Inducing emesis in cats: what's to be done?

Cats do not tend to ingest poisons as often as dogs do, this we know, and therefore the scenario in which one may be considering inducing emesis in a cat is encountered less often. That said, the Veterinary Poisons Information Service (VPIS), based in the UK, gets more or less one telephone enquiry a day about a cat that has ingested a toxin (personal communication, 2014) so it is not totally unheard of! I am going to skip some of the other talking points about gastrointestinal decontamination, especially in cats, here and just consider the circumstance in which it has been decided to induce emesis in a cat. What are the options?

Before proceeding I would like to state two points in particular outright:

  1. We need to set everything that follows in the context of evidence-based medicine principles and critique. It is clear that we are really scratching around here for evidence and such things as a number of prospective randomised controlled trials followed by systematic review/meta-analysis are extremely unlikely to ever be forthcoming.
  2. By referencing experimental studies I do so to convey the available information without condoning them. This is not the place to have that debate but one point that must be borne in mind, and relates to point 1. above, is that the translatability of experimental studies on small populations of cats to decision-making for individual clinical patients needs to be kept in the forefront of our minds. Admittedly cats that have poisoned themselves and in whom emesis is being considered are typically healthy but nevertheless the point is salient.

Alpha2-adrenergics

For many years it has been said that xylazine is the agent of choice for inducing emesis in cats. I have never personally used it but I have met people who have and they seem anecdotally to support the notion that it is effective There are some experimental reports looking at xylazine-induced emesis (e.g. Lucot, Crampton, 1986). Colby et al (1981) found a dose of xylazine of 0.66 mg/kg injected intramuscularly in normal cats caused vomiting in 20/21 cases; other doses have been reported too (e.g. 0.4-0.5 mg/kg). I also found the Moye, Pailet, Smith (1973) paper listed below but I cannot access it to see just how ‘clinical’ it really is. There are a number of papers you can find that study the anti-emetic effects of various agents or methods of neuroinhibition on cats that have been or are scheduled to be treated with xylazine to induce emesis. For example see Chiu-Ming Ho et al, 2001; Kolahian, Jarolmasjed, 2010;  Kolahian, Jarolmasjed, 2012; there are quite a few others!

But it is not just xylazine. Other alpha2-adrenergic agonists are reported to cause vomiting in cats. You can find papers where the potential for medetomidine and dexmedetomidine to cause emesis in cats is discussed/studied. For example see Santos et al (2011) in which dexmedetomidine was used at 40 µg/kg intramuscularly or Wiley et al (2016) in which a dose of dexmedetomidine of 10 µg/kg is suggested; there are other papers including reference to using medetomidine at 20 µg/kg.

Clearly the main clinical use of alpha2-adrenergic agonists is as sedative agents with emesis typically occurring if it does as an unwanted side-effect. A sedate cat that vomits is at increased risk of aspiration, and moreover these agents can also cause potentially profound dose-dependent cardiorespiratory compromise. I am sure it must be quite distressing to be vomiting and nauseous when also in a state of sedation! So their use is far from ideal but anecdotally relatively reliable at inducing emesis and reversal agents do exist. Atipamezole is used for (dex)medetomidine. Yohimbine has traditionally been recommended for xylazine but availability is likely to be very limited nowadays; it is suggested that atipamezole may also reverse xylazine’s effects but I am not sure whether there is any substantive evidence.

Xylazine is I think still used in larger species but with the increase in small animal-only practices worldwide the availability of xylazine is something we need to consider. I know some practices that stock it solely for inducing emesis in cats; I believe an open vial must be discarded after 28 days and in most cases this will mean discarding the vial after use in only one cat. Otherwise (dex)medetomidine is the option and widely available.

Apomorphine

But the question that always comes up is what about apomorphine – can we use it in cats? Is there evidence that it works for inducing emesis? What are the potential risks? What is the risk-benefit analysis and moreover how does it compare to using the agents mentioned above?

For as long as I can remember resources that I have come across have said that apomorphine should not be used in cats. Often they do not explain why or offer substantive references; however some reasons that I have occasionally read are that apomorphine is associated with more significant side-effects in cats, especially cardiovascular depression or sedation, or that it is ineffective. I spent some time seeing what I could find in the literature.

In Batchelor at al. (2013) it says “certain important differences exist between dogs, cats…For example, D2 dopamine receptors in the AP [area postrema, chemoreceptive area] are much less important in cats than in dogs, explaining the comparative resistance to apomorphine-induced vomiting in cats. In contrast, α2 adrenergic receptors are important in the areas of the cat brainstem controlling vomiting, explaining why the α2 agonist xylazine is an effective emetic agent in cats”. Unfortunately I cannot access the reference they cite in this paper to substantiate the idea that cats are comparatively resistant to apomorphine-induced vomiting.

In Graf et al (1979) it says in the abstract “among xylazine, ipecacuanha solution, apomorphine and copper sulphate, xylazine was the most reliable emetic (1 mg/kg body weight s/c). Apomorphine was unsuitable for cats in a dose of 10-20 mg because it produced excitement and seldom vomiting”. This is obviously a considerably higher dose than we would use clinically; a typical clinical dose range in dogs is 40-100 µg/kg but you will not find a dose range for cats listed in any/many resources. You can also come across papers where emesis is reported to have been induced in cats using apomorphine as part of experimental research; for example see Ognean (2000) or Boyd (1953) – in the latter it says in the abstract “an account of experiments which indicated that, in amounts corresponding to the usual human therapeutic doses, none of the antihistaminics tested-three diphenhydramine derivatives and prornethazine hydrochloride, methapyrilene hydrochloride, and methapyrilene-8-chlorotheophyllinate-prevented apomorphine-induced emesis in dogs and cats”. Unfortunately I cannot access these papers to review them especially with respect to what doses were used.

Apomorphine administered intravenously at a dose range which included at the very bottom end doses used clinically but also very high doses (10-750 µg/kg) reportedly produced a dose-dependent fall in mean systemic arterial blood pressure in cats; this was accompanied by marked bradycardia at the higher doses (500-750 µg/kg)(Ramirez, Enero, 1980). Similar findings were also reported in a later study (De Meyer, Buylaert, Bogaert, 1982) and there are others.  However we must note that apomorphine administered intravenously at actually lower doses (1.25-20 µg/kg) than we would use clinically reportedly caused a dose-dependent decrease in blood pressure in dogs as well (Bogaert, Buylaert, Willems, 1978). Of course the relevance of such experimental studies in anaesthetised animals to conscious clinical patients is questionable; while both cohorts may typically be healthy, anaesthesia and anaesthetic drugs are clearly confounders to any reliable comparison before we even get into details about the animals being comparable etc.

At (much) higher doses that we would use clinically apomorphine has been reported to cause motor activity, including limb flicking for example, in experimental cats that may be due to a central dopamino-mimetic action of the drug. For example in one study doses of between 100-2000 µg/kg were used and “apomorphine elicited limb flicking, dose-dependent hypermotility and increase in olfactory behavior, the last two reactions with stereotypy characteristics. The animals appeared as if being scared, hyperreacting to sudden stimuli and showing total indifference to the surrounding environment”(Motles, Martinez, Concha et al, 1989). Clearly the bottom end of this dose range is 5-10 times the starting doses we may use clinically. There are other similar papers reportedly showing similar things, i.e. motor activity and behavioural changes, but again at high doses sometimes given by routes we would not use clinically.

Naloxone is said to be able to reverse adverse effects of apomorphine without impairing its emetic effect. Again I am not aware of and have not had chance to investigate what evidence if any there is for this assertion but I am pretty sure it is based on the theory behind the mechanisms by which apomorphine induces emesis versus causes other side-effects (dopamine versus opiate effects etc.).

I should also mention at this point that I have again never personally tried this but soda crystals may be considered in cats. You will also find some people suggesting that hydrogen peroxide can be used; I personally do not like this idea in cats or dogs for that matter and again have never done it. I am not going to say any more about these substances here as this is already a long blog!

So what’s the bottom line?

Well, it is a good question. Clearly we would love for all this to be evaluated ‘properly’ and according to robust evidence-based medicine principles in clinical patients…but we must not hold our breaths! I have in the past used apomorphine in 3 cats at a dose of 20 µg/kg and emesis occurred in 2 of these cats. According to some of the material above, this makes little sense as this dose is half the dose I usually start with in dogs and cats are meant to be more resistant to apomorphine! The reason I chose this ‘lower than in dogs’ dose was due to the concerns that I had come across in resources about using apomorphine in cats. I have seen some cases in which medetomidine was used as 10-20 µg/kg and emesis occurred; but I have also seen cats become very sedated with nausea but no emesis. I must re-emphasise that we are talking about very small numbers of cats here.

Based on this present round of research I think I will be tempted to give the next cat in which I want to induce emesis apomorphine at an initial dose of 40 µg/kg and then decision make from there based on what occurs. Above there are some references to cats maybe being more resistant to the emetic effects of apomorphine than dogs but thus far I am struggling to find evidence of increased susceptibility to adverse effects, especially in the dose range that we would likely use clinically. While I continue to mull this over I would love to hear your experiences/thoughts/suggestions…

References

Batchelor DJ, Devaucjelle P, Elliott J, et al. Mechanisms, causes, investigation and management of vomiting disorders in cats: a literature review. J Fel Med Surg 2013. 15(4):237-265.

Bogaert MG, Buylaert WA, Willems JL. Hypotension produced by intravenous apomorphine in the anaesthetized dog is not centrally mediated. Br J Pharmacol 1978. 63(3):481-484.

Boyd EM, Boyd CE. Antihistaminics and apomorphine-induced vomiting. Can J Med Sci 1953. 31:320-325.

Chiu-MingHo, Shung-TaiHo ,  Jhi-JoungWang et al. Effects of dexamethasone on emesis in cats sedated with xylazine hydrochloride. Am J Vet Res 2001. 62(8):1218-1221.

Colby ED, McCarthy LE, Borison HL. Emetic action of xylazine on the chemoreceptor trigger zone for vomiting in cats. J Vet Pharmacol Therap 1981. 4:93-96.

De Meyer JM, Buylaert WA, Bogaert MG. Hypotension and bradycardia by intravenous apomorphine in the anaesthetized cat: no evidence for a central mechanism. Arch Int Pharmacodyn Ther 1982. 256(1):166-167.

Graf R, Kraft W, Ackermann U. Emetics in the cat (Emetica bei der Katze). Kleintierpraxis 1979. 24(8): 371-373.

Kolahian S, Jarolmasjed SH. Antiemetic efficacy of promethazine on xylazine-induced emesis in cats. Can Vet J 2012. 53(2):193–195.

Kolahian S, Jarolmasjed S. Effects of metoclopramide on emesis in cats sedated with xylazine hydrochloride. J Fel Med Surg 2010. 12(12):899-903.

Lucot JB, Crampton GH. Xylazine emesis, yohimbine and motion sickness susceptibility in the cat.  J Pharmacol Exp Therap 1986 . 237(2):450-455.

Motles E, Martinez I, Concha E, et al.Comparative study of the behavioral changes evoked by d-amphetamine and apomorphine in adult cats. Dose-response relationship. Pharmacology Biochemistry and Behavior 1989. 33(1):115-121.

Moye RJ, Pailet A, Smith Jr JW. Clinical use of xylazine in dogs and cats. Vet Med/Sm Anim Clini 1973.  68:236- 241.

Ognean L. Functional manifestation in emesis induced with apomorphine HCl in dogs and cats. Buletinul Universităţii de Ştiinţe Agricole şi Medicină Veterinară Cluj-Napoca, Seria Zootehnie, Biotehnologii ş Medicină Veterinară 2000 Vol. 54 pp. 135-138.

Ramirez AJ, Enero MA. Blood pressure and heart rate response to apomorphine in urethane anesthetized rats. Acta Physiol Lat Am 1980. 30(3):199-203.

Santos LCP, Ludders JW, Erb HN, et al. A randomized, blinded, controlled trial of the antiemetic effect of ondansetron on dexmedetomidine-induced emesis in cats. Vet Anaesth Analg 2011. 38(4):320-327.

Willey JL et al. Evaluation and comparison of xylazine hydrochloride and dexmedetomidine hydrochloride for the induction of emesis in cats: 47 cases (2007-2013). J Am Vet Med Assoc 2016;248:923-928.