In: Recent Advances in Veterinary Anesthesia and Analgesia: Companion Animals, R. D. Gleed and J. W. Ludders (Eds.

) Publisher: International Veterinary Information Service (www.ivis.org), Ithaca, New York, USA.

Injectable Anesthesia and Analgesia of Birds ( 5-Aug-2001 )

J. Paul-Murphy and J. Fialkowski
School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA. Isoflurane is the anesthetic of choice for most avian anesthetic procedures. However, inhalation anesthesia is not always available in field situations involving wild birds, although small portable inhalation anesthesia units are available. Certain surgical procedures, such as tracheal resection, may warrant the use of injectable anesthesia regardless of whether or not an anesthesia machine is available [1]. Anesthetic gases can escape from the bird during surgical procedures that disrupt air sacs, or the extension of air sacs into pneumatic bones, and thereby expose staff to anesthetic gases. Advantages of injectable anesthetic agents include rapid administration, low cost, and minimal equipment. Some anesthetic agents can be reversed, an important advantage when working in field situations. Injectable anesthetics are frequently used in large, long legged birds, such as ratites, when physical restraint is impossible or dangerous. Injectable anesthetics used in birds include barbiturates, chloral hydrate, alpha chloralose, phenothiazines, dissociatives, alpha-2 adrenergic agonists, alphaxalone/alphadolone and propofol [2]. Some of these anesthetics, such as barbiturates, chloral hydrate, alpha chloralose and alphaxalone/alphadolone, are no longer recommended and will not be discussed here. The greatest disadvantage of injectable anesthetics is individual and species variation relative to drug dose and response to a specific drug. Elimination of an injected drug depends on distribution, biotransformation and excretion. While we recognize species differences within domestic animals and tailor drug and dose accordingly, we nonetheless tend to treat all birds as if they belonged to one genus or species; as if, for instance, the pigeon is the same as an ostrich when in fact these two birds are as phylogenetically different from each other as the horse is from the cat. Pharmacokinetic studies of antimicrobial drugs in different species of birds have shown that kinetics vary significantly between species and even between birds of the same order such as cockatiels and Amazon parrots (both Psittaformes). Therefore data collected on an injectable anesthetic using a pigeon may not be directly transferable to another species of bird. Nevertheless, information collected on one avian species is likely to be better for extrapolation to another avian species than are data from mammalian species. It is important that the overall clinical condition of the bird be considered during selection of an anesthetic protocol. Precise body weight in grams is essential for accurate dosing. When using injectable anesthetics for birds it is difficult to maintain a surgical plane of anesthesia. The risk of cardiopulmonary depression is high and warrants careful monitoring during an anesthetic procedure. Orotracheal intubation of the anesthetized patient allows for supplemental oxygen and positive pressure ventilation if needed. A ventilation rate of 2 breaths per minute assists the spontaneously ventilating bird. When birds are apneic, the ventilatory rate should be 10 - 15 breaths per minute. In the bird, both inspiration and expiration require skeletal muscle activity and most anesthetics depress muscular activity, thus reducing air flow rate and oxygen exchange. Assisted or controlled ventilation ensures air flow and improves gas exchange at the level of the parabronchus and air capillaries. Intubation provides a patent airway that permits easy control of ventilation in emergency situations. Nevertheless, intubation is not recommended in very small birds because dried mucus may obstruct very narrow endotracheal tubes and the endotracheal tube may increase resistance to airflow because of a significant decrease in tracheal diameter. It is recommended to calculate and prepare doses of standard emergency and supportive drugs such as epinephrine, doxapram, lidocaine, and atropine before inducing anesthesia. The small size of many avian patients requires accurate dosing of very small volumes or dilution of standard concentrations. Having these drugs prepared and in labeled syringes saves time and anxiety in critical situations. Rapid anesthetic recoveries are best for birds. Birds appear very disoriented during recovery and tend to flap their wings and twist their head and neck. Holding the patient in a light towel wrap or rolling the bird into a loose newspaper "burrito" provides mild restraint to prevent chaotic body movements. Keeping the bird in a warm, quiet, dark place also aids a smooth recovery. Injection Sites In most birds, intramuscular injections are best given in the pectoral muscles. In flightless birds, such as ratites, pectoral

muscle mass is minimal, thus the thigh muscles are preferred. Subcutaneous injections are not advocated because uptake of anesthetic is slowed, but if selected the recommended site is the inguinal region. Intravenous sites for injection or catheterization include the right jugular vein, brachial vein, or the medial metatarsal vein. Intraosseous catheters are useful when venous access is difficult, as occurs with hypotensive birds or very small birds. Intraosseous catheters can be placed in the proximal ulna or the cranial tibiotarsus. Uptake of the drug is comparable to intravenous injection of the drug [3]. Local Anesthetics The toxicity of lidocaine is similar for birds as it is for mammals and it has been reported to cause seizures and cardiac arrest [4]. Toxicity can be prevented by using appropriate concentrations and volumes. Lidocaine (1 - 2 mg/kg) can be used as a local anesthetic or to treat ventricular arrhythmias [4], and the maximal dose is 4 mg/kg. For the small avian patient this often requires that the stock concentration of lidocaine (2%; 20 mg/ml) be diluted. Because of reluctance to use local anesthetics in birds, information regarding long-acting local anesthetics, such as bupivacaine, is sparse. Topical benzocaine has been used for local analgesia during repair of minor wounds in small birds [5]. A 1:1 mixture of bupivacaine and dimethyl sulfoxide (DMSO) was applied to amputated chicken beaks immediately after amputation and feed intake was improved [6]. Intraarticular bupivacaine, at a dosage of 3 mg in 0.3 ml saline, was reported to be effective for treating arthritic pain in chickens [7]. Benzodiazepines Diazepam and midazolam can reduce anxiety during anesthetic induction and recovery. These sedatives work best if given 10 - 20 min prior to further manipulations. The birds behavior does not often reflect pre-anesthetic sedation, but birds appear to struggle less during restraint. High doses of midazolam produced sufficient sedation in geese to facilitate restraint for diagnostic procedures [8]. This is highly advantageous with dangerous birds such as large raptors, and long-legged birds such as cranes and ratites. The sedative effect of these drugs is evident during recovery which is slow and smooth. No studies have been done to determine the duration of effect for diazepam or midazolam. The benzodiazepines provide muscle relaxation when used in conjunction with ketamine and reduce the level of isoflurane needed for anesthesia [9]. Flumazenil administered IV, helps to reverse benzodiazepine-induced sedation and restores alertness as long as enough time has passed so that additional anesthetic agents are no longer effective. Dissociatives Ketamine is rarely used alone because it is associated with poor muscle relaxation, muscle tremors, myotonic contractions, opisthotonus and rough recoveries [1, 10-12]. The dose of ketamine depends on body weight, and its dosing follows the principles of allometric scaling so that large birds (>1 Kg) respond to 10 - 20 mg/kg whereas small birds (< 50 grams) require much higher doses, e.g. 70 - 80 mg/kg. Additionally, there is inter-species variability in the response to ketamine. For example, ketamine causes salivation, excitation and convulsions when given to vultures but these signs are rare in other birds [12]. When effective, anesthesia occurs within 5 - 10 min of intramuscular injection and may last 5 - 20 min depending on the dose and size of the bird. Recovery from ketamine, until the bird can perch or stand, can take 40 - 100 min, depending on dose, body temperature, metabolic health, and size of the bird. It is recommended that ketamine not be used alone and be combined with benzodiazepines or alpha2-adrenergic agonists to improve relaxation and depth of anesthesia. Tiletamine and Zolazepam Telazol combines the effects of a dissociative drug (tiletamine) and a benzodiazepine (zolazepam). This combination has similarities to ketamine plus midazolam, but the smaller volume of Telazol that is typically used for anesthesia can be an advantage. At doses of 5 or 10 mg/kg it was an effective and safe anesthetic for great horned owls and screech owls although decreased heart and respiratory rates were noted [13]. Telazol at the same dose was unsatisfactory for anesthesia of red tailed hawks as they responded with salivation, and elevated heart and respiratory rates [13]. Despite the lack of information on Telazol in a variety of avian species, the primary disadvantage seems to be that a high dose provides anesthesia of short duration followed by a long (2 - 4 hour) and sometimes difficult recovery [11]. Alpha2-adrenergic agonists Xylazine, detomidine and medetomidine are usually used in combination with ketamine. The alpha-2-adrenergic agonists provide muscle relaxation, analgesia and sedation which smoothes induction and recovery. The greatest advantage of this group of drugs is the availability of specific antagonists to reverse the effects, allowing for smooth and rapid recovery. Atipamezole is recommended to reverse medetomidine and detomidine, and will also reverse the effects of xylazine. Yohimbine has been used in raptors and psittacines to reverse the effects of xylazine, both alone or in combination with ketamine [14-16]. Similar results were noted when tolazoline was used in turkey vultures to shorten xylazine plus ketamine anesthesia [17]. When reversing an alpha2-adrenergic agonist used in combination with ketamine, reversal must be timed so

as to avoid the bird recovering under the effects of ketamine alone as this can result in a rough recovery. Alpha2-adrenergic agonist drugs are not recommended as single anesthetic or immobilization agents for birds. In pigeons and Amazon parrots, high doses of medetomidine had a sedative effect but did not immobilize the birds [18]. Xylazine administered alone causes respiratory depression, excitation, convulsions and prolonged recovery [12]. All alpha2-adrenergic agonists have profound cardiopulmonary effects. Xylazine and medetomidine cause decreases in HR, RR, blood pH, hypoxemia, and hypercarbia [4,12,14,18]. The arrythmogenic effects of the alpha2-adrenergic agonists can lead to cardiovascular instability and, when coupled with hypoventilation and hypercarbia, can have an irreversible, fatal effect. Alpha2-adrenergic agonist drugs are a poor choice of anesthetic, alone or in combination, when a bird is highly stressed. General excitement can effectively over-ride the sedative effects of alpha2-adrenergic agonists, although the mechanism for this effect is not clear. Therefore, when using alpha2-adrenergic agonist drugs, approach the bird quietly, inject the drug and place the bird back into a familiar, quiet and dimly lit enclosure while waiting for the drug to take effect. The induction period is 5 - 10 min, depending on dose and size of the bird. Ratites, raptors and long-billed birds can have a hood placed over the head for calming when a dark cage is not available. Xylazine plus ketamine combinations have been evaluated in several avian species. Blood pressure becomes elevated, heart rate is decreased, and hypoxemia, hypoventilation, and hypercapnia occur [19-20]. An anesthetic combination consisting of medetomidine, midazolam and ketamine was evaluated and found to be unsafe for use in ducks [21] as it caused bradycardia, primarily attributed to the medetomidine [21,22]. Medetomidine also decreases respiratory rate. Apnea followed by a fatal decrease in heart rate and blood pressure was documented in four of twelve ducks receiving medetomidine [21]. Atipamezole and flumazenil were given intravenously to reverse medetomidine and midazolam, respectively, and the ducks rapidly regained consciousness and voluntary movement [21]. Propofol Propofol is an intravenously administered anesthetic with rapid onset, smooth induction, short duration of effect, and smooth, rapid recovery. Intravenous catheters are highly recommended for its administration because the drug must be given slowly for induction and often given repeatedly to maintain anesthesia. A maximum of 2 mg/kg bolus every 30 seconds is recommended for induction, after which 0.5 - 1.0 mg/kg/min is used to maintain surgical anesthesia [1,23]. In a study using ducks, propofol was given as an initial IV bolus and was constantly bolused at 1 - 4 mg/kg every 5 min to maintain a light plane of anesthesia [21]. In studies that monitored cardiopulmonary responses to propofol, mean arterial pressure (MAP) decreased significantly [1,23]. A short period of apnea following induction is a consistent finding [21,22,24] and respiratory depression can occur during induction and maintenance with propofol [23, 24]. Cardiac arrhythmias including ventricular premature contractions and ventricular tachycardia, were common in chickens and profound bradycardia was noted in ducks after the initial bolus of propofol [21,23]. Propofol has a narrow margin of safety in birds and supplemental oxygen and respiratory assistance must be provided to counteract apnea, hypoventilation and hypoxemia [21,23-25]. Anticholinergics The use of anticholinergics for birds is controversial. Indeed, atropine and glycopyrrolate are effective for the treatment of vagally induced bradycardia [26]. Some argue, however, that they cause respiratory secretions to become more viscous and thus more likely to plug narrow endotracheal tubes [27]. Others [28] recommend anticholinergics for their ability to reduce respiratory mucus production and prevent formation of mucus plugs in small endotracheal tubes [4]. The oculocardiac reflex has been reported in a cockatiel and suggests that treatment with an anticholinergic prior to or during ocular surgery may prevent this reflex which is thought to be caused by ocular manipulation resulting in cardiac dysrhythmias [29]. Ratites (Ostriches, Emus, Cassowaries and Rheas) In these large birds, injectable anesthetics are frequently used for short procedures and for induction of anesthesia prior to inhalation anesthesia. Several reports have been written on anesthetic protocols for ratites and a recent review compared the most common protocols [22,30-35]. These bird, when healthy, are too strong and unpredictable for simple mask induction with inhaled anesthetics. Intravenous injections can be given in the jugular vein or brachial vein, although the emus brachial vein is small and difficult to access. Placing a catheter in the jugular, brachial, or medial metatarsal vein will facilitate IV injection and induction. Injectable anesthetics most commonly used for ratites include combinations of Alpha2-adrenergic agonists followed by ketamine, or a benzodiazepine followed by ketamine, tiletamine-zolazepam, carfentanil or etorphine [28,34]. Benzodiazepines given prior to induction help produce smooth inductions and smooth but slow recoveries. Induction with tiletamine/zolazepam is excellent and rapid, although when given IV, violent recoveries have been reported [30,34]. Benzodiazepines given with tiletamine-zolazepam will smooth recovery [30]. Induction with xylazine-ketamine is adequate, but recovery can be difficult [34]. Carfentanil is not recommended due to an excitatory response even when used with xylazine [34]. When etorphine was combined with medetomidine, recumbency occurred rapidly, birds were sedate and muscle relaxation was adequate [33]. Other etorphine combinations, when given to free-ranging ostriches, caused initial

excitement [33], although darting procedures, regardless of the anesthetic, can create a period of excitement. Medetomidine as a sole anesthetic agent is ineffective in the ostrich [35]. When medetomidine was combined with ketamine and followed by intravenous propofol, it was an effective combination for chemical immobilization of captive ostriches, although positive pressure ventilation was recommended [22]. Apnea is a common occurrence during ostrich anesthesia, regardless of the induction agents selected. Ventilatory support is highly recommended for this group of birds. Analgesia Opioids The early literature regarding the use of opioids in birds is confusing and contradictory. For example, one study used two different strains of chickens to evaluate the analgesic effect of equal doses of morphine. Based on their response to a noxious thermal stimulus, one strain had a hyperalgesic response while another strain had an analgesic response [36]. With many such conflicting results in the literature, it was assumed that opioids were not effective analgesics for birds. More recently, the physiological effects of opioids on birds have been documented using isoflurane-sparing techniques [37-39]. In these studies, unpremedicated birds are anesthetized with isoflurane. The minimal anesthetic concentration (MAC) is determined in each bird, after which each bird is injected with an analgesic and MAC is again determined. A significant reduction of MAC indicates that the drug being tested has analgesic properties. Using this technique, the analgesic effects of butorphanol were evaluated in cockatoos, African grey parrots, and Amazon parrots. Butorphanol at 1 mg/kg was found to be analgesic in African gray parrots and cockatoos, but not Amazon parrots [38,39]. Following injection of butorphanol, heart rate, tidal volume, and inspiratory and expiratory times were all significantly decreased [38,39]. A similar study compared mu and kappa opioids in chickens and both drugs had isoflurane-sparing effects [37]. Recent studies evaluated the effects of butorphanol and buprenorphine in conscious parrots [40,41]. In African grey parrots, butorphanol (1 - 2 mg/kg, IM) had an analgesic effect while large doses of buprenorphine had no significant analgesic effect [41]. In Hispanolian parrots, higher doses of butorphanol (3 mg/kg) were needed to produce a similar analgesic effect (J. Paul-Murphy, personal observation). Species variability in response to opioids does occur and caution is advised when extrapolating butorphanol doses from one avian species to another. Fentanyl (0.02 mg/kg, IM), a synthetic mu agonist, was tested in a similar fashion in cockatoos, and was found to have little analgesic effect; a higher dose (0.2 mg/kg, SQ) was analgesic (S. Hoppes, unpublished data). This may be due to fentanyl binding both mu and kappa receptors when given at high doses. An excitement phase was noted in several of the birds shortly after fentanyl was injected (S. Hoppes, unpublished data). The duration of effect of all of these opioids has only been evaluated empirically and their duration of effect may be as short as 2 - 4 hours. Pharmacodynamic studies have demonstrated that pigeons have more kappa opioid receptors than mu opioid receptors [42]. This one piece of information in pigeons is used to explain why birds do not respond as do mammals to mu agonists like morphine, buprenorphine and fentanyl, and why kappa opioids, such as butorphanol, may be more efficacious analgesic in birds. Butorphanol is currently recommended for opioid analgesia in birds, and it can be given as a pre-operative and postoperative analgesic. When butorphanol is used as an induction agent and pre-operative analgesic the concentration of isoflurane needed for anesthesia will be reduced. Non-steroidal anti-inflammatory drugs There are several categories of nonsteroidal anti-inflammatory drugs (NSAIDS), but few have been investigated in birds and even fewer have been evaluated for clinical application [26,43]. Much of the information about doses and effects for birds has been gained through practical application. Studies using chickens have provided pharmacokinetic information on oral dosing of a few NSAIDS and short half-life and low bioavailability were common findings, but pharmacokinetic studies are a poor predictor of analgesic efficacy [44-46]. In mammalian species, NSAIDS are synergistic with other classes of analgesic agents and may be most effective for perioperative analgesia when used in combination with opioids [47]. In birds, as in other species, pre-emptive use of NSAIDS may decrease tissue sensitization caused by surgical trauma and may reduce the period of post-operative opioid therapy. The most commonly used NSAIDS in avian medicine today are carprofen and ketoprofen. The proprionic acid class of NSAIDS are analgesic, anti-inflammatory and antipyretic in mammals and are expected to have similar effects in birds. Chickens given a 1 mg/kg subcutaneous dose of carprofen had peak plasma levels 1 - 2 hours after injection and pain thresholds were raised for at least 90 min [48]. When carprofen-treated feed was offered to chickens, lame chickens selected more drugged feed than sound birds and the amount of carprofen consumed increased with the severity of lameness [49]. Low plasma concentrations of carprofen (0.28 g/ml) provided some analgesia for birds, but to reach plasma levels of 8.3 g/ml, similar to therapeutic plasma levels in mammals, an equivalent of 40 mg/kg body weight per bird was needed in the feed [48]. A documented side effect of NSAIDS in mammals is gastrointestinal ulceration and bleeding due to inhibition of prostaglandin synthesis. A similar toxic effect in birds was reported when high dosages of flunixin meglumide (10 mg/kg)

caused regurgitation and tenesmus in budgerigars [43]. The most serious complication of flunixin meglumide in birds is renal ischemia. Bobwhite quail experimentally given daily intramuscular injections of flunixin meglumide for 7 days had histological evidence of renal damage in all birds, even at doses as low as 0.1 mg/kg. Severity of the lesions was directly correlated to the dose of flunixin meglumide with acute necrotizing glomerulitis, tophi in the renal tubules and visceral gout occurring at 32 mg/kg [50]. Renal ischemia and necrosis has been documented in Siberian cranes treated with flunixin meglumide (5 mg/kg) for muscle and skeletal trauma [51]. The use of flunixin meglumide currently is contraindicated in cranes and used with great caution with other avian species. Piroxicam is used in mammals to treat chronic inflammatory conditions such as arthritis. It as been used to treat chronic degenerative joint disease in cranes and other species of birds and appears to provide mild to moderate improvement and willingness to bear weight on affected limbs over extended treatment periods.

Drug

Dosage (Dose), Route 182 - 281 mg/kg (250 mg dose), IV 0.2 mg/kg, IV; and 0.2 mg/kg, SC

Species / Remarks Mallard ducks: to reverse medetomidine; rapidly regained consciousness, struggled & flapped wings; tachycardia and tachypnea observed. Ostriches: to reverse medetomidine; half of the total 0.4 mg/kg dose was given IV, the other half SC; recovery was smooth and ranged from ~14 - 28 min Pigeons (Columbia livia) and Amazon Parrots (Amazona spp.): Used to reverse medetomidine; the dose given was 2.5 or 5 times the medetomidine dose administered. No differences were seen between the higher and lower doses. Recovery was smooth and rapid; standing times were all within 4 min Various avian species: Recommends a dose 5 times that of medetomidine to reverse its effects. Various avian species: Recommends a dose 5 times that of medetomidine to reverse its effects. Red-necked ostriches (Struthio camelus): to reverse meditomidine/etorphine combination; lead to a fast but violent recovery. Mallard ducks: to reverse medetomidine/midazolam, respectively; rapidly regained consciousness, struggled & flapped wings; tachycardia and tachypnea observed. Ratite; used to treat bradycardia. African grey parrots (Psittacus erithacus): 6/11 birds had an increased pain threshold to a noxious electrical stimulus after administration of 1 mg/kg B (this may represent the ED50 for the drug); higher dosages such as 2 - 3 mg/kg have been used to treat pain in subsequent studies without adverse side effects (unpublished findings). Cockatoos (Cacatua spp.): reduced isoflurane requirement in cockatoos; heart rate was reduced by 12%; apnea was not observed; respiratory rate increased by 77%, while tidal volume decreased by 25%, thus having no significant net effect on minute ventilation. Psittacines: significantly reduced isoflurane ED50 in cockatoos (Cacatua spp.) and African grey parrots (Psittacus erithacus), but had no affect on the isoflurane ED50 in blue-fronted Amazons(Amazona aestiva aestiva).

Reference Machin [21] Langan [22]

Atipamezole

3.75 - 10 mg/kg

Sandmeier [18]

0.25 - 1.0 mg/kg

Jalanka [52] Berthier [53] Ostrowski [33]

0.5 - 2.5 mg/kg (A) 40 - 161 mg/kg (5 - 20 mg dose) (D) 12 - 20 mg/kg (15 - 25 mg dose), IV (A) 182 - 281 mg/kg (250 mg dose) (F) 18 - 28 mg/kg (25 mg dose), IV 0.006 mg/kg, IV

Atipamezole (A) / Diprenorphine (D)

Atipamezole (A) Flumazenil (F) Atropine

Machin [21] Lin [30]

Butorphanol (B)

1 - 2 mg/kg, IM

PaulMurphy [41]

1 mg/kg, IM

Curro [38]

1 mg/kg, IM

Curro [39]

Drug

Dosage (Dose), Route

Species / Remarks Ostrich (Struthio camelus): darted; marked initial excitement phase, onset took 2 - 3 min, characterized as breaking away from the group and running in an uncontrolled manner; walking backwards, circling or courtship behavior prior to recumbency; smooth reversal with naltrexone, 3.0 mg/kg. Ratites: initial excitement phase, 5 min; apnea while under 5% isoflurane maintenance anesthesia and after isoflurane was discontinued. Ostrich (Struthio camelus): darted; initial excitement phase, onset took 2 - 3 min; recumbency in ~ 5 min; subjective assessment was that xylazine decreased the initial excitement level; smooth reversal with naltrexone/yohimbine, 3.0 / 0.125 mg/kg, respectively. Chickens: improved ability of moderately lame birds to walk. Broiler Chickens: Self-selection of three doses of carprofen coated feed (3.4, 34.3, and 343 mg/kg of feed) or normal feed; carprofen feeding improved gait in lame birds; lame birds selected more feed containing carprofen than did sound birds; consumption of carprofen-feed increased with the severity of lameness. Chickens: D diluted to a 0.2% solution prior to use; D administered prior to K into opposite thigh muscles; smoothly induced anesthesia within 4 min and lasted ~ 47 min; analgesia evident in 8 min and lasted 28 min; muscle relaxation good; respiratory rate significantly decreased from baseline; corneal reflex remained present. Chickens: duration of analgesia and anesthesia significantly prolonged with 20 mg/kg vs.10 mg/kg dosage of K, as noted above; smoothly induced anesthesia within 3 min and lasted for ~94 min; analgesia was evident in 6 min and lasted 63 min Ratites: used to smooth recovery from tiletamine/zolazepam. Red-necked ostriches (Struthio camelus): to reverse etorphine; lead to a fast but violent recovery. Ostriches (Struthio camelus): experiencing respiratory distress; ventilated mechanically. Chickens: drowsiness observed 3 - 5 min after administration; pain reflexes remained and birds were easily aroused. Chickens: D administered 15 min after E resulted in immediate surgical anesthesia which lasted 60 - 90 min, for long-duration surgical procedures; depth of anesthesia increased with increased diazepam doses. Ostriches (Struthio camelus): darted; initial excitation phase; mean time to recumbency 12 min; deep sedation but short duration, 9 - 15 min; risk of over-exertion myopathy, apnea, and bradycardia; reversal with diprenorphine resulted in quick but violent recoveries.

Reference

Carfentanil

~0.03 mg/kg (3.3 mg dose), IM

Raath, et al. [31]

Carfentanil (C) / 5% Isoflurane

(C) 0.3 mg/kg, IM (C) 0.03 mg/kg (3 mg dose) / (X) 1.5 mg/kg (150 mg dose), IM 1.0 mg/kg, SC

Cornick and Jensen [34]

Carfentanil (C) / Xylazine (X)

Raath, et al. [31]

Carprofen

McGeown, et al. [48]

0.4 - 40 mg/kg/day

Danbury, et al. [49]

Detomidine (D) / Ketamine (K)

(D) 0.3 mg/kg, IM / (K) 10 mg/kg, IM

Mohammad, et al. [55]

(D) 0.3 mg/kg, IM / (K) 20 mg/kg, IM

Mohammad, et al. [55]

Diazepam

0.13 - 0.41 mg/kg, IV ~100 - 240 mg/kg (12 - 30 mg dose), IV 5 mg/kg, IV or intralingual

Lin [30] Ostrowski [33] Ostrowski [33] Christensen, et al. [10]

Diprenorphine

Doxapram

Equithesin

2.5 ml/kg, IM

Equithesin (E) / Diazepam (D)

(E) 2.5 ml/kg, IM / (D) 2.5 mg/kg, IV (E) 40 - 72 mg/kg (5 - 9 mg dose) / (K) 1.0 - 1.5 mg/kg (120 180 mg dose), IM

Christensen, et al. [10]

Etorphine (E) / Ketamine (K)

Ostrowski [33]

Drug

Dosage (Dose), Route (E) 64 - 72 mg/kg (8 - 9 mg dose) / (M) 32 - 64 mg/kg (4 - 8 mg dose), IM

Species / Remarks Ostriches (Struthio camelus): darted; initial excitation phase; mean time to recumbency 8 min; deep sedation but short duration, 8 - 16 min; risk of over-exertion myopathy, apnea, and bradycardia; reversal with diprenorphine/atipamezole resulted in quick but violent recoveries. African grey (Psittacus erithacus) and blue-fronted Amazon parrots (Amazona aestiva aestiva): Does not have an isoflurane-sparing effect. Northern bobwhite (Colinus virginianus): Six dosage groups were administered FM, SID, for 7 days; all six groups had significantly more mineralized deposits in renal glomeruli than seen in controls and the severity increased with dosage; no changes in renal function indicators; at highest dosage, 32 mg/kg, necrosis was observed at the injection site. Mallard ducks (Anas platyrhynchos): Thromboxane (TBX) levels significantly suppressed for at least 4 hr; pain responses were not assessed, so there was no correlation made between degree of TBX inhibition and degree of analgesia; muscle necrosis of ~1 - 2 cc at the injection site; may not be suitable for use in ducks. Broiler Chickens: survival times improved when treated water was supplied for three days prior to heat stress; peripheral prostaglandin F was unaffected by treatment; mechanism of action unclear. Quail (Colinus virginianus): reversal of midazolam (6 mg/kg); time to complete recovery from heavy sedation averaged 1.6 min; birds progressed from dorsal recumbency to flight without relapse into sedation. Ostriches (Struthio camelus): to treat bradycardia Chickens: pharmacokinetic study with no assessment of analgesic effects; shorter half-life than in dogs; low bioavailability (F= 46.7% IM and 24.2% PO) compared to mammals. high pH in the crop may have precipitated the drug in the g.i. tract; unpredictable crop emptying and decreased motility of the crop due to handling the birds could have affected absorption. Broiler Chickens: Acute toxicity! Exhibited hyperexcitability, respiratory distress and death within 3 min; these central nervous system signs have not been reported in other species; postulated that this may be a nonpharmacological effect such as the displacement of other albumin bound ions (Ca or Mg) that leads to acute toxicity. Chickens: pharmacokinetic study with no assessment of analgesic effects; a large volume of distribution (suggesting tissue retention by peripheral tissues and/or high binding to plasma proteins with a slow return of the drug to the blood); slow but sustained oral absorption, attributed to high pH and unpredictable emptying of the crop, lead to mean residence times that were five times larger with the PO route than by IV administration; from the oral Cmax range of 0.5 - 1.1 mg/ml observed, they inferred that this was an effective anti-inflammatory dose based studies in mammals.

Reference

Etorphine (E) / Medetomidine (M)

Ostrowski [33]

Flunixin meglumine (FM), (NSAID)

4 mg/kg IM

Curro [39]

0.1 - 32.0 mg/kg, IM

Klein, et al. [50]

5 mg/kg, IM

Machin et al., [56]

5.26 mg/liter of drinking water

Oliver and Birrenkott [54]

Flumazenil

0.1 mg/kg, IM

Day and Roge [57] Ostrowski [33]

Glycopyrrolate

0.011 mg/kg, IV

Ibuprofen

25 mg/kg, IV 50 mg/kg, IM, PO

Roder, et al. [44]

50 mg/kg, IV

Roder, et al. [44]

Indomethacin

2 mg/kg, IV, PO

Cristofol, et al. [45]

Drug

Dosage (Dose), Route

Species / Remarks Chickens: tendency towards decreased heart rate and systolic blood pressure after administration; failure rate for cannulation and induction of anesthesia was 21% (3/14); some thrashing during induction; time to induction ~ 20 seconds; time to recovery ~ 19 - 34 min Great horned owls (Bubo virginianus): The (+) isomer provided an equal duration of immobility and significantly greater muscle relaxation compared to a three-fold greater dose of the (-) isomer. Apnea and cardiac irregularities occurred only with the (-) isomer and the racemate. Chickens: K administration brought on a tranquilized state, arousal from which elicited excitation; pain reflexes remained and handling brought on muscle contractions or tremor; D administration after 10 min deepened the tranquilized state but did not reach a surgical plane of anesthesia; heart rate was significantly decreased during the anesthetized period. Pet Birds: (K) doses can be halved for IV use; less cardiac depressant effect than a ketamine/xylazine combination; good choice for very sick birds, but only if isoflurane anesthesia is not available. Raptors: diazepam decreased the ketamine dosage; owls may require < half of this dosage; overweight individuals need divided doses; if the total dose of ketamine exceeds 50 mg it should be given in divided doses of < 50 mg at 2 3 min intervals Ostriches (Struthio camelus): preanesthesia: profound sedation & sternal recumbency in 6/8 birds, two birds were moderately sedated but remained standing; provided immobilization; reversed with atipamezole (after propofol anesthesia was discontinued) Raptors: induction 2 - 7 min, IM, and 10 - 30 sec., after IV administration; induction period was calm; injection volumes were small; respiration deep and regular; myorelaxation was good; owls were especially susceptible to the anesthetic effects; spontaneous recoveries were calm and began ~10 - 20 min after injection; Reversal with atipamezole was rapid. Psittacines: induction 2 - 7 min, IM, and 10 - 30 sec., after IV administration; induction period was calm; injection volumes were small; respiration deep and regular; myorelaxation was good; spontaneous recoveries were calm and began ~10 - 20 min after injection; Reversal with atipamezole was rapid. Geese: induction 2 - 7 min, IM, and 10 - 30 sec., after IV administration; induction period was calm; injection volumes were small; respirations deep and regular; myorelaxation was good; spontaneous recoveries were calm and began ~10 - 20 min after injection; Reversal with atipamezole was rapid. 16 avian species with 1 - 11 birds/species (60 birds total); the median dosage of ketamine was 8.2 mg/kg and the ~ median dosage of medetomidine 250 - 300 mg/kg; Reversal with atipamezole

Reference

Ketamine

30 mg/kg, intraosseous

Valverde, et al. [3]

Ketamine, D (+), L (-), or D/L (+/-) racemic mixture

10 mg/kg (+), IV; or 20 mg/kg (+/-), IV; or 30 mg/kg (-), IV

Redig, et al. [58]

Ketamine (K) / Diazepam (D)

(K) 75 mg/kg, IM / (D) 2.5 mg/kg, IV

Christensen, et al. [10]

10 - 50 mg/kg, IM / 0.5 2.0, IM or IV

Wheler [59]

Ketamine (K) / Diazepam (D) / Atropine (A)

(K) 30 - 40 mg/kg / (D) 1.0 - 1.5 mg/kg / (A) 0.05 mg/kg, IV

Redig & Duke [60]

Ketamine (K) / Medetomidine (M)

(K) 2 mg/kg, IM / (M) 80 mg/kg, IV

Langan [22]

(K) 3 - 5 mg/kg / (M) 50 100 mg/kg, IM; or (K) 2 - 4 mg/kg / (M) 25 75 mg/kg, IV (K) 3 - 7 mg/kg / (M) 75 150 mg/kg, IM (K) 2 - 5 mg/kg / (M) 50 100 mg/kg, IV

Jalanka [52]

Jalanka [52]

(K) 5 - 10 mg/kg / (M) 100 - 200 mg/kg, IM or IV

Jalanka [52]

(K) 4.6 - 28.0 mg/kg / (M) 93 - 500 mg/kg, IV

Berthier [53]

Drug Ketamine (K) / Medetomidine (Me) / Midazolam (Mi) Ketamine (K) / Midazolam (M)

Dosage (Dose), Route (K) 7.3 - 11.2 mg/kg (10 mg dose) / (Me) 36.5 - 56.2 mg/kg (50mg dose) / (Mi) 1.46 - 2.25 mg/kg (2 mg dose), IV (K) 10 - 25 mg/kg / (M) 0.5 - 1.0 mg/kg, IM

Species / Remarks Mallard ducks: 20 min duration; transient hypertension, bradycardia, and apnea; decreased respiratory rate after induction; resuscitation often required; survival risk; reversal with atipamezole, 0.25 mg, and flumazenil, 0.025 mg, IV Pet Birds: (M) is short-acting & contraindicated when severe hepatic disease is present. Pigeons (Columbia livia): ketamine followed by repeated doses of propofol provided ~ 3.5 min loss of muscle tone and pedal reflexes for each dose of propofol. Increased heart rate and decreased respiration within first minute after propofol administration. Apnea occurred after 62% of the propofol incremental doses. Assisted ventilation was necessary to revive the bird if the apnea was prolonged. Budgerigars (Melopsittacus undulatus): no response to toe pinch within 5 min; anesthesia was effective for 45 + min 2/14 birds died; one at 44 min and the other at 220 min after ketamine/xylazine administration. Reversal with yohimbine. Goshawks (Accipiter gentilis): lethal dose! Great Horned Owl (Bubo virginianus): immobilization noted within five min; transient apnea during initial 5 min; normal ventilation returned after 10 min Advise caution in using repeated doses due to an observed deterioration in cardiopulmonary stability. Supplemental oxygen improved cardiopulmonary performance. Pigeons: no satisfactory induction of anesthesia was observed at this dosage. Red-tailed hawks (Buteo jamaicensis): adequate anesthesia for ~ 15 min of diagnostic or surgical procedures; significant respiratory and cardiovascular depression; reversal with yohimbine, 0.10 mg/kg, IV Ostrich (Struthio camelus) chicks (9 - 10 weeks): rapid induction; corneal reflexes remained present while pedal reflexes were lost in 3 of 4 birds for 2 - 7 min; anesthesia maintained with the use of alphaxalone/alphadolone Turkey vultures (Cathartes aura): Induction was observed in ~5 min and anesthesia (dorsal recumbency) lasted ~110 min; good muscle relaxation was observed; reversal with tolazoline was rapid. Mallard ducks (Anas platyrhynchos): Thromboxane (TBX) levels significantly suppressed for at least 4 hr; pain responses were not assessed, so there was no correlation made between degree of TBX inhibition and degree of analgesia. Quail: pharmacokinetic study (poor predictor of NSAIDS efficacy); "extremely short" half life and low bioavailability (F= 23%) when administered orally. Birds > 2 kg: local anesthetic; standard formulary must be diluted prior to use to accurately measure usable volumes. Chickens (Gallus gallus domesticus): Used to treat ventricular tachycardia causing an arrhythmia in one bird.

Reference

Machin [21] Wheler [59]

Ketamine (K) / Propofol (P)

(K) 20 mg/kg, IM / (P) 4.1 - 8.6 mg/kg (to effect), IV

Fitzgerald & Cooper [25]

Ketamine (K) / Xylazine (X)

(K) 40 mg/kg / (X) 10 mg/kg, IM (K) 50 mg/kg / (X) 4 mg/kg, IM

Heaton and Brauth [16] Lumeij [20]

(K) 15 mg/kg / (X) 0.15 mg/kg, IM

Raffe, et al. [19]

(K) 50 mg/kg / (X) 4 mg/kg, IM (K) 4.4 mg/kg / (X) 2.2 mg/kg, IV

Lumeij [20] Degernes [14]

(K) 5.0 mg/kg / (X) 1.0 mg/kg, IV

Gandini, et al. [32]

(K) 10 mg/kg / (X) 1 mg/kg, IM

Allen and Oosterhuis [17]

Ketoprofen

5 mg/kg, IM

Machin et al., [56]

2 mg/kg, PO

Graham [46] Ludders [4] Lukasik [23]

Lidocaine

2 mg/kg, IV

0.5 mg/kg, IV

Drug

Dosage (Dose), Route

Species / Remarks Amazon Parrots (Amazona spp.): Sedation characterized by laying on sternum and just able to support their head; birds could be placed in dorsal recumbency were they remained if undisturbed. If disturbed they would stand up, open their eyes, and lift their heads. A 1.5 mg/kg dose did not allow placing the birds in dorsal recumbency. An anesthetic state was not acheived. The sedation level may facilitate radiography, venipuncture, or beak and nail trims. Reversal acheived with atipamezole. Pigeons (Columba livia): Sedation was characterized by laying on their sternums and just able to support their head; birds could be placed in dorsal recumbency were they remained if undisturbed. If disturbed they would stand up, open their eyes, and lift their heads. A 1.5 mg/kg dose allowed placing only 3 out of 4 birds in dorsal recumbency; the other pigeon remained standing. Reversal acheived with atipamezole. Red-necked ostriches (Struthio camelus) (two sub-adults): Darted; showed no signs of sedation or behavioral abnormalities Chickens: rapid tranquilization & loss of consciousness by ~ 1 min; pain reflexes remained but were diminished; duration of action was short, ~ 5 - 10 min; adverse reactions to M in 2/8 birds, one bird recovered after 1 min of apnea, the other died; respiration & blood pressure increased, while heart rate decreased after M admin; diazepam administered 10 min after M resulted in surgical plane of anesthesia for ~15 min in the majority of the birds; 3 birds pain reflexes were abolished; 2 birds never reached a surgical plane of anesthesia. Canada geese (Branta canadensis): moderate sedation at 15 - 20 min; 1.0 mg/kg was inadequate for sedation; significantly increased respiratory rate at 10 - 30 min post injection; did not significantly affect blood pressure, heart rate, or temperature Quail (Colinus virginianus): induced heavy sedation (defined as being in dorsal recumbency with both wings easily extended) in 9/10 birds, and mild sedation in one bird; peak time to heavy sedation was at 10 min but ranged from 5 - 30 min; no arousal due to noise was observed. Dosages of 2 & 4 mg/kg were tested but the level of sedation varied and inadvertent noise aroused the birds. Ratites to reverse Carfentanil, fair recovery

Reference

Medetomidine

2.0 mg/kg, IM

Sandmeier [18]

2.0 mg/kg, IM

Sandmeier [18]

Metomidate

~18 mg/kg (2 g dose), IM

Ostrowski [33]

Metomidate (M) / Diazepam (D)

(M) 20 mg//kg, IM / (D) 2.5 mg/kg, IV

Christensen, et al. [10]

Midazolam

2.0 mg/kg, IM

Valverde [8]

6 mg/kg, IM

Day and Roge [57]

Naloxone Naloxone (N) / Diprenorphine (D) Naltrexone (N) / Yohimbine (Y)

0.02 mg/kg, IV (N) 0.02 mg/kg, IV / (D) 0.04 mg/kg, IM (N) 3.0 mg/kg / (Y) 0.125 mg/kg, IV

Cornick [34] Cornick [34] Raath, et al. [31]

Ratites to reverse Carfentanil, good recovery Ostrich (Struthio camelus): reversal of Carfentanil/xylazine mixture

Drug

Dosage (Dose), Route

Species / Remarks Barn Owl (Tyto alba): induced anesthesia with 4 mg given in 1 mg boluses at 30-sec intervals; an additional 8 mg was given over the next 10 min due to birds response to feather plucking; a constant infusion of propofol was used to maintain a stable plane of anesthesia; transient decrease in SAP, DAP, and MAP observed immediately after induction; after infusion was stopped wing movement occurred within 5 min and ability to lift head up and maintain sternal posture within 30 min; appropriate for short surgical procedures (in this case a tracheal resection) (case report). Chickens (Gallus gallus domesticus); maintained by constant infusion of propofol, 0.5 - 1.2 mg/kg/min; arrhythmias common; significant respiratory and cardiovascular depression; hypoxemia also common; narrow margin of safety, 3 times the induction dose was fatal. Mallard ducks; 1 to 4 mg IV bolus maintenance doses (0.7 - 4.5 mg/kg) at ~ 5 min intervals; apnea after induction bolus, but increased in respiratory rate with time; risk of severe bradycardia; light plane of anesthesia; intraoperative analgesia required Ostriches (Struthio camelus); ketamine/medetomidine (preanesthetic) allowed sufficient sedation to place IV catheter; propofol induction & maintenance (0.2 mg/kg/min constant rate infusion); apnea & bradycardia observed; anesthesia rated good Pigeon (Columbia livia): bolus dose produced a smooth, rapid induction, with good muscle relaxation, and loss of voluntary reflexes lasting 2 - 7 min. Lethal Dose determined to be ~ 20 - 26 mg/kg if ventilation was not assisted. Wild Turkeys; maintained surgical plane of anesthesia with 0.5 mg/kg/min of propofol, IV; apnea immediately after induction lasted 10 - 30 sec; risk of hypoxemia; smooth recovery Chickens: time to induction was ~12 - 21 seconds; allowed intubation; increased respiratory rate; time to recovery ~ 13 - 20 min; failure rate for cannulation and induction of anesthesia was 21% (3/14). Great Horned Owls (Bubo virginianus): Induction times ranged from ~5.5 - 12 min; times to standing ranged from ~60 - 77 min. Rapid decrease seen in heart rate within 2 min after induction then remained constant. Respiration rates decreased for the initial 20 min of anesthesia. Inductions and recoveries were smooth. Great Horned Owls (Bubo virginianus): Induction times ranged from ~3.2 - 4.0 min; times to standing ranged from ~81 - 95 min. Heart rates within first 2 min after induction remained higher than after a 5 mg/kg dosage but decreased over time. Respiration rates decreased for the initial 20 min of anesthesia. Inductions and recoveries were smooth. Total recover times ranged from ~210 - 283 min. Ratites: used to induce sternal recumbency; rapid and smooth; 3.4 - 4.9 mg/kg for emus; 3.0 - 5.8 mg/kg for rheas; 2.3 - 4.0 mg/kg for ostriches

Reference

Propofol

4 - 12 mg, IV, for induction / 0.5 mg/kg/min, IV, maintenance

Mama, et al. [1]

4.5 - 9.7 mg/kg, IV

Lukasik [23]

7.3 - 11.2 mg/kg (10 mg dose), IV

Machin [21]

3 mg/kg (induction), IV

Langan [22]

14 mg/kg, IV

Fitzgerald & Cooper [25]

5 mg/kg (in 20sec), IV

Schmacher [24]

Thiopental

20 mg/kg, intraosseous

Valverde, et al. [3]

Tiletamine (T) / Zolazepam (Z)

5 mg/kg, IM

Kreeger, et al. [13]

10 mg/kg, IM

Kreeger, et al. [13]

2.3 - 5.8 mg/kg, IV

Lin [30]

Drug

Dosage (Dose), Route

Species / Remarks Ratites: induced with tiletamine/zolazepam; maintained with isoflurane, 1 - 4%; bradycardia & apnea observed; diazepam (0.21 - 0.41 mg/kg, IV) administered post-op to smooth recovery Red Tailed Hawks: None of these doses induced a loss of consciousness. Screech Owls(2): Induction times ranged from 1.5 - 2.7 min; time to first raise their heads ranged from ~60 - 63 min. Total recover times were > 5 hours. Turkey vultures (Cathartes aura): to reverse the effects of xylazine (see ketamine/xylazine combination above); regained consciousness in ~ 2 - 6 min; normal standing postures were observed in under 20 min but appeared to have a dull mentation and moderately sedated for 30 - 60 min after administration. Ostrich (Struthio camelus) (n=1): darted; marked excitation but no immobilization and the bird was unapproachable Ostriches & emus: produced a calming effect; drowsy and ataxic 10 - 15 min after injection Rheas: higher dosages of xylazine/butorphanol needed to produce a similar tranquilizing effect as seen in ostriches and emus; maintained on isoflurane, 1 - 5%; midazolam (0.15 mg/kg, IV) or diazepam (0.33 mg/kg, IV) administered post-op to smooth recovery Ratites: tranquilized with X/B; induced with Tz; maintained with 1 - 3.5% isoflurane; bradycardia & apnea observed; diazepam (0.13 - 0.40 mg/kg, IV) administered post-op to smooth recovery Ratites: Xylazine given prior to carfentanil. good induction allowing intubation; apnea, hypercapnia, IPPV needed; Ostrich; used to reverse xylazine during a prolonged recovery period Red-tailed hawks (Buteo jamaicensis): optimal dosage to significantly reduce standing times after 20 min anesthesia with a 4.4 mg/kg ketamine and 2.2 mg/kg xylazine without causing profound cardiovascular or respiratory responses Budgerigars (Melopsittacus undulatus): reversal of ketamine/xylazine combination. Significantly reduced recovery times indicated by a head lift, standing unaided without ataxia, and perching.

Reference

2.3 - 4.9 mg/kg, IV

Lin [30]

10, 15, 20, or 40 mg/kg, IM 10 mg/kg, IM

Kreeger, et al. [13] Kreeger, et al. [13]

Tolazoline

15 mg/kg, IV

Allen and Oosterhuis [17]

Xylazine Xylazine (X) / Butorphanol (B)

~1.1 - 1.3 mg/kg (150 mg dose), IM (X) 1.06 - 2.03 mg/kg / (B) 0.10 - 0.14 mg/kg, IM (X) 2.26 - 2.75 mg/kg / (B) 0.12 - 0.20 mg/kg, IM

Ostrowski [33] Lin [30]

Lin [30]

Xylazine (X) / Butorphanol (B) / Tiletaminezolazepam (Tz) Xylazine (X) / Carfentanil (C) Yohimbine

(X) 1.06 - 2.21 mg/kg / (B) 0.10 - 0.55 mg/kg, IM / (Tz) 3.5 mg/kg, IV (X) 0.5 mg/kg, IM / (C) 0.15 mg/kg, IV 0.11 mg/kg, IM

Lin [30] Cornick and Jensen [34] Lin [30] Degernes [14] Heaton and Brauth [16]

0.10 mg/kg, IV

Yohimbine

0.275 mg/kg, IM

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