<figure><img src="image_27.png" /></figure>

Figure 1. Modes of action of immunostimulatory and immunoregulatory probiotics on the innate and adaptive immune system.

Most of the proposed benefits and **mechanisms of action of probiotics** are still directly or indirectly related to the GI tract, i.e. either through **interaction or competition with less beneficial luminal or adherent microorganisms** (competition for nutrients, binding of toxins, production of vitamins, antimicrobial peptide production, changes of the microenvironment), effects on **intestinal epithelial cells** (affecting barrier function, permeability, production of mucus and protective proteins, stimulation of innate immune receptors) or the **mucosal immune system**. The latter likely involves both modulating signalling pathways **of innate immune cells** (ie. macrophages [Mφ], dendritic cells [DCs]) and maturation of **adaptive immune cells** (ie. induction of a certain Th cell profile, class-switching of immunoglobulins [Ig] or strain-specific IgA production) (see figure 2). Through this, a systemic immune effect is also proposed.

The probiotic most commonly used in small animals, *Enterococcus (E.) faecium*, has undergone some *in vitro* testing of its properties: it adheres to human as well as canine intestinal mucus, produces lactic acid, and survives sufficiently in 1% bile (up to 98%) and at a pH of 3 for 3 hours (87%). Results of testing of the effect of *E.faecium* on immune parameters in dogs and cats are limited. It increased total faecal and serum IgA levels (but not IgG) in healthy puppies, increased lymphocyte counts in kittens and might influence some parameters of routine biochemistry in healthy adult dogs, but results of these studies are of unknown value in ill animals. Conditions in which probiotics have been tested in dogs & cats are summarised in the table below.
<figure><img src="image_28.png" /></figure>

Figure 2. Proposed mechanisms of action of probiotics on the intestinal epithelial cells and local mucosal immune system.

But what about critically ill patients? In people, recent data shows that critically ill patients undergo dysbiosis ("unbalancing" of the composition and richness of the microbiota) at several organ sites including the skin, GI tract and the lungs, with loss of microbial diversity and a propensity for potential pathogens to dominate. This appears to contribute to nosocomial infections, sepsis, multiple organ dysfunction syndrome and can even be predictive of poor outcomes. A role for probiotics in reducing the risk of infections in human ICU settings was initially described in 2012. Even before that, the use of probiotics has been advocated for antibiotic-induced diarrhoea or C. difficile colitis in people. Since then, most trials have focused on the role of reducing ventilator-associated pneumonia (VAP), where the role of probiotics remains controversial. A Cochrane review found a low quality of evidence that probiotic therapy is associated with reduction of VAP. However, two separate meta-analysis showed that probiotics continue to show a significant reduction in infections following critical illness. A trend toward a decrease in ICU length of stay was also observed. However, a wide range of probiotic species and doses was utilised, so no recommendations can be made for the dose or type, with the exception of *Saccharomyces boulardii*, which should not be used in human ICU patients.

The theoretical benefits from probiotics in the ICU (for both people and animals) are easy to see: protection from infection and sepsis through maintenance of epithelial barrier function, generation of nutritional support for the host epithelial cells, change of the metabolic transcriptional landscape, thereby editing of the local and systemic immune system, and inhibition of colonisation with harmful bacteria. The latter is mainly believed to be due to effects of short chain fatty acid fermentation, ie. either through a boost of β-oxydation in colonocytes, which promotes an hypoxic environment, or through the production of lactic acid, which reduces luminal pH in the colon.

A landmark trial in the benefit of probiotic and symbiotic therapy against sepsis in infants was recently published. This randomised double-blind, placebo-controlled trial of an oral symbiotic (*Lactobacillus plantarum* plus fructooligosaccharide) demonstrated a significant reduction in the primary outcome (sepsis and death) in children in a developing country.
In addition to probiotic use, faecal microbiota transplantation (FMT) has shown a more than 90% effectiveness in curing *C. difficile* colitis in people. This treatment is now increasingly considered for other critically ill patients, and a case report of successful treatment of refractory severe sepsis and diarrhoea with an FMT has been published recently.

However, prior to widespread implementation and large clinical trials of "dysbiosis" therapy, in the form of probiotics, synbiotics or FMT, a greater understanding and characterisation of the microbiome changes in the ICU using culture-independent, amplicon and metagenomics-based sequencing techniques are needed in broader ICU populations, both in human and veterinary medicine.

<table><thead><tr><td>Condition assessed</td><td>Probiotic used</td><td>Outcome/ results</td></tr></thead><tbody><tr><td>Parvoviral enteritis (D)</td><td>VSL#3 probiotic mix</td><td>90% survival vs. 70% in control group, faster recovery, faster leucocyte increase</td></tr><tr><td>Ancylostoma infection (D)</td><td>Mixture of LABs</td><td>Reduced egg shedding</td></tr><tr><td>Giardia sp. infection (D)</td><td>E. faecium SF68</td><td>No difference in cyst shedding, faecal antigen, faecal IgA or leucocyte phagocyte activity</td></tr><tr><td>Tritrichomonas foetus (C)</td><td>E. faecium NCIMB 10415 E1707 & FOS, butyrogenic</td><td>Faster recovery & improvement of faecal parameters</td></tr><tr><td>Feline herpes virus (C)</td><td>E. faecium SF68</td><td>No convincing clinical or immunological effect</td></tr><tr><td>Kennelling stress-associated diarrhoea (D&C)</td><td>E. faecium SF68<br>Bifidob. animalis AHC7<br>Metronidazole ± E.faecium NCIMB 10415 E1705</td><td>No effect<br>Improved faecal scores<br>Shorter duration of diarrhoea, larger proportion of normal faecal scores at day 7</td></tr><tr><td>AHDS (D)</td><td>Visbiome probiotic mix</td><td>Faster recovery, more beneficial microbiota profile, less C. perfringens toxins</td></tr><tr><td>Acute idiopathic "enteritis" (D)</td><td>Bifidob. animalis AHC7<br>Mixture of LABs</td><td>Shorter duration of clinical signs, less dogs treated with metronidazole<br>Shorter duration of clinical signs</td></tr><tr><td>Food responsive chronic enteropathy (D)</td><td>E. faecium NCIMB 10415 E1707<br>L. acidophilus & L. johnsonii</td><td>No effect on clinical activity score, histology score or gene expression<br>Reduction of IL-10 and IFNγ expression, but no clinical benefit</td></tr><tr><td>Idiopathic IBD (D)</td><td>VSL#3 probiotic mix</td><td>"As good as" a combination of prednisolone and metronidazole in reduction of CIBDAI, histology scores, lymphocytes in tissues. Marked increase in Tregs only in the treated group</td></tr><tr><td>IBD/ PLE (D)</td><td>Saccharomyces boulardii</td><td>Improvement of CIBDAI, increase in serum albumin, no difference in histology</td></tr><tr><td>Chronic constipation/ megacolon (C)</td><td>SLAB51 probiotic mix</td><td>Significant decrease in activity index, improved histology score (incl. increase in ICC)</td></tr></tbody></table>

Table. Selection of conditions in which probiotics have been assessed as treatment modality in dogs (D) and cats (C).
# REFRESHING GI PHYSIOLOGY: A JUICY STORY

Ingrid Borgmann; RVN, VTS (ECC)

I:nstaaa, The Netherlands

## The tube

The digestive tract of dogs and cats is formed as a long tube containing lips, oral cavity, pharynx, oesophagus, stomach, small and large intestines, rectum and anus. To perform the absorption of nutrients and fluids and the excretion of waste products it also includes the liver, gallbladder and pancreas.

In the digestive phase food is taken into the mouth using lips, teeth and tongue. The tongue and the buccinators, temporal and masseter muscles mix and move the food bolus. The rugae of the hard palate help directing the bolus towards the pharynx. Stimulation of the palate or touch receptors in the pharynx initiates the swallowing reflex. This reflex causes the epiglottis, the vocal cords and the soft palate to close, the upper oesophageal sphincter to relax and oesophageal peristalsis then takes the bolus through the cardiac sphincter into the stomach. The oesophagus, similarly to the other portions of the gut tube, is composed of two layers of muscle tissue, an outer longitudinal and an inner circular one. The lumen of the tube is dilated by a contraction of the longitudinal muscle. This is followed by a contraction of the circular muscle. The effect is a moving ring of luminal constriction, called peristalsis. The stomach stores the chyme, and, in the more distal part, mixes the content and performs some mechanical digestion. Bit by bit the chyme leaves the stomach through the pyloric sphincter. The luminal face of the small intestines is covered with fingerlike structures called villi. This one cell layer of enterocytes, covered with microvilli, mucus and glycocalyx, increases the surface area for absorption and secretion by tenfold or more. Segmentation, the nonpropulsive pattern of intestinal motility, mixes the content by a periodic, repeating pattern of constrictions. By short waves of peristalsis the ingesta are moved aborally to be worked on again by segmentation. Finally the ingesta enter the colon through the ileocecolocolic valve/ileocecal sphincter. The cecum has almost no function in cats and dogs. Faeces in the colon is moved not only by segmentation and peristalsis but also by retropulsion/antiperistalsis initiated by pacemakers, and by mass action contraction. By this simultaneous contraction of smooth muscle over a large part of the colon faeces is moved through the colon and into the rectum. When the anal sphincter allows it, faeces leaves the body.

## Regulation

In general, regulation of digestion is mediated by the autonomic nervous system. Stimulation of the parasympathetic part increases intestinal motility and tone, digestive secretion and relaxation of sphincters. Stimulation of the sympathetic part has the opposite effect. Also there are two main ganglionated plexuses in the GI tract, the myenteric/Auerbach plexus and the submucosal/Messner plexus, that are considered to be a third portion of the autonomic nervous system called the enteric nervous system. The GI hormones gastrin, secretin, cholecystokinin, motilin, gastric inhibitory polypeptide/glucose-dependent insulinotropic peptide play a role in e.g. gastric secretion, emptying of the gallbladder and gastric emptying. We should also note some negative feedback loops.
## The juices

Mastication, or chewing, would be difficult if the food bolus were dry. Therefore salivary glands, such as the parotid, mandibular and lingual glands, deliver mucus. But enzymatic digestion also starts with the salivary glands. Feline saliva contains just a little amylase, canine saliva somewhat more. Amylase breaks down starch into simpler carbohydrates. Some saliva, gastric and pancreatic fluids start to get produced at the smell or vision of food, or any sign that is learned to be a precursor of a meal by classical conditioning. As soon as food is taken into the mouth saliva production increases. When the oral mucus membrane is triggered pancreatic fluid starts to flow.

Peristalsis in the oesophagus stimulates the release of fluid in the stomach as does the arrival of the bolus in the stomach. Dogs and cats have a "true" stomach: one with enzyme production. Chief cells, located at the bottom of the pits of the parietal and pyloric stomach mucosa, produce inactive pepsinogen, a zymogen. The acidic environment triggers the transformation into active pepsin which is important in protein digestion. Mucous cells all over the stomach, and especially in the cardiac mucosa, produce mucus to lubricate the chyme and to buffer the stomach tissue against the low pH. Parietal cells, halfway down the stomach pits of the parietal mucosa, secrete hydrochloric acid (HCl) after stimulation by histamine, gastrin and acetylcholine. HCl helps to break down chyme and especially bacteria by virtue of its acidic nature. As a by-product of HCl production bicarbonate travels from the gastric cells into the bloodstream and raises blood pH. This is known as the alkaline tide. Gastrin is produced by G cells in the pyloric glands and the duodenum. Gastrin by itself and through production of histamine triggers parietal cells to increase HCl production. This works with a negative feedback loop after a certain point: the higher the blood pH and the lower the gastric pH, the lower the gastrin production.

Pancreatic cells are triggered by acetylcholine, cholecystokinin and secretin to secrete more than 10 different enzymes and proenzymes to the duodenum, including amylase, trypsin and lipase. In the luminal phase of digestion lipase breaks down fats, and trypsin divides proteins into amino acids. The hydrochloric acid from the stomach is being neutralized in the duodenum by sodium bicarbonate from the pancreas and in the bloodstream $H^+$ ions from the pancreas bring balance to the alkaline tide that was created by gastric acid secretion.

Lipids are already warmed and broken into smaller droplets in the stomach. They are further emulsified by bile acids. These are produced in the liver and stored in the gallbladder. The arrival of ingesta in the duodenum triggers the release of bile. Only after emulsification lipase can work together with other pancreatic enzymes to break down fat in the jejunum. In the enterocytes chylomicrons are formed of the lipids. Because these are too big to pass into the capillaries they are transported through the abdominal lymph and thoracic duct to empty into the vena cava. Nearly all bile acids are reabsorbed in the ileum and circulate back to the liver to be reused and suppress bile production (negative feedback loop).

On the luminal side of the enterocytes anchored enzymes are completing hydrolysis in the membranous phase of digestion and the final products of carbohydrate and protein digestion are absorbed into the underlying epithelial cells. Some proteins still need to be broken down into amino acids inside the enterocytes before they can enter the bloodstream.
A part of absorption is passive osmotic movement, but we also see co transport and active transport, aided by a pumping function of the villi. On the lateral side of the enterocytes, through “tight” junctions, water and electrolytes pass relatively free between the intestinal lumen and the intestinal capillaries.

All the blood from the GI tract, except from the distal colon and the rectum, travels through the enterohepatic/portal circulatory system. The absorbed nutrients are processed in the liver and released to the general circulation or back to the GI tract together with waste products from the liver, as the liver filters toxins and breaks down medication. The enterohepatic circulation is easily impaired because it works with a small pressure gradient.

In the colon a good amount of fluid is resorbed and certain vitamins are synthesised. Bacteria and funghi help enzymes to process the ingesta.

The last fluid to be added is from the anal glands. This fluid actually has no function in digestion, but rather in communication.

## References

1. Anatomy and Physiology for Veterinary Technicians and Nurses, Robin Sturtz and Lori Asprea, Wiley-Blackwell, 2012

2. Applied Pharmacology for Veterinary Technicians, Boyce P. Wanamaker and Kathy Lockett Massey, Elsevier Saunders, 2015

3. Cunningham's Textbook of Veterinary Physiology, Bradley G. Klein, Elsevier Saunders, 2013
# DEALING WITH DIFFICULT WOUNDS

Louise O'Dwyer MBA BSc(Hons) VTS(ECC) DipAVN(Medical&Surgical) RVN
Clinical Support Manager, Vets Now
louise.odwyer@vets-now.com

Non-healing, or difficult to heal wounds in veterinary practice rarely pose an immediate risk to life, however they can result in prolonged periods of veterinary care which can be very costly to the owner, uncomfortable and stressful for the patient, and potentially may result in euthanasia, or limb amputation in some cases.

There are numerous underlying causes of non-healing wounds and these can generally be divided into wound factors, patient factors and surgeon factors.

## WOUND FACTORS

### Wound aetiology

Traumatic wounds may be more difficult to heal, dependent on the amount of damage caused to the surrounding skin. Also, when dealing with shearing injuries to the lower limbs, it is not uncommon for exposed bone to be present. Exposed bone is often encountered in distal limb degloving wounds and inhibits wound contraction and epithelialization. When allowed to heal by second intention, a bed of granulation tissue is required for second-intention healing to progress. During the wound healing process the majority of exposed bone becomes covered with granulation tissue that arises from the viable periosteum or viable soft tissues adjacent to the bone surfaces, but there is always the risk of potential for osteomyelitis or sequestrum formation. One useful technique is to drill a number of small holes into the vascular medullary canal of the bone (forage), which will promote granulation tissue formation. This obviously needs to be done carefully, to ensure the bone is not weakened, resulting in fracture.

### Contamination

Wounds are commonly classed as clean, clean contaminated, contaminated and dirty. It is important to determine the wound type from this perspective order to plan wound management. Only clean or clean-contaminated wounds should be considered for closure, with all other wounds requiring at least a period of open wound management to convert them to a clean-contaminated state, whereby they may be considered for closure.

### Infection

When infection is present within a wound, this will cause inhibition of wound healing throughout all stages of the wound healing process. In order to identify infection a deep tissue culture should be obtained, this is preferable to a surface swab, as surface contaminants do not truly reflect infection. Infection is thought to be present in around 3% of all wounds at the time of suture removal, but infection rates are very variable, dependent on the degree of wound contamination. The aetiology of the wound also will affect the likelihood of infection occurring, with bite wounds having a high probability of infection due to the wound and its surrounding tissues creating the ideal environment for bacterial replication, along with poor drainage and a hypoxic environment. There are also surgical
causes of infection e.g. duration of the procedure, number of theatre staff, placement of surgical drains, suture material, underlying disease and the use of propofol, have all been associated with increased incidence in surgical site infections in veterinary patients. When faced with chronic wound infections, where a purulent discharge is present, a multimodal approach to dealing with infection is recommended. The following approach was recommended by Demetriou and Stein when dealing with wound infection:

* Investigate and address any underlying causes or contributing factors, e.g. malnutrition, anaemia, systemic disease;

* Maintain an 'open' wound environment, while fully exploring any pockets between soft tissue planes using an aseptic technique;

* Debride necrotic, devitalised tissue;

* Ensure thorough lavage of the affected areas with sterile isotonic fluids is performed;

* Obtain deep tissue samples for aerobic and anaerobic bacteriological culture and sensitivity testing;

* Commence empirical antibiotics (which can be changed according to culture results);

* Use bandaging to help with debridement (e.g., wet-to-dry bandages, or antimicrobial dressings);

* Continue open wound management until infection is controlled

## Wound location

Wounds over joints present a challenge to healing in that they are subject to tension, compression, or shearing forces. The desired result of wound healing is for the two sides of a wound to heal together. If they are exposed to these forces, however, healing is impaired. Wounds over extension surfaces of joints (e.g. carpus, stifle) are subject to tension when joint flexion pulls wound edges apart. Thus, meticulous closure is necessary. Casting or splinting the joint is necessary to prevent joint flexion for proper healing. Footpads are shock absorbing and spread as weight is applied. Thus, in the presence of an open wound, edges are pushed apart, impeding healing. If sutures are present in the pad, such pad spreading results in sutures tearing through the tissues. It is therefore necessary to relieve pressure on footpads to attain adequate healing, especially in large dogs. Various bandaging and splinting techniques have been evaluated as to their efficacy in reducing pressure on digital and metacarpal or metatarsal pads using various forms of foam rubber pads, metal splints, and combinations of these. Wounds in the axillary and inguinal areas may result from forelimb entrapment in a collar, vehicular trauma, burns, neoplasia, and infections. A primary factor in the impaired healing of such wounds is the shearing movement between the two wound surfaces as the animal ambulates. If such wounds have been present for a long period, it is possible that there may be infection with an atypical organism. Thus, a biopsy for culture and sensitivity testing is indicated. Techniques for closing such wounds have included meticulous closure and the use of skin fold flaps, omental pedicle flaps, axial pattern skin flaps, or combinations of these.

## Patient factors

Underlying disease can be considered from two viewpoints: disease arising due to the trauma that caused the wound to be sustained, and pre-existing concurrent disease. Trauma can cause a number of issues which will have a knock-on effect in respect to wound healing times including; shock, hypoperfusion, or dehydration, concurrent organ dysfunction, e.g. respiratory, renal, gastrointestinal
compromise/damage. Patients may also have a concurrent disease process that can hinder wound healing. Hyperadrenocorticism (Cushing's disease), diabetes mellitus, hypothyroidism, anaemia, are some of the disease processes, which can delay wound healing.

## Nutritional status

Adequate nutritional intake is vital for wound healing to occur, and should be a priority in all critical/ trauma patients. A catabolic state, attributable to malnutrition, is a major contributing factor to nonhealing wounds. In this condition, the body does not have the necessary protein and energy sources (fats and carbohydrates); therefore, existing stores of protein are broken down to maintain basal functions. This means, the increased calorific and protein demands for healing are not available, and the wound becomes quiescent. Glucose and protein are important for normal progression of wound healing. Glucose is the primary source of energy for leukocytes and fibroblasts. It is the integral molecule within the ground substance that is laid down by the fibroblasts. Deposition of this is necessary before collagen formation. Thus, glucose deficiency can affect collagen formation and wound strength. Depletion of protein stores can result in attenuated fibroplasia and prolonged healing time. It is vital that patients receive adequate protein levels, as they are necessary for animals undergoing healing. Sufficient protein levels help to prevent oedema and promote increased fibroplasia with increased wound strength. Vitamins may also affect wound healing. Excess vitamin A labilizes lysosomes to enhance inflammation. Because steroids stabilize lysosomes and inhibit wound repair, vitamin A can counteract this negative effect. Likewise, vitamin E stabilizes lysosomes similar to steroids and thus can inhibit healing in large doses. Again, vitamin A can reverse the effects of vitamin E. Vitamin C deficiency can impair healing in that it is necessary for the hydroxylation of proline and lysine in collagen synthesis. Although dogs and cats do not require exogenous sources of vitamin C, there is the possibility that the vital levels of ascorbic acid in the blood may decrease after trauma (i.e. wounding). Once all other factors affecting wound healing have been ruled out there could be an indication for vitamin C supplementation in these animals. Zinc deficiency can result in lack of replication of epithelial cells and fibroblasts, causing a weak wound and lack of epithelialization. At the other extreme, an elevated zinc concentration can inhibit macrophages, decrease phagocytosis, and interfere with collagen cross linking to have a negative effect on healing, and should be considered once other factors have been excluded. Ideally the patient's nutritional status on admission to the practice should be noted, including a Body Condition Score (BCS) and weight and this should be performed daily during the hospitalization period. If there is concern that the patient is unable to achieve its resting energy requirement (RER) alone, then assisted feeding techniques such as the placement of oesophagogostomy or gastrotomy tubes should be commenced. Many of these patients will require general anaesthesia as part of a wound management protocol, e.g. wound debridement, and so the opportunity for the placement of a feeding tube is likely to be available. For patients requiring sedation or anaesthesia over a prolonged period of time, nutritional status may also need to be addressed in terms of prolonged periods of starvation prior to anaesthesia, and in these cases the patient's calorific requirements should be calculated and compared against the actual calorie intake of the patient.

## Surgeon factors

The surgeon dealing with the wound management of the patient will ultimately have an effect on the likelihood of complications occurring. There are various issues that can be created during wound closure:
## Postoperative haemorrhage and haematomas

The presence of post-operative haemorrhage, or haematoma formation, may delay wound healing by putting pressure on suture lines, providing a rich environment for infection and cause discomfort to the patient, thus resulting in self-trauma. In addition to the indirect effect on wound tension, there is experimental evidence that postoperative haematoma formation can directly affect flap survival where reconstructive surgery has been performed. Adherence to Halstead's principles, including effective haemostasis, can help to prevent this. Minor incisional haemorrhage can be controlled with direct manual pressure for 10 to 15 minutes, but moderate to severe haemorrhage will require further intervention. Conservative management involving placement of pressure bandages, movement restriction and fluid deficit replacement can be instituted initially if the patient is stable. In more severe cases of haemorrhage, or those not responding to conservative management, surgical intervention may be required to identify the source and provide definitive haemostasis.

## Wound dehiscence

Dehiscence is defined as the breakdown of a surgically closed wound. Signs of a problem incision may be erythema, oedema or pain with signs of imminent wound dehiscence including necrosis of the skin edges, extensive cutaneous bruising, the presence of serum beneath the skin and serosanguinous discharge from the suture line. The most common causes of wound dehiscence include:

* Excessive tension

* Ischaemic or necrotic wound edges

* Inappropriate suture material or suture pattern selection

* Accumulation of moisture leading to tissue maceration

* Underlying pocket of infection, necrosis, foreign body or neoplasia

* Lack or inappropriate postoperative protection/support (e.g. bandage, Elizabethan collar)

* Premature suture removal

* Delayed healing caused by administration of corticosteroids and other agents

## Assessment of the small animal wound

The treatment of small animal wounds will commonly require a staged approach. Definitive treatment will often be delayed whilst emergency treatment of the patient and its wound, and initial stabilisation is performed. Analgesia and effective restraint is often required, until the animal is stable enough for sedation or GA. Wounds can be classified by their cause and the type of tissue damage caused: incisional, abrasion, avulsion (or degloving), shearing, puncture or perforated, and burns. Regardless of the aetiology of the wound, the factor which has the single biggest impact of future healing is the presence of contamination and necrotic tissue.

Once the patient is stable a more thorough evaluation may be carried out. Appropriate chemical restraint may be required for examination. Diagnostic imaging may be used to check for foreign material, penetrating injuries, associated fractures, dislocations and tendon or ligament damage. A management plan should take into account the wound's location, size, damage to local structures and the amount of tissue loss.

## Preparation and lavage

The aim of wound lavage (or irrigation) is to remove loose foreign material and necrotic tissue from the wound, while diluting the bacterial contamination present. In so doing, lavage aims to remove
impediments to wound healing, and reduce the risk of infection.

Variations exist in the technique employed for lavage, and in the choice of lavage fluid used.

However, some factors are agreed on:

* The greater the volume of lavage fluid, the lesser the risk of infection

* The more contaminated the wound, the greater the volume of fluid required

* Warmed fluids are more comfortable than room temperature fluids

* The earlier the wound is lavaged, the better the removal of bacteria

Lavage fluids are generally administered as a controlled jet directed over the wound surface. The pressure at which the fluid is applied is crucial to achieve the goal of removing impediments to healing; pressures need to be sufficient to dislodge debris and loose tissue, and overcome adhesive forces of bacteria, but excessive pressure will drive bacteria and debris deeper into the wound, and open up previously uncontaminated tissue planes.

Pressures of 8–12 pounds per square inch (psi) are strong enough to overcome adhesive forces of bacteria (Longmire et al, 1987). Pressures greater than 15 psi may cause wound trauma and drive bacteria deeper into wounds. Pressures lower than 4 psi are insufficient to remove surface contamination and bacteria.

In a practical situation, correct pressures can be achieved with a 20 or 30 ml syringe, and a 19 gauge needle or intravenous cannula, this provides an output pressure range of 11–31 psi, but the end pressure of the jet that reaches the wound is probably about 8 psi. The syringe can be rapidly refilled by incorporating a 3-way tap and a giving set attached to a bag of lavage fluids. An alternative technique which achieves similar pressures is to connect a fluid bag to a giving set with a 19 gauge intravenous (IV) cannula on the end, and squeeze the fluid bag with a pressure cuff or pressure bag inflated to 400 mmHg. The stream of lavage fluid should be directed at 45 degrees to the wound bed to maximise dislodgement of debris.

Other techniques such as lavage with bulb syringes, or manually squeezing punctured fluid bags deliver insufficient pressures and are not as effective at reducing infection.

In human medicine suggestions exist for the volume of lavage fluid deemed necessary based on the size of the presenting wound; volumes of 50–100 ml per centimetre of laceration or per square centimetre of wound have been suggested. In veterinary texts suggestions are made regarding the minimum volume per wound — 500 ml. Required volumes are likely to be higher in veterinary patients due to an increased risk of contamination from hair, environment and patient interference. As mentioned previously, the greater the amount of contamination, the greater the volume of lavage required.

## Choice of lavage fluid

Controversies exist in the choice of lavage solution, and whether antiseptics should be added to the solution. Solutions need to be non-toxic to tissues, reduce the number of microorganisms, not cause sensitivity reactions and be widely available and cost effective.
A lot of information in veterinary wound management is derived from human medicine, which in turn is often based on studies conducted on wound models in experimental animals.

However, whereas normal saline is used extensively in human wound lavage, and is seen as the 'standard' solution, most veterinary texts recommend Hartmann's solution (Lactated Ringers) as the wound lavage solution of choice. This choice seems to be based on a paper that described the effects of wound lavage solutions on canine fibroblasts in a Petri dish (in vitro). The cells were exposed to phosphate buffered saline, normal saline, tap water and Hartmann's solution, for time periods of between 30 seconds and 10 minutes. Tap water damaged the fibroblasts at all time intervals, and normal saline caused cytotoxic effects after 10 minutes. Neither phosphate buffered saline, nor Hartmann's caused any significant fibroblast injury. No clinical randomised veterinary study exists to confirm the significance of this finding on the healing and infection rates of acute wounds.

While both normal saline and Hartmann's are isotonic, and evidence suggests lavage should be carried out with a fluid that has similar osmotic pressure to that found in living cells, recent human literature has looked at the use of ordinary drinking water as an alternative lavage solution for acute wounds. Drinking water has the advantage of being readily available and cheap. A study on contaminated musculoskeletal animal wound models showed identical reduction in bacterial counts following lavage with identical volumes of normal saline and drinking water, even in open fractures. While studies in humans have shown no difference in infection rates or healing rates when comparing normal saline to drinking water in the lavage of acute wounds.

The addition of antiseptics to lavage fluid can have cytotoxic effects on important cells involved in healing, such as keratinocytes and fibroblasts. Hydrogen peroxide and povidone-iodine reduce proliferation and migration of fibroblasts in a dose-dependent fashion. Chlorhexadine and silver-containing antiseptics also reduce proliferation at high concentrations, but at lower concentrations they may actually enhance epithelial growth. If chlorhexadine is used in a wound, it should be used at low concentrations (a solution of 0.05%); used at this dilution chlorhexadine causes no significant difference in wound contraction or epithelialisation compared to sterile saline or Hartmann's in dogs, while achieving 100% bacterial kill rates against *Staphylococcus intermedius*, a common skin commensal bacteria.

The addition of antiseptics is often used in infected wounds; the aim of lavage is to reduce bacterial levels to a where the immune system can prevent critical colonisation or infection. Lavage of a 6 hour old wound with 9 litres of saline or tap water reduced bacterial counts to 71% of the pre-lavage levels in a contaminated wound model; in an infected wound these remaining levels of bacteria may exceed the critical bioburden and infection may ensue. The use of an antiseptic in the lavage fluid may lower residual bacterial counts by killing as well as diluting.

Addition of antibiotics to lavage solution is not recommended. Antibiotics may cause a sensitivity reaction in the patient, they are unlikely to maintain effective local levels for a suitable length of time, they are costly, and the pro-motion of resistance is a concern.

Soap or surfactants are commonly used in lavage of open fractures in human patients, where their use has been shown to reduce the complication rate compared with lavage with normal saline. Soaps have lipophilic components which block bacterial cell adhesion in a wound, so assisting their removal.
Soaps may also be of use in chronic wounds where they are more effective at re-moving adherent denatured proteins, such as dry fibrin and blood compared with saline or Hartmann's

## Aims of Debridement

Debridement is defined as the removal of damaged tissue or foreign material from a wound. Necrotic tissue will delay wound healing and increase the risk of wound breakdown by acting as a focus for infection. The presence of necrotic tissue also slows wound healing by obstructing re-epithelialisation and wound contraction.

One of the most important considerations in deciding whether, and when, to close a wound are the degree of contamination (bacterial and foreign material) and necrotic tissue present. Decreasing the presence of these impairments to wound healing will enable the reduction of the level of contamination and the presence of necrotic tissue to a point where the closure technique chosen can be safely carried out. This may not be possible in a single procedure; wounds that have extensive contamination and ischaemia may require repeated debridement, and the use of more than one debridement technique, before closure can be considered. The mainstays of debridement in acute wounds are surgical and mechanical debridement.

## Conclusion

In wound management, it is vital that veterinary staff have a good understanding of the processes in wound management, along with good knowledge of the actions of wound dressings, so that an appropriate dressing can be match for the specific stage of wound management, in order to optimise wound healing. Wound management is an ever-evolving field so it is essential that staff remain up to date on the novel technologies.

When dealing with a non-healing wound it is important to re-assess the patient, and consider the various factors that could be contributing to the problem, in order to create an effective and appropriate wound management plan.
IT IS AS EASY AS ABC: NURSING THE DOG WITH A GDV

Louise O'Dwyer MBA BSc(Hons) VTS(ECC) DipAVN(Medical&Surgical) RVN
Clinical Support Manager, Vets Now
louise.odwyer@vets-now.com

Introduction

Gastric dilatation and volvulus (GDV), commonly known as bloat, is an acute life threatening condition, which is characterized by the malposition of the stomach when it rapidly fills with air and rotates. Gastric dilatation (the expanding of the stomach) and gastric volvulus (the twisting of the stomach without expansion) can occur separately, however when they occur simultaneously the disease process to the body results in death if left untreated. Despite the first report of GDV in 1906, researchers have been unsuccessful in identifying a cause. Mortality rates range from 15-33%. While GDV can occur in many species (including cats and primates), deep chested and giant breed dogs are most commonly affected. Prompt recognition, rapid treatment and surgery are required to increase the chance of survival.

Risk Factor

Approximately 22% of giant breed dogs and 24% of large breed dogs will develop GDV in their lifetime.

The Great Dane has the highest incidence (42.4%). The other most common breeds affected breeds are the Weimaraner, Saint Bernard, Gordon setter, Irish setter and the standard poodle. As these breeds get older, the risk of developing GDV also increases.

Some behaviour studies have suggested that fearful or anxious dogs may have an increased risk to developing GDV. It is speculated that the gastrointestinal tract may be adversely affected during times of stress, especially in the fearful dogs, which may lead to an increase risk to developing GDV.

Though there is no exact cause for GDV, many proposed risk factors could contribute. Exercise after a large meal, especially a meal of highly processed food or water, may be a risk factor. Dogs that were fed only one type of food appear to have an increase in risk, while dogs that were fed table scraps or canned food appear to have a lower risk. Despite the myriad of reports suggesting that it is food related, there has not been one definitive report showing a link between GDV and the types of food. Dogs that are male, geriatric, eating only one meal a day, eating too quickly or having a raised food dish may all increase the risk to developing GDV. One published report showed that large breed dogs that ate quickly out of a raised food dish had a 20% increase in risk and giant breeds had an increase of 50%.

Dogs that have developed GDV have been found to have increased gastrin concentrations. Gastrin is a hormone produced in the stomach that increases the release of gastric juice. In digestion, gastrin constricts the pyloric sphincter, causes oesophageal spasming and slows the rate of gastric emptying. This can lead to aerophagia and decreases the chance of vomiting with gastric dilation. Other risk factors include a decrease in oesophageal sphincter tone, myoelectric dysfunction and dogs that experience a delay in gastric emptying.
## Pathophysiology

Most commonly the stomach rotates 90-270 degrees in a clockwise motion (viewed from behind). The fundus will generally shift to lie against the ventral abdominal wall while the pylorus will move along the ventral abdominal floor, eventually sitting dorsally and on the left side. This will cause the body of the stomach to shift right. Because the spleen is attached to the stomach by the gastroplenic ligaments and vessels, the spleen will also follow the stomach and will become displaced, if not twisted as well.

Both air and fluid become entrapped within the stomach causing it to become enlarged. The gas may have become trapped because of aerophagia, but it may also be formed from bacterial formation. As the stomach fills with air, the caudal vena cava becomes compressed, leading to a decrease in venous return from the heart. A distended stomach can cause up to a 75% decrease in arterial flow to the gastric mucosa. Depending on the degree of rotation of the stomach, a partial or complete blockage of the portal vein may also occur. This may cause the liver or pancreas to become ischaemic to some degree. With the rotation of the spleen it too may become ischaemic.

As mentioned typically the patient presenting with a GDV will be a large breed, deep chested dog; however, it is important not to make this your only guideline. GDV has been documented in smaller deep chested breeds such as Dachshunds or dogs prone to over-eating such as Spaniels and Labradors. It has also been seen in puppies that have over-eaten. It can also occur in cats and other species though it is less common.

## Pre-Surgical Treatment

Patients presenting with GDV usually have unmistakable signs. Signs include non-productive retching, abdominal distension, abdominal pain, anorexia and restlessness. The stomach may be tympanic. Most patients will present in shock.

Treatment of the shock is the first priority. Because the patient is in shock and usually has severe abdominal pain, intravenous (IV) catheter placement, IV fluid therapy and pain medication should be started before diagnostics. Two large-bore short peripheral catheters should be placed to maximize fluid resuscitation efforts. Short, large diameter catheters allow for higher fluid flow. Oxygen should be administered (generally given by flow-by) because many GDV patients are in respiratory distress due to the enlarged size of the stomach pressing on the diaphragm. All vitals and parameters should be monitored including pulse, respiration rate, blood pressure, mucous membrane colour and ECG. Many GDV patients experience ventricular arrhythmias.

Fluid resuscitation is performed in stages to end-point parameters of improved perfusion, normal heart rate and normal blood pressure. Isotonic replacement crystalloids (e.g. Hartmann's) are always administered with incremental doses.

The rapidly deteriorating hypovolaemic patient without significant haemorrhage can benefit from the infusion of hypertonic saline (4 ml/kg 7% solution) with synthetic colloid added in an effort to augment exogenous fluid infusion with interstitial fluid redistribution. As these patients are frequently large dogs, the use of hypertonic saline may enable rapid improvement of cardiovascular signs compared to isotonic crystalloids.
Analgesia should be administered immediately because it will, not only help alleviate the acute abdominal pain, but also it will help to reduce the stress for the patient.

Radiographs are not to be taken until fluids and temporary decompression has been initiated, unless euthanasia is an option over surgery. Radiographs should not delay surgical preparation. Abdominal x-rays are not performed routinely in our institution. Indication to go to surgery is given if orogastric decompression is not possible. However, if oral decompression is possible, a right lateral abdominal radiograph will show if a volvulus is present and will also indicate surgical treatment.

## Laboratory database

Obtaining pre-fluid blood samples for PCV/TS, electrolytes, venous gas, azostick and glucose, platelet count, activated clotting time, and saving samples for coagulation profile, serum chemistries, complete blood count and urinalysis are recommended.

Pre-fluid values provide a baseline from which subsequent values are compared to and monitored. In addition, any significant abnormalities are addressed prior to surgical intervention.

Any clinical evidence of coagulation abnormalities in addition to laboratory abnormalities requires appropriate treatment prior to surgery; frozen plasma if DIC or coagulation factor defect is suspected.

Initial bloodwork should be obtained prior to starting IV fluids (obtain blood at the same time catheters are placed) to ensure that values are those of initial presentation. With any patient suspected of ischaemic disease, a blood lactate level should be obtained. Lactate acid build-up occurs when the body is unable to perform aerobic metabolism. During the anerobic process, lactate will start to build up indicating a worsening of illness. During GDV, blood supply to the stomach is decreased if not completely stopped (an ischaemic event). This causes the body to switch to an anerobic process, thus causing a build-up of lactate. Blood lactate values under 2mmol/L are normal. In the case of gastric dilatation volvulus, levels greater than 6mmol/L are associated with increased gastric necrosis. In 1999 one study of 102 dogs with GDV found that only 58% of dogs survived with a blood lactate greater than 6mmol/L, while 99% of dogs survived with levels less than 6mmol/L. However a retrospective study showed this should not be a reason for euthanasia. The results of a second retrospective study in 2011 indicated that an initial presenting plasma lactate concentration >6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations >50% within 12 hours may be a good indicator for survival. Other bloodwork that should be run includes a complete blood count, packed cell volume, total protein, coagulation profile, serum chemistry profile and electrolytes. Though it seems excessive, it is important to know whether any pre-existing disease exists and how decompensated the patient is. Since all GDV patients require surgery it is equally important to make sure that all electrolyte or other blood work abnormalities be rectified before the animal is placed under general anaesthesia. Since disseminated intravascular coagulopathy (DIC) can occur whenever there is major change in the vascular system, all GDV patients are considered at risk, which is why it is important to check a coagulation profile.
## Decompression

Once GDV has been diagnosed and therapy for shock has been initiated, gastric decompression should be performed. Gastric decompression helps to improve cardiac output and blood pressure by alleviating pressure on the vena cava and portal vein. There are two methods that can be used to decompress the stomach: orogastric and gastrocentesis. Placement of an orogastric tube, which allows for the most decompression of the stomach. This method, however, generally causes more stress to the patient, and some patients may not tolerate it at all. A tube should be measured and marked from the point of the nose to the last rib. A roll of tape should be placed in the mouth just behind the incisors with someone shutting the animal's mouth on the roll. The tube is then advanced with slightly firm pressure and a twisting motion. Be careful not to apply too much force on the tube because you could cause an oesophageal or gastric tear. Once you are in the stomach, contents should flow out of the tube into a bucket below the patient. If an orogastric tube cannot be placed, then a gastrocentesis should be performed, or gastrocentesis may be performed initially since it is often quicker, to remove some of the gas from the stomach. Since GDV patients are prone to DIC, it is important to check coagulation factors prior to starting this procedure. A gastrocentesis is done by inserting a 14 to 18 gauge needle or over-the-needle catheter into the stomach. The patient should be lying in left lateral recumbency to allow for the gastrocentesis to take place on the right side. The area should be clipped and prepped. Once the gastrocentesis has been performed and air has been removed, orogastric decompression can be attempted again to remove more of the air and contents.

Prior to surgery, broad-spectrum antibiotics are usually given because of the risk of gastric necrosis and perforation.

## Lidocaine treatment

Lidocaine is used in our institution for various effects in a GDV patient. Lidocaine is an effective pain relieving substance, it is a viable option for treatment of ischaemic arrhythmias and it is potentially helpful in the prevention of reperfusion injuries.

## Blood pressure and ECG

Hypotension is usually present in the critical GDV patient. If significant haemorrhage and/or DIC are present, hypovolaemic resuscitation may be warranted until exploration. This entails careful endpoint resuscitation techniques using crystalloids and colloids/HBOC to a MAP of approximately 80 mmHg (systolic around 100 mmHg). The goal is to initiate some reperfusion without disturbing any clots that have formed until haemostasis is achieved surgically. A constant rate infusion (CRI) of hetastarch can be administered after resuscitation of the hypotensive animal at a rate of 0.8 ml/kg/hr to help maintain blood pressure until cardiovascularly stable.

Normal to increased blood pressures is assessed with respect to intravascular volume status. Adequate or increased blood pressure may be the result of a compensatory response to hypovolaemia, and aggressive fluid resuscitation is still indicated.

Any auscultable or ECG arrhythmia should be treated with oxygen therapy. Any acid-base and electrolyte (potassium, calcium and magnesium) abnormalities should be corrected. When improvement of perfusion does not occur, antiarrhythmics are administered. The most common
arrhythmia treated is a ventricular tachycardia, and lidocaine is administered IV up to 4 mg/kg slow bolus. If this improves the rhythm, then a 50 mcg/kg/min CRI is started. Constant ECG is required.

If the blood pressure is not responsive to fluid resuscitation, dobutamine infusion (5-10 mcg/kg/min) may be required and underlying causes of nonresponsive shock investigated. Dopamine infusion (5-15 mcg/kg/min) may also be necessary. Clinical experience has shown, that animals in need of catecholamines to maintain blood pressure have decreased survival rates compared to animals that do not need catecholamines.

## Oxygenation

As a result of circulatory compromise these patients may present hypoxic and also due to low blood pressure/poor perfusion have reduced tissue oxygen delivery, therefore increasing the fraction of inspired oxygen (FiO2) will be beneficial.

Flow-by techniques are often used during the initial stages but this, particularly for larger patients, is usually only a short-term option. A useful technique is the placement of nasal oxygen catheters, which can be utilised both pre- and post-surgery. Humidification of the oxygen is important if using nasal oxygen catheters for a period of longer than 3-4hrs since this technique will bypass a portion of the patient's upper airway. GDV patients will frequently have compromised ventilation due to the over-distension of the stomach. Sternal recumbency offers the best opportunity for a patient to ventilate itself properly BUT these patients are normally extremely uncomfortable and should be allowed to assume the position most comfortable for them.

## Intraoperative/Anaesthesia considerations

Pre-anaesthetic protocols vary and the individual patient should be assessed to determine what is appropriate. Phenothiazine tranquilizers (acepromazine) usually avoided as they can cause vasodilation and hypotension. Ideally, a benzodiazepine (diazepam) should be included in the pre-anaesthetic protocol because it serves as a muscle relaxant and can help reduce anxiety by slowing down the central nervous system. Other pre-anaesthetic drugs include: fentanyl and alfaxan or propofol. Propofol can cause vasodilation and respiratory distress and should be limited to those animals that have been stabilized. Once intubated, the patient should be monitored very closely, which should include ECG, blood pressure, pulse oximetry and capnography. Mechanical ventilation may be required in order to maintain adequate oxygenation.

It is imperative that intraoperative blood pressure be maintained at a mean arterial pressure of 80 mmHg. 'Surgical rate' fluids generally include using a crystalloid at 5-10ml/kg/hr. Using a CRI of analgesics may allow for a decrease in inhalant anaesthesia and help increase blood pressure. However, because some medications can cause respiratory depression it is important to have mechanical or assisted ventilation ready if needed. If the patient is hypovolaemic despite efforts (be sure that the patient is on an appropriate plane of anaesthesia), vasoactive medications should be started. Commonly dobutamine (5-20mcg/kg/min) and/or dopamine (5-10mcg/kg/min) are administered as a CRI to help improve cardiac contractility. If inotropic support alone does not improve blood pressure, then a pressor agent such as noradrenaline (at 0.05-0.4 mcg/kg/min) can be used.
## Post-Operative considerations

Continuous or intermittent monitoring of the vital signs will detect development of hypotension and/or dysrhythmias that may require immediate therapy. Monitoring PCV/TS, glucose, BUN, albumin, electrolytes, acid/base status, and lactate levels may uncover organ decompensation. Intravenous analgesia and antibiotic administration is continued until oral feedings and medications are tolerated. The use of promotility agents such as metoclopramide and cisapride may improve gastric emptying more rapidly than without. Supplemental oxygen therapy is also recommended in the post-operative period.

Maintaining gastric decompression post operatively is recommended in the critical GDV patient. Gastrostomy tube placement allows large volume decompression and removal of large clots that can occur with large resections. Nasogastric tubes are appropriate when gastric resection is not required. Nasogastric tubes are preferably placed intraoperatively with proper placement assured by palpation. Small volume infusion of electrolyte/glucose/glycine containing fluids feeds the gastric mucosal cells, which rely on intraluminal contents for nutrition. Placed appropriately, intestinal feeding tubes provide immediate intestinal feeding postoperatively. It allows home care if gastric feeding is not possible once the animal is ready to be discharged. It also reduces the cost of parenteral nutrition because caloric requirements can usually be supplied within a few days.

Monitoring nasogastric tube suction volumes assists in more accurately determining volumes lost. When suction volumes decrease, this may indicate when refeeding may be initiated. Infusion of a balanced electrolyte/carbohydrate solution promotes gastric mucosal healing and feeding. Regular assessment of the patient's abdomen size is also recommended to assess for rebloating.

GDV patients can be particularly challenging and require intensive nursing care but it is these aspects of their care which make a successful outcome so rewarding.

The GDV patient is one of the most challenging but perhaps the most rewarding patient to Nurse. By close observation and monitoring, good communication with the Veterinary Surgeon and taking the time to give TLC, all of the things that make us veterinary nurses we can have a really positive impact on the outcome of these cases.

## References are available upon request
HOW TO INTERPRET BLOOD GAS

Lindsey Dodd BSc(Hons) VPAC PgCert in HE FHEA VTS(ECC) RVN

Lumbry Park Veterinary Specialists, Hampshire, UK

Handheld analysers are allowing blood gas analysis to become more common place in veterinary Emergency and Critical Care. Blood gas analysis allows acid-base and respiratory function; oxygenation and respiration, to be interpreted.

The regulatory systems; chemical buffering, most importantly bicarbonate maintain homeostasis as well as active regulation from the lungs and kidneys in response to changes in the blood gases and acid-base status to alter hydrogen ion concentration. The functions of all body systems are affected by changes in the concentration of hydrogen ions and are regulated and maintained within narrow limits. pH is the measurement of the concentration of hydrogen ions. The concentration of hydrogen ions is the result of acid-base balance. Hydrogen ion concentration has an inverse relationship with pH; an increase in hydrogen ions, an acidaemia equals a lower pH (pH < 7.35), and a decrease in hydrogen ions, an alkalemia equals a higher pH (pH > 7.45).

The bicarbonate buffering system is expressed by the Henderson-Hasselbalch equation:

$$CO_2 + H_2O \leftrightarrow H_2CO_3 \leftrightarrow H^+ + HCO_3^-$$

which shows that pH (the concentration of hydrogen ions) corresponds to the amount of bicarbonate (HCO₃⁻) and to the partial pressure of carbon dioxide (PCO2). Therefore, acidaemia (a low pH < 7.35) could be due to a decrease in bicarbonate, an increase PCO2 or both and alkalaemia (a high pH > 7.45) could be due to an increase in bicarbonate, a decrease in PCO2 or both.

The body's buffering system acts very quickly resisting changes in hydrogen ion concentration using bicarbonate, phosphate and plasma proteins to keep pH within normal limits, between 7.35 – 7.45. When required active regulation of acid-base balance will be compensated by the lungs and kidneys. For example, an increase in hydrogen ions (by ingestion or an increase in metabolic production) will create a decrease in blood pH (< 7.35), an acidosis. A decrease in pH will stimulate an increased rate and depth of breathing, which will increase the pulmonary removal of carbon dioxide (CO2); effectively 'breathing off' excess CO2 (acid). Respiratory compensation is rapid. The kidneys react to compensate differently depending on if the patient has acidosis or alkalosis. During acidosis the kidneys will excrete excess hydrogen ions and produce bicarbonate (HCO₃⁻) to try to reduce the acidity. During alkalosis they will excrete bicarbonate (HCO₃⁻) to remove excess base (bicarbonate). Compensation from the lungs and kidneys will not return the pH to within normal limits but will aim to return the pH towards normal limits; important to remember when reading blood gases as over compensation does not occur.

Sampling

Arterial blood is often preferred for blood gas analysis however there are instances when a venous sample will also be useful. It is important to remember there will be differences in PCO2; blood pH, between arterial and venous blood samples in the critical or emergent patient. Therefore, it is important to recognise when arterial vs venous blood is collected. Generally arterial blood is collected from the dorsal pedal artery or the femoral artery using a commercially available blood gas syringe
pre filled with anticoagulant (heparin powder), with an air dispenser and air tight bung to reduce potential sampling errors. The area is clipped and prepared prior to sampling; ensure the area is not scrubbed, instead wiped to avoid spasm of the vessel which may reduce blood flow. Blood should be collected over several respiratory cycles. Once blood is collected any visible air should be dispelled from the syringe and a cap placed immediately. The patient will require pressure to be put over the arterial sampling site and may require a firm bandage to be placed following sampling; ensure tight bandages are not left in place for longer than 5 mins and monitor to ensure a haematoma has not formed. Samples should be run as quickly as possible but can be placed on ice if required for approximately 10 mins. Before running the sample the first few drops of blood should be discarded before immediately filling the blood gas analyser cartridge to the required amount.

## Sampling errors

- A clotted sample – using a syringe without coagulant

- A sample exposed to air either left within the syringe or following sampling being left without a cap or not run promptly

- A mixed venous sample collected mistaken for arterial blood; arterial blood tends to pulsate into the syringe when collected rather than needing to draw back on the sampling syringe

## Respiratory vs metabolic acid-base disorders

Acid-base disorders are either respiratory or metabolic and may be one of four primary disorders: respiratory acidosis (an increase in PCO2, a decrease in pH < 7.35), respiratory alkalosis (a decrease in PCO2, an increase in pH > 7.45), metabolic acidosis (a decrease in $HCO_3^-$, a decrease in pH < 7.35) and metabolic alkalosis (an increase in $HCO_3^-$, an increase in pH > 7.45). In primary acid-base disorders there is the required amount of compensation in the opposite system; lungs vs kidneys.

## Mixed disorders

When there is both a respiratory and a metabolic acid-base disorder a mixed disorder is present; the required amount of compensation is not happening in the patient between the lungs and the kidneys.

## Reading a blood gas

1. Evaluate the PaO2 (the partial pressure of oxygen in the blood. The ideal value can be approximated by multiplying FiO2 (fraction of inspired oxygen) by 5, e.g. if the FiO2 = 21%, then ideally PaO2 = 100mmHg) from arterial samples only – check: is the patient hypoxaemic?

2. Evaluate the pH (concentration of hydrogen ions) – check: is the blood pH within normal limits (between 7.35 – 7.45), acidotic (< 7.35), alkalotic (>7.45)?

3. Evaluate the PaCO2 (the partial pressure of carbon dioxide in the blood)- check: does it support the pH findings? Yes- primarily respiratory, No- not primarily respiratory.

4. Evaluate the $HCO_3^-$ (bicarbonate)- check: does it support the pH findings? Yes- primarily metabolic, No- not primarily metabolic.

5. Evaluate the parameter NOT responsible for the abnormal condition to assess for compensation. (Base excess (BE) gives an indication of the metabolic component of acid-base disturbances and is generally unaffected by changes in the PaCO2 - therefore if the base excess is not normal then it is a primary metabolic disorder).
Reference range

<table><tr><td>pH</td><td>7.351 – 7.463</td></tr><tr><td>PaCO<sub>2</sub> mmHg</td><td>31 -43</td></tr><tr><td>HCO3- mmol/L</td><td>18.8 – 25.6</td></tr><tr><td>Base excess</td><td>-3 to 0</td></tr></table>

Examples

<table><tr><td>pH</td><td>7.058</td><td>pH</td><td>7.240</td><td>pH</td><td>7.485</td></tr><tr><td>PaCO<sub>2</sub> (mmHg)</td><td>105.6</td><td>PaCO<sub>2</sub> (mmHg)</td><td>18.9</td><td>PaCO<sub>2</sub> (mmHg)</td><td>48.4</td></tr><tr><td>HCO3- (mmol/L)</td><td>28.5</td><td>HCO3- (mmol/L)</td><td>7.2</td><td>HCO3- (mmol/L)</td><td>34.8</td></tr><tr><td>Base excess</td><td>-4</td><td>Base Excess</td><td>19</td><td>Base excess</td><td>11.2</td></tr></table>

References and further reading

1. DiBartola, SP. 2012. Metabolic acid-base disorders. In: DiBartola, SP. ed. Fluid, Electrolyte and Acid-Base Disorders in Small Animal Practice. 4th edition. Elsevier Sauders, St Louis. pp.253-286.

2. Hooper, K J. 2019. Acid-Base Disorders. In: Drobatz, K. J., et al. ed. Textbook of Small Animal Emergency Medicine. Hoboken, NJ: Wiley Blackwell. pp.683-689.
PERSONAL HYGIENE: NEW CHALLENGES WITH RESISTANT BACTERIA

Andreas Kuntz

Multi-resistant bacteria, antibiotic therapy, hand wash, hand disinfection, gloves, wound infection, are all things we deal with on a daily basis.

In the news, there are reports of cases of severe infection in patients in human medicine. In our clinics, we deal with antibiotics every day, we wash our hands several times every day, how often do we disinfect our hands per day? When we disinfect our hands, how do we do it?

Do you wear gloves? If wound infections are a common problem in our clinic, do we talk about it?

Are multi-resistant bacteria in human medicine a problem for us in vet medicine? We will discuss in this lecture which bacteria in human medicine are multi-resistant and if they are a risk for us in the veterinarian world. Furthermore, we will have a look, how those bacteria find their way from a human clinic into your clinic.

Numbers from the CDC (Center for Disease Control, US) will show us, how dangerous they really are. We will also discuss preventive strategies and how bacteria develop a resistance and what we can do in our everyday work, to prevent that.

We will also discuss hygiene guidelines, and explore the advantages and disadvantages of hand washing and hand disinfection, including prevention of bacteria colonisation in our body, and prevention of skin problems, such as dermatitis.

A copy of the power points from this lecture will be disseminated to all delegate e-mail addresses after the Congress
# ANTIBIOTIC STEWARDSHIP: TIME FOR REAL INFECTION CONTROL

Louise O'Dwyer MBA BSc(Hons) VTS(ECC) DipAVN(Medical&Surgical) RVN
Clinical Support Manager, Vets Now
[louise.odwyer@vets-now.com](mailto:louise.odwyer@vets-now.com)

Whenever prescribing antibiotics, ideally their selection should be based on results of culture and MIC susceptibility. The minimum inhibitory concentration (MIC) is the concentration of a particular antibiotic that prevents visible growth of the bacteria in question after incubation for up to 18 hours. Bacteria are considered to be susceptible if growth is inhibited with ½ the average clinically obtainable blood concentration of the drug (or ¼ peak plasma concentration). In cases where antibiotics must be administered before culture results are obtained &/or are given empirically, it is imperative to identify the following: 1) if the patient has a treatable microbial infection; 2) location of infection; 3) identification of most likely pathogens; 4) identification of antibiotics most likely to be effective; 5) determining the appropriate route of administration; and 6) determining treatment length. If at all possible a sample of the infected material should be obtained and gram stained. This will give a minimum database of information to guide antibiotic selection. Then the antibiotic should be selected based on the knowledge of the most likely pathogen present and usual antibiotic susceptibility patterns.

Antibiotic resistance can develop in most bacterial lines by one of two mechanisms, being either chromosomal or plasmid mediated. If antibiotics are improperly dosed or given for inappropriate lengths of time then conditions favorable for these chromosomal mutations are provided. Underdosing antibiotics in either fashion kills off the susceptible bacteria and leaves the resistant ones intact, offering them a survival advantage. These resistant bacterial strains, usually present in low numbers, can now propagate freely, creating a stronger, more resistant strain.

## Hospital Acquired Infections

Hospital-acquired infections are defined as infections that were not present or incubating at the time of hospital admission. Typically, these infections develop more than 48 hours after admission due to the incubation period of most hospital-acquired pathogens. As a general rule, infections are considered hospital-acquired if they develop within 30 days of hospitalization (1 year if an implant placed).

There is a vast and rapidly growing body of knowledge pertaining to hospital-acquired infections in human medicine. The veterinary literature is much more limited and consists mostly of reports describing epidemic outbreaks from isolated sources within the hospital. Little is known about the role that patient colonization and patient to patient transmission plays in veterinary hospital-acquired infections.

## Epidemic Vs Endemic Infections

Epidemic infections represent those infections that develop due to contamination of a point source. It is estimated that these epidemic outbreaks represent less than 2% of all hospital-acquired infections in people. The remaining 98% of infections represent what are referred to as endemic infections. These infections occur continuously over time and come from multiple sources. Some endemic
infections are not preventable and represent the minimal failure rate for certain procedures. For example, no matter how meticulous the surgical technique a small number of surgical patients will always develop surgical site infections. Other endemic infections occur as a result of preventable causes such as poor technique during intravenous or urinary catheter placement or inappropriate perioperative antimicrobial prophylaxis.

## Pathogenesis

Most epidemic outbreaks result from contamination or colonization of a point source. The contaminated source then spreads the organism to patients where it causes infections. These outbreaks can be investigated using well described epidemiologic methods in an effort to identify the point source.

Endemic infections typically begin with bacterial colonization of critically ill patients. Critical illness, particularly when combined with antimicrobial therapy, acts to alter the normal host flora. The flora of the oropharynx, gastrointestinal tract, and occasionally the skin is replaced by potential pathogens. This patient colonization represents the major reservoir for nosocomial pathogens within the ICU environment. Microorganisms are transferred from patient to patient either through direct contact or transient contamination of the environment or hospital personnel. The environment does not typically represent a long term reservoir for microbial growth, but is instead repeatedly contaminated by colonized patients.

The high level of antimicrobial use in ICU patients predisposes to the evolution of antimicrobial resistant microorganisms. Infection with these organisms is associated with increased morbidity and mortality in numerous human studies. Numerous strategies have been proposed to limit the development of antimicrobial resistance including limiting antibiotic use, rotation of antibiotic choices, and reserving specific drugs for the treatment of hospital-acquired infections.

## Prevention of Hospital Acquired Infections

Most hospital-acquired infection fall into one of the following categories: 1) pneumonia 2) surgical site infections 3) catheter related infections and 4) urinary tract infections. Since these four categories represent the vast majority of infections most prevention measures are focused towards them. The most important step in preventing hospital-acquired infections is the prevention of colonization. It is believed that the veterinary staff represents the major source of this transmission. Hand washing between patient contact is the single most important preventative measure. Glove wearing augments this effect but does not replace the need to wash hands.

## Pneumonia

Hospital-acquired pneumonias represent the second most common hospital-acquired infection in people but account for almost 50% of mortality. As a result, much effort has been focused on their prevention and treatment. Numerous potential risk factors have been identified including intubation, positive pressure ventilation, neurologic injury/surgery, use of H₂ blockers, NG tube placement, propofol use, and sedation.

Many of these risk factors represent breaches in the normal defense mechanisms that are designed to prevent aspiration of potentially infectious material. Such breaches, especially when combined with
colonization of the oropharynx by pathogenic bacteria, greatly increase the risk of gross or micro-aspiration either of which can lead to the development of pneumonia.

## Surgical site infections

Surgical site infections (SSI) are probably the best studied of the veterinary hospital-acquired infections. A combination of duration of anaesthesia, degree of wound contamination, proper surgical technique, and appropriate antimicrobial prophylaxis represent the most significant risk factors. Of these, duration of anaesthesia and degree of wound contamination are probably the most important. Lengths of anaesthesia greater the 90-120 minutes are associated with significantly higher SSI rates. Appropriate antimicrobial prophylaxis involves administration of antibiotics so that they have peak blood levels at the time of the first incision. This requires that the antibiotics be given 45 minutes prior to the start of surgery (not anaesthesia). Antibiotics should be re-dosed every 90 mins. Continuation of prophylaxis for more than 24 hours in wounds that are not infected is not associated with a lower rate of SSI.

One of the most effective controls of SSI in humans has been found to be prospective surveillance to determine the rate of SSI for the surgery department as a whole and reporting of individual surgeon SSI rates to each surgeon. This necessitates a high degree of confidentiality since each surgeon should be supplied with his/her SSI rate as well as the department's SSI rate without being informed of other surgeons' SSI rates. This approach is thought to encourage self policing by the surgical staff, but should not be viewed as a witch hunt. It should always be remembered that surgeon who routinely fixes open fractures will have a higher SSI rate than one who does mainly spays and neuters.

## Intravenous catheter-related infection

Catheter related infections (CRI) are thought to occur most frequently due to catheter contamination at the time of placement. They may also occur due to migration of bacteria along the catheter or from contamination of the catheter tip by systemic bacteraemia. The vast majority of these cases resolve spontaneously upon catheter removal. True catheter related blood stream infections are thought to be rare in veterinary medicine. Prevention of CRI should focus on appropriate catheter placement and maintenance. Unfortunately, there is little research into the best way to place and manage intravenous catheters in veterinary patients.

## Urinary tract infections

Urinary tract infections (UTI) are the most common hospital-acquired infection in people, but they are associated with the least morbidity and mortality. It is important to distinguish between colonization and contamination when making the diagnosis of UTI. Intermittent catheterization has been shown to be superior to indwelling catheters in people but no studies have examined this in veterinary patients.

Control of UTI should focus on minimisation of urinary catheter use, and adherence to sterile technique during placement and maintenance. Antimicrobial prophylaxis does not prevent the development of UTI but rather guarantees that the infection will be resistant to the antimicrobial employed and should be avoided.

## Treatment of Hospital Acquired Infections
Treatment of hospital-acquired infections requires a knowledge of the antimicrobial resistance pattern of the likely pathogens. Such resistance patterns are highly hospital specific and result from the individual hospital's antibiotic choices and the intensity of antibiotic use. A review of several months culture may aid in the appreciation of resistance patterns. Suspected cases of hospital-acquired infections should be treated with an appropriate antimicrobial. This should be continued until culture results are available and antimicrobial therapy can be further refined.
# VASCULAR ACCESS: PLACEMENT AND USE WITH LESS SIDE-EFFECTS

Andreas Kuntz

Placing peripheral IV access catheters is a standard daily procedure in every vet clinic and performed by veterinarians and nurses/ technicians. In some cases, an IV catheter (IVC) can stay remain in place for up to 3 days, in other cases, the catheter site shows signs of inflammation after a few hours and should be replaced quickly.

What is the reason for this inflammation? Is it the catheter itself, the way of placing it, the medication? Let us have a closer look and let us experience this lecture we will discuss what we can do to increase the indwelling time of an IVC in our patients. If we can increase the indwelling time, we can reduce stress for our patients, stress for ourselves and we can save money for the IVCs reduce the amount of materials used in each case.

The most common reason to remove the IVC is the development of a phlebitis or a thrombophlebitis.

The phlebitis is an inflammation of the veins intima and has three causes - bacterial, mechanical and chemical.

A bacterial phlebitis refers to the non-intended or accidental introduction of infectious material like bacteria or their toxins and by-products. In this case, pathogens can directly reach the systemic circulation and cause catheter-related blood stream infections.

Mechanical phlebitis is the phlebitis that involves the IVC directly. Depending on the catheter material and the relation between the catheter's diameter and the diameter of the vein, a mechanical phlebitis is more or less likely. A mechanical phlebitis develops if the catheter touches the intima of the vein.

Chemical phlebitis is caused by an insufficient insertion site for the medication that needs to be administered.

Osmolarity of the medication and the pH value indicates to us whether a distal or proximal vein should be used - to avoid chemical phlebitis.

During the lecture, we will take a closer look into this topic and will focus on handling techniques to avoid complications and to have an enable IVC placement for longer periods.

A copy of power points for this lecture will be disseminated to all delegate e-mail addresses after the Congress
# HOW TO MANAGE THE CONTAGIOUS PATIENT: A DEMONSTRATION

Ingrid Borgmann; RVN, VTS (ECC)

I:nstaaa, The Netherlands

A chain is only as strong as its weakest link. This is also true regarding hygiene in veterinary hospitals, somebody once said. A veterinary hospital is a complex work field and a balanced range of protocols is necessary. Quite often the weakest link is you. Something done unaware can transfer a disease. To be aware of the risks is the start of a mental and physical training to prevent zoonosis and nosocomial infections. A zoonosis means a disease that passes from an animal to a human and/or vice versa. A nosocomial disease is one that is not present when a patient enters a hospital. It is hospital acquired.

So the goal of good hygiene protocols is multiple: to prevent spreading of a disease from one of your patients to you; to prevent a weak patient getting even more ill from something you carry with you; to prevent one patient catching something from another patient directly, via you or the hospital environment. Also you do not want to take some disease home to your own animals or your family. Think about rabies, Bartonella henselae, infections from bite wounds, leptospirosis, dermatomycosis, worm infections, MRSP, MRSA, tetanus, parvovirus, Coxiella Burnetii, psittacosis, giardia, kennel cough, feline herpes virus and a lot more. To prevent transmission you obviously need to know how these diseases are transferred. And this is as diverse as the diseases themselves. Transfers can happen through a scratch, via bodily fluids, through aerosol transmission or via skin contact. Some are spread via fomites, objects that are contaminated for different lengths of time. A study examining the white coats of 100 medical students found bacterial contamination on all coats. Other studies suggest you should clean your stethoscope, cell phone, computer keyboards and touchscreens better. Bedding and environmental surfaces, as well as medical devices such as blood pressure cuffs, can serve as fomites. Some bacteria form a biofilm that gives them a good degree of protection against antimicrobial agents. These biofilms are found on medical devices such as central venous catheters, indwelling urinary catheters and endotracheal tubes. Often colonization occurs within 3 days of placement. This is just one of the reasons why the longer the stay in hospital the greater the risk of a nosocomial infection. The severity of the underlying disease state plays a role in infection and mortality, and also the use of antibiotics prior to and during hospitalization, as well as the use of corticosteroids and chemotherapy. That is why our patients in the ICU are at greater risk. Prophylactic intravenous catheter changes every 3 days do not decrease the incidence of catheter-related colonization or bacteraemia in humans. It is advised to inspect and clean the catheter site regularly. The same policy applies to urinary catheters, especially in female dogs and cats. A closed collection system is not only better at reducing the risk of an ascending urinary tract infection, but it also decreases the risk of spreading a possible infection from the urine, e.g. leptospirosis.

Most important in infection control is still hand hygiene. Hand-washing reduces bacterial numbers by 50%, the proper use of alcohol-based disinfectants is even more effective with a reduction of bacterial numbers by 88%. Take care when smearing the disinfectant and be patient while it dries. Nail polish does not seem to increase bacterial counts. But your nails should be kept short, no longer than 2 mm. Some hospitals adopt a "bare below the elbows" policy to avoid rings, wrist watches or long sleeves to serve as fomites.
Some of the hygiene protocols should be observed with every patient. Studies examining animals for methicillin-resistant staphylococci found that animals may have an infection, or be colonized at one point and might clear the organism on their own, or only be contaminated. So there could be more to it than meets the eye. Caring for a possibly contagious patient starts before the patient enters the clinic. Do you have a designated examination room for these patients? Can you minimise the route of this patient through your facility? Can you minimise the staff involved? Can you minimise the stuff that might get contaminated?

Once a specific contagious disease is determined a barrier nursing plan should be chosen. Whether you need eye protection, a gown or a mouth mask depends on the expected route of transmission. Which kind or gloves are advised? If chemotherapy is involved you might have special orange medical grade gloves in your hospital. If not, make sure to use nitrile ones as they give better protection against chemicals than latex gloves. Barrier nursing has an important role in reducing zoonosis and nosocomial infections. But a gloved hand can still spread a disease throughout the hospital. Make sure that you shed your gloves and gowns inside out and leave them in the isolation area. Train your body and mind to be aware of possible transmissions. When you first started in theatre did it not cost quite some concentration to keep sterility? Get everything you need –and not more- together before you cross into isolation. Try to plan treatments carefully, if possible at the end of shifts, not in the middle of that one hour in which owners call for an update, not during an understaffed lunch hour. Try to make some time for TLC as well as other treatments. Gloved cuddles are better than none and speaking in a friendly way should always be possible.

Last, but not least, a straightforward waste management and an easy to follow environmental disinfection protocol is what you need for the final part of the treatment of a contagious patient.

## References

- Jade M. Hardy MS, et al. The effect of nail characteristics on surface bacterial counts of surgical personnel before and after scrubbing. Veterinary Surgery, June 2017

- Amy M. Treakle, et al. Bacterial contamination of health care workers' white coats. Am J Infect Control 2009

- Jennifer S. Ogeer-Gyles, et al. Nosocomial infections and antimicrobial resistance in critical care medicine. JVECC, 2006

- Leah A. Cohn, John R. Middleton. A veterinary perspective on methicillin-resistant staphylococci. JVECC, 2010
TOP TIPS FOR TRAUMA

Alex Lynch, BVSc(Hons) DACVECC MRCVS

North Carolina State University, Raleigh, NC

Trauma cases have the potential to be overwhelming and stressful for clinicians and owners alike. This lecture will provide some practical tips that may help you logically and confidently approach trauma cases presented to you even if budgets are tight.

**Tip 1: Major body systems matter most.** The initial goal with trauma is to triage major body systems even if other injuries might be more eye catching. Specifically, the neurological system (brain), cardiovascular system (heart), and respiratory system (lungs). Derangements of these systems can result in patient death and addressing issues with these systems are treatment priorities. Major body systems can be assessed rapidly (within a few minutes) and should provide objective 'yes-no' style pieces of data. A careful physical examination provides lots of helpful information that can then be supplemented with other diagnostics.

**Neurological system:** Assessment of patient mentation/level of consciousness is often done quickly and somewhat unconsciously. Level of mentation can be classified as normal, obtunded, stuporous, or coma. When traumatic brain injury is suspected, additional physical examination parameters (i.e. pupil size, motor ability, oculocephalic reflex) may be assessed to formulate the modified Glasgow Coma Scale. Animals with intracranial hypertension secondary to traumatic brain injury may exhibit the Cushing's response (i.e. systemic hypertension with inappropriate bradycardia). This is vitally important to recognize, as it suggests critically elevations of intracranial pressure, and emergent treatment (e.g. hypertonic saline, mannitol) should be instituted immediately.

**Cardiovascular system:** Identification of haemorrhage is the most important initial priority after trauma. Cardiovascular stability is determined by assessment of the perfusion parameters, specifically heart rate, pulse quality, mucous membrane color, capillary refill time, mentation, and temperature. Dogs tend to have a predictable response to hypovolaemia, characterized by progressive sinus tachycardia, alterations in pulse quality (hyperdynamic initially, progressing to weaker), progressive pallor, prolongation of CRT, diminishing mentation, and cold periphery compared to core. Cats with advanced hypoperfusion are more likely to have muted responses, characterized by hypothermia, bradycardia, and hypotension. When the possibility of cardiovascular instability is detected, it is usually appropriate to start some treatment (e.g. fluid resuscitation) concurrent to performing ancillary diagnostics. Tachycardia may develop after trauma for several reasons other than haemorrhage (e.g. pain, anxiety).

**Respiratory system:** Initial assessment should include respiratory rate and effort. A variety of traumatic injuries may be encountered (e.g. pulmonary contusions, pneumothorax, diaphragmatic hernia). It is also important to consider non-respiratory lookalikes that could alter the respiratory character of a patient (e.g. pain, anxiety, hypovolaemia, compensation for acidaemia). In the emergent setting, it is always reasonable to provide supplemental oxygen until you can confidently separate respiratory from non-respiratory causes of tachypnoea. Not all cases of true respiratory dysfunction improve considerably with oxygen administration however. For example, significant
pleural space disease will require emergency therapeutic thoracocentesis in order to relieve the
distress in an affected patient.

**Tip 2: Are the limbs functioning normally?** As an extension of the triage neurological exam, it is important to assess spinal cord function early on. Triage questions that need to be answered quickly and confidently are (1) is the dog ambulatory or non-ambulatory? and (2) if the dog is non-ambulatory, do they have intact motor and/or sensation? Any locomotor abnormalities can then be further characterized as ataxia, paresis, or plegia. If an animal has motor ability, it is not necessary to assess for deep pain, but checking if sensation is present is prognostically very important for plegic patients. Recognition of the Schiff Sherrington response is seen with severe thoracolumbar lesions (e.g. fractures, luxations, traumatic disks) but is not synonymous with only irreparable lesions. Two important points are worth considering here – firstly analgesia may confuse your neurological examination. In the time it takes for a colleague to calculate a dose and draw up analgesia, it should be possible to tell if the pet has intact motor and/or sensation. Secondly, animals that have sustained trauma may be unable to stand for a non-neurological lesion including fractures (especially pelvic and femoral) or haemodynamic compromise (e.g. internal bleeding causing hypovolaemia).

**Tip 3: PCV and total solids are cheap and helpful.** Even when budgets are tight, spinning a PCV and assessing a total solids with a refractometer should be considered essential information for any trauma case. After acute haemorrhage, the PCV takes time to equilibrate and is not a sensitive indicator of acute blood loss. A drop in total solids will occur rapidly however and is a very useful, inexpensive hint towards blood loss. As a guide, identification of a TS <60 g/L (6g/dL) in an acute trauma case should prompt the clinician to hunt for haemorrhage. Reasonably common sites of haemorrhage include the abdominal cavity, pelvic fracture sites, and femur fractures. Haemothorax is a fairly uncommon injury but may be encountered in larger dogs and may be a fatal lesion in cats and small dogs. In the absence of a definitive physical bleed, presence of coagulopathy should be considered. Spontaneous endogenous coagulation dysfunction is recognized in severely traumatized people and may also develop in some dogs. Haemostatic dysfunction following resuscitation with large volumes of crystalloids and synthetic colloids (i.e. resuscitation associated coagulopathy) may also be encountered from time to time.

**Tip 4: A-FAST usually help more than abdominal radiographs.** Focused assessment with sonography for trauma or point of care ultrasound has revolutionized bedside assessment of patients in the ER. It has become an extension of the physical exam in the triage setting. For trauma, abdominal or A-FAST is a sensitive means of identifying free peritoneal effusion. Effusion following trauma usually represents haemorrhage but other fluids (e.g. urine, bile) may also be encountered. In comparison, abdominal radiographs are generally less sensitive than ultrasonography for identification of effusion. There are some specific situations where radiographs of the abdomen may prove to be very helpful however (e.g. identifying displaced abdominal organs, diagnosing ruptured abdominal walls/hernias).

**Tip 5: Thoracic radiographs probably help more than TFAST.** The disclaimer to the above statement will depend on your experience and comfort level with ultrasound! Focused ultrasound of the thorax (T-FAST) is a convenient and rapid way of identifying pleural effusion. As mentioned above, haemothorax is not an especially common lesion in traumatized animals since internal thoracic bleeds are often catastrophic. Ultrasound is also very helpful for identifying large and overt diaphragmatic
rents (e.g. identify abdominal organs in the thorax). Basic echocardiography skills may also aid your interpretation of a patient's volume status via left ventricular end diastolic diameter (LV-EDD) and confirm the presence of pericardial effusion. Many of the common thoracic injuries seen after trauma are reliably identified with radiographs (e.g. contusions, pneumothorax). While there will be a radiographic lag time associated with the severity of pulmonary contusions on radiographs, they are often clearly seen in clinically compromised pets shortly after trauma. With training and practice, T-FAST can help rule out pneumothorax by visualizing a convincing glide sign (movement of lung relative to the chest wall) and ultrasound can be used to identify lung infiltrates (i.e. B lines). In some cases, radiographs and ultrasound may still prove inconclusive for some thoracic injuries (e.g. small diaphragmatic defects) and CT scans may be recommended if available.

**Tip 6: Lactate may be more helpful than blood pressure.** Lactate, as a byproduct of anaerobic respiration, may be elevated following trauma in animals with haemodynamic instability. Hyperlactataemia can be used to gauge patient illness severity and may clue clinicians in to situations where patients are more compromised than they appear. Serial monitoring may provide even more insight into patient stability and progress, since failure for lactate to improve despite treatment is considered a negative prognostic indicator in people. Blood pressure is used as another clinical correlate to haemodynamic stability and indicator of systemic perfusion. It is a quite late stage marker of hypoperfusion, so the blood pressure may be preserved during the compensated stages of shock. The accuracy of blood pressure is also dependent on the modality used (i.e. direct, Doppler vs. oscillometric) and should be interpreted in the light of the individual patient (e.g. anxiety level, patient cooperation). Simplistically, a low blood pressure reading in the face of a collapsed dog or cat with signs suggestive of haemodynamic instability is likely believable. There is a risk that blood pressure readings may be reassuringly normal however even when occult haemodynamic compromise is present.

**Tip 7: Hypertonic saline is helpful.** Resuscitation with isotonic crystalloids is reasonable for many cases of trauma. Hypertonic saline can also be very helpful in a select population of patients. Proprietary 7.2% hypertonic saline can be provided 3-4 mL/kg as both a low volume resuscitation strategy and as a hyperosmolar therapy for traumatic brain injury/brain oedema. The low volume can be convenient when resuscitating large breed dogs, since a considerably lower volume can be administered rapidly compared to isotonic fluids. As a rule of thumb, 3-4 mL/kg is expected to have a similar volume expansive effect to 20 mL/kg of isotonic crystalloids. The actual haemodynamic endpoints are unlikely to be superior with hypertonic or isotonic fluids however. Hypertonic saline functions by rapidly liberating water from other bodily sources (primarily from the interstitial space). Consequently, if hypertonic saline is administered the patient should have normal hydration (i.e. fluid in interstitial space available for movement) and isotonic fluids must be administered afterwards to replenish the interstitial deficit. Hypertonic saline is an attractive option for traumatized pets with suspected brain injury since it confers that volume expansive effect, whereas alternatives like mannitol are osmotic diuretics and could worsen volume status.

**Tip 8: Transfuse early!** For some animals, fluid resuscitation is not always sufficiently effective and blood products may be helpful in some of these patients especially those with acute haemorrhage (i.e. replacing 'like with like'). Acute haemorrhage will result in the loss of red cells, platelets, and plasma. In many hospitals, blood components (i.e. packed cells or plasma) will be available but fresh whole
blood may be obtained when needed by a donor. The latter is an attractive option in cases of acute
haemorrhage since haemostasis may be improved as well as improved oxygen delivery by providing
red cells. In addition, antifibrinolytic agents (e.g. aminocaproic acid, tranexamic acid) may prove
helpful for acute traumatic haemorrhage.

**Tip 9: Urinary tract trauma can be sneaky.** Some traumatic injuries can easily be overlooked at the time of initial exam with urinary tract trauma being particularly easy to overlook. Urinary tract trauma is typically initially associated with a low volume of effusion that progresses over time. Sampled effusion will usually be blood tinged, rather than an expected yellow color that can also confuse the likely source of fluid. Triage blood work may identify modest azotaemia initially, which will worsen overtime. Biochemical analysis of effusion will identify >2 x concentrations of creatinine and potassium compared to peripheral values. Definitive identification of the anatomical lesion will require diagnostic imaging (e.g. contrast studies, ultrasound).

**Tip 10: Pattern recognition can help.** For trauma cases, certain patterns do appear to crop up that may help with initial triage assessment and diagnostic prioritization. For example, roll over injuries (i.e. high impact low velocity trauma) can result in several serious injuries including urinary bladder rupture, pelvic fractures, body wall rupture, and diaphragmatic rupture. This approach therefore could help prioritize useful diagnostics in situations where the clinician has to be selective in the tests recommended due to financial concerns. Likewise, recognizing that most dogs affected by traumatic haemoabdomen typically can be managed conservatively rather than surgically.
# MANAGEMENT OF THE HEAD TRAUMA PATIENT

Katja-Nicole Adamik, PD Dr. med. vet., DACVECC, DECVECC, Vetsuisse Faculty, University of Bern, Switzerland

## Introduction

Head trauma (HT) or traumatic brain injury (TBI) have been used as synonymous terms, but they are two different entities. HT is defined as a head injury that is clinically evident due to the presence of external injuries (ecchymosis, lacerations, deformities) produced by an external force. TBI refers specifically to an injury of the brain itself, caused also by an external force but is not always clinically evident. Management of cats and dogs suffering from HT or TBI can be challenging. HT is a complex disease and most patients suffer from additional injuries due to the initial trauma. In dogs, HT is mostly due to blunt vehicular trauma, and in cats due to high-rise syndrome. Severe TBI is associated with a high mortality in both humans and small animals. Treatment of the brain injured patient is focused on reestablishment of global perfusion and on maintaining adequate cerebral perfusion.

## Pathophysiology

Cerebral perfusion pressure (CPP) is determined by intracranial pressure (ICP) minus the mean arterial pressure (MAP) and gives an indication of the pressure gradient driving blood flow across the brain (the cerebral blood flow [CBF]). As ICP increases towards MAP, cerebral perfusion becomes impaired. Systemic blood pressure must increase to prevent a decrease in cerebral perfusion pressure and subsequent decrease in CBF.

Brain injury after HT can be separated in two categories: primary and secondary injury:

Primary injury is not treatable or reversible and is due to the initial trauma. It is a result of the direct mechanical damage to brain parenchyma such as contusions, haematomas, lacerations, and diffuse axonal injury. Secondary injury is a result of the combination of systemic extracranial insults and intracranial physical and biochemical changes, which occur within minutes to hours after trauma. This stage of intracranial injury is largely mediated through increased activity and accumulation of excitatory neurotransmitters (i.e., glutamate, asparate), generation of reactive oxygen species (ROS), lipid peroxidation, and production of proinflammatory cytokines. These substrates can contribute to neuronal cell damage and possibly cell death, with resultant cerebral oedema formation, followed by increased intracranial pressure (ICP), a compromised blood-brain barrier (BBB) and alterations in cerebrovascular reactivity. Further factors contributing to secondary brain injury are hypoxaemia and ischaemia, hypercapnia, systemic hypotension, intracranial hypertension which lead to ATP depletion, accumulation of intracellular sodium and calcium, nitric oxide accumulation, and cerebral lactic acidosis. Acute increases in ICP often trigger the "Cushing's reflex", a characteristic combination of systemic hypertension and sinus bradycardia. Decrease in CPP due to high ICP leads to a dramatic increase in sympathetic tone. This results in vasoconstriction, increase in cardiac output and significant increase in systolic and mean blood pressure. This increased blood pressure (systolic blood pressure values up to >200 mmHg) induces a reflex bradycardia. The presence of a Cushing's reflex in a HT patient is a sign of life threatening intracranial hypertension and has to be treated immediately and aggressively with hyperosmolar therapy.
## Initial Patient Assessment

Patients must be assessed and treated for abnormalities in their respiratory, cardiovascular, and neurological systems first. Assessment and stabilization of the respiratory tract is mandatory during initial management of the traumatized patient. In addition, head and facial trauma is frequently associated with injuries to the upper airways and can significantly impair respiratory function. Cats and dogs with pleural space disease (pneumothorax, diaphragmatic herniation) can be identified by an asynchronous or inverse breathing pattern in combination with decreased lung sounds on auscultation. Pulmonary contusion and pneumothorax are the most common abnormalities after chest trauma. For assessment of the cardiovascular status, mentation, mucous membrane colour, capillary refill time, heart rate, pulse quality, and body temperature are determined.

## Stabilization of the head trauma patient – Extracranial Therapy

Adequate oxygenation, ventilation, and volume replacement are the cornerstones of initial stabilization of any trauma patient, and especially of the HT patient. Patient stabilization is based on the A (Airway) B (Breathing) C (circulation) scheme. Airway patency should be assessed as soon as possible. Oxygen supplementation can be provided by flow by oxygen, via a loose fitting face mask, or in an oxygen cage. Target values for oxygenation are $SpO_2$ >95%, and $PaO_2$> 80 mmHg, respectively. Nasal oxygen tubes are contraindicated in animals with HT, due to sneezing which can occur after nasal irritation, which results in increased ICP. Hypoventilation has to be avoided because even mild hypercapnia leads to increase in ICP. In addition, hyperventilation and hypocapnia should be avoided, because it leads to vasoconstriction with resultant decrease in cerebral blood flow leading to cerebral ischaemia. The venous $PCO_2$ should be maintained between 35-45 mmHg. Animals with pneumothorax need thoracocentesis and may need a chest tube to evacuate the chest and allow adequate ventilation. The primary goal of fluid therapy in trauma is rapid restoration of the effective circulating volume. Major concerns in patients with TBI are that aggressive fluid therapy may exacerbate brain oedema. In the injured brain the blood brain barrier may be disrupted which leads to increased permeability to both ions and colloids. However, hypotension has to be avoided. Suitable types of fluids are isotonic crystalloids, artificial colloids, hypertonic crystalloids (NaCl 7%), or blood products. Boluses of isotonic crystalloids (20 mL/kg in the dog and 5-10 mL/kg in the cat) are administered over 10-15 minutes, until improved tissue perfusion is archived. Hypertonic saline (NaCl 7%) is another option for fluid resuscitation of trauma patients, which is explained later in this text. Synthetic colloids (6% HES 130/0.4 or 0.42) are indicated if fluid therapy with isotonic crystalloids is insufficient and are administered in a dose of 5-10 mL/kg in dogs and 3-5 mL/kg in cats over 10 minutes (maximum 30 mL/kg/24h). Mean arterial pressure (MAP) should be maintained at 80-100 mmHg and systolic arterial pressure at 100-120 mmHg to preserve normal cerebral perfusion pressure. If the animal is euvolemic and not in shock, isotonic crystalloids should be administered at a maintenance rate (2-3 mL/kg/h) and the patient should be monitored for ongoing blood loss. Red blood cell transfusions are indicated to restore oxygen-carrying capacity and should be started at PCV not lower than 20% in animals with acute haemorrhage.

## Neurologic Assessment

A thorough neurological examination in a traumatized patient has to be delayed until the patients' respiratory and cardiovascular status is stable! Initial neurologic assessment is therefore focused on the mental status and if possible, brain stem reflexes (size and symmetry of the pupils, pupillary light reflex). Once the primary survey is complete and conditions that are life threatening have been
addressed, the patient can undergo neurologic evaluation. Primary goals are to determine whether the nervous system is indeed affected, to localize the problem and obtain an anatomical diagnosis, and to gain information about the prognosis. The modified Glasgow coma scale (GCS) has been proposed in veterinary patients and provides an objective way for the clinician to grade the patient with TBI at the time of admission and to monitor the patient's response to treatment. The scale incorporates three domains: (1) level of consciousness, (2) posture and limb motor function, and (3) brain stem reflexes (see table at the end of the text). Neurological assessment should be repeated every 30-60 minutes.

**Level of consciousness**-The level of consciousness is classified as normal, depressed, obtunded, stuporous, or comatose, depending on response to external stimuli. Stuporous patients are unconscious, but can be aroused with painful stimuli; comatose patients fail to respond to any environmental stimulus. Coma typically indicates severe bilateral or global cerebral injury or severe brainstem damage, and carries a guarded prognosis. However, extensive blood loss, moderate or severe hypothermia or hypoxaemia can also severely alter the level of consciousness. **Posture and limb motor function**-Decerebrate posture (rigid extension of all limbs and opisthotonus + stupor or coma) is observed as a result of a rostral brainstem lesion and carries a guarded to poor prognosis. Decerebellate posture (opisthotonus, with the forelimbs extended, mentation normal) is often caused by an acute cerebellar lesion and can sometimes be episodic. **Brain stem reflexes**-Normally, the two pupils should be symmetrical in shape and equal to each other in size. In the absence of concurrent ocular trauma, miotic pupils indicate diffuse forebrain injury. Progression to mydriasis may indicate brain herniation and a progressive brainstem lesion and is an indication for immediate, aggressive therapy. Bilateral mydriasis with no response to light is usually indicative of an irreversible midbrain lesion or brain herniation and carries a poor prognosis. Fixed, unresponsive and mid-range pupils are usually seen with cerebellar herniation. The oculocephalic reflex (physiological nystagmus) can be induced by rotating the head in the vertical and horizontal planes. This reflex can be impaired in an animal with a brainstem lesion as a result of involvement of central vestibular nuclei, medial longitudinal fasciculus or cranial nerve nuclei that innervate the extra-ocular muscles.

## Intracranial Therapy

Simple therapies may be instituted to help minimize increases in ICP. Positioning of the head in an elevated fashion (15-30°) and avoidance of compression of both jugular veins are important.

Hypertonic therapy is the treatment of choice for increased IPC after HT/TBI and hypertonic saline (HTS) and mannitol are currently used hypertonic agents. For **mannitol 20%** the recommended bolus dose is 0.5-1 g/kg IV over 20 minutes. It has beneficial effects on ICP, CPP, and CBF as well as on brain metabolism. The mechanism of action is a transient plasma expansion with a decrease in blood viscosity. This results in cerebral vascular vasoconstriction and leads to a decreased cerebral blood volume (CBV) and ICP with maintained CBF. Further, mannitol promotes the shift of water from the intracellular and interstitial cerebral spaces into the vasculature, inducing an osmotic diuresis, thereby reducing cerebral oedema. This effect peaks 1 hour after administration and may persist for 6-8 hours.

In addition free radical scavenging and limitation of secondary oxidative injury in the brain has been reported. Mannitol administration is contraindicated in hypovolaemic patients. If multiple doses of mannitol or a constant rate infusion of mannitol is administered, a reverse osmotic shift can occur (accumulation of mannitol in the extravascular space and cerebral oedema). The benefits of **HTS 7%** were discovered from studies on "small volume resuscitation". The dose for 7% HTS is 2-4 mL/kg over
2-5 minutes and results in an immediate restoration of intravascular volume. HTS improves the microvasculatory flow, controls intracranial pressure, improves cardiac performance, and stabilizes arterial blood pressure. An osmotic force, shifting water from the interstitial and intracellular spaces into the intravascular space is created, with resultant reduction in brain water content and ICP. In addition, regional CBF and oxygen delivery are improved due to dehydration of cerebrovascular endothelial cells and reduction of endothelial oedema. HTS solutions have also been shown to decrease brain excitotoxicity and modulate the inflammatory response. Combining HTS with an artificial colloid can prolong the volume expanding effect. Because of their rapid volume expanding effect, HTS and mannitol both carry the risk of aggravating pulmonary oedema in patients with cardiac or respiratory pathology. If an individual patient is not responding to one of the two fluids, the other may yield a beneficial response. In several studies HTS resulted in a greater absolute ICP decrease and a more sustained effect than mannitol.

## ADDITIONAL THERAPEUTIC OPTIONS

### Glycaemic control

Hyperglycaemia has been shown to have detrimental effects in patients with TBI and so iatrogenic hyperglycaemia, such as may occur with corticosteroid administration, must be prevented. Hyperglycaemia increases free radical production, excitatory amino acid release, cerebral oedema, and cerebral acidosis, and alters the cerebral vasculature.

### Pain control

Adequate analgesia is critical in prevention of further increase in ICP. Opioids are commonly used due to their relative lack of adverse cardiovascular effects and ease of reversal. **Methadone** (0.1-0.2 mg/kg) or **fentanyl** (0.005-0.01 mg/kg) are fast acting μ-agonists. Due to its short action, fentanyl has to be administered as a constant rate infusion (5μg/kg/h). A disadvantage of opioids is that assessment of the neurogenic status is impaired. However, if needed, fentanyl or methadone can be antagonized with naloxone, in contrast to buprenorphine which cannot be antagonized.

### Anticonvulsive therapy

Risk factors for posttraumatic seizures include severity of injury, skull fractures, epidural, subdural, and intracerebral haematomas, penetrating head wounds, and a seizure within the first 24h following injury. Adverse effects of seizure activity include hyperthermia, hypoxaemia, and cerebral oedema, with resultant intracranial hypertension. **Diazepam** is the anticonvulsant of choice for stopping an ongoing seizure due to its rapid onset of action and reliable efficacy. For prevention of further seizures **phenobarbital** is recommended. Barbiturates have the ability to decrease the energy requirements of cerebral tissue, which may decrease oxygen demand by neuronal tissue resulting in vasoconstriction and decreased blood flow. This may, in turn, lead to decreased ICP. In case of ongoing seizures despite loading with phenobarbital, intravenous administration of pentobarbital or propofol can be used for induction of coma. **Propofol** is given at a rate of 0.1 mg/kg/min via syringe pump, but can be titrated to effect. Anaesthesia is often maintained with 0.4 mg/kg/min.
**Corticosteroids**

Because of the lack of evidence of any beneficial effect after TBI and strong evidence from human literature showing a detrimental effect on neurologic outcome, corticosteroids should *not* be administered to dogs and cats with TBI.

**Furosemide**

Furosemide should be reserved for patients with pulmonary oedema or oliguric renal failure. Due to its volume depleting effect, it can lead to systemic hypotension and to decreased CPP.

**References upon request**
# MANAGEMENT OF POTASSIUM DISORDERS IN THE EMERGENCY ROOM

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

Vetsuisse Faculty, University of Bern, Switzerland

Disorders of potassium homeostasis are frequently encountered and associated with a wide range of diseases. Moderate to severe hyper- and hypokalaemia can have immediately life-threatening consequences and ER clinicians must be adept at rapid recognition and correction of dyskalaemias.

## REVIEW OF NORMAL POTASSIUM HOMEOSTASIS

Potassium is the major intracellular cation and is located predominantly in skeletal myocytes.¹,² Normal extracellular and intracellular potassium concentrations are approximately 4 mmol/L, and 140 mmol/L, respectively. The concentration gradient between the intracellular and extracellular space is maintained by the active Na⁺-K⁺-ATPase pump that transports potassium into the cell and sodium out of the cell.³ Potassium regulation must adapt to both the addition of potassium to the extracellular compartment by oral potassium intake in the diet or parenteral administration in intravenous fluids in hospitalized patients.³ Two mechanisms are of great importance in maintaining a normal serum potassium concentration, 1) the distribution of potassium between the intra- and extracellular fluid compartment (internal potassium balance), and 2) the renal excretion of excess potassium (external potassium balance).³ Abnormalities in serum potassium concentrations can therefore arise from abnormal potassium intake or generation, disturbances in internal potassium balance, or from abnormal potassium excretion.³

## HYPOKALAEMIA

### Definition and etiology

Normal serum potassium values for dogs and cats are expected to range from 3.5 mmol/L to 5.5 mmol/L and hypokalaemia is defined as serum potassium concentrations **less than 3.5 mmol/L**.¹,² An abnormality in any of the processes of potassium homeostasis can lead to hypokalaemia and the three general causes for hypokalaemia include 1) decreased daily potassium intake, 2) disorders of internal potassium balance (increased intracellular shift of potassium), and 3) disorders of external potassium balance (increased renal and more rarely, gastrointestinal potassium losses).¹,²,⁴

Due to increased renal potassium reabsorption in states of low serum potassium, decreased dietary intake alone is unlikely to lead to significant hypokalaemia.¹,⁴ Administration of intravenous fluids with a potassium deficient isotonic crystalloid, however, can lead to iatrogenic hypokalaemia.¹ An increased flux of potassium into cells can be observed with metabolic or respiratory alkalosis, refeeding syndrome, periodic hypokalaemic paralysis, hypothermia, rattle snake envenomation, or activation of the Na⁺-K⁺-ATPase pump due to increased insulin or catecholamine levels, beta adrenergic agonist therapy or toxicosis.¹,⁵⁻¹⁰ Increased gastrointestinal and urinary losses are the most important causes of hypokalaemia due to increased potassium loss and can be seen secondary to vomiting, diarrhoea, chronic kidney disease, diuretic administration, and several endocrinopathies.¹,²

### Symptoms

Symptoms of hypokalaemia are generally not seen until potassium concentrations reach 3.0 mmol/L to 2.5 mmol/L.⁴ Hypokalaemia can affect multiple cellular functions, and acid- base balance, glucose
metabolism, neuromuscular function, cardiovascular, and renal function can be impaired<sup>1,2,4</sup>. Acute potassium depletion can therefore lead to metabolic acidosis, hyperglycaemia, polyuria, polydipsia, decreased renal concentration ability, profound skeletal muscle weakness, as well as cardiac arrhythmias.<sup>1,4,11-14</sup>

In cats specifically, hypokalaemic myopathy frequently manifests as ventroflexion of the neck and head. In severe cases of hypokalaemia, respiratory muscle fatigue can require ventilatory support until the hypokalaemia and polymyopathy have resolved.<sup>15</sup> A variety of electrocardiographic (ECG) changes and cardiac arrhythmias have been observed in hypokalaemic dogs and cats but are less predictable than in hyperkalaemia. They can include atrial and ventricular tachyarrhythmias, ST segment depression, decreased amplitude of T waves, prolongation of the QT interval, and the appearance of U waves.<sup>1,16,17</sup>

## Treatment

Potassium deficits should be corrected, but immediate correction of the full deficit commonly is not urgent. Potassium replacement can generally be performed enterally or parenterally.

Parenteral administration of potassium solutions (e.g. potassium chloride, potassium phosphate) is indicated in patients with moderate (2.5 mmol/L to 3.4 mmol/L) to severe (< 2.5 mmol/L) hypokalaemia.<sup>1,2</sup> The rate of intravenous potassium administration should generally not exceed 0.5 mmol/kg/hr to avoid potential life threatening effects of iatrogenic hyperkalaemia.<sup>1</sup> Guidelines for potassium supplementation based on degree of hypokalaemia are provided below:

<table><caption>Table 1 Guidelines for Intravenous Potassium Supplementation in Dogs and Cats<sup>35</sup></caption><thead><tr><th>Serum Potassium<br>Concentration (mEq/L)</th><th>mEq KCL to add to<br>250ml Fluid</th><th>mEq KCL to add to 1L<br>Fluid</th><th>Maximal Fluid Rate<br>(ml/kg/hr)</th></tr></thead><tbody><tr><td>&lt;2.0</td><td>20</td><td>80</td><td>6</td></tr><tr><td>2.1 to 2.5</td><td>15</td><td>60</td><td>8</td></tr><tr><td>2.6 to 3.0</td><td>10</td><td>40</td><td>12</td></tr><tr><td>3.1 to 3.5</td><td>7</td><td>28</td><td>18</td></tr><tr><td>3.6 to 5.0</td><td>5</td><td>20</td><td>25</td></tr></tbody></table>

Patients that present in shock or dehydrated should be resuscitated or rehydrated prior to potassium repletion. Only in severely hypokalaemic animals should potassium substitution be started at the time of rehydration. Similarly, the administration of sodium bicarbonate and insulin to patients in diabetic ketoacidosis should be delayed until rehydration is achieved and serum potassium levels are > 3.5 mmol/L as sudden correction of acidaemia and insulin replacement can worsen hypokalaemia by enhancing intracellular potassium shifts.<sup>2,4</sup> In a subset of hypokalaemic patients, simultaneous correction of magnesium deficits is likely to allow for more rapid and thorough correction of potassium deficit.<sup>18</sup> When supplementing flexible intravenous fluid bags, extreme care must be taken to sufficiently mix the content of the bag to avoid inadvertent administration of fluids containing life threateningly high potassium concentrations.<sup>19</sup>
Oral potassium most commonly is administered in the form of potassium gluconate powder or tablets with food. The recommended dose is 0.5 mmol/kg body weight orally once to twice daily and should be titrated to effect.²⁰ Oral potassium substitution is limited to patients experiencing mild hypokalaemia (serum potassium concentration >3.4 mmol/L) and patients that voluntarily intake food or can be fed by oesophageal or gastroenteral feeding tubes.

## HYPERKALAEMIA

### Definition and etiology

Hyperkalaemia is defined as serum potassium concentrations that **exceed 5.5 mmol/L** and can be life threatening at concentrations greater than 7.5 mmol/L.¹ As outlined above, potassium intake occurs orally, by intravenous infusion, or by increased potassium release from intracellular sites. Initially, most excess potassium is taken up and transiently stored intracellularly and then excreted primarily by the kidneys.³ Therefore, an abnormality in any process of potassium intake or generation, translocation from cells into extracellular fluid, or decreased renal excretion can lead to hyperkalaemia.³

Hyperkalaemia occurs more commonly due to excessive potassium supplementation in intravenous fluids than with increased oral intake. Renal potassium excretion is usually so efficient that an increase in potassium intake alone will not cause hyperkalaemia in a normal subject.¹ For hyperkalaemia to develop, urinary excretion of potassium must be reduced and prerenal (e.g. decreased effective circulating volume), renal (e.g. acute or chronic renal disease, hypoaldosteronism), and postrenal diseases (e.g. ureteral obstruction, urethral obstruction, uroabdomen) are the most common causes for persistent hyperkalaemia in companion animals.¹,³

Transcellular shift of potassium out of cells is a common cause of hyperkalaemia and can be seen secondary to accumulation of uraemic acids, respiratory acidosis, hydrogen chloride, or calcium chloride infusions.²,²¹,²² Release of potassium from the intracellular space can occur when the rate of tissue breakdown is increased such as in severe exercise, trauma, heat stroke, administration of cytotoxic agents or radiation therapy to patients with malignant lymphoma (tumour lysis syndrome), and during spontaneous reperfusion of the limbs or following treatment with thrombolytic agents in cats that suffer from aortic thromboembolism.²³⁻³²

### Symptoms

The clinical manifestations of hyperkalaemia are limited to skeletal muscle weakness and abnormal cardiac conduction and reflect the physiologic effect of potassium on resting membrane potential and membrane excitability.¹,²¹ Skeletal muscle weakness can develop when serum potassium concentration exceeds 8.0 mmol/L.¹ Severe hyperkalaemia can lead to atrial standstill, bradycardia, and ventricular asystole due to impaired membrane excitability of the cardiac conduction system.²¹ Rarely, wide complex tachycardia can be seen in cats with severe hyperkalaemia.³³

### Treatment

The most appropriate treatment of hyperkalaemia is dependent on the degree of hyperkalaemia, the timeframe of onset, and the underlying cause. An ECG should be performed in every patient with moderate to severe hyperkalaemia as rapid onset of even moderate hyperkalaemia can cause cardiac arrhythmias.¹,² Animals capable of normal urine potassium excretion (i.e. with normal urine output)
and without clinical signs associated with hyperkalaemia in the range of 5.5 mmol/L to 6.5 mmol/L might not require immediate treatment, however, exogenous potassium administration should be discontinued and the cause for the hyperkalaemia investigated.¹ Potassium free (e.g. 0.9% NaCl) or potassium deficient fluids (e.g. Lactated Ringer's) can be administered to patients with normal urinary output to promote diuresis and may be sufficient to decrease serum potassium concentrations to normal ranges. The goals of treatment of patients suffering from severe hyperkalaemia or exhibiting clinical signs associated with hyperkalaemia is aimed at restoring the resting membrane potential of cells, normalizing cardiac action potential conduction velocities, and ultimately lowering the serum potassium concentration. 10% calcium gluconate antagonizes the effect of hyperkalaemia on myocardial resting membrane potential, but will not lower the potassium concentration ¹. Regular insulin with dextrose to prevent hypoglycaemia or the sole administration of dextrose solutions to increase endogenous insulin levels, sodium bicarbonate, and beta adrenergic agonists can all be successfully used to decrease serum potassium concentrations by promoting increased intracellular shifts of potassium.²,³⁴ A summary of treatments for life threatening hyperkalaemia is provided below.

<table><caption>Table 2 Treatment of severe hyperkalaemia ¹,²,³⁴</caption><thead><tr><td>Drug</td><td>Dosage</td><td>Mechanism of Action</td></tr></thead><tbody><tr><td>10% Calcium Gluconate</td><td>0.5 to 1.5mL/kg IV over 5 to 10min with ECG monitoring</td><td>Reduces cardiac excitability by reestablishing the normal gradient between the resting membrane and threshold potentials. Does not lower serum potassium concentrations.</td></tr><tr><td>Insulin and 50% Dextrose</td><td>Regular insulin 0.5U/kg IV with Dextrose 2g/U of insulin (4mL of 50% dextrose)</td><td>Promotes intracellular shift of potassium through activation of Na<sup>+</sup>-K<sup>+</sup>-ATPase</td></tr><tr><td>50% Dextrose</td><td>0.7 to 1g/kg IV over 3 to 5min</td><td>Same as above</td></tr><tr><td>Sodium Bicarbonate</td><td>1 to 2 mEq/kg IV slowly over 15min</td><td>Increases extracellular pH and promotes intracellular shift of potassium in exchange for H<sup>+</sup> ions</td></tr><tr><td>Terbutaline</td><td>0.01mg/kg IV slowly</td><td>Promotes intracellular shift of potassium through activation of Na<sup>+</sup>-K<sup>+</sup>-ATPase</td></tr></tbody></table>
References

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8. Malik R, Musca FJ, Gunew MN, Menrath VH, Simpson C, Culvenor J, et al. Periodic hypokalaemic polymyopathy in Burmese and closely related cats: A review including the latest genetic data. J Feline Med Surg. 2015 May 1;17(5):417-26.

9. Matos MJ, Jenni S, Fischer N, Bienz H, Glaus MT. Myokardschädigung und Paroxysmale Ventrikuläre Tachykardie bei einem Hund nach Albuterolintoxikation. Schweiz Arch Für Tierheilkd. 2012 Jul 1;154(7):302-5.

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14. Bilbrey GL, Herbin L, Carter NW, Knochel JP. Skeletal Muscle Resting Membrane Potential in Potassium Deficiency. J Clin Invest. 1973 Dec;52(12):3011-8.

15. Hammond TN, Holm JL. Successful use of short-term mechanical ventilation to manage respiratory failure secondary to profound hypokalemia in a cat with hyperaldosteronism. J Vet Emerg Crit Care. 2008 Oct 1;18(5):517-25.

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# 10 THINGS TO CONSIDER MANAGING SEPTIC PERITONITIS

Dominic Barfield BSc BVSc MVetMed DACVECC DECVECC FHEA MRCVS
The Royal Veterinary College, North Mymms, Hertfordshire, UK

There are multiple things that need to be considered with managing a septic peritonitis patient, though here are 10 (well 11) to consider.

## Diagnosis

If you are concerned about a patient having a septic process then identifying the source of sepsis is important. If there is abdominal pain, or peritoneal effusion then the patient should be screened to assess for septic peritonitis. All peritoneal fluid should be evaluated under microscopy for neutrophils with intracellular bacteria, dilute samples might require centrifugation to concentrate the cells, or even evaluation by a clinical pathologist. It depends on the site of the gastrointestinal lesion whether a bacterial load might be identified, for example a patient with a perforated gastric ulcer might have no obviously identifiable intracellular bacteria, however a patient with a colonic lesion would have a marked load. It was reported in 2003 retrospectively that a difference in concentration of >20mg/dl (1.11mmol/L) between blood and peritoneal fluid glucose concentration can differentiate a septic peritoneal effusion from a non-septic peritoneal effusion (Vet Surgery 32 (2003) 161-166). Koenig and Verlander re-examined this using a point of care glucometer in cases with confirmed septic peritonitis and found the following: >20mg/dl, sensitivity 41% and specificity 100%, however the difference >38mg/dl (2.11mmol/L) supported a more accurate diagnosis.

A diagnostic peritoneal lavage, if there is no obvious free peritoneal fluid visible can be used to see if there are any neutrophils with intracellular bacteria. To do this you need to insert 10mL/kg of sterile saline, prior to sampling.

Radiographs, ultrasound and even CT might be able to identify free peritoneal gas, which would merit an exploratory laparotomy.

## Preoperative stabilisation

It is likely that some fluid resuscitation is required if there is a hypovolaemic component to the patient's shock. Though if the patient is hypotensive then some fluid might be required prior to starting vasopressor therapy. Although there is limited evidence in our species, norepinephrine should be started if after a sensible bolus the patient's blood pressure remains ≤65mmHg. Once the source of sepsis is identified then broad spectrum antibiotics should be given intravenously. A pre-operative serum albumin concentration of <25g/L, a left shift prior to surgery and dogs that required a resection and anastomosis due to an intestinal foreign body were more likely retrospectively to leak (J Am Vet Med Assoc, 2003: 233:73-77). Foreign bodies have not been shown to be a risk factor in all studies.

## Anaesthesia

Care is required to maintain blood pressure and minimise the amount of anaesthetic agents used. Often fentanyl, midazolam might be all that is required for endotracheal intubation. Maintaining the patient's body temperature and minimising heat loss is important. Hypotension should be avoided as this is a risk factor for leakage (J Am Vet Med Assoc. 2011;238:486-494).
## Surgery

A full exploratory laparotomy is important when trying to locate the source of GI leak, and retractors are invaluable for making sure that you have adequate visualisation. Pyloric ulcers can be tricky to identify. If an enterotomy, enterectomy, or resection and anastomosis is required care should be taken to make sure that the closure is appropriate and secure. Care should be taken if the surgeon is suspicious of a neoplasia as the underlying cause of the leak, as this has been identified as a cause of leakage following surgery. Preoperative septic peritonitis is a risk factor in itself for dehiscence (Vet Surgery, 2018; 47:125-129) in intestinal resection and anastomosis. Staples in that study were less likely to dehisce compared with hand sewn, however this was not found in a previous study (Vet Surg 2016; 45:100-103). It is probably evidence enough that large prospective studies are required to evaluate if there are any consistent identifiable factors in leakage following surgery, however identifying one solitary factor is unlikely.

## Post-operative care

### Blood pressure

Maintain MAP ≥65mmHg. It is likely that some vasopressor would be required to help maintain perfusion to the vital organs, however care must be taken when deciding upon a target, e.g. blood pressure. There is little evidence in dogs and cats for a preferred vasopressor though norepinephrine (noradrenaline) seems to be the most appropriate currently.

### Antibiotics

Depending on the clinical picture of the patient antibiotics might not require changing even if a resistant bacterial species is cultured. However initial appropriate antibiotic therapy is likely to be a major factor in having a successful outcome.

### Fluid therapy

Fluid therapy should be based upon the hydration status of the patient, monitoring the patients urine output and drain output, if abdominal drains are used. Recording these findings on the patient's clinical record and calculating the ins and outs, and if possible the patient's weight regularly can give some objective information for assessing hydration status. It is not uncommon for sick, septic peritonitis patients to become oedematous, and it should prompt the clinician to think about the fluid balance of the individual patient, particularly if the patient's albumin is low.

### Drainage

A variety of different abdominal drains have been used and it might make some sense to remove the peritoneal fluid although there is no evidence that it improves outcome. It was reported that closed suction drainage: left in place for a median of 6 days (2-11), had a survival 85% in a referral population (Adams et al, Vet Surg 43 (2014) 843-851). Open abdomens might be the surgeon's preference based on visual appearance of the abdomen, though there is no evidence that this improves outcomes, however it will mean that the abdomen will be examined and flushed again prior to closure.
**Dehiscence**

Often occurs within 5 days though can be longer. Leakage <24 hours is likely to occur from surgical failure. It is important if there are drains in place to not look at fluid collected in them to identify leakage, as often these receptacles will be colonised and therefore abdominocentesis is preferred. It is more common that if dehiscence and leakage occur that the patient will become tachycardic, pyrexic and likely have abdominal pain.

**Kirby's Rule of 20**

Twenty things to consider when looking after critical patients, it includes what is listed above.
Nutrition is key.

**Going back in**

This might be the 11th thing. Repeat surgery following dehiscence carries a higher mortality though can be effective in approximately 50% of cases. Although hypotension, hypoalbuminaemia and initial appropriate antibiotics are important they were not shown to be significant when examined retrospectively.

**References available on request**
# HOW TO AVOID MISTAKES IN THE ICU

Dominic Barfield BSc BVSc MVetMed DACVECC DECVECC FHEA MRCVS

The Royal Veterinary College, North Mymms, Hertfordshire, UK

Intensive care units in small animal hospitals will have a variety of patients. Depending on the hospital structure the ICU might have any patient where there is any concern of a problem arising, e.g. brachycephalic breed or a patient on seizure watch, which might require limited interventions and plans, to patients which require multiple interventions and treatments by the patient care team, such as those on mechanical ventilation, peritoneal dialysis, or patients with stage III tetanus. It is logical that the more interventions that you and your team have with a patient the more likely a mistake will occur, even if the error/mistake rate is 1%, when a mechanical ventilation patient would have over 100 interventions in a 24 hour period it is likely that a mistake or error will happen. It is likely that the majority of these errors will not lead to patient harm, though it is important to recognise when one occurs so that other team members can learn from them and attempt to put systems in place that minimise these errors in the future. Some of the recent human literature has included any intervention that did not lead to a successful outcome as an error, and that is probably responsible for the perceived medical error epidemic, rather than known complications.

There are a variety of ways in which you can characterise mistakes; active errors, adverse event, confirmation bias, human error, lapse, latent error, near miss, omissions, redundancy, resilience, safety culture, slips, system safety and there can be confounding factors; distractions and interruptions, fatigue, stress. These will not be fully explained in these notes and would suggest the following website for further definitions (https://chfg.org).

Regardless of the errors that are occurring you need some system to capture them, an error recording system, whether that is bespoke or off the shelf (VetSafe, from the Veterinary Defence Society). The importance is in whatever system that is used, you are trying to work out what happened, it is not a witch hunt and you are not going to blame anyone – you need to have a no blame culture in order to actually find out the problems that you have. There are common problems and problems that you are likely to have worked out, though there are always going to be new issues arising whether it is from a new piece of equipment or a new drug.

The following are things to consider, though certainly not exhaustive.

## Communication

Poor, lack of or misunderstood communication can be linked to the majority of errors in large workforces and it is important to consider five aspects of every communication: who, when, where, how and what?

**Who?** Who needs to be involved in the communication, who are you trying to communicate with?

**When?** For example patient handover rounds should be at a fixed time (and start promptly)

**Where?** Close to or in the ICU where everyone can be present.

**How?** Two-way communication using a formal structure -SBAR

**What?** Written notes and two-way communication
Listening is a complex skill and we can understand many more words spoken per minute than the speed of normal conversations. We often think that we are listening when we are really just thinking of what we are going to say next. It is important to be patient when listening, ask questions and paraphrase, making eye contact with the person that you are speaking to and using positive body language, you should not debate what is being spoken in your mind, try to change the subject, interrupt, finish what people are saying, tune out or think about what else needs to be done.

For example, patient handover you could consider a standard way of presenting cases such as SBAR (Situation, Background, Assessment, Recommendations), prior to the first patient it good to have introductions for all the members present in rounds, as not everyone is likely to know each person or their role. It is prudent as well to make sure that the person(s) finishing their shift informs if there are treatments/interventions that have not been performed for whatever reason so that the starting team know that needs to be done first.

## Medication errors

These are still very common in human medicine regardless of the systems that are in place. It could be: an active error, such as prescribing something that the patient has a known allergy to; or a human error, such as a 10x overdose (reading mg instead of mcg); a latent error, such as administering the wrong drug as it has a similar name; a lapse, forgetting a current medication that the patient is on; a near miss, remembering at patient discharge that they should be going home with a medication that hasn't been prescribed; omissions, failing to prescribe a medication that is known to improve outcome.

It is important that handwriting or electronic records are clear and cannot be misunderstood as well as using the same way throughout the hospital to prescribe, for example total dose, or mg/kg. Drug names are usually preferred compared to trade names, though it should be consistent.

## Teamwork

There are a number of considerations to improve teamwork: communication, followership, non-technical skills, shared mental models, team culture, team leadership, teamwork. All of these can be worked upon. Simulation can be a tool that is used to bring the team together to perform a task, whether that is CPR training or how to manage a trauma case, the challenge is finding the time for these exercises, though they can have profound effects on the team culture.

## Mental health

Fatigue and stress are often cited as contributory factors, we are human after all. What we need to do is recognise these in ourselves and know when to ask for help at the workplace when you are affected, for example if you are tired asking someone to check your drug calculation. You need to bring your best self to work and it is not easy day in, day out. Though any improvements in your own health and wellbeing are going to have benefits on your work. It is making sure that you carve out enough time to look after yourself, and that is going to be different for everyone.
## How can you implement change?

You need to think about what does good look like. An environment where constructive challenge is viewed positively and rewarded, where staff feel empowered to prioritise safety, that clients are seen as part of the safety team, where procedures are reviewed on the basis of what is right, not who is right (everyone should adopt the best practice), where task priority is maintained in challenging work settings (for example staff to reduce distractions and resist pressure to attend competing demands – keep patient handover quiet, do not interrupt someone who is calculating medicine for doses).

There is a lot of information on patient safety and medical errors, though is it important to remember to learn lessons from previous incidents and use them to improve practice. Think about practical ways to learn about improving communication using briefing and debriefing techniques. Make it possible that potentially unsafe behaviours are challenged by anyone in the team and that situations where error is more likely are recognised and conditions created to reduce risks. We all have a role in patient safety.

References available on request
# ACUTE ABDOMEN IN THE ER – INITIAL STEPS

René Dörfelt, DVM, Dr. vet. med., DECVECC, DECVAA

Clinic of Small Animal Medicine, LMU Munich, Germany

Acute abdomen describes multiple painful disorders and disease processes around or in the abdomen. Some of these are acutely life threatening, others can be self-limiting. Multiple causes have to be considered in the diagnostic work-up. During the initial assessment, the following questions should be answered:

* Is the patient dying?

* What is the patient dying from?

* What can I do to improve the patient's survival and well-being?

* Does the case require surgical or medical management?

* Does the patient require in-house management or is outpatient care also possible?

Initial assessment includes triage and secondary survey, including physical examination, minimum database and diagnostic imaging.

## Triage:

**Airway:** Usually airways are not affected in patients presenting with acute abdomen. In some cases, vomited material or mucous can be found in the oral cavity. In these cases, the material should be removed.

**Breathing:** Intra-abdominal disorders may lead to pulmonary complications. Abdominal masses or gas filled organs cause compression of the diaphragm, which may lead to atelectasis, decreased tidal volume, polypnoea and hypoxaemia. Patients with severe vomiting and salivation may aspirate vomited material or saliva. These can cause aspiration pneumonia. Additionally, inflammatory causes of acute abdomen, like severe pancreatitis, may lead to systemic inflammation and disseminated intravascular coagulation, which are predisposing factors for acute respiratory distress syndrome. Emergency treatment consists of adequate oxygen therapy.

**Circulation:** In most cases of acute abdomen, patients suffer from significant fluid losses including hypovolaemic and distributive shock. Clinical diagnosis focusses on the clinical shock parameters. Keep in mind that cats often react with hypothermia and bradycardia to shock.

Adequate fluid therapy is mandatory to keep the patient alive. Especially if the patient is in distributive shock, potentially decreased colloid osmotic pressure should be noted and therapeutically addressed. These patients may require colloids, plasma or albumin substitution.

**Other:** Abdominal pain is a major finding. It should be actively looked for. Adequate analgesia should be initiated very early during the patient's resuscitation and diagnostics. The author prefers pure µ-agonists, like methadone or fentanyl.

The use of anti-emetics in the acute abdomen accompanied by vomiting and nausea is often controversial. Anti-emetics improve the well-being of the patient. On the other hand, symptoms will
be less severe, which may convince some owners and inexperienced vets not to work up the patient and send it home with symptomatic treatment. Therefore, initiation of patient work-up should be decided on the basis of the initial symptoms and not on the basis of the symptoms after anti-emetics.

**Secondary survey:**

<u>History</u> should focus on duration of the symptoms, ingestion of foreign material, frequency of vomiting, consistence and colour of the material, pre-treatment and or signs of pre-existing diseases.

<u>Physical examination</u> aims to find the cause and sequelae of the acute abdomen. It should include assessment of volume and hydration status, temperature, rectal examination and proper abdominal palpation. Be prepared to look for localized, painful structures especially in cats.

During physical examination, acute abdomen should be differentiated from spinal pain. A proper neurologic examination is helpful. Some patients with respiratory disorders show signs of abdominal discomfort during palpation. Respiratory diseases should be included in the differentiation.

<u>Initial blood work</u> should consist of Hct, WBC count, electrolytes, lactate, glucose and creatinine and/or urea. It is often helpful to include a differential WBC count and a blood gas analysis. Blood gas values help to access severity of hypoperfusion and may give further information on the underlying cause, e. g. hypochloraemic metabolic alkalosis is often seen in proximal intestinal obstruction.

<u>Diagnostic imaging</u> should be initiated in the early course of the case work-up, because some diseases presenting as acute abdomen may require immediate surgical intervention. In recent years, point of care ultrasound has gained increasing recognition in the emergency world, not only for trauma patients. It helps to in the diagnosis of free fluid, free gas, large masses and intestinal obstruction. The choice between performing ultrasound or doing radiography depends on the clinician's experience with the technology and the most likely underlying disease. The next lecture will focus on this topic.

<u>Free abdominal fluid analysis</u> is a large area of interest in the acute abdomen. It is often helpful in differentiating surgical indication from conventionally manageable diseases. Leukocytosis >10,000/µl, intracellular bacteria, karyolitic neutrophils, decreased glucose concentration and increased lactate concentration in the fluid are indicative of a septic or severe inflammatory process as peritonitis or intestinal wall injury. A PCV in the fluid that is greater than the blood PCV indicates haemoabdomen. An increase of creatinine or bile in the fluid more than 2-fold compared to the blood concentration indicates uroabdomen or bile peritonitis.

Indications for <u>surgical management</u> of the non-traumatic acute abdomen are:

* Free air

* Septic peritonitis

* Bile peritonitis

* Necrotizing pancreatitis

* Foreign body, sub-ileus

* Volvulus

* GDV

* Non-traumatic, non-coagulopathic haemoabdomen
* Some neoplasia

* Abscess

* Uroabdomen with significant urinary tract perforation

* Torsion of abdominal organs such as spleen, liver, uterus or intra-abdominal testes

Conservative treatment can be initiated for e. g.

* Pancreatitis

* Moderately dilated intestines without obstruction

* Paralytic ileus

* Uroabdomen without significant urinary tract perforation

In-patient care should be considered if the patient suffers from severe systemic abnormalities as follows:

* Dehydration > 8%

* Severe ongoing fluid losses

* Hypothermia

* Hypoglycaemia

* Severe hypokalaemia

* Moderate to severe pain

* Paralytic ileus

Regular reassessment of the patient is mandatory, especially in compensated intestinal diseases, peritonitis, sepsis and diseases with fluid losses that may decompensate in a short time. This should not only include clinical examination but also imaging such as ultrasound and laboratory analysis.
# IMAGING: GI DISEASE SHALL I BRING IT TO THEATRE OR NOT?

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

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

Abdominal radiography can occasionally be sufficient to determine whether surgery is necessary or not in a patient with gastrointestinal (GI) disease. For example, in most cases of gastric dilatation volvulus or when a GI foreign body (FB) is radiographically visible no further imaging is required prior to surgery.

In many cases, however, GI foreign bodies are not identified on plain radiographs despite being the cause of GI symptoms. Ultrasound is routinely used to differentiate between mechanical and functional ileus. When available, it has eliminated the need for gastrointestinal contrast radiography. Luminal dilatation resulting in jejunal diameter of more than 1.5 cm has been suggested as a useful indicator for presence of small intestinal obstruction in dogs.¹

Once intestinal dilatation is observed, a thorough ultrasonographic search for a possible cause of obstruction should be undertaken. Ultrasound enables us to identify and distinguish between intraluminal obstructive structures and mural masses. Foreign bodies on ultrasound are characterised by variable degrees of distal acoustic shadow and surface reflection. The ultrasonographic appearance of foreign bodies is totally dependent on the nature of the material. Many common foreign bodies (e.g. bones) have a hyper-reflective interface and cause a strong acoustic shadow, however some foreign bodies have ultrasound propagation characteristics similar to soft tissue; therefore they do not cause a strong acoustic shadow.

Partial intestinal obstruction, recent obstruction and duodenal obstruction may present without obvious radiographic signs of intestinal dilatation. In cases of duodenal obstruction, the duodenum is dilated but the dilatation is not clearly identified on the radiographs because the duodenum contains soft tissue/fluid dense material and no gas. The absence of gas in the dilated loop of intestine decreases the chance to confidently diagnose an obstruction on the basis of radiography alone, except when the FB is radiographically obvious. In these cases further investigation with ultrasound or abdominal CT is necessary.

Linear foreign bodies and intestinal intussusceptions are readily identified with ultrasound. In the case of linear foreign bodies the intestine presents with a typical plicated appearance and the intraluminal linear foreign body is very commonly seen. Intestinal plication must be differentiated from intestinal corrugation on ultrasound because the two are very different entities; bowel wall corrugation has been associated with pancreatitis, enteritis, peritonitis, neoplasia, or bowel wall ischaemia.² Intestinal intussusception has a pathognomonic appearance of multiple concentric mural layers when viewed in transverse section. In cats intestinal intussusception is more frequently associated with an underlying intestinal neoplasia compared to dogs that seem more likely to develop it due to underlying inflammatory disease.

In private practice ultrasound is commonly used to differentiate between mechanical obstruction, gastroenteritis and pancreatitis. The ultrasonographic finding of an enlarged, hypoechoic pancreas
surrounded by hyperechoic mesenteric fat and possibly by some peritoneal fluid is compatible with pancreatitis.

In a recent study comparing ultrasound and computed tomography for the diagnosis of canine GI mechanical obstructions, with findings of exploratory surgery as the reference standard, the sensitivity and specificity of abdominal ultrasonography were 100% and 67%, respectively. The positive predictive value (PPV) for ultrasonography was 93%, and the negative predictive value (NPV) was 100%. For CT, sensitivity and specificity for the diagnosis of mechanical gastrointestinal obstruction were both 100%, and the PPV and NPV were also both 100%.³

In another study comparing abdominal radiology and CT for detecting mechanical intestinal obstruction in dogs, CT was more sensitive (95.8% vs. 79.2%) and specific (80.6% vs. 69.4%) compared to radiographs, but the difference was not statistically significant.⁴

In some cases of gastrointestinal disease, the diagnostic utility of abdominal ultrasound over other diagnostic tests (such as endoscopy) is debated. Investigation of the stomach with ultrasound can be challenging, particularly in deep chested dogs. It is reported that in dogs presenting with chronic vomiting the contribution of abdominal ultrasound was high only in 27% of the cases.⁵ This study suggests that ultrasound is more indicated in older patients, in patients presenting with a greater number of vomiting episodes and weight loss, and when a neoplastic disease is suspected.

Ultrasound and CT are used to look for non-perforated gastro intestinal ulcerations whereas radiology can only be used to detect pneumoperitoneum in case of perforated GI ulcers or abdominal fluid in case of peritonitis. In a recent study sensitivities of radiography, ultrasonography and CT were 30, 65 and 67% in dogs with non-perforated ulcers and 79, 86 and 93% in dogs with perforated ulcers, respectively.⁶ In this article the reviewed cases span over 10 years and have been seen in ultrasound by various radiologists; no information is provided about the possibility of operator dependent accuracy of ultrasound for detection of GI ulcerations. However, in practice, this variable is likely to affect the results. Other factors that may affect the ultrasonographic ability to identify ulcerations are location (gastric versus intestinal), number and size of the ulcers.

The use of ultrasound to detect focal accumulation of peritoneal fluid and guide sampling of the fluid facilitates the early detection of septic peritonitis secondary to GI ulcerations.

In conclusion the clinician should decide whether radiology, ultrasound, CT or a combination of these imaging techniques is most appropriate in each particular case depending on the nature of the underlying GI disease.

## References

1. Sharma A, Thompson MS, Scrivani PV, et al. Comparison of radiography and ultrasonography for diagnosing small-intestinal mechanical obstruction in vomiting dogs. Vet Radiol & Ultrasound 2011; 52(3): 248-255

2. Moon ML, Biller DS, Armburst LJ. Ultrasonographic appearance and etiology of corrugated small intestine. Vet Radiol and Ultrasound 2003; 44(2): 199-203
3. Winter MD, Barry KS, Johnson MD et al. Ultrasonographic and computed tomographic characterization and localization of suspected mechanical gastrointestinal obstruction in dogs. JAVMA 2017; 251(3): 315-321

4. Drost WT, Green EM, Zekas LJ et al. Comparison of computed tomography and abdominal radiography for detection of canine mechanical intestinal obstruction. Vet Radiol Ultrasound. 2016 57(4): 366-375.

5. Leib MS, Larson MM, Panciera DL et al. Diagnostic utility of abdominal ultrasonography in dogs with chronic vomiting. J Vet Intern Med 2010; 24: 803-808.

6. Fitzgerald E, Barfield D, Lee K et al. Clinical findings and results of diagnostic imaging in 82 dogs with gastrointestinal ulceration. JSAP 2017; 58(4): 211-218.
# IMMUNE MEDIATED HAEMOLYTIC ANAEMIA: TREATMENT UPDATES

Alex Lynch, BVSc(Hons) DACVECC MRCVS

North Carolina State University, Raleigh, NC

Immune mediated haematological diseases are commonly identified in dogs and to a lesser extent in cats. Immune mediated destruction of mature erythrocytes (i.e. immune mediated haemolytic anaemia [IMHA]) and platelets (i.e. immune mediated thrombocytopaenia) are most commonly encountered. This lecture will focus on treatment strategies for IMHA, with discussion of newer developments that may help with these cases.

## Pathophysiology of IMHA

An understanding of the basic mechanisms underpinning immune-mediated diseases is helpful to understand the principles behind case management¹,². Under normal circumstances, the immune system is adept at recognizing and removing foreign entities (e.g. bacteria). In the case of bacteria, molecular characteristics on their cell surface termed pathogen associated molecular patterns (PAMPs) like lipopolysaccharide interact with specialized receptors on immune system cells (pattern recognition receptors or PRRs). The engagement of PAMPs with PRRs kick starts intracellular signaling pathways within immune system cells leading to the transcription of genes involved in the adaptive immune response. The adaptive immune system is the specialized portion of the immune system based on the presence of 'immunological memory' mediated through a complex variety of cellular (white blood cell mediated) and humoral (antibody based) mechanisms. The endpoint of the interaction between the innate and adaptive immune responses is the elimination of foreign pathogens with the potential for established long-term protection through acquisition of immunological memory. In the context of immune mediated disorders, specifically when considering auto-immune conditions, there may be inappropriate engagement of PRRs with self-antigens that have been falsely identified as being foreign. This might include red blood cell or platelet surface antigens leading to their elimination, much in the same way the immune system will target invading pathogens. The factors necessary for autoimmunity to occur are complex and multifactorial, including genetic predisposition, age, breed, neuter status,³ environmental triggers, the role of infection, as well as drug reactions. Clinically it can prove challenging to identify whether animals with immune-mediated disorders have primary ('autoimmune') diseases or whether their immune-mediated disorder has developed secondary to another comorbidity (e.g. infection, neoplasia).

In cases of IMHA, immune mediated targeting and destruction of red blood cells occurs.⁴,⁵ The destruction may occur within the vasculature affecting circulating erythrocytes (intravascular IMHA) or in organs of the haematopoietic system like the spleen (extravascular haemolysis). Middle aged to older dogs are commonly affected, with a possible predilection for females, with certain breeds of being over represented (e.g. Cocker spaniels, Maltese terriers, Dobermans). Clinical signs commonly seen in dogs with IMHA including tachypnoea and tachycardia are typically related to issues with impaired oxygen delivery to tissues due to anaemia (i.e. reduced haemoglobin mass impairing oxygen carrying capacity) rather than an inability to oxygenate normally (i.e. lungs are usually normal). Additional symptoms relating to the haemolytic process may be noted by owners, including very dark ('port wine') urine due to haemoglobinuria, pallor with icterus, and lethargy. Some pathophysiological differences likely occur between intravascular and extravascular forms of IMHA. Intravascular IMHA
appears to be largely mediated by IgM antibodies, with affected dogs usually being severely affected, associated with their massive acute red cell destruction, and more likely to have haemoglobinuria. Extravascular haemolysis results in haemolysis of red cells in the erythrophagocytic system (e.g. spleen) and tends to be IgG mediated. A diagnosis of IMHA is ideally made by identifying regenerative anaemia (often a robust regenerative response characterized by marked reticulocytosis) with at least two of spherocytosis, autoagglutination, or positive Coomb's test. The Coomb's test, also known as the direct antibody test, effectively enables visual recognition of antibodies mediated towards red cells in the laboratory setting. In addition, it is typical for dogs with IMHA to have leukocytosis (neutrophilia with left shift), normal or slightly elevated total proteins, and hyperbilirubinaemia (which can be very high in some dogs). If a dog does not perfectly fit these signs, an immune-mediated condition could still be present, but directed at red cell precursors. The American College of Veterinary Internal Medicine has recently published a consensus statement on the diagnosis of IMHA in dogs.⁵

A diagnostic work up focused on identifying any potential triggers for immune-mediated disease is recommended in case of suspected IMHA. Large disease categories to consider include underlying infectious disease (especially vector borne diseases), neoplasia and drug/toxin exposure. Consequently, comprehensive blood work (CBC and serum chemistry), urinalysis +/- urine culture, vector borne testing for disease endemic to your area (e.g. babesia), thoracic radiographs and abdominal ultrasound are all reasonable recommendations for these patients. In individual patients aspirating abnormal tissues (e.g. enlarged peripheral lymph nodes, abdominal organs with abnormal ultrasonographic appearance) may also help confirm underlying disease processes (e.g. lymphoma). Understandably not all budgets can stretch to as comprehensive a work up as this and some variation on these plans may be necessary. Another important rule out for dogs with haemolysis is the potential for zinc toxicity that may occur following ingestion of zinc containing metallic objects (e.g. pennies, zippers). For cats, retroviral testing should be performed in any cat with suspected IMHA with a particular concern for FeLV in affected individuals.

## Treatment of IMHA

**Immunosuppressive drugs:** Immunosuppressive drugs are the core therapeutic strategy for dogs with IMHA. The current evidence base demonstrates that corticosteroids (dexamethasone, prednisone) are the only consistently effective immunosuppressive agent for this disease. Clinical remission is considered when the haematocrit stabilizes and the dog is no longer transfusion dependent. With corticosteroids, this usually takes 5-7 days. No convincing evidence exists that additional agents necessarily speed up the recovery process⁴ but additional benefits of dual therapy may exist. Long term administration of corticosteroids are renowned for inducing a variety of unpleasant side effects (e.g. panting, polyuria, polyphagia). Once remission has been achieved, co-administration of other immunosuppressive drugs may enable faster weaning of the steroid component, without adversely increasing the risk of relapse. It is generally advisable and necessary to immunosuppress pets with IMHA for a protracted period of time (6 months or more) with cautious dose reduction in this time period.

Cyclosporine functions as an immunosuppressive by inhibition of T lymphocyte function. Cyclosporine has theoretical advantages over steroids for IMHA since it is considered to induce immunosuppression faster than steroids. There is no convincing evidence it more reliably achieves remission for IMHA than steroids alone however. It is recommended that cyclosporine therapeutic monitoring be used to tailor
dosing in individual patients. Another important pharmacological feature of cyclosporine is that it is
metabolized by the cytochrome P450 system. Consequently, concurrent administration of drugs also
metabolized by P450 enzymes (e.g. ketoconazole) could help to reduce the dosage and therefore cost
of cyclosporine. Azathioprine is also commonly employed as a second line immunosuppressive agent
in dogs. It is a thiopurine analog and interferes with purine metabolism within cells inhibiting normal
synthesis of DNA, RNA, and proteins.¹ Its onset of action is considered to be quite slow taking at least
7 days to achieve immunosuppression. Consequently, it may be less helpful in acute IMHA but can be
helpful in the long term for its glucocorticoid sparing effects. Mycophenolate works similarly to
azathioprine but has a reported faster onset of action.¹ It is a prodrug of mycophenolic acid, which
inhibits the inosine monophosphate dehydrogenase enzyme needed for purine synthesis. Disruption
of purine synthesis leads to both inhibition of T lymphocytes, B lymphocytes, and antibody production.
Oral and intravenous formulations exist but oral administration is much more common. A practical
limitation is the gastrointestinal intolerance of some dogs to mycophenolate. Myelosuppression could
theoretically also occur. There is again no convincing evidence that mycophenolate with steroids
confers any advantage over steroids alone for IMHA. Other miscellaneous medications have also been
considered as adjunctive immunosuppressive agents, including danazol and leflunomide.¹ In many
circumstances, personal clinician preference may dictate their 'go to' second line immunosuppressive
agent or patient factors (e.g. drug cost for size of patient) will influence the drugs used.

Human intravenous immunoglobulin (HIVIG) is another therapeutic option that has been used in dogs with IMHA. The mechanism of action for HIVIG likely involves saturation of Fc receptors on macrophages with the antibodies contained in this product. The saturated Fc receptors will then not interact with the antibody coated red cells or platelets, preventing their clearance from the body by phagocytosis. A prospective study performed in dogs with IMHA found no advantage of glucocorticoid and HIVIG administration with respect to achievement of clinical remission or length of hospitalization compared to glucocorticoid monotherapy.⁶ In contrast, HIVIG does appear to expedite time to clinical remission in dogs with ITP also treated with glucocorticoids, yet did not prove superior to glucocorticoid and vincristine.⁷ Safety concerns also exist in using allogenic protein sources in dogs, although overall tolerability appears to be good based on the current veterinary evidence base. It is also a costly product and this will play a role in the likelihood of recommending its usage in veterinary patients.

*Extracorporeal options:* An emerging alternative therapeutic strategy for IMHA is plasmapheresis or therapeutic plasma exchange (TPE).⁸⁻¹⁰ This technique involves separation of plasma and red cells, removal of this plasma that contains immunoglobins, and replacement with donated plasma from healthy dogs. Some clinicians replace only with plasma, while others will use a combination of synthetic colloid with plasma. The rationale for TPE is that efficient removal of immunoglobulins will limit the number available to target red blood cells. The author has seen this technique used in dogs that appear refractory to conventional therapy. Some dogs have responded very well to this therapy and this therapy may become a more important and available treatment option in the future.

*Ancillary supportive strategies:* Non-immunological management of IMHA cases may involve red blood cell transfusion. There has historically been concern that providing red cells to an actively haemolysing animals may add 'fuel to the fire'. There is no compelling evidence that this is true, while severe anaemia is life threatening in affected patients. Provision of extra red cells/haemoglobin to
improve oxygen delivery to their tissues is helpful, even if it is a short lived therapeutic measure. Some dogs with IMHA are transfusion dependent, meaning several transfusions are needed to support them before their immunosuppression is optimized and their haematocrit stabilizes. Interestingly it is uncommon for dogs with IMHA to be hypovolaemic, with normovolaemia (or even hypervolaemia) being more common. Consequently, replacement fluids (e.g. lactated Ringer's solution, colloids) are unlikely to be helpful in ameliorating their clinical signs associated with anaemia. In a similar vein, while oxygen administration (e.g. flow by) will not be harmful in the short term, abnormal breathing patterns early in the disease course in these pets are typically due to their anaemia. Later on, new onset respiratory effort and tachypnoea in a dog with IMHA could be indicative of other complications (e.g. pulmonary thromboembolism).

**Antithrombotic strategies:** Thromboembolic complications of IMHA are important causes of morbidity and mortality in dogs with IMHA. Multiple factors are likely present in these dogs to explain their prothrombotic tendency. Previous work has demonstrated improved outcome for dogs receiving antithrombotic medications.¹¹ The best drugs to use to lower the risk of thromboembolic complications are open to debate. Currently a combination therapy of a drug to inhibit platelet function (clopidogrel or low dose aspirin) with a drug to slow down the clotting cascade (e.g. heparin, rivaroxaban) is usually recommended. Challenges exist with administering oral medications in sick dogs in the acute setting however, with further issues relating to optimal at-home therapy (e.g. drug choice, duration of treatment) after discharge from the hospital. Newer anticoagulant medications (e.g. rivaroxaban) are growing in popularity since they are once daily oral medications, although our clinical experience of these medications is in our infancy. The greatest risk of thromboembolism is present in the first two weeks of therapy and the ideal duration of antithrombotic prescription in these dogs is not known. There is evidence that inflammation is closely associated with thromboembolic risk, so weaning antithrombotic medications when inflammation wanes in affected dogs is a reasonable strategy. It is also important to consider treating underlying disease processes when present (e.g. antimicrobials for infectious diseases). Recently, the American College of Veterinary Emergency and Critical Care have published evidence based guidelines on the use of antithrombotics in small animals.¹²

## References

1. Whitley NT, Day MJ. Immunomodulatory drugs and their application to the management of canine immune-mediated disease. J Sm Anim Pract. 2011;52(2):70-85.

2. Lewis DH, et al. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med. 2012;26(3):457-482.

3. Sundburg CR, et al. Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study. BMC Vet Res. 2016;12(1):278.

4. Goggs R, et al. Predicting Outcome in dogs with Primary Immune-Mediated Hemolytic Anemia: Results of a Multicenter Case Registry. J Vet Intern Med. 2015;29(6):1603-10.

5. Garden OA, Kidd L, et al. ACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats. J Vet Intern Med 2019;1:1-22

6. Whelan MF, et al. Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia. J Vet Emerg Crit Care. 2009;19(2):158-64.
7. Balog K, et al. A prospective randomized clinical trial of vincristine versus human intravenous immunoglobulin for acute adjunctive management of presumptive primary immune-mediated thrombocytopenia in dogs. J Vet Intern Med. 2013;27(3):536-41.

8. Tovar T, Deitschel S, Guenther C. The use of therapeutic plasma exchange to reduce serum bilirubin in a dog with kernicterus. J Vet Emerg Crit Care. 2017;27(4):458-64.

9. Scagnelli AM, Walton SA, et al. Effects of therapeutic plasma exchange on serum immunoglobulin concentrations in a dog with refractory immune-mediated hemolytic anemia. J Am Vet Med Assoc. 2018;252(9):1108-1112.

10. Crump KL, Seshadri R. Use of therapeutic plasmapheresis in a case of canine immune-mediated hemolytic anemia. J Vet Emerg Crit Care. 2009;19(4):375-80.

11. Helmond SE, Polzin DJ, et al. Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs. J Vet Intern Med. 2010;24(3):597-605.

12. Blais MC, Bianco D, et al. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 3 – Defining antithrombotic protocols (dose, frequency, route, complications) for use in dogs and cats at risk of thrombosis. J Vet Emerg Crit Care 2019; 29(1):60-74
# PANCREATITIS ASSOCIATED ACUTE KIDNEY INJURY

Alex Lynch, BVSc(Hons) DACVECC MRCVS

North Carolina State University, Raleigh, NC

Inflammation of the pancreas, which can either be acute or more chronic in nature, is an important disease process affecting dogs and cats. Pancreatitis develops when there is excessive activation of digestive enzymes (e.g. trypsin) within the pancreas, which overwhelms local defences, leading to intrinsic damage of the organ.¹ The resulting inflammation can vary in severity, which corresponds to variability in clinical symptoms and illness severity in affected pets. Some cases of acute pancreatitis may lead to considerable morbidity and potentially mortality. The ensuing systemic inflammatory response triggered by acute pancreatitis may lead to downstream organ failure (e.g acute kidney injury [AKI]).² This lecture will review the pathophysiological mechanisms underpinning pancreatitis associated AKI and outline the clinical approach to these cases.

## Pathophysiology of pancreatitis associated AKI

The pathophysiology of pancreatitis is quite complex. Under normal circumstances pancreatic digestive enzymes do not cause intrinsic damage to the pancreas since they are stored as zymogens (biologically inactive enzymes) within compartmentalized organelles.¹ In addition, endogenous inhibitors of these enzymes (e.g. pancreatic secretor trypsin inhibitor) are produced within the same region of these enzymes. Therefore, in the event of inappropriate zymogen release and activation, safeguards are present to limit any potentially deleterious effects. There are also circulating antiproteases within the blood should there be systemic release of activated pancreatic enzymes.¹ In cases of pancreatitis, these safeguards become overwhelmed and an acute inflammatory response is triggered. Inflammation is characterized by vasodilation and increased vascular permeability, which promotes tissue oedema, as well as extravasation of neutrophils into the local tissues. Further complications may develop associated with excessive cytokine release leading to systemic inflammation, as well as oxidative damage. Therefore, severe acute pancreatitis can lead to patients exhibiting systemic signs of severe inflammation (systemic inflammatory response syndrome or SIRS). These include, but are not limited to, tachycardia, hypotension, altered respiratory function, pyrexia, leukocytosis, and third spacing of fluids.

Animals with severe signs of acute pancreatitis are at risk of developing other organ dysfunctions. In some instances, several organ dysfunctions may occur simultaneously and fulfil criteria of multiple organ dysfunction (MODS). MODS describes a situation where acute organ dysfunctions develop such that homeostasis cannot be maintained.³ Mechanisms underpinning MODS development are complex and only partially understood. Different theories exist regarding the development of MODS. The one hit theory suggests that a very severe primary insult leads to organ dysfunction. The two hit theory, in contrast, describes a situation where a primary insult (e.g. pancreatitis) leads to a second insult (e.g. AKI). An alternative explanation is described as the sustained hit theory where there is an ongoing disease process. AKI secondary to pancreatitis may best fit with either the two hit or sustained hit theories, although there may be variation in individual patients. Other important considerations for organ dysfunction during inflammation, are that there is cross talk between inflammation and coagulation. Consequently, there is a prothrombotic tendency during inflammation that may lead to ischaemic end organ damage.
AKI is an important organ dysfunction, since its impact on mortality can be so profound, as well as contributing to the morbidity of an individual animal. Several mechanisms may be relevant to the development of pancreatitis associated AKI.³,⁴ Third spacing of fluids, as well as gastrointestinal fluid losses, from patients with pancreatitis may lead to hypovolaemia. This therefore risks renal hypoperfusion and upregulation of the renin-angiotensin-aldosterone system that will impair glomerular filtration rate. There may also be renal tubular cell death via apoptosis or necrosis. In some instances, marked abdominal fluid accumulation may cause rapid rises in intra-abdominal pressure risking abdominal compartment syndrome. In these situations, intra-abdominal hypertension will also severely limit renal perfusion and risks AKI development. Cross talk with inflammation may also lead to intravascular coagulopathy (thrombotic microangiopathy) that will further contribute to the pathophysiology of AKI.

## Diagnosing pancreatitis and AKI

The symptoms of pancreatitis in dogs can vary in terms of severity. More severe cases may be accompanied by vomiting, inappetance, lethargy, fever, dehydration, abdominal discomfort and diarrhoea. Symptoms in cats can be quite vague and typically less severe than symptoms in dogs. In severe cases, other symptoms related to organ dysfunction can be identified. In instances of AKI, this may include oligoanuria or polyuria depending on the phase of their disease. Other organ system dysfunctions may include respiratory dysfunction (e.g. tachypnoea, hypoxaemia), coagulation abnormalities (e.g. thrombocytopenia, prolonged coagulation times), and cardiovascular instability (e.g. hypotension, arrhythmia). Definitive diagnosis of pancreatitis would require histopathology (e.g. biopsy) but is rarely performed in clinical cases. More commonly a clinical diagnosis is made based on a compelling clinical picture based on symptoms, diagnostic imaging findings, and laboratory abnormalities. Although radiographic findings may be suggestive of pancreatitis, ultrasonographic changes are typically more helpful. Classic changes on ultrasound for acute pancreatitis are hypoechoic pancreas with regional surrounding hyperechoic mesentery. One consideration for ultrasonographic pancreatitis changes however is that the severity of clinical symptoms imperfectly relates to the ultrasound images. Several laboratory abnormalities may also be encountered in patients with pancreatitis. These may include increased amylase, lipase, liver enzymes, and potentially hyperbilirubinaemia. Canine and feline specific pancreatic lipase (cPLI and fPLI) are also commonly measured. Based upon the sensitivity and specificity of these tests, negative results are helpful for ruling out pancreatitis, although false positives may be encountered with other acute GI disorders.⁵ A combination of compatible clinical signs, compelling diagnostic imaging findings, and fitting laboratory abnormalities can usually allow a clinical diagnosis of pancreatitis to be made. In cats, consideration for whether concurrent inflammation in the GI tract and liver may be present (i.e. triaditis) is also an important consideration.

Traditionally, measurement of serum urea and creatinine have been used to identify kidney disease. Any level of azotemia is then ideally interpreted in light of urinalysis, particularly urine concentrating ability, as well as other clues towards chronicity (e.g. body condition score, muscle scoring, haematocrit). The limitation of creatinine is that it is a relatively late stage marker of kidney dysfunction. Consequently, small rises in creatinine in the hospitalized patient are considered relevant and are used to clue clinicians into the possibility of acute kidney injury. Commonly an increase in serum creatinine of 26 µmol/L (0.3 mg/dL) or more is used in AKI scoring schemes.⁶ There is growing interest in novel urinary and serum biomarkers that may clue us into the presence of AKI sooner than
conventional renal biomarkers. Two additional clinical indicators when monitoring an animal for AKI are serial body weights and urine output.⁷ In the hospitalized pet, fluctuations in body weight can be very helpful gauges of water shifts (e.g. loss of water will reduce body weight). Weighing hospitalized animals at least once daily or even more frequently is both a cheap and helpful monitoring tool when there is concern for volume overload. This is especially helpful when used in combination with urine output. For example, an animal that is receiving intravenous fluids and gaining weight but not urinating reliably may be third spacing fluids. The most accurate means of quantifying urine output is by placement of an indwelling urinary catheter. While this is a common procedure in more severely compromised pets, there is a risk of infection associated with the procedure and a risk-benefit analysis should be considered before placing a catheter. When a urinary catheter is not placed, more subjective assessment of voided urine is a reasonable alternative. When an animal is weighed serially, it is good practice to weigh them after they have voided urine.

### Clinical management of pancreatitis associated AKI

Management of pancreatitis associated AKI involves both treatment of the primary insult (i.e. pancreatitis), as well as specific considerations for AKI. Treatment directed at the likely trigger for pancreatitis is uncommonly possible. Infection is rarely the primary cause of pancreatitis, although antibiotics may be considered if there is concern for GI translocation in dogs or concurrent cholangitis in cats. Other triggers for pancreatitis include dietary indiscretion and dyslipidaemias in certain breeds of dogs (e.g. miniature schnauzers). Most therapy for pancreatitis is largely supportive in nature. This includes anti-emetics, gastroprotectants and assisted feeding (e.g. nasogastric tubes). Analgesia is an incredibly important aspect of pancreatitis management. Providing systemic analgesia, for example opioids, ketamine and lidocaine, is commonly done. There are some disadvantages with this approach however since opioids can be associated with adverse systemic effects including nausea and ileus. Alternative approaches to analgesia, for example epidural analgesia may be good alternatives in some pets. Antithrombotic strategies (e.g. heparin) may be considered given the prothrombotic tendency associated with pancreatitis in dogs.

Fluid therapy for pancreatitis has particular relevance when considering the risk for pancreatitis associated AKI. Replacement fluids (e.g. lactated Ringer's solution) are often used for treatment of hypovolaemia and dehydration. Ongoing fluids for maintenance while patients are not eating and drinking are also commonly provided. As mentioned earlier, very careful monitoring of fluids is needed in animals with pancreatitis since it may worsen third spacing. In animals with acute kidney injury, intolerance of fluid therapy risks worsening kidney infection. Consequently a fairly restrictive fluid therapy plan is recommended for pancreatitis cases. In situations where patients remain hypotensive despite fluid therapy, the use of vasopressor agents (e.g. noradrenaline) can be very helpful additions. In the event of AKI development associated with oligoanuria, discontinuation of fluids and diuretic therapy (e.g. furosemide) is indicated to facilitate offloading excessive fluid. When extracorporeal techniques are available, haemodialysis would be reasonable to offer in animals with AKI. The benefits of dialysis include clearance of nitrogenous wastes/uraemic toxins, assistance with acid-base and electrolyte balance, as well as to expedite correction of volume overload by removing excessive water. Although fish oils may be beneficial in some case of AKI, they are likely best avoided in cases of pancreatitis given the fear of exacerbating symptoms with an oral fat source. Although prognosis for animals with pancreatitis associated AKI is more guarded, it is certainly possible to manage these cases
successfully with good attention to detail and careful tailoring of therapeutics for the individual patient.

References

1. Mansfield C. Pathophysiology of acute pancreatitis: potential applications from experimental models and human medicine to dogs. J Vet Intern Med 2012;26:875-887.

2. Zhang XP, Wang L, et al. The pathogenic mechanism of severe acute pancreatitis complicated with renal injury: A review of current knowledge. Dig Dis Sci 2008;53:297-306.

3. Osterbur K, Mann FA, et al. Multiple organ dysfunction syndrome in humans and animals. J Vet Intern Med 2014;28:1141-1151.

4. Manokaran S, Edwin Fernando M, et al. A study of acute kidney injury in severe acute pancreatitis in a tertiary care hospital from South India

5. Haworth MD, Hosgood G, et al. Diagnostic accuracy of the SNAP and SPEC canine pancreatic lipase tests for pancreatitis in dogs presenting with clinical signs of acute abdominal disease. J Vet Emerg Crit Care. 2014;24(2):135-43.

6. Cowgill LD, Langston C. Acute kidney insufficiency. In: Bartges J, Polzin DJ, eds. Nephrology and Urology of Small Animals. Wiley & Sons, 2011.

7. DeLoor J, Daminet S, et al. Urinary biomarkers for acute kidney injury in dogs. J Vet Intern Med 2013;27(5):998-1010.
Scil Grant Award

ENDOVASCULAR SHEDDING MARKERS IN CRITICALLY ILL PATIENTS

Briganti A<fnref n="1" />, Di Franco C<fnref n="1" />, Meucci V<fnref n="1" />

**Objective:** To compare serum and plasma levels of syndecan-1 and hyaluronan in dogs with systemic inflammatory response syndrome (SIRS) and healthy dogs.

**Methods:** Thirty critically ill dogs with SIRS (Hauptmann criteria) were enrolled in a prospective observational study. Hematobiochemical parameters, arterial blood gas analysis, Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores were calculated on presentation and each day until discharge or death. Serum and plasma samples for syndecan-1 and hyaluronan measurements were taken on presentation (T0), after 24, 48, and 72 hours, and after 1 week, and stored in different aliquots at -20°C. Twenty healthy dogs were also enrolled as a control group for comparison of syndecan-1 and hyaluronan levels. Two different ELISA kits were used (canine and human) for syndecan-1 and a canine ELISA kit for hyaluronan measurement. Conventional statistical analyses was performed.

**Results:** Three critically ill dogs were excluded due to incomplete data. Of the 27 remaining dogs, 10 survived and 17 were non-survivors. All samples from healthy dogs were below the limit of detection for canine syndecan-1 and only 5 dogs (all non-survivors) in the critically ill group had detectable levels (189±178 pg/mL). Human syndecan-1 was significantly lower (P=0.01) in healthy dogs (n=7, 293±310 pg/mL) compared to critically ill dogs (n=8, 1013±587 pg/mL), all non-survivors. There were no significant differences in hyaluronan concentrations between healthy (1.34±0.5 ng/mL) and critically ill (1.63±0.6 ng/mL) dogs, or between survivors (1.29±0.5 ng/mL) and non-survivors (1.28±0.5 ng/mL). SOFA scores were significantly higher (P=0.001) in non-survivors, 7 (3-12) compared with survivors 1 (0-7).

**Conclusions:** This study found it is not possible to differentiate critically ill from healthy or survivors from non-survivors using the canine ELISA kit for syndecan-1 and hyaluronan. The human kit may be a better prognostic indicator, although it is still not able to detect low concentrations of syndecan-1. Further studies are necessary to evaluate the impact of storage length and temperature on biomarker detection. The SOFA score appears to predict mortality, although there is still considerable overlap between survivors and non-survivors.

<footnote n="1">¹Department of Veterinary Science, Veterinary Teaching Hospital “Mario Modenato”, University of Pisa, Italy.</footnote>
# GASTROINTESTINAL BLEEDING

Michael D Willard, DVM, MS, DACVIM

Haematemesis necessitates a slightly different approach than we take with other vomiting cases because some rule-outs become more likely while others become much less likely. We will be including upper gastrointestinal bleeding of any cause in this discussion. For starters, we will not be discussing vomiting that produces “flecks” of blood because this can be seen in any dog (and perhaps cat) with vigorous vomiting in which the gastric mucosa is traumatized by the physical act of vomiting. It is easy to identify fresh blood in the vomited material as long as the patient is not eating something that is red or that produces a pink color to the vomited material simply secondary to pigment leaching out of the food material. Most of the time, haematemesis is denoted by a “coffee-grounds”-like material that most clients (and some veterinarians) do not recognize as blood. A common mistake is being concerned over “dark stools”. Noting that a patient has dark stools is generally useless. Lots of dogs have dark stools and no problems or GI blood loss at all. The color of the stool is not an issue until the stool is pitch-tar-coal-asphalt black. Then it may be melaena (if it is not due to Bismuth or a lot of green bile giving it a near-black appearance). If in doubt, just place some fresh faeces on absorbent white paper and see if a reddish color diffuses out from the faeces, confirming that there is blood present. Melaena is only seen if there is acute loss of a lot of blood into the upper GI tract. Most dogs losing blood in the upper GI tract do not have any important changes in the colour of the faeces. Rather, you might see anaemia and hypoalbuminaemia. Also remember, you may or may not see hypoglobulinaemia; it all depends upon what the serum globulin concentration was before you started losing blood. Sometimes the BUN is higher than expected based upon the serum creatinine, but again this is only expected if there is a lot of blood being lost in a short period of time. Faecal occult blood tests are seldom that helpful or necessary, but can occasionally be informative in confusing cases. However, you need to use a test for which the laboratory has substantial experience in dogs so that the results can be meaningfully interpreted. Some faecal blood tests will routinely give a positive reaction when used on canine faeces.

When there is a substantial amount of blood being ejected from the mouth, there tend to be 3 major reasons: coagulopathy, swallowing blood from elsewhere and gastrointestinal ulceration/erosion (GUE).

## ULCERS AND EROSIONS:

Drugs are still a very important cause of GUE in the dog, despite all the newer, “safe” NSAIDs. High doses of dexamethasone also have substantial potential for significant GUE. Prednisolone by itself is generally not ulcerogenic unless it is used in very high doses (e.g., > 2-3 mg/lb/day) or is administered to a patient with other “ulcerogenic” risk factors (e.g., hypoxia, poor perfusion), and even then it is not particularly bad. Combining steroids and non-steroidal drugs can be devastating. You can use ultra-low dose aspirin (0.5 mg/kg once daily) when treating IMHA dogs with steroids.

There continues to be a substantial problem with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in dogs. All NSAIDs have the potential to cause devastating GUE, and some of these non-steroidal drugs are renowned for their toxic effects (i.e., indomethacin, naproxen, flunixin). Ibuprofen is also particularly ulcerogenic in the dog because it undergoes an enterohepatic circulation. Flunixin