Pain management in avian patients (Proceedings)

When one speaks of pain management in dogs they are discussing one species with research to back up their statements. Did you realize there are over 8000 species of birds? Even if we limit our discussion to the order Psittaciformes (parrots), that includes 353 different species and subspecies that are as diverse as a parakeet at 30 grams and a blue and gold macaw at 1000 grams. Not only are they different in size, but some parrots are from the rain forest and some are from the desert, some are New World species (from South America for example) and others are Old World species (from Australia or Africa for example). In addition, it is known that different species of psittacine birds metabolize several drugs differently than other psittacine birds. For example, macaws often regurgitate on "regular" avian doses of trimethoprim-sulfa, and African grey parrots often become profoundly depressed on "regular" avian doses of itraconazole. Another example is Old World Gyps Vultures developing visceral gout, renal necrosis and death a few days after exposure to small doses of diclofenac, an NSAID, (median lethal dose in this species is 0.1 – 0.2 mg/kg; low enough to be exposed to lethal doses by ingesting tissues of cattle given the drug), whereas turkey vultures receiving doses of up to 25 mg/kg had no ill effects recognized either clinically or histologically. This has led to the recent ban by the Indian, Nepali, and Pakistan governments on the use of diclofenac in cattle. Recent pharmacokinetic studies in several species of Gyps vultures showed meloxicam, another NSAID, to be safe for use. There are probably many unknowns in regards to the metablolism or action of pain relieving drugs in the many species of psittacine birds, or just even in the 10 most commonly kept psittacine species in captivity. Therefore, when assessing an avian patient for signs of pain, or deciding on which pain reliever to use, or what dose and how often to administer, it must be taken into account that there is NO GENERIC PARROT, and one must be familiar with the very limited scientific research that has been conducted regarding pain management in psittacine birds. Also, each patient must be evaluated and re-evaluated individually and constantly.

What research has been done in psittacine birds and what is known?

Most recent studies in psittacine birds have been performed by Dr. Joanne Paul-Murphy and her colleagues at the University of Wisconsin. They have shown the following:

1994 – butorphanol at 1.0 mg/kg IM had an isoflurane-sparing effect in cockatoos (11 of 3 different species of cockatoo)

1999 – developed a model for assessing analgesic effects in birds using a perch that was half electrified and half thermal; 31 African grey parrots (2 sub-species) lifted a foot or flinched their wings in response to a stimulus; the response to the thermal stimulus was variable, but the response to the electrified perch was predictable

1999 – using the above electrified perch model, 29 African grey parrots (2 sub-species) had a significantly increased threshold value after administration of butorphanol at 1.0 mg/kg IM, but not with buprenorphine at 0.1 mg/kg IM

2004 – pharmacokinetic (PK) study of buprenorphine at 0.1 mg/kg IM given once achieved plasma concentrations that would be analgesic in humans (0.5-1.0 ng/ml) for 2 hours, but the authors recommended that further PK and analgesic studies be performed with higher doses before using this dose

2006 – PK and analgesic study using the above model in 11 Hispaniolan Amazon parrots showed that liposomal encapsulated butorphanol tartarate (LEBT) (15 mg/kg SQ) had plasma levels and analgesic effects lasting 3-5 days compared to standard butorphanol tartarate (STDBT) (5 mg/kg IM) lasting less than 24 hours; unfortunately LEBT is not yet available commercially

Future work may involve evaluating the percentage of types of opiate receptors in birds. It is thought that birds possess more kappa than mu opiate receptors.

Formulary doses and references (from Carpenter's formulary):

In my experience, tramadol (an opiate) at 4 mg/kg orally once or twice daily worked well long term in a parrotlet with debilitating gout (since there were renal issues, an NSAID was not the best choice). Since that first bird, we have used tramadol in several other species and studies are currently being conducted.

How do you assess pain in birds and when do you give analgesics?

It is very difficult to assess pain in birds and there are no standard methods or assessments available to assess the level of pain in birds. Therefore, you are left with past experience, observation and anthropomorphism (if I had a fractured bone I would want an opiate). Birds are very stoic and do not cry out in pain despite the fact that they can be very loud when they want to be. Birds have a flock mentality; meaning they are a prey species and if they make their illness conspicuous to the rest of the flock they risk being ostracized by the rest of the flock (so as not to attract the attentions of a predator). So, try to observe your patient before they are aware of you are observing them. When they realize you are there, you will probably observe them straightening up, opening their eyelids more and they may even turn to partially to face you in an attempt to look alert.

Birds do not seem to become profoundly depressed on analgesics, therefore I tend to give analgesics at any hint of pain in a bird. In most cases I tend to give both an opiate (butorphanol) and an anti-inflammatory (meloxicam) the first 6 – 48 hours and then use only the anti-inflammatory for about 3 - 5 days. If renal disease is suspected, I will use tramadol instead of an NSAID.

Examples (this is what I currently due and will probably change as we all learn more):

Elective salpingohysterectomy: A common presentation is a chronically egg laying cockatiel and the owner elects surgery over hormonal injections. A parmedian incision is commonly made with a radiosurgical unit and scissors. Ideally lidocaine should be infused into the muscle layers around the area to be cut just prior to cutting. The lidocaine should not be infused right at the incision site because extra liquid interferes with proper function of the radiosurgical unit. I would use butorphanol at 2 mg/kg about 15 minutes prior to cutting. We also administer IM meloxicam 0.5 mg/kg at this point. It is better to restrain the bird briefly at 15 minutes prior to induction with isofluorane just to give the injections and then restrain again to mask induce with isofluorane, but for some birds this is too stressful. After intubation, any surgery in a bird is ideally completed within an hour. Forced heated air blankets are superb for maintaining a near normal temperature in birds under anesthesia and since we have been using them, birds are recovering faster and with more strength. Generally butorphanol is given IM at 2 hours after the first injection, then every 4 - 8 hours until the next morning (10 am, noon, 4p, ±8p, midnight, ±8 am). We use appetite, gait and general activity of the bird to assess whether not to give the 8 pm and 8 am doses. We will generally skip those doses if the bird is eating and active. If the bird is profoundly depressed, which is unusual, we will reassess the situation and sometimes decrease or discontinue the analgesics to observe if that action causes a change. The morning after surgery we generally switch to oral meloxicam and give it once daily for 5 days.

Cat attack: There is usually much swelling associated with cat bites and infection/sepsis is a concern. Fractures can be present. Sometimes stabilization is necessary in birds before jumping into diagnostics to fully determine the extent of the damage. At first all medications are administered IM because GI absorption may be compromised due to shock. Besides fluids, warmth, and a broad spectrum, bacteriocidal antibiotic, I would administer butorphanol at 2 mg/kg IM every 4 hours and an anti-inflammatory such as meloxicam at 0.5 mg/kg IM every 24 hours. Once the bird is stable and eating I would switch to oral meloxicam and possibly add in oral tramadol. In one severe case involving an Amazon parrot with multiple fractures of the mandible and quadrate bone, I administered butorphanol IM for 3 days, at first every 4, then every 8, then every 12 hours, in conjunction with meloxicam every 24 hours. The bird was switched to oral melxicam via a feeding tube placed on the second day.

References

Rattner BA, Whitehead MA, Gasper G, Meteyer C, Link WA, Taggert MA, Meharg AA, Pattee OH, Pain DJ. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac. Environ Toxicol Chem, 2008, May 13:1 (Epub ahead of print).

Naidoo V, Wolter K, Cromarty AD, Bartels P, Bekker L, McGraw L, Taggert MA, Cuthbert R, Swan GE. The pharmacokinetics of meloxicam in cultures. J Vet Pharmacol Ther, 2008, 31(2):128-34.

Curro TG, Brunson DB, Paul-Murphy J. Determination of the ED50 of isoflurane and evaluation of the isoflurane-sparing effect of butorphanol in cockatoos (Cacatua spp. ). Vet Surg, 1994, 23:429-433.

Paul-Murphy JR, Brunson DB, Miletic V. A technique of evaluating analgesia in conscious perching birds. Amer J Vet Res, 1999, 60(10):1213-7.

Paul-Murphy JR, Brunson DB, Miletic V. Analgesic effects of butorphanol and buprenorphine in conscious African grey parrots (Psittacus erithacus erithacus and P. erithacus timneh). Amer J Vet Res, 1999, 60(10):1218-21.

Sladky KK, Krugnes-Higby L, Meck-Walker E, Heath TD, Paul-Murphy J. Aerum concentration and analgesic effects of liposomal-encapsulated and standard butorphanol tartarate in parrots. Amer J Vet Res, 67(5):775-81.

Paul-Murphy J, Hess JC, Fialkowski JP. Pharmacokinetic properties of a single intramuscular dose of buprenorphine in African grey parrots (Psittacus erithacus erithacus). J Avian Med Surg, 2004, 18(4):224-8.

Pollack C, Carpenter JW, Antinoff N. Birds. In: Carpenter JW (ed). Exotic Animal Formulary, 3rd ed., Elsevier, St. Louis, 2005, pp.135-346.

Wison GH, Hernandez-Divers S, Budsberg SC. Pharmacokinetics and use of meloxicam in psittacine birds. Proc Annu Conf Assoc Avian Vet, 2004; 7-9.