# ACUTE CANINE PANCREATITIS

Michael D Willard, DVM, MS, DACVIM

## DIAGNOSIS

History and physical examination are, as always, critically important; but, they are not that helpful for diagnosing pancreatitis. Rather, they are more useful for finding other problems that may be mimicking pancreatitis. Regarding signalment, Schnauzers and Yorkies are famous for acute pancreatitis, but these breeds get many other diseases that cause vomiting. Furthermore, acute pancreatitis can be found in any breed of dog. Canine pancreatitis is classically considered to present with acute vomiting and anorexia. Abdominal pain is frequently present, but it is easy to miss during physical examination, and fever is occasionally seen. However, we are recognizing more and more and more cases in which a) vomiting is not as severe as we have come to expect, and b) in which we are initially strongly drawn to other diagnoses. To some extent, many of us are no longer sure what a "typical" case of canine pancreatitis is. Some dogs (especially those with pancreatic abscesses) may have relatively mild, intermittent, unimpressive vomiting and continue to eat a reasonable amount of food. Many of the severely ill patients may present in classic systemic inflammatory response syndrome (SIRS) which is what used to be called septic shock (until we found out that you can have the same thing occur with any cause of massive inflammation). Many dogs with very severe acute pancreatitis present as though they had an acute, septic abdomen. Some have substantial amounts of abdominal fluid. If acute pancreatitis is associated with or due to pancreatic carcinoma (rare), you may rarely see a dog that has widespread subcutaneous fat necrosis causing sterile abscesses that are typically painful and cause cutaneous discoloration. Most cases of canine pancreatitis seem to be temporarily related to either ingestion of fat or lipaemia associated with diabetic ketoacidosis. Trauma and drugs can also cause canine pancreatitis. Drugs that are suspected of causing pancreatitis in people and animals include azathioprine, sulfonamides, tetracycline, and potassium bromide.

CBCs often show an inflammatory leukogram, but 1) this is a very nonspecific finding and may be due to any number of problems and 2) not all animals with acute pancreatitis have a notable leukocytosis. Degenerative left shifts and substantial toxicity of circulating WBCs can be seen if the patient is in SIRS. Likewise, thrombocytopenia due to DIC is often found in severely affected patients. However, some animals with clinically severe pancreatitis have absolutely normal leukograms. There are no findings on CBC that definitively diagnose or definitively eliminate pancreatitis

Serum biochemical panels are not as helpful as we would like. Serum lipase and amylase activities are insensitive (each is about 50%) and nonspecific (again, about 50%) for pancreatitis. We no longer request them in dogs or cats. Dogs with acute pancreatitis and even pancreatic abscesses have had normal serum lipase activities. We have also identified dogs with drastically increased serum lipase activities that have intestinal foreign objects or gastritis, but no gross evidence of acute pancreatitis. Lipase is produced by the canine gastric mucosa which explains why inflammation or damage to the stomach can result in excessive serum lipase activity. Canine TLI is slightly more specific than amylase and lipase, but it is still not a sensitive test (approximately 35%). Therefore, it too has very poor negative predictive value. We have seen plenty of dogs with pancreatitis that had normal serum TLIs.
The immunoreactive canine pancreatic lipase assay (i.e., cPLI or Spec cPL) appears to be the most sensitive (approximately 80-85%) test for pancreatitis available. There are a few false negative results with this test, but it is clearly much more sensitive than any other blood test available. The real question is how specific it is for clinically important disease (i.e., lesions of the pancreas that are causing clinical disease as opposed to microscopic lesions that are clinically silent). To some extent, you can best think about cPLI like "ALT for the pancreas". The biggest advantage is that if the cPLI test is negative, it is much less likely that pancreatitis is the real problem and you need to look very hard for extra-pancreatic disease in the dog.

Blockage of the main pancreatic duct due to swelling due to generalized pancreatitis, an intrapancreatic granuloma, or an abscess that subsequently blocks the pancreatic duct may cause extrahepatic biliary tract obstruction (EHBO) with a notable increase in serum alkaline phosphatase and serum bilirubin. Pancreatitis is probably the most common cause of EHBO in the dog. Thus, while EHBO is very suggestive of acute pancreatitis (assuming that the patient does not have a mucocoele, which is usually easy to detect with ultrasound), relatively few dogs with acute pancreatitis develop EHBO. Furthermore, there are reasons for this triad of signs besides acute pancreatitis and extrahepatic biliary tract obstruction (e.g., cholangitis-cholangiohepatitis). Ultrasonographic evaluation of the abdomen (discussed below) is particularly helpful in these patients.

Plain abdominal radiographs help eliminate other diseases which may mimic acute pancreatitis. Not finding evidence of other abdominal disease (e.g., foreign object) is helpful in eliminating obstruction and narrowing the list of differential diagnoses. Occasionally, one finds radiographic signs which specifically suggest acute pancreatitis. A sentinel loop (i.e., a dilated, air-filled segment) in the descending duodenum, and/or lack of serosal detail in the upper right abdominal quadrant, and/or lateral displacement of the descending duodenum on the ventro-dorsal projection, and/or a mass medial to the descending duodenum (on the ventro-dorsal projection) and/or a mass just behind the liver and just below the pylorus (on the lateral projection) are somewhat suggestive of acute pancreatitis. These findings are only meaningful if present; many (probably most) dogs and cats with acute pancreatitis do not have any of these radiographic findings. Probably the greatest value of abdominal radiographs is that they help eliminate other diseases that could be causing signs similar to those caused by pancreatitis.

Abdominal ultrasonography often finds abnormalities that suggest or are consistent with pancreatitis as well as eliminate other potential causes of vomiting and abdominal pain. Ultrasonography has been suggested to be about 40-70% sensitive in finding canine pancreatitis. One may sometimes detect hypoechogenicity surrounded by hyperechoic fat in the region of the pancreas that is due to pancreatitis. At other times, a markedly thickened pancreas may be found. Both findings are very specific evidence of pancreatitis. Evidence of EHBO (i.e., dilated bile ducts, not just a big gall bladder) is very suggestive of pancreatitis. Rarely, you will find dilated bile ducts due to inflammatory biliary tract disease, but this is not nearly as common a cause as is biliary tract obstruction. Any dog with extra-hepatic biliary tract obstruction (that does not have a mucocoele) and that is vomiting/anorexic should be assumed to have pancreatitis until proven otherwise. It is very important to note that the ultrasonographic appearance of the pancreas can change dramatically within a few hours, so repeating abdominal ultrasound later on the same day or early the next day can sometimes be most revealing.
Diagnosing pancreatitis during laparotomy is the least desirable method of diagnosis. Some patients present exactly like acute septic peritonitis but are ultimately diagnosed as having non-septic pancreatitis. There is nothing wrong with doing an exploratory laparotomy in a patient in which septic abdomen is a major consideration, only to find out that the patient has non-septic pancreatitis. We very rarely have reason to biopsy a normal appearing canine pancreas, and what grossly appears to obviously be pancreatitis in the dog seldom requires a biopsy unless carcinoma is a concern. However, you should never simply look at what appears to be an obviously neoplastic mass in the pancreas and make a diagnosis of carcinoma without biopsy of it, no matter how extremely terrible it appears. Pancreatitis is much more common in dogs than pancreatic carcinoma, no matter how bad the pancreas looks or how many adhesions are present. If you biopsy the pancreas, it is important to obtain a biopsy that goes deeper than the superficial necrotic surface or adhesions. Cytology can be useful for making a presumptive diagnosis; however, I have seen at least one case in which cytology of a pancreatic mass was read out as carcinoma by two accomplished cytologists and yet multiple biopsies all came back as necrotic pancreatitis. Anecdotally, there appears to be more risk of causing iatrogenic pancreatitis with surgery in the dog than in the cat. Maintaining excellent mesenteric perfusion during anaesthesia and performing the surgical biopsy with reasonable care and good technique minimizes the risks. Laparoscopic biopsy of the pancreas might be safer than surgical biopsy, but that is just anecdotal at this time.

Chronic pancreatitis (i.e., chronic pancreatitis with intermittent, relatively mild recurrences) can be challenging to diagnose. Dogs with episodic vomiting due to recurrent bouts of pancreatitis may not have any other signs of disease, and they invariably are admitted to your clinic for a work up after the last bout has run its course or is on the mend. Episodes of vomiting and anorexia due to recurrent pancreatitis can be random and unpredictable. In such patients, the previously mentioned diagnostics may be attempted, especially when acute exacerbations occur. Very rarely, upper gastrointestinal barium contrast radiographs may rarely reveal duodenal abnormalities (e.g., dilatation, stricture) which suggest that recurrent bouts of acute pancreatitis have caused scarring of the pancreas which in turn have compromised the maximum size of the duodenal lumen. Ultrasonographic changes are nice if they are present, but they can be minor making it difficult to accurately interpret them. Feeding an ultra-low fat diet for 3-4 times longer than what was previously the longest interval between episodes may sometimes be helpful in making a presumptive diagnosis. If episodic vomiting/anorexia does not recur while feeding such an ultra-low fat diet for an interval so long that you would have been sure to experience another episode, then we can often assume (rightly or wrongly) that the signs were due to pancreatitis (or perhaps some other dietary-responsive disease). Anytime you find exocrine pancreatic insufficiency (diagnosed with TLI) in a breed that is not commonly affected with pancreatic acinar atrophy (e.g., German Shepherd Dog, rough-coated Collie), then chronic pancreatitis becomes a major concern.

Pancreatic abscesses in dogs (as opposed to cats) are almost invariably sterile. Affected dogs typically can have a much more chronic, smouldering course (e.g., vomiting for a month or more, mild loss of appetite) than most dogs with more typical acute pancreatitis. We have even found a few dogs that had pancreatic abscesses that were completely asymptomatic. Abdominal pain may be present or absent. CBC and serum biochemistry findings are unpredictable. Diagnosis requires ultrasound.
Treatment may be surgical marsupialization, percutaneous ultrasonographic drainage or just
observation.

THERAPY

As of this writing, there is not a single, well-designed, robust, prospective, stratified study on the
treatment of canine acute pancreatitis. Therefore, all any of us has is opinions, period.

Nothing per os (NPO) has been the classic therapy for pancreatitis for many years. While it is true that they feed people with pancreatitis earlier than we feed dogs, you must remember that human pancreatitis is unassociated with dietary fat. People get pancreatitis from alcohol, trauma, gall stones and MOF (multiple organ failure). Canine pancreatitis is associated with dietary fat (as well as surgical trauma when poor technique is used around the pancreas). An initial study in Australia suggests that it is safe and perhaps beneficial to feed dogs with acute pancreatitis per os or with an oesophagostomy tube as soon as they can tolerate it (i.e., they do not get worse, even if they are still vomiting). I recommend that a) you feed a diet with as low a fat content as possible, and b) if the feeding is associated with worsening of the vomiting, that you stop it and either try again in a day or two, or go to jejunostomy feeding. Do not try to get full caloric intake into the patient; rather, start with small amounts to see if the patient will hold down the food. Obviously, if feeding is associated with worsening of the vomiting or general condition, stop the feeding. I generally start feeding potato or rice (i.e., no fat) and gradually work my way up to commercial diets with low fat content. Try hard to avoid parenteral nutrition.

Fluid therapy is critical, and subcutaneous administration of fluids is clearly inferior to IV fluids for all but mildly affected animals. IV fluid administration is often sufficient, even in dogs in which a pancreatic granuloma has temporarily blocked the main bile duct. Adequate pancreatic circulation is probably crucial for healing damaged pancreatic tissue; therefore, it is probably better to provide a little too much fluid rather than a little too little fluid unless the patient has congestive heart failure or oliguric renal failure. The abdominal viscera is not "first in line" to receive circulation when the patient is dehydrated (which most dogs with pancreatitis are when they come to your office). Obese and fat dogs (which describes many dogs with pancreatitis) do not necessarily have skin tenting when they are dehydrated. Likewise, although you might expect dry, tacky oral mucus membranes, a nauseated animal may be salivating enough to make the mucus membranes moist even though it is dehydrated. If a vomiting dog is not eating or drinking, then it is dehydrated regardless of how well hydrated it appears on physical examination. However, if you give substantially too much crystalloid and dilute the serum protein concentrations, this could be detrimental.

One should monitor the serum albumin concentration during fluid therapy in these patients. If the serum albumin concentration decreases significantly (i.e., to < 2.0 gm/dl), then the plasma oncotic pressure likewise decreases which diminishes the effective perfusion at the capillary level. Since perfusion is so critical to treating dogs with pancreatitis, one should probably become concerned whenever the serum albumin concentration falls below 2.0 gm/dl. It is very hard to administer enough plasma to significantly raise the plasma albumin concentration. Half of the albumin in the plasma that you administer will end up in the extravascular compartment instead of the intravascular compartment. Hetastarch is a better choice because it will stay in the circulation and raise the plasma oncotic pressure for much longer than plasma. Be careful with hetastarch; it occasionally is associated with worsening of clinical signs. It is best to give small amounts repeatedly than just give a large
amount. Human albumin can be used effectively, but it occasionally causes anaphylactoid reactions that can kill the patient; therefore, it is not recommended. Canine albumin is safer, but it does not last as long as hetastarch. Plasma might be more effective than hetastarch because plasma might also restore circulating protease inhibitors and replenish AT III (which is a treatment for DIC). This is a very contentious point. One retrospective study has shown that plasma did not help treat dogs with pancreatitis; however, this study suffers from the problems inherent in all retrospective studies.

If the patient cannot tolerate early refeeding (i.e., the vomiting becomes worse), then jejunostomy feeding is another option. It is safer, less expensive, and less dangerous than parenteral nutrition, and has been associated with a better prognosis. In particular, it should be considered if an exploratory laparotomy was performed when the pancreatitis was diagnosed because a J-tube can be placed at that time. Alternatively, one can place a jejunostomy tube via laparoscopy, through a G-tube, and via the nose (naso-jejunostomy).

Antiemetics are useful in patients that are vomiting repeatedly or that feel so nauseated that they feel terrible. I prefer to only use antiemetics for short periods of time because I want to see if the patient is improving enough so that it no longer needs the antiemetic to stop vomiting. However, if the patient is vomiting multiple times per day or obvious feels terrible due to the nausea, then maropitant (1 mg/kg SQ) appears to be very useful. Maropitant might also have the advantage of providing some analgesia because it blocks Substance P binding. Dolasetron (0.3-1.0 mg/kg qd) and ondansetron (0.25 mg/kg qd) can be effective, but maropitant is preferred.

H-2 receptor antagonists have been used to "prevent gastric ulceration and erosion". It is doubtful that ulceration/erosion is a common problem in all but the sickest patients. Furthermore, if one desires to protect the gastric mucosa, the proton pump inhibitors are far superior to the H-2 receptor antagonists. Pantoprazole (1 mg/kg IV qd) or omeprazole (1-2 mg/kg PO bid) are the most commonly used drugs. I suspect that they provide more benefit by being antidyspepsic in nature (thereby making the patient feel better) than they do by preventing ulcers, but that is a guess. They probably offer minimal benefit to the patient.

Antibiotics have been used to "prevent" secondary bacterial infection of the inflamed pancreas, which is supposed to be "fertile ground" for infection. However, there is minimal evidence that bacterial infection is of any significance in routine canine pancreatitis. Antibiotics do not hurt these patients, but it is very questionable how helpful they are. However, dogs in SIRS due to pancreatitis may be a different story. Any dog in SIRS from any reason is potentially at increased risk of infection due to severely compromised mesenteric circulation.

Corticosteroids are very controversial in the treatment of pancreatitis. While they increase serum amylase and lipase activities, they do not cause pancreatitis. It is possible (and this is controversial) that they may be useful in treating patients that are in Systemic Inflammatory Response Syndrome (i.e., SIRS, which used to be called "septic shock") due to the pancreatitis. At this time, there are good data showing that it is probably reasonable to give physiologic doses because dogs in SIRS typically can have what has been termed "Critical illness related corticosteroid insufficiency" (CIRCI), that is to say that they are relatively hypoadrenal. This is another very controversial statement. If steroid
therapy for pancreatitis is contemplated, it should probably be reserved for the severely ill dog that is
not responding to fluid resuscitation.

If DIC appears to be a major problem, aggressive administration of fresh frozen plasma to replace
clotting factors and anti-thrombin III concentrations is probably more effective than heparin.

Analgesics are critically important. One must remember that dogs are clearly much “tougher” than
people, and they often hide their pain well. Unless there is some good reason to the contrary, it is
best to routinely assume that dogs with acute pancreatitis are in pain and will benefit from analgesic.
In only the very mildest of cases is butorphanol sufficient. In moderate cases, methodone is
reasonable. As the pain becomes more severe, we progress to constant rate infusions of fentanyl. Is
the most severe cases, we administer a constant rate infusion of fentanyl, lidocaine and ketamine.
# PARVOVIRUS UPDATE

Isabelle Goy-Thollot, Dr Vet, PhD, DECVECC
SIAMU, VetAgro Sup, Lyon, France

Canine parvovirus infection could lead to sepsis, septic shock, MODS and death if left untreated. This lecture aims to present an update of diagnostic tests, prognostic factors, fluid replacement, use of plasma and albumin, use of antibiotics, alternative therapies, gastrointestinal motility and integrity support (i.e. early enteral nutrition) as well as gastrointestinal parasites treatment.

## Introduction

Parvoviruses (Parvoviridae) are small, non-enveloped, single-stranded DNA viruses that replicate in actively dividing cells. Canine Parvovirus-1 (CPV-1) was first discovered in the early 1960's, and caused mild clinical signs of diarrhoea in dogs. In 1978, a new form of CPV, CPV-2, caused a widespread pandemic in adult domestic and wild dogs. In 1979, CPV-2a was discovered, then progressively worsened in virulence and pathogenicity to CPV-2b discovered in 1984. CPV-2b is now the most prevalent form of canine parvovirus worldwide, however a new genetic variant, CPV-2c, is being found in Europe (Italy) and Asia, as well as North and South America. In susceptible canine populations, parvovirus infection most often presents as a severe systemic and even life-threatening illness. It is associated with a survival rate as low as 9% in the absence of treatment, and 64% with treatment.

## 1. Pathophysiology

Infection is acquired by the faeco-oral route of transmission. Canine parvovirus has a predilection to infect rapidly dividing cells of the gastrointestinal tract, lymphoid tissue, and bone marrow, leading to haemorrhagic diarrhoea, vomiting, marked leukopenia, and immunosuppression within 4 to 5 days of exposure. Viral replication within crypt cells causes collapse of the villi and villi necrosis, which leads to a break in the normal blood epithelial barrier. Translocation of enteric bacteria and bacterial endotoxin into systemic circulation, combined with a lack of production of protective leukocytes from the infected bone marrow leads to systemic sepsis, septic shock, SIRS, and can lead to MODS and death if left untreated. The rate of lymphoid and intestinal cell turnover appears to be the main factor determining the severity of the disease. Stress factors, in particular parasitic or weaning, may predispose dogs to clinical disease by increasing mucosal cell activity. Inadequate immunization to parvovirus during the 1st year of life is an additional risk factor for disease. Surviving infected animals will shed parvovirus in their feces for up to 39 days following exposure. These viruses are hardy, persisting for long periods of time in the environment (5-7 months), and are ubiquitous.

## 2. Signalment and Clinical Signs

The majority of cases of clinical disease are observed in younger puppies from 6 to 20 weeks of age. Initial clinical signs associated with CPV enteritis are nonspecific, and include anorexia, depression, and fever. They often become progressively worse over time. Lethargy, inappetance, vomiting, diarrhoea (often haemorrhagic) are cornerstones of disease. Weakness can be due to dehydration, or secondary to hypoglycaemia from depletion of glycogen stores and sepsis. The most severely affected animals can develop seizures, thromboembolic disease, disseminated intravascular coagulation (DIC) and death if left untreated.
### 3. Laboratory Diagnoses

Practitioners can utilize a readily available cage-side enzyme-linked immunosorbent assay (ELISA) test to demonstrate CPV in the stool of infected puppies. In some cases, false positive or false negative results can occur. However, the presence of a positive test with concomitant clinical signs of vomiting, diarrhoea, lethargy and inappetance support a diagnosis of parvovirus. Other diagnostic tests (i.e. PCR) are also available, but take longer for results.

The white blood cell count (WBC) during CPV enteritis is generally characterized as being low to severely low. Leukopenia occurs in only 50% of affected dogs, and is, therefore, not a sensitive or specific indicator of parvovirus in infected animals. While infected animals are often evaluated for neutropenia, an absolute lymphocyte value of less than 1000 lymphocytes/uL within 48 hours of admission has been correlated to be a negative prognostic indicator in affected animals. Other non-specific biochemical parameters, which may be altered during parvoviral infection include hypoproteinaemia, hypoalbuminaemia, anaemia, extrahepatic cholestasis of sepsis, pre-renal azotaemia, coagulation defects including thrombocytopenia and prolonged coagulation times, hypoglycaemia, and hypokalaemia. Significantly higher plasma acute phase protein concentrations (C-reactive protein and ceroplasmin) have been found to be significantly increased in dogs with parvovirus, and can help predict mortality.

### 4. Treatment and Monitoring

The cornerstone of management of CPV enteritis remains supportive care.

#### 4.1. Fluid therapy

Re-establishment of effective circulating blood volume in puppies that present in hypovolaemic shock and fluid replacement for losses secondary to ongoing diarrhoea and vomiting is mandatory. The initial fluid of choice is a balanced electrolyte solution (i.e., lactated Ringer's solution). The preferred rate and route of initial fluid therapy varies with the condition of the patient. Fluid deficits should be replaced as soon as possible (within 1–2 hours of presentation) in dogs that present in hypovolaemic shock. A short, large-bore catheter (18 or 20 gauge) can be placed in the cephalic or lateral saphenous vein, and fluids for treatment of shock should be administered at a rate and volume dictated by physiologic endpoints. Serum lactate values can be used to guide fluid therapy and evaluate response to methods to improve perfusion. During the maintenance period, frequent urination in a patient with normal renal function, combined with appropriate weight gain, supports that fluid therapy is effective at maintaining hydration and perfusion in the face of gastrointestinal losses.

Due to loss of protein in diarrhoeic faeces, hypoalbuminaemia and decreased colloid osmotic pressure (COP) is common. Albumin can be supplemented in very small patients using fresh frozen plasma at a dose of 15–20 mL/kg for each 5 g/L increase in serum albumin concentration. For larger patients, canine specific or concentrated human albumin (if available) infusion can be provided. To help maintain oncotic pressure, additional use of hydroxyethyl starches at doses of 20 – 30 mL/kg/day are often proposed but their use remains controversial.

Patients with ongoing anorexia, vomiting, and diarrhoea are prone to the development of hypokalaemia and metabolic acidosis. Potassium chloride is added to the fluids as needed to prevent the development or worsening of hypokalaemia. When possible once to twice daily monitoring of
venous blood gas with electrolytes can help guide necessary supplementation. If a patient has refractory hypokalaemia, empiric addition of magnesium in the form of magnesium chloride (0.75 mEq/kg/day IV CRI) should be considered.

**4.2. Oxygenation and Ventilation**

Careful monitoring of a patient's respiratory rate and effort, as well as pulse oximetry may become necessary in the most severely affected patients. If a patient shows signs of increased respiratory effort or hypoxaemia (SpO2 < 94%), oxygen supplementation should be provided.

**4.3. Treatment of hypoglycaemia**

Hypoglycaemia, secondary to profound malnutrition, hypermetabolism, underlying liver dysfunction, or sepsis, is commonly observed with CPV enteritis. Intravenous supplementation of 2.5–5% dextrose added to the balanced electrolyte solution, may be necessary.

**4.4. Transfusion**

If red cell mass becomes significantly diminished from loss in haemorrhagic faeces, packed red blood cell or whole blood transfusions may become necessary. In general daily to twice daily monitoring of a patient's packed cell volume is recommended. If hypocoagulability can be demonstrated, replenishment of coagulation factors in the form of fresh frozen plasma or cryoprecipitate may be warranted.

**4.5. Antibiotics**

Immune status is often severely impaired in patients with parvoviral enteritis. Careful selection of broad-spectrum bactericidal antibiotics that will affect gram-positive and –negative, as well as aerobic and anaerobic bacteria should be considered. The parenteral route is preferred over enteral delivery. A combination of a β lactam antibiotic (ampicillin, 22 mg/kg IV TID) with an aminoglycoside (gentamicin, 6 mg/kg IV SID) or quinolone (enrofloxacin, 5 mg/kg IV SID) will provide excellent coverage against gram-negative and anaerobic bacteria that may translocate from the gut. Aminoglycosides may cause acute renal failure, and should be administered only in well-hydrated patients; enrofloxacin has been associated with the development of cartilage abnormalities in young, growing dogs. In the most severe cases, metronidazole (10 – 15 mg/kg IV Q8- Q12h) can also be added for improved anaerobic coverage.

**4.6. Antiemetic therapy, GI motility and integrity protection**

Gastrointestinal motility and integrity is severely compromised in the patient with parvoviral enteritis. Antiemetics may be necessary in cases of severe vomiting. The two drugs most commonly used are metoclopramide (1 – 2 mg/kg/day IV CRI) and maropitant (1 mg/kg IV or SQ Q24h). Anti-acids IV could be added (i.e. ranitidine, 1 mg/kg IV Q8h). Placing a naso-gastric tube can allow for both enteral nutrition, as well as gastric decompression as necessary to help prevent additional vomiting. The presence of gastrointestinal parasites can worsen patient morbidity and response to therapy, so careful evaluation of faecal flotation, smears and with ELISA for giardia, coccidia, isospora and other gastrointestinal parasites is necessary. Empiric deworming is recommended in severely affected cases.
## 4.7. Nutrition

Fasting/NPO promotes negative changes in the intestinal mucosa, such as decreased villus height and crypt depth, decreased antioxidants within enterocytes, and increased enterocyte apoptosis, leading to increased permeability of the mucosal barrier and higher chances of bacterial translocation. Parenteral nutrition should only be used when the gastrointestinal tract cannot tolerate any form of enteral feeding, and partial parenteral nutrition to provide calories in combination to enteral feeding is preferable to total parenteral nutrition.

Early enteral feeding in patients with GI diseases has been shown to improve healing of damaged enterocytes, resulted in more rapid clinical improvement, increased weight gain and decreased possibility of bacterial translocation (hence lower risk of development of systemic inflammation and sepsis), and is currently recommended, after 12 hours of hospitalization even when there is persistent vomiting and diarrhoea. The percentages of prescribed nutrition delivered and the frequency of gastrointestinal complications are not significantly different between patients fed continuously and patients fed intermittently via nasoenteric tubes, hence those are both viable options.

It is important to use diets with very high digestibility and with the highest possible energy density to cover the pet's needs in a reduced feeding volume. Supplementation with EPA and DHA can help limit inflammatory processes, and antioxidants (such as vitamin E, vitamin C, taurine, carotenoids...) can be helpful in restoring antioxidant status and in supporting the immune system.

When tube-feeding puppies, the starting point is the quantity calculated according to RER (Resting Energy Requirement) equation: $RER = 70 \text{ kcal/kg}^{0.75}$ of current bodyweight, divided into several meals and reached progressively if there has been a period of anorexia. Serial monitoring of bodyweight and body condition is then crucial, to progressively adapt the food quantity to cover the puppy's energy needs (which might be 2 times higher than RER).

## 4.8. Patient comfort

Cramping and ileus can decrease feeding tolerance. As opioids often can promote ileus at doses necessary to provide analgesia, lidocaine (30 mcg/kg/min) in combination with low doses of a partial mu agonist such as buprenorphine (0.01 mg/kg IV Q8h) may be beneficial in improving patient comfort. Nursing care, and patient mobilization are important in maintaining patient cleanliness. Catheter sites should be monitored closely, cleaned and changed daily to evaluate for catheter thrombosis and contamination. Bleach solutions (6%) must be used to clean the animal environment.

## 5. Alternative Therapies

Alternative therapies include the use of antiviral drugs such as oseltamivir. None of the alternative therapies have been associated with proven benefit in survival or decreasing patient morbidity. Feline interferon omega has been shown to significantly decrease clinical signs and mortality in naturally infected patients (2.2 units/kg IV once daily for 3 consecutive days). A recent randomized clinical trial (Pereira et al 2018) showed that faecal microbiota transplantation was associated with faster resolution of diarrhoea in 66 puppies with acute haemorrhagic diarrhoea syndrome due to parvovirus infection.
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18. Prittie J. Canine parvoviral enteritis: a review of diagnosis, management, and prevention J Vet
Emerg Crit Care 2004; 14: 167-176

19. Reineke EL, Walton K, Otto CM. Evaluation of an oral electrolyte solution for treatment of mild to moderate dehydration in dogs with hemorrhagic diarrhea. J Am Vet Med Assoc 2013; 243:851-857.

20. Savigny MR, Macintire DK. Use of oseltamivir in the treatment of canine parvoviral enteritis. J Vet Emerg Crit Care 2010; 20:132-142

21. Sime TA, Powell LL, Schildt JC, Olson EJ. Parvoviral myocarditis in a 5-week-old Dachshund. J Vet Emerg Crit Care 2015; 25: 765-769

22. Unterer S, Busch K, Leipzig M, Hermanns W, Wolf G, Straubinger RK, Mueller RS, Hartmann K. Endoscopically Visualized Lesions, Histologic Findings, and Bacterial Invasion in the Gastrointestinal Mucosa of Dogs with Acute Hemorrhagic Diarrhea Syndrome. J Vet Intern Med 2014; 28: 52-58

23. Unterer S, Strohmeyer K, Kruse BD, Sauter-Louis C, Hartmann K. Treatment of Aseptic Dogs with Hemorrhagic Gastroenteritis with Amoxicillin/Clavulanic Acid: A Prospective Blinded Study. J Vet Intern Med 2011; 25: 973-979.

24. Venn EC, Preisner K, Boscan PL, DC Twedt, Sullivan LA. Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis. J Vet Emerg Crit Care 2017; 27: 52-65

25. Will K, Nolte I, Zentek J. Early enteral nutrition in young dogs suffering from haemorrhagic gastroenteritis. J Vet Med Series A 2005;52(7):371-376.
# IMAGING OF THE DYSPNOEIC CAT

Livia Benigni, DVM, CertVDI, PGCertAP, MRCVS, FHEA, DipECVDI

Youliv4 Imaging Referrals and The Ralph Veterinary Referral Centre, London, UK

## Introduction

Radiography remains a fundamental technique for thoracic imaging. However, in some situations, thoracic ultrasound proves to be a better alternative or complementary to radiology. Ultrasound is very useful in feline thoracic medicine; it does not require sedation and is less stressful than radiology or computed tomography. Furthermore the feline conformation is amenable to producing good quality thoracic ultrasound images.

## Ultrasound Technique

The thorax can be examined by using a subcostal, intercostal or a thoracic inlet window. When using a subcostal window the thorax is imaged through the liver.¹ To optimize this approach it is preferable to examine the patient when the stomach is empty (12 hours fasting). Fasting is also indicated if sedation or general anaesthesia is needed (e.g. uncooperative patients or when biopsies are indicated).

Most cats are relatively cooperative when examined standing, furthermore the standing position proves more comfortable for most dyspnoeic cats. When using an intercostal window with the patient in sternal or standing position, the thorax should be flexed away from the ultrasonographer in order to increase the space between the ribs. Flexion of the trunk in the direction of the ultrasonographer should be avoided as by doing so the intercostal space is reduced. A sternal or standing position is recommended to visualise and sample a small volume of pleural fluid as the fluid collects ventrally.

Sector probes are often used for the thorax as they have a small footprint and they can easily fit into the intercostal spaces. Mechanical probes (no longer produced) are inconvenient because the close ultrasound field is not displayed. Linear probes provide excellent detail but penetrate less and have the disadvantage of a large footprint so the ribs get often in the way causing acoustic shadow.

## Use of diagnostic imaging in clinical cases

Pleural effusion is a common cause of dyspnoea in cats. The list of common causes of a moderate to large pleural effusion in cats is relatively short; it has been reported that feline infectious peritonitis (FIP), congestive heart failure (CHF), pyothorax and neoplasia together accounted for 88-100% of cases with a confirmed etiology.² Thoracic ultrasound offers a fast and definitive diagnosis in patients with suspected pleural effusion. Therefore ultrasound should be considered as the first imaging modality to use in dyspnoeic cats. Furthermore, ultrasound is more sensitive than radiography to detect small volume pleural effusion. The echogenicity of the pleural fluid may give an idea of the nature of the fluid; transudate, modified transudate and chylothorax are anechoic or hypoechoic whereas pyothorax and haemothorax are generally hyperechoic. In case of localized pyothorax, thoracic radiographs are helpful to guide the ultrasonographic examination.

Thoracic ultrasound is an excellent method to check for presence of mediastinal, parietal, pleural or pulmonary masses, particularly in patients with pleural effusion, whereas on radiographs, the
presence of pleural fluid often obscures these lesions. Mediastinal masses are frequently neoplastic, with some exceptions (e.g. mediastinal cysts). Mediastinal cysts are easily recognized on ultrasound; they are round or oval, have thin, well-defined walls, and, usually, anechoic contents.

In presence of thoracic masses biopsies are required to reach a final diagnosis. Ultrasound guided biopsies (fine needle aspirate or tissue core biopsies) should be performed with the patient under general anaesthesia or heavy sedation to allow a level of control over the patient and the lung movements. Possible complications are: pneumothorax, haemorrhage and pyothorax.

The ultrasonographic appearance of normal lung is mostly composed of artefacts. A series of horizontal lines, parallel to the pleural line are seen in the deeper region of the field of view; these are called "A-lines" and represent reverberation artefacts. The distance between A-lines is equal to, or a multiple of, the distance between the skin and the pleural line. In the normal lung the pleural line moves synchronously with respiration: this dynamic horizontal movement is called lung sliding.

It is not possible to visualize structures positioned behind air (e.g. an air-filled pulmonary bulla cannot be identified with ultrasound). Atelectasis, pulmonary consolidation and pulmonary masses can be visualised when there is little or no air in between a lesion and the probe. Therefore the lesions listed above are seen either when they are in contact with the thoracic wall or when they are surrounded by pleural fluid. Pulmonary lesions can also be visualised from a trans-hepatic window when they are located against the diaphragm.

Lung ultrasound is used in human patients to diagnose cardiogenic pulmonary oedema (CPO). In case of CPO the normal ultrasonographic appearance of a pleural line with A-lines is lost because of artefacts called "B-Lines" (also called comet-tail, ring-down, or lung rockets artefacts). These artefacts are perpendicular to the pleural line and cause disruption of the A-lines.³ However, it is very important to keep in mind that B-lines are not a pathognomonic sign of CPO. In dogs and cats lung ultrasonography cannot be used to differentiate CPO from other causes of diffuse interstitial or alveolar disease.⁴

Feline pleural effusion can result from left and/or right CHF causing a transudate, a modified transudate or a chylous effusion. Feline CHF may cause pulmonary oedema, pleural effusion or both. Cardiogenic pulmonary oedema in cats has a variable radiographic appearance and is associated with a range of pattern and distribution.⁵ Pulmonary congestion precedes pulmonary oedema but is not always identified radiographically. Therefore radiographically feline cardiogenic oedema is often confused with respiratory disease. The non-characteristic appearance of feline cardiogenic pulmonary oedema, plus the fact that feline cardiac disease does not always result in radiographic cardiomegaly, complicates the radiographic diagnosis of cardiac disease. Echocardiography is necessary in these cases to demonstrate the underlying cardiac disease.

In case of suspected pulmonary disease and thoracic trauma, the suggested imaging technique to start with is radiography or, when available, CT. Radiographs offer an overview of the thorax, including the musculoskeletal system, and are used to determine whether there are any lesions that could be visualized by ultrasound in order to guide biopsies. When a mass is not in contact with the thoracic wall, CT guided biopsies should be considered as an alternative to ultrasound guided biopsies.
Radiology, ultrasound or a combination of these two imaging modalities is generally sufficient to diagnose diaphragmatic ruptures. When using a trans-hepatic approach, the mirror image artefact should not be misinterpreted as a diaphragmatic rupture.

In case of pneumothorax the normal sliding movement of the pleural line is lost however ultrasound is not a reliable technique to diagnose pneumothorax in dogs and cats following trauma.⁶ CT is the most accurate technique to detect pneumothorax and the preferred imaging modality in case of trauma because of its ability to demonstrate also minimally displaced fractures and subtle pulmonary changes. CT pulmonary angiography (CTPA) is used to identify pulmonary thromboembolism (PT); however more work is needed to determine the accuracy of CTPA for PT in dogs and cats.⁷

## References

1. Neelis DA, Mattoon JS, Nyland TG. Chapter 7: Thorax. Small Animal Diagnostic Ultrasound 3rd edition. Saunders 2015.

2. Beatty J and Barrs V. Pleural effusion in the cat: a practical approach to determining aetiology. J Feline Med Surg 2010; 12: 693

3. Gargani L, Volpicelli G. How I do it: lung ultrasound. Cardiovasc Ultrasound 2014 4:12

4. Ward JL, Lisciandro GR, Keene BW et al. Accuracy of point-of-care lung ultrasonography for the diagnosis of cardiogenic pulmonary edema in dogs and cats with acute dyspnea. J Am Vet Med Assoc 2017 15;250(6):666-675

5. Benigni L, Morgan N, Lamb CR. Radiographic appearance of cardiogenic pulmonary oedema in 23 cats. J Small Anim Pract. 2009 Jan;50(1):9-14

6. Walters AM, O'Brien MA, Selmic LE et al. Evaluation of the agreement between focused assessment with sonography for trauma (AFAST/TFAST) and computed tomography in dogs and cats with recent trauma. J Vet Emerg Crit Care 2018 28(5):429-435 2018.

7. Goggs R, Chan DL, Benigni L, et al. Comparison of computed tomography pulmonary angiography and point-of-care test for pulmonary thromboembolism diagnosis in dogs. J Small Anim Pract. 2014 Apr;55(4):190-7
# TRANSFUSION: BLOOD COMPATIBILITY TESTING

Isabelle Goy-Thollot, Dr Vet, PhD, DECVECC
SIAMU, VetAgro Sup, Lyon, France

Providing safe and effective transfusion therapy is essential. Blood typing is clinically important to ensure blood compatibility. This lecture aims to describe blood typing and cross match (XM) techniques and their clinical relevance.

## 1. Canine blood types

### 1.1. Canine blood group system

Blood types are inherited antigens present on the RBCs surface membrane. Previous studies led to the initial international recognition of blood groups termed dog erythrocyte antigens (DEA). DEA 1 is considered the most important blood group in dogs due to its strong antigenicity and nearly equal distribution of DEA 1+ and DEA 1- dogs among many breeds worldwide. New common blood types named Dal, Kai 1 & 2 have been recently described. Currently, canine donors and recipients that have not been previously transfused are considered to have no clinically important alloantibodies and thus are expected to be compatible in a minor and major XM test. However, after transfusion, canine recipients may become sensitized, even when DEA 1 matched, which may lead to blood type incompatibilities recognized by incompatible major XM results, acute haemolytic transfusion reactions, or both. Acute haemolytic transfusion reactions due to blood group incompatibilities between recipient and donor are serious complications, but can usually be avoided when transfusing DEA 1-matched and cross-matched blood in previously transfused dogs.

### 1.2. Canine blood typing

In-clinic kits with monoclonal anti-DEA 1 antibodies are available for DEA 1 typing. In contrast, only polyclonal typing reagents are available on a limited basis for DEA 3, 4, and 7. Furthermore, polyclonal or monoclonal typing reagents for Dal and Kai 1 & 2, respectively, have recently been introduced by specific laboratories (i.e. Animal Blood Resource International, USA). The necessity of extended type screening of donors is controversial given the low risk of significant transfusion reactions related to these antigens; however, it may be extremely helpful in understanding cases of XM incompatibility, especially after previous transfusion(s). Moreover, the high prevalence of Dal negative dogs should lead to the development of a specific test for this group.

Blood typing is based on an agglutination reaction, using polyclonal or monoclonal antibodies to react with red cell antigens. When using these antibodies, the presence or absence of agglutination detects the presence (positive) or absence (negative) of the particular red cell antigen being tested respectively.

One of these in-clinic kits using monoclonal anti-DEA 1 antibodies is a rapid test commercialized by Alvedia®. The blood typing Quick Test® uses the technique of immunochromatography. This technology is based on the migration of RBCs on a specially treated paper strip. Monoclonal anti-DEA 1 antibody is incorporated on the strip. It binds to DEA 1 + RBCs. This causes a red line to appear in front of the DEA 1 mark. Quick Test® detects all levels of DEA 1 antigen expression, from very strong to very weak. Whatever the intensity of the line, even very weak, the dog is classified as DEA 1 +. There
is another rapid blood type technique: DMS (CARD), based on an agglutination reaction with a monoclonal anti-DEA1 antibody. Recent studies comparing these techniques showed a good agreement with some differences in dogs with immune-mediated haemolytic anaemia.

## 2. Feline blood types

### 2.1. Feline blood group systems

The major feline blood group system is known as the feline AB blood group system and contains three types: type A, type B, and type AB (rare). The distribution of these blood types varies geographically. Recent genetic work has determined that mutations in the enzyme, cytidine monophospho-N acetylneuraminic acid hydroxylase (CMAH), are responsible for the B blood type. Cats with type A have N-glycolylneuraminic acid (NeuGc) on their RBC membranes while type B have N-acetylneuraminic acid (NeuAc). CMAH converts NeuAc to NeuGc so lack of this enzyme leads to accumulation of NeuA. Type A cats may have weak anti-B alloantibodies which can cause shortened RBC survival if a B donor is used. Type B cats, however, have very strong anti-A antibodies and can have a fatal reaction from as little as 1 mL of transfused Type A blood. Type AB cats have no alloantibodies against either type A or B. They should receive either AB or A blood if they need a transfusion due to the strong anti-A antibodies present in cat B serum.

AB typing of patients and donors is generally recommended to assure A-B compatibility. A-B matched transfusions are required to be effective. In addition, Mik has been proposed as an additional blood group system with potentially naturally occurring alloantibodies in some Mik- cats. Most cats have this antigen but in cats who do not, naturally occurring antibodies can be present which can lead to a haemolytic transfusion reaction with an initial incompatible transfusion.

### 2.2. Feline blood typing

There are now two commercially available in house typing kits for cats (Rapid VetH Feline, DMS laboratories, NJ [CARD] and Quick test A+B, Alvedia, France [CHROM]). Both kits use monoclonal antibodies against type A and type B. In a recent study comparing typing methodologies in cats, a gold standard tube agglutination, CARD and CHROM gave identical results in 52 of 58 cats. CARD had overall accuracy of 91.4% and CHROM had overall accuracy of 94.8%. In 2 of the 6 cats with discordant resultants, FeLV infection was present. It is recommended that B and AB cats be confirmed by a second method or through an outside laboratory. There is currently no in house typing system for Mik.

## 3. Cross-matching

Cross-matching determines the serological compatibility between patient and donor bloods, based on an agglutination reaction, allowing detection of preformed alloantibodies (cats) or previous sensitization (dogs and cats). The major XM is an assessment of the compatibility between the donor RBC and patient plasma/serum, with the minor XM being the opposite (donor plasma/serum and patient RBCs). Minor XM incompatibilities are mostly of concern when large volumes of plasma or whole blood are to be administered. Patient auto-agglutination or haemolysis may result in incompatibility and a control should be run with the patient RBCs and patient serum. Auto-agglutination or severe haemoglobinemia precludes testing. Washing the blood three times with physiologic saline may disperse auto-agglutination and "rouleaux" formation.
Some use the immediate-spin XM. This technique employs a 3- to percent suspension of donor red cells suspended in saline, with 2 drops of recipient serum, centrifuged at 3400 rpm for 15 seconds (Serofuge, Sorvall, Wilmington, DE).

Major and minor XM testing is offered by clinical pathology laboratories which use the standard tube, microtiter plate, or neutral saline gel column method without canine antiglobulin at either room temperature or 37°C. Because of the need for washing RBC and the involvement of several steps, XMing of dogs and cats is rarely done in veterinary practice. A gel tube-based XM kit has been available for in-clinic use. Moreover, an antiglobulin-enhanced immunochromatographic strip kit, similar to the direct antiglobulin test (DAT), recently has been introduced for XMing dogs. A recent study (Goy-Thollot et al 2017) showed that the antiglobulin-enhanced immunochromatographic strip kit as well as the antiglobulin-enhanced gel column technique are practical tests for XMing in the clinic and laboratory, respectively.

**3.1. Cross-match in dogs**

Since dogs do not have naturally occurring alloantibodies, the initial XM between a dog which has never been transfused and his donor should be compatible. Acute haemolytic transfusion reactions and incompatible XMs have been reported clinically in previously transfused dogs receiving a transfusion ≥ 4 days after the first transfusion. However, documentation of post-transfusion alloimmunization by a major XM test is sparse, and the RBC antigen specificity is rarely if ever identified in any transfused dog. In a recent study (Goy-Thollot et al 2017), the antiglobulin-enhanced immunochromatographic strip kit as well as the antiglobulin-enhanced gel column technique identified alloantibodies on RBCs of some transfused dogs (44%). This high post-transfusion alloimmunization rate by a major XM test leads to warrant major XM in any dog that previously had received DEA 1-matched RBC before the next transfusion.

**3.2. XM in cats**

In case AB typing is not available as well as in previously transfused cats, major and minor XMs are recommended. XMing cats is technically restricted by the difficulty to obtain blood from recipient and donor cat prior to transfusion, limited availability of standardized XM protocols, and lack of any in-clinic kits for XMing cats.

RBC incompatibilities may be present in transfusion-naive cats which could justify the recommendation to perform a major XM before all (including the first) RBC transfusions in cats in a non-emergent setting. However, one could argue that XMing all cats would result in additional cost and unnecessary delay in time to transfusion. Although the clinical relevance of major XM incompatibilities detected in transfusion-naive cats is unknown, previous documentation of anti-Mik RBC alloantibodies causing acute haemolytic transfusion reactions in transfusion-naïve cats suggests erring on the side of caution. Future prospective studies evaluating the effect of XM on transfusion efficacy in cats are warranted.

**References**

1. Abrams-Ogg ACG. Feline Recipient Screening. In: Yagi K, Holowaychuk M, editors. Manual of Veterinary Transfusion Medicine and Blood Banking. Iowa: Ames; 2016. p322-375.
2. Blois SL, Richardson DM, Abrams-Ogg ACG. Comparison of a gel column blood typing method and a point-of-care cartridge for Dog Erythrocyte Antigen 1.1. J Vet Emerg Crit Care. 2013; 00:1-4

3. Bovens C, Gruffydd-Jones T. Xenotransfusion with canine blood in the feline species: review of the literature. J Feline Med Surg. 2013; 15:62-7.

4. Euler CC, Lee JH, Kim HY, Raj K, Mizukami K, Giger U. Survey of Two New (Kai 1 and Kai 2) and Other Blood Groups in Dogs of North America. J Vet Intern Med. 2016; DOI: 10.1111/jvim.14572

5. Euler CC, Raj K, Mizukami K, Murray L, Chen CY, Mackin A, Giger U. Xenotransfusion of anemic cats with blood compatibility issues: pre-and posttransfusion laboratory diagnostic and XMing studies. Vet Clin Pathol. 2016; 76: 969-974

6. Giger U. Blood Typing and cross-matching to Ensure Blood Compatibility. In: Bonagura JD, Twedt DC, editors. Current Veterinary Therapy. Missouri: St. Louis; 2014. e143.

7. Goulet S, Giger U, Arsenault J, Abrams-Ogg A, Euler CC, Blais MC. Prevalence and Mode of Inheritance of the Dal Blood Group in Dogs in North America. J Vet Intern Med. 2017;31:751-758

8. Goy-Thollot I, Giger U, Boisvineau C, Perrin R, Guidetti M, Chaprier B, Barthélemy A, Pouzot-Nevoret C, Canard B. Pre- and Post-Transfusion Alloimmunization in Dogs Characterized by 2 Antiglobulin-Enhanced Crossmatch Tests. J Vet Intern Med. 2017; DOI: 10.1111/jvim.14801

9. Goy-Thollot I, Nectoux A, Guidetti M, et al. Detection of naturally occurring alloantibody by an in-clinic antiglobulin-enhanced and standard crossmatch gel column test in non-transfused domestic shorthair cats. J Vet Intern Med. 2018; 1-8.

10. Guzman LR, Streeter E, Malandra A. Comparison of a commercial blood crossmatching kit to the standard laboratory method for establishing blood transfusion compatibility in dogs. J Vet Emerg Crit Care. 2016; 1-7

11. Hourani L, Weingart C, Kohn B. Alloimmunisation in transfused patients: serial crossmatching in a population of hospitalised cats. JFMS. 2017; https://doi.org/10.1177/1098612X1668857

12. Hourani L, Weingart C, Kohn B. Evaluation of a Novel Feline AB Blood Typing Device. JFMS. 2014; 16:826-31.

13. McClosky ME, Brown DC, Weinstein NM, Chappini N, Taney MT, Marryott K, Callan MB. Prevalence of naturally occurring non-AB blood type incompatibilities in cats and influence of XM on transfusion outcomes. J Vet Intern Med. 2018; 32:1934-1942.

14. Seth M, Jackson KV, Winzelberg S, Giger U. Comparison of gel column, card, and cartridge techniques for dog erythrocyte antigen 1.1 blood typing. Am J Vet Res. 2012; 73:213-219

15. Spada E, Perego R, Viñals Flórez LM, Perlado Chamizo MDR, Baggiani L, Dall'Ara P, Proverbio D. Comparison of crossmatching method for detection of DEA 7 blood incompatibility. J Vet Diag Invest. 2018; DOI: 10.1177/1040638718806023.

16. Spada E, Proverbio D, Baggiani L, et al. Evaluation of an Immunochromatographic Test for Feline AB System Blood Typing. J Vet Emerg Crit Care. 2016; 26:137-41.

17. Sylvane B, Prittie J, Hohenhaus AE, Tozier E. Effect of crossmatch on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats. J Vet Intern Med. 2018; 1-7.

18. Tasker S, Barker EN, Day MJ, Helps CR. Feline Blood Genotyping versus Phenotyping, and Detection of Non-AB Blood Type Incompatibilities in UK Cats. J Small Anim Pract. 2014;55:185-89.

19. Villarnovo D, Burton SA, Horney BS, MacKenzie AL, Vanderstichel R. Preliminary evaluation of a gel tube agglutination major crossmatch method in dogs. Vet Clin Pathol. 2016; 45:411-4
20. Weinstein NM, Blais MC, Harris K, et al. A Newly Recognized Blood Group in Domestic Shorthair Cats: The Mik Red Cell Antigen. J Vet Intern Med. 2007;21:287-92.

21. Weinstein NM, Sink CA. Blood typing and cross-matching, In: Burkitt Creedon JM, Davis H. eds. Advanced Monitoring and Procedures for Small Animal Emergency and Critical Care, 1st ed. Chichester UK: John Wiley & Sons; 2012, pp. 682-692.

22. Weltman JG, Fletcher DJ, Rogers C. Influence of crossmatch on Posttransfusion Packed Cell Volume in Feline Packed Red Blood Cell Transfusion. J Vet Emerg Crit Care. 2014;24:429-36.
# HAEMORRHAGIC SHOCK: PATHOPHYSIOLOGY, DIAGNOSIS, AND TREATMENT

Guillaume L. Hoareau, DVM, PhD, DACVECC, DECVECC
Clinical Investigation Facility, Travis Air Force Base

Haemorrhagic shock (HS) is characterized by a systemic reduction in tissue oxygen delivery due to blood loss. HS is a common syndrome in veterinary patients, both in the emergency and critical care settings. It can result from a wide range of etiologies such as trauma, neoplasia, or coagulopathies. Iatrogenic injuries (surgery or procedures such as abdominocentesis or pericardiocentesis) may also lead to serious blood losses. While the initial approach in the management of HS can be similar across diseases, the underlying etiology ultimately dictates both patient management and prognosis. While it is characterized by hypovolaemia, some patients may progress to vasodilatory shock, in particular those who have undergone resuscitation. A thorough understanding of the disease mechanisms along with knowledge of current clinical evidence is of the utmost importance for acute care clinicians.

## PATHOPHYSIOLOGIC ALTERATIONS INDUCED BY HAEMORRHAGIC SHOCK

Similar to other causes of shock, haemorrhage may reduce systemic tissue oxygen delivery, ultimately leading to a cellular shift from an aerobic to an anaerobic metabolism. The hallmark of shock regardless of the underlying disease in a reduction in systemic ATP production. Cells become unable to maintain their cellular membrane integrity, which may lead to swelling (oedema). Cell death can be mediated via necrosis although apoptosis or necroptosis may also be at play.

There is a paucity of mechanistic studies of HS in veterinary patients. Furthermore, much of the human HS literature arises from trauma populations. Much of the following information is therefore derived from translational or human trauma research.

### Microcirculatory dysfunction

Despite improvement in microcirculation parameters such as heart rate, blood pressure, etc, some HS patients progress to multiple organ failure. This discrepancy is partially attributed to microcirculation anomalies. Endothelial dysfunction is a corner stone of microcirculation failure. Tight junctions between endothelial cells are under complex regulation and loss of endothelial barrier integrity is an early sign of endothelial injury. Various molecules are involved in maintaining endothelial integrity. For instance, the angiopoietin/Tie2 system mediates endothelial health and function in health and after injury. Both human and animal studies showed that while angiopoietin 1 binding to its receptor Tie2 helped maintain endothelial barrier integrity, angiopoietin 2 (which is upregulated after trauma) was associated with endothelial injury.

### Endothelial injury and glycocalyx shedding

The glycocalyx consists of a complex arrangement of glycoproteins, proteoglycans, and glycolipids at the apical surface of endothelial cells. The glycocalyx can be damaged following HS and endothelial injury; its components are then shed into the systemic circulation, where they promote inflammation. While the ideal resuscitation strategy for HS patients is still debated, it has been accepted that approaches based on rapid administration of large volume of isotonic crystalloids should be avoided. In dogs with HS, this approach has been associated with increased hyaluronan shedding from the endothelium and a pro-inflammatory state.
## Nitric oxide pathway dysregulation

The nitric oxide pathway is also a major contributor to the cascade of events occurring in HS. In the early phase of HS, red blood cell mass reduction is associated with a decrease in vascular wall shear stress, which in turn downregulates nitric oxide production and sustains capillary dysfunction. In contrast, later in the disease, nitric oxide can be overproduced and lead to vasoplegia.

## Release of damage-associated molecular patterns (DAMPs or alarmins)

Following non-specific injury, cells release endogenous mediators that not only can be used as biomarkers but also have biological functions; those are named damage-associated molecular patterns (DAMPs or alarmins). For instance, mitochondrial DNA or formyl peptides are rapidly released after trauma and incite a systemic inflammatory response. Cold-inducible RNA-binding protein (CIRP) is another DAMP of interest due to its deleterious effects. DAMPs may activate cytoplasmic inflammasomes, which are multiprotein complexes, that can upregulate inflammation and induce apoptosis; they are thought to be involved in multiple organ and immune dysfunctions observed in trauma patients. Studies in canine trauma patients have shown that in contrast to high mobility group box-1 (HMGB1) or cell-free DNA, plasma nucleosomes have prognostic value.

## Trauma-induced coagulopathy

HS patients may suffer from various coagulopathies, whether due to consumptive processes or loss of platelet and coagulation factors through blood losses. In the subset of trauma-induced HS, patients often suffer from a continuum of coagulation disorders termed trauma-induced coagulopathy (TIC). TIC can be characterized by acute traumatic coagulopathy (ATC) and resuscitation induced coagulopathy (RIC). Disorders of fibrinolysis are an important part of ATC. While interest in hyperfibrinolysis has led to significant research in tranexamic acid in trauma patients, the trauma community has also established that some patients may also present with a state of fibrinolysis shutdown.

## Host response to injury

It has been traditionally accepted that similar to infection-induced tissue damage, trauma is associated with a systemic inflammatory response syndrome (or SIRS) followed by a compensatory anti-inflammatory response syndrome (or CARS). Imbalances between these two responses have been associated with morbidity and mortality. Individual patient's genetic response has been under scrutiny. Following massive blunt trauma, more than 80% of the WBC genetic expression was changed. Gene expression is not only altered in the early phase but also later in the progression of the disease. Return to pre-injury levels may range from 1 day to weeks depending on the gene of interest. Components of the innate system were upregulated while genes associated with acquired immunity were down-regulated.

## DIAGNOSIS

HS diagnosis is mostly based on the recognition of shock (which is mainly based on physical examination findings) and identifying a source of significant blood loss. Shock can be diagnosed via evidence of alteration in perfusion parameters: mentation, heart rate, mucous membrane colour, capillary refill time, extremity-to-core temperature, pulse quality (femoral and dorsal pedal being the most commonly evaluated). Patients will most often display features of hypovolaemic shock:
prolonged capillary refill time, pale pink to white mucous membranes, and cold extremities. Some patients may present vasodilatory features, especially the sickest ones who have undergone resuscitation. Additional diagnostics such as plasma lactate concentration or arterial blood pressure provide further information to gauge disease severity and guide resuscitation measures.

The source of blood loss can be identified through the history or physical examination. For instance, patients that are victims of trauma may have lost a significant amount of blood at the point of injury. Furthermore, physical examination may reveal the presence of haemoptysis or epistaxis. Point-of-care ultrasound examination and cavitary fluid analysis is a rapid and inexpensive tool to further locate possible sources of blood loss.

## TREATMENT

### Source control

While fluid resuscitation is undertaken, external sources of haemorrhage should be controlled as soon as possible. Direct pressure can be applied whenever possible. Application of haemostatic gauze on wounds with ongoing bleeding might provide additional assistance in arrest of haemorrhage.

### Fluid and vasopressor resuscitation

Similar to other conditions, HS patients can be resuscitated with isotonic crystalloids, hypertonic crystalloids, synthetic colloids, and/or blood products. Clinicians should keep in mind the dose-dependent anticoagulant effects of synthetic colloids. Much of the literature in human medicine supports the use of blood products at a ratio of 1:1:1 (of packed red blood cell: fresh frozen plasma: platelets) for severe haemorrhagic shock. This remains an unusual scenario in veterinary medicine and is most appropriate in massive haemorrhage. The use of blood products in traumatized canines has been studied. Common reasons for blood product administration were treatment of shock, perioperative haemodynamic support, or worsening anaemia. In patients with cavitary haemorrhage without bacterial contamination, autologous blood transfusion can be considered. Patients with hypotension despite fluid resuscitation will benefit from vasopressor administration titrated to maintain arterial blood pressure within target range.

Caution should be exercised to prevent and treat hypothermia in these patients as it is a significant source of morbidity and mortality.

### Tranexamic acid

In humans, there is evidence to support the early use of fibrinolysis inhibitors after trauma to reduce the rate of bleeding-related death as well as all causes of mortality. Tranexamic acid is a lysine analog that inhibits plasminogen activation and at much higher concentrations, is a noncompetitive inhibitor of plasmin. Tranexamic acid also has anti-inflammatory effects. The currently recommended dose is 10-15 mg/kg SC, IM, or slow IV followed by 1 mg/kg/hr CRI for 5-8 hours. In humans, early administration of tranexamic acid is associated with improved outcomes. The beneficial serum levels of tranexamic acid are unknown and it is still an area of active research. There is limited data in clinical veterinary medicine regarding the benefits of tranexamic acid in trauma patients. Clinicians should bear in mind that some patients may be in a fibrinolysis shutdown state.
## Damage control resuscitation

Some patients will not respond to medical interventions and will require rapid surgical haemorrhage control. It is therefore important that acute care clinicians have protocols in place whereby patients with massive haemorrhage refractory to medical management are rapidly transferred to an operating theatre with properly trained personnel.

## New avenues

Since recent advances in the pathologic consequences of HS have identified pathways that contribute to worsening of the condition, novel therapeutic interventions have been investigated and will hopefully translate to clinical practice. Molecules such as vasculotide or histone deacetylase inhibitors have been studied as resuscitation adjuncts.

## References

1. Tachon, G, Harrois, A, Tanaka, S, Kato, H, Huet, O, Pottecher, J, Vicaut, E, Duranteau, J. Microcirculatory alterations in traumatic hemorrhagic shock. Crit Care Med 2014; 42:1433–41

2. Ince, C. The rationale for microcirculatory guided fluid therapy. Curr Opin Crit Care 2014; 20:301–8

3. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):104-7

4. Timmermans K, Kox M, Vaneker M, van den Berg M, John A, van Laarhoven A, van der Hoeven H, Scheffer GJ, Pickkers. Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients. Intensive Care Med. 2016 Apr;42(4):551-561

5. Aziz M, Brenner M, Wang P. Extracellular CIRP (eCIRP) and inflammation. J Leukoc Biol. 2019 Jan 15

6. Bortolotti P, Faure E, Kipnis E. Inflammasomes in Tissue Damages and Immune Disorders After Trauma. Front Immunol. 2018 Aug 16;9:1900

7. Goggs R, Letendre JA. High Mobility Group Box-1 and pro-inflammatory cytokines are increased in dogs after trauma but do not predict survival. Front. Vet. Sci., 30 July 2018

8. Letendre JA, Goggs R. Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs Following Trauma. Front. Vet. Sci., 30 July 2018

9. Smart L, Boyd CJ, Claus MA, Bosio E, Hosgood G, Raisis A. Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model. Inflammation. 2018 Aug;41(4):1515-1523

10. Schechter AN, Gladwin MT. Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med. 2003 Apr 10;348(15):1483-5

11. Moore HB, Moore EE, Liras IN, Gonzalez E, Harvin JA, Holcomb JB, Sauaia A, Cotton BA. Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients. J Am Coll Surg. 2016 Apr;222(4):347-55

12. Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I; Antifibrinolytic Trials Collaboration. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018 Jan 13;391(10116):125-132

13. Trieu M, van Meurs M, van Leeuwen ALI, Van Slyke P, Hoang V, Geeraedts LMG Jr, Boer C, van den Brom CE. Vasculotide, an Angiopoietin-1 Mimetic, Restores Microcirculatory Perfusion and Microvascular Leakage and Decreases Fluid Resuscitation Requirements in Hemorrhagic Shock. Anesthesiology. 2018 Feb;128(2):361-374
14- Williams AM, Dennahy IS, Bhatti UF, Biesterveld BE, Graham N, Li Y, Alam HB. Histone Deacetylase Inhibitors: A Novel Strategy In Trauma And Sepsis. Shock. 2018 Dec 21
# GASTROINTESTINAL MICROBIOME: THE FORGOTTEN ORGAN

Maxime Cambournac, DV, ECVECC Resident, DIU Assistance respiratoire, DU Réanimation, soins-intensifs, surveillance continue, Certificate of Veterinary Hemodialysis
CHV Fregis, 94110 Arcueil

The gastrointestinal microbiome is a dynamic consortium of bacteria, archaea, fungi, protozoa, and viruses, implicated in a range of vital physiologic processes including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The collective of microbes in a population is referred to as the microbiota and the genetic content as the microbiome. The real value of all this novel knowledge for the clinical care of patients in the intensive care unit (ICU) still has to be established.

## The microbiome

The recent advent of high-throughput DNA sequencing technologies, coupled with advances in bioinformatics, has revolutionized the field of microbiomics. To date, consistent data suggest that the microbiome is dynamic and subject to important changes during the life of the host in response to a variety of factors including diet, environment, medical interventions, and disease states (Wolff, Hugenholtz, and Wiersinga 2018).

Before birth, all mammals are thought to be sterile with inoculation with microbes occurring at the time of birth (Barko et al. 2018). Recent studies in laboratory animals suggested that the intestinal microbiome directs the development of the immune system, gut epithelium, and brain, among other body systems. Although most studies in dogs and cats have focused on the characterization of the faecal microbiome, there are substantial differences in the composition of the microbiome in different segments of the gut in dogs and cats (Barko et al. 2018). Enterobacteriales had a higher relative abundance in the canine small intestine, and Clostridiales was the predominant order in the duodenum and jejunum (40% and 39%, respectively) (Barko et al. 2018). This contrasts with the ileum and colon in which Fusobacteriales and Bacteroidales were the predominant bacterial orders. In cats, Lactobacillales is also distributed along the length of the gut, particularly in the jejunum and colon (Hooda et al. 2012).

## Role of microbiome in healthy states

The microbiome participates in vital physiologic and immunologic processes including energy homeostasis and metabolism, the synthesis of vitamins and other nutrients, endocrine signaling, prevention of enteropathogen colonization, regulation of immune function, and metabolism of xenobiotic compounds (Hooda et al. 2012). The microbiome in small intestinal crypts, for instance, regulates enterocyte proliferation by influencing DNA replication and gene expression, while the microbiome at the tips of the villi regulates the expression of genes involved in metabolic and immune function. Microbial fermentation of complex carbohydrates produces short-chain fatty acids (SCFA), which are essential in providing energy for colonocytes, maintaining the epithelial barrier by strengthening tight junctions, helping to regulate intestinal motility, and stimulating the production of anti-inflammatory compounds.
## Role of microbiome in pathogenesis of diseases

Despite the paucity of data, and lack of clarity regarding the microbiome's role in the pathogenesis of small animal diseases, there are clear links between the intestinal microbiome and systemic health. Murine experiments have suggested that the gut microbiome plays a role in the acute kidney injury induced by ischaemia-reperfusion as well as in the pulmonary host defense against invading pathogens and acute respiratory distress syndrome (Andrade-Oliveira et al. 2015). The gut microbiota plays a protective role in the host defense against pneumococcal pneumonia (Dickson et al. 2016). To date, it is unclear whether the microbiome participates directly in the pathogenesis of these disease states or via modulation of the immune system. Nevertheless, virtually all patients in the ICU are continuously exposed to a wide range of endogenous modulators (e.g. increased production of catecholamines, altered glucose metabolism and gastrointestinal dysmotility) as well as clinical interventions (e.g. use of proton-pump inhibitors, opioids, nutritional support and most of all antibiotics) that have all been shown to affect gut microbial composition (Wolff et al. 2018). These insights into the composition of the microbiome during critical illness also fuel the ongoing debate on the optimal route of the administration of nutrition.

## Therapeutic manipulation of the microbiome for ICU conditions

The therapeutic targets of these interventions and their efficacy are not well established in veterinary medicine and have only recently been described in the human literature. These therapies are intended to shift microbial community steady states associated with dysbiosis to those associated with health (Barko et al. 2018), and can be categorized into three groups: faecal microbiota transplantation, probiotics and synbiotics.

## Prebiotics

Prebiotics are fermented by colonic bacteria, generating end-products such as SCFAs that provide essential nutrients for the enteric epithelium. Although few studies exist, the potential benefits of prebiotic supplementation, especially by the addition of plant-derived polysaccharides, is a mainstay of treatment directed at modification of the intestinal microbiome.

## Probiotics

Probiotics are formulations of live organisms that confer beneficial effects on the recipient when delivered in adequate amounts. Proposed mechanisms through which probiotics improve host health include reducing intestinal permeability by upregulation of tight junction proteins, increasing mucin secretion by goblet cells, increasing secretion of defensins which prevent pathogen colonization, production of SCFAs, stimulation of IgA secretion, decreasing luminal pH, and enhancing and directing immune cells to promote tolerance to commensals while maintaining protection against pathogens.

## Antibiotic administration

Recent studies have demonstrated that resistance patterns of enteric bacteria change in response to increased exposure to antibiotics (Guard et al. 2015). Given that on any one day, three-quarters of all human patients in the ICU are treated with antibiotics, it is easy to understand why the gastrointestinal tract is considered a major reservoir for the emergence and dissemination of antibiotic-resistant bacteria (Akrami and Sweeney 2018). The emergence of antibiotic-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry, and a growing threat to public health in general, because it is a major cause of failure in the treatment of infectious diseases in humans as well.
as animals (Jones et al., 2008; Marshall et al., 2009). Moreover, transmission of resistant bacteria or resistance is likely to be enhanced because there is an overlap in classes of antimicrobial agents used in human medicine and in small animal practice, while domestic animals are commonly kept as pets living in close contact with humans, and as such, resistant bacteria might spread between animals and humans (Guardabassi, Schwarz, and Lloyd 2004). Ideally antibiotics would treat an infection at one particular site with minimal impact on neighboring microbiomes. Beta-lactam antibiotics are known to dramatically alter the gut microbiome even when administered intravenously as these agents are excreted in the bile and reach the intestine as fully functional antibiotics. Monitoring the antibiotic susceptibility pattern of *E. coli* from fecal samples revealed that exposure to amoxicillin causes increased expression of antibiotic resistance against several unrelated drugs, while two weeks postexposure, the resistance patterns were returned to pre-exposure level in three of four dogs, demonstrating that withdrawal of amoxicillin decreased the prevalence of antibiotic-resistant fecal *E. coli* in this study (Grønvold et al. 2009). Even with judicial antibiotic usage, dysbiosis may be an unavoidable consequence of critically ill patients being treated for a life-threatening infection.

## Faecal microbiome transplantation

Recent evidences in human patients, as well as in veterinary, suggests that faecal microbiota transplantation may be associated with a more favourable outcome in some diseases (Pereira et al. 2018).

## CONCLUSION

Patterns of dysbiosis within the various microbiomes of critically ill patients are becoming better understood and may be predictive of clinical outcomes. During a patient's stay in ICU, their microbiota is influenced by both their illness and the care provided. These changes in the microbiota can, in turn, affect patient outcome and susceptibility to infection. The importance of these microbiotas is pushing us towards new types of treatments, in which we also start to treat the microbiota. Promising results in microbiome-based ICU therapies, however, must be tempered by the fact that there is potential harm with this approach. Nonetheless, growing appreciation of the critical illness microbiome has already impacted critical care by highlighting the need for judicious antibiotic usage and stewardship. In the future, critical illness may be treated with equal parts anti and probiotic therapy in an attempt to balance the dangers of infection and sepsis with the harm of dysbiosis.

## References

* Akrami, Kevan and Daniel A. Sweeney. 2018. "The Microbiome of the Critically Ill Patient:" *Current Opinion in Critical Care* 24(1):49–54.

* Andrade-Oliveira, Vinicius, Mariane T. Amano, Matheus Correa-Costa, Angela Castoldi, Raphael J. F. Felizardo, Danilo C. de Almeida, Enio J. Bassi, Pedro M. Moraes-Vieira, Meire I. Hiyane, Andrea C. D. Rodas, Jean P. S. Peron, Cristiane F. Aguiar, Marlene A. Reis, Willian R. Ribeiro, Claudete J. Valduga, Rui Curi, Marco Aurelio Ramirez Vinolo, Caroline M. Ferreira, and Niels Olsen Saraiva Câmara. 2015. "Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion." *Journal of the American Society of Nephrology: JASN* 26(8):1877–88.

* Barko, P. C., M. A. McMichael, K. S. Swanson, and D. A. Williams. 2018. "The Gastrointestinal Microbiome: A Review." *Journal of Veterinary Internal Medicine* 32(1):9–25.

* Dickson, Robert P., Benjamin H. Singer, Michael W. Newstead, Nicole R. Falkowski, John R. Erb-Downward, Theodore J. Standiford, and Gary B. Huffnagle. 2016. "Enrichment of the Lung
Microbiome with Gut Bacteria in Sepsis and the Acute Respiratory Distress Syndrome.” *Nature Microbiology* 1(10):16113.

Grønvold, Anne-Mette R., Trine M. L'Abée-Lund, Henning Sørum, Ellen Skancke, Anthony C. Yannarell, and Roderick I. Mackie. 2009. "Changes in Fecal Microbiota of Healthy Dogs Administered Amoxicillin." *FEMS Microbiology Ecology* 71(2):313–26.

Guard, Blake C., James W. Barr, Lavanya Reddivari, Cory Klemashevich, Arul Jayaraman, Jörg M. Steiner, Jairam Vanamala, and Jan S. Suchodolski. 2015. "Characterization of Microbial Dysbiosis and Metabolomic Changes in Dogs with Acute Diarrhea" edited by D. Monleon. *PLOS ONE* 10(5):e0127259.

Guardabassi, Luca, Stefan Schwarz, and David H. Lloyd. 2004. "Pet Animals as Reservoirs of Antimicrobial-Resistant Bacteria." *The Journal of Antimicrobial Chemotherapy* 54(2):321–32.

Hooda, Seema, Yasushi Minamoto, Jan S. Suchodolski, and Kelly S. Swanson. 2012. "Current State of Knowledge: The Canine Gastrointestinal Microbiome." *Animal Health Research Reviews* 13(01):78–88.

McDonald, Daniel, Gail Ackermann, Ludmila Khailova, Christine Baird, Daren Heyland, Rosemary Kozar, Margot Lemieux, Karrie Derenski, Judy King, Christine Vis-Kampen, Rob Knight, and Paul E. Wischmeyer. 2016. "Extreme Dysbiosis of the Microbiome in Critical Illness." *MSphere* 1(4).

Pereira, Giorgio Q., Lucas A. Gomes, Iago S. Santos, Alice F. Alfieri, J. S. Weese, and Marcio C. Costa. 2018. "Fecal Microbiota Transplantation in Puppies with Canine Parvovirus Infection." *Journal of Veterinary Internal Medicine* 32(2):707–11.

Wolff, Nora Suzanne, Floor Hugenholtz, and Willem Joost Wiersinga. 2018. "The Emerging Role of the Microbiota in the ICU." *Critical Care* 22(1).
# RESUSCITATIVE ENDOVASCULAR BALLON OCCLUSION OF THE AORTA (REBOA): WHAT'S THE SCOOP?

Guillaume L. Hoareau, DVM, PhD, DACVECC, DECVECC
Clinical Investigation Facility, Travis Air Force Base

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an endovascular haemorrhage control intervention which was first described in the Korean war. Thanks to the development of smaller and wire-free balloon-tipped catheters, REBOA has recently re-gained popularity as a replacement to thoracotomy and aortic cross-clamping in human trauma patients. Current research efforts aim at improving occlusion technique to minimize post-deflation complications while maximizing occlusion benefits.

## REBOA INDICATIONS

REBOA has mainly been used in trauma patients with non-compressible torso haemorrhage, which refers to the presence of hypovolaemic shock in a patient with disruption of a named axial vessel or injured solid organ. REBOA has thus been used in patients with blunt or penetrating trauma with lesions distal to the diaphragm. Such lesions would be abdominal aortic tear, spleen or liver lacerations, pelvic fractures with large vessel disruptions, etc. Evidence of haemorrhage in the chest is a contra-indication to the deployment of a REBOA catheter for fear of worsening haemorrhage since upon balloon inflation, arterial blood pressure above the occlusion point is often elevated. Since it is less invasive and safer for the care team than resuscitative thoracotomy with aortic cross-clamping, REBOA has also been used in other settings. For instance, it is sometimes used during oncologic or obstetric surgery to control life-threatening haemorrhages.

## REBOA IMPLEMENTATION

While the technique has been described in humans and pigs, there is currently no description of the clinical use of REBOA in dogs or cats. Femoral arterial access can be achieved by either pulse palpation or using anatomical landmarks. Since patients with severe haemorrhagic shock may present with weak or no pulses, ultrasonographic guidance is a popular tool to facilitate prompt catheter insertion. The use of ultrasound also facilitates vessel evaluation to avoid venous catheterization or observe puncture-induced complications such as haematomas. An introducer sheath is placed in the femoral artery. Currently, there are two commercial REBOA catheters, the CODA catheter and the ER-REBOA. The CODA catheter requires a 12Fr introducer sheath and is advanced over-the-wire, the ER-REBOA catheter is placed through a 7Fr catheter and does not require wire guidance. The balloon at the tip of the REBOA catheter can be placed at various levels, or zones, of the aorta. Zone 1 encompasses the segment of the aorta between the left subclavian artery and the celiac trunk, zone 2 extends from the celiac trunk to the lowest renal artery, and zone 3 is between the lowest renal artery and the aortic bifurcation. Thus, in patients with profound haemorrhagic shock due to abdominal trauma and haemorrhagic peritoneal effusion, if the source of bleeding is unknown the balloon can be placed in zone 1. If the lesion is deemed infrarenal, the balloon can be placed in zone 3. Zone 2 placement is seldom performed. Proper balloon placement can be verified either via fluoroscopy or manual palpation during celiotomy. Measurement of catheter length of insertion using anatomical landmarks has been described in humans and dogs.
Following catheter placement, the balloon is inflated using 0.9% saline. Initially the balloon should be inflated to fully occlude the aorta. Full occlusion can be confirmed by the absence of distal pulse either by palpation or waveform observation via arterial pressure transduction from the femoral sheath. Full aortic occlusion allows for haemorrhage cessation, clot formation, as well as augmentation of perfusion to organs cranial to the balloon (heart and brain). Complete aortic balloon occlusion (complete REBOA) is associated with a significant ischaemic burden caudal to the balloon. Current REBOA guidelines recommend a maximum complete occlusion time of 30 to 45 minutes. To reduce the ischaemic burden, clinical and translational research has focused on partial REBOA whereby following a brief period of complete REBOA (approximately 10 minutes) a small amount of blood is allowed around the catheter to maintain oxygen delivery to tissue beds caudal to the balloon and reduce the ischaemia-reperfusion burden at the time of balloon deflation. Partial REBOA relies on precise balloon volume titration, which is hard to achieve since small changes in balloon volume result in large increases in aortic blood flow. Our team has therefore developed an automated platform capable of precise titration of balloon volume to control aortic blood flow or proximal and distal mean arterial pressures. The dynamic, automated, and precise control of endovascular aortic balloon has been termed endovascular variable aortic control or EVAC.

## REBOA CHALLENGES AND FUTURE AVENUES

While REBOA is a life-saving intervention that rapidly temporizes patients in or with impending cardiac arrest, it comes with a host of downsides and complications that require cautious management. Ischaemia-reperfusion is a significant concern and minimizing the time of occlusion is of the utmost importance. Furthermore, ischaemic damage to organs caudal to the balloon, to include the gastro-intestinal tract, kidney, and spine, have been documented. Similarly, organs above the balloon may suffer from supraphysiologic arterial pressure. Myocardial damage has been documented with extended occlusion period and our team has documented myocardial injury in clinically relevant occlusion periods (data not published as of this date). REBOA should be carefully implemented in patients with traumatic brain injury as ongoing haemorrhage sustained by supraphysiologic arterial blood pressure may worsen intracranial pressure and precipitate herniation of intracranial tissue.

Patients that received REBOA have almost universally sustained significant injury, which in conjunction with REBOA-induced ischaemia-reperfusion injury makes them prone to significant vasoplegia requiring careful fluid and vasopressor resuscitation. Artificial intelligence-driven balloon volume may prove helpful in tightly controlling patients' aortic flow.

## References

1. Osborn LA, Brenner ML, Prater SJ, Moore LJ. Resuscitative endovascular balloon occlusion of the aorta: current evidence. Open Access Emerg Med. 2019 Jan 14;11:29-38

2. Ribeiro Junior MAF, Feng CYD, Nguyen ATM, Rodrigues VC, Bechara GEK, de-Moura RR, Brenner M. The complications associated with Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). World J Emerg Surg. 2018 May 11;13:20

3. Hoareau GL, Cassiday PA, Stewart IJ, Studer A, DuBose JJ, Neff LP, Williams TK, Johnson MA. Acute kidney injury following resuscitative aortic occlusion. Journal of Endovascular Resuscitation and Trauma Management
3- Wasicek PJ, et al. Extended resuscitative endovascular balloon occlusion of the aorta (REBOA)-induced type 2 myocardial ischemia: a time-dependent penalty. Trauma Surg Acute Care Open 2019;4:e000194

4- Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, Desoucy ES, Faulconer ER, Dubose JJ, Neff LP, Grayson JK, Johnson MA, Williams TK. Stepwise reperfusion after zone 1 REBOA: is repositioning to zone 3 a useful maneuver. Journal of Endovascular Resuscitation and Trauma Management

5- Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, Desoucy ES, Faulconer ER, Dubose JJ, Neff LP, Grayson JK, Williams TK, Johnson MA. Location is everything: the hemodynamic effects of REBOA in zone 1 versus zone 3 of the aorta. J Trauma Acute Care Surg

6- Williams TK, Neff LP, Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, DeSoucy ES, Robert Faulconer R, Grayson JK, Johnson MA. A novel automated endovascular variable aortic control device to expand function of standard REBOA catheters. Journal of Endovascular Trauma Management

7- Johnson MA, Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, DeSoucy ES, Faulconer ER, Grayson JK, Neff LP, Williams TK. Endovascular Perfusion Augmentation for Critical Care: Partial Aortic Occlusion for Treatment of Severe Ischemia-Reperfusion Shock. Shock 2018; June 5

8- Williams TK, Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, DeSoucy ES, Robert Faulconer R, Grayson JK, Neff LP, Johnson MA. EVAC versus REBOA in a swine model of hemorrhage and ischemia reperfusion injury. J Trauma Acute Care Surg 2018
# GASTROINTESTINAL COMPLICATIONS IN MECHANICALLY VENTILATED PATIENTS:
## WHAT'S THE EVIDENCE?

Sabrina N. Hoehne, Dr. med. vet., DACVECC

Vetsuisse Faculty, University of Bern, Switzerland

## Introduction

Dogs and cats receiving mechanical ventilation represent one of the most critically ill and intense patient populations with regards to their nursing and supportive care needs. One of the challenges frequently encountered in critically ill patients is gastrointestinal (GI) dysfunction and many factors have been found to contribute to the development of GI complications in this patient population. Most commonly, they constitute a combination of underlying illness factors and therapeutic interventions, such as positive pressure ventilation.

In critically ill people, the presence of GI dysfunction has been associated with worse outcomes and it remains possible that this is, at least in part, due to its interference with the provision of nutritional support. Adequate nutritional support is especially important in the critically ill and mechanically ventilated patient to prevent malnutrition and associated negative effects. Respiratory muscle weakness, decreased wound healing, and impaired immune function have all been described as a result of malnutrition and they can lead to lower rates of successful ventilator weaning, increased patient morbidity, and mortality.

## Definition and pathophysiology

Even though intact GI function is an important factor in the outcome of critically ill patients, objective definitions of dysfunction have long been lacking, hampering both research in the area and the development of evidence-based management strategies. In 2012, the European Society of Intensive Care Medicine (ESICM) suggested the term acute gastrointestinal injury (AGI) to describe gastrointestinal *digestive* dysfunction in people and defined it as “malfunctioning of the GI tract in critically ill patients due to their acute illness”. A grading scheme for AGI severity was also provided, defining AGI grade I as risk of developing GI dysfunction or failure, AGI grade II as gastrointestinal dysfunction where the GI tract is not able to perform adequate digestion and nutrient absorption, AGI grade III as GI failure with complete loss of GI function, and AGI grade IV as GI failure with severe impact on distant organ function. Other than the digestive function, the GI tract also serves important barrier functions and roles as an endocrine and immune organ, all of which can be diminished in critical illness. Definitions, as well as standardized diagnostic and therapeutic approaches for dysfunctions of those aspects continue to be lacking.

Clinically, GI dysfunction can have various manifestations, such as stress related mucosal disease (SRMD) including mild to severe mucosal haemorrhage, GI hypomotility, vomiting, regurgitation, abdominal pain and or distension, diarrhoea, constipation, and enteral feeding intolerance.

The pathophysiology of GI dysfunction in the critically ill, mechanically ventilated patient is not completely understood, but several factors are thought to be contributing. Positive pressure ventilation increases pleural pressures and during the application of positive end-expiratory pressure (PEEP) intrathoracic pressures remain positive throughout the whole respiratory cycle. Reduced
venous return and preload will result in decreased cardiac output and diminished splanchnic perfusion, reducing GI function. Systemic hypoperfusion can further lead to an upregulation of the renin-angiotensin-aldosterone axis and to an increase in endogenous catecholamines, both of which can exacerbate splanchnic hypoperfusion. Furthermore, the splanchnic vasoconstriction due to neurohormonal changes can continue to exist even after patients have been haemodynamically stabilized. Systemic inflammatory conditions and reperfusion injury of the GI tract both lead to cytokine release that can contribute to continued splanchnic hypoperfusion and impair intestinal smooth muscle motility. Additionally, medications that are commonly used in critically ill patients also exhibit a transient effect on gastrointestinal motility and barrier function and include the administration of opioid drugs, alpha adrenergic agonists, anticholinergic drugs, benzodiazepines, and other sedative drugs.

## Incidence and implications

Gastrointestinal complications are encountered commonly in the critically ill patient with up to 62% of human patients displaying at least one sign of GI dysfunction during at least one day of an intensive care unit stay. Examining the veterinary literature available makes it clear that, in contrast to human medicine, a smaller proportion of veterinary patients receive gastrointestinal function assessment and nutritional support throughout the course of mechanical ventilation.

In the few studies describing enteral nutrition in mechanically ventilated veterinary patients, nutritional support had to be interrupted in up to 60% of patients due to some form of GI dysfunction (e.g. regurgitation, high gastric residual volumes (GRV), and aspiration), putting patients at risk of experiencing ill effects from a negative energy balance.

## Diagnosis and management

The majority of symptoms of GI dysfunction (such as vomiting, diarrhoea, and macroscopic gastrointestinal bleeding) is well defined and can be diagnosed clinically. GI dysmotility and reduced gastric emptying leading to intolerance of gastric feeding is more difficult to recognize and is frequently indirectly assessed by measuring gastric residual volumes (GRV).

In human as well as veterinary medicine, there is no scientific evidence to define normal GRV. In a veterinary study comparing the tolerance of intermittent versus continuous enteral nutrition in critically ill dogs, no difference was found in the tolerance and GRV between the two modes of nutritional support and no association between GRV and vomiting or regurgitation frequency or aspiration of GI contents could be shown. Therefore, the use of GRV driven nutritional support remains controversial and should be applied with caution. Alternatively, GI motility can be assessed by contrast radiography or bedside ultrasonography, but these tools also only allow for its qualitative or semiquantitative assessment.

It is currently recommended by the ESICM to initiate enteral nutrition in patients suffering from AGI grade I within 24-48h and to limit drugs impairing GI motility further. Patients suffering from AGI grade II should be treated with prokinetic drugs, while parenteral nutrition within 7 days of ICU admission should be considered in patients with AGI grade III. Emergency surgical interventions are usually required for patients suffering from AGI grade IV in which GI dysfunction has a severe negative impact on distant organ function.
In veterinary medicine, no evidence-based management guidelines for the treatment of GI dysfunction exist. The mainstays of treatment include haemodynamic stabilization of the mechanically ventilated patient to optimize splanchnic perfusion, treatment of the underlying disease and metabolic optimization of the patient, multimodal analgesia, early nutritional intervention, and pharmacological intervention using prokinetic drugs. A review of available prokinetic drugs is beyond the scope of this lecture but due to a lack of evidence for a single prokinetic drug of choice in small animal medicine, a multimodal approach to prokinetic pharmacotherapy is recommended.

## References

1. Armitage-Chan EA, O'Toole T, Chan DL. Management of prolonged food deprivation, hypothermia, and refeeding syndrome in a cat. Journal of Veterinary Emergency and Critical Care. 2006 Jun;16(s1):S34-41.

2. Bardou M, Quenot J-P, Barkun A. Stress-related mucosal disease in the critically ill patient. Nature Reviews Gastroenterology & Hepatology. 2015 Feb;12(2):98-107.

3. Beal MW, Paglia DT, Griffin GM, Hughes D, King LG. Ventilatory failure, ventilator management, and outcome in dogs with cervical spinal disorders: 14 cases (1991-1999). Journal of the American Veterinary Medical Association. 2001 May 1;218(10):1598-602.

4. Campbell JA, Jutkowitz LA, Santoro KA, Hauptman JG, Holahan ML, Brown AJ. Continuous versus intermittent delivery of nutrition via nasoenteric feeding tubes in hospitalized canine and feline patients: 91 patients (2002-2007). Journal of Veterinary Emergency and Critical Care. 2010;20(2):232-6.

5. Campbell VL, King LG. Pulmonary function, ventilator management, and outcome of dogs with thoracic trauma and pulmonary contusions: 10 cases (1994-1998). Journal of the American Veterinary Medical Association. 2000 Nov 1;217(10):1505-9.

6. Chalmers AF, Kirton R, Wyse CA, Dickie A, Cumming D, Cooper JM, et al. Ultrasonographic assessment of the rate of solid-phase gastric emptying in dogs. Veterinary Record. 2005 Nov 19;157(21):649-52.

7. Chan DL. Nutritional Management of Hospitalized Small Animals. John Wiley & Sons; 2015. 266 p.

8. Chan DL, Freeman LM, Labato MA, Rush JE. Retrospective Evaluation of Partial Parenteral Nutrition in Dogs and Cats. Journal of Veterinary Internal Medicine. 2002;16(4):440-5.

9. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Critical Care Medicine. 1999 Dec;27(12):2812.

10. Crabb SE, Freeman LM, Chan DL, Labato MA. Retrospective evaluation of total parenteral nutrition in cats: 40 cases (1991-2003). Journal of Veterinary Emergency and Critical Care. 2006;16(s1):S21-6.

11. Doley J, Mallampalli A, Sandberg M. Nutrition Management for the Patient Requiring Prolonged Mechanical Ventilation. Nutrition in Clinical Practice. 2011;26(3):232-41.

12. Edwards TH, Coleman AE, Brainard BM, DeFrancesco TC, Hansen BD, Keene BW, et al. Outcome of positive-pressure ventilation in dogs and cats with congestive heart failure: 16 cases (1992-2012). Journal of Veterinary Emergency and Critical Care. 2014;24(5):586-93.

13. Elke G, Felbinger TW, Heyland DK. Gastric Residual Volume in Critically Ill Patients. Nutrition in Clinical Practice. 2015;30(1):59-71.
14. ESICM Working Group on Gastrointestinal Function, Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Medicine. 2017 Mar;43(3):380-98.

15. Fruhwald S, Holzer P, Metzler H. Gastrointestinal motility in acute illness. Wiener klinische Wochenschrift. 2008 Jan;120(1-2):6-17.

16. Gajanayake I, Wylie CE, Chan DL. Clinical experience with a lipid-free, ready-made parenteral nutrition solution in dogs: 70 cases (2006-2012). Journal of Veterinary Emergency and Critical Care. 2013;23(3):305-13.

17. Gattinoni L, Marini JJ, Collino F, Maiolo G, Rapetti F, Tonetti T, et al. The future of mechanical ventilation: lessons from the present and the past. Critical Care. 2017;21(183).

18. Hersch M, Krasilnikov V, Helviz Y, Zevin S, Reissman P, Einav S. Prokinetic drugs for gastric emptying in critically ill ventilated patients: Analysis through breath testing. J Crit Care. 2015 Jun;30(3):655.e7-13.

19. Hoareau GL, Mellema MS, Silverstein DC. Indication, management, and outcome of brachycephalic dogs requiring mechanical ventilation. Journal of Veterinary Emergency and Critical Care. 2011;21(3):226-35.

20. Holahan M, Abood S, Hauptman J, Koenigsknecht C, Brown A. Intermittent and Continuous Enteral Nutrition in Critically Ill Dogs: A Prospective Randomized Trial. Journal of Veterinary Internal Medicine. 2010;24(3):520-6.

21. Hopper K, Haskins SC, Kass PH, Rezende ML, Aldrich J. Indications, management, and outcome of long-term positive-pressure ventilation in dogs and cats: 148 cases (1990-2001). Journal of the American Veterinary Medical Association. 2007 Jan 1;230(1):64-75.

22. King LG, Hendricks JC. Use of positive-pressure ventilation in dogs and cats: 41 cases (1990-1992). J Am Vet Med Assoc. 1994 Apr;204(7):1045-52.

23. Lee JA, Drobatz KJ, Koch MW, King LG. Indications for and outcome of positive-pressure ventilation in cats: 53 cases (1993-2002). Journal of the American Veterinary Medical Association. 2005 Mar;226(6):924-31.

24. Marshall A, West S. Nutritional intake in the critically ill: Improving practice through research. Australian Critical Care. 2004 Feb 1;17(1):6-15.

25. Mutlu GM, Mutlu EA, Factor P. GI Complications in Patients Receiving Mechanical Ventilation. Chest. 2001 Apr 1;119(4):1222-41.

26. Mutlu GM, Mutlu EA, Factor P. Prevention and treatment of gastrointestinal complications in patients on mechanical ventilation. Am J Respir Med. 2003;2(5):395-411.

27. Purro A, Appendini L, De Gaetano A, Gudjonsdottir M, Donner CF, Rossi A. Physiologic Determinants of Ventilator Dependence in Long-term Mechanically Ventilated Patients. Am J Respir Crit Care Med. 2000 Apr 1;161(4):1115-23.

28. Putensen C, Wrigge H, Hering R. The effects of mechanical ventilation on the gut and abdomen. Curr Opin Crit Care. 2006 Apr;12(2):160-5.

29. Pyle SC, Marks SL, Kass PH. Evaluation of complications and prognostic factors associated with administration of total parenteral nutrition in cats: 75 cases (1994-2001). Journal of the American Veterinary Medical Association. 2004 Jul;225(2):242-50.

30. Queau Y, Larsen JA, Kass PH, Glucksman GS, Fascetti AJ. Factors Associated with Adverse Outcomes during parenteral Nutrition Administration in Dogs and Cats. Journal of Veterinary Internal Medicine. 2011;25(3):446-52.
31. Ravasco P, Camilo ME. Tube Feeding in Mechanically Ventilated Critically Ill Patients: A Prospective Clinical Audit. Nutrition in Clinical Practice. 2003;18(5):427-33.

32. Reintam A, Parm P, Kitus R, Kern H, Starkopf J. Gastrointestinal symptoms in intensive care patients. Acta Anaesthesiologica Scandinavica. 2009;53(3):318-24.

33. Reintam Blaser A, Jakob SM, Starkopf J. Gastrointestinal failure in the ICU. Current Opinion in Critical Care. 2016;22(2):128-141.

34. Reintam Blaser A, Malbrain MLNG, Starkopf J, Fruhwald S, Jakob SM, De Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Medicine. 2012 Mar;38(3):384-94.

35. Reintam Blaser A, Poeze M, Malbrain MLNG, Björck M, Oudemans-van Straaten HM, Starkopf J, et al. Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study. Intensive Care Med. 2013 May 1;39(5):899-909.

36. Reuter JD, Marks SL, Rogers QR, Farver TB. Use of Total Parenteral Nutrition in Dogs: 209 Cases (1988-1995). Journal of Veterinary Emergency and Critical Care. 1998;8(3):201-213.

37. Rutter CR, Rozanski EA, Sharp CR, Powell LL, Kent M. Outcome and medical management in dogs with lower motor neuron disease undergoing mechanical ventilation: 14 cases (2003-2009). Journal of Veterinary Emergency and Critical Care. 2011;21(5):531-41.

38. Silen W, Merhav A, Simson JN. The pathophysiology of stress ulcer disease. World J Surg. 1981 Mar;5(2):165-74.

39. Tsukamoto A, Ohno K, Tsukagoshi T, Maeda S, Nakashima K, Fukushima K, et al. Real-Time Ultrasonographic Evaluation of Canine Gastric Motility in the Postprandial State. Journal of Veterinary Medical Science. 2011;73(9):1133-8.

40. Whitehead K, Cortes Y, Eirmann L. Gastrointestinal dysmotility disorders in critically ill dogs and cats. Journal of Veterinary Emergency and Critical Care. 2016;26(2):234-53.
PLENARY SESSION: ACUTE ABDOMEN AND INTRA-ABDOMINAL PRESSURE MONITORING

**Joel Starkopf:**

Joel Starkopf is a professor of anaesthesia and intensive care at the University of Tartu, head of the Anaesthesia and Intensive Care Clinic, Tartu University Hospital. He graduated from University of Tartu, Estonia, in 1991, and received his training as an anaesthetist and intensive care specialist. From 2009 to 2015 he was dean of the Faculty of Medicine, and since then he has headed up the Institute of Clinical Medicine, University of Tartu. His scientific experience ranges from animal experiments to multicentre clinical trials and systematic reviews. His research has focused on abdominal problems in intensive care patients; ischaemia-reperfusion of the heart and myocardial preconditioning; and pharmacokinetics of antibacterial drugs in severe sepsis and septic shock. He has published more than 70 peer reviewed scientific papers. He has broad clinical practise as intensivist, and supervises the University Hospital department with the highest caseload for anaesthesia, intensive care and emergency medicine in Estonia.
TRAUMATIC ABDOMINAL INJURY AND SURGICAL MANAGEMENT

Peep Talving:

Professor Peep Talving is a Trauma Surgeon, Professor of Surgery at the University of Tartu, and Director of Acute Care Surgery Division of the North Estonia Medical Center in Tallinn, Estonia. He was previously an Assistant Professor of Surgery and Emergency Medicine at the Division of Trauma and Acute Care Surgery at the University of Southern California, Keck School of Medicine and an Attending Surgeon at the Los Angeles County General Hospital. He defended his PhD thesis at the Karolinska Institute in Stockholm, Sweden. Dr. Talving is a Fellow of the American College of Surgeons and the American Association for the Surgery of Trauma (AAST). He is the National Chair and Course Director of ATLS in Estonia.
## EXTRACORPOREAL THERAPY: BEYOND HAEMODIALYSIS AND APHERESIS

Guillaume L. Hoareau, DVM, PhD, DACVECC, DECVECC
Clinical Investigation Facility, Travis Air Force Base

Extracorporeal blood purification has made significant advances in veterinary patients over the recent years with a rising number of hospitals providing intermittent haemodialysis, continuous renal replacement therapy, or even apheresis. Novel advances in human ICUs have led to the development of novel extracorporeal blood purification techniques that may find application in veterinary emergency and critical care.

### EXTRACORPOREAL POTASSIUM ADSORPTION

Hyperkalaemia is a common problem in both veterinary and human acute care. Medical management (with insulin, dextrose, bicarbonate, beta agonists, and calcium) along with treatment of the underlying disease, whenever possible, is often sufficient to reduce plasma potassium concentrations below life-threatening levels. Unfortunately, a subset of patients are refractory to medical therapy alone and may require extracorporeal blood purification in the form of haemodialysis or continuous renal replacement therapy until hyperkalaemia resolution. Those therapies require a technical platform along with possible large volume of replacement fluids in addition to the need for trained personnel. Those limitations have stimulated interest in potassium adsorption technologies. While there is no commercially available product at the moment, research in swine has shown that circulation of ultrafiltrate through cartridges containing potassium adsorbing beads could control plasma potassium concentrations in both anephric and crush injury swine models without the need for replacement fluids. Those studies showed that the beads had no significant effect on other electrolytes, platelet counts, or resuscitation requirements. This intervention does not control concomitant uraemia and other disorders associated with acute kidney injury (other electrolyte imbalances, azotaemia, fluid overload). There is still a need to circulate the blood in an extracorporeal circuit but this circuit could be simpler to manage than that of haemodialysis or continuous renal replacement therapy.

### EXTRACORPOREAL MEMBRANE ADSORPTION

Sepsis is a serious condition, which is often associated with a high rate of morbidity and mortality in veterinary medicine. A subgroup of patients sometimes progresses to septic shock; these patients then suffer from severe hypotension despite adequate fluid resuscitation which requires the use of vasopressors. Despite these intensive resuscitation efforts, these patients still have a minimal survival rate. Novel cartridges have been developed to non-specifically adsorb cytokines and chemokines in a concentration-driven manner. Molecules ranging from 5 to 60 kDa are bound to the cartridge membrane.

The cartridges have also been used to remove myoglobin following severe rhabdomyolysis. The cartridge may also find application in cases of intoxication. Evidence is building in human ICU patients with a wide range of diseases.

### EXTRACORPOREAL MEMBRANE OXYGENATION

In recent years there has been an increased interest in extracorporeal membrane oxygenation (ECMO) not only for intensive care patients but also for those presenting to the emergency room with highly
compromised cardiovascular and/or pulmonary functions. There have also been reports of in-field initiation of ECMO, thus underlying the ability to implement this resource-intense intervention even in unfavourable conditions. ECMO has also been used in patients in cardiac arrest, an intervention termed extracorporeal cardiopulmonary resuscitation (ECPR).

Patients undergoing ECMO therapy are placed on a by-pass circuit where blood is circulated through a membrane acting as an artificial lung, which removes carbon dioxide and enriches the blood in oxygen. This requires a large, well-coordinated team along with costly materials at the moment. ECMO can be VA or VV, whereby blood is pumped from a large vein into a large artery or vein, respectively. VA ECMO supports both the lung and heart and VV ECMO is used in patients with respiratory failure but sufficient cardiovascular function.

## References

1. Hoareau GL, Beyer CA, Wilson C, Kashtan H, Wishy A, Grayson JK, Walker L, Ross JD, Stewart IJ. Extracorporeal potassium binding for the management of hyperkalemia in an anephric model of crush injury. J Trauma Acute Care Surg. 2019 Jan 10

2. Hoareau GL, Kashtan H, Walker L, Beyer C, Wishy A, Grayson JK, Ross JD, Stewart IJ. A novel perfusion system for damage control of hyperkalemia in swine. Shock

3. Schädler D, Porzelius C, Jörres A, Marx G, Meier-Hellmann A, Putensen C, Quintel M, Spies C, Engel C, Weiler N, Kuhlmann M. A multicenter randomized controlled study of an extracorporeal cytokine hemoadsorption device in septic patients. Crit Care. 2013; 17(Suppl 2): P62.

4. Peng ZY, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med. 2008 May; 36(5): 1573–1577

5. Kogelmann K, Jarczak D, Scheller M, Drüner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care. 2017; 21: 74

6. Lamhaut L, Hutin A, Puymirat E, Jouan J, Raphalen JH, Jouffroy R, Jaffry M, Dagron C, An K, Dumas F, Marijon E, Bougouin W, Tourtier JP, Baud F, Jouven X, Danchin N, Spaulding C, Carli P. A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis. Resuscitation. 2017 Aug;117:109-117

7. Tonna JE, Selzman CH, Mallin MP, Smith BR, Youngquist ST, Koliopoulou A, Welt F, Stoddard KD, Nirula R, Barton R, Fair JF, Fang JC, McKellar S. Development and Implementation of a Comprehensive, Multidisciplinary Emergency Department Extracorporeal Membrane Oxygenation Program. Ann Emerg Med. 2017 Jul;70(1):32-40
## VOLUME ASSESSMENT: WHERE ARE WE?

Søren Boysen, DVM, DACVECC,

University of Calgary, Faculty of Veterinary Medicine, Canada (srboysen@ucalgary.ca)

Kris Gommeren, DVM, DECVECC,

University of Liège, Faculty of Veterinary Medicine, Belgium (kris.gommeren@uliege.be)

Although appropriate early resuscitative fluid therapy improves ICU patient outcomes, it must be balanced against excessive fluid therapy and fluid overload. Fluid overload in critically ill human patients is associated with longer hospitalization, increased mechanical ventilation, acute kidney injury, abdominal compartment syndrome, organ dysfunction and increased mortality. With evidence that critically ill patients may benefit from avoidance of excessive fluid administration during resuscitation, and further benefit from removal of excess fluids once shock has resolved, there is a trend in the human profession towards what has been termed "fluid stewardship". This involves the 4 D's of fluid therapy (drug, duration, dosing and de-escalation) as well as a 4-phase "ROSE" (resuscitation, optimization, stabilization and evacuation) fluid resuscitation strategy. Although the four D's and the ROSE protocol are great in theory, determining which clinical phase of resuscitation a patient is experiencing, and subsequently the timing, dose, rate or even need for fluid removal can be very challenging. Furthermore, different types of shock may require different fluid resuscitation strategies. For example, ICU patients with sepsis tend to be more susceptible to fluid overload than patients suffering simple hypovolaemia secondary to vomiting/gastro-intestinal losses. Not knowing the volume status of critically ill dogs and cats makes administration of fluid therapy in the resuscitation phases of shock challenging.

### Blood volume vs. Fluid responsiveness

Fluid responsiveness can be defined by the extent to which fluid administration will improve cardiac output (CO) and is a reflection of the myocardium to improve contractility with increased sarcomere stretch due to preload (the Frank-Starling curve). Unfortunately, many human studies have shown that up to 50% of haemodynamically unstable children and adults in the ICU are not fluid responsive (regardless of blood volume). This is probably true in veterinary patients as well. Therefore, although knowing a patient's intravascular volume status is important, it does not necessarily predict which haemodynamically unstable patients are fluid responders and which might need vasopressors. Ideally, knowing which patients are hypovolaemic, and subsequently which subcategory of patients within a hypovolaemic group are likely to respond to fluid challenges would allow fluid therapy to be tailored to individual patient needs. Patients unresponsive to fluid boluses (the flat portion of the Frank-Starling curve) are more likely to benefit from vasopressors and positive inotropes, while patients on the steep aspect of the Frank-Starling curve are likely to benefit from continued fluid boluses. The challenge lies in identifying the transition point along the Frank Starling curve where patients progress from being fluid responsive (steep curve where fluid boluses may be indicated) to fluid unresponsive (flat portion of the curve where vasoplegic and cardiac management may be more important).

### Fluid responsiveness vs. fluid tolerance vs. fluid requirements

It is important to keep in mind that "fluid responsiveness" does not equate to "fluid tolerance". For example an animal that is septic may be a classified as a fluid responder (has improved CO following fluid administration - see below) but due to other complex interactions (e.g. increased vascular
permeability, extra vascular lung water, etc.) may not be able to tolerate additional fluid boluses. Finally, it is also important to realize that not all patients that are fluid responders require fluids; studies show that up to 50% of healthy volunteers are fluid responders (based on a 10% increase in CO following a passive leg raise manoeuvre) but obviously do not require fluids.

## Static indices

Although practical and important in the assessment of any critically ill patient, human and veterinary studies have shown the assessment of haemodynamic status based on physical examination and routine non-invasive monitoring is too nonspecific and is not sensitive at predicting intravascular volume status. Central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) have traditionally been used to help guide fluid therapy in both human and veterinary patients, but recent studies have questioned the value of CVP and PAOP in predicting fluid responsiveness. Physical exam findings, CVP and PAOP are referred to as static indices of cardiac preload, and mounting evidence suggests static indices have limited value in guiding fluid resuscitation. A recent review of the use of CVP in veterinary medicine (Hutchinson and Shaw 2016) details the potential value and controversies of CVP in cats and dogs: The authors conclude that “CVP monitoring of critically ill canine and feline patients should not have a primary role in patient monitoring until such time that additional studies supporting its use are performed”. Despite this, recent surveys suggest up to 90% of human clinicians continue to use static indices to help guide decisions regarding fluid therapy, including CVP. There may however still be value in measuring CVP in extreme cases (patients on the far ends of hypovolaemia or volume overload spectrum) if CVP is trended over time, interpreted in conjunction with other factors, and its limitations are considered.

## Dynamic indices

To help identify where an individual is on the Frank Starling curve many investigators have suggested monitoring “dynamic” indices of fluid responsiveness, as opposed to traditional “static” indices. Dynamic indices use heart-lung interactions to assess fluid responsiveness. The principle is to observe an effect on cardiac output induced by a change in preload in conjunction with the respiratory phases. This is most often assessed in mechanically ventilated patients but can be measured in spontaneously breathing patients in some instances. There are typically 3 factors involved in measuring dynamic variables: 1) measurement of an index reflective of blood volume (e.g. diameter of the inferior vena cava, pulse pressure variation etc.), 2) intrathoracic pressure changes (which is one variable that affects preload) occurring as a result of the respiratory cycle and 3) a change in blood volume (a second known preload-changing factor) such as administration of a fluid challenge or performing some manoeuvre (e.g. passive leg raise, tidal volume challenge). The change in cardiac output is the dynamic response assessed, either measured directly (i.e. direct cardiac output monitoring), or indirectly (e.g. systolic blood pressure). Although multiple techniques are available to directly measure and estimate cardiac output, both invasively and non-invasively, the procedures tend to be somewhat time consuming and are not readily available in most veterinary clinical settings. Readers are referred elsewhere for a review of cardiac output measurement and its application in veterinary critical care (Sheral et al 2016).

Indirect dynamic indices that have been successfully used to predict fluid responsiveness in mechanically ventilated humans and dogs most often include the respiratory variation in systolic pressure, pulse pressure, and stroke volume. During positive pressure ventilation there is a decrease
in venous return and pulmonary artery blood flow during inspiration (vena cava blood flow is impeded during the inspiratory phase of positive pressure ventilation). Within 2-3 heart beats (pulmonary transit time) the decrease in venous return is apparent at the level of the left heart, which results in a decrease in left ventricular end diastolic volume and consequently stroke arterial blood pressure (particularly systolic) and plethysmographic waveform amplitude. Under positive pressure ventilation, the magnitude of the variation at all levels is greater in hypovolaemic fluid responsive patients than non-fluid responsive patients, as fluid responsive patients are functioning on the steep portion of the Frank-Starling curve. Dynamic variables can be quantified as a percentage difference between the maximal and minimal measured value of a single PPV breath (see figure 1). For example, the systolic pressure variation can be calculated as: $SPV (\%) = (SAPmax - SAPmin) / [(SAPmax + SAPmin) / 2] \times 100$. Other dynamic variables can be calculated with similar equations. In human patients, a pulse pressure variation < 12 - 13% indicates patients that are unlikely to respond to a fluid challenge as there is minimal effect of ventilation on venous return. In contrast, patients with a pulse pressure variation > 13% may be relatively hypovolaemic and respond to a fluid bolus by increasing stroke volume. Several studies in dogs have demonstrated the value of dynamic variables in assessing responsiveness to blood loss and fluid therapy. A recent study in dogs demonstrated that pulse pressure variation can predict fluid responsiveness in isoflurane-anaesthetized dogs, and that it can be used to guide fluid therapy with a cut-off value of 15% distinguishing responders from non-responders, when mechanically ventilated with a tidal volume of 10 mL/kg and 3 cmH2O PEEP. Although a > 15% increase in the dynamic variable measured is generally thought to be clinically meaningful in people, the threshold value to define fluid responsiveness varies between studies and smaller changes in variation may also indicate fluid responsiveness depending on the patient's baseline values, age, vascular tone, underlying pathology, and the manoeuvre used to invoke the dynamic change. For example, some studies suggest a threshold of > 10% in CO following passive leg raise manoeuvres or even > 5% CO change following a tidal volume challenge (see below) are sufficient to identify fluid responders. Unfortunately, dynamic variables are limited by the fact they rely on patients receiving positive pressure ventilation and require an arterial catheter in most cases.

Furthermore, although dynamic variables show promise in adult humans and dogs, a recent systematic review found these variables were not predictive of fluid responsiveness or volume status in children. They have also been reported to be inaccurate in patients with decreased lung compliance (eg. ARDS) and in patients being ventilated with low tidal volumes (<8 ml/kg). However, a novel approach in human medicine that may prove promising uses a “tidal volume” challenge when using PPV < 8 ml/kg tidal volume. This test is performed to assess fluid responsiveness in patients in shock, ventilated using low tidal volume without spontaneous breathing activity. The pulse pressure variation is recorded from a bedside monitor at baseline (tidal volume 6 ml/kg). The tidal volume is then transiently increased from 6 ml/kg to 8 ml/kg for one minute and the pulse pressure variation is recorded. The tidal volume is returned to 6 ml/kg. The Δ pulse pressure variation 6–8 is calculated. A Δ pulse pressure variation 6–8 greater than 3.5% predicts fluid responsiveness with high accuracy. Alternatively, in humans a passive leg raise manoeuvre (PLRM) is often used as the preload manoeuvre (this is essentially a “virtual” fluid challenge that can be reversed as it relies on increasing venous return via fluids already contained in the vascular system). A PLRM is performed by bringing the patient's trunk as close as possible to supine position with the legs elevated up to 45 degrees for 3 minutes. The legs are then returned to 0 degrees, reversing the transient increase in venous return.
The PLRM is not practical in veterinary medicine, and therefore a true fluid challenge is often required to assess fluid responsiveness.

Although there is variation in the reported quantity and speed at which a fluid bolus must be given to assess fluid responsiveness, recent evidence in both human and veterinary literature suggests as little as 4ml/kg of isotonic crystalloids given IV over 5 minutes might be adequate to assess fluid responsiveness.

## Sonographic assessment of fluid responsiveness

### Caudal vena cava evaluation

The inferior vena cava (IVC) has also been investigated as a non-invasive means of predicting blood volume in humans. The venous capacitance system contains two thirds of the intravascular volume, with the caudal vena cava (CVC) being the largest capacitance vessel in animals. The thin wall and elastic nature of the CVC makes it a responsive and dynamic blood vessel. Similar to other dynamic variables that fluctuate with changes in the respiratory cycle, the high compliance of the caval wall allows its size and geometry to fluctuate in response to relative and absolute intravascular volume changes depending on both the respiratory and cardiac cycle. Spontaneous and PPV respirations results in a change in positive and negative pressures within the thorax. These pressure changes influence the vascular volume within the thorax and abdomen. With spontaneous respirations, negative pressure draws blood into the thoracic CVC from the abdominal CVC, causing the CVC to decrease in size within the abdomen while the positive pressure of expiration pushes blood from the thoracic CVC into the abdominal CVC.

Measurement of the IVC can be performed in a static fashion, measuring the maximum and minimum values and/or calculating a ratio relative to the aorta, all of which has been shown to correlate well with CVP measurements in people. In human patients suffering trauma, patients in shock upon arrival had a smaller IVC diameter compared with those not in shock (7.7 vs. 13.4 mm). The IVC diameter has been shown to help predict response to fluid resuscitation of patients in shock states. A change in CVC diameter in response to hypovolaemia and fluid overload has also been shown to correlate well to CVP in dogs when measured via ultrasound at the level of the liver via a right parasternal window. A strong correlation between gall bladder wall thickness and increasing CVP in dogs has also been demonstrated. Given variation in body weight and patient size will impact IVC diameter references, the use of the IVC:aorta ratio has been validated in humans to account for differences in body size and weight, particularly in children and paediatric patients. A static index ratio of the CVC to aorta has recently been investigated in dogs undergoing blood donation. One study showed no change in CVC:aorta ratio in 8 dogs pre and post blood donation when measured at the suprailiac location. A more recent study demonstrated the CVC:aorta ratio measured at the sublumbar region of the left kidney (spleno-renal location of abdominal focused assessment with sonography for trauma) could be used to predict a change in blood volume following blood donation in 12 dogs. The technique was easily learned, performed in under a minute with good repeatability and shows promise in the veterinary emergency/critical care setting in helping to identify hypovolaemia, particularly as a result of haemorrhage. Further investigation is needed to determine the extent to which this protocol and be applied in veterinary patients and its ability to predicting fluid responsiveness in small animal patients.
Assessment of the IVC and IVC:aorta ratio has been criticized in human literature as being a static index, which implies similar limitations to the role of CVP in assessing volume status and fluid responsiveness. A dynamic measurement of the IVC has subsequently been investigated in human medicine and has shown promise predicting both volume status as well as responsiveness to fluid therapy. Initial dynamic indexes of the IVC were performed in patients undergoing PPV, but more recent studies have demonstrated the IVC index can be performed in critically ill spontaneously breathing human patients. The IVC collapsibility index (IVC-CI) is a dynamic index that involves calculating the percentage change in the diameter of the vena cava during the respiratory cycle. For example, in spontaneously breathing patients the IVC-CI = end-expiratory diameter (max IVC diameter) - end-inspiratory diameter (min IVC diameter) / end-expiratory diameter. The measurement is based on the impedance of vena cava blood flow during the respiratory cycle. The interpretation is different between PPV ventilated patients and spontaneously breathing patients because of the impact of intrathoracic pressures on the impedance of blood flow in the vena cava. With PPV, the extra-thoracic vena cava diameter increases during inspiration, while the extra thoracic vena cava decreases in diameter during inspiration in spontaneously breathing patients. The CVC-CI values found in humans vary by study but the mean values for IVC-CI reported in healthy, adult human studies are 47.3% +/- 8.9%. Changes less than 20% are associated with hypervolaemia while change greater than 60% are associated with hypovolaemia.

In humans and dogs, the location and technique to assess the percentage change in CVC diameter with respiratory cycle varies. In people, the IVC can be measured at the subxyphoid, lateral, and even suprailiac locations. The superior vena cava has also been evaluated in people, however it requires Transoesophageal Echocardiography (TOE) to obtain accurate and reliable measurements. Body condition and formation can be a potential barrier in obtaining accurate measurements in people. Further limitations to the IVC measurement in people have been demonstrated in patients with high intra-abdominal pressures, patients with marked respiratory disease/effort, and pressure artifact. In dogs, the vena cava has been evaluated via a right sided transverse intercostal view of the liver where the CVC, aorta and portal vein are all visualized in the same sonographic view. It has also been evaluated at the subxiphoid site where the CVC crosses the diaphragm, at the suprailiac location and at the level of the kidneys. Further studies are needed to determine the role of the CVC diameter, CVC collapsibility index, and CVC:aorta ratio in determining the blood volume of dogs, which dogs are more likely to be responsive to fluid challenges, and dogs at risk for volume overload. To date, there is limited to no veterinary literature available on the role of the CVC in estimating blood volume or response to fluid therapy in cats. Studies in dogs have demonstrated there is good inter and intra-rater variability for some but not all CVC measurements.

## Cardiac evaluation

There are also limited studies in dogs assessing echocardiographic changes in the heart in relation to blood volume status. In most species, including cats and dogs, hypovolaemia can induce a decrease in left ventricular lumen size with thickening of the intraventricular septum and left ventricular free wall referred to as "pseudohypertrophy". Pseudohypertrophy is reversible following adequate fluid resuscitation. The left atrial size decreases in size with hypovolaemia and increases with overzealous fluid administration. The contractility of the heart is also worth assessing as it will change with alterations in intravascular volume status. Although used in several hospitals in a clinical setting,
scientific evidence on the use of echocardiographic assessment of the hypovolaemic heart is lacking
in veterinary medicine.

Fluid intolerance and overzealous fluid therapy

There are a number of sonography protocols used in human ICU patients to help determine if a patient is fluid intolerant and at risk of complications due to continued fluid therapy. For example, combining the evaluation of IVC changes, cardiac assessment with screening for alveolar interstitial syndrome (AIS, often reflective of pulmonary oedema), in people allows for individually tailored fluid therapy (e.g. FALLS protocol). Although veterinary evidence to support the use of such protocols in our small animal patients is currently lacking, some institutions have already started to incorporate some of these principles into veterinary point of care ultrasound. By doing so, clinicians gain a better systemic picture of the patients volume status, fluid responsiveness and fluid tolerance, although proof of improved outcome is also lacking at this time. Through evaluation of the caudal vena cava and monitoring of the LA/Ao-ratios and screening for the appearance of B-lines and/or gall bladder wall oedema, point of care thoracic ultrasonography should allow volume replacement to be tailored to the individual small animal patient that presents with hypovolaemic shock.

Wet or dry lung determined via ultrasound: Knowing if fluid is present in the lungs (along with volume estimation/cardiac function) is very helpful when deciding what fluid rates might be tolerated by the patient. Sonographic evaluation of the lungs has been used in humans and veterinary patients to evaluate the lung to determine if it is "wet" or "dry". The "wet" vs "dry" lung is based on detecting the presence of absence of B lines (also called lung rockets), which are vertical white lines extending from the pleural line distally through the far field of the ultrasound image which move to and fro with respirations. The presence of one to three B line is considered normal in dogs, however, the presence of multiple (>3) to coalescing B lines at a single site, particularly if they are present at more than one site over the thorax, is suggestive of interstitial alveolar syndrome. For example, the presence of numerous easily detectable B lines following trauma suggests pulmonary contusions while the presence of multiple B lines in a dog with cough and a heart murmur is more suggestive of cardiogenic pulmonary oedema, particularly if evaluation of the heart supports cardiac disease. By recording the number and location of B lines within lung fields it is possible to gain a greater understanding of the degree of fluid in the lungs, which can be used to help guide fluid therapy decisions. If a patient presents with dry lungs and then develops > 3 B lines in a single ultrasound window during fluid resuscitation, the patient's CVC, cardiac chamber size and cardiac contractility should all be assessed to help decide further treatment options. Aggressive fluid therapy should be discontinued until all the sonographic parameters in conjunction with the overall clinical picture can be evaluated more thoroughly.

**In summary,** the first question to decide is does the patient require fluids? If yes, will the patient benefit from fluids (is the patient fluid responsive), and finally can the patient tolerate fluids (is the patient fluid tolerant). Layered on top of this question one must ask if the patient also requires vasopagic and cardiac management, and if so when should they be initiated, but the latter is a discussion for another time.
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8. Nelson NC1, Drost WT, Lerche P, Bonagura JD. Noninvasive estimation of central venous pressure in anesthetized dogs by measurement of hepatic venous blood flow velocity and abdominal venous diameter. Vet Radiol Ultrasound. 2010;51(3):313-23.

9. Klein AV, Teixeira-Neto FJ, Garofalo NA, et al. Changes in pulse pressure variation and plethysmographic variability index caused by hypotension-inducing hemorrhage followed by volume replacement in isoflurane-anesthetized dogs. Am J Vet Res. 2016;77(3):280-7.

10. Rabozzi R, Franci P. Use of systolic pressure variation to predict the cardiovascular response to mini-fluid challenge in anaesthetised dogs. Vet J. 2014;202(2):367-71.

11. Fine DM1, Durham HE Jr, Rossi NF, et la. Echocardiographic assessment of hemodynamic changes produced by two methods of inducing fluid deficit in dogs. J Vet Intern Med. 2010;24(2):348-53.

12. Gan H, Cannesson M, Chandler JR, Ansermino JM. Predicting fluid responsiveness in children: a systematic review. Anesth Analg. 2013;117(6):1380-92.

13. Fantoni DT, Ida KK, Gimenes AM, et al. Pulse pressure variation in anesthetized dogs Pulse pressure variation as a guide for volume expansion in dogs undergoing orthopedic surgery. Vet Anesth Anal 2017;44:710-718

14. Corl KA, George NR, Romanoff J, et al. Inferior vena cava collapsibility detects fluid responsiveness among spontaneously breathing critically-ill patients. J Crit Care. 2017;41:130-137.

15. E. Darnis; A.C. Merveille; L. Desquilbet; S. Boysen; K. Gommeren. Interobserver Agreement When Measuring Ultrasonographic Inferior Vena Cava Diameter and Basic Echocardiographic Parameters by Non-Cardiologist Veterinarians Following a 6-Hour Training Course. Abstract. 26th ECVIM-CA Congress, 2016

16. Cambournac M, Goy-Thollot I, Violé A, Barthélemy A, Boisvineau C, Pouzot-NEvoret C. Sonographic assessment of volemia (SAV) in dogs: determination and validation of a new method. Abstract. EVECCS Dublin Ireland 2017.

17. Darnis E, Merveille AC, Desquilbet L, et al. Establishment of the caudal vena cava reference values in healthy dogs through different views of FAST-Ultrasonography. Abstract. EVECCS Dublin Ireland 2017.

18. Merveille AC, Darnis E, Boysen S, Gommeren K. Caudal vena cava assessment in dogs with rightsided congestive heart failure: a pilot study. Abstract. 27th ECVIM-CA Congress, 2017
19. Herreria-Bustillo V, Humm K, Fitzgerald E. Caval-aortic ratio and caudal vena cava diameter in dogs before and after blood donation. Abstract. J Vet Emerg Crit Care doi: 10.1111/vec.12516

20. Drozdzynska MJ, Chang YM, Stanzani g, Pelligand L. Evaluation of dynamic predictors of fluid responsiveness in dogs receiving goal-directed fluid therapy. Vet Anesth Anal 2018;45:22-30.

21. Monnet X, Teboul JL. My Patient has received fluid. How to assess its efficacy and side effects. Ann Intensive Care 2018;8:54.

22. De Freitas Chaves RC, Correa TD, Neto AS et al. Assessment of fluid responsiveness in spontaneously breathing patients : a systematic review of the literature. Ann Intensive Care 2018;8:21.

23. Elwan MH, Roshdy A, Reynolds JA et al. What is the normal haemodynaic response to passive leg raise? A study of healthy volunteers. Emerg Med J 2018;0:1

24. Jafee W, Hodgins S, McGee T. Tissue edema, fluid balance, and patient outcomes in severe sepsis: an organ systems review. J Intensive Care Med. 2017; 1 doi: 10.1177/0885066617742832. [Epub ahead of print]

25. Myatra SN, Monnet X, Teboul JL. Use of 'tidal volume challenge' to improve the reliability of pulse pressure variation. Crit Care 2017;21:60

26. Malbrain ML, Regenmortel NV, Saugel B et al. Principles of fluid management and stewardship in septic shock : is it time to consider the four D's and four phases of fluid therapy? Ann intensive Care 2018;8:66.

27. Aya H, Rhodes A, Ster IC et al. Hemodynamic effect of different doses of fluids for a fluid challenge: A quasi-randomized controlled study. Crit Care Med 2017;45:e161-e168.
# WELLNESS IN YOUR PRACTICE AND YOUR LIFE

Lindsey Dodd BSc(Hons) VPAC PgCert in HE FHEA VTS(ECC) RVN
Lumbry Park Veterinary Specialists, Hampshire, UK

Wellness is to most the opposite to illness, however it goes beyond that idea. The session will introduce wellness and highlight its importance for us as individuals and our practice. Personal experiences will be shared along with ideas to help implement wellness into your practice and your life.

The World Health Organisation describes wellness as 'a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity.' As Veterinary professionals we are aware of the pressures we face in our daily lives and when working in emergency and critical care these pressures and the expectation we have from our clients, our managers and ourselves can sometimes feel unachievable. We will have all experienced days when reading that wellness is 'a state of complete physical, mental and social well-being' we feel far from that as an individual and a team. Wellness programmes are available from many larger corporations and smaller businesses however there is still much we can consider to improve our personal wellness and the wellness of our practice team. As individuals we will all have preferences and, more or less successful interventions to help with our physical, mental and social well-being, as will practice teams so, be open to what works for you and your colleagues and be at ease with what doesn't.

## Individual wellness

As a Veterinary nurse I know how often we are checking in, monitoring and nursing our patients, however how often do we check in with ourselves? When was the last time you ate, drank, went to the bathroom, exercised, slept and how well? Practicing self care doesn't detract from our nursing abilities in fact if we are OK as individuals it will enhance our professional abilities and enable us to work better and smarter for all involved. Self-focus and self-care are vital for us to maintain wellness and are particularly important in our profession, yet it would seem many of us forget or don't think to practice. Ensuring you take your annual leave entitlement and spreading your breaks throughout the year helps to plan for your rest periods and breaks away from work. Although I appreciate in a busy practice with potentially short staffing this can be easier said than done. So, consider what else can be implemented in your practice and your life to help focus on wellness on a day to day basis.

Attempting to create your life in which a state of physical, mental and social well-being can be achieved can to some, feel like a daunting concept but making small but, significant changes or improvements can be hugely beneficial. Practicing self-care is something that takes practice, and when scheduled into your daily life can become as routine as brushing your teeth!

To practice physical wellness doesn't have to mean signing up to a gym; getting outside for a short walk during your break has been shown to improve mental and physical wellbeing. Organising to go with a colleague could also improve your social wellbeing. Signing up for exercise classes can help with not only physical but also social and mental wellbeing. Classes such as yoga and Pilates can help release tension through stretching and improve physical and mental wellbeing also; classes are readily available online as well in most locations around the world.
Try to keep a positive mindset by practicing and recording your gratitude; listing three things every day that you are grateful for. Talking to colleagues, your line manager, your friends, family, counsellor or life coach helps keep a prospective on life events and events that happen in work. It also gives you opportunity to ask for help to gain support when needed. Don't be afraid to ask for help! Random acts of kindness; bringing in cake for your colleagues, organising a night out for the team can create happiness for others and in yourself and help with positivity.

Meditation and mindfulness have shown to help reduce stress, anxiety, help with focus, mood and self-compassion; creating a space for individuals to practice self-care. Using apps such as Headspace routinely can positively impact mental and physical wellbeing and take up no more than 10 minutes of your day.

## Practice wellness

Traditional wellness schemes routinely offer exercise and healthy eating packages however research indicates that wellness goes much further beyond that of a company/practice exercise and healthy eating scheme. Individuals also seek to feel connected, cared for, valued, and appreciated. Consider how we can feel like ourselves, in work as well as at home and how as leaders we can make changes or improvements in the practice to help.

The practice culture can make or break a team and it is vital for it be considered and nurtured. Creating a no blame, caring and kind team culture can have a positive impact on the individuals in the team as well on the business. For this to work it needs to be practiced proactively; for team members to be reminded when needed which may, on occasion be a reminder to the person leading the development. Remember we are all human and we learn from our mistakes and misjudgements, we are not robots, thank goodness as this allows us to be as good as we are at what we do!

Social connections are important for the whole team so consider how this can be implemented or supported at your practice. Most practices have a lunch room, is it set out as a comfortable place for people to take a break? During the summer months can an area be used to eat outside to assist the team to get out into the fresh air? Is there an area in the practice that could be made into a comfortable room with bean bags, cosy chairs to allow the team to take a real break from the work environment with others in the team to help enable social connections day to day? Healthy snacks and refreshments could be made available in this area to assist with physical and mental wellness; I'm sure we've all eaten a bag of sugary sweets or a sugary drink as a quick lunch or snack, and later feel the negative effects, as do the team. If space is short, instead or additionally, could a working group in the practice get together once a fortnight/month and plan social events for the team? Social connection is important for mental wellbeing and helps create a balance; without connections in the work place people can feel isolated, unsupported and uncared for and as an individual you can lose the opportunity to share thoughts, ideas, concerns and prospective can also be lost. Is there something you can do as an individual to welcome a new recruit or support another team member to make sure they feel as much a part of the practice team? Remember caring for others is good for our individual wellbeing also.
Is there a space for a quiet area or room to enable staff to take a quiet 5-10 minutes; potentially to practice mindfulness meditation during the day? This may seem unrealistic, particularly in a smaller practice but spaces can be used for dual purposes, maybe a room can be used for a quiet break at certain times in the day. Consider implementing a 'mindfulness Monday' in which everyone has an opportunity to take 5-10 mins to practice mindfulness meditation.

The practice can consider types of leave to allow for team members to have the required time for life events and charity work; such as your birthday day off (or a day in which they can take if they prefer to work on their birthday), time off to settle in a new pet at home, or for a child's first day at school, time off to do charity work.

Team training doesn't only have to focus on clinical development, consider team training from a life coach, mindfulness meditation, resilience, healthy eating, well-being training as important topics for inhouse learning. Can the practice host a yoga or Pilates session for the team or a hire a masseuse for a day or perhaps arrange for a personal trainer for the summer to take short classes before/after work or during lunch time? Not everyone will be keen for all activities but ask the team their preferences and gain feedback after events.

Remember we don't need to have the title head, senior, management or equivalent within our job title to lead; it is everyone's responsibility, so be kind and help foster a culture of well-being in your clinics and importantly, practice doing so in your life.

## References and further reading

1. Alison, SO, et al., 2016;249(8):879-881. Implementing wellness in the veterinary workplace. (online). J Am Vet Med Assoc. Available from: https://avmajournals.avma.org/doi/abs/10.2460/javma.249.8.879?journalCode=javma&

2. Jureski, W. 2018. Looking Out for Number One! Achieve Mental Well-Being by Practicing Self-Care. (online). Vetsuccess. Available from: https://vetsuccess.com/blog/achieve-mental-well-being-by-practicing-self-care/?utm_source=SFMC&utm_medium=email&utm_campaign=2018.11_Newsletter_Members

3. Mamo, E. 2018. Why creating a mentally healthy workplace is so important in veterinary practice. (Online). In Practice. Available from: https://inpractice.bmj.com/content/38/7/355

4. https://www.globalwellnessday.org/about/what-is-wellness/

5. https://www headspace.com/

6. https://www.mckinsey.com/business-functions/organization/our-insights/wellness-at-work-the-promise-and-pitfalls

7. https://www.mind.org.uk/workplace/mental-health-at-work/taking-care-of-your-staff/employer-resources/wellness-action-plan-download/

8. https://www.snacknation.com/blog/employee-wellness-program-ideas/

9. https://vetwellbeingawards.org.uk/wellbeing-checklist/
# MYTHBUSTERS: ECC NURSING MYTHS AND FACTS

Kenichiro Yagi, MS, RVT, VTS (ECC, SAIM)

Cornell University College of Veterinary Medicine

Ithaca, New York, United States

## Is heparinized saline necessary to keep catheters patent?

Proper maintenance of peripheral intravenous (IV) catheters 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 and leads 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 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 are uncertain. For example, studies surrounding heparinized saline use in central venous catheters currently provide 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 have 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 in clinically-indicated replacement and 166 of 2441 cases seen in routine replacement methods (p=0.75). Significant reduction of catheter placement costs were seen in the clinically-indicated group, of approximately AUD 7.00. The reviewers 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 catheters 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, tunneling, 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 haematological 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.

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 is in 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 diarrhoea 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 faecal volume, and frequency of defaecation. 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 diarrhoea. 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.

However, there are numerous veterinary studies that support the institution of enteral nutrition early in the stages of hospitalization. A study involving patients with haemorrhagic 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 propionic 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.

## Nasogastric tube or nasooesophageal tube?

Nasoenteral tubes are used in hospitalized patients to provide enteral nutrition with liquid diets on a short term basis, especially when anaesthesia is undesirable. Nasoenteral tubes can be inserted to be terminated either in the oesophagus or the stomach, called nasooesophageal (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, diarrhoea, 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, gastrooesophageal reflux, and resultant oesophagitis or stricture as the tube being placed across the lower oesophageal 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, diarrhoea, clogged tube, tube malpositioning, aspiration pneumonia, hyperglycaemia, 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 oesophagitis existed, there were no patients that showed clinical signs of oesophagitis. 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 artifact due to the retrospective nature of the study. Because NG tubes provides the benefit of allowing gastric decompression and there seemingly being no clinical signs of resultant oesophagitis, clinicians should be feeling less hesitation on using NG tubes over NE tubes.

## 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 labeled with different densities of biotin. These labeled 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.
Labeled 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 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 product, 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.

**Does Premedicating Reduce 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, have 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 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.

**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.

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**Keywords:** Transfusions, Evidence-based Medicine, Premedication, Transfusion reactions, Blood pump
# EVIDENCE-BASED CPR: THE RECOVER GUIDELINES

Kenichiro Yagi, MS, RVT, VTS (ECC, SAIM)

Cornell University College of Veterinary Medicine

Ithaca, New York, USA

In June of 2012, the Reassessment Campaign on Veterinary Resuscitation (RECOVER) published the first evidence based guidelines for veterinary cardiopulmonary resuscitation (CPR). The initiative was launched after considering the difference in survival rates of CPR between human (20%) and veterinary (6-7%) settings, with the human counterpart having established evidence-based guidelines through the American Heart Association. While there are definitely physiologic and anatomic differences between human patients and veterinary patients, a comprehensive, evidence-based treatment strategy on execution of CPR through optimization of protocols would be expected to improve the outcome. The RECOVER initiative was carried out through the involvement of over 100 experts from the American College of Veterinary Emergency and Critical Care (ACVECC) and American College of Veterinary Anesthesia and Analgesia (ACVAA) of multi-national background evaluating published studies available to answer clinical questions organized into 5 different subtopics to arrive at a consensus guideline. This groundbreaking effort not only produced a guideline that is now utilized all over the world as an accepted standard to refine CPR practices, but has also injected fuel into the drive towards evidence-based practices in veterinary medicine and sparked many other similar movements in the process.

## Evidence in CPR

Many clinical questions asked in 5 different "domains" of (1) Preparedness & Prevention, (2) Basic Life Support, (3) Advanced Life Support, (4) Monitoring, and (5) Post-Cardiac Arrest Care were answered to confirm or disprove existing beliefs, provide new knowledge, and also allow us to identify gaps in the knowledge available to come to definitive answers.

The guideline emphasizes importance in early initiation of CPR as a key factor in successful outcome. Preparation for swift intervention when a patient going into cardiac arrest can be accomplished through thorough training of the staff in both didactic (knowledge) and psychomotor (physical) aspects of CPR. CPR drills simulating the arrest and response allow staff members to better understand the sequence of events and potential turns the event may take. Periodic refresher training sessions at least every 6 months are recommended. Preparation of the facility through setup of a crash cart in a central location, which is regularly checked for stock with a detailed checklist will allow for easy access to supplies and equipment required for CPR. Cognitive aides consisting of the CPR algorithm, drug dosage charts, CPR priority checklist should be readily available in the emergency area, with the staff trained on their usage prior to the event, helping adherence to proper protocol.

Cardiopulmonary arrest (CPA) should be recognized quickly, and CPR initiated as soon as possible. The Airway, Breathing, and Circulation (ABC) assessment of the patient for CPA should be performed in no more than 10-15 seconds through a standardized approach. If CPA is even suspected, chest compressions should be started right away since any delay can significantly reduce the chance of success, accurate assessment of a lack of a pulse is difficult without taking a long time, and performing compressions on a patient that is not in CPA brings very little harm. In an inpatient situation, clear identification of patients at risk of CPA to the staff should allow for earlier recognition.
## Basic Life Support

CPR starts with provision of basic life support (BLS) as the priority, and most important aspect of CPR. The mnemonic CAB is now used to describe the priority order of circulation, airway, and breathing, because breathing is not helpful in oxygen delivery if circulation of blood has ceased and evidence points towards delay in initiation of compressions leading to lower success rates in CPR. In regards to compressions, there were no differences seen between right and left lateral recumbency. Chest compressions should be performed to 1/3 to 1/2 of chest width (which takes quite a bit of force for large animals, while moderation may be required for smaller patients) at a rate of 100-120 compressions per minute while allowing full chest recoil in between. The compressions should be focused at the highest point of the chest for dogs with normal conformation, over the heart for keel-chested dogs, and over the sternum in flat-chested dogs (such as some bulldogs). Small dogs and cats should have compressions performed over the heart, and compressions may be performed with a circumferential or two-handed technique. The use of a metronome, songs, or other methods of keeping the rate consistent to recommended rates is useful. Even when compressions are executed properly, it may only produce about 30% of normal cardiac output, which illustrates the need for swift and proper compressions during CPR. Interrupting of compressions significantly reduces the forward flow created through consistent application of compressions, and is best avoided.

Compressions should not be stopped to auscultate the heart, check for pulses, assess the patient, or place an endotracheal tube for a full 2 minutes per cycle of compressions. 10-15 seconds in between 2 minute cycles should be used for assessment of the patient, and compressions resumed promptly if no change in CPA is seen. The compressor should be switched between cycles as well, to prevent physical fatigue as 2 minutes of repetitive compressions is physically demanding.

Endotracheal intubation should be performed without interruption of compressions, and ventilations performed approximately at 10mL/kg tidal volume (or 20 cmH₂O of pressure if no spirometer) at 10 breaths per minute with an inspiratory time of 1 second. Hyperventilation is best avoided to prevent vasoconstriction from low CO2 levels leading to poor cerebral perfusion. Mouth-to-snout ventilation may be used if a single rescuer is performing CPR or supplies for endotracheal intubation are not available. In these cases, two brisk mouth-to-snout breaths in between 30 consecutive chest compressions is recommended.

## Advanced Life Support

With basic life support provided, the attention of the CPR team should be directed to providing advanced life support, including monitoring, vascular access, drug therapy, and electrical defibrillation if warranted. The two forms of monitoring that prove useful during CPR is end-tidal carbon dioxide (ETCO2) electrocardiogram (ECG) monitoring. Pulse oximeters and oscillometric or Doppler blood pressure monitoring are not effective in assessment during CPR due to movement and poor perfusion state.

Capnography, or measurement of CO2 in the breaths coming out of the patient, is monitored easily in a patient that is endotracheally intubated. ETCO2 measurement is the most reliable form of monitoring for effective compressions since the level of CO2 measured correlates to the level of perfusion the lungs are receiving, given there is no severe pulmonary pathology. ETCO2 levels higher than 10-15mmHg during CPR were observed to give a higher chance of return of spontaneous
circulation (ROSC). Upon ROSC, ETCO2 increases significantly as perfusion to the lungs is re-established, and can be used as an indicator of ROSC.

The electrocardiogram is also prone to motion artifacts during compressions, making any attempts at interpretation unreliable. The ECG is useful during the assessments in between compression cycles, guiding ALS therapy. Non-shockable rhythms such as asystole and pulseless electrical activity (PEA) require continued chest compressions and vasopressor therapy. Shockable rhythms such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (PVT) require defibrillation.

Drugs can be administered intravenously (IV) or intraosseously (IO) during CPR, and access should be established without interruption of compressions. Vasopressors, parasympatholytics, anti-arrhythmics, reversal agents, IV fluids, and alkalinizing agents are used in specific situations during CPR. Vasopressors are indicated for use in CPR when non-shockable rhythms (asystole or pulseless electrical activity) are diagnosed in between compression cycles to increase systemic vascular resistance and optimize perfusion through the reduced cardiac output. Adrenaline (epinephrine), an alpha-1, beta-1 and beta-2 adrenergic agonist causes vasoconstriction, and is given at a low dose (0.01mg/kg) initially, and at a high dose (0.1mg/kg) with prolonged duration of CPR. Vasopressin is an alternative that may be used in place of adrenaline at 0.8U/kg. Both vasopressors are given every other cycle of compressions due to its half-life.

Atropine has traditionally been given as an anticholinergic and a sympatholytic drug. There is minimal evidence indicating benefits of atropine administration during CPR, though there is also no evidence of harm. Atropine is given at 0.04mg/kg IV or IO at the initiation of CPR or as soon as IV or IO access is established, with redosing performed every other cycle of compressions. Atropine may be warranted in patients suspected to be with high vagal tone. Anti-arrhythmics may be useful in ventricular fibrillation (VF) that does not respond to electrical defibrillation. Amiodarone at 2.5-5mg/kg IV or IO is recommended, with lidocaine at 2mg/kg slow IV or IO being a secondary option. Reversal of any anaesthetic or analgesic drugs seems reasonable though clear evidence of better outcome has not been seen. Opioids can be reversed with naloxone (0.04mg/kg), benzodiazepines with flumazenil (0.01mg/kg), and alpha-2 agonists with atipamezole (0.1mg/kg) or yohimbine (0.1mg/kg), each IV or IO.

Intravenous fluids may be beneficial if the patient has known or suspected hypovolaemia to help restore intravenous volume and perfusion, but are unlikely to be of any benefit (and may even be detrimental) to those that are euvolaemic or hypervolaemic. Corticosteroid administration may have been traditionally performed, though evidence suggests more potential harm than benefits, discouraging its use. Sodium bicarbonate administration is considered in patients with prolonged CPA (10-15 minutes) to counter effects of metabolic acidosis that is likely to be present.

Electrical defibrillation is useful in patients with shockable ECG rhythms (VF and pulseless ventricular tachycardia) and has been associated with a higher rate of ROSC in these cases. Electrical defibrillation delivers an electrical shock to the heart "resetting" the myocytes and allowing them to resume a more orderly conduction and contraction pattern. Monophasic and biphasic defibrillators are available on the market. Biphasic models are recommended over monophasic because of the higher success rate and less damage caused by a lower current used. Defibrillation should be performed as soon as
possible when shockable rhythms are observed, but compressions should be resumed and continued until the defibrillator is fully charged. Otherwise, defibrillation should be performed in between compression cycles to minimize interruptions, provide circulation to the myocardium before the next shock, and allow for recharging of the defibrillator should repeated discharges be necessary.

## Post-Resuscitation Care

The survival to discharge rate of a patient that successfully achieves ROSC is quite low, reported to be 2-7%. The final outcome has a multitude of factors including underlying disease, the cause of CPA, and damage to tissues sustained during and after CPR. Post-resuscitative care is directed towards respiratory optimization performed through monitoring and providing adequate ventilation and oxygenation, haemodynamic support with IV fluids, vasopressors, and inotropes as indicated, and neuroprotective therapy consisting of seizure control, permissive hypothermia, and intracranial pressure control. Optimization of the respiratory, cardiovascular, and nervous systems allows the best chance for patient life to continue while the underlying disease is treated.

## Non-medical Aspects

Even when patients at risk of CPA are identified ahead of time and the team is prepared with the appropriate facilities to perform CPR, administration of CPR can be quite chaotic. The aim is to bring as much organization and order to the chaos as humanly possible. One of the biggest factors to keeping the order is the organization of a team. There are several roles to be established ahead of time in training for any one person to be comfortably able to fill all roles necessary. The roles needed are: CPR leader, compressor, ventilator, record keeper, drug handler, and the veterinarian. The CPR leader should be identified at the beginning of CPR, so assigning of subsequent tasks can begin immediately. Staffing permitting, the CPR lead should be freed from tasks aside from assigning and keeping the team organized. Compressor and ventilators provide the compression and ventilation, and may make sense to alternate with each other between compression cycles if staffing is limited. The record keeper should keep a detailed medical record during CPR, and this task is facilitated with a CPR record form. The drug handler will prepare and administer drugs in most cases. The veterinarian ideally is not fulfilling any of these roles, being able to focus on the patient and making judgments on whether CPR efforts should continue, decisions on drug administration, communication with the owners, and any medical interventions that are necessary for the patient.

Communication during CPR is also vital in organizing the effort and preventing mistakes. Closed-loop communication, performed through the person making a request addressing an individual clearly by name, the addressed individual repeating back their understanding of the request, the request being fulfilled being announced, and the requestor acknowledging the completion.

Keeping the communication loops closed each time may feel awkward if it is not used on a regular basis, but contributes to very organized communication allowing everyone on the scene to stay on the same page on the status of the CPR. Double checking each other on tasks being performed is also possible, preventing the preventable mistakes.

Debriefing is another form of communication that is hugely beneficial for the team, regardless of the outcome. After the conclusion of CPR, every member should participate in a 5-15 minute debriefing session discussing the CPR. The discussion will be led by the CPR lead, discussing the following points: