fluid volume in the extracellular space (intravascular and interstitial) and improving renal perfusion prior to starting insulin therapy. Fluid administration decreases glucose levels through dilution of blood glucose and increased renal perfusion (improved GFR and increased renal glucose clearance). Fluid administration alone (prior to insulin therapy) has been shown to decrease glucose levels by 30-50% in children with DKA (and may be similar in HHS) during the first hour of fluid therapy. Fluid therapy also decreases levels of counter-regulatory hormones and reduces serum osmolality, which makes cells more responsive to insulin. Starting both fluids and insulin simultaneously can cause potentially dangerous changes in osmolality with subsequent rapid shifts in fluid between intracellular and extracellular spaces. If insulin therapy is initiated prior to restoring intravascular volume and establishing good tissue perfusion, rapid movement of glucose and water from the vascular space into the cells can lead to vascular collapse, shock, and death. It is therefore recommended to delay

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 94 of 226 insulin therapy for at least 2 hours following the initiation of fluid therapy in critically ill HHS patients, especially in cases with severe hyperglycaemia and/or hypotension. Once the patient is no longer in shock and renal perfusion (urine output) has improved, insulin therapy should be initiated. In patients with HHS that present without shock and with adequate tissue perfusion, dehydration should be corrected gradually. Decreasing serum osmolarity too quickly can cause cerebral edema. Chronic hyperglycaemic hyperosmolarity (>48 hours) results in the production of idogenic osmoles in brain cells (to counterbalance increased plasma osmolarity). These idogenic osmoles take time to be eliminated. If plasma osmolarity is corrected too quickly with administration of intravenous fluids, idiogenic osmoles in brain cells cannot be eliminated quickly enough to keep pace with decreasing intravenous osmolarity, and cerebral edema may result. To reduce the risk of cerebral edema during fluid therapy in patients with HHS, it has been recommended that the plasma osmolality should decrease by no more than 1-2 mOsm per hour. Isotonic fluids are recommended for patients with HHS, because hypotonic fluids are more likely to contribute to rapid decreases in serum osmolarity which increases the risk of cerebral edema. Fortunately, development of clinically significant cerebral edema is rare, but this possibility should be considered in HHS patients, particularly patients that fail to respond appropriately to initial therapy. A practical approach to monitoring serum osmolality clinically is to calculate the effective osmolality. As described above, effective serum osmolality (mOsm) = 2x[serum sodium concentration (mmol/L)] + [serum glucose concentration (mmol/L)]. It is important to remember that this equation represents total effective osmolality, so it is the NET change in effective osmolality that is important in reducing the risk of cerebral edema rather than individual changes in sodium and glucose concentrations independently. For example, a decrease in osmolality of 5mOsm per hour due to a decrease in serum glucose concentration, coupled with an increase in osmolality of 4mOsm per hour caused by an increase in serum sodium concentration, would result in an overall decrease in effective osmolality of only 1 mOsm per hour. To monitor changes in effective serum osmolality, it is recommended that blood glucose be evaluated hourly and electrolytes be measured once during the first two hours of therapy and every 4-6 hours thereafter until normal hydration status is restored. If evaluation of electrolytes is not readily available, blood glucose should be monitored hourly to prevent any

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 95 of 226 decrease greater than 5 mmol/L/hr. If the glucose concentration is decreasing too rapidly (>5mmol/L/hr), then dextrose (2.5%) can be added to IV fluids and/or the insulin infusion rate can be adjusted if insulin therapy has already been initiated (see below). Hourly blood glucose evaluation can be facilitated by placement of a peripheral inserted central (PIC) line or central venous catheter to allow repeated blood sampling, or by use of the marginal ear vein to obtain capillary blood samples. Potassium In patients with HHS, fluid therapy and insulin administration often result in a rapid decrease in potassium concentration within the few hours of therapy. Potassium supplementation is required in the majority of cats and dogs with HHS. If patients present with hyperkalemia, fluid therapy should be initiated with non-potassium-containing fluids until renal perfusion has improved and underlying oliguric or anuric renal failure has been ruled out (a urinary catheter can be placed to monitor urine output). Once renal perfusion is adequate (urine output > 2.0 ml/kg/hr), potassium should be supplemented according to serum potassium levels (see table 1). If patients present with normal potassium concentration or hypokalemia, then potassium should be added to the fluids administered and insulin administration should be withheld until intravascular volume is restored and hydration status has improved (see table 1). After starting fluid or insulin therapy, electrolytes should be re-evaluated 1-2 hours later, then every 4-6 hours afterwards until normal hydration and glucose control are achieved. If electrolyte monitoring is unavailable, it is usually safe to add 20-40 mEq/L of potassium to fluids in patients with normal renal function. In patients that remain hypokalemic despite aggressive potassium supplementation (up to 0.5 mEq/kg/hr), the magnesium concentration should be evaluated. Correcting potassium concentration may not be possible without concurrently correcting magnesium concentration. If hypomagnesemia is present and associated with refractory hypokalemia or arrhythmias, an infusion of magnesium should be started: magnesium sulfate added to 5% dextrose in water, 0.75-1 mEq/kg/day CRI, with the CRI dose reduced by 50% for the following 3-5 days. Phosphorus Patients with HHS may require phosphorus supplementation in the first 12-48 hours of therapy. Clinical signs associated with hypophosphatemia are rare, usually restricted to

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 96 of 226 hemolytic anemia in cats and possibly stupor and seizures in dogs. However, serum phosphorus concentrations should be measured and it is recommended to start phosphate supplementation if phosphorus concentrations are < 0.5 mmol/L. Phosphorus supplementation involves administering 0.01-0.06 mmol/kg/hr of potassium phosphate in 0.9% saline. Infusions of up to 0.12 mmol/kg/hr have been used to rapidly increase phosphate levels to 0.8 mmol/L, however caution should be used as higher doses may lead to hypocalcaemia, tetany, and soft tissue mineralization. Repeated phosphorus and calcium measurements (every 12-24 hours) are recommended during phosphorus supplementation. Insulin Insulin corrects hyperglycaemia, decreases ketone production (inhibits lipolysis and decreases glucagon secretion), and may augment ketone utilization. In critically ill patients with HHS, regular crystalline insulin (short half-life, rapid acting) should be administered as a low dose CRI or by intermittent intramuscular injections. Low dose insulin therapy allows a more gradual decrease in glucose of 2-4 mmol/L/hr to prevent rapid changes in osmolality (reduces the risk of cerebral edema) and decreases the risk of inducing hypoglycaemia, hypokalemia, and other electrolyte imbalances. Low dose insulin IV protocol involves adding regular insulin (2.2 U/kg for dogs and 1.1 U/kg for cats) to 250 ml of 0.9% saline and adjusting the rate of administration based on hourly evaluation of glucose and the use of a sliding scale (table 2). Low dose insulin IM protocol involves an initial dose of 0.2 U/kg of regular insulin IM, followed by 0.1 U/kg IM hourly. Blood glucose should be monitored hourly. Once blood glucose reaches 14 mmol/L, the injection schedule is adjusted to 0.1-0.4 U/kg SC every 4-8 hrs and 50% dextrose is added to fluids to make a 5% solution. Injections are continued SC at 0.1-0.4 U/kg every 4-8 hours, with the insulin dose and injection interval readjusted depending on glucose measurements every 1-2 hours. The goal is to maintain blood glucose between 11-16.5 mmol/L. These IM and IV protocols are only initial guidelines. Higher or lower doses of regular insulin and shorter or longer injection intervals may be required based on the patient’s response. If the IM or IV insulin protocols described above do not result in decreasing glucose concentration by 2-3 mmol/L/hr within the first hour, hydration status should be reassessed.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 97 of 226 If hydration status is acceptable, the insulin dose should be increased every hour (by 50-100%) until a decrease of 2-4 mmol/L/hr in plasma glucose concentration is observed. Thereafter, the insulin dose should be adjusted to maintain plasma glucose concentration between 11-16.5 mmol/L. Regular insulin therapy should be continued until the patient is eating and drinking, at which time the patient can then be switched to longer acting subcutaneous insulin. Table 1 Potassium supplementation (amount of potassium to add to 1 liter of intravenous fluid when given at maintenance fluid rates). NOTE: do not add potassium to fluids used for initial resuscitation! Serum K (mEq/L) K supplement/L 3.5 20 3.0–3.5 30 2.5–3.0 40 2.0–2.5 60 2.0 80 Table 2 Recommended adjustments for intravenously administered regular crystalline insulin and intravenously administered dextrose in DKA or HSS patients, after initial rehydration (dogs: 2.2 U/kg in 250 mL 0.9 % saline; cats: 1.1 U/kg in 250 mL 0.9 % saline). Blood glucose (mmol/L) Fluid type (250-mL bag) Fluid rate (mL/h) >15 0.9% saline 10 12–15 0.9% saline + 2.5% dextrose 7 8–12 0.9% saline + 2.5% dextrose 5 5–8 0.9% saline + 5% dextrose 5 <5 0.9% saline + 5% dextrose Stop insulin infusion Adapted from Macintire DK. Emergency therapy of diabetic crisis: insulin overdose, diabetic ketoacidosis, and hyperosmolar coma. Vet Clin North Am Small Anim Pract 1995;25(3):646; with permission.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 99 of 226 PROFESSIONAL DILEMMAS DISCUSSION FORUM With panellists including Amanda Boag MA VetMB DipACVIM DACVECC FHEA DipECVECC MRCVS, Sophie Adamantos BVSc CertVA DACVECC DipACVECC MRCVS FHEA, and Louise O’Dwyer MBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVN The challenges we face on a daily basis in clinical practice relate as much to our professional issues as our clinical ones – areas such as communication, teamwork and interpreting our Professional Codes of Conduct across the full range of situations we find ourselves in can be really difficult. In this session the panel will explore a range of scenarios where issues relating to professional standards arise and will debate with the audience the best way to approach them. Professional dilemmas discussion forum

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 101 of 226 ACUTE LUNG INJURY/ACUTE RESPIRATORY DISTRESS SYNDROME Søren Boysen, DVM, DACVECC University of Calgary, Faculty of Veterinary Medicine srboysen@ucalgary.ca INTRODUCTION Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are pulmonary complications that can develop secondary to an inflammatory state anywhere in the body. ALI and ARDS are associated with abnormal lung function and respiratory distress. HISTORY AND CLINICAL SIGNS ALI and ARDS occur secondary to an inflammatory process anywhere in the body, so patients may initially present with history and clinical signs associated with the primary inflammatory disease and not develop clinical signs of respiratory distress until several days later. For example, a dog may present with multiple long bone fractures following motor vehicle trauma with no initial respiratory issues, but later develop signs of respiratory distress while in hospital. In this case, an inflammatory process distant from the lungs (long bone fractures) creates systemic inflammation that subsequently results in ALI/ARDS. In other cases, the animal may present with a primary lung problem (i.e. aspiration pneumonia), which fails to improve or deteriorates while hospitalized, which may indicate the onset of ALI/ARDS. Once ALI/ARDS has developed, the most frequently reported clinical signs include tachypnea, dyspnea (increased effort of breathing, often pronounced), cyanosis, and hypoxemia. A cough may also be present, and the cough associated with ALI/ARDS is often paroxysmal on tracheal palpation. Physical examination may reveal increased breath sounds or crackles on auscultation. The patient may also display abdominal breathing, open mouth breathing, and/or frothy pink exudate coming from the respiratory tract. Not all patients that develop respiratory distress while hospitalized have ALI or ARDS. The most common causes for hospital-acquired respiratory distress include ALI and ARDS, aspiration or bacterial pneumonia, congestive heart failure (CHF) secondary to fluid overload, and pulmonary thromboembolism. DIAGNOSIS In 2007, a panel of veterinary experts published a set of five criteria to accurately diagnose Acute lung injury/acute respiratory distress syndrome

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 102 of 226 ALI/ARDS in veterinary patients. Four of these criteria are required for a diagnosis, and the fifth is optional. Criteria 1 - acute onset: the patient must be dyspneic at rest and dyspnea should have developed in less than 72 hours. The timing of the onset of dyspnea should be determined based on the patient's history. Criteria 2 - risk factors: the patient must have a primary underlying disease process (risk factor) that causes enough inflammation to precipitate a reaction in the lungs. A thorough history, physical exam, and diagnostic testing (complete blood count, serum chemistry profile, urinalysis, imaging) is usually sufficient to detect the underlying inflammatory state. See table 1 for common risk factors for ALI/ARDS. Note that this list is not all-inclusive (any disease process associated with significant inflammation can cause ALI/ARDS). Table 1. Risk factors for ALI/ARDS in veterinary patients. Immune mediated diseases Infection Sepsis Systemic inflammatory response syndrome (SIRS) Severe trauma Long bone fracture Head injury Pulmonary contusion Multiple transfusions Smoke inhalation Near-drowning Aspiration of stomach contents Drugs and toxins Criteria 3 - evidence of pulmonary capillary leak without evidence of increased hydrostatic pressures: this criterion can be verified by one or more of the following: 1) diffuse or bilateral infiltrates on thoracic radiographs (more than 1 quadrant), 2) proteinaceous fluid within the conducting airways, 3) bilateral dependent density gradient on CT, 4) increased extravascular lung water.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 103 of 226 This criterion is designed to rule out heart failure as the cause of abnormal lung function. CHF produces low protein pulmonary edema due to increased hydrostatic pressures, while ALI and ARDS produce a high protein content edema through increased vascular permeability. Proteinaceous fluid within the conducting airways is therefore consistent with ALI and ARDS. In patients with suspected ALI/ARDS, heart disease or CHF should be ruled out with echocardiography and imaging of the lungs is required to document pulmonary changes consistent with ALI/ARDS. Imaging: the typical fluid distribution in ALI and ARDS results in a bilateral or diffuse pattern of infiltrate on thoracic radiographs that involves more than one quadrant or lobe. These changes can be quite variable, however, and may range from increased interstitial and peribronchial patterns to diffuse, bilateral alveolar infiltrates. The pulmonary vasculature should appear normal (no evidence of venous congestion/distension which would suggest CHF). Cardiac function assessment: if pulmonary infiltrates are present on thoracic radiographs, the next step is to rule out edema resulting from CHF. Echocardiography evaluates left atrial size and systolic function quickly and accurately. A lack of left atrial enlargement or systolic dysfunction supports the finding of non-cardiogenic pulmonary edema associated with ALI and ARDS. Criteria 4 - evidence of inefficient gas exchange: this criterion can be verified by one or more of the following: 1) hypoxemia defined by PaO2/FiO2 ratio, 2) increased alveolar-arterial oxygen gradient, 3) venous admixture (non-cardiac shunt). Inefficient gas exchange is confirmed by the presence of hypoxemia, which may be defined by arterial oxygen pressures or arterial hemogolobin oxygen saturation. PaO2: the PaO2 should be 80-110 mmHg in patients that are breathing room air at sea level. If the patient is receiving oxygen supplementation, the PaO2 should be approximately five times the percentage of oxygen being supplemented. SpO2: pulse oximetry is a widely available non-invasive tool that can be used to provide a quick assessment of oxygenation by indirectly measuring the oxygen saturation of hemoglobin (SpO2). This tool may be useful when blood gas analysis is not available, but it has several disadvantages. SpO2 measurement can be difficult to perform in animals with a thick coat, pigmented skin, or poor perfusion (SpO2 may underestimate the true oxygen saturation in these circumstances). Strategies to ensure accurate SpO2 readings include

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 104 of 226 minimizing movement of the patient, using the probe on thin skin that is adequately perfused, comparing the measured heart rate to the actual heart rate of the patient, ensuring a proper waveform (on machines that record wave forms), and taking several consistent SpO2 readings. Finally, SpO2 cannot differentiate PaO2 values >100 mmHg; the results will all be 97-100% regardless of the PaO2 value >100 mmHg. Therefore, animals receiving oxygen supplementation that have significant lung dysfunction may still have a SpO2 of 99-100% as long as their PaO2 remains above 100 mmHg. PaO2/FiO2 ratio: arterial blood gas results can be further analyzed to determine the ratio of PaO2 to the fraction of inspired oxygen (FiO2). The PaO2/FiO2 ratio is used to determine the severity of respiratory compromise and is the only factor that distinguishes ALI from ARDS. A ratio of <300 indicates ALI, and a ratio <200 is diagnostic of ARDS in veterinary patients. A recent consensus statement in the human literature (Berlin definition) suggests categorizing ARDS into 3 classes of severity (not just two) in the following manner: mild (PaO2/FiO2 <300), moderate (PaO2/FiO2 <200), severe (PaO2/FiO2 <100). The PaO2/FiO2 ratio also allows accurate comparison between different arterial samples (PaO2) taken when the patient may have been receiving different levels of oxygen supplementation (FiO2). Criteria 5 - evidence of pulmonary inflammation: this is the only criterion for diagnosing ALI and ARDS that is optional (not strictly necessary for diagnosis but provides strong confirmatory evidence). Transtracheal wash or bronchoalveolar lavage samples taken from animals with ALI or ARDS demonstrate the presence of inflammation; cytologic examination reveals predominantly neutrophils (suppurative inflammation but not necessarily septic inflammation). When these diagnostic samples are tested for inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1, these substances are increased from normal values. However, these tests may be contraindicated due to the risks associated with anesthesia or the procedure itself. PROGNOSIS In humans, the mortality rate associated with ARDS varies between references of 30-60% depending on the study and severity of ARDS. The presence of more than one risk factor significantly increases the likelihood of developing ARDS. Genetic and environmental factors (such as smoking) play a role. The most common risk factors for ARDS reported in the human literature include aspiration pneumonia, pancreatitis, pulmonary contusion, traumatic injury, fat embolism, ischemia/reperfusion, and sepsis. A study in dogs showed similar results. ARDS is often complicated by the development of non-pulmonary organ failure,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 105 of 226 which results in higher mortality. TREATMENT Supportive therapy and treatment of the underlying cause are the most important aspects of therapy for ALI and ARDS. Patients that develop ARDS carry a very guarded prognosis, are labor intensive, and can be very expensive to treat. They often require referral to a 24-hour facility for proper care. Patients with ALI carry a better prognosis, and response to therapy will often provide a more accurate prognosis to help guide therapeutic decisions. The underlying disorder (risk factor) should be fully evaluated and treated aggressively and specifically, if possible. Fluid therapy: supportive care should include maintaining organ perfusion with appropriate fluid therapy. Some clinicians advocate conservative use of fluids due to increased permeability of lung vasculature with associated risk of inducing or exacerbating pulmonary edema in these patients. Blood pressure should be closely monitored to ensure that the patient does not become hypotensive, which occurs frequently in septic patients. If the patient has been sufficiently volume-loaded and hypotension persists, use of vasopressors such as dobutamine, dopamine, vasopressin, or norepinephrine may be required. Oxygen therapy: oxygen therapy is vital in managing patients with ALI and ARDS. Animals can tolerate 100% oxygen for up to 24 hours, and then up to 60% oxygen thereafter without concern for oxygen toxicosis (prolonged exposure of the alveoli of the lung to high oxygen concentrations can lead to oxygen free radical production in the lung and subsequent cell injury). High oxygen concentrations may be difficult to obtain unless a tightly sealed oxygen cage is available. Closely monitor the patient’s response during oxygen supplementation, and consider obtaining samples for serial blood gas analysis to check for hypoxemia. If a patient remains persistently hypoxemic with a PaO2 <60 mm Hg, a PaCO2 >60 mm Hg, or increased respiratory effort despite receiving oxygen therapy, consider mechanical ventilation (see below). Mechanical ventilation: almost all humans with ARDS require ventilation for respiratory support. ARDS reduces lung compliance, so over time respiratory effort increases, which eventually causes respiratory muscle fatigue. Ventilator therapy helps decrease fatigue by performing the work required for breathing. Any animal with excessively labored respirations may be a candidate for mechanical ventilation. Additionally, ventilator therapy allows the delivery of higher oxygen concentrations than can be obtained through routine methods and may re-inflate alveoli that were collapsed, which can help keep patients alive until the

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 106 of 226 underlying cause can be reversed. Other therapies: additional supportive care measures that have been attempted in people include antibiotics, gastric ulcer prophylaxis, nitric oxide administration, surfactant replacement, specific cytokine therapy, glucocorticoid therapy, and nutritional management. No strong evidence supports or negates these treatment options, and further studies are required before such therapies can be recommended in veterinary patients. CONCLUSION ALI and ARDS are secondary disorders caused by a severe inflammatory reaction originating somewhere in the body (in the lung or at a site distant from the lung). Diagnosis is based on the presence of four main criteria: acute onset of respiratory distress, presence of underlying risk factors, evidence of pulmonary capillary leak without increased hydrostatic pressures, and evidence of inefficient gas exchange. The most important diagnostic tests include a thorough history, thoracic radiography, echocardiography, and arterial blood gas analysis. Treatment involves addressing the underlying inflammatory condition and providing supportive therapy. Mechanical ventilation may also be required. ALI and ARDS are common complications that develop in hospitalized patients, so it is important for all small animal practitioners to be able to diagnose them and initiate treatment early and aggressively, with referral to a critical care facility if necessary. However, by the time ALI or ARDS is diagnosed, safe referral may be difficult unless a critical care facility is only a short distance away or veterinary care can be provided during transport. Diagnosing ALI or ARDS provides important prognostic information for clients. REFERENCES Matthay M, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest. 2012;122(8):2731-2749. Barbas, C.S., Matos, G.F.J., Amato, M.B.P. and Carvalho, C.R.R. (2012) Goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome. Critical Care Research and Practice. 2012 Article ID 952168, 13 pages. Wilkins, Otto, Baumgardner et al. Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: The Dorothy Russell Havemeyer working group on ALI and ARDS in veterinary medicine. J Vet Emerg Crit Care. 2007;17(4):333-339

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 107 of 226 RADIOLOGY OF THE PATIENT WITH ACUTE DYSPNOEA. WHERE IS THE PROBLEM? Jennifer Kinns VetMB DipECVDI DACVR MRCVS IDEXX Telemedicine Radiographs play a key role in evaluation of many acutely dyspnoeic patients. Radiographic interpretation in conjunction with clinical evaluation should differentiate upper and lower airway, cardiovascular and mediastinal or pleural space disease. Thoracic radiology is challenging, and a systematic approach to interpretation is essential to best determine the underlying disease process. Evaluation of any thoracic radiograph should include assessment of the extra-thoracic structures, included upper airway, mediastinum and pleural space as well as the pulmonary parenchyma and cardiovascular structures. Accurate interpretation depends in part on the quality of the radiographic study. Inappropriate exposure or positioning can result in missed lesions or over-interpretation. Appropriate patient preparation and restraint (chemical or with positioning aids) is necessary. Clinical assessment can help to determine the appropriate study. If an upper airway lesion is possible for example, inclusion of the pharyngeal, laryngeal and cervical region is recommended. This lecture will use case examples to illustrate some of the radiographic findings associated with various causes of acute dyspnoea in canine and feline patients. Upper Airway lesions Tracheal collapse is a frequent cause of acute dyspnea in predisposed breeds and may occur as a co-morbidity and be exacerbated by inflammatory disease. Radiographically any part of the cervical on intra-thoracic trachea or the mainstem bronchi may be narrowed. Dynamic airway collapse is not always evident on survey radiographs. A redundant dorsal tracheal membrane may be visible and has been associated with collapse in predisposed patients, but should not be confused with luminal narrowing. If collapse is suspected but is not identified on survey radiographs, dynamic imaging could be used for further assessment. Other causes of tracheal narrowing should not be overlooked. Severe tracheitis can cause diffuse radiographic narrowing. Mass lesions can cause focal narrowing, deviation or compression of the upper airway and mediastinal haemorrhage secondary to toxic coagulopathy can result in marked tracheal narrowing and acute dyspnea. Occasionally inhaled foreign material may be identified radiographically, though more often this is considered due to the secondary changes that occur. Radiology of the patient with acute dyspnoea. Where is the problem?

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 108 of 226 Respiratory and cardiac causes of acute dyspnoea Differentiating respiratory from cardiac disease is a primary reason for obtaining thoracic radiographs in dyspnoeic patients. The pulmonary pattern, distribution of pulmonary changes and appearance of the cardiovascular structures contribute to this distinction. In canine patient’s cardiogenic oedema typically has a caudodorsal and perihilar distribution, though it can be more patchy, and in some patients peribronchial oedema causes radiographic “cuffing” of the airways. Left sided congestive failure is typically accompanied by radiographic enlargement of the left atrium, which causes a loss of the caudal cardiac waist on lateral views, and general cardiomegaly. Venous distension is often present, but will be masked by prior diuresis. Left cardiac enlargement is frequently seen in small breed dogs with endocardiosis but co-morbities such as airway collapse may be present, and systematic radiographic evaluation and close clinical correlation is necessary to determine the cause of acute dyspnoea. It should also be noted that large breeds with dilated cardiomyopathy, such as the Doberman, can present in cardiac failure with minimal radiographic changes to the cardiac silhouette. In feline patients, differentiating primary respiratory from cardiac disease presents a unique challenge. Cardiogenic oedema in cats has a very variable distribution and can be patchy and dorsal or ventral in distribution, and may also be peribronchial. The vertebral heart scale can be useful to determine which patients are more likely to have cardiac disease as a cause of acute dyspnea. A VHS of >9.3 has been closely associated with a cardiac origin in acute respiratory patients.1 Some patients with cardiomyopathy may have a normal cardiac size, and an echocardiogram may be necessary for definitive diagnosis when radiographs are equivocal. Trial treatment for cardiac failure may be administered and can be assessed with follow up radiographs in 12-24 hours. Appropriate differentials for respiratory disease can be determined by the radiographic appearance and distribution. Non-cardiogenic oedema typically has a markedly caudodorsal radiographic distribution of an interstitial and alveolar pattern and can be symmetric or asymmetric. This diagnosis is correlated with an appropriate clinical history such as head trauma, seizure, upper airway obstruction, electrocution or anaphylaxis. SIRS or ARDS associated oedema should also be considered. Haemorrhage can have an interstitial or alveolar appearance and is patchy in distribution. Trauma associated pulmonary contusion is often associated with other radiographic evidence of trauma such as pneumothorax, 1 Sleeper, MM; Roland R and Drobatz KJ; J Am Vet Med Assoc 2013; 242:366-371

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 109 of 226 pleural effusion and osseous trauma. Bacterial bronchopneumonia (due to aspiration or primary infection) is most often a patchy ventrally distributed alveolar pattern. The right middle and left cranial lung lobes are predisposed. Acute exacerbation of lower airway disease has radiographic changes associated with the underlying disease process. Feline allergic airway disease is characterized radiographically by pulmonary hyperinflation and a diffuse bronchial pattern. There is poor correlation between the radiographic changes and the severity of the acute presentation. Pulmonary thromboembolism is often a radiographic diagnosis of exclusion and can present with normal radiographs. If present changes are often minimal and include regional hyperlucency and blunting of peripheral pulmonary arteries. Acute pleural space and mediastinal disease Pleural effusion has a similar appearance regardless of the underlying cause. Peripheral soft tissue/ fluid opacity, pleural fissures and lung lobe retraction determine the presence of fluid. Systematic radiographic evaluation may help to determine the underlying cause. A cardiac origin is likely if there is right sided cardiac enlargement or radiographic evidence of pericardial fluid. A mediastinal mass effect, pulmonary mass or nodules or aggressive skeletal lesions suggest a neoplastic process. Thoracocentesis is often appropriate for therapeutic and diagnostic purposes, and repeating radiographs after removal of the pleural fluid can help to determine the underlying cause. Pneumothorax appears radiographically as peripheral hyperlucency with lung lobe retraction. Spontaneous pneumothorax, though uncommon, can occur secondary to ruptured bullae or necrotic lesions, and close assessment may help to determine the cause. Bullae appear as thin walled hyperlucent structures which may be more apparent in underinflated lungs. Radiographs are poorly sensitive to the presence of bullae, and thoracic CT is often recommended in cases of recurrent pneumothorax. Recommended reading 1. Textbook of veterinary diagnostic radiology, sixth edition. Donald E. Thrall. 2012. Elsevier. 2. BSAVA Manual of Canine and Feline Thoracic Imaging Tobias Schwarz and Victoria Johnson 2008.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 111 of 226 DO I NEED TO CUT THIS NOW? RADIOLOGY OF THE ACUTE ABDOMEN Jennifer Kinns VetMB DipECVDI DACVR MRCVS IDEXX Telemedicine Abdominal radiographs play an important role in helping to determine if acute abdominal cases require surgical or medical management. Ultrasound or contrast radiography may provide further information in some cases, but survey radiographs are considered to be the first step in general and emergency practice. Gastrointestinal emergencies Mechanical obstruction is characterized by static or progressive segmental distension of small intestine – a mechanical ileus. Functional ileus, which results in diffuse distension of bowel, is often seen in cases of gastroenteritis or even pancreatitis. Differentiating these can be the difference between medical or surgical management but it can be very difficult, particularly when the small intestine and colon must be recognised. Some serious emergencies, such as mesenteric torsion, can also result in diffuse distension of small intestine, and must be recognized. Linear foreign body obstruction is more difficult to diagnose and rather than segmental distension this is characterized by plication; multiple elliptical and fragmented gas lucencies are present and the margin of the bowel is often irregular and folded. This should be differentiated from corrugation, which can occur with enteritis or less frequently ischaemia. Gastric dilatation and volvulus (GDV) presents as non-productive retching/vomiting and the diagnosis is often radiographic. This is one circumstance where a single lateral view is indicated. On a right lateral projection, the appearance is characteristic. There is typically a soft tissue band resulting in radiographic compartmentalization of the stomach, and the pylorus is abnormally gas filled and dorsally displaced on that view. Not all volvulus cases follow the classic pattern however. 360 torsion is a critical condition which is much more difficult to recognize. Secondary changes that accompany GDV can be helpful in making that diagnosis. The spleen is usually also displaced and frequently enlarged, the small intestines are often diffusely distended, and the oesophagus is usually gas filled. In any case of suspected GDV radiographs should also be assessed for evidence of gastric wall necrosis or perforation (free peritoneal gas). Use of contrast studies in gastrointestinal imaging is less common than previously. Ultrasound provides more detailed evaluation of the gastrointestinal walls in addition to Do I need to cut this now? Radiology of the acute abdomen

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 112 of 226 parenchymal evaluation of the intra-abdominal organs. However, the success of ultrasound evaluation depends on the experience of the sonographer. Focal intestinal lesions are easily missed. An upper GI study could be used to differentiate surgical from non-surgical conditions and the use of barium does not preclude subsequent surgical intervention. A pneumocolonogram is also a very useful method to differentiate the colon from small intestine that could provide an immediate answer as to whether there is small intestinal distension. Upper GI study The upper GI study is an excellent method for additional evaluation of the gastrointestinal tract when ultrasound expertise is not available. The interpretation of an upper GI study is arguably easier than ultrasound, and can be a more definitive means for excluding surgical obstruction. It is essential that the procedure is performed with an adequate volume of contrast and with orthogonal views obtained at regular intervals for this procedure to be diagnostic. Indications Suspected gastrointestinal obstruction is the foremost indication for an upper GI study in emergency practice. This can help determine if surgical intervention is necessary when survey radiographs are not definitive or difficult to interpret. If the patient is clinically stable and survey radiographs are inconclusive I would usually initially recommend follow up fasted survey radiographs in 4-6 hours after any necessary fluid therapy and medical management. Obstructive patterns are either static or progressive. It may also be possible to determine if acute gastrointestinal signs presenting as an emergency are secondary to a more chronic process such as neoplasia. Method The stomach should ideally be empty of food prior to the study. This is not always going to be the case in patients that are potentially obstructed, and the study will help to determine if any gastric contents are retained ingesta or foreign material. Sedation should be avoided due to the effects on gastrointestinal motility, but Acepromazine may be administered at 0.1-0.25mg/kg IM if necessary. For canine patients 5-10ml/kg of 30% weight per volume of micropulverised liquid barium should be administered by either orogastric tube (ideal) or oral syringe. If necessary confirmation of the position of the tube can be obtained with a lateral radiograph. The larger dose would be recommended in smaller animals. For feline patients 12-20ml/kg of contrast

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 113 of 226 is necessary for a diagnostic study. A lesser volume can markedly increase gastric emptying time and lead to a false diagnosis of delay and limited gastric evaluation. Contrast should never be mixed with food for this study. This will also lead to delayed gastric emptying and there will be an irregular appearance to the contrast which can confound interpretation. Immediately after contrast administration initial radiographs should be obtained. A lateral and ventrodorsal view is necessary as a minimum. If there is any concern for a gastric lesion dorsoventral and opposite lateral views will also be necessary as a filling defect associated with a lesion of the wall may only be visible on one view. Follow up lateral and ventrodorsal views are ideally recommended at 30 min, 1 hr, 2 hrs and until contrast has filled the colon and gastric emptying has occurred. Follow up radiographs obtained at 12 hours can help to confirm that all the contrast reaches the colon. If this sequence is not followed a partially obstructive surgical lesion or focal intestinal abnormality could be missed. In cat’s gastrointestinal transit is more rapid and images should also be obtained at 15min. Other contrast agents can be used. Iodinated contrast is typically recommended if gastrointestinal perforation is suspected. However, this does not provide an ideal study. Ionic iodinated contrast is hyperosmolar and will draw water in to the intestines leading to gradual decreased opacification and intestinal dilation which can confuse interpretation and can also lead to decompensation is dehydrated patients. Non-ionic agents are better, but are very expensive for this purpose. Interpretation Gastrointestinal obstruction is characterized by segmental distension of intestine that persists over multiple time points. The distension can be very focal, or more diffuse on the oral side of the obstruction. There will be a delay in passage of contrast beyond the point of obstruction. However, some fluid may pass, and the presence of contrast beyond this does not exclude an obstructive process. A persistent filling defect is frequently (but not always) seen in association with obstructive foreign material. With linear foreign material the focal distension is often not present. Instead there is plication of intestine rather than normal tubular contrast filled bowel. If obstruction is within the pyloric outflow tract there will be delayed gastric emptying, and if there is foreign material there is often a filling defect in the pyloric antrum. Gastric outflow obstruction can also occur with neoplasia, pyloric hypertrophy or pylorospasm, in which case the outflow is persistently narrow on multiple views and can have a ‘beak like’ appearance.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 114 of 226 Pneumocolonogram Diagnosis of an obstructive pattern on survey radiographs relies on the differentiation of small intestine from colon, and this is not always easy. A pneumocolonogram involves the administration of gas (room air is fine) in to the colon. Mild distension of the colon with gas will often confirm its location as compared to potentially distended bowel. Caution should be taken to avoid over-distension of the colon, which can result in damage. Ultrasound evaluation of gastrointestinal emergencies Where ultrasound expertise is available this can be an excellent modality to differentiate surgical from medical causes of acute vomiting. Large volumes of gas do limit ultrasound assessment and, in the author’s experience, this is not a good means to assess for torsion of the stomach, mesentery or colon. It can be very useful to confirm a suspect linear foreign body or mechanical obstruction. It should be noted however that a focal intestinal lesion can be missed as systematic evaluation of the gastrointestinal tract is challenging. Extra-intestinal causes of acute vomiting can be well assessed sonographically. This is an excellent means to diagnose pancreatitis in canine patients, to identify a distended uterus or parenchymal lesion of other organs. As with all sonography, a systematic approach to evaluation of the abdomen is recommended. Imaging pancreatitis With the advent of pancreatic lipase testing, pancreatitis is more easily diagnosed in general practice, and a suspected case of pancreatitis, with supportive bloodwork, is often treated medically without diagnostic imaging. It is known that false positive cPL tests do occur, and supportive imaging can confirm a diagnosis of pancreatitis while ruling out other aetiologies for abdominal pain and vomiting. Survey radiographs can be used to assess for the changes that occur with pancreatic disease. Enlargement of the right pancreas can cause rounding of the gastroduodenal angle on the ventrodorsal view. The transverse colon may be displaced caudally by enlargement of the body of the pancreas with increased distance between the stomach and colon. The duodenum may be gas filled or corrugated due to secondary inflammation. The presence of free fluid results in a loss of serosal detail which can be localized. If the left pancreas is inflamed the loss of detail may be seen adjacent to the head of the spleen. In this author’s experience these radiographic changes are not always present or are very subtle, even in confirmed cases. The importance of radiographs is largely in ruling out other differentials for the clinical signs, as gastrointestinal obstruction can present in a similar way.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 115 of 226 Abdominal ultrasound is an excellent means for evaluating canine pancreatitis. The right pancreas is located adjacent to the duodenum and the left pancreas is found between the stomach, spleen and left kidney. The inflamed pancreas is hypoechoic and the surrounding issue is hyperechoic with pockets of fluid often present. The duodenum also becomes inflamed and can appear corrugated. In severe cases the whole pancreatic region becomes quite difficult to image with hyperattenuation of ultrasound resulting in incomplete shadowing and poor penetration. Ultrasound is also an excellent means to assess for the secondary complications of pancreatitis. Pancreatic abscesses or pseudocysts appear as focal fluid accumulation within or adjacent to the parenchyma. Secondary extrahepatic biliary obstruction results in distension of the common bile duct, which is not easily seen in normal patients. Pancreatitis in cats is much more difficult to diagnose songraphically and ultrasound is both poorly sensitive and specific for the disease, though we know that chronic pancreatitis is relatively common. Extrahepatic biliary disease Extrahepatic biliary obstruction in canine patients can be associated with pancreatitis and secondary obstruction of the common bile duct. This may occur with acutely inflamed pancreatic tissue, fibrosis and scarring from chronic inflammation or due to a secondary abscess or pseudocyst. Obstruction of the biliary outflow tract may also occur due to the presence of choleliths or a neoplastic lesion resulting in obstruction of the bile duct or major duodenal papilla. Biliary mucocele can also result in clinical icterus. With extrahepatic disease the liver may appear normal in size radiographically, and the gallbladder is not often visible. Gallbladder distention can be seen in feline patients, as the enlarged gallbladder protrudes beyond the ventral margin of the liver on the lateral view, delineated by falciform fat. Cholelithiasis or mineralized biliary sediment may be evident radiographically. In the absence of icterus, these findings can be seen incidentally. Ultrasonography is recommended in evaluation of patients with suspected extrahepatic obstruction. The sonographic findings associated with acute pancreatitis in canine patients are described above. Due to the associated inflammation resulting in hyperattenuation in addition to hyperechogenicity of the mesentery, it can be difficult to image the entire common bile duct. Distention of the cystic duct and common bile duct to the point of obstruction may be evident. Obstructive choleliths are hyperechoic with distal shadowing,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 116 of 226 and can be present anywhere within the bile duct or duodenal papilla. Neoplastic or inflammatory tissue compressing or within the bile duct or papilla may be uniformly echogenic or heterogeneous. Gallbladder mucocele has the characteristic ultrasonographic appearance of a “kiwi” with non-dependent echogenic organized and peripherally striated tissue that fills the gallbladder lumen. Recommended reading 1. The handbook of veterinary contrast radiology. Seth T. Wallack. 2003. Published by the author, San Diego Veterinary Imaging Inc., 361 North Sierra Avneue, Solana Beach, CA 92075 2. Textbook of veterinary diagnostic radiology, sixth edition. Donald E. Thrall. 2012. Elsevier. 3. BSAVA Manual of Canine and Feline Ultrasonography. Edited by Frances Barr and Lorrie Gaschen. 2011. British Small Animal Veterinary Association.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 117 of 226 ANGIOSTRONGYLUS VASORUM - AN UPDATE Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA Clinician in Emergency and Critical Care, Langford Veterinary Services sophie.adamantos@bristol.ac.uk Angiostrongylus vasorum (lungworm) is a metastrongylid nematode that infects dogs and foxes, although clinical signs are more commonly seen in dogs. Although historically confined the South Wales and Cornwall, over the last 10 years there has been a spread of the infection, initially through the southern part of the UK, but more recently including Northern England and Scotland. Recent papers describing infection of foxes in Scotland and disease through all parts of the UK suggests that the parasite should now be considered endemic to the UK. Angiostrongylus vasorum has an indirect lifecycle. The L1 larvae are excreted in dog faeces and infect the intermediate hosts, slugs and snails. They mature to L3 larvae in the snail where they are then ingested by dogs. It is currently unclear as to whether the whole slug needs to be ingested, or whether ingestion of the excretions/slime trails of the slug is enough. Paratenic hosts have also been identified, including frogs which ingest the slugs, but through whom no further development of the larvae occurs. After ingestion, the L3 larvae migrate out of the intestinal tract and through the lymph nodes to the right side of the heart and pulmonary artery where they mature to adults. The eggs that they lay hatch and the larvae migrate to the lung tissue. In the lung tissue the presence of the larvae results in an inflammatory response leading to signs of coughing and breathing problems. The larvae remain in the alveoli of the lung and are then coughed up, swallowed and then excreted via the faeces and the cycle continues. Clinical presentation Angiostrongylosis affects any age of dog, young dogs are more frequently affected clinically. There seems to be a breed predisposition with Cavalier King Charles spaniels and Staffordshire bull terriers more commonly affected in the UK. There is no sex predilection. Angiostrongylosis causes a number of clinical signs. Most typically it causes respiratory signs including dyspnoea and coughing. Other common signs include neurological signs; most commonly seizures, obtundation, paralysis and blindness; and hypocoagulability causing haemorrhage into a number of different sites and associated clinical signs. It is likely that the majority of neurological signs are secondary to bleeding with the CNS, with a Angiostrongylus vasorum- an update

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 118 of 226 relative minority being cause by aberrant larval migrans. Less common syndromes include hypercalcaemia which may present as PU/PD, weight loss and GI signs and pulmonary hypertension which can cause right sided heart failure manifesting as ascites, pleural effusion and syncope. Most commonly in first opinion practice, A.vasorum causes respiratory signs. The pathogenesis of the coagulopathy associated with A.vasorum is poorly understood. In referral populations, in excess of 50% of dogs presenting with A.vasorum will have signs of haemorrhage and it is a common cause of bleeding diathesis. It should therefore be considered a differential for dogs presenting with non-traumatic haemorrhage, particularly if the worming history is unknown. It seems likely that the hypocoagulability is associated with a chronic form of DIC. D-dimer concentrations are increased in dogs presenting with A.vasorum and fibrinogen concentrations are significantly lower in dogs with bleeding compared with those that don’t supporting a consumptive coagulopathy. Coagulation times are not predictive of a risk of bleeding, but thromboelastography confirms that hypocoagulablity is associated with haemorrhage. Further research in this area is needed and other possibilities including platelet dysfunction and hyperfibrinolysis have been suggested as contributing to the hypocoagulability. Diagnosis Diagnosis of A.vasorum has recently become much easier! Until late 2013 diagnosis relied on faecal examination for larvae, either using Zinc floatation or a Baermann sedimentation technique. More recently a lateral-flow test (IDEXX Angio Detect) has become available and can be performed on blood as it looks for lungworm antigen. This test is quick and easy to perform and is reasonably priced. It has an excellent specificity, so a positive test is indicative of a diagnosis of Angiostrongylosis, however its sensitivity is approximately 85%, meaning than approximately 15% of dogs with Angiostrongylosis will be negative on the test. If this test is not available at your practice faecal examination can be performed and a Baermann is recommended. A minimum of 5g of faeces should be collected, and many people recommend collecting a pooled sample of faeces over 3 days, although in many clinical cases this does not seem to be necessary and a single sample will provide a positive result. If a more rapid result is required a faecal smear can be examined under a microscope. A small (grain of rice sized) amount of faeces is placed on a microscope slide and mixed with a tiny drop of water. No cover slip is required. The slide is examined under 20x magnification and the larvae, if present, should be visible and moving! This technique is accurate in experienced hands, but less experienced people often mistake artefacts e.g. bits of hair for worms and there is therefore a chance for false positives. Other larvae are very

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 119 of 226 rare in the faeces of dogs. However, it is easy to miss larvae and so the technique is not very reliable. A faecal sample should always be submitted to a lab as well as doing this technique. Treatment The clinical signs associated with the infection, particularly the neurological or bleeding signs, can complicate treatment of A.vasorum. Management of the infection itself is relatively easy. A number of parasiticides including (in no particular order!) imidacloprid/ moxidectin (Advocate®), milbemycin (Milbemax®), and fenbendazole (Panacur®) can be used, although fenbendazole is not licensed for this use. It is useful to confirm infection prior to instituting therapy if possible. Dogs with dyspnea should be provided with oxygen therapy in a stress free manner. Other therapies such as antibiotics, diuretics and bronchodilators are not typically required or helpful. The dyspnea may take a number of days to resolve and during this time the dog should be kept rested and excitement should be avoided. Some people will use anti-inflammatory doses of steroid for 3-5 days during treatment. This is based on the reports of worsening clinical signs after treatment, which is thought to be related to a reaction to the dying worms. This is only clearly described following therapy with levamisole which is rarely used today. However, the use of steroids is common. Typically, this author does not currently use steroids but historically has! There is no good consensus for management of the coagulopathy. Clinically dogs seem to stop bleeding soon after treatment of the infection. The use of blood products can be useful, particularly if there is anaemia or severe prolongation in clotting times. However, as the coagulopathy is poorly understood it is not known how useful plasma therapy is in these cases. Generally, when there is a risk of life threatening haemorrhage, such as bleeding into the CNS or lungs, plasma therapy is recommended. Prognosis is generally good, however, when there are severe neurological signs for example seizures or coma the prognosis is grave. In Denmark they recognize a chronic syndrome of poor exercise tolerance associated with infection, however this is poorly described. A.vasorum can be a life threatening infection and preventative therapies are recommended by the drug companies. Advocate® and Milbemax® are both licensed for this use on the regular schedule for worming/flea therapy. Many practices in endemic areas will

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 120 of 226 recommend preventative measures, or at least therapy prior to surgery to prevent bleeding complications. This should be a discussion with owners and will depend upon their decisions/risk aversion and financial constraints. However, in areas where the infection is common preventative therapy seems to be common sense. Testing or therapy prior to surgery is commonly practiced. If your practice decides to do this consideration needs to be taken as to timing. I would recommend treatment a minimum of 1-2 weeks prior to planned surgery to ensure that the disease, if present, has been effectively treated. There is currently no data examining the use of Angio Detect ™ for monitoring of therapy. References: Adamantos, S., Waters, S. and Boag, A. (2015), Coagulation status in dogs with naturally occurring Angiostrongylus vasorum infection. J Small Anim Pract, 56: 485–490. doi:10.1111/jsap.12370 Helm et al (2015) Epidemiological survey of Angiostrongylus vasorum in dogs and slugs around a new endemic focus in Scotland. Veterinary Record 177: 46 Helm, J. R., Morgan, E. R., Jackson, M. W., Wotton, P. and Bell, R. (2010), Canine angiostrongylosis: an emerging disease in Europe. Journal of Veterinary Emergency and Critical Care, 20: 98–109. doi:10.1111/j.1476-4431.2009.00494.x

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 121 of 226 BIOMARKERS OF ACUTE KIDNEY INJURY Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA Langford Veterinary Services, University of Bristol Sophie.adamantos@bristol.ac.uk What is a Biomarker? Biomarkers are objective measures of a biological or medical state observed from outside the patient, which can be measured accurately and repeatedly. The National Institutes of Health Biomarkers Definitions Working Group have defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” In veterinary medicine much of the recent development of biomarkers has focussed on biochemical molecules that can be measured in bodily fluids including blood, urine and effusions. Commonly used biomarkers in clinical practice include Cardiac troponin I, NT-pro BNP, C-reactive protein, canine pancreatic lipase immunoreactivity. Why are biomarkers important in kidney injury? Biomarkers allow us to evaluate specifically for the presence of pathogenic processes. Assessment of renal function in veterinary medicine has traditionally been limited to the measurement of biomarkers including urine output, urea and creatinine. While these biomarkers are good indicators of chronic kidney disease they are not thought to perform as well in acute kidney injury, particularly in the early stages. Problems identified with the currently used biomarkers in human medicine include a lack of sensitivity as they increase too late (i.e. in the advanced stages of disease), lack of specificity and a lack of association with prognosis. There is a huge amount of on-going research into the use of newer biomarkers in both human and veterinary practice, however all of these have problems associated with them so far. It is likely that the use of panels of biomarkers will provide more information in the future, however we are a long way from this at the moment. The ideal biomarker for acute kidney injury will be both sensitive and specific for and increase acutely in a linear manner following injury. It will be unaffected by patient characteristics. All the currently available biomarkers have problems with them, including the newer ones! Biomarkers of acute kidney injury

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 122 of 226 Diagnosis of AKI in animals There are a number of systems that have been described to define AKI in animals including the RIFLE criteria, AKIN and IRIS grading. There is some evidence to suggest that increasing severity of AKI is associated with poorer prognosis and some evidence that suggests even mild degrees of AKI increase morbidity and mortality. Traditionally diagnosis of AKI is based upon an acute increase in plasma or serum creatinine. This may be further defined as polyuric, oliguric or anuric. The use of defined criteria allows us to grade the severity, which may allow us to provide prognostic information. Traditional Biomarkers Urine output This is easy to measure in most patients and cheap to perform. In acute kidney injury urine output will be decreased. There are a number of other causes of oliguria, including hypoperfusion and dehydration hence this is poorly specific, in people it is less than 10% specific as very few people with oliguria will go on to develop AKI. In people oliguria and anuria is highly sensitive for AKI. Oliguria should therefore prompt assessment for AKI. Urine specific gravity Measurement of USG alongside UOP can allow further classification of oliguria. Increased concentrating ability in the face of oliguria implies a physiologic response. Assessment of isosthenuria (1.008-1.012) is more difficult especially if the animal is on fluid therapy. Hyposthenuria implies some renal function as there is an ability to actively dilute. However, this is rare in veterinary practice. Serum creatinine concentration Serum creatinine is well validated and commonly used. It is also widely available, with most in-house biochemistry analysers and some hand-held analysers able to measure it. Creatinine is influenced by a number of non-renal effects including age, muscle mass and breed. It is a marker of renal function rather than injury and hence increases typically occur sometime (24-48 hours) after the injury and a significant decrease in GFR is required before creatinine increases. Trends in serum creatinine are most useful when assessing renal function. Most AKI systems use very small increases in creatinine to define AKI. These changes will often be within the reference interval. Animals that have small increases in creatinine on a daily basis should be monitored or assessed for risk factors or causes of AKI, including toxicity e.g. NSAID, hypotension/hypoperfusion, hypertension etc.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 123 of 226 Newer biomarkers in clinical use Symmetric dimethylarginine (SDMA) This biomarker has recently become commercially available. Like creatinine it is an indirect marked of GFR. It is thought to more accurately reflect renal function than serum creatinine as its rate of production is relatively constant, it is not highly protein bound and it is filtered freely through the glomerulus. Most importantly for identification and management of chronic kidney disease SDMA is not influenced by muscle mass. This benefit is unlikely to be as important in acute kidney injury. SDMA is thought to increase earlier in the course of CKD, i.e. when there is a loss of 40% of nephrons as opposed to 75% with serum creatinine. SDMA has not been evaluated in AKI in dogs and cats but I suspect that there will be a number of studies published in the not too distant future. Interestingly despite its relatively recent introduction, the use of SDMA has already been incorporated into the IRIS-CKD staging system. Cystatin-C This is rarely measured clinically. Cystatin C is another endogenous indirect marker of GFR. It is a marker of proximal tubular damage. There is currently no published work evaluating its use in clinical cases of AKI in dogs and cats. Urinary albumin Albumin is a negative acute phase protein and is relatively easy to measure in serum and urine. Urinary albumin is thought primarily to indicate glomerular damage, but can also be present with tubular or vascular damage and so is not specific. Proteinuria is also commonly seen in non-renal inflammatory and immune-mediated conditions decreasing its specificity further. Proteinuria is likely an important factor in the pathogenesis of on-going renal damage and so plays an important role in the progression of disease. It is of limited use in the evaluation of AKI due to its lack of specificity. Novel biomarkers in experimental use/early phase evaluation Retinol-binding protein (RBP) RBP is a lipocalin produced by a number of tissues in the body. It is small enough to be freely filtered in the glomerulus, but it usually reabsorbed by tubular epithelial cells. Tubular damage or release of large amount of RBP hence results in loss of RBP into the urine. Increases in urinary RBP have been identified in dogs with naturally occurring AKI. In dogs with pyometra uRBP/c decreased following ovariohysterectomy providing that this may be a useful measure for monitoring of progression. Marked pyuria or haematuria will cause artefactual increases though so care is needed for interpretation.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 124 of 226 Neutrophil gelatinase-associated lipocalin (NGAL) NGAL is a member of the lipocalin-binding protein family and is present in neutrophils and many other normal tissues. Due to the availability of a canine ELISA NGAL has been evaluated in a number of clinical studies in dogs. Urinary tract infections and lower urinary tract diseases increase urinary NGAL (uNGAL) even without the presence of azotaemia. Furthermore, uNGAL has been shown to increase in dogs with sepsis. Interpretation of NGAL should therefore be performed with care and, at this stage, it cannot be used alone to diagnose AKI. One of the purported benefits of NGAL is the rapidity of its increase following a renal insult. This has not been thoroughly evaluated in clinically affected dogs yet. A study in dogs with experimentally induced AKI using gentamycin concluded that uNGAL was a sensitive marker of AKI in this model, however it did not perform better than more traditional measures for rapid detection in other similar studies. Urinary enzymes The most commonly evaluated of these enzymes is NAG (N-acetyl-beta-D-glucosaminidase). As with other biomarkers this is increased in the urine in renal injury. Urinary NAG originates from the renal tubules and is therefore thought to be specific for tubular injury. In contrast with NGAL and RBP pyuria and bacterial infections do not increase NAG, but pyelonephritis does. NAG has been evaluated experimentally using gentamycin induced AKI as the model and uNAG increased following injury and continued to do so over the study period. Other studies have identified that urinary enzymes are more sensitive and reliable than other markers for identification of acute renal tubular damage. There are however few studies in clinically affected dogs and those that have been performed have inconsistent results. Use of biomarkers in suspected AKI There is likely to be a surge in the availability of renal biomarkers over the coming years. One of the limits of the use of these markers is the impact on management. As we are limited in what we can do when managing animals with suspected AKI early detection of AKI is unlikely to change our management unless nephrotoxic drugs are being administered. There may be a role for their use in screening patients at risk. However, a panel of biomarkers may be more useful for this than a single analyte. Further work is needed in this area.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 125 of 226 References and further reading: Cobrin AR, Blois SL, Kruth SA, Abrams-Ogg AC,Dewey C. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat. J Small Anim Pract.2013;54:647–655. Hokamp, J. A. and Nabity, M. B. (2016), Renal biomarkers in domestic species. Vet Clin Pathol, 45: 28–56. doi:10.1111/vcp.12333 Segev G, Palm C, LeRoy B,Cowgill LD, Westropp JL.Evaluation of neutrophil gelatinase-associated lipocalin as a marker of kidney injury in dogs. J Vet Intern Med. Steinbach S, Weis J,Schweighauser A, Francey T, Neiger R. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease. J Vet Intern Med.2014;28:264–269.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 126 of 226 Notes page

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 127 of 226 BLOODY TRUTHS: TRANSFUSION MEDICINE, MYTHS AND FACTS Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com Can RBCs Be Given Through an Infusion Pump? Whether there is an optimal method of red blood cell transfusion administration has been a point of discussion. Studies evaluating the effect of various administration methods on the integrity of blood cells exist, focused on the in vitro effect of infusion pumps, measuring the degree of free RBC content (free haemoglobin, potassium, lactate dehydrogenase, bilirubin) and osmotic fragility. The results vary from observing significant increases to insignificant increase in values, while transfusions with red cells with longer storage time resulting in a larger increase of haemolysis markers than those with shorter storage times. The variability in results, in addition to the anecdotal evidence of patients benefiting from RBC transfusions administered with infusion pumps are a cause for varying opinions. A study assessing in vivo survival time of RBCs infused with various infusion methods, compared the use of gravity flow, volumetric peristaltic pump and syringe pump in autologous transfusions in dogs. Blood was collected from 9 healthy dogs, washed, and separated into 3 portions labelled with different densities of biotin. These labelled red cells were transfused through either gravity flow with a 170-260 µm filter, volumetric peristaltic infusion pump with a 170-260 µm filter, or a syringe infusion pump with an 18 µm aggregate filter at 2mL/kg/hr. Blood was sampled from test subjects at day 1, and every 7 days until day 49, measuring the proportion of red cells with biotin labels through flow cytometry. Additional in vitro testing was conducted, measuring plasma haemoglobin and osmotic fragility testing. Labelled RBCs infused through gravity flow, volumetric pump, and syringe pump were detectable in 100% (8/8), 50% (4/8), and 14.3% (1/7) samples, respectively post-transfusion. The quantity and half-life between RBCs infused by gravity flow and volumetric pump that were detectable (4/8) were not different. The RBCs infused via syringe pump detected at 24 hours post transfusion was no longer detectable at 7 days, indicating complete removal of those cells from circulation sometime between 24 hours and 7 days’ post transfusion. No differences were seen in in vitro values examined. The study concluded that delivery of RBCs with a syringe pump and microaggregate filter is associated with significant decrease in in vivo survival time. Volumetric pump delivery was Bloody truths: transfusion medicine, myths and facts

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 128 of 226 associated with a 50% probability of loss of transfused RBCs within the first 24 hours, and gravity flow allowed for highest chance of RBC survival. The reason behind this difference is speculated to be the mechanical shear damage to the RBC membranes when transfused through the microaggregate filter, causing preferential removal of damaged cells upon entry into the circulation and exposure to the mononuclear phagocytic system. Though unconfirmed, there is a potential for microclots to have formed in the blood during resuspension in sub-room temperature plasma, which placed a higher degree of shearing stress on the RBCs going through the filter, causing this effect. Early denaturation and oxidation of haemoglobin due to the mechanical stress induced by syringe pump and volumetric pump methods, leading to IgG binding to the red cell surface and removal from circulation, is another possible cause for early removal. Small sample sizes limiting the power of the results is a common limitation in the veterinary field and this study is no exception. The results are most relevant to exact methods used in the study, and we can only make speculations on alternate setups to remove the use of microaggregate filters with the syringe pump (use of an in-line pediatric 170-260 µm filter or extraction of blood through a 170-260 µm filter administration set into a syringe, for example). The authors of the study recommended against using a syringe pump with 18 µm aggregate filters in the light of the results of their study, though considering the limitations, drastic changes to clinical protocols was not stated to be necessary. The current best practice, considering this evidence, would be to administer blood products via gravity flow for larger volume, higher flow rate transfusions as long as consistency in flow rate is monitored closely (as it can be influenced by catheter patency, positioning and motion by the patient and amount of blood left in the bag). The syringe pump method is particularly useful when performing small volume transfusions such as in felines. A similar study performed with feline blood stated their observation of RBC survival time being unaffected by the syringe pump method. There are a couple of infusion pumps approved for blood products, one of which is an internal approval, and the other of FDA approval for human blood products. These pumps could be the next best solution and validation with veterinary blood products is warranted.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 129 of 226 PRBC Has an Expiration Date of 42 Days? Current practices in blood banking involve the usage of APS and additive nutrient solution which are labelled for 42 days of storage. Other studies have observed significant changes in degree of haemolysis, ATP level, and 2, 3 DPG concentrations by 31 days. More recent evidence gathered over the past decade indicates stored red blood cells to have impaired RBC survival, reduced efficacy as an oxygen carrier, and even incite adverse effects in the recipient causing mortality and morbidity. These changes are seen as early as 7 to 14 days into storage, and involve a collection of biochemical, biomechanical, and oxidative changes to the RBC and storage solution, all collectively referred to as “storage lesions”. Mature RBCs lack mitochondria and rely on glycolysis for ATP production, leading to a lowered pH. ATP production is reduced by the acidic environment, combined with depletion, leads to decreased RBC membrane integrity. Lowered pH also affects 2,3 diphosphoglycerate (2,3 DPG) level reducing haemoglobin’s effectiveness as oxygen carriers, though this effect is reversible and not significant in cats. Haemoglobin in longer stored RBC products contain free haemoglobin and microparticles that scavenge nitrous oxide (NO) upon transfusion and cause a vasoconstrictive effect impairing blood flow, stimulate coagulation, induce oxidative damage, and cause proinflammatory effects. Microparticles, which are vesicles that have budded off cellular components, induce proinflammatory and procoagulant effects. Stored RBCs show morphologic changes to echinocytes and spheroechinocytes leading to a loss of deformability and impairment in normal flow through capillaries. Oxidative damage leads to increased haemolysis and methaemoglobin formation decreasing viable RBC count and oxygen carrying capacity. There are many complicated mechanisms in play during RBC storage. To summarize the effects, storages lesions can lead to impaired RBC survival, reduce the efficacy of RBCs as oxygen carriers, and induce adverse effects such as arrhythmias, thrombosis, systemic inflammation, transfusion-related acute lung injury (TRALI), acute respiratory distress syndrome (ARDS), hypotension and multiple organ dysfunctions. These changes occur as early as 7-14 days into storage, making supplying our patients with safe transfusion products a realistic challenge. Clinical impact of storage lesions is a topic of ongoing investigation while blood banks strive to balance provision of fresher products and minimizing wasting. First Transfusions Are “Free”? Compatibility testing for canine blood transfusions has traditionally been omitted in the interest of swift transfusions and financial considerations. This comes from a widespread notion that the “first transfusions are free for dogs”, intended to state that canine RBC

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 130 of 226 transfusions can be given without blood type matching (without typing the donor or recipient) or cross matching yet be performed without signs of immunologic complications, namely acute haemolytic transfusion reactions or anaphylaxis. This statement is made with the understanding that the most clinically significant dog erythrocyte antigen (DEA) is DEA 1, responsible for inciting acute haemolytic transfusion reactions when preexisting alloantibodies for the antigen is present. In 98% of the population, these antibodies are not present, so the first mismatched transfusion will only result in sensitization of the immune system to the antigen, leading to the development of antibodies over a course of approximately 4 days. This leads to a delayed haemolytic transfusion reaction, often asymptomatic as long as the patient has overcome the initial incident of anemia, or clinical symptoms of anemia as well as bilirubinemia and bilirubinuria may arise. Given the asymptomatic or mild nature of clinical signs, many have accepted this reason to forgo compatibility testing. However, the sensitization will lead to an acute haemolytic transfusion reaction in subsequent mismatched transfusions, resulting in haemolysis of transfused cells and likeliness of anaphylaxis. By omitting compatibility testing, we run the risk of priming a patient for such reaction in the next transfusion which may be handled similarly if the patient’s transfusion status is not noticed. A medical team may be placed in a situation where the transfusion status of the patient may be unknown (pet brought in by pet sitter who thinks there had been no transfusions, or adopted dogs who “probably” has not had a transfusion). In the case a patient presents with risk of imminent death from anemia, this practice may be justified with the knowledge of the risk. Blood typing of all blood donors and stocking of DEA 1 negative blood is highly recommended for use in these situations to avoid sensitization of the patient to DEA 1. If there is any uncertainty in the transfusion history of the patient, cross matching is appropriate as erythrocyte antigens aside from DEA 1 exist with limited knowledge on consequences from patients sensitized for these miscellaneous antigens (some reports of AHTR exist). Transfusions of canine RBCs without compatibility testing are not “free”, and certainly have the hidden costs of DHTR and sensitization. Cats possess alloantibodies for the RBC antigens foreign to them (aside from the very rare type AB cats), leading to haemolytic transfusion reaction even with first exposure. DEA 1 Negative is the Universal Blood Type? The concept of “universal” blood type indicates a blood type that can be given to any member of the same species without expectation of an immunologic reaction related to blood type mismatches. Because DEA 1 is the one antigen we know most about and leads to AHTR when mismatched for the second time, blood from DEA 1 negative dogs can be

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 131 of 226 given without sensitization of DEA 1 negative and DEA 1 positive recipients, and often is considered as “universal”. There are, however, other RBC antigens such as DEA 3 through 8, dal, and other less known antigens confirmed to exist which can lead to sensitization when mismatched transfusions occur. Therefore, a donor should be tested negative for every RBC antigen we are capable of testing in order to truly considering it “universal”. This creates a challenge as 98% of the canine population is positive for DEA 4, and a donor negative in DEA 4 is virtually impossible to find. Fortunately, this is not a clinical issue since the recipient is likely DEA 4 positive as well, allowing the blood types to match. Another challenge lies in our current inability to routinely test for DEA other than 1, 4, and 7 through a reference lab due to a lack of testing anti-sera (and anything aside from DEA 1 not available as in-house kits), preventing complete typing of our donors and timely testing of our recipients. Given our knowledge of additional RBC antigens, we should consider DEA 1 negative, 4 positive, 7 negative blood type as the “least antigenic”, and type our donors for all DEAs we are capable of, given finances permit it. DEA 1 negative can be considered safe blood to use from anecdotal evidence as reports of haemolytic transfusion reactions are rare, and cross matches should detect incompatibility issues arising from repeated exposure to the less known erythrocyte antigens. Cats have no universal donors, though type AB cats may receive transfusions from both type A and B donors. Are Blood Transfusions between Different Species Possible? Despite common knowledge that blood product transfusions should be between members of the same species to prevent immunologic consequences, there is ongoing research to test interspecies transfusions, or xenotransfusions. Early experiments in blood transfusion in the 1600s document a human patient receiving sheep blood, and showing no signs of reaction (at least on first exposure). Porcine red blood cells with modified antigens have been a topic of research in compatibility as human blood substitute. In the veterinary field, feline blood is consistently in short supply, especially for patients with the rare blood type of B. Type B cats can only be transfused with type B blood as introduction of a small volume of type A blood will result in an acute haemolytic reaction and anaphylaxis. In addition, even for type A patient’s, blood supply may be short causing delays or inability to obtain blood products in a timely manner as the patient suffers life-threatening anemia. In these situations, veterinarians have attempted to use canine blood as a source of blood as it is more readily available, and can easily tolerate the small volume donations. There is limited amount of evidence available from a few studies conducted on canine to feline transfusions. The results of the studies concluded felines do not possess naturally occurring alloantibodies against canine erythrocytes. Compatibility testing methods such as

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 132 of 226 slide-agglutination test and cross-matching only revealed agglutination on the minor-crossmatch. Of the total of 62 transfusions performed between the various studies, 5 cats showed signs of mild reactions, with tachypnea and pyrexia within 24 hours of the start of transfusion. Development of antibodies against canine RBCs were seen 4 to 7 days after the transfusion, indicating the transfusion led to sensitization of the immune system to the foreign antigens. Because of this, the life span of the transfused RBCs was approximately 4 days due to delayed haemolytic transfusion reactions while feline to feline transfusions allow RBCs to last 30 days. Subsequent transfusions resulted in anaphylaxis and were fatal in 66% of documented cases. While transfusion of dog blood to a feline patient is not the best solution to supplementing oxygen carrying capacity, it may be justifiable when faced with imminent death of the feline patient and without blood. A responsible medical team would discourage dog to cat transfusion and consider the method only when the patient 1) has no source of compatible cat blood (Type B cat with no stocked blood, donor, or nearby hospital with stock, for example) or haemoglobin based oxygen carrier solutions, 2) is imminently going to pass away without a transfusion or compatible blood will not be obtained soon enough (truly dying animal), 3) is expected to benefit from a short term oxygen carrying capacity gain, and 4) the owner understands risks and consequences. Xenotransfusions should not become a common practice and maintaining a good source of cat blood should always be pursued without considering canine blood as “backup”. Premedicating Reduces Chances of Reactions? Premedication, or administration of antihistamines, glucocorticoids or antipyretics in anticipation of immunologic complications to counter histamine and inflammatory mediators and suppress the effects, has been a traditional practice in transfusion medicine. There are a number of human studies observing no difference in incidence of type I hypersensitivity reactions (allergic reaction) or febrile non-haemolytic transfusion reactions (FNHTR). Some clinicians reason that administration of premedication potentially masks early symptoms of immunologic complications delaying required interventions for treatment, advocating against it. Evaluation of the difference in severity between recipients with premedication or without premedication has not been performed, and remains a question whether this reasoning is valid. Human evidence is unfortunately not always directly translatable into veterinary practice, though expectations of similar physiological mechanisms exist. A recent veterinary retrospective study evaluating the effect of premedication on acute transfusion-related reactions saw no beneficial effect. There might be a beneficial effect to administration of diphenhydramine in decreasing chances of acute allergic reactions, though further studies

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 133 of 226 were recommended by the authors since the incidence of allergic reaction in the non-premedicated group was already low (2.6%). Studies evaluating effects of premedication and efficacy in prevention of haemolytic transfusion reactions are not apparently available, and the theoretical benefit is no justification for forgoing proper compatibility testing. Is Warming of Blood Products Necessary? Warming of blood products in the interest of prevention hypothermia in the recipient is a consideration during blood product administration. Concerns for haemolysis of erythrocytes when warming during transfusion exist, and studies point towards little to no difference in markers for haemolysis in vitro when blood is warmed to typical body temperature. However, at non-emergent administration rates, blood reaching the patient through the line placed in a room temperature environment is easily at room temperature upon reaching the patient, and will not contribute to a significant decrease in body temperature. In the case of rapid transfusions of large volumes into small patients, warming of the blood may be indicated with care taken to be evenly warmed to 35-37°C and not exceed 42°C close to the patient to minimize loss of heat. Hypothermia is also a documented complications related to massive transfusions. Aside from these situations, in many cases warming effort directed at the patient is most effective in treating hypothermia. Is Plasma Indicated for Use in Hypoproteinemia? Parvoviral Enteritis? Plasma contains many proteins of interest, namely haemostatic proteins, albumin, and immunoglobulins. Hypoproteinemia, specifically hypoalbuminemia, occurs in many critically ill patients with protein-losing disorders including protein-losing enteropathies, protein-losing nephropathies, liver failure, trauma, burn wounds, etc. This leads to a loss of intravascular colloid osmotic pressure (COP) and subsequent consequences. Administration of plasma products (fresh frozen plasma, frozen plasma, or cryosupernatant) have been used as a method in supplementing albumin for COP. However, the amount of plasma required to raise the patient’s albumin level by 1g/dL is approximately 40-50mL/kg. This is equivalent to 1.1L of plasma (9.5 units) for a ~20 kg patient. The amount of plasma required to make a significant difference in the measurable level of albumin is both cost prohibitive and pose a large immunologic risk to the patient. Whether increasing the albumin level to a normal value (>2g/dL) will lead to increased chances of a positive outcome is still unclear, and difficult to advocate. Similar concepts can be applied to the usage of plasma products derived from survivors of parvovirus infection. Clinicians have theorized that transfusion of plasma containing antibodies against canine parvovirus (CPV) will aid in recovery from CPV infections. A study

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 134 of 226 evaluating use of a single dose of plasma containing CPV antibodies in its efficacy versus saline placebo saw no significant difference in reducing clinical signs, viremia, or speeding recovery. The volume used in this study (12mL) may be a limitation to the efficacy of the compared treatment, though the amount of plasma required for an adequate dosage of antibodies is unknown, and is likely to be at similar or higher levels of dosage for albumin supplementation. Thus, same concerns prevent use of plasma in this manner.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 135 of 226 B-HARMONY: ARE YOU THE RIGHT TYPE FOR ME? Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com INTRODUCTION Blood component transfusions are regularly utilized as a method of treatment for various ailments. Red blood cells (RBCs) are utilized for anemia to supplement oxygen carrying capacity; plasma and its contents are used to provide coagulation factors in coagulopathies; platelets, when available, are used to aid in haemostasis in patients with life threatening haemorrhaging due to thrombocytopenia; and supportive evidence is emerging for canine specific albumin to positively affect the outcome in hypoalbuminemic patients. Less commonly, intravenous immunoglobulin (IVIG) is administered for its immunomodulatory effect in immune-mediated haemolytic anemia (IMHA), immune-mediated thrombocytopenia (ITP), and sudden acquired retinal degeneration syndrome; in addition, specific immunoglobulins are utilized as antitoxins for snake envenomation and tetanus. Complication rates are variable depending on the component being transfused, and can be immunologic or non-immunologic in nature. IMMUNOLOGIC RESPONSE AND ANTIGENIC BLOOD COMPONENTS Immunologic complications are a result of the body’s immune system responding to the foreign blood components transfused. Hypersensitivity reactions result from exposure to antigenic proteins in the transfused blood component. While a hypersensitivity response can occur at first exposure, the response may be even more severe with repeated exposures to the antigens due to the body’s ability to “remember” past exposures and elicit a secondary ("anamnestic") immune response. Hypersensitivity reactions prompted by blood component transfusions are classified as Type I (Allergic), Type II (Cytotoxic), and Type III (Immune Complex) hypersensitivity reactions in a traditional classification scheme. Type I Hypersensitivity Type I hypersensitivity reactions, commonly known as allergic reactions, are mediated by immunoglobulin E (IgE) resulting in the production and release of inflammatory mediators. When IgE expressed on the surface of mast cells is cross-linked with an introduced antigen, the mast cell is triggered to release its granules (degranulation). These granules contain inflammatory mediators, enzymes, and cytokines which stimulate the production of more inflammatory mediators. The release of these mediators such as histamine, serotonin, prostaglandins, and leukotrienes results in an acute inflammatory reaction. B-harmony: are you the right type for me?

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 136 of 226 Clinical signs can arise in seconds to minutes, giving type I hypersensitivity its other name of “immediate hypersensitivity”. Symptoms of type I hypersensitivity are usually mild, and include vomiting, diarrhea, fevers, hives (urticaria), pruritus, and facial swelling. In severe cases, a type I hypersensitivity reaction may result in anaphylaxis. Anaphylaxis in dogs typically manifests as haemodynamic collapse due to the occlusion of the hepatic veins leading to a lowered venous return, cardiac output, and arterial blood pressure. These dogs can show signs of weakness or collapse, become comatose, convulse, or die in a very short time. In cats, anaphylaxis can lead to salivation, vomiting, dyspnea, collapse, and may also lead to death. Evidence of bronchoconstriction, pulmonary haemorrhage, and edema in the respiratory system are seen on necropsy of these feline patients. These reactions can be triggered by any blood product but seem most commonly triggered by antigens on donor white blood cells and platelets. In addition, RBCs that have been stored longer have a higher tendency to cause type I hypersensitivity. Cytokines produced by leukocytes having a role in the hypersensitivity reaction may be the reason for this observation. Any signs of an acute hypersensitivity reaction should prompt the staff to immediately stop the transfusion. In the case of mild reactions an H1 antihistamine, such as diphenhydramine, may be used for treatment and cautious administration may be possible after the signs subside. In the case of anaphylaxis, administration of epinephrine, a glucocorticoid, such as dexamethasone, and aggressive fluid resuscitation is recommended. Type II Hypersensitivity Type II hypersensitivity reactions can occur in response to genetically different RBCs being transfused into a recipient. Surface glycoproteins and glycolipids, which function as cell membrane components such as transport channels, serve as antigens for antibody response and complement activation, leading to intravascular haemolysis. The antibodies also serve as opsonins, which allow for phagocytosis and destruction of the RBCs. This leads to extravascular haemolysis through the mononuclear phagocyte system. The combination of this intravascular and extravascular haemolysis is known as type II hypersensitivity, or cytotoxic hypersensitivity. The time to onset depends on the existence of antibodies against the erythrocyte antigens being introduced. Presence of preexisting antibodies can result in agglutination and haemolysis of the transfused cells. When type II hypersensitivity is triggered due to preexisting antibodies, it is known as an acute haemolytic transfusion reaction (AHTR) due to its rapid onset. If there are no preexisting antibodies to the novel erythrocyte antigens, a delayed haemolytic transfusion reaction (DHTR) may still occur as the transfused cells circulate within the body while antibodies are produced against them,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 137 of 226 leading to elimination of these red cells. Any subsequent exposure to these antigens will result in AHTR. Clinical signs of type II hypersensitivity vary in severity depending on the amount of incompatible red cells transfused, and the antigenic property of the erythrocyte antigen. The mildest sign is a febrile response. Most severe cases of AHTR can be seen in incompatible transfusions to a previously sensitized patient. These transfusions result in haemolysis of the transfused cells, leading to haemoglobinemia and haemoglobinuria. A large amount of intravascular haemolysis can trigger the coagulation cascade and result in disseminated intravascular coagulation (DIC). Activation of the complement system results in degranulation of mast cells, leading to systemic release of cytokines and inflammatory mediators, ultimately resulting in circulatory consequences of hypotension, bradycardia, and resulting shock. Salivation, vomiting, and diarrhea may also be seen as a result of sympathetic response. DHTR can be symptomatic or asymptomatic. The most common sign is a significant drop in PCV or Hb after the transfusion. Less common signs are fever, hyperbilirubinemia and reduced urine output. These signs can manifest 3-21 days’ post transfusion. Type II hypersensitivity reactions are of concern primarily when RBCs are transfused (whole blood, PRBC). However, a potential for red cell contamination of plasma products exist, and while rare, should not be ignored as a possibility. When a reaction is seen, the transfusion should be stopped immediately. Treatment for AHTR involves IV fluids, vasopressor and/or inotropic therapy to combat shock, glucocorticoid administration to suppress the immune response, and supportive care, especially to offset the nephrotoxic effects of haemoglobin, until the foreign red cells are eliminated from circulation. Type III Hypersensitivity Generalized type III hypersensitivity reactions occur when antigens are introduced intravenously. Serum antibodies form immune complexes with the antigens, and these complexes are normally removed from circulation by binding to erythrocytes and platelets, or eliminated by the mononuclear phagocyte system. In the face of a large antigenic load overwhelming clearance mechanisms, complexes are deposited on vessel walls, leading to vasculitis or arteritis; sites of high blood flow resulting in glomerulonephritis or synovitis; and on blood cells themselves, causing anemia, leukopenia, or thrombocytopenia. Clinical signs of type III hypersensitivity include fever, erythema, edema, urticaria, neutropenia, lymph node enlargement, joint swelling, and proteinuria, and can be seen 1-3

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 138 of 226 weeks after exposure. The signs seem to be more severe in healthier patients, possibly because of a stronger immune response. Because type III hypersensitivity reactions are caused by formation of immune complexes, blood products containing unbound antigens are potential triggers. Type III reactions have been reported in dogs receiving human serum albumin, and are postulated to occur with IVIG, snake antivenom, tetanus antitoxin, and incompatible plasma transfusions. Patients with symptoms are treated with supportive care. Transfusion-Related Acute Lung Injury (TRALI) A clinical syndrome characterized by an acute onset of dyspnea and hypoxemia with diffuse pulmonary infiltrates without signs of circulatory overload has been described in human transfusion recipients. This syndrome, called transfusion-related acute lung injury (TRALI), is seen within 6 hours of the start of transfusions, and can include signs such as fever, hypotension, dyspnea and tachypnea. The pathophysiology of TRALI is not well understood, but is thought to include at least two simultaneously occurring factors. The first factor involves the patient’s underlying disease causing endothelial activation and adherence of neutrophils to the pulmonary endhothelium. The second factor involves transfused biologically active lipids and cytokines activating the adhered neutrophils to cause endothelial damage, leading to pulmonary edema. In addition, donor leukocyte antibodies reacting with recipient leukocyte antigens causing an immune reaction leading to lung injury may be involved. The endothelial damage is believed to cause an increase in permeability in the pulmonary circulation, leading to protein containing fluid entering the alveoli and interstitium. Plasma containing blood products are usually the cause, though TRALI can be seen with red cell transfusions. A study evaluating the incidence of acute lung injury (ALI) in canine patients receiving transfusions observed much lower incidence of ALI when compared to humans (25% vs 3.7%), implying TRALI may not be a significant concern for veterinary patients. Management of a patient with TRALI is largely supportive, involving oxygen supplementation. In severe cases, mechanical ventilation may be required. Glucocorticoid administration is thought to be beneficial, though definitive evidence in its efficacy has not been established. COMPATIBILITY TESTING While there are a many possible immunologic responses to blood products, immunologic complications are relatively rare. This observation may partially be due to a low natural occurrence of incompatibilities or a depressed immune response in critically ill patients.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 139 of 226 However, our ability to test for compatibility of blood components and select appropriate blood products is the largest factor in minimizing the chances of complications. Blood Typing Since type II hypersensitivity reactions are triggered by RBC surface antigens, blood typing of the donor and recipient is essential for a safe transfusion and is the first step in testing for compatibility. Matching donor and recipient blood types will minimize the chances of a transfusion reaction. The DEA (dog erythrocyte antigen) blood group system has been described for canines, where DEA 1, 3, 4, 5, 6, 7, and 8 are recognized, with 5 additional antigens described. Previous texts may indicate the existence of DEA 1.1, 1.2, and 1.3 antigens. A recent study has confirmed them to be the same antigen, just expressed in different quantities, changing the nomenclature to simply DEA 1 (with strong versus weak expression). An additional blood group antigen called dal has also been identified as lacking in some Dalmatians. Type II hypersensitivity due to DEA 1 has been known to cause severe AHTR, but because of the lack of naturally occurring antibodies to these antigens in dogs, an acute reaction is not seen when DEA 1 positive blood is transfused to a transfusion naïve, negative patient. However, a first transfusion of positive blood results in sensitization to the DEA, which leads to severe AHTR on repeated exposure. Naturally occurring antibodies for DEA 3 and 5 (10% of population) and DEA 7 (20-50%) are seen in dogs typed negative for these DEAs, but as they occur at a low titre level, clinically significant reactions do not occur. While full DEA typing is only available through commercial blood banks and university laboratories, in-house typing kits for DEA 1 are available. Typing every recipient for DEA 1 prior to transfusion will allow use of both DEA 1 negative and positive donor blood for transfusion, increasing the donor pool, and avoiding sensitization. DEA 1 negative or “universal” blood (though the notion of “universal” blood is questionable due to the existence of antigens we are unable to test for) can be used without prior typing in patients certain to never have been transfused, or emergency situations when time is of the essence. Cats are known to have the AB blood group system, where 75-95% have the blood type A, 5-25% have type B, and a very small (~1%) number have type AB. About 35% of type A cats have naturally occurring anti-type B antibodies at a low titre level. When these type A cats are transfused type B red cells, a mild form of type II hypersensitivity occurs. Type B cats have naturally occurring anti-A antibodies at a high titre level, such that even transfusions of a small amount (~1mL) of type A blood will cause severe, haemolytic reactions. Plasma transfusions of the incorrect type can also cause a haemolytic reaction due to the anti-A and

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 140 of 226 anti-B antibodies present. Type AB cats lack both anti-A and anti-B antibodies, making them a universal recipient for pRBCs. However, haemolytic transfusion reactions can be seen in both type A and B plasma or whole blood transfusions to AB cats due to the antibodies present in the plasma. The Mik antigen is a blood group identified in cats distinct from the AB group, for which there are currently no methods to type in clinical settings. Because mismatched transfusions in the AB group system will result in mild to severe reactions, feline donors and recipients should be typed prior to both red cell and plasma transfusions. In-house agglutination based card tests are available for both canine DEA 1 and feline A/B. The DEA 1 test kit has a DEA 1 positive control, negative control, and the test well. The feline test kit has patient control, type A test, and type B test wells. The test well contains murine monoclonal antibodies against erythrocyte antigens to be tested. Agglutination occurs with antibody-antigen complex formation, indicating that the patient is positive for the blood type under evaluation. The control wells can serve to identify any presence of auto-agglutination due to auto-immune disease. However, because the test relies on agglutination for blood type detection, interpretation of blood samples obtained from a patient with auto-agglutination is unreliable. Another type of available in-house blood typing test utilizes immunochromatography to determine blood types. Immunochromatography uses a porous strip impregnated with antibodies in two locations. In the initial sample area, red cells with the target antigens form immune complexes with antibodies that are labelled with a chromatographic substance such as colloidal gold or selenium. The red cells then pass through the detection area with antibodies fixed in place, which stops the migration of the red cells by attaching to them. This results in a coloured band as the indicator for the blood type if positive, and a lack of a band if negative. Immunochromatographic tests have the advantage that they can filter agglutinated cells, allowing for blood type determination even when auto-agglutination is present. A comparison study of agglutination card, immunochromatographic cartridge, and gel column (not readily available in clinical settings) blood typing kits for DEA 1 found all methods to be highly accurate (89-91%, 93%, and 100% respectively), making both cage-side test types viable options for blood typing. The immunochromatographic cartridges have the advantages of removing subjectivity on interpretation and allowing typing even with auto-agglutination present as advantages.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 141 of 226 Cross-Matching Cross-matching is the act of exposing donor red cells to recipient plasma (major cross-match) and recipient red cells to donor plasma (minor cross-match), with agglutination or haemolysis indicating incompatibility. While the exact protocol for cross-matching is slightly variable depending on the practice, it involves suspending RBCs in saline to achieve a 3-5% solution, washing the red cells 3-4 times, and preparing four different combination mixtures of recipient red cells and plasma with donor red cells and plasma (major and minor cross match, recipient and donor control). The tubes are then incubated, centrifuged and graded for the level of agglutination and haemolysis. Some protocols call for microscopic evaluation for agglutination in the absence of macroscopic agglutination, or for comparison of the degree of agglutination in the case of recipient auto-agglutination or when samples from all potential donors show a positive cross-match. This allows for determination of the least reactive match, which would indicate selection of blood least likely to cause harm, and most likely to survive the longest within the recipient. Commercial cross-matching kits are also available, which may help standardize the process, though adding expense. For first time transfusions in canines, the necessity for a cross-match is often debated due to the lack of naturally occurring antibodies for DEA 1 and the unlikelihood of an obvious incompatibility reaction. However, if there is any uncertainty in the transfusion history, or if there is a definite history of a previous transfusion, a cross-match would be in order. However, there are good reasons for feline transfusions to be cross-matched despite our ability to match the blood types through AB type testing. There have been reports of AHTR occurring even with an AB system match, likely due to the Mik positive blood being transfused to Mik negative cats. Some evidence also exists for antigens not belonging to the AB and Mik antigen groups. Because of these observations, a cross-match prior to all feline transfusions is indicated, in addition to mandatory typing. BEYOND THE COMPATIBILITY TESTING While the above mentioned methods are quite effective in minimizing transfusion reactions caused by erythrocyte antigens and alloantibodies contained within plasma products, the compatibility tests available to us cannot screen for every possibility of type II hypersensitivity reactions and reduction of red cell life span. In addition, there are no readily available laboratory methods to test for compatibility of plasma component products. This leads us to think about methods to minimize transfusion-related complications in conjunction with compatibility testing. One of these approaches is appropriate blood product selection through application of concepts in blood component therapy. Reducing the transfusion of unnecessary components or the use of alternatives when available will only help minimize

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 142 of 226 occurrences of immunologic complications. In addition, proper administration protocols and the technical staff’s role in the monitoring of patients receiving transfusions is invaluable in early detection and treatment of complications, should they arise. References 1Acierno MM. J Vet Intern Med 2014:28(2);592-598. 2Craft E, Powell L, J Vet Emerg Crit Care 2012;22(6):631-639. 3Creedon J and Davis H, Advanced Monitoring and Procedures for Small Animal Emergency and Critical Care 2012;Ch.59:p759-775. 4Tizard I, Veterinary Immunology 2013;Ch.28-30:p326-364. 5Seth M et al, Am J Vet Res 2012;73(2):213-219. 6Thomovsky EJ J Am Vet Med Assoc 2014:244(2);170-174.. 7Tocci LJ, J Vet Emerg Crit Care 2009;19(1):66-73. 8Weiss DJ and Wardrop KJ, Schalm’s Veterinary Hematology 2010; Ch 92:711-724.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 143 of 226 RVN CLINICAL DISCUSSION FORUM With panellists including Louise O’Dwyer MBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVN, and Racheal Marshall CertVNECC RVN and Chloe Walker RVN RVN clinical case discussion As veterinary nurses we all see cases that challenge our thinking and where we struggle to know if we are doing the right thing. Come along to this panel discussion and hear some of our speakers discuss cases from their past that caused them to think twice. Expect some lively debate! RVN clinical discussion forum

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 144 of 226 Notes page

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 145 of 226 MYTH BUSTERS: USING EVIDENCE TO GUIDE CRITICAL CARE NURSING Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com Is heparinized saline necessary to keep catheters patent? Proper maintenance of peripheral intravenous (IV) catheter is critical in the treatment of patients in critical care, used for fluid delivery, drug administration, blood product transfusion, and parenteral nutrition. The best method in maintaining the catheter is of interest, including catheter patency, maintenance protocol, and dressing methods. Occlusion of IV catheters is a common complication that necessitates replacement of the catheter leading to additional patient discomfort and medical care cost. While catheter material and patient-related factors can be contributors to clot formation, one of the key elements to maintaining patency has been flushing of the catheter with heparinized saline. The use of heparinized saline has associated concerns including coagulopathy, drug incompatibilities, allergic reactions, thrombocytopenia, and thrombosis syndrome. The first veterinary study conducted to determine whether there is any difference in effectiveness between heparinized saline and normal saline compared the use of 10 IU/mL heparinized saline with 0.9% sodium chloride. An 18-ga catheter of 1.25 inch in length was placed in each test subject that were separated into three groups. The first group had their catheters flushed with heparinized saline every 6 hours throughout a 42-hour period. The second group had their catheter flushed with normal saline every 6 hours throughout a 42-hour period. The third group served as a control group used to determine the amount of time it took for a catheter to clot if it were not flushed. Blood was attempted to be aspirated from the catheter prior to each flushing, and also evaluated for any signs of phlebitis. The study observed that all catheters of both treatment groups were able to be flushed without any resistance or occlusion. The number of catheters that allowed for blood to be aspirated back were higher in the heparinized saline group, but the difference was not statistically significant (9 of 12 vs 5 of 12 at 42 hours, p = 0.065). No signs of phlebitis were seen in any group. The authors concluded that the use of heparinized saline flushes did not yield benefits when compared to 0.9% sodium chloride in maintaining peripheral 18-ga catheters in a 42-hour period. This veterinary study follows some of the human studies observing that intermittent flushing of IV catheters with normal saline is as effective as flushing with heparinized saline. It also Myth busters: using evidence to guide critical care nursing

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 146 of 226 suggests that 18-ga IV catheters might not require any flushing at all for the first 24 hours. There are some studies, however, that observed heparinized saline as being superior, muddying the waters on the issue. Some other limitations should be considered, such as the duration of the study being 42 hours. Many catheters in critical care settings are used longer than 42 hours, making information beyond 42 hours’ desirable before heparinized saline is replaced with normal saline completely for flushing. The patency of the catheter was determined through a qualitative evaluation of resistance by the investigators, and so objective measurements of clot formation were available. The study also evaluated a single size of catheter, and the data’s applicability to other sizes and lengths is uncertain. For example, studies surrounding heparinized saline use in central venous catheters currently provides even less definitive conclusions due to the variability in maintenance protocols in regards to heparin concentration and flushing frequency. Other factors within the study that can be different from clinical situations include the catheter diameter, as well as the disease state of the patient (hypercoagulable patients could be more prone to catheter occlusion). A future study of longer duration measuring the effects objectively is desirable to shed more light on the topic. Should IV catheters be replaced routinely? Hospital protocols often recommend replacement of IV catheters in a patient every 72-96 hours as it is thought to reduce the risk of phlebitis and bloodstream infections. The US Centers of Disease Control guideline recommends replacement no more frequently than 72-96 hours. Routine replacement of IV catheters exposes the patient to additional stress and discomfort, venipuncture, and restraint. It also adds financial burden to the owners or at the very least increased staff time and supply demand to the hospital. More recently, many practices have instituted protocols calling for catheter replacement only when clinically indicated, attempting to alleviate the morbidity and costs associated with routine replacement. An assessment of the effects of the two approaches would be beneficial in setting hospital protocols. Numerous studies related to the topic has been conducted on human subjects, being summarized as a systematic review through the Cochrane Collaboration. The systematic review summarized that there was no significant difference in occurrence of catheter-related bloodstream infection (CRBSI) for clinically-indicated or routine replacement with 1 of 2365 and 2 of 2441 patients, respectively (p=0.64). There was no difference in phlebitis seen with 186 of 2365 cases seen in clinically-indicated replacement and 166 of 2441 cases seen in routine replacement methods (p=0.75). Significant reduction of catheter placement costs was seen in the clinically-indicated group, of approximately AUD 7.00. The reviewers

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 147 of 226 concluded that there is no clinically significant difference between clinically-indicated replacement and routine replacement of peripheral IV catheters. Because there is no difference seen between the two methods, a recommendation can be made to adopt a protocol to replace peripheral IV catheter only when clinically-indicated. Patients will avoid being subjected to unnecessary pain and the clients and practice will not incur unnecessary drain on resources. There is currently no veterinary evidence available to provide insight in our practice. There could be differences between species or practice setting such as the higher tendency for veterinary patients to soil or tamper with the catheter insertion site, and any unexpected differences in physiology. With that said, many practices have instituted a clinically-indicated replacement approach without subjective increases in complications. If the clinically-indicated replacement approach is taken, structured protocols on routine inspection of the catheter site of at least every 24 hours for signs of inflammation, infiltration, occlusion or infection should be followed. Do antimicrobial impregnated central venous catheter supplies prevent CRBSI? Central venous catheters (CVC) are often used in critical care for variety of reasons including blood sampling, central venous pressure measurement, infusion of high osmolarity fluid, simultaneous infusion of incompatible drugs through multiple lumens, and parenteral nutrition. A major concern with placement and maintenance of CVCs in a patient is the possibility of CRBSI adding to patient morbidity and mortality. A variety of strategies have been adopted to prevent this common complication, including catheter maintenance bundles, antimicrobial treatment of the catheter and antimicrobial treatment of catheter insertion site or dressings. A Cochrane review of antimicrobial-treated (AMT) (antiseptic or antimicrobial impregnation, coating, or bonding) CVCs compared the difference between AMT and non-AMT CVCs, the difference between the effect of antimicrobial impregnation and antimicrobial modification (antiseptic dressing, hubs, tunnelling, needleless connectors, etc.) and any differences between identifiable subgroups such as length of catheter use and practice setting. The review consisted of 16,784 catheters and 11 impregnation types. The review summarized that catheter impregnation significantly reduced CRBSI. However, it did not reduce the incidence of sepsis, mortality, and catheter-related local infections. There were significant benefits seen in ICU settings when compared to hematological and oncological units or CVC use for parenteral nutrition. AMT did not affect the incidence of other adverse events such as thrombosis, thrombophlebitis, bleeding, erythema or tenderness at the insertion site.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 148 of 226 A review of antimicrobial dressing in CVC placement in human infants saw that chlorhexidine dressing/alcohol skin cleansing reduced catheter colonization in a similar manner to polyurethane dressing/povidone-iodine cleansing, and was no different in its effect on sepsis and CRBSI. Chlorhexidine dressing seemed to cause higher incidence of contact dermatitis, however. Silver-alginate patches did not cause adverse effects, but their efficacy is unclear. A separate review of dressing and securement devices for CVCs evaluated various devices and their effect on CRBSI, catheter colonization, site infection, skin colonization, skin irritation, failed securement, dressing condition, and mortality. The review summarized that chlorhexidine gluconate-impregnated dressing reduced incidence of CRBSI and catheter tip colonization when compared to standard polyurethane dressing. Medication-impregnated dressing reduced CRBSI rate when compared with non-impregnated dressing. Of all, the use of sutureless securement device was the most effective and chlorhexidine gluconate impregnated dressing the second most effective in reducing CRBSI. While the evidence evaluated by these reviews are of human subjects, some messages can be extracted for potential benefits in the veterinary field. The use of AMT CVCs might not be as effective as theorized as incidence of sepsis and mortality was not significantly different. The use of antimicrobial-impregnated dressing should be encouraged, and implementation of sutureless securement devices explored. Implementation of antimicrobial-impregnated dressing is a relatively inexpensive intervention available, and should be considered if current protocols include the use of standard polyurethane dressing or gauze. Should patients with gastroenteritis be fasted? Patients exhibiting gastroenteritis with signs of vomiting and diarrhea are often placed on a nil per os (NPO) nutritional plan as it is considered to be beneficial for the patient. The reasoning behind this thought are various. One of which is the resting of the bowels by minimizing stimulation for contractions, reducing fecal volume, and frequency of defecation. Another is to reduce the chance of vomiting due to stimulation through distension of the stomach. By fasting, the vomitus is thought to contain less nutrients that can increase the chances of bacterial proliferation and pneumonia if aspirated. The presence of undigested food in the gastrointestinal system is also thought to have detrimental effects such as promoting bacterial proliferation and secondary infections, or inducing osmotic effusion into the gastrointestinal lumen leading to exacerbation of diarrhea. Offering of food while a patient is nauseated can also lead to food aversion, contributing to the delay in regaining of appetite when the patient is feeling less ill. Because of these reasons, a traditional approach to gastroenteritis is to withhold food for 24-72 hours before offering food.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 149 of 226 However, there are numerous veterinary studies that support the institution of enteral nutrition early in the stages of hospitalization. A study involving patients with hemorrhagic gastroenteritis having a hydrolyzed protein diet introduced early in hospitalization observed that it did indeed increase the frequency of vomiting, but only initially. These patients saw a reduction in the frequency of vomiting and regained tolerance to feeding within 2 to 3 days. It is thought that the introduced food serves as a prokinetic and thus reduces the amount of vomiting when compared to a fasted state. Another study involved patients with parvoviral enteritis being split into a group that was fasted and a group that was given enteral feeding. The investigators observed that patients that were fed stopped vomiting significantly sooner than patients that were fasted, leading to the conclusion that early enteral nutrition is beneficial for cessation of vomiting. However, food-high in fat, soluble fibre or poorly digestible starch can promote emesis instead. Gastric distention does contribute to stimulation of vomiting as well. With these points in mind, feeding small, low fat meals frequently is recommended. Providing nutrition early will also prevent patients from experiencing vigorous peristaltic action that is described by people as “hunger pains”, as the presence of food promote normal peristaltic action. The presence of volatile fatty acids such as proprionic acid and butyric acid provides an acidic environment in the gastrointestinal lumen suppressing the proliferation of pH sensitive pathogens such as Campylobacter and Clostridium spp. likely having some beneficial effects in preventing secondary bacterial infections. In terms of structure of the gastrointestinal mucosa, fasted animals experience a reduction in villous height and crypt depth, decreased antioxidant content in mucosal tissues, and increased induction of enterocyte apoptosis. The gastrointestinal mucosa provided food will instead experience healthier mucosal turnover and strengthening of the mucosal barrier. The gastrointestinal mucosa seems to rely on luminal nutrients to passively obtain glutamine, amino acids, essential fatty acids, folate, zinc, vitamin A, and vitamin B12, which are all necessary for healthy mucosal turnover. Each of these factors serve to reduce chances of bacterial translocation in patients provided nutrition. Presence of luminal nutrients also reduce the expression of adhesion molecules and subsequent neutrophil sequestration and activation, and keeps the function of T and B lymphocytes to produce IgA and cytokines intact, providing benefits to immunologic functions. These reasons support providing enteral nutrition as soon as fluid deficits are replenished. Many negative effects of feeding can be alleviated through providing smaller amounts of a highly digestible diet that is low in fat. Other evidence supports the importance of earlier nutritional intervention in many critical illnesses.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 150 of 226 Nasogastric tube or nasoesophageal tube? Nasoenteral tubes are used in hospitalized patients to provide enteral nutrition with liquid diets on a short term basis, especially when anesthesia is undesirable. Nasoenteral tubes can be inserted to be terminated either in the esophagus or the stomach, called nasoesophageal (NE) and nasogastric (NG) tubes, respectively. Each of these tubes are associated with shared complications such as epistaxis, dacrocystitis, rhinitis, aspiration pneumonia, occlusion of tubes, diarrhea, vomiting or regurgitation, and unintended removal. The selection of NE versus NG tube placement is a choice presented to the veterinary team. NG tubes had been avoided by some because of the potential for an increase in the risk of regurgitation, gastroesophageal reflux, and resultant esophagitis or stricture as the tube being placed across the lower esophageal sphincter prevents full closure. NE tubes will allow these risks to be circumvented, though the potential for unintended displacement of the tube might be increased, and NE tubes will also deny the ability to decompress the stomach or measure gastric content that NG tubes provide. The optimal type of nasoenteral tube chosen has been largely up to the clinician’s preference. A retrospective veterinary study evaluated the incidence of complications between the two methods to determine any advantage of one over the other. The study evaluated the occurrence of complications including epistaxis, vomiting, regurgitation, diarrhea, clogged tube, tube malpositioning, aspiration pneumonia, hyperglycemia, and refeeding syndrome. The study also evaluated differences including feeding method (bolus vs CRI), amount fed (% RER), and administration of medications by tube. The study observed no significant difference of complication rate between NE and NG tubes, nor other factors (feeding methods, amount fed, and medications). The lack of a difference seen in the study makes us think that there is likely no difference between the placements of NE or NG tubes. While there is a possibility that subclinical esophagitis existed, there were no patients that showed clinical signs of esophagitis. There was a significantly higher amount of deaths seen in patients receiving NG tubes, though this is likely to be attributed to NG tubes being utilized in more critically ill patients and an artefact due to the retrospective nature of the study. Because NG tubes provide the benefit of allowing gastric decompression and there, seemingly, being no clinical signs of resultant esophagitis, clinicians should be feeling less hesitation on using NG tubes over NE tubes.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 151 of 226 References Bradford NK, Edwards RM, Chan RJ. Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review. Int J Nurs Stud 2016;59:51-59. Liu DT, Brown DC, Silverstein DC. Early nutritional support is associated with decreased length of hospitalization in dogs with septic peritonitis: A retrospective study of 45 cases (2000–2009). Journal of Veterinary Emergency and Critical Care 2012;22(4):453-459. Mohr AJ, Leisewitz AL, Jacobson LS, et al. Effect of Early Enteral Nutrition on Intestinal Permeability, Intestinal Protein Loss, and Outcome in Dogs with Severe Parvoviral Enteritis. J Vet Int Med 2003;17:791-798. Ueda Y, Odunayo A, Mann FA. Comparison of heparinized saline and 0.9% sodium chloride for maintaining peripheral intravenous catheter patency in dogs. J Vet Emerg Crit Care 2013;23(5):517-522. Webster J, Osborne S, Rickard CM, New K. Clinically-indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database Syst Rev 2015;14(8):CD007798. Will K, Nolte I, Zentek J. Early Enteral Nutrition in Young Dogs Suffering from Haemorrhagic Gastroenteritis. J Vet Med Ser A 2005;52(7):371-376. Yu MK, Freeman LM, Heinze CR. Comparison of complication rates in dogs with nasoesophageal versus nasogastric feeding tubes. J Vet Emerg Crit Care 2013;23(3):300-304.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 153 of 226 PRIOR PLANNING PREVENTS POOR PERFORMANCE Louise O’Dwyer MBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVN Clinical Support Manager, Vets Now, UK louise.odwyer@vets-now.com Introduction Patients requiring anaesthesia can present with a wide variation in clinical signs and systemic conditions, all of which require some consideration before anaesthesia is commenced. Evaluation of patients should include a full clinical history, physical examination, diagnostic testing, as well as individual patient considerations, e.g. breed, reason for anaesthesia. The aim of the preoperative evaluation is to determine if there is any disease present that will affect the uptake, action, metabolism, elimination, and safety of the anaesthetic. Primarily the cardiopulmonary, nervous, renal and hepatic are the systems of greatest concern. The history and physical examination are the best determinants of disease. Laboratory tests should only be performed on the basis of history/physical examination. It has been shown that the use of extensive laboratory screening has not improved outcome in human or veterinary medicine. What is normal? The reference ranges, ‘normal’ for laboratory tests are presumed to be within +/- 2 standard deviations of the mean, and therefore 5% of normal animals fall outside this range. The upper and lower values do not represent a cut off between normal and disease. Indeed, a normoglycaemic diabetic, or an animal with cirrhosis with normal hepatic enzymes and bilirubin will seem unremarkable on screening and therefore fall into the ‘normal’ category when that is far from the case. There seems to be no relationship in most cases between the presence and severity of disease and the extremeness of the laboratory values! These points stress the importance of accurate history taking and physical examination. History This should include previous and current health status questions, complaint severity and duration and other associated symptoms (diarrhoea, vomiting, PU-PD, exercise tolerance, dyspnoea etc.), exposure to drugs (OPs, digitalis, diuretics, beta-blockers, anticonvulsants, steroids, NSAIDs, ABs etc.), anaesthetic history, pregnancy and time of last feed. Clinical Examination Prior planning prevents poor performance

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 154 of 226 A thorough clinical examination of all the body systems should be completed by both the vet and the nurse. Depending on the history and examination laboratory tests or X ray, ECG etc. can be ordered. Following this initial evaluation, it is useful to place the patient in ASA category I-V. Category Physical Status Examples I Patient is normal and healthy OHE, castration II Patient has a degree of mild systemic disease Localised infection, F# no shock, skin tumour, cardiac disease-compensated III Patient has severe systemic disease Anaemia, fever, dehydration, cachexia IV Patient has severe systemic disease that is constant threat to life Toxaemia, severe dehydration, anaemia, CHF decompensated, emaciation V Patient is moribund and unlikely to survive >24 hours Severe trauma, terminal malignancy, shock Table 1. American Society of Anesthesiologists (ASA) Classification of Health Status Signalment Breed sensitivities are often quoted, but other than sight hound barbiturate sensitivity, BOAS and toy breeds (SA:Bdwt) all breeds have been successfully anaesthetised using the standard regimes. Age should be considered. <11 weeks and the geriatric patient will not metabolise drugs as well. Neonates have altered body water, respiratory dynamics and immature p/s nervous system and reduced thermoregulatory capacity. Healthy geriatric patients should receive sedative drugs at a reduced dose (30%). Intravenous fluids will be indicated in the geriatric patient to improve organ perfusion. Patient preparation Healthy dogs and cats should be starved for at least 6 hours prior to anaesthesia. The reason is twofold, firstly to reduce the risk of aspiration during induction and recovery (silent aspiration can occur too) and secondly, to reduce the pressure on the diaphragm and maximize functional residual capacity (FRC) thereby improving ventilation. Dogs and cats

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 155 of 226 less than 8 weeks old should not be fasted for longer than 1-2 hours. Water is made available to the patient up to the time of premedication. In older dogs with nephritis the stress of the procedure/illness/hospitalization can be detrimental and intravenous fluids are indicated to induce a moderate diuresis. The Anaesthetic Plan The considerations for devising a plan are listed below and these should be considered before premedication. 1. Procedure being planned a) Duration b) Type of surgery/investigation/medical vs surgical c) Anticipated post-op pain 2. Temperament of the patient a) Nervous or excitable b) Vicious c) Recumbent/comatose d) Calm and relaxed 3. Available equipment/expertise a) Anaesthetic machine/inhalant available b) Expertise of team surgeon/anaesthetist c) Restraint d) IPPV facilities 4. Breed 5. ASA category Breed Considerations Breed considerations can also influence anaesthetic protocols:  The brachycephalic group should prompt us to consider possible difficult intubation and late extubation, careful monitoring after pre-medication and in recovery in addition to the considerations previously outlined.  Dobermans are known to be a breed with a high incidence of abnormally low von Willebrands factor concentrations. Screening or at the least a buccal mucosal bleeding time should be assessed in all cases prior to anaesthesia. Dogs that are shown to be deficient in von Willebrands factor will require treatment usually with desmopressin and cryoprecipitate.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 156 of 226  Boxers appear to have a genetic disposition to acepromazine sensitivity and therefore acepromazine should be avoided altogether or doses should be significantly reduced.  Miniature Schnauzers are at risk for developing sick sinus syndrome and should have an electrocardiogram (ECG) evaluated prior to anaesthesia, other breeds in which cardiac disease is prevalent are geriatric cats (hypertrophic cardiomyopathy) and giant breeds. Ventricular arrhythmias are also a common feature of patients with abdominal, e.g. GDVs, septic abdomen, splenic disease. Anaesthesia Complications and Fatalities In 2006 Dr. David Brodbelt of the Royal Veterinary College (London, UK) completed a detailed prospective Confidential Enquiry into Peri-operative Small Animal Fatalities (CEPSAF), reporting overall mortality figures of 0.17% and 0.24% for dogs and cats respectively. Healthy dogs and cats had mortality rates of 0.05% and 0.11%, respectively, while ‘sick’ animals had figures of 1.33% and 1.4% for dogs and cats, respectively. For the purposes of CEPSAF, an anaesthetic-related death was defined as “perioperative death within 48 hours of termination of the procedure, except where death was due solely to inoperable surgical or preexisting medical conditions”. Perhaps one of the most alarming issues to arise from the study was the timing of anaesthetic-related death: almost 50% of dogs and >60% of cats that died, did so in the recovery period, with around 50% of them succumbing within the first 3 hours after termination of the anaesthetic, and many animals were unattended at this time. This suggests that greater attention should be made to continued observation, monitoring and support of animals in the post anaesthetic period. CEPSAF identified a number of factors that may be associated with an increase in the odds ratio (OR) of mortality in different species. Dogs Overall, when compared to control dogs, there was a 6-fold increase in odds of dying for every 1 point increase in ASA status, i.e. as dogs became sicker, anaesthetic mortality increased proportionally. This is perhaps not surprising, but emphasises the need, where feasible, to stabilise patients as much as possible prior to undertaking anaesthesia. There was also a 2.5 fold increase in odds associated with the urgency of the procedure the animal was undergoing, from elective, through urgent to emergency. While this may be confounded by the animal’s health status discussed above, there seemed to be a genuine trend towards increasing mortality, independent of the ASA status.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 157 of 226 1. Patient age 2. Body weight 3. Duration of procedure 4. Complexity of procedure 5. Drug effects 6. Mode of ventilation 7. Pre-anaesthetic blood testing Cats In both the Clarke and Hall and CEPSAF studies, mortality was higher in cats than in dogs, for both healthy and sick individuals. In common with the canine data, mortality increased in cats with increasing ASA status (odds ratio of 3.2 for every 1 increment in ASA status), and also with the urgency and complexity of the procedure. A number of other factors were also shown to contribute to increased mortality in this species: 1. Patient age 2. Bodyweight 3. Duration of procedure 4. Complexity of procedure 5. Drug effects 6. Endotracheal intubation 7. Fluid therapy 8. Monitoring 9. Nitrous oxide Conclusion Anaesthesia planning is multifactorial, and all aspects of the anaesthetic should be considered and planned for. Additionally, the use of anaesthesia checklists should be considered, as they will improve the efficiency in which the anaesthetist can ready, and can help ensure no aspect of anaesthesia is missed. Checklists include the anaesthetic machine, breathing systems, monitoring equipment, resuscitation supplies etc.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 159 of 226 ANAESTHESIA MONITORING PARAMETERS Louise O’Dwyer MBA BSc(Hons) VTS(Anesthesia & ECC) DipAVN(Medical & Surgical) RVN Clinical Support Manager, Vets Now, UK louise.odwyer@vets-now.com INTRODUCTION Performing the monitoring of a patient’s vital parameters during general anaesthesia is a hugely important and vital aspect of any diagnostic or surgical procedure. As well as using our eyes, ears, hands and brain, the use of electronic monitoring equipment, allows decisions made during anaesthesia to be based on several, rather than one, physiological variable. Multiparameter monitors, in recent years, have become more commonly available in both general as well as specialty practice. The importance of good monitoring during anaesthesia cannot be underestimated. This should involve the use of both manual and electronic methods, but should allow the anaesthetist to act on the information gained in a timely manner. When using electronic equipment, it is essential that the anaesthetist is able to interpret the values and waveforms displayed and act upon them, with one major issue being not understanding the information and being able to act in order to correct the abnormality. PULSE OXIMETRY Pulse oximetry is a non-invasive method of measuring the haemoglobin (Hb) oxygen saturation (SpO2) in arterial blood. Pulse oximetry involves the placement of a clip over a peripheral area of tissue, most commonly the tongue, although other areas can be used. There are other types of probes available, which wrap around tissues or are used in the rectum. LEDs in the pulse oximeter clip emit infrared light (IR). The absorption of red and IR light differs between the Hb species and pulsatile blood flow is used to distinguish arterial from venous blood. The pulse oximeter uses this data to calculate SpO2. The SpO2 should be above 97 per cent in the anaesthetised patient breathing 100 per cent oxygen, and any persistent value below this should be investigated. The first step that often alleviates this problem is to alter the probe position, thereby allowing tissue beds to re-perfuse. If SpO2 is low, then the heart rate (HR) measured by the monitor should be checked against a manual rate from the patient. If they do not agree, the SpO2 is likely to be inaccurate. If the value is definitely low then the patient, anaesthetic machine and breathing system should be checked. Pulse oximetry is a useful monitoring tool because it requires blood flow and, therefore, tissue perfusion to display any information. The addition of a displayed HR and, in Anaesthesia monitoring parameters

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 160 of 226 some cases a plethysmograph (pulse waveform), add additional information on pulse rate and quality. Errors can occur due to factors including movement, peripheral vasoconstriction, ambient light and inadequate or excess tissue depth. BLOOD PRESSURE MEASUREMENT Arterial blood pressure is derived from the relationship between cardiac output and systemic vascular resistance. During general anaesthesia, a mean arterial pressure greater than 60mmHg (systolic arterial pressure greater than 90mmmHg) is considered the minimum to maintain autoregulation of blood flow to tissues such as the kidney, brain and liver. There are two categories of blood pressure measurement – invasive and non-invasive. The non-invasive method is the most commonly utilised, is easy to apply and reliable in most patients. It does not provide continuous measurement though and may be inaccurate in patients with severe hypotension and those with arrhythmias. Assessment of obtained blood pressure values may be used to aid any adjustment in depth of anaesthesia. Mean arterial blood pressure (MAP) above 60mmHg is recommended during anaesthesia and the range 60 mmHg to 90mmHg is often referred to. If a patient is hypotensive fluid therapy should be started, if not already begun, and a 10ml/kg (5ml/kg cats) bolus of crystalloid administered over 15 to 20 minutes. MAP should then be reassessed and, if it remains low, a second crystalloid bolus may be administered and/or a 2ml/kg to 5ml/ kg colloid bolus. Only after these steps should drug therapy be considered. If the patient is not at too deep a plane of anaesthesia then administration of further analgesia (such as an opioid) is likely to be required to enable the vaporiser setting to be reduced, if necessary, and fluid therapy instituted as above. If hypertensive (MAP > 90mmHg) then the patient may be at too light a plane of anaesthesia or insufficient analgesia is present for the current level of surgical stimulation. Depending on which may be present then either increasing the depth of anaesthesia or administering additional analgesia should be considered. The use of inotropes and vasopressors can also be considered once the cause of hypotension is determined. Other possible causes of hypotension include haemorrhage, reduced venous return, bradycardia, arrhythmias, sepsis and cardiac disease. Non-invasive methods – Oscillometric Oscillometric blood pressure measurement is the most commonly used in small animal veterinary practice. Commercially available machines consist of an electronic display and control unit connected via hosing to an appropriate sized cuff. This method provides intermittent, indirect measurement of blood pressure. The cuff width should be approximately

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 161 of 226 40 per cent of the limb circumference and the centre of the cuff placed over the peripheral artery. The cuff should be firmly in place, but not excessively tight. A transducer converts the oscillations into an electrical signal and the machine displays the systolic, mean and diastolic blood pressure. The use of changes or trends of blood pressure over time is probably most useful when assessing a patient during anaesthesia. – Doppler ultrasonic detection This technique uses the Doppler effect to detect arterial blood flow. The Doppler probe consists of an ultrasonic crystal and transducer, which is placed over a peripheral artery, most commonly the dorsal metatarsal, plantar metatarsal or palmar metacarpal artery to provide an audible signal to blood flow. The concave surface of the probe should have ultrasound gel applied to it prior to placing and securing over the artery. This can be used not only to aid in blood pressure measurement but also to provide an audible pulse rate. Again, the cuff width should measure 40 per cent of the limb circumference and is attached to a sphygmomanometer, to allow measurement of pressure. The Doppler crystal is taped in place over the peripheral artery after detection of a pulse. The cuff is then inflated to around 10mmHg above the point at which the pulse is no longer audible. The cuff is then slowly deflated until the pulse is once again audible. The pressure reading at this point is recorded. This should be repeated several times and the average reading taken. This method is useful in smaller patients; particularly cats where the oscillometric method might be unreliable. The audible pulse is of benefit in patients where other methods of pulse detection may fail due to, for example, cold extremities and vasoconstriction. Care should be taken to securely attach the Doppler unit to prevent loss of signal if the patient is moved during anaesthesia. Invasive methods – Direct arterial catheterisation Direct arterial catheterisation is the gold standard in blood pressure measurement and is recommended in sick and compromised patients. It requires arterial catheterisation, which in the majority of small animal patients will involve a peripheral artery. Vessels suitable for catheterisation include the dorsal metatarsal artery and plantar metacarpal or metatarsal artery. Some veterinary anaesthetists use the coccygeal artery in cats. Arterial catheterisation is a skilled procedure that is not without potential complications. These include significant haemorrhage, infection and tissue ischaemia distal to the catheter insertion site – but these are rare. As well as displaying SAP, DAP and MAP, it also displays a continuous, arterial trace waveform, which allows for further evaluation of the cardiovascular system. The advantages of this method are that it is a continuous, direct measurement and, therefore, significant hypotension and arrhythmias do not interfere with

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 162 of 226 its readings. CAPNOGRAPHY Capnography is used to assess adequacy of ventilation. A capnograph displays a capnogram and the end-tidal carbon dioxide partial pressure (ETCO2), whereas a capnometer displays only the ETCO2. Capnography is an indirect monitoring tool and provides information on CO2 production, pulmonary perfusion, respiratory rate and pattern and CO2 elimination. Normal PaCO2 ranges between 35mmHg and 45mmHg and ETCO2 is also considered to have the same reference range, although it is likely to be slightly lower than PaCO2 due to ventilation and perfusion mismatching during anaesthesia. CO2 is measured in the gas sampled between the end of the patient’s endotracheal tube and the breathing system. Two types of capnograph are available: • A mainstream device where gas is analysed at the patient end and a side stream device where gas is pumped to the monitor and analysed. Care must be taken not to damage this part of the device as repairs are costly. • The side stream device is most commonly used and has the advantage of being less bulky around the patient, although it has an associated time lag due to the tubing carrying gas from the sampling site. In practice this is not a concern. The shape of the capnogram is of benefit when assessing problems affecting ventilation, such as partial or complete airway/endotracheal tube obstruction, rebreathing of expired gases or bronchoconstriction. It is also of benefit when confirming correct placement of an endotracheal tube, alerting the clinician to disconnection of the patient from the breathing system and cardiac arrest. Rebreathing of expired gases may occur due to inadequate fresh gas flow in a non-rebreathing system, expired CO2 absorbent in a rebreathing system or a rapid respiratory rate may also be diagnosed with capnography. The trace baseline will be elevated from zero, due to the presence of CO2 in the inspired gas mixture and some monitors will also display an inspired CO2 concentration (FiCO2). ELECTROCARDIOGRAPHY Electrocardiography (ECG) displays cardiac rhythm and electrical activity only and, therefore, gives no indication as to the circulation and tissue perfusion. It is a useful additional monitoring tool, but because of the above limitations, should not be relied on as the sole method of monitoring during anaesthesia.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 163 of 226 The normal ECG is a result of summation of the action potentials of each cardiac cell and is made up of three main parts: • the P wave corresponding to atrial depolarisation; • the QRS complex corresponding to ventricular depolarisation; and • the T wave corresponding to ventricular repolarisation. Atrial repolarisation is lost within the QRS complex in most ECGs and, therefore, is not assessed. Lead attachment and setup The normal lead configuration used during anaesthesia in small animal patients is a three lead ECG, using lead II for the waveform generation. ECG interpretation The ECG trace should be observed and assessed for rhythm, the presence of a P wave for every QRS complex and a QRS complex for every P wave should be determined. The R-R interval may be used to assess rhythm. The QRS complexes should be assessed for uniformity, as any difference in shape or size may suggest a ventricular arrhythmia is present. The commonly encountered ECG abnormalities will be discussed here. For further ECG interpretation, refer to the reading list. Sinus arrhythmia is a normal variation in healthy patients and may become more pronounced after premedication or during anaesthesia and is associated with the respiratory cycle. CONCLUSION Good patient monitoring is vital for safe anaesthesia. Electrical equipment provides very useful information but there is no substitute for manual monitoring of a patient’s vital signs. No single piece of monitoring equipment can give us all the information we need so several methods should be available to assess any trends that develop.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 165 of 226 WHAT POINT OF CARE LUNG ULTRASOUND CAN TELL US: CANINE CASES WITH RESPIRATORY DISTRESS (Vet BLUESM IN DOGS) Gregory R. Lisciandro, DVM, Dipl. ABVP, Dipl. ACVECC Hill Country Veterinary Specialists & FASTVet.com, San Antonio, Texas USA Email FastSavesLives@gmail.com Text Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley © 2014 Introduction and History The use of lung ultrasound (LUS) dates back into the late 1980s, notably with the ultrasound diagnosis in 1987 of pneumothorax (PTX) by a veterinarian, an equine practitioner, Dr. Norman Rantanen. Within a year, the ultrasound diagnosis of PTX was similarly described in human medicine. In 1988, Dr. Roy Philly dubbed the ultrasound probe the “modern stethoscope”, an unbelievably remarkable foresight made 28 years ago. More recently, the ultrasound probe has been dubbed the “visual stethoscope” because LUS artefacts are objectively and clearly discernible independent of patient or ambient noise. Moreover, LUS has been definitively shown to exceed traditional means of chest auscultation and supine chest radiography in humans with common respiratory conditions. As long ago as 1997, the LUS finding, then referred to as comet tails and representing forms of alveolar-interstitial edema, was documented in human lung by Lichtenstein and colleagues. After that time, it seemed that the focus of LUS over the next several years changed from the pursuit of lung pathology the LUS diagnosis of pneumothorax (PTX). Several comparative studies clearly showed that PTX could be accurately diagnosed, rapidly and point-of-care, by LUS; and importantly that lung ultrasound exceeded the accuracy, sensitivity and specificity of supine chest radiography. Furthermore, ultrasound-diagnosed PTX was shown to compare quite favourably with computerized tomography (CT), considered the gold standard for the diagnosis of PTX. During this same time, a structured lung ultrasound format was developed called “EFAST” for “extended FAST” by Kirkpatrick and colleagues (2004). EFAST was named as such since it was an additional FAST scan that extended from the FAST abdominal views. Because PTX was a real-time finding during B-mode use, other ultrasound modalities were created to document PTX in medical records including the “Power Slide” using power Doppler (Kirkpatrick) and the “seashore sign” and “stratosphere sign” using M-mode Point of care lung ultrasound: canine cases with respiratory distress

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 166 of 226 (Lichtenstein and colleagues), representing dry lung and PTX, respectively. Again, power Doppler and M-mode were primarily modes for documenting PTX and not necessarily for diagnosing PTX. The author has found in small animal medicine there often is too much thoracic wall movement to effectively use these documenting modalities in spontaneously breathing dogs and cats. In addition to clearly demonstrating the ultrasound diagnosis of PTX, Lichtenstein and colleagues showed how the search for the “Lung Point”, where lung re-contacts the chest wall, not only helped determined the degree of PTX, but also increased the sensitivity of diagnosing PTX using ultrasound (2000). The “Lung Point” debunked the myth that the ultrasound diagnosis of PTX was an “all or none” phenomenon by showing that partial vs. massive PTX could be determined using LUS. Another offshoot of the use of LUS in trauma, was the finding that lung contusions, referred to a B-lines or ultrasound lung rockets, could be easily recognized by non-radiologist sonographers and the finding rapidly ruled out PTX. In 2004, Jambrik and colleagues refocused lung sonographers on the pursuit of lung pathology in non-trauma subsets of human patients. In 2006, Volpicelli and colleagues showed that the counting of ultrasound lung rockets (ULRs), also called B-lines, correlated with the degree of lung edema found on computerized tomography. In Chest 2008, Lichtenstein and colleagues published a clinical paper in which they showed that a pattern-based, regional approach, called the BLUE Protocol, could diagnose the most common presenting causes of respiratory disease in human patients with high sensitivity, specificity and accuracy including asthma, COPD, lung edema, PTE, and pneumonia. The BLUE Protocol had a remarkable overall accuracy of 90.5%; and the BLUE Protocol only took minutes helping direct clinical course and diagnostics without the insensitivity of traditional means of physical examination and chest auscultation; and without the delays of waiting for chest radiography and other testing. In another Lichtenstein publication (2009), a direct correlation between pulmonary capillary wedge pressure (invasive) and the presence of lung edema (B-lines or ULRS) was found; and conversely they found that in the absence of lung edema (B-lines or ULRs) that clinically relevant left-sided congestive heart failure could be rapidly ruled out (minutes) with high sensitivity and specificity, point-of-care, and within minutes of patient presentation. In 2012, an international LUS consensus statement was made by a group of international LUS experts. In an evidence-based document, statements were developed regarding the efficacy and clinical utility of LUS use for various respiratory conditions, re-affirming the positive diagnostic and monitoring potential of LUS.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 167 of 226 However, the use of terms such as lung sliding (glide sign in veterinary medicine), and A-lines, and B-lines, C-lines/C Profiles and PLAP continue to thwart the evolution and widespread use of LUS. These terms are confusing and difficult to grasp in contrast to analogous visual terms proposed by the author and still appearing in the human literature including glide sign (veterinary term, same as lung sliding in human medicine), A-lines (same, air reverberation artefact), ultrasound lung rockets (B-lines in human medicine), and Shred Sign (Wedge Sign, PTE), Tissue Sign, and Nodule Sign for lung consolidation/infiltration (called C-lines/C Profiles, PLAP, in human literature). These terms have been proposed in the veterinary literature in a clinical review (Lisciandro 2011), a textbook available in English, Greek and Spanish (and soon in Japanese, and Chinese) Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014, and in a few peer-reviewed clinical study by Lisciandro, Ward, DeFrancesco and colleagues. These terms have also appeared in the human literature (Lichtenstein several reviews); and a textbook Point-of-Care Ultrasound, Eds. Soni, Arntfield, Kory. Elsevier ©2015. Use of Lung Ultrasound Formats in Small Animals The reluctance to pro-actively apply LUS to small animals with respiratory distress is irrational in many respects. The overriding belief that air-filled lung creates insurmountable obstacles, and the continued belief in small animal medicine that imaging lung is difficult to perform leading to mistakes, perpetuate LUS delayed use in small animal veterinary medicine. Thoracic FAST called TFAST (2008) was the first standardized abbreviated veterinary ultrasound exam of the thorax that included the Chest Tube Site (CTS) for lung surveillance for detection of PTX and lung contusions. However, because of the finding of lung pathology found during TFAST, the author extended lung surveillance from the TFAST CTS with the addition of 6 more lung views applied to non-trauma subsets of small animals. The name of this novel regionally-based LUS exam has been studied and published by Lisciandro and colleagues in 2014 as the Vet BLUE Protocol (“Vet” for veterinary and “BLUE” blue for cyanosis and bedside lung ultrasound exam or in emergency). The Vet BLUE regional sites include the caudo-dorsal (Cd) lung region, the peri-hilar (Ph) lung region, the middle (Md) lung region, and the cranial (Cr) lung region. Each is named as a region because the views do not directly correlate with anatomical names of lung lobes. This is important to appreciate because 2 parts of a lung lobe or 2 different lung lobes may be coming into view over the same intercostal space during Vet BLUE. As an example, dry lung, then wet lung, then dry lung, then wet lung may interchange during phases of respiration; or dry lung, and a shred sign, and dry lung then a shred sign,

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 168 of 226 as the patient inspires and expires, This phenomenon in fairly common. Expect cats (and dogs) without respiratory disease to have dry LUS artefacts predominate as normal. This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014. How to Perform Vet BLUE Patient Preparation Generally, no Vet BLUE sites are shaved! All images shown by the author are unshaved sites at which the fur is parted and alcohol is applied to the skin and a small amount of acoustic gel or alcohol-based hand sanitizer to the probe head. Keep in mind that most ultrasound manufacturers warn against placing alcohol directly on the probe head because of alcohol’s potentially damaging effects. No images from cases in this talk were shaved. Patient Positioning Vet BLUE is performed in sternal recumbency or standing and is safer for dogs and cats in respiratory distress. A roll of towels or paper towels under the forelegs of a cat is an easy tolerated maneuver to gain access to the lower ventral Vet BLUE and TFAST Pericardial Site views. Vet BLUE may also be performed in dogs and cats in lateral recumbency. The “Gator Sign” – Basic Lung Ultrasound Orientation Figure. The rounded rib heads are likened to the eyes, and the pulmonary-pleural (PP-line) interface to the bridge of its nose, as a partially submerged gator (alligator) peers at the sonographer. The proximal white line is the focus of all LUS. The major orientation error is looking beyond the PP-line (or “Lung Line”) and mistaking A-line artefacts for the PP-line or “lung line” or being over the abdomen and mistaking liver, stomach (especially when air-filled), or the gallbladder for lung pathology. This material is reproduced with permission of

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 169 of 226 John Wiley & Sons, Inc., Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014. Reproduced with Permission Lisciandro, JVECC 2011;20(2):1104-122. Probe Orientation and Type LUS orientation is always the same with the visualization of the “Gator Sign” to properly identify the pulmonary-pleural interface or the “Lung Line”, actual surface of the lung. The probe is held perpendicular to the long-axis of the ribs; depth is generally set between 4-7cm; frequency is generally set between 5-10 MHz; and a microconvex probe is preferred over a linear probe because the probe is acceptable for all 3 formats - AFAST, TFAST and Vet BLUE – combined called Global FAST or GFAST. A phase-array or sector probe is generally not recommended because its focal point is too small, although this is unknown. A linear probe may be used, however, it is generally not ideal for the AFAST and TFAST portions of Global FAST. Vet BLUE Examination This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014 How to Perform The Vet BLUE lung examination is a screening test performed identically as the probe is positioned at the CTS view of TFAST. The probe is then moved through regional locations that are bilaterally applied as follows: caudodorsal lung region (Cd - same as the TFAST3 CTS view, upper third, 8-9Th intercostal space), perihilar lung region (Ph – 6-7th intercostal space, middle third), middle lung region (Md – 4-5th intercostal space, lower third), and cranial lung region (Cr – 2nd-3rd intercostal space, lower third).

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 170 of 226 Figure. A) No ULRs B) A single ULR scored as “1” or 2 or 3 not shown C) >3 ULRs where there are more than 3 but ULRs are still recognized as individual ULRs and D) ∞ or infinity ULRs. FASTVet.com ©2015, 2016 The maximum number of ULRs over a single representative intercostal space at each respective Vet BLUE view is recorded. The counting system is as follows: 0; 1; 2; 3; >3, when ULRs are still recognized as individuals; and ∞ or infinity, when the ULRs blend into one another becoming confluent. Because most typing keyboards do not have an infinity symbol, we use the “&” sign for infinity ULRs. ULRs are counted because they have been shown to correlate with the degree of alveolar-interstitial edema on computerized tomography. Key Point Best way to perform Vet BLUE accurately is to locate the left TFAST Chest Tube Site directly above the xiphoid in the area of the 8-10th intercostal space in the upper 1/3rd of the thorax, then cheating by moving 1 or 2 intercostal spaces cranially to make sure the probe is over lung/pleural space and not over liver/stomach/abdominal contents. From the left TFAST CTS, which is the same as the left Vet BLUE Cd view, draw a line with your alcohol or acoustic coupling gel to the elbow, and halfway to the elbow is the Vet BLUE Ph view, and near the elbow is the Vet BLUE Md view. If the heart is in view at the Vet BLUE Md view, slide above the heart until you see the lung line or in larger dogs you may slide caudally toward the diaphragm until the heart is lost and a lung line is seen. The final site is the Vet BLUE Cr view, which requires pulling the foreleg cranially to get the probe placed in the 2nd-3rd intercostal space. If too ventral at the Cr view, you will see the striations of the pectoral muscles; and if too high and cranial at the Cr view, you will be in the thoracic inlet with soft tissue and vessels. The author uses the thoracic inlet as a landmark counting caudally 2-3 spaces for the Vet BLUE Cr view.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 171 of 226 The author’s preference is to start high (dorsal) on the left moving from Cd to Cr, and then do the same on the right hemithorax. By always performing in the same manner, findings are better remembered; and if you do not have the Gator Sign Orientation, then you are not over lung. Key Point Perform the Vet BLUE the same way every time. We suggest that you begin on the left hemithorax, and go from dorsal (high) to ventral, then move to the right side and do the same systematic approach. This allows you to think about the pattern in the same manner every time and helps you remember the findings during Vet BLUE. Also, by completing the Vet BLUE at the right cranial lung region (Cr) region, you may then increase your depth, and then do your right TFAST Pericardial Site view. After the right PCS view, with the increased depth, you may place your patient in right lateral recumbency and proceed to AFAST. In this manner depth changes are minimized and Global FAST is completed in < 4-7 minutes by the appropriately trained, experienced, GFAST sonographer. Vet BLUE for Respiratory Distress – 5 Basic Lung Ultrasound Findings Wet vs. Dry Lung – Basic Lung Ultrasound Basic easily recognizable LUS findings are categorized into the Wet Lung vs. Dry Lung concept. A Glide Sign with A-lines (reverberation artefact) at the lung line is considered “Dry Lung” only to be confounded with PTX (A-lines and No Glide Sign). However, many patients in which the probability of PTX is very low, then spending additional time finding the Glide Sign becomes less important and A-lines alone suffice. Ultrasound Lung Rockets (ULRs) are considered “Wet Lung” and oscillate to and fro with inspiration and expiration and must extend to the far field obliterating A-lines. Shred Sign, Tissue Sign, and Nodule Sign (plus Wedge Sign) – Advanced Lung Ultrasound These are the 3 more advanced LUS signs we have created in progressive order of increasing consolidation/infiltration. The Shred Sign is similar to an air bronchogram on TXR or rather consolidation with aeration of the lung; the Tissue Sign is similar to hepatization of lung or rather consolidation without aeration; and the Nodule Sign or rather consolidation/infiltration in discreet nodules. The Wedge Sign is a subset of the Shred Sign and represents pulmonary thrombo-embolism (PTE) or rather infarcts at the lung periphery.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 172 of 226 Figure. A) Dry Lung B) Wet Lung, ULRS C) Shred Sign D) Tissue Sign and E) Nodule Sign. This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014 Regionally-based Respiratory Pattern Approach Using Vet BLUE Clinical Cases Figure. Examples of Vet BLUE regionally-based patterns. A) Dry Lung all fields rules out clinically relevant Left-sided Congestive Heart Failure, suggests upper airway obstruction, Feline Asthma, COPD, PTE and non-respiratory look-a-likes. B) Wet Lung or ULRs in dorsal, perihilar, and middle lung regions suggests Cardiogenic Lung Edema (left-sided congestive heart failure, volume overload from intravenous fluids). C) Wet Lung in dorsal lung regions suggests forms of Non-cardiogenic Lung Edema. D) Wet Lungs in ventral fields with or without signs of consolidation (Shred Sign/Tissue Sign), suggest Pneumonia. E) Solitary nodule. F) Multiple nodules suggest Metastatic Disease or Granulomatous Disease. KEY: D=Dry lung; W=Wet lung; Sh=Shred Sign; Ti=Tissue Sign; Nd=Nodule Sign. This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 173 of 226 Vet BLUE Diagnostic Algorithm for Respiratory Distress and Conditions This material is reproduced with permission of John Wiley & Sons, Inc., Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 174 of 226 Table 1. Rule Outs for “Dry Lung All Fields” or Absent B-lines All Fields (ABAV) Rule Outs for DRY All Fields on Vet BLUE RESPIRATORY Pulmonary Thrombo-embolism (PTE) Upper Airway Conditions (e.g., Collapsing Trachea, Laryngeal Paralysis), Obstruction (e.g., Mass) Chronic Obstructive Pulmonary Disease (COPD), Feline Asthma Centrally located lung pathology away from the lung line (missed by Vet BLUE) CARDIAC Cardiac Tamponade, Cardiac Arrhythmia, Dilated Cardiomyopathy (DCM) UNDIFFERENTIATED HYPOTENSION Anaphylaxis Hemoabdomen, Hemothorax, Hemoretroperitoneum, other cavitary or hemorrhage in a space OTHER NON-RESPIRATORY Pyrexia or High Fever Severe Metabolic Acidosis Severe Anemia NOTE: Dry Lungs ALL Fields is a Rapid (<90 seconds) Highly Sensitive Test Ruling Out Left-sided CHF (Dogs 88%, Cats 96%) FASTVet.com ©2015, 2016 – Greg Lisciandro, DVM at FastSavesLives@gmail.com Pneumothorax (PTX) and the Lung Point PTX is defined at the presence of the strong proximal pleural line (air is in the pleural space in PTX) and strong A-lines (horizontal bars) without a Glide Sign. PTX is most commonly ruled out by the finding of A-lines with a Glide Sign (called Dry Lung above) or the presence of ULRs (we call Wet Lung above). Neither can be seen when free air is present in the pleural cavity at THAT specific point on the thoracic wall. When PTX is suspected the sonographer should then search for the Lung Point by essentially performing Vet BLUE to move to the middle 3rd (peri-hilar lung region Vet BLUE view), then the lower 3rd (middle lung region Vet BLUE view) searching for evidence of where collapsed lung re-contacts the thoracic wall.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 175 of 226 Search for the “Lung Point” – The Degree of Pneumothorax Figure. A) Thorax in which pneumothorax (PTX) has been excluded. B) PTX has been determined at position 1 and the Lung Point is found at position 2 (PTX is partial). C) PTX has been determined and a Lung Point is non-existent at any of the 3 probe positions (PTX is massive). Reproduced with Permission Lisciandro, JVECC 2011 20(2):104-122. The Lung Point When PTX is suspected at the TFAST CTS view, then the search for the “Lung Point” is an extremely important concept to understand. The Lung Point is the position along the thorax where collapsed lung re-contacts the thoracic wall. The finding of the Lung Point increases the sensitivity of PTX. The Lung Point is determined by finding either A-lines with a Glide Sign or ULRs or other LUS findings supporting lung against the thoracic wall. The “Lung Pulse” has been described in people and its frequency is unknown in veterinary medicine. The Lung Pulse if the finding of lung against the thoracic wall, however, because of severe collapse, the Glide Sign does not move with inspiration and expiration but rather with the heartbeat. Key Point By dividing the thorax into thirds, for all intents and purposes just go through the Vet BLUE scan, when searching for the Lung Point, a subjective assessment of partial vs. massive PTX may be made. Do not move in small increments when searching for the Lung Point since time is important, rather move the probe down to the middle third then lower third of the thorax searching for evidence that lung re-contacts the thoracic wall. If a Lung Point is found them move the probe dorsally until the PTX is again appreciated. The transition between lung contacting the thoracic wall and its loss because of PTX is the patient’s Lung Point. Recording the distance from the CTS is a way to monitor PTX (worsening, improving, and resolution). We use a simple system for where the Lung Point is found by upper third, middle third and lower third. In the author’s experience, Lung Point in the upper third is generally trivial in

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 176 of 226 contrast to Lung Points in the middle and lower thirds that are generally moderate to severe and warrant thoracocentesis. Moreover, the Lung Point is very useful for monitoring PTX as being static, resolving or worsening point-of-care with little patient stress nor restraint. Further reading: 1. Lisciandro GR. Chapter 10: The Vet BLUE Lung Scan. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 2. Lisciandro GR. Chapter 9: The Thoracic (TFAST) Exam. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 3. Lisciandro GR and Armenise A. Chapter 16: Focused or COAST3 - CPR, Global FAST and FAST ABCDE. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 4. Boysen SR, Lisciandro GR. The use of Ultrasound in the Emergency Room (AFAST and TFAST). Vet Clin North Am Small Anim Pract 2013;43(4):773-97. 5. Lisciandro GR. Abdominal (AFAST) and thoracic (TFAST) focused assessment with sonography for trauma, triage, and tracking (monitoring) in small animal emergency and critical care. J Vet Emerg Crit Care 2011; 21(2):104-119. 6. Lisciandro GR. Chapter 55: Ultrasound in Animals. In Critical Care Ultrasound (human textbook), Editors Lumb and Karakitsos. Elsevier: St. Louis, MO 2014. 7. Lisciandro GR, et al. Absence of B-lines on Lung Ultrasound (Vet BLUE protocol) to Rule Out Left-sided Congestive Heart Failure in 368 Cats and Dogs. Abstract, J Vet Emerg Crit Care 2016. 8. Lisciandro GR, et al. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet blue (veterinary bedside lung ultrasound exam) in cats with radiographically normal lung findings. J Vet Emerg Crit Care 2016, In Press. 9. Ward JL, Lisciandro GR, Tou SP, Keene BW, DeFrancesco TC. Evaluation of point-of-care lung ultrasound (Vet BLUE protocol) for the diagnosis of cardiogenic pulmonary edema in dogs and cats with acute dyspnea. J Am Vet Med Assoc 2015, In Press. 10. Lisciandro GR, et al. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet blue (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings. Vet Radiol and Ultrasound 2014;55(3):315-22.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 177 of 226 WHAT POINT OF CARE LUNG ULTRASOUND CAN TELL US: FELINE CASES WITH RESPIRATORY DISTRESS (Vet BLUESM IN CATS) Gregory R. Lisciandro, DVM, Dipl. ABVP, Dipl. ACVECC Hill Country Veterinary Specialists & FASTVet.com, San Antonio, Texas USA Email FastSavesLives@gmail.com Text Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley © 2014 Introduction and History See Vet BLUE Dog Proceedings Use of Lung Ultrasound Formats in Small Animals The reluctance to pro-actively apply LUS to small animals with respiratory distress is irrational in many respects. The overriding belief that air-filled lung creates insurmountable obstacles, and the continued belief in small animal medicine that imaging lung is difficult to perform leading to mistakes, perpetuate LUS delayed use in small animal veterinary medicine. Thoracic FAST called TFAST (2008) was the first standardized abbreviated veterinary ultrasound exam of the thorax that included the Chest Tube Site (CTS) for lung surveillance for detection of PTX and lung contusions. However, because of the finding of lung pathology found during TFAST, the author extended lung surveillance from the TFAST CTS with the addition of 6 more lung views applied to non-trauma subsets of small animals. The name of this novel regionally-based LUS exam has been studied and published by Lisciandro and colleagues in 2014 as the Vet BLUE Protocol (“Vet” for veterinary and “BLUE” blue for cyanosis and bedside lung ultrasound exam or in emergency). The Vet BLUE regional sites include the caudo-dorsal (Cd) lung region, the peri-hilar (Ph) lung region, the middle (Md) lung region, and the cranial (Cr) lung region. Each is named as a region because the views do not directly correlate with anatomical names of lung lobes. This is important to appreciate because 2 parts of a lung lobe or 2 different lung lobes may be coming into view over the same intercostal space during Vet BLUE. As an example, dry lung, then wet lung, then dry lung, then wet lung may interchange during phases of respiration; or dry lung, and a shred sign, and dry lung then a shred sign, as the patient inspires and expires, This phenomenon in fairly common. Expect cats (and dogs) without respiratory disease to have dry LUS artefacts predominate as normal. Point of care lung ultrasound: feline cases with respiratory distress

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 178 of 226 This material is reproduced with permission of John Wiley & Sons, Inc., Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014. How to Perform Vet BLUE Patient Positioning Vet BLUE is performed in sternal recumbency or standing and is safer for dogs and cats in respiratory distress. A roll of towels or paper towels under the forelegs of a cat is an easy tolerated manoeuver to gain access to the lower ventral Vet BLUE and TFAST Pericardial Site views. Vet BLUE may also be performed in dogs and cats in lateral recumbency. Patient Preparation Generally no Vet BLUE sites are shaved! All images shown by the author are unshaved sites at which the fur is parted and alcohol is applied to the skin and a small amount of acoustic gel or alcohol-based hand sanitizer to the probe head. Keep in mind that most ultrasound manufacturers warn against placing alcohol directly on the probe head because of alcohol’s potentially damaging effects. No images from cases in this talk were shaved. The “Gator Sign” – Basic Lung Ultrasound Orientation Figure. The rounded rib heads are likened to the eyes, and the pulmonary-pleural (PP-line) interface to the bridge of its nose, as a partially submerged gator (alligator) peers at the sonographer (middle image, B). The proximal white line is the focus of all LUS. The major orientation error is looking beyond the PP-line (or “Lung Line”) and mistaking A-line artefacts for the PP-line or “Lung Line” or being over the abdomen and mistaking liver, stomach (especially when air-filled), or the gallbladder for lung pathology. This material is reproduced with permission of John Wiley & Sons, Inc., Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014. Reproduced with Permission Lisciandro, JVECC 2011;20(2):1104-122.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 179 of 226 Probe Orientation and Type LUS orientation is always the same with the visualization of the “Gator Sign” to properly identify the pulmonary-pleural interface or the “Lung Line”, actual surface of the lung. The probe is held perpendicular to the long-axis of the ribs; for cats, depth is generally set between 4-6 cm; frequency is generally set between 5-10 MHz; and a microconvex probe is preferred over a linear probe because the probe is acceptable for all 3 formats - AFAST, TFAST and Vet BLUE – often combined, and when combined called Global FAST or GFAST. A phase-array or sector probe is generally not recommended because its focal point is too small, although usefulness of a phase array probe is unknown. A linear probe may be used, however, it is generally not ideal for the AFAST and TFAST portions of Global FAST. Vet BLUE Examination How to Perform Figure. The Vet BLUE lung examination is a screening test performed identically as the probe is positioned at the CTS view of TFAST. The probe is then moved through regional locations that are bilaterally applied as follows: caudo-dorsal lung region (Cd - same as the TFAST CTS view, upper third, 8-9Th intercostal space), peri-hilar lung region (Ph – 6-7th intercostal space, middle third), middle lung region (Md – 4-5th intercostal space, lower third), and cranial lung region (Cr – 2nd-3rd intercostal space, lower third). This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014 Key Point The best way to perform Vet BLUE accurately is to locate the left TFAST Chest Tube Site directly above the xiphoid in the area of the 8-10th intercostal space in the upper 1/3rd of the thorax, then cheating by moving 1 or 2 intercostal spaces cranially to make sure the probe is over lung/pleural space and not over liver/stomach/abdominal contents. From the left TFAST CTS, which is the same as the left Vet BLUE Cd view, draw a line with your alcohol or acoustic coupling gel to the elbow, and halfway to the elbow is the Vet BLUE Ph view, and

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 180 of 226 near the elbow is the Vet BLUE Md view. If the heart is in view at the Vet BLUE Md view, slide above the heart until you see the Lung Line or in larger dogs you may slide caudally toward the diaphragm until the heart is lost and a Lung Line is seen. The final site is the Vet BLUE Cr view, which requires pulling the foreleg cranially to get the probe placed in the 2nd-3rd intercostal space. If too ventral at the Cr view, you will see the striations of the pectoral muscles; and if too high and cranial at the Cr view, you will be in the thoracic inlet with soft tissue and vessels. The author uses the thoracic inlet as a landmark counting caudally 2-3 spaces for obtaining an accurate Vet BLUE Cr view. The author’s preference is to start high (dorsal) on the left hemithorax moving from Cd to Cr, and then perform the same routine on the right hemithorax. By always performing in the same manner, findings are better remembered; and if you do not have the Gator Sign Orientation, then you are not over lung. Key Point Perform the Vet BLUE the same way every time. We suggest that you begin on the left hemithorax, and go from dorsal (high) to ventral, then move to the right side and do the same systematic approach. This allows you to think about the pattern in the same manner every time and helps you remember the findings during Vet BLUE. Also, by completing the Vet BLUE at the right cranial lung region (Cr) region, you may then increase your depth, and then do your right TFAST Pericardial Site view. After the right PCS view, with the increased depth, you may place the patient in right lateral recumbency and proceed to AFAST. In this manner depth changes are minimized and Global FAST is completed in < 4-7 minutes by the appropriately trained, experienced, GFAST sonographer. Counting Lung Rockets – ULRs Correlate with Degree of Alveolar-Interstitial Edema The maximum number of ULRs over a single representative intercostal space at each respective Vet BLUE view is recorded. The counting system is as follows: 0; 1; 2; 3; >3, when ULRs are still recognized as individuals; and ∞ or infinity, when the ULRs blend into one another becoming confluent. Because most typing keyboards do not have an infinity symbol, we use the “&” sign for infinity ULRs. ULRs are counted because they have been shown to correlate with the degree of alveolar-interstitial edema on computerized tomography. Key Point Expect cats (and dogs) without respiratory disease to have dry lung artefacts predominate. In other words, cats and dogs without respiratory disease have none to rare ULRs during Vet

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 181 of 226 BLUE. We found in our clinical studies that cats and dogs with normal radiographic lungs have no more than a single ULR at a single Vet BLUE view approximately 10-12% of the time. It seems that giant breed dogs are more likely to have a few ULRs as a normal finding. Figure. A) No ULRs B) A single ULR scored as “1” or 2 or 3 not shown C) >3 ULRs where there are more than 3 but ULRs are still recognized as individual ULRs and D) ∞ or infinity ULRs. FASTVet.com ©2015, 2016 Vet BLUE for Respiratory Distress – 5 Basic Lung Ultrasound Findings Wet vs. Dry Lung – Basic Lung Ultrasound Basic easily recognizable LUS findings are categorized into the Wet Lung vs. Dry Lung concept. A Glide Sign with A-lines (reverberation artefact) at the lung line is considered “Dry Lung” only to be confounded with PTX (A-lines and No Glide Sign). However, many patients in which the probability of PTX is very low, then spending additional time finding the Glide Sign becomes less important and A-lines alone suffice. Ultrasound Lung Rockets (ULRs) are considered “Wet Lung” and oscillate to and fro with inspiration and expiration and must extend to the far field obliterating A-lines. Shred Sign, Tissue Sign, & Nodule Sign (plus Wedge Sign) – Advanced Lung Ultrasound These are the 3 more advanced LUS signs we have described in progressive order of increasing consolidation/infiltration. The Shred Sign is similar to an air bronchogram on TXR or rather consolidation with aeration of the lung; the Tissue Sign is similar to hepatization of lung or rather consolidation without aeration; and the Nodule Sign or rather consolidation/infiltration in discreet nodules. The Wedge Sign is a subset of the Shred Sign and represents pulmonary thrombo-embolism (PTE) or rather infarcts at the lung periphery.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 182 of 226 Figure. A) Dry Lung B) Wet Lung, ULRS C) Shred Sign D) Tissue Sign and E) Nodule Sign. This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014 Regionally-based Respiratory Pattern Approach Using Vet BLUE Clinical Cases Figure. Examples of Vet BLUE regionally-based patterns. A) Dry Lung all fields rules out clinically relevant left-sided congestive heart failure, and suggests upper airway obstruction, feline asthma, COPD, PTE and non-respiratory look-a-likes (see Table). B) Wet Lung or ULRs in dorsal, perihilar, and middle lung regions suggests cardiogenic lung edema (left-sided congestive heart failure, volume overload from intravenous fluids) classically in dogs other than Dobermans and cats that are exceptions have more sporadic generalized patchy infiltrate. C) Wet Lung in dorsal lung regions suggests forms of non-cardiogenic lung edema. D) Wet Lung in ventral fields with or without signs of consolidation (Shred Sign/Tissue Sign), suggest pneumonia. E) Solitary nodule. F) Multiple nodules suggest metastatic disease or granulomatous disease. KEY: D=Dry lung; W=Wet lung; Sh=Shred Sign; Ti=Tissue Sign; Nd=Nodule Sign. This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com © 2014

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 183 of 226 Vet BLUE Diagnostic Algorithm for Respiratory Distress and Conditions This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 184 of 226 Table 1. Rule Outs for “Dry Lung All Fields” or Absent B-lines All Fields (ABAV) Rule Outs for DRY All Fields on Vet BLUE RESPIRATORY Pulmonary Thrombo-embolism (PTE) Upper Airway Conditions (e.g., Collapsing Trachea, Laryngeal Paralysis), Obstruction (e.g., Mass) Chronic Obstructive Pulmonary Disease (COPD), Feline Asthma Centrally located lung pathology away from the lung line (missed by Vet BLUE) CARDIAC Cardiac Tamponade, Cardiac Arrhythmia, Dilated Cardiomyopathy (DCM) UNDIFFERENTIATED HYPOTENSION Anaphylaxis Hemoabdomen, Hemothorax, Hemoretroperitoneum, other cavitary or hemorrhage in a space OTHER NON-RESPIRATORY Pyrexia or High Fever Severe Metabolic Acidosis Severe Anemia NOTE: Dry Lungs ALL Fields is a Rapid (<90 seconds) Highly Sensitive Test Ruling Out Left-sided CHF (Dogs 88%, Cats 96%) FASTVet.com ©2015, 2016 – Greg Lisciandro, DVM at FastSavesLives@gmail.com Pneumothorax and the Lung Point See Vet BLUE in Dogs Proceedings The Use of Vet BLUE in Respiratory Distressed Cats – The Tale of 4 Cats

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 185 of 226 The use of thoracic auscultation and breathing patterns for respiratory distress is insensitive and prone to error, coupled with the dangers of transport and restraint in radiology and thoracic radiographic interpretation, making the proactive use of Vet BLUE lung ultrasound incredibly powerful for differentiating respiratory distress in cats. Vet BLUE is a pattern-based regional approach of using our 5 described basic lung ultrasound findings – Dry Lung (Glide with A-lines), Wet Lung (Ultrasound Lung Rockets also called B-lines), Shred Sign (Wedge Sign, PTE), Tissue Sign and Nodule Sign. A Veterinary Cardiologist Once Said - “I Can’t Tell the Difference Between Feline Asthma and CHF” – However, You Can Using Point-of-care Vet BLUE in < 60-90 Seconds In the Tale of 4 Cats, we have Cat #1 with Left-sided CHF that is wet all fields; Cat #2 with Feline Asthma that is dry all fields; Cat #3 with pleural effusion, but don’t stop at the pleural effusion, look through the Lung Line; and Cat #4 with Metastatic Disease that has the Nodule Sign with various-sized nodules at nearly every Vet BLUE view. On physical examination, considering auscultation and breathing patterns, all 4 cats look exactly the same with nostril flaring, abdominal breathing, and harsh lung sounds. We will work through these 4 cats emphasizing the evidence-based power of Vet BLUE that better directs care and diagnostic testing. Key Points 1) The use of Vet BLUE rapidly differentiates the 4 different cats all with similar physical exam findings because each has a radically different Vet BLUE pattern. 2) Use the presence of wet vs. dry lung to guide diuretic usage. 3) Look beyond pleural effusion at the “Lung Line” for the Shred Sign, Tissue Sign, and Nodule Sign; and repeat Vet BLUE a few hours post-thoracocentesis to allow pressure atelectasis to resolve, which often appears as a Shred Sign or Tissue Sign. Final Comments We have described 5 (or 6) basic LUS findings that are easily teachable, that in a pattern-based approach help better direct care without having patients shot-gun or empirically treated, or dying or decompensating in radiology because of the stress of restraint and travel to that department. The use of the ultrasound probe as your stethoscope is superior to guessing by lung auscultation and breathing patterns that are insensitive.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 186 of 226  Vet BLUE serves as an effective screening test to rule out left-sided CHF in cats by the finding of dry lung all view (complete absence of lung rockets or B-lines) with a Se of 96%!  Vet BLUE helps better interpret thoracic radiography and is far more sensitive to detect conditions at the lung periphery and may be as accurate as CT.  Proactive use of Vet BLUE is truly a colossal change for small animal respiratory medicine. Further reading: 1. Lisciandro GR. Chapter 10: The Vet BLUE Lung Scan. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 2. Lisciandro GR. Chapter 9: The Thoracic (TFAST) Exam. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 3. Lisciandro GR and Armenise A. Chapter 16: Focused or COAST3 - CPR, Global FAST and FAST ABCDE. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 4. Boysen SR, Lisciandro GR. The use of Ultrasound in the Emergency Room (AFAST and TFAST). Vet Clin North Am Small Anim Pract 2013;43(4):773-97. 5. Lisciandro GR. Abdominal (AFAST) and thoracic (TFAST) focused assessment with sonography for trauma, triage, and tracking (monitoring) in small animal emergency and critical care. J Vet Emerg Crit Care 2011; 21(2):104-119. 6. Lisciandro GR. Chapter 55: Ultrasound in Animals. In Critical Care Ultrasound (human textbook), Editors Lumb and Karakitsos. Elsevier: St. Louis, MO 2014. 7. Lisciandro GR, et al. Absence of B-lines on Lung Ultrasound (Vet BLUE protocol) to Rule Out Left-sided Congestive Heart Failure in 368 Cats and Dogs. Abstract, J Vet Emerg Crit Care 2016, In Press. 8. Lisciandro GR, et al. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet blue (veterinary bedside lung ultrasound exam) in cats with radiographically normal lung findings. J Vet Emerg Crit Care 2016, In Press. 9. Ward JL, Lisciandro GR, Tou SP, Keene BW, DeFrancesco TC. Evaluation of point-of-care lung ultrasound (Vet BLUE protocol) for the diagnosis of cardiogenic pulmonary edema in dogs and cats with acute dyspnea. J Am Vet Med Assoc 2015, In Press.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 187 of 226 10. Lisciandro GR, et al. Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet blue (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings. Vet Radiol and Ultrasound 2014;55(3):315-22.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 188 of 226 Notes page

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 189 of 226 APPLYING Global FASTSM TO SMALL ANIMAL CASES: MONITORING, CPR AND ADVANCED LIFE SUPPORT Gregory R. Lisciandro, DVM, Dipl. ABVP, Dipl. ACVECC Hill Country Veterinary Specialists & FASTVet.com, San Antonio, Texas USA Email FastSavesLives@gmail.com Text Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley © 2014 Introduction The evolution of veterinary abbreviated ultrasound formats has extended beyond the abdominal format and a simple fluid positive or fluid negative approach since the landmark publication by Boysen and colleagues (2004). In 2008, the thoracic FAST format was developed by Lisciandro and colleagues and referred to as TFAST for the rapid diagnosis of pneumothorax and other thorax-related injury. In 2009, the abdominal FAST referred to as AFAST was studied by Lisciandro and colleagues with a target-organ approach rather than naming of external sites - so that sonographer would be more aware anatomically about the actual organs and structures at each of the AFAST views. In the same study, the AFAST-applied fluid scoring system provided more meaning to what a positive AFAST exam meant by semi-quantitating the degree of hemorrhage. This same study advocated the use of serial AFAST exams with abdominal fluid scoring to detect ongoing hemorrhage before patients decompensate. It was found that AFAST-positive dogs could be subdivided into major injury, small volume bleeders, unlikely to develop anemia as long as their scores remained low (AFS 1 or 2), and major injury, large volume bleeders (AFS 3 or 4), that predictably developed anemia. Moreover, it was found that of the high-scoring dogs, approximately 33% required blood transfusion within the author’s institution and fluid resuscitation strategies. Most recently, a rapid, abbreviated, lung ultrasound screening format has been developed by Lisciandro and colleagues called Vet BLUE (Vet for veterinary and BLUE for cyanosis and BLUE for bedside lung ultrasound exam). The Vet BLUE is an extension from the TFAST chest tube site. The Vet BLUE is a pattern-based regional approach premised on 5 basic lung ultrasound findings including Dry Lung (A-lines with Glide Sign), Wet Lung (Ultrasound Lung Rockets [ULRs] also called B-lines), Shred Sign, Tissue Sign, and Nodule Sign (and Wedge Sign for PTE). In 2011, it was proposed that veterinary ultrasound terminology be standardized to prevent the onslaught of confusing acronyms in human medicine for abbreviated ultrasound formats, Applying global fast to small animal cases: monitoring, CPR and advanced life support

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 190 of 226 many of which have similar objectives. Thus, AFAST and TFAST, more than trauma only exams being helpful in most non-trauma subsets of dogs and cats, including those triaged (non-trauma, collapse, weakness, unexplained hypotension/shock, etc.) and tracked post-interventionally (exploratory surgery, laparoscopy, percutaneous needle or Tru-cut biopsy, thoracoscopy, Advanced Life Support [ALS]). Thus, by adding a T3 to the acronym there is no need at this time to create additional acronyms. Hence, AFAST3 and TFAST3 formats apply to in actuality all subsets of dogs and cats, including trauma, triage (non-trauma, collapse, weakness, unexplained hypotension/shock, CPR) and tracking (post-interventionally, monitoring during hospitalized care, ALS). Vet BLUE should also be applied with the T3 mindset. When performing all 3 formats the author uses the term Global FAST. In fact, the author is now using Global FAST3 as an “extension of the physical exam” for any suspect or abnormal patient; and using Global FAST as a pre-anesthetic screening test. In a busy daytime or first line practice, a veterinarian should be doing 3-7 Global FAST studies a day! Paradigms are Changing with the Use of FAST Ultrasound The NEW Central Venous Pressure is Via Ultrasound In 2012, measurement of central venous pressure via central venous catheters for guiding fluid therapy was debunked in human medicine because the practice is unreliable for patient assessment. The non-invasive use of ultrasound for volume assessment has become an accepted and popular means to assess preload and is our new central venous pressure assessment. During AFAST or TFAST, both use the Subxiphoid, Diaphragmatico-hepatic (DH) View at which the caudal vena cava is readily imaged as it traverses the diaphragm. The use of the characterization of the CVC and its associated hepatic veins for hepatic venous distension screen for right-sided heart problems, e.g. right-sided failure, pulmonary hypertension and pericardial effusion. The NEW Way to Assess Patients with Imminent Cardio-Pulmonary Arrest (CPA) and during CPR is Ultrasound The use of ultrasound to prevent CPA in patients that have unexplained or undifferentiated shock has been developed and called the RUSH Exam (RUSH=Rapid Ultrasound in Shock). Global FAST accomplishes everything RUSH does and more through its abdominal fluid scoring system (see AFAST Proceedings), more comprehensive lung evaluation (Vet BLUE), and a urinary bladder volume estimation formula gained at the AFAST Cysto-colic (CC) View as measured in centimeters Length x Width x Height x 0.625 estimates urinary

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 191 of 226 bladder volume in milliliters. Thus, with serial measurements urinary output may be estimated non-invasively. The FEER and FEEL protocols (Focused Echocardiography Evaluation during Resuscitation, Focused Echocardiography Evaluation during Life support) documented how ultrasound exceeds physical examination, electrocardiography, end tidal CO2 monitoring for the detection of return of spontaneous circulation (ROSC). In fact, these studies documented the misdiagnoses of asystole and pulseless electrical activity (PEA) based on physical examination and electrocardiogram findings by documenting coordinated cardiac movement using ultrasound in these same human patients. Knowing Your American Heart Association Hs and Ts for Rapidly Detecting Treatable Conditions during CPR or Imminent CPA The veterinary profession should be well commended for standardizing CPR Guidelines through RECOVER. However, the reason why your patient is going to experience CPA, or why you are doing CPR in the first place has been overlooked using ultrasound. Global FAST can rapidly detect treatable causes for imminent CPA and help rapidly detect treatable causes for CPR when minutes count. Global FAST detects conditions easily missed or only suspected based on physical exam, laboratory testing, and radiography, rapidly with evidence-based information point-of-care. The RUSH exam in human medicine was developed for these same reasons. The American Heart Association (AHA) CPR Guidelines advocate knowing your Hs and Ts for treatable causes of CPA and need for CPR. The Hs include acidosis [H+], Hyper-, hypokalemia, Hypoglycemia, and Hypotension and are generally quickly ruled in or ruled out by a venous or arterial blood gas analysis with the rate-limiting step being the blood draw. The Ts include Tamponade (pericardial effusion), Tension pneumothorax, Thrombo-embolism (PTE), and Toxins. Global FAST Rapidly Evaluates an H and the Ts of the AHA Guidelines for Treatable Causes of CPR The author has modified the AHA Hs and Ts by adding within Hypotension internal hemorrhage, which can be detected in 4 spaces (intra-abdominal, retroperitoneal, pleural and pericardial), and lung (ULRs) using Global FAST. Furthermore, if hemorrhage is suspected and diagnosed, the abdominal fluid scoring system can help semi-quantitate the degree of hemorrhage through the small volume vs. large volume bleeder concept (see

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 192 of 226 AFAST Proceedings). For example, if a dog or cat has experienced CPA and has an AFS of 1 or 2, the cause may be within the abdominal cavity but the cause is not a large enough bleed to cause anemia and likely the reason is elsewhere (see the Ts). The author has modified the Ts by including anaphylaxis with Toxin in addition to Tamponade (pericardial effusion), Tension pneumothorax, and Thrombo-embolism. Table 2: Use of Global FAST for rapidly ruling out your Ts in patients nearing CPA and during CPR modified from AHA CPR Guidelines. Knowing Your Hs and Ts During Cardio-Pulmonary Arrest and Advanced Life Support The Hs Evaluated for Using Venous Blood Gas, Physical Exam, Vital Signs The Ts Evaluated for Using Global FAST Hypothermia Tension PTX (TFAST) Hypotension (AFAST, TFAST, Vet BLUE) Trauma, Hemorrhage (AFAST, TFAST, Vet BLUE) Hyperkalemia, Hypokalemia Thrombo-embolism (PTE) (TFAST, Vet BLUE) Hypoglycemia Tamponade, PCE (TFAST, FAST DH View) Hydrogen Ion (Acidosis) Toxin, Anaphylaxis (FAST DH View) © 2015, 2016 Hill Country Veterinary Specialists and FASTVet.com Ruling Out the Ts Explained The Ts are ruled out as follows: Tension PTX by presence of A-lines without a Glide Sign and the search for the Lung Point; Trauma Hemorrhage through the detection of free fluid in the intra-abdominal cavity, the retroperitoneal space, the pleural cavity and the pericardial sac, and the presence of ULRs during Vet BLUE in trauma patients (plus the abdominal fluid scoring system, see below); PTE is diagnosed by the severe dilation of the RV during TFAST and the RV:LV Ratio (see below), and/or the presence of the Wedge Sign during Vet BLUE; and Tamponade at the FAST DH View with or without additional PCS views; and Toxin-Anaphyaxis by the observation of the gallbladder halo sign (edema causing striation of the gall bladder wall).

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 193 of 226 Key Point See Table for other causes of the gallbladder halo sign as it is not pathognomic for anaphylaxis. In collapsed, weak, critical dogs, always look at the heart through the FAST DH view for pericardial effusion; and the heart at the TFAST views for right-sided problems, generalized systolic dysfunction (DCM, PHT), before diagnosing anaphylaxis. Causes of Gallbladder Wall Edema (the Gallbladder Halo Sign) Anaphylaxis (acute collapse, flat caudal vena cava) – massive histamine release results in hepatic venous congestion Right-sided heart failure/dysfunction (collapse, weakness, FAT caudal vena cava) – backflow of blood flow from the right heart results in hepatic venous congestion Pericardial effusion (acute collapse, weakness, FAT caudal vena cava) – obstruction of blood flow to the right heart results in hepatic venous congestion Cholecystitis Pancreatitis Hypoalbuminemia, 3rd Spacing Right-sided volume fluid overload (iatrogenic) Immune-mediated Hemolytic Anemia (IMHA), unknown cause, speculate immune-mediated Post-Blood Transfusion, unknown pathogenesis, speculate immune-mediated FASTVet.com ©2015, 2016 - Greg Lisciandro, FASTSavesLives@gmail.com The Use of Global FAST for Patient Volume Status & Monitoring Breaking It Down to Volume and Contractility, Right-sided and Left-sided Cardiac Function The Global FAST strategy accomplished left- and right-sided cardiac function by non-echo views which can be difficult to acquire in many critically unstable patients, whereas use of Vet BLUE for the left heart and use of the FAST DH View (part of AFAST and TFAST) for characterizing the caudal vena and hepatic veins are reliably attainable without fighting aerated lung or patient movement during echo views. General Cardiac Function and Status  Left Ventricular Short-axis View by observing at the level immediately below the mitral valves where M-mode is used for cardiac measurements contractility and left ventricular filling.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 194 of 226 Left-sided Heart Function  Echo View: the Left Atrial to Aortic Ratio (LA:Ao) on short-axis view referred to as the “quick peek” view. In dogs the ratio should be < 1.3 and in cats < 1.6.  Non-echo View: the use of Vet BLUE and finding of absent B-lines all fields or no ULRs all fields, which we refer to as “Dry Lung All Fields.” The use of the Vet BLUE strategy is very helpful in critical and fragile patients in which it is too risky to obtain the echo view(s). Right-sided Heart Function  Echo View: the Right Ventricular to Left Ventricular Ratio (RV:LV). In dogs and cats the ratio should be 1:3-4.  Non-echo View: the use of the FAST DH view and characterization of the caudal vena cava and hepatic veins. In dogs and cats the hepatic veins should not be obvious at the FAST DH view. The caudal vena cava should have a dynamic change to its diameter we refer to as a “bounce” when central venous pressure (CVP) is in the normal range; flat and of small diameter with no dynamic change in hypovolaemia or low CVP; and fat or distended along with distended hepatic veins in hypervolaemia or high CVP. Summary of Global FAST Triad for Patient Volume Assessment and Left- and Right-sided Cardiac Status Figure. The Global FASTSM Triad for Volume Status. Top Row: The 3 Echo Views of TFAST are the Left Ventricular Short-axis View (LVSA) for Volume and Contractility (shown), the Right Ventricular to Left Ventricular Ratio (RV:LV) on the Long-axis 4 Chamber View (not shown), and the Left Atrial to Aortic Ratio (LA:Ao) on the Short-axis View (not shown). Middle Row: The presence of Dry vs. Wet Lung screens for Left-sided Cardiac Failure/Overload. Bottom Row: The characterization of the Caudal Vena Cava and Hepatic Veins screens for Right-sided Cardiac Failure/Overload. This material is reproduced with

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 195 of 226 permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 and FASTVet.com ©2014 FASTVet.com © 2015 Figure. The 3 TFAST Echo Views taught during Global FASTSM training. The Use of the TFAST Echo Views for Volume and Contractility, Right-sided Problems and Left-sided Problems The Left Ventricular Short-axis View (LVSA) at the Level of the Chordae Tendinae for Volume and Contractility The short-axis left ventricular “mushroom” view (LVSA) is easily learned by the non-radiologist, non-cardiologist veterinarian. The view is helpful to re-enforce the clinical impression of volume status assessed by characterization of the CVC (FAT, flat or bounce) at the FAST DH View. Moreover, contractility may be assessed subjectively, using the eyeball approach, as normal contractility and filling, poor filling, and poor contractility. The Right Ventricular to Left Ventricular Ratio (RV: LV) The normal RV: LV ratio is 1:3-4 with the RV being a small triangle when compared to the LV. When the RV is nearly the same size of the LV then right heart problems and pulmonary hypertension should be suspected, and complete echocardiography is indicated until proven otherwise. However, by recognizing the abnormality, patient therapy may be adjusted based on clinical impression to better head off complications. In an acutely respiratory distressed cat or dog that develops acute RV dilation, massive PTE has likely occurred. The author recommends a recorded baseline Global FAST on all admitted hospitalized patient’s pre-treatment. The Left Atrial to Aortic Ratio (LA:Ao) The normal LA:Ao Ratio is <1.3 in dogs and <1.6 in cats. This is the most challenging view to obtain in the author’s opinion and emphasizes the importance of doing the easier Vet BLUE to evaluate for left-sided heart problems. Dry Lung all Vet BLUE views rules out any relevant left-sided CHF in dogs and cats with high Sensitivity.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 196 of 226 The Use of the FAST DH for Caudal Vena Cava and Hepatic Venous Distension Preload and Right-sided Cardiac Status The caudal vena cava (CVC) where it traverses the diaphragm may be rapidly characterized as FAT (distended, high CVP), flat (collapsed, low CVP), or having a bounce (bobs, in the ballpark of normal CVP). The normal “bounce” should be ~ 50% change in diameter during inspiration and expiration in spontaneously ventilating dogs and cats. Measuring the CVC using M-mode can be challenging without more advanced ultrasound training and may be difficult with a lot of patient movement. However, by visually characterizing the CVC at the FAST DH view, called the “eyeball approach”, and correlating with clinical impression and other findings (blood pressure, physical exam findings, blood lactate), the clinician has a much better idea of patient preload (CVP) and right-sided cardiac status. Figure. Shows the classic FAT or distended CVC as it traverses the diaphragm with associated hepatic venous distension likened to tree trunks and branching referred to as the “Tree Trunk Sign.” This material is reproduced with permission of John Wiley & Sons, Inc, Focused Ultrasound Techniques for the Small Animal Practitioner, Wiley ©2014 FASTVet.com ©2015 Figure. Shows the B-mode real-time eyeball approach on these still images with A) being a collapsed or flat CVC due to low CVP B) being a bounce or bob to the CVC due to an “in the ballpark” normal range of CVP and C) a distended or FAT CVC due to high CVP. In the case of B) if the patient needs a fluid challenge, then it should be given as needed. However, once the CVC becomes FAT or distended, indicating high CVP, fluid resuscitation strategy needs to be re-evaluated because the right heart is become overloaded.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 197 of 226 The Use of Vet BLUE – “Wet Lung” vs. “Dry Lung” Because the “wet lung” vs. “dry lung” concept is easily recognized using lung ultrasound (Vet BLUE), the presence or absence of ultrasound lung rockets (ULRs) also called B-lines provides important clinical information regarding left-sided cardiac status and left-sided volume overload. The author recommends acquiring a baseline Vet BLUE on all hospitalized dogs and cats prior to intravenous fluid therapy. ULRs have been shown to correlate with extravascular lung water, and thus are sentinels for worsening respiratory status. If treatment strategy is not adjusted, the interstitial-alveolar edema may progress to alveolar flooding which is much more difficult to treat. Using the pattern-based approach, other causes of wet lung artifacts, such as pneumonia, can often be discriminated using the Vet BLUE pattern-based approach. Moreover, the use of lung ultrasound potentially triggers additional testing and imaging. See Vet BLUE Proceedings. FASTVet.com © 2015 Figure. Showing the counting scheme published by the author for counting ULRs. The more the ULRs, the more alveolar-interstitial edema or extravascular lung water. This can be a sign of left-sided volume overload depending on the ULR distribution.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 198 of 226 The Use of Global FAST for Shock and the Hypotensive Patient Table 1: Use of Global FAST for rapid assessment and monitoring of the critical dog and cat modified from the RUSH exam.14 Global FAST Evaluation Hypovolemic Shock Cardiogenic Shock Obstructive Shock Distributive Shock Pump – How Contracting? Inotropy Works Hypercontractile Heart Small Chamber Size Dry Lung Deficient Hypocontractile Heart Dilated Heart Wet Lung Works -Overloaded Hypercontractile Heart PCE/Tamponade RV Strain (Increased RV:LV) When PTE, Cardiac thrombus Dry >> Wet Lung Works – Deficient Hypercontractile Heart (early sepsis) Hypocontractile Heart (late sepsis) Dry > Wet Lung Tank – How Full? Volume Empty Flat CVC Flat jugular veins Dry Lung Overfilled Distended CVC Distended jugular vein ULRS (lung edema) Wet Lung Overfilled Distended CVC Distended jugular PTX (A-lines and no Glide Sign) Dry or Wet Lung Empty or Overfilled Normal or small CVC (early sepsis) Peritoneal fluid (exudate/sepsis source) PE (exudate/ sepsis source) Dry or Wet Lung Pipes – Leaky? Leaky Peritoneal fluid (loss) PE (loss) *Splenic or other intra-abdominal bleeding tumor Normal Peritoneal fluid (ascites) PE Obstructed Thrombo-embolism Leaky Or Distended ARDS 3rd Spacing Comments Use Vet BLUE and AFS Use Vet BLUE and AFS Vet BLUE Can Detect PTE Vet BLUE and TFAST Can Detect Non-cardiogenic Edema ©2015 Hill Country Veterinary Specialists and FASTVet.com

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 199 of 226 What the Global FAST Approach has Over the RUSH Exam Abdominal Fluid Scoring System Figure. The Abdominal Fluid Scoring System is a 0-4 system in which negative for fluid at all 4 AFAST views is a 0, and positive based on numbers of views ranges from 1-4. Abdominal fluid score (AFS) helps in discriminating between small volume bleeders that will not become anemic (AFS1,2) and large volume bleeders (AFS 3,4) that predictably become anemic. AFS 3,4 may require blood transfusion and/or exploratory surgery based on their clinical profile and reason. See AFAST Proceedings. The Vet BLUE Exam The rapid pattern-based regional approach of Vet BLUE helps detect lung problems that may be occult on physical exam and radiography. Vet BLUE is an extension off the TFAST Chest Tube Site view and has been shown to be an effective means to accurately diagnose many common respiratory conditions point-of-care upon presentation, without the delay of radiographic imaging. The Use of Our AFAST CC Urinary Bladder Volume Estimation Formula By measuring the urinary bladder in centimeters during the AFAST CC View, the formula, Length x Width x Height x 0.625 will give you an estimation of urine volume. Over time urinary output may be estimated. Baseline Admission Global FAST and Serial Exams are Key The importance of repeat Global FAST exams cannot be overemphasized. Minimally a 4-hour post-admission exam should be performed and the author incorporates Global FAST as part of daily rounds immediately after a complete physical exam. Summary of Global FAST for Patient Volume Status and CPR and ALS The use of the Global FAST is an effective, point-of-care evaluation that is non-invasive and low risk for critical patients providing invaluable information for patient volume status during

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 200 of 226 resuscitation and during advanced life support (ALS) post-CPR. Furthermore, Global FAST should be used as standard of care for rapidly surveying for treatable and reversible causes of uncharacterized hypotension/shock and CPR. By incorporating Global FAST, many conditions missed by traditional training without ultrasound are detected, and clinical course is modified and adjusted earlier in their course, and as result lives are saved, complications better avoided, and next best tests are better determined. Global FAST Saves Lives! Further Reading 1. Lisciandro GR. Focused abdominal (AFAST) and thoracic (TFAST) focused assessment with sonography for trauma, triage and monitoring in small animals. J Vet Emerg Crit Care 2011;20(2):104-122 . 2. Lisciandro GR. The use of the diaphragmatico-hepatic (DH) views of the abdominal and thoracic focused assessment with sonography for triage (AFAST/TFAST) examinations for the detection of pericardial effusion in 24 dogs (2011-2012). J Vet Emerg Crit Care 2016; 26(1):125-31. 3. Lisciandro GR, Fosgate GT. Use of AFAST Cysto-Colic View Urinary Bladder Measurements to Estimate Urinary Bladder Volume in Dogs and Cats. J Vet Emerg Crit Care, in press, January 2016. 4. Armenise A, Neri L, Storti E, et al. Evaluation of a FAST-ABCDE protocol (Focused Assessment with Sonography for Trauma- Airway, Breathing, Circulation, Disability, and Exposure) to detect multiple injuries in canine trauma patients: Preliminary data. Abstract. J Vet Emerg Crit Care 22(S2):S20. 5. Lisciandro GR and Armenise A. Chapter 16: Focused or COAST3 - CPR, Global FAST and FAST ABCDE. In Focused Ultrasound for the Small Animal Practitioner, Editor, Lisciandro GR. Wiley Blackwell: Ames IA 2014. 6. McMurray J, Boysen S, Chalhoub S. Focused Assessment with Sonography in Non-trauma dogs and cats in the emergency and critical care setting. Abstract. J Vet Emerg Crit Care, 2014; 24(S1):S28. 7. Boysen SR, Lisciandro GR. The use of Ultrasound in the Emergency Room (AFAST and TFAST). Vet Clin North Am Small Anim Pract 2013;43(4):773-97. 8. Breitkreutz R, Price S, Steiger HV, et al. 2010. Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: A prospective trial. Resuscitation 81: 1527-33. 9. Breitkreutz R, Walcher F, Seeger FH, et al. 2007. Focused echocardiographic evaluation in resuscitation management (FEER): Concept of an advanced life support–conformed algorithm. Crit Care Med 35(S5):1527-33.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 201 of 226 10. Lichtenstein D. 2012. Fluid administration limited by lung sonography: the place of lung ultrasound in assessment of acute circulatory failure (the FALLS-protocol). Expert Rev Respir Med 6(2):155-62. 11. Ferrada P, Evans D, Wolfe L et al. Findings of a randomized controlled trial using limited transthoracic echocardiogram (LTTE) as a hemodynamic monitoring tool in the trauma bay. J Trauma Acute Care Surg 2013;76(1):31-38. 12. Marik PE, Callazo R. Does Central Venous Pressure Reflect Fluid Responsiveness? An Updated Meta-analysis and a Plea for Some Common Sense. Crit Care Med 2013;41(7):1774-81. 13. Neumar RW, Otto CW, Link MS, et al. 2010. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 122:S729-S767. 14. Perera P, Mailhot T, Riley D, Mandavia D. The RUSH exam: Rapid Ultrasound in SHock in the evaluation of the critically lll. Emerg Med Clin North Am 2010; 28(1):29-56.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 203 of 226 COMPARATIVE MEDICINE: POINT OF CARE ULTRASOUND IN HUMAN EMERGENCY MEDICINE Dr Karen Jones BM BCh (Oxon), MA, MSc SEM, PGDip Medical Ultrasound, FRCEM, MRCP, MFSEM Consultant in Emergency Medicine University Hospitals Coventry & Warwickshire Club Doctor Worcester Warriors RFC Point of care ultrasound has gained increasing prominence in the field of human Emergency Medicine over recent years and is now a core skills of Emergency Physicians1. In this presentation I aim to give a case-based overview of the uses of ultrasound within human Emergency Medicine. Emergency ultrasound is defined as “diagnostic or procedural ultrasound that is performed and interpreted by the emergency physician during the initial patient encounter for the evaluation of emergent conditions”2. The production of more compact and portable ultrasound machines over the past 10 years has been instrumental to the expansion of point of care ultrasound1. Importantly it is not a replacement for traditional radiologist-performed ultrasonography as it is often performed in suboptimal conditions and under significant time pressure and therefore many patients will require subsequent formal imaging. Ultrasound initially gained acceptance within Emergency Medicine due to evidence for its effectiveness in assessing for internal bleeding in blunt trauma victims through FAST (focused abdominal sonography in trauma) scanning3. Its scope has now expanded to include a wide variety of applications including diagnosing aortic aneurysms, assessment of fluid status and focused echocardiography in cardiac arrest. The American College of Emergency Physicians (ACEP) classifies emergency ultrasonography into five broad categories4:  Resuscitative - cardiac arrest, peri-arrest and shock  Diagnostic – pulmonary, cardiac, abdominal, gynaecological, musculoskeletal and ophthalmological applications  Symptom or sign based – e.g. shortness of breath  Procedure guidance – line/chest tube placement or to guide aspirations/injections  Therapeutic or monitoring – used to provide treatment or for monitoring of response Comparative medicine: point of care ultrasound in human emergency medicine

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 204 of 226 During cardiac arrest, bedside ultrasound can be utilised to answer three clinical questions. Firstly, whether there is cardiac activity, secondly whether there is organised cardiac contraction and thirdly to identify a reversible cause for the arrest. The absence of any cardiac activity on ultrasound during arrest has been shown to be associated with a significantly lower likelihood of achieving return of spontaneous circulation and therefore can be utilised as part of the decision making process for stopping resuscitative efforts5. Organised cardiac activity may indicate a low output state rather than a true cardiac arrest and hence guide a clinician away from potentially harmful chest compressions and high dose adrenaline towards fluid resuscitation and inotropic infusions. Ultrasound can rapidly assess for the presence of reversible causes such as pericardial tamponade, signs of right ventricular overload suggestive of pulmonary embolism, tension pneumothoraces or occult intra-abdominal bleeding. Focused assessment with sonography in trauma (FAST) was initially used to assess hypotensive patients for occult bleeding2. This is now considered the “entry level” for Emergency Ultrasound and is taught on level one courses although many centres are moving away from its use in trauma due to the availability of CT scanning. FAST is now more commonly used to assess for intra-abdominal free fluid in ectopic pregnancies, bowel perforations and non-traumatic bleeding. In patients presenting with haemodynamic shock, ultrasound can be used to guide therapy and identify the underlying cause6,7. Ultrasound demonstration of inferior vena cava collapsibility along with a hyper-dynamic left heart is indicative of hypovolaemia and repeated scanning can be used to guide fluid resuscitation. Cardiac scanning can assess for pericardial tamponade, pulmonary embolism and overall cardiac contractility. Abdominal scanning can identify abdominal aortic aneurysm rupture as the underlying cause of shock. Point of care or Emergency Ultrasound is a rapidly growing field with a large number of clinical applications. This session aims to give a case-based overview of how Emergency Ultrasound can be utilised to augment clinical care.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 205 of 226 References: 1. Stawicki, S.P., Bahner, D.P. (2015). Modern sonography and the bedside practitioner. Evolution of ultrasound from curious novelty to essential clinical tool. European Journal of Trauma and Emergency Surgery, 41 (5), 457-460. 2. Henneberry, R.J., Hanson, A., Healy, A., et al. (2012). Use of point of care sonography by emergency physicians. Canadian Association of Emergency Physicians position statement. Canadian Journal of Emergency Medicine, 14, 106-112. 3. Boulanger, B.R., McLellan, B.A., Brenneman, D.S., et al. (1999). Prospective evidence of the superiority of a sonography based algorithm in the assessment of blunt abdominal trauma. Journal of Trauma, 47, 632-637. 4. American College of Emergency Physicians (2008). Emergency ultrasound guidelines 2008. American College of Emergency Physicians, available at: http://www.acep.org [Accessed 01 September 2016]. 5. Blyth, L., Atkinson, P., Gadd, K. et al. (2012). Bedside focused echocardiography as a predictor of survival in cardiac arrest: a systematic review. Academic Emergency Medicine, 19 (10), 1119-1126. 6. Rose, J.S., Bair, A.E., Mandavia, D. et al. (2001). The UHP ultrasound protocol: a novel ultrasound approach to the empiric evaluation of the undifferentiated hypotensive patient. American Journal of Emergency Medicine, 19 (4), 299-302. 7. Stawicki, S.P., Adkins, E.J., Eiferman, D.S. et al. (2014). Prospective evaluation of intravascular volume status in critically ill patients: does inferior vena cava collapsibility correlate with central venous pressure? Journal of Trauma and Acute Care Surgery, 76 (4), 956-963.

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 207 of 226 PAPERS THAT HAVE MADE ME THINK Sophie Adamantos BVSc CertVA DACVECC DipECVECC MRCVS FHEA Langford Veterinary Services, University of Bristol Sophie.adamantos@bristol.ac.uk This lecture will discuss the follow papers, why they are important to me and how and why they have impacted my clinical practice. If you would like a copy of any of the papers discussed please let me know and I will send them to you by email. Okuyama el al (2014) Speaking up for patient safety by hospital0based health care professionals: a literature review. BMC Health Services Research 2014, 14:61 Papers that have made me think

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ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 211 of 226 ABSTRACTS Four abstracts will be presented in this session Abstract 1: Retrospective Study Of Vitis Vinifera Ingestion In 606 Dogs In Emergency Clinics Rachel Croft MA VetMB MRCVS, Elisabetta Clementi MVD MRCVS, Ava Firth DVM DACVECC MRCVS Introduction Ingestion of the fruits of Vitis Vinifera (grapes, raisins, sultanas and currants) is a common intoxication in dogs and can lead to acute renal failure and death. This study analysed the treatment and short-term outcomes of dogs treated at out-of-hours emergency clinics for grape/raisin (G/R) ingestion. Methods and Materials The patient database of Vets Now was queried for all dogs with a diagnosis coded as G/R intoxication. Cases were included if the owner had witnessed G/R ingestion, if G/R was found in vomitus, or if the patient was transferred from another practice for management of G/R ingestion. Cases were excluded from analysis if the patient had concurrent toxin ingestion (such as chocolate), if ingestion could not be confirmed, or if the patient had pre-existing medical conditions. Records were reviewed for information regarding signalment, time since ingestion, clinical signs, treatments given, diagnostic tests and short-term (<48 h) survival. These parameters were analysed using descriptive statistics. Results 855 cases were retrieved from the period between November 2012 and February 2016. 249 cases were excluded, leaving 606 cases for analysis. 74/606 (12%) cases presented with clinical signs. Of these, 49/74 (66%) were vomiting, 17/74 (23%) had diarrhoea, 18/74 (24%) were lethargic, and 7/74 (9%) had abdominal pain. Other signs seen less frequently included hypersalivation, abdominal distension, tachycardia, pollakiuria and increased water consumption. Abstract session

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 212 of 226 506/606 (83%) of dogs received apomorphine. 494/506 (98%) vomited some form of G/R and 16/494 (3%) of these patients had ingested G/R more than 6 hours previously. 282/606 (47%) of dogs were treated as outpatients. Of the remaining 324 dogs that were admitted, 241 (74%) were discharged in <24 h, 79 (24%) were discharged between 24-48 h, and 4 (1%) were hospitalised for > 48 h. 321/324 (99%) of admitted patients were treated with intravenous fluids. Of those, 157/321 (49%) were given an initial fluid rate of ‘twice maintenance’ or 4 ml/kg/hr. The incidence of renal failure could not be definitively evaluated from this data set due to the short-term nature of the patient records. However, of 43 patients with a creatinine measured at >24 h post-admission, only 1 had elevated results (135 mmol/L, reference range 44-115 mmol/L). 100% of cases survived until discharge. Conclusions and Clinical Relevance Gastrointestinal signs are the most common clinical signs. Induction of emesis can retrieve G/R >6 h post ingestion. In this set of patients, short-term outcomes were good.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 213 of 226 Abstract 2: Efficacy and safety of 0.2mg/kg dose of apomorphine in the induction of emesis in the dog Michelle Dawson VetMB MRCVS 1, D. O’Rourke MVB FRCVS 2, Ava. Firth DVM DACVECC MRCVS 1 AFFILIATION: 1 Vets Now Emergency, Penguin House, Castle Riggs, Dunfermline, FIFE KY11 8SG, United Kingdom 2 Ortec Consultancy, 1 Friary Way, Canterbury, Kent CT2 7RL. Introduction The purpose of this study was to evaluate the efficacy and safety of a 0.2 mg/kg dose of apomorphine in dogs for the induction of emesis subsequent to toxin or foreign body ingestion. Materials and Methods This study was a prospective clinical trial in fifteen private after-hours emergency clinics in the United Kingdom. Dogs presented for management of known/suspected toxin ingestion, or smooth/soft material foreign body ingestion, within the preceding four hours were enrolled in the study. The study protocol required a single dose of apomorphine (Apometic®) 0.2 mg/kg to be administered subcutaneously to induce emesis. Dogs were then observed for a 45-minute period. Data recorded included patient demographics; reason for inducing emesis; time since ingestion; time since last meal; time from injection to emesis; frequency and duration of emesis; incidence of side effects, including any interventions required; and discharge status. For the purpose of this study, protracted emesis was defined as greater than 45 minutes. Results 150 dogs were enrolled in the study. 18 dogs were excluded from data analysis due to incorrect dose or incomplete data. Of the 132 dogs analysed, 114 (86%) presented for toxin ingestion and 18 (14%) presented for gastric foreign body. Emesis was successfully induced in 100% of dogs. All dogs presented for management of gastric foreign body successfully vomited the object. The average time from injection to emesis was 7 minutes (range 1-20

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 214 of 226 minutes). The mean number of vomiting bouts was 7 (range 1-23). 88 dogs (66%) had ceased vomiting within 20 minutes. 64 dogs (48%) showed side effects. The most common side effects were: drowsiness/sedation (n=7, 5.3%), pytalism (n=9, 7.6%), protracted emesis (n=8, 6.0%), ataxia (n=7, 5.3%), and CNS depression (n=4, 3.0%). 6 dogs were given maropitant. No patients were hospitalised due to side effects. Conclusion A 0.2 mg/kg dose of apomorphine results in reliable induction of emesis with a 48% incidence of side effects. Clinical Significance This is the first study to establish the efficacy and safety of a 0.2mg/kg dose of apomorphine under field conditions, including speed of onset and duration of emesis. This is useful to all primary practitioners making decisions when managing patients presenting for toxin ingestion, as well some gastric foreign bodies.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 215 of 226 Abstract 3: Aetiology and Outcome In 1440 Dyspnoeic Cats Presented To First-Opinion Emergency Clinics (2012-2015) Amanda-Jane Erne RVN CertVN ECC, Ava Firth DVM DACVECC MRCVS, Michelle Dawson VetMB MRCVS Introduction While there are numerous studies about specific causes of dyspnoea in cats, only one study of cats with dyspnoea as a presenting sign has been published. In that study of a referral population, 37.7% of cats had cardiac diagnoses, followed by respiratory (32.2%), neoplastic (20.0%) and traumatic (8.9%) conditions. The aim of this study was to describe the population and outcomes of dyspnoeic cats presenting to primary out-of-hours practitioners, and to compare it with previously reported data. Materials and Methods The Vets Now patient database was queried to retrieve case records of cats with the presenting complaints of ‘breathing difficulties with/without coughing’ and for which a provisional diagnosis was recorded. The diagnostic code was then used to allocate patients to body systems or categories, namely respiratory, cardiac, neoplasia, trauma, miscellaneous or open. The ‘miscellaneous’ category included diagnoses that fell within other body systems, such as anaemia, seizures, or intoxications. The ‘open’ category included patients that had been coded with the VeNom terms of ‘condition under investigation’ or ‘diagnosis not made’. Within each diagnostic category, age, gender, breed and short-term outcome (< 48 h) were analysed. Data was analysed using descriptive statistics. Results 1440 case records were retrieved. This represented 27% of all cats with the presenting complaint ‘breathing difficulties with/without coughing’. Of those, 643/1440 (44.7%) cats died or were euthanised, 380/1440 (26.5%) were discharged normally, 400/1440 (27.8%) were transferred to another veterinary practice and 17/1440 (1.2%) were discharged against veterinary advice. 585/1440 (40.6%) patients had a respiratory diagnosis, followed by cardiac (493/1440, 34.2%), neoplasia (84/1440, 5.8%), and trauma (69/1440, 4.8%). 141/1440 (9.8%) of patients had a diagnosis categorised as ‘miscellaneous’ and 68/1440 (4.7%) had an ‘open’ diagnosis. The overall mortality rate of cardiac patients was 297/493 (60%) compared to 173/585 (29.6%) in respiratory patients. Male neutered cats accounted

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 216 of 226 for 34% of the patients in both the cardiac and respiratory categories, compared to 15-19% for other sex/neuter groups. Conclusions Respiratory conditions occurred most frequently, but cardiac cases had the highest mortality rate. The distribution of diagnostic categories was similar to those previously reported. Clinical Relevance This is the first large-scale study of cats presenting with dyspnoea in a first-opinion emergency setting. While there are limitations to this study, such as reliance upon the clinician’s recorded diagnosis, the information may be useful to inform first-opinion veterinary practice and will serve as a basis for future studies.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 217 of 226 Abstract 4: Synthetic Cannabinoid Intoxication; An online survey of veterinary surgeons, technicians and nurses observations of clinical signs, experience of treating and outcomes in dogs with actual or suspected poisoning. Jane Langham BVSc CertVR MANZCVS(Emergency and Critical Care) AP (Emergency and Critical Care) MRCVS Ava Firth BS DVM MVS MANZVS DACVECC DECVECC MRCVS Introduction Synthetic cannabinoids (SC) are a diverse group of compounds which are known to cause toxicity in people, resulting in symptoms similar to those of marijuana toxicity. Only one case report has been published in the veterinary literature regarding SC intoxication in a dog,1 but anecdotal reports suggest that SC toxicity may be occurring. The aim of this study was to explore the clinical experiences of veterinarians in treating SC intoxication in dogs. Materials and Methods An online retrospective recall survey was designed and distributed to Vets Now employees and through veterinary networks of the authors and colleagues in Britain, Europe, United States and Australia. Questions were asked about presenting signs, treatments and outcomes of the cases respondents had treated. Results 61 veterinary surgeons, technicians and nurses from seven countries responded to the survey. Of those, 16 veterinary staff (11 from UK, 3 from USA, 1 from Canada and 1 from Norway) reported having treated a total of 112 patients with suspected SC intoxication. Clinical signs seen included seizures, aggression, ataxia, central nervous system depression, mydriasis, miosis, tachycardia and bradycardia. Outcomes were reported for 98 patients of which 92 (97%) survived to discharge, 4 (4%) died and 2 (2%) were euthanased. A variety of gastric decontamination strategies were employed, using emetics, activated charcoal and gastric lavage. Sedatives were used in one of 97(1%) of dogs and anticonvulsants were used in 3 of 62 (5%) of the patients. Intravenous lipid emulsion was used by 2 of 16 veterinarians. Conclusions This survey shows that veterinary staff in the United Kingdom, USA, Norway, and Canada have treated cases of SC intoxication in dogs. SC intoxication may result in a wide variety of clinical signs, which may be due to the wide variety of SC analogues that are available. This

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 218 of 226 differs significantly from phytocannabinoid intoxication in dogs where the signs are those of central nervous depression only. Symptomatic treatment provided an excellent outcome as 97% of the cases reported in this survey recovered and were discharged. This included the three patients treated with intralipid emulsion. A retrospective online survey is subject to recall bias. Prevalence could not be assessed in this voluntary study as there is an inherent self-selecting bias. The survey’s targeted distribution may have created a bias towards emergency personnel. Clinical Relevance. In dogs, as in humans, synthetic cannabinoid intoxication appears to vary in presentation and potency from phytocannabinoid intoxication. This study has shown that severe effects in dogs include aggression and seizure activity. Further investigation could include coding SC intoxication to allow a retrospective case series.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 219 of 226 AUTOTRANSFUSION AND XENOTRANSFUSION Kenichiro Yagi BS RVT VTS (ECC SAIM) Adobe Animal Hospital/Foothill College, Los Altos, California kenyagirvt@gmail.com Our ability to perform blood component transfusions has become a vital therapeutic option in treating many ailments affecting our patients. One of the most common uses of blood components involve replacement of red blood cells (RBC) in the case of clinical anemia leading to tissue hypoxia. The amount of oxygen delivered (DO2) being reduced to the point critical oxygen exchange ratio is exceeded (signifying inadequate DO2 to meet oxygen demand, VO2) leads to reliance on anaerobic respiration for energy production, and is ultimately unsustainable. Supplementation of oxygen carrying capacity is warranted in these cases, and the most accessible method in providing this is through RBC transfusions. Thus, the demand for RBC products has historically been high, and the struggle for blood banks to meet demands still continues. The unavailability of RBC product is exacerbated by the presence of RBC antigens (blood types) and the potential for immunologic complications without careful consideration of compatibility risks. Alternative methods of transfusions are sought out in the effort to minimize our reliance on homologous transfusions to meet oxygen carrying capacity demands. Xenotransfusions A recent news report of a feline patient who was determined to require a RBC transfusion with the alternative being death has brought to the forefront of our minds of the challenge obtaining feline blood matching our patient can be. A practice, for example, with an in-house bank has two units of type B blood banked regularly, with a type B donor in the donor program ready to donate at beck-and-call would be considered very well prepared for a type B patient requiring transfusions. The practice still would be out of options for RBCs of this rare feline blood type if a patient requires multiple transfusions, or multiple patients come in and happen to be of the same type. Many practices face shortage of RBC products in general, regardless of the type. In this particular news report, the feline patient received canine blood as a part of his treatment; an example of xenotransfusion in practice. Xenotransfusions, or transfusion of blood products between individuals from different species, has been recorded in literature dating back to 1667 involving transfusion of blood from lambs, calves, and dogs to human for various reasons. Xenotransfusion has been employed in the 1800s with a good degree of success, though the discovery of blood types Autotransfusion and xenotransfusion

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 220 of 226 and improved knowledge on blood compatibility from the 1900s encouraged the practice of intraspecies or homologous, transfusions. The practice of intraspecies transfusions has significantly improved the safety and effectiveness of RBC transfusions since varying degree of hemolysis and shortened life span of RBCs were seen in xenotransfusions, with the development of high antibody titre against foreign RBCs leading to immunologic consequences. Veterinary transfusion largely is practiced in this manner, with adequate feline blood supply being challenging to sustain with the small donor pool and more complicated collection process. Being able to use, for example, canine donors of a typical donation volume of 450mL to supply our feline patients with a typical (whole blood) unit volume of 50mL would allow a single donation to give us enough blood for nine transfusions. This seems like a great opportunity for a solution to the blood shortage. Let’s discuss this further. In order to implement xenotransfusion into our practices, we would first need to ensure the effectiveness and safety of xenotransfusions. There are several published studies specifically evaluating the effects of canine to feline transfusions, evaluating pre-transfusion predictors of immunologic complications, immunologic complication signs seen during and after transfusions, and the same on repeat xenotransfusions at varying timings. Efficacy: The studies that have been conducted heavily focused on compatibility testing and immunologic complications and less information on efficacy of the transfusion is available. Literature giving insight to the efficacy of canine to feline transfusion indicates a rapid improvement of clinical symptoms, leading to the conclusion that a positive effect of the transfusion is expected. In a case report involving a type B cat receiving blood from a Labrador Retriever resulted in an increase in PCV taken after the transfusion performed over 48 hours. The effect is relatively short lived, however, since the transfused RBCs seem to have an average lifespan of 4 days. In comparison, a typical life span of RBCs of homologous feline transfusion is 30 days. The loss of transfused RBCs is attributed to delayed hemolytic transfusion reaction resulting from antibody production against RBC antigens introduced. The production of antibodies by the immune system when exposed to foreign antigens (sensitization) occurs in a delayed manner reaching significant titre levels 4-7 days post transfusion, allowing the transfused RBC to persist for 4 days on average. The recipients have been observed to develop icterus from increased intravascular hemolysis and bilirubin load. Safety: Statements regarding safety of canine to feline transfusions can be separated into three specific situations. In almost all transfusions performed in these studies, there were no

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 221 of 226 acute clinical consequences to performing canine to feline transfusions as long as there was no history of previous canine blood transfusions. Subsequent transfusions performed within 4 days of the initial exposure also were performed without acute symptoms of immunologic complications. Subsequent transfusions performed more than 46days past initial exposure resulted in anaphylaxis, which is often fatal. Cats seem to be tolerant of the first canine blood transfusion they receive without signs of acute hemolytic or allergic reactions, indicating a lack of naturally occurring antibodies against canine RBC antigens. These observations correlate with the majority of compatibility testing methods (slide agglutination and cross match hemolysis testing) showing no signs of incompatibility. Occasional positive reactions were seen on the minor (recipient RBC mixed with donor plasma) cross match, which upon transfusion would cause some hemolysis of recipient RBC. This effect is minimized from the use of pRBC, containing very little plasma, and dilution by recipient blood volume upon transfusion. Cats in the studies rarely exhibited signs of complication, and when they did they were mild, involving tachypnea and pyrexia during or within 24 hours of the transfusion. Delayed hemolysis occurring after 4-7 days of transfusion seems inevitable, with presence of anti-canine RBC antibodies made evident through positive slide-agglutination and cross match results when performed after this timing. Subsequent transfusions, after the initial exposure within the 4-7 day period, did not result in clinical signs. Slide agglutination and cross match tests performed during this time period did not result in a positive reaction as well. This indicates a “grace period” in which antibodies are being produced to incite an anamnestic response when the next exposure occurs. Felines in the study that were given doses of canine RBC 1 and 2 days after initial exposure did not exhibit signs of immunologic complications. Test subjects having subsequent transfusions performed later than 6 days after the initial exposure showed signs of anaphylaxis with more than 66% resulting in death. Some of these cats were treated with cyclophosphamide as an immune suppressant prior to second exposure with the hypothesis of immune suppression reducing chances or severity of immunologic complications, with no positive effect seen. This serves as further evidence of the ineffectiveness of immune suppressive agents as premedication for transfusion (human studies show premedication to be ineffective). Summary: Transfusion of canine blood, whether whole blood or packed RBC, can be performed without immediate consequences if it is the first transfusion of this kind. However, the benefit is short lasting, and should be reserved for patients in dire need of blood. The

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 222 of 226 basic considerations in employing this therapeutic option should include situations where all of the following conditions are met. (1) The patient has no source of RBCs with compatible blood type (type B cat with no stocked blood, donor, or nearby hospital with stock, for example) or hemoglobin-based oxygen carrier solution. (2) The patient is imminently going to pass away or is thought to be in danger of sustaining irreversible, hypoxic damage (certainly up to clinical judgment) without the ability to obtain compatible blood in a timely manner. (3) The patient is expected to benefit from a short term oxygen carrying capacity gain. In this case, the patient may have a condition where the cause of anemia can be controlled swiftly enough to allow regenerative response to take over, or allow for time to obtain sources of compatible RBCs in the meantime. (4) The patient has never received canine blood products. (5) The owner understands the risks and consequences of performing a canine to feline transfusion. As the method is non-traditional, the owner should know our exact state of knowledge and potential consequences to give fully informed consent to the procedure. If these conditions are met, use of transfusions of canine RBC to feline patients can be a life-saving therapeutic option in true emergency situations. If a xenotransfusion is decided on, a major and minor cross match should be performed to screen donor-recipient matches resulting in any signs of immunologic complications, and a therapeutic plan formulated with the benefit lasting 4-7 days in mind. Clear understanding of outcomes of future canine to feline xenotransfusion by the owners is important in preventing a second exposure beyond the 4-7 day mark. As responsible veterinary professionals, xenotransfusion should not become common practice in its current state. Effort invested in maintaining a good source and stock of feline RBC products should not decrease simply because “we can always turn to dog blood if we really need to”. “In its current state” is used as a qualifier in the previous passage because there is research ongoing for the human medical field involving “immunocamouflaging”, or biochemical alteration of RBC antigens to prevent detection of the antigen as foreign by the immune system. The technique is still under development and its application to veterinary medicine would have an unknown timeline. Implementation of such techniques in xenotransfusions is theoretically beneficial in preventing immunologic consequences. Autologous Transfusions Several forms of autologous transfusions, or the act of infusing blood products derived from the patient themselves, are available in providing the patient with components necessary. These techniques can be useful in specific situations.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 223 of 226 Autotransfusion: Autotransfusion is the act of recycling blood lost by the patient by collection and reinfusion. The term autotransfusion is specific to the form of autologous transfusion involving blood that is lost from the patient’s condition or injury. In veterinary medicine, autotransfusion is most commonly performed as unwashed red cells transfused through a filter. This is accomplished through transfer of suctioned blood into an intravenous fluid bag and administered with a blood administration set. An alternative method involves the use of a 3-way stopcock attached to a syringe and extension sets. The stopcock is first opened to the extension leading to the pooled blood and syringe, and blood pulled into the syringe. The stopcock is then opened to the syringe and another extension leading to an intravenous catheter, and the blood pushed through an in-line blood filter into the patient. The syringe method can also be employed prior to surgical intervention, through percutaneous insertion of a catheter into a body cavity hemorrhaging is occurring in. Autotransfusion is observed to be effective in alleviating compensatory signs from anemia and improvement in consciousness, whereas replacement of the volume with lactated ringers did not result in the same effect. An autologous RBC salvage system or cell-saver device is a piece of equipment with the capability of collecting blood lost into the patient, separating blood components through centrifugation, washing the RBC, and suspending them back into a suspension for administration. The salvage process can be discontinuous (batched) or continuous (uninterrupted reinfusion) depending on the device, and has the advantage of having the ability to provide higher concentration of RBC than collected blood containing fluid, as well as removing contaminants through the separation and wash process. Autotransfusion has advantages, including the alleviation of blood bank demands in performing transfusions. Blood bank supply is often strained, with upkeep being a significant financial and staff training investment. In addition, by administering autologous blood, the concerns of immunologic complications are eliminated. Blood typing and cross-matching can also be omitted, since there should be no better match to a recipient than their own blood. Storage lesions, which include accumulation of hazardous levels of electrolytes, metabolites, and inflammatory mediators as well as RBC changes reducing their efficacy as oxygen carriers lead to blood stored longer than 14 days to be less effective in treatment of anemia, have shorter survival time, and incite negative effects. These storage lesions can be virtually completely avoided through employment of autotransfusion, as no storage time is involved. One of the main concerns with autologous transfusions is the theoretical potential for iatrogenic metastases of neoplastic cells that may be contained in the blood suspension.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 224 of 226 While no veterinary evidence is available, human studies indicate the lack of such consequences upon autotransfusion. This may be a combination of several factors, such as the thought of the cell salvage process and leukoreduction of the blood leading to effective removal of neoplastic cells. In addition, neoplastic cells may already be in circulation in many cases. Furthermore, allogenic transfusions are known to cause transfusion related immunomodulation resulting in down-regulation of the immune system, associated with increased incidences of cancer recurrence. There is potential for autologous transfusions to be more beneficial for cancer patients. Another concern with autologous transfusions lies in the case of bacterial contamination of the blood being salvaged. In the case of blood salvaged by cell-saver devices undergoing leukoreduction, 99% of the bacterial load is seen to be removed prior to transfusion, eliminating this concern. Blood collected in clean procedures not involving obvious sources of bacterial contamination, such as bowel perforation or penetrating trauma, is seen to contain bacteria as well, questioning the notion of all bacterial contamination being avoidable as well. While the effect of bacterial load in blood prepared for autotransfusion without cell-saver devices and leukoreduction is uncertain, the general approach to these patients involves antibiotic therapy, and there is no evidence supporting increased incidences of bacteremia as a result of autotransfusion. The use of cell-salvage devices may also lead to cell-salvage syndrome resulting in disseminated intravascular coagulation, acute respiratory distress syndrome, acute kidney injury, or death, and is a potential consequence. Pre-operative donation: Autologous transfusions may be performed as an intentional form of blood collection prior to procedures with reasonable chances of it resulting in hemorrhaging and subsequent demand for a transfusion. Pre-emptively collecting blood from the patient, typically a week prior to the procedure will allow for regenerative response to have helped replace the RBC lost through collection. The collected blood is stored in preparation for the anticipated blood loss, serving as a source of autologous RBC product if need arises. Advantages similar to autotransfusion techniques exist with this form of autologous transfusion, including the elimination of need for compatibility testing and alleviation of allogenic blood demand. A differing severity of storage lesion will be seen depending on the timing of blood collection and can lead to increase in complication related to storage lesions. The risk of bacterial contamination upon blood collection should be at a rate similar to allogenic units, dependent on quality of blood collection procedures and storage. Acute euvolemic hemodilution: The detrimental effects of storage anticipated by performing autologous transfusions through pre-operative donation can be circumvented through a

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 225 of 226 technique called acute euvolemic hemodilution. The technique involves blood collection from the patient undergoing a surgical procedure with likelihood of hemorrhaging just prior to the procedure, with replacement of lost blood volume with crystalloids to prevent hypovolemia. While the patient will have reduced circulating RBC mass as the procedure is started, the amount of blood collected is limited to tolerable amounts to meet oxygen demands. The blood lost during the procedure will be diluted in concentration of RBC (PCV), reducing the RBC mass lost when compared to the same volume of blood with the original concentration. The collected blood can be transfused if the need for a RBC transfusion arises, with the same benefits of any autologous transfusion technique, with the additional benefit of the blood being fresh. The technique serves as a method in alleviating allogenic blood transfusion need, though is often not sufficient to eliminate needs. The quest for providing a sufficient supply of safe RBC product is an area of ongoing improvement, as the demand for blood products is ever-present, while the negative effects of blood transfusions in current practice are increasingly understood. Ensuring supply and safety in transfusions rely on methods in reducing the need for RBC transfusions (conscientious blood sampling, assertive treatment of underlying cause, proper assessment of indication), use of alternatives to RBC transfusions, proper risk assessment and compatibility testing, proper patient monitoring, and swift response to complications. Xenotransfusions and autologous transfusions are a couple of strategies increasing our supply of RBC products, each with their situational effectiveness and appropriate considerations.

ECC UK 2016 Copyright Vets Now Ltd Nov 2016 Page 226 of 226 References Bovens, C., Gruffydd-Jones, T. Xenotransfusion with canine blood in the feline species: review of the literature. J Fel Med Surg 2012;15(2):62-67. Hirst, C., Adamantos, S. Autologous blood transfusion following red blood cell salvage for the management of blood loss in 3 dogs with hemoperitoneum. J Vet Emerg Crit Care 2012;22(3):355-360. Kellett-Gregory, L.M., Seth M, Adamantos, S., Chan, D.L. Autologous canine red blood cell transfusion using cell salvage devices. J Vet Emerg Crit Care 2013;23(1):82-86. Kisielewicz, C., Self, IA. Canine and feline blood transfusions: controversies and recent advances in administration practices. Vet Anaesth Analg 2014;41:233-242. Prittie, J.E. Controversies related to red blood cell transfusion in critically ill patients. J Vet Emerg Crit Care 2010;20(2):167-176. Safaei, M., Takami, H.M. Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding. J Res Med Sci 2011;16(10):1332-1339.

Page numbers in italics refer to tables or images. A A lines 23, 171, 173, 174 AB antigen 139–140 abdominal fluid score 7, 189, 199 abdominocentesis indications 15, 16 sites 5 acetoacetic acid 91 acidosis 58, 91 acute haemolytic transfusion reaction 136–137 acute kidney injury (AKI) biomarkers cystatin C 123 early detection 124 NGAL 124 RBP 123 SDMA 123 serum creatinine 122 urinary albumin 123 urinary enzymes 124 urine output 122 urine specific gravity 122 colloids and 35 diagnosis 122 grape/raisin intoxication 211–212 adenosine diphosphate 55 adenosine monophosphate 55 adenosine triphosphate 55 AFAST (abdominal focused assessment with sonography) (see also GFAST; TFAST; vet BLUE) equipment 4, 169, 179 indications 3 interpretation 7–8 abdominal fluid score 7, 189, 199 algorithms 15–16 haemorrhage 8 halo sign 2–3 negative scans 7, 8 positioning 3–4 post-intervention cases 8 serial 3, 8, 13, 14 technique 4–6 caudal vena cava evaluation 9–11, 190, 196 cysto-colic site 5, 6, 190–191 hepato-renal (right paralumbar) site 5, 6 spleno-renal (left paralumbar) site 5, 6 subxiphoid site 2, 5, 6, 20–21, 22 urinary bladder volume estimation 199 aggressive behaviour, clients 83 albumin plasma transfusion and 133 urinary 123 ALI/ARDS (acute lung injury/acute respiratory distress syndrome) clinical signs 101 diagnosis PaO2:FiO2 ratio 57, 104 radiographic signs 102, 103 prognosis 104–105 risk factors 102 treatment 105–106 A-lines 23, 167, 171, 174, 181 alkalosis 58 alloimmunization 67 alveolar-arterial gradient 58 American Cocker Spaniel, IMHA 43 American College of Emergency Physicians 203 American Society of Anesthesiologists categories 154 anaesthetic mortality and 156, 157 anaemia clinical signs 49–50 decreased production 52–53 defined 41, 47 differential diagnosis 41–42 haemolytic 50–52 immune-mediated (IMHA) 42–46, 51–52 in haemorrhage 48–50 iron-deficiency 53 regenerative versus non-regenerative 48 anaesthesia breed considerations 155–156 monitoring blood pressure 160–162 capnography 162 ECG 162–163 pulse oximetry 159–160 mortality 156–157 patient preparation 154–155 plan 155 preoperative evaluation 153–154 signalment 154 anaphylaxis 2, 136, 193 angiostrongylosis clinical signs 117–118 Index

diagnosis 118–119 prevention 119–120 screening for 120 treatment 119–120 Angiostrongylus vasorum 117–120 anticoagulants 45–46 antithrombin 63 anuria 122 apologising 83 apomorphine 213–214 ARDS (see ALI/ARDS) arterial blood gases DO2 55–56 FiO2 57 PaCO2 58–59, 162 PaO2 56–58, 103 PaO2:FiO2 ratio 57 in ALI/ARDS 57, 104 reference ranges 59 samples collection 59–60 handling 60 SaO2 56, 57 SpO2 159 temperature correction 60 arterial catheterization 60, 161 arterial thromboembolism 209 aspirin 46, 209 autoagglutination 44 autologous transfusion 222–225 B B lines 13, 14, 18–19, 23–24, 25–28, 166–167, 173 Babesia canis 51 bacterial translocation 149 Baermann sedimentation technique 118–119 barium 70–71, 112–113 base deficit, reference ranges 59 Beagle, inherited anaemia 53 beta-hydroxybutyric acid 91 biomarkers, in AKI 121–124 blood arterial samples collection 59–60 handling 60 carbon dioxide 58–59 clotting factors 61–62 erythrocytes autoagglutination 44 defects 41, 50 haemolysis 41–42 Heinz bodies 50 lifespan 48 oxygen delivery 41, 55–56 production 47–48 reticulocytes 44, 48 rouleaux 44 spherocytes 42 storage times 129 toxins 41, 50 film evaluation, in IMHA 43–44 haemostasis 61–63 oxygenation 55–58 pH 58 platelets activation 61–62 dysfunction 67–68 products (see blood products) volume cats 49 dogs 49 blood pressure measurement in anaesthesia 160–162 direct arterial catheterisation 161–162 Doppler 161 oscillometric 160–161 in sepsis 34–35 blood products (see also transfusion) IVIG 135 plasma 133–134 red cells cross-matching 141 infusion pumps and 127–128 storage times 129 typing 129–131, 139–140 blunt trauma clinical presentation 3 haemorrhage 8 TFAST 13–14 bone marrow, dysfunction 52 Border Collie, inherited anaemia 53 Boxer, anaesthesia 156 bronchopneumonia 109 C Campylobacter 149 cannabinoid intoxication 217–218 capnography 162 carbon dioxide 58–59 capnography 162 cardiac tamponade 12, 13, 14

cardio-pulmonary arrest 190–191 cardio-pulmonary resuscitation 191 catheter-related bloodstream infection (CRBSI) 147–148 catheters arterial 60, 161 central venous antimicrobial-treated 147–148 infection 147–148 intravenous heparinized saline and 145–146 occlusion 145–146 replacement 146–147 cats abdominal fluid score 7 anaesthetic mortality rates 156, 157 anaphylaxis 136 blood pressure measurement 161 blood typing 139–140, 141 blood volume 49 cardiac versus respiratory disease 108, 185–186 cyanosis 56 diabetic crisis 97 dyspnoea 215–216 haemolysis 50 Heinz bodies 50 hypophosphatemia 50, 95–96 pancreatitis 65, 115 transfusion reaction 130 vet BLUE 184–186 xenotransfusion 131–132, 221 caudal vena cava, ultrasonography 9–11, 190, 196 Cavalier King Charles spaniel, angiostrongylosis 117 central venous catheters 147–148 central venous pressure 190 cerebral oedema 94 chest tube TFAST sites 20, 21, 22, 170, 177, 189 chlorhexidine 148 cholelithiasis 115–116 clients aggressive behaviour 83 apologising to 83 difficult situations 81–83 experience of service 77–79 listening to 82 responding to 83 stress in 81 clinical examination 154 clodronate, in IMHA 45 clopidogrel 209 Clostridium 149 clotting factors 61–62 coagulation 61–63 coagulation inhibitors 67 coagulopathies in angiostrongylosis 118, 119 coagulation inhibitors 67 consumptive 43, 66 dilutional 66–67 fibrinolysis defects 67 in hepatic dysfunction 66 platelet dysfunction 67–68 rodenticide toxicity 66 Cochrane Collaboration 146, 147 Collie, IMHA 43 colloids 35 communication anger 83 apologising 83 difficult situations 81–83 empathy 82, 83 LEARN model 81–83 in-practice 83 responding 83 stress and 81 voicing concerns 207 comparative medicine 203–204 competency ladder 88 congestive heart failure (CHF) versus ALI/ARDS 103 halo sign 2 radiographic signs 108 vet BLUE 166, 174, 184, 185, 186, 195 consumptive coagulopathy 43, 66 contrast media 70–71, 112–113 Coombs' test 44 corticosteroids in angiostrongylosis 119 in sepsis 35–36 creatinine, in AKI 122 cross-matching 141 cyanosis 56 cyclosporine, in IMHA 45 cystatin C 123 cysto-colic AFAST site 5, 6, 190–191 Cytauxzoon felis 51 D DEA antigen 130–131, 139, 140, 141 dead space ventilation 56 death, anaesthetic 156–157 delayed haemolytic transfusion reaction 136–137

dexamethasone, in IMHA 45 diabetes mellitus (see diabetic ketoacidosis; hyperosmolar hyperglycaemic state) diabetic ketoacidosis acidosis 91 fluid therapy 93, 97 and HSS 90 DIC (see disseminated intravascular coagulation) dilated cardiomyopathy (DCM) 108 dilutional coagulopathy 66–67 direct antiglobulin test 44 direct arterial catheterisation 161–162 direct arterial pressure 60 disseminated intravascular coagulation (DIC) in IMHA 42–43 SIRS and 65–66 DO2 55–56 Doberman anaesthesia 155 DCM 108 von Willebrand disease 155 dopamine 34 Doppler ultrasonic detection 161 dry lung all fields 172, 174, 182, 194 dyspnoea cardiac versus respiratory 108–109, 185–186 in cats 215–216 hospital-acquired 101 mediastinum 109 pleural space 109 radiographic views 71–72 ultrasonography 171–176 upper airway 107 E early goal directed therapy 33–34, 208 echocardiography 195 electrocardiography (ECG) 162–163 emesis induction 213–214 empathy 82, 83 employee engagement 85 end-tidal CO2 59, 162 English Springer Spaniel, IMHA 43 enteral nutrition in gastroenteritis 149 nasogastric versus nasoesophageal 150 erythrocytes autoagglutination 44 defects 41, 48, 50 haemolysis 41–42 Heinz bodies 50 lifespan 48 and nutritional deficiencies 52–53 oxygen delivery 41, 47 production 47–48 reticulocytes 44, 48 rouleaux 44 spherocytes 42 toxins 41, 50 erythropoiesis 47–48, 52 erythropoietin 43, 47–48, 52 ETCO2 59, 162 Evan’s syndrome 42 exposure factors 69 extrahepatic biliary obstruction 115–116 F faecal analysis, in angiostrongylosis 118–119 FAST (focused assessment with sonography for trauma) (see also AFAST; GFAST; TFAST) 17–18, 189–190 FATE 64 febrile non-haemolytic transfusion reactions 132–133 feeding tubes, nasogastric versus nasoesophageal 150 fibrinolysis 62 defect 67 Finnish Spitz, IMHA 43 FiO2 57 fluid therapy in ALI/ARDS 105 dilutional coagulopathy 66–67 in DKA 93, 97 in HSS 93–95, 97 in hypotension 160 in IMHA 45 in sepsis 35 focused echocardiography evaluation during life support (FEELS) 191 focused echocardiography evaluation during resuscitation (FEER) 191 folate metabolism 53 foreign body duodenal 70 linear 111, 113 ultrasonography 114 pyloric 70 fractures, and ALI/ARDS 102

fresh frozen plasma 67 front-of-house team 77, 79 G gallbladder extrahepatic obstruction 115–116 halo sign 2–3, 192–193 mucocele 116 gastric dilatation volvulus (GDV) radiographic signs 111 radiographic views 70 gastroenteritis enteral nutrition 149 fasting 148 gator sign 21, 23, 168 GFAST (global focused assessment with sonography) 169, 171, 198–200 Giant Schnauzer, inherited anaemia 53 glide sign 12, 13, 14, 20, 22–23, 28, 167, 171, 175, 181 glomerular nephropathies 64 grape intoxication 211–212 H haemoabdomen AFAST 8 blunt versus penetrating trauma 8 haemoglobin, oxygenation 55–58 haemoglobin-based oxygen carrier solutions 45 haemoglobinuria, in IMHA 41, 41–42, 44 haemophilia 67 haemorrhage causes 48–49 in platelet dysfunction 68 sequelae 49–50 treatment 49 haemostasis 61–63 haemostatic disorders coagulopathies 66–68 thrombosis 63–66 halo sign 2, 192–193 HCO3, reference ranges 59 heart, ultrasonography 195 Heinz bodies 50 heparinized saline, and intravenous catheters 145–146 hepatic dysfunction, coagulopathies and 66 hepatic venous distension, ultrasonography 9, 196 hepato-renal AFAST site 5 hepcidin 52 hirudin 67 history-taking 153 hospital-acquired respiratory distress 101 diagnosis 101–104 hydroxyethyl starches 35 hyperadrenocorticism, thrombosis and 65 hypercapnia 58–59 hypercoagulability 42–43, 63–66 hyperfibrinolysis 67 hyperglycaemia (see hyperosmolar hyperglycaemic state) hypernatremia, in HSS 92 hyperosmolar hyperglycaemic state (HSS) complications acidosis 91 fluid imbalance 92 potassium/phosphorus depletion 92 sodium imbalance 92 diagnosis 90 pathophysiology 89–90 prognosis 91 treatment fluid therapy 93–95, 97 insulin 93–94, 96–97 phosphorus 95–96 potassium 95, 97 hypersensitivity, in transfusion 135–138 hyperventilation 59 hypoalbuminemia 64, 133–134 hypocapnia 59 hypofibrinolysis 63 hypokalaemia, in HSS 92 hypomagnesemia 95 hyponatremia, in HSS 92 hypophosphatemia and haemolysis 50 in HSS 92, 95–96 in IMHA 44 hypoplasminogenemia 63–64 hypoproteinemia 64, 133–134 hyposthenuria 122 hypothermia, in transfusion 133 hypoventilation 56, 58–59 I icterus, in haemolytic anaemia 42, 44, 50 idiogenic osmoles 94 ileus 111

immune mediated haemolytic anaemia (IMHA) diagnosis 43–45 DIC 42–43 Evan’s syndrome 42 pathophysiology 42–43 prognosis 46 thromboembolism 42, 64–65 prevention 45–46 treatment fluid therapy 45 immunosuppression 45, 51 transfusion 45, 52 immune-mediated thrombocytopenia 42 infusion pumps, in transfusion 127–128 insulin therapy, in HSS 93–94, 96–97 interspecies transfusion 131–132, 219–222 intoxication grape/raisins 211–212 phytocannabinoids 217–218 synthetic cannabinoids 217–218 intravenous immunoglobulin (IVIG) 135 iron-deficiency anaemia 53 isosthenuria 122 J jaundice (see icterus) K ketosis 91, 92 L leadership drivers 85 versus management 85 models of 86 conferring 87–88 controlling 87 delegating 88 flexible 87, 88 influencing 87 involving 88 personal best 86–87 Leadership challenge: how to keep getting extraordinary things done in organisations 86 LEARN model 81–83 leeches 67 left atrial to aortic ratio 194, 195 left ventricular short-axis view 194 leukocytosis, in IMHA 44 linear foreign body 111, 113 luflunomide, in IMHA 45 lung point 166, 174–176 lungs (see also specific conditions) ultrasonography 171–176 history of 165–167 ventilation 56 mechanical 105–106 lungworm (see angiostrongylosis) M magnesium supplementation 95 management (see also practice management) 85 mechanical ventilation 105–106 mediastinum, radiography 109 medical value 77 mesenteric torsion 111 metabolic acidosis 59, 91 microaggregate filters 127–128 Miniature Schnauzer anaesthesia 156 IMHA 43 sick sinus syndrome 156 mitochondria 55 mortality, anaesthetic 156–157 mucous membranes, cyanosis 56 mushroom view 194, 195 mycophenolate, in IMHA 45 N nasoesophageal tubes 150 nasogastric tubes 150 neonates, preoperative evaluation 154 neoplasia, thrombosis and 64 neutrophil gelatinase-associated lipocalin (NGAL) 124 nodule sign 25, 27, 167, 171, 172, 181, 182, 185 nutritional deficiencies, erythrocytes and 52–53 O Old English Sheepdog, IMHA 43

oliguria 122 oscillometric blood pressure measurement 160–161 osmolality, serum 90, 94 oxidative phosphorylation 55 oxygen delivery (DO2) 55–56 oxygen supplementation, in ALI/ARDS 105 oxygen toxicosis 105 oxygenation measurement 56–58 physiology 55–56 oxygen-haemoglobin dissociation curve 47, 57 P PaCO2 58–59, 162 pancreas radiography 114 ultrasonography 115 pancreatitis diagnosis 114–115 thrombosis and 65 PaO2 56–58, 103 reference ranges 59 PaO2:FiO2 ratio 57 in ALI/ARDS 103, 104 paralumbar AFAST sites 5, 6 parasiticides 119 parvoviral enteritis 133–134 patient safety 207 PCO2 58–59 penetrating trauma, haemorrhage 8 pericardial TFAST sites 20, 21, 22 pH, blood 58, 59 phlebitis 146 phosphorus in HSS 92 supplementation 95–96 phytocannabinoid intoxication 217–218 plasma transfusion 133–134 plasmin 62 plasminogen 62 platelets activation 61–62 dysfunction 67–68 pleural effusion, radiographic signs 109 pneumocolonogram 112, 114 pneumonia 27, 109 pneumothorax radiographic signs 109 ultrasonographic signs 12, 13, 14, 22–23, 165–166, 174–176 Poodle, IMHA 43 potassium in HSS 92 supplementation 95, 97 practice management client experience 77–79 difficult situations 81–83 employee engagement 85 leadership (see leadership) medical value 77 reception team 77–79 prednisone, in IMHA 45 propylene glycol 50 protein C 63 protein-losing nephropathy 64 proteinuria 123 pulmonary contusions 12, 13, 14, 24, 108, 166, 177 pulmonary inflammation 104 pulmonary oedema in ALI/ARDS 102–103 in CHF 103 radiographic signs 108 pulmonary thromboembolism 42 radiographic signs 109 pulse oximetry 103–104, 159–160 pyrexia, in sepsis 36 Q quick peek 194, 195 R radiography abdomen extrahepatic biliary obstruction 115 gastric outflow obstruction 113 GDV 111 ileus 113 linear foreign body 111, 113 pneumocolonogram 112, 114 upper GI contrast studies 70–71, 111–113 views 70 in ALI/ARDS 103 contrast studies, upper GI 70–71, 111–113 dyspnoea mediastinum 109 pleural effusion 109

respiratory versus cardiac 108–109 upper airway 107 views 71–72 exposure factors 69 positioning 69–70 spinal 70 in trauma 69–70 raisin intoxication 211–212 Rantanen, Norman 165 rapid ultrasound in shock (RUSH) 190, 191, 198 reception team 77, 79 red blood cells (see erythrocytes) reference ranges 153 reticulocytes 44, 48 retinol-binding protein (RBP) 123 rodenticide toxicity 66 rouleaux 44 S saline agglutination test 44 SaO2 56, 57 sepsis antibiotics 36 blood pressure management 34–35 corticosteroids 35–36 early goal directed therapy 33–34, 208 fever 36 fluid therapy 35 human 6 serum osmolarity 90, 94 shock hypovolaemic 49 ultrasonography 198 shred sign 25, 27, 167, 171, 172, 177, 181, 182, 185 silver-alginate 148 SIRS (see systemic inflammatory response syndrome) small intestine, foreign bodies 111 snake envenomation 66 sodium, in HSS 92 specific gravity, urine 122 spherocytes 42 spleno-renal AFAST site 5, 6 SpO2 103–104, 159 Staffordshire bull terrier, angiostrongylosis 117 stress, in clients 81 stress erythropoiesis 48 subxiphoid site 2, 5, 6, 20–21, 22 Surviving Sepsis Campaign 33 symmetric dimethylarginine (SDMA) 123 synthetic cannabinoid intoxication 217–218 syringe pumps, in transfusion 67 systemic inflammatory response syndrome (SIRS) and ALI/ARDS 102 thrombosis and 65–66 T TFAST (thoracic focused assessment with sonography for trauma) (see also AFAST; GFAST; vet BLUE) echo views 195 equipment 19–20 indications 19 interpretation 22–24 algorithms 12–14 negative scans 28 positioning 19 technique 20–22 caudal vena cava evaluation 9–11, 190, 196 chest tube sites 20, 21, 22, 170, 177, 189 left atrial to aortic ratio 195 left ventricular short-axis view 194 pericardial sites 20, 21, 22 subxiphoid site 2, 5, 6, 20–21, 22 thoracocentesis, indications 12, 13, 14 thrombin 61, 62 thrombocytopenia, in IMHA 44 thromboelastography 64, 118 thrombosis 63–66 in hyperadrenocorticism 65 in IMHA 42, 65–66 in neoplasia 64 in pancreatitis 65 pathophysiology 63–64 prevention 45–46 in protein-losing nephropathy 64 thromboembolism 42–43 prevention 209 pulmonary, radiographic signs 109 thromboxane A2 63, 65 tissue factor 61, 63 tissue sign 25, 27, 167, 171, 172, 181, 182, 185 tissue-type plasminogen activator 62 tracheal collapse 107 tracheitis 107 tranexamic acid 210

transfusion (see also blood products) autologous 222–225 compatibility testing 129–131, 139–140, 141 complications 67, 129, 132–133 TRALI 138 type I hypersensitivity 135–136 type II hypersensitivity 136–137 type III hypersensitivity 137–138 in dilutional coagulopathy 67 in IMHA 45, 52 indications 219 infusion pumps and 127–128 plasma 133–134 premedication 132–133 warming 133 xenotransfusion 131–132, 219–222 transfusion-related acute lung injury (TRALI) 138 U ultrasonography (see also AFAST; TFAST; vet BLUE) in acute abdomen 111–112, 114 cardio-pulmonary arrest and 191–192 caudal vena cava 9–11, 190, 196 extrahepatic biliary obstruction 115–116 in human emergency medicine 203–204 lungs 171–176 pancreas 115 in shock 190, 191, 198 terminology 189–190 volume status monitoring 190, 193–194 ultrasound lung rockets 13, 14, 166, 171, 172, 173, 180–181, 182, 197 unfractionated heparin 46 upper GI contrast studies 70–71, 111–113 urinary bladder, volume estimation 199 urine albumin 123 enzymes 124 output 95, 122 specific gravity 122 urokinase plasminogen activator 62 V ventilation 56 perfusion mismatch 162 vertebral heart scale 108 vet BLUE (veterinary bedside lung ultrasound exam) abnormal findings 171–172 algorithms 12, 173 dry lung all fields 172, 174, 182, 184, 194 interpretation 27–28, 174 lung point 166, 174–176 negative scans 28 patient preparation 168 pneumothorax 174–175 positioning 168 probe 169 technique 24–27, 167–171 wet lung versus dry lung 171, 172, 181, 182, 197 Virchow’s triad 63 vitamin K 66 Vitis vinifera 211 volatile fatty acids 149 W wedge sign 25, 167, 171, 181 Willebrand disease 155 X xenotransfusion 131–132, 219–222

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