Critical care is defined in Saunders Comprehensive Veterinary Dictionary as 'the care of a patient in a life-threatening situation of an illness'. In rabbits, there are many life-threatening situations and any painful or stressful situation can cause one. Pain and stress can trigger a sequence of events that may result in death. Critical care is aimed at avoiding those situations and treating, as well as treating the cause of the life threatening illness. Reducing stress and maintaining gut motility are vital parts of critical care.

The Effects of Stress in Rabbits

Rabbits are a prey species, with many predators. If they are injured or ill, they seldom show overt signs of pain. They usually sit quietly in the back of their cage and subtle behavioural changes can be easily overlooked. This does not mean they are not suffering and stressed. The effects of stress are:

 Elevated blood glucose levels. Handling or unfamiliar surroundings can elevate blood glucose levels that can be as high as 30mmol/l in rabbits with acutely painful conditions such as intestinal obstruction.

 Immunosuppression and flare-ups of latent infections. Stress can trigger clinical signs of infections that are latent in many rabbits. Examples include Encephalitozoon cuniculi, pasteurellosis or enterotoxaemia. It is not unusual for acute neurological episodes, such as head tilt, to follow a stressful incident. In general, the use of corticosteroids is not recommended in rabbits because of their immunosuppressive effects and the risk of flare-ups of latent infections.

 Slow gut motility, triggered by stimulation of the sympathetic nervous system, inhibits activity of the gastrointestinal tract and reduces gut motility. The stomach doesn't empty but water is resorbed so the contents become dry and impacted. Fermentation within the stagnant gut causes pockets of gas, especially in the caecum and hindgut.

 Hepatic lipidosis. Once gut stasis and anorexia have been present for a time, there is a reduction in the supply of fluid and nutrients to the foregut and to the caecal microflora. Absorption of carbohydrates from the small intestine is reduced and volatile fatty acid synthesis and absorption also falls. The rabbit goes into a negative energy balance, which stimulates the mobilisation of free fatty acids from adipose tissue. These are transported to the liver to be metabolised as an energy source. A metabolic bottleneck develops in the liver, which impairs the metabolic pathways that result in lipid transport to other tissue. Fat accumulates in the hepatocytes causing cholestasis and eventual liver failure. Rabbits with hepatic lipidosis are totally anorexic and have probably not eaten for a few days although the owners may not have noticed. Faecal output is absent. The rabbit is often ataxic and cold. Blood results can be bizarre due to the degeneration of the liver and kidneys and organ failure. Lipaemia is usually present, often in conjunction with severe hyperglycaemia. Liver enzymes and bile acid levels are elevated. There are no pathognomonic radiographic signs. Ultrasonography is more useful as increased echogenicity of the liver is seen.

 Ketoacidosis. During periods of negative energy balance, β-oxidation of free fatty acids in the liver increases, which causes ketone body production and metabolic acidosis. Rabbits are particularly susceptible to the effects of ketoacidosis because they lack some important metabolic pathways. For example, carbonic anhydrase is absent from the thick ascending limb of the renal tubule of rabbits, whereas in other species carbonic anhydrase is present in large amounts in the ascending tubule epithelial cells.¹ This enzyme catalyses the reversible conversion of water and carbon dioxide to carbonic acid, which is an important step in renal correction of acidosis. In other species, another renal response to acidosis is to increase ammonia production in response to either a fall in plasma pH or a fall in bicarbonate concentrations, but in the rabbit, ammonia is only produced in the kidney in response to a fall in bicarbonate concentrations and not a fall in blood pH.¹ As a result, rabbits have a limited ability to rapidly transfer hydrogen or bicarbonate ions between blood and urine, and therefore, cannot correct metabolic acidosis easily and can die.

 Gastric ulceration. The stomach of rabbits is very acidic and gastric ulcers can develop rapidly.

 Renal function. Oliguria lasting 30 to 120 minutes can be induced by stress because of the effects of adrenaline on renal plasma flow and glomerular filtration.² Rabbits also have limited capacity to concentrate urine, and dehydration results in marked pre-renal azotaemia that resolves once the animal is rehydrated. Blood urea concentration is not a reliable indicator of the degree of kidney damage. Caecal fermentation affects urea synthesis, so the type and amount of food that is undergoing bacterial degradation has an effect on blood urea concentrations. Also, severe renal pathology may only result in marginal increases in urea and creatinine levels. More than 50-75% of renal function needs to be lost before blood urea nitrogen and creatinine concentrations increase.⁴

 Shock. As in other species, shock develops rapidly in seriously ill rabbits and is manifested by hypothermia, bradycardia, poor peripheral circulation, a drop in blood pressure, mental confusion, and ataxia.³ Whatever the diagnosis, monitoring the mental state, heart rate, rectal temperature, mucous membrane colour, and respiration are useful to assess the rabbit's response to treatment. If the equipment and expertise are available, monitoring blood pressure is also useful. The normal systolic pressure is 90-130mm Hg and diastolic 80-90mm Hg.

Causes of Life Threatening Illnesses

Apart from stress induced illness, there is also a long list of other common life threatening diseases, such as intestinal obstruction and gastric dilation, abdominal catastrophes ( burst abdominal abscesses, pyometra), enterotoxaemia, paralytic ileus, flystrike, ureteral obstruction, urethral obstruction, trauma, liver lobe torsion, septicaemia, heart failure, viral haemorrhagic disease, nasal or pharyngeal foreign bodies, etc. The prognosis for many of these conditions is poor, no matter how good the critical care is.

Protocol for Critical Care

The aims of critical care are to treat the underlying condition, maintain gut motility, prevent and treat shock, maintain hydration and kidney function without overloading the circulation, and preventing hepatic lipidosis. Reducing stress and encouraging rabbits to eat are essential parts of the protocol which is:

 Diagnose and, if possible treat underlying cause. Radiography is usually indicated.

 Reduce stress by providing a warm, secure quiet environment and gentle handling. Consider the stressful effects of catheters, bandages, cannulae and collars and only use them if absolutely necessary.

 Maintain body temperature. Hypothermia is a common sequel to result of shock and inadequate food intake. The body temperature should be between 38.5-40°C and maintaining optimum body temperature is very important, although care is required to prevent rabbits becoming too warm. Rabbits are unable to sweat or pant effectively to dissipate body heat. Their main thermoregulatory mechanism is by heat exchange in the large arteriovenous anastomotic system in the ears.

 Provide analgesia. Analgesia is required for all sick rabbits based on the presumption that the underlying diagnosis may be painful. Fentanyl/fluanisone (Hypnorm, 0.2mls/kg SC) is a potent analgesic that is also sedative and is a good premedicant prior to anaesthesia. Buprenorphine (0.03mg/kg SC 2-3 times daily) has less sedative effects. NSAIDS, such as meloxicam (0.3mg/kg SC or PO, 1-2 times daily) can be given alongside opioids, although, if the rabbit is shocked and moribund, there is a risk of compromising renal circulation, so it is preferable to administer NSAIDS after the rabbit has responded to warmth and intravenous fluids. Tramadol (5mg/kg SC 2-3 times daily) is also useful and can be given in addition to other analgesics.

 Consider antibiotics. Although there may be no specific indication for antibiotic therapy, it is often advisable for anorexic rabbits without an obvious diagnosis. Dogs and cats with sepsis show a raised body temperature and although this can happen in rabbits, body temperature is not a reliable indicator of infection. Peracute pneumonia can present as sudden onset anorexia.

 Give fluids. Oral fluid therapy is satisfactory and sufficient for most ill rabbits, although intravenous fluid therapy is indicated for shocked rabbits. Routine intravenous therapy is not recommended as it is not without risk. The blood volume of a rabbit is 55-65 ml/kg in comparison with 90ml/kg in the dog, and high rates of infusion and excessive amounts of intravenous fluids can cause problems. Cardiac disease is not unusual and compromised circulatory function is common in shocked, moribund rabbits. These rabbits are cold and have a very low blood pressure and it is not uncommon for them to die within a minute or two of the start of fluid therapy. The initial bolus of fluid appears to overload the heart and cause heart failure. In many of these cases, death was probably inevitable but it is advisable to administer slow rates of warm fluid at the outset. Warming the rabbit prior to administration of fluids is also important. The overall amount of fluids that is given is also important, especially if it is given rapidly. Overperfusion causes pleural effusion, pulmonary and peripheral oedema. Lethargy, tachypnoea, heart murmurs, gallop rhythm, increased lung sounds and peripheral oedema are clinical signs of iatrogenic fluid overload, which is very difficult to reverse. An initial infusion rate of approximately 10 ml/kg/hour is recommended, i.e., 1 drop every 2-3 seconds for an 'average' (approximately 2.5kg) pet rabbit, using a giving set that delivers 60drops/ml. If necessary, this rate can be increased to 15ml/kg/hour after 10-15 minutes when the rabbit has warmed up. Hetastarch has been recommended³ (5ml/kg over 5-10minutes) instead of the high rate of crystalloid. It reduces the risk of cardiac overload and pulmonary oedema that is associated with high rates of crystalloids. Once the colloid has been given, the infusion rate of crystalloid can be dropped to maintenance rate of 2-4ml/kg/hour (i.e., 1 drop every 5 seconds for most rabbits). The total volume of fluid is <100ml/kg but this amount varies with the clinical condition of the rabbit and its response to treatment. Maintaining rabbits on fluids for more than a few hours is seldom necessary and can be stressful. Although ill or moribund rabbits seldom interfere with the drip, once they are rehydrated and warm, most rabbits require Elizabethan collars, extensive bandaging or even sedation to prevent them from pulling out the catheter or chewing through the tubing. At this point, it is preferable to electively take out the catheter out and maintain fluid balance orally.

 Nutritional support is advisable for all critically ill rabbits, except those with gastric dilation. In the author's opinion, syringe feeding is the best way and there are commercially available foods that are designed for syringe feeding rabbits and other small herbivores. These diets contain fibre which is both beneficial and problematic. Large particles of fibre stimulate gut motility but tend to clog the syringe. Small fibre particles provide substrate for caecal microflora. Adding baby cereal to the mixture makes it sweet, palatable and a source of calories that is quickly absorbed from the small intestine. Adding the cereal and leaving the mixture to stand gives it a smoother consistency so it goes through the syringe more easily. Syringe feeding requires time and patience but is possible in the vast majority of rabbits. Nasoesophageal or nasogastric tubes are rarely, or never, necessary. They carry a risk of iatrogenic complications such as inhalational pneumonia, gastric reflux, oesophagitis and stricture⁵ and an Elizabethan collar is often necessary to prevent the rabbit from removing the tube. Elizabethan collars add to the stress levels of the rabbit, and prevent cecotrophy. Stress increases the risk of anorexia and gut stasis.

 Prokinetic therapy with domperidone, metoclopramide, cisapride or ranitidine is indicated for most cases of anorexia. The choice of product depends on availability, which varies between countries.

 Tempting food is important. Hay encourages rabbits to eat, stimulates gut motility and provides a sense of security and familiarity. Other palatable foods include freshly picked grass, dandelions, spring greens, cabbage, kale, carrots or apple.

References

1.  Brewer, et al (1994). In The Biology of the Laboratory Rabbit 2nd Edition. pp. 63-70,

2.  Brod, et al (1949). Am. J. Physiol., 157, 31-3,

3.  Lichtenberger M. Vet Clin Exot Anim 10 (2007) 275-291,

4.  Campbell TW. (2004) in Veterinary Haematology and Clinical Chemistry, p469 ,

5.  Powers LV. (2006). J Exot Pet Med., 15, 201-209.