Introduction

Anorexia is one of the most common clinical signs of disease in cats presenting to the veterinary hospital. Unfortunately it is non-specific and a thorough medical workup is required to determine the underlying cause. Nutritional support is critical during the period of time that the primary problem is being sought and addressed. Additionally, several chronic diseases, such as chronic kidney disease and neoplasia, are common in cats and may result in inadequate caloric intake. Thus management of long term hyporexia is important. Poor body condition is associated with decreased prognosis in several species and has a negative effect on immune function, wound healing and strength.¹ Most importantly owners are distressed when their pet does not eat and it has a negative effect on owner perception of quality of life.

The Unique Feline

Cats have a higher requirement for protein and amino acids than other species. When nutrition is inadequate, energy is derived from mobilization of amino acids from muscles stores as opposed to fat.¹ Elderly cats are also unique in comparison to other species as they have stable to increased level of metabolism, as opposed to decreased metabolism.² A reduced ability to digest protein and fat has been documented in elderly cats. These combined factors make the utilization of high quality, easily digestible food product critical for these patients.³ Cats are also particularly sensitive to changes in environmental factors, such as the timing and location of feeding, as well as the food type; smell and “mouth feel” may also play into their willingness to eat.⁴

Pathophysiolgy

A meal can be thought of as having three parts; initiation, maintenance and termination. Different stimuli are responsible for each phase. Initiation of a meal depends heavily upon environmental stimuli such as olfactory, visual, tactile and auditory cues.⁴ Termination of a meal occurs as a result of negative feedback mechanisms such as gastric distention or presence of nutrients in the intestine. Suppression of appetite may occur as a result of psychological, environmental or physical factors such as decreased olfaction, nausea, pain, fever, ileus, vomiting that interfere with this process.^1,4 Circulating inflammatory mediators such as TNF-a, IL-1, and IL-6 may play a role in suppression of appetite.¹ As vomiting is a common manifestation of disease in cats, and nausea is likely involved even if vomiting does not occur, examining the pathophysiology of vomiting centers and receptors may help in determining the etiology of the inappetence and appropriate medical management.

Learned Food Aversion

Care should be taken to select the appropriate patients for appetite enhancement as learned food aversion is thought by most to be prevalent in cats. ⁴ Learned food aversion occurs when the patient associates nausea, pain or other physical manifestations of disease with the act of eating or the sight or scent of food. Even after the underlying illness is resolved, this aversion may remain. Therefore it is critical that cats that are overtly nauseous – drooling, gagging, turning away from food - particularly in hospital or in acute illness are not forced to eat lest food aversion be created. ⁴

If cats are too nauseous or critical to even consider oral feeding, or have not responded to appetite encouragement after 3-5 days, placement of an enteral feeding tube should be considered. Nasoesphageal, esophageal or gastrotomy tube can be chosen depending on the type and duration of feeding desired.¹ Parenteral feeding should be considered in cats that cannot tolerate enteral feeding. Additionally many clinicians feel that prescription diets (i.e. renal) should not be fed in hospital during a crisis lest an aversion be created to the diet desired for long term management. The best candidates for pharmacological enhancement of appetite are cats leaving the hospital with their acute crisis resolved, and cats with chronic disease in the home environment.

Therapies

Medical Management of Underlying Disease

Whenever possible it is obviously ideal to address the underlying disease condition. However in some chronic diseases, i.e. kidney disease, this is not possible and therefore medical management of complications of chronic disease are ideal. Dehydration, anemia, high blood pressure, and electrolyte imbalances can potentially play a role in inappetence and therefore should be addressed when applicable.

Environmental Factors and Food Choices

As cats are particularly sensitive to environmental factors, suggestions for appetite enhancement include: quiet environment with exclusive access without interference from bothersome household members, novel food type in cases of possible aversion, similar food type in case of food exclusivity, warming the food particularly if olfaction is an issue, alternatively chilling the food if aromas appear to result in nausea, social interaction while eating, feeding small frequent meals as premature satiety is associated with many disease states.

Pain Management

For both acute and chronic medical conditions, appropriate management of pain is critical to improving appetite. Opioids are perhaps most commonly utilized. Buprenorphine has a significantly longer half-life and may be useful for in home palliation of chronic pain. Butorphanol may also have some visceral analgesic properties. Opioids should be used with caution in patients with ileus. Maropitant may also have some visceral analgesic properties.⁵

Anti-nausea/Anti-emetic Medications

Assessment of nausea in the feline patient is of course subjective, but if suspected based on the underlying condition, treatment is merited both to prevent learned food aversion and to improve appetite in general. Ondansetron and dolasetron have been used in human renal failure patients and appear to have potent anti-nausea and anti-emetic properties.^6,7 Maropitant is an anti-emetic, but is thought to also have anti-nausea properties and clinical trials for its use in kidney disease cats are currently underway. Mirtazapine demonstrates anti-nausea properties in addition to its appetite stimulating properties as it acts at the 5HT3 receptor similarly to ondansetron.⁸ All four of these drugs work centrally as well as peripherally on receptors. Many are available as an injection which may be a welcome alternative to owners. Metoclopramide is thought to be a weak anti-emetic in cats do to a lack of receptors in the CRTZ, but may be useful as a promotility drug.⁹

Appetite Stimulants

Cyproheptadine has been used for some time as an appetite stimulant and has anecdotal efficacy in many patients, however its efficacy has never been scientifically evaluated. Twice daily administration is necessary in many cases and this can prove a challenge for owners, particularly longterm. Mirtazapine has become more commonly used and recent exploration of its pharmacodynamics and pharmacokinetics have provided information for more effective use in cats.^10,11 Pharmacodynamic studies have illustrated that it can be a potent appetite stimulant, but higher doses are more commonly associated with side effects (hyperexcitability, vocalization, tremors). Smaller, more frequent doses are recommended. The half-life is short enough that it could be administered daily in normal cats. Renal disease delays clearance and in these patients, every other day administration is recommended.¹¹ A recent clinical trial demonstrated that administration of mirtazapine to cats with CKD lead to a statistically significant increase in appetite and weight and a decrease in vomiting.¹² Owner should be aware mirtazapine and cyproheptadine cannot not be administered concurrently, cyproheptadine is in fact used as an antidote for serotonin effects of mirtazapine overdose.

References

1. Chan D. J Fel Med Surg 2009;11:925.

2. LaFlamme DP. Vet Clin Small Anim 2005;35:713.

3. Sparkes AH. Top Companion Animal Med 2011; 26:37.

4. Michel KE. J Fel Med Surg 2001;3:3.

5. Boscan et al. Am J Vet Res 2011; 72:1576.

6. Santos LCP et al. Vet Anaesth Analg 2011;38:320.

7. Ljutic D et al. Kidney Blood Press Res 2002;25:61.

8. Reichelmann RP et al. Am J Hospice and Palliative Med 2010; 27:106.

9. Trepanier L. J Fel Med Surg 2010;12:225.

10. Quimby JM. J Vet Pharmacol Therap 2010;34:388.

11. Quimby JM. J Vet Intern Med 2011;25:985.

12. Quimby JM. Vet J 2013 (in press).