The reversal of xylazine/ketamine immobilisation of fallow deer with yohimbine

Fallow deer were immobilised using a combination of xylazine and ketamine. Adult males (n = 10) and adult females (n = 10) received 4 mg/kg of each drug intramuscularly. Juveniles (n = 11) received 2 mg/kg of each drug, intravenously. Times to recumbency were as follows: adult males 4.9 +/- 2.9 min, adult females 4.1 +/- 1.9 min, juveniles 2.3 +/- 1.1 min. After 30 min each deer received 0.2 mg/kg of yohimbine, or an equal volume of sterile diluent intravenously. Yohimbine substantially reduced the recovery times of treated deer. Adults males were releasable 7.2 +/- 4.3 min after yohimbine administration, whereas control males were not releasable until 165 +/- 18 min. Treated adult females were releasable after 6.6 +/- 4.3 min, while control females were not releasable until 84 +/- 29 min. Juveniles were releasable 2.1 +/- 0.8 min after administration of yohimbine but control juveniles were not releasable until 62 +/- 16 min. Xylazine/ketamine administration produced statistically significant changes in packed cell volume, total plasma protein, albumin, sodium, glucose, creatine phosphokinase and inorganic phosphate values after 30 min. Yohimbine administration had no effect on these changes.     

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats

Yohimbine, 4-aminopyridine, and a combination of the 2 drugs were studied to assess their potential as antagonists to xylazine in goats. Twenty-four small East African goats were divided randomly into 4 groups of 6 goats each in a placebo-controlled study. They were all treated with intramuscular xylazine at 0.44 mg/kg. At the time of maximum sedation, sterile water was administered intravenously to the control group, 0.15% 4-aminopyridine at 0.4mg/kg to Group 2, 0.1% yohimbine at 0.25 mg/kg to Group 3, and the combination of the 2 drugs at the same dose rates to Group 4. The yohimbine/4-aminopyridine combination was also used to antagonise xylazine at 0.88mg/kg in 6 goats. The heart rate, respiratory rate and rate of ruminal movements, the pedal and palpebral reflexes as well as the reaction to noxious stimuli, the standing time and the total recovery time were established and evaluated to assess the effects of the treatments. The drugs reversed the xylazine-induced decrease in the heart rate, respiratory rate and rate of ruminal movements, and also rapidly restored the reflexes as well as the reaction to noxious stimulation. In addition, they significantly (P < 0.05) decreased the mean standing time. The mean total recovery time was decreased significantly (P < 0.05) by 4-aminopyridine and the yohimbine/4-aminopyridine combination, but non-significantly (P > 0.05) by yohimbine. No relapse in sedation occurred. Overall, the combination of yohimbine and 4-aminopyridine produced better responses than the individual drugs, and may therefore be used for rapid reversal of xylazine-induced sedation in goats. Yohimbine or 4-aminopyridine may also be useful for this purpose but recovery may be prolonged.     

Anesthesia of male axis deer (Axis axis): evaluation of thiafentanil, medetomidine, and ketamine versus medetomidine and ketamine.

Thiafentanil oxalate, previously known as A-3080, is a synthetic opioid used for chemical immobilization of a variety of nondomestic hoofstock species. This study compared the combination of thiafentanil oxalate, medetomidine, and ketamine (TMK; 0.09 +/- 0.02 mg/kg, 0.01 +/- 0.003 mg/kg, and 1.36 +/- 0.33 mg/kg, respectively) with the combination of medetomidine and ketamine (MK; 0.09 +/- 0.02 mg/kg and 3.48 +/- 0.55 mg/kg, respectively) for anesthetization of 17 captive male axis deer (Axis axis) for vasectomy. Nine deer received TMK and eight deer received MK via projectile syringe during the months of January and February, 2005. Mean induction and arousal times, vital signs, and arterial blood gas values were monitored and compared. All animals received supplemental oxygen during the surgical procedure. Animals receiving TMK were reversed with naltrexone (100 mg/mg thiafentanil) and atipamazole (5 mg/mg medetomidine). Animals receiving MK were reversed with atipamazole (5 mg/mg medetomidine). Two MK animals and three TMK animals required supplementation with ketamine i.v. immediately upon handling. Six of the nine animals immobilized with TMK required intubation for positive-pressure ventilation. Two of these six animals also required isoflurane to maintain anesthesia. Mean induction time was 3.5 +/- 2.0 min in the TMK group, and 9.8 +/- 6.7 min in the MK group. Despite shorter mean induction times, animals anesthetized with TMK experienced unpredictable inductions, apnea, muscle rigidity, limb movement, and significant respiratory and metabolic lactic acidosis. MK resulted in smoother inductions, better respiratory function, and less adverse metabolic disturbances, and thus was considered superior to TMK for anesthesia in captive axis deer at the dosages tested.     

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.     

Immobilization of captive plains zebras (Equus quagga) with a combination of etorphine hydrochloride,acepromazine, and xylazine hydrochloride

The plains zebra (Equus quagga) is a zebra species commonly kept in zoos around the world. However, they are not tame like their domestic relatives and are difficult to immobilize. We immobilized 30 captive plains zebra with a combination of etorphine hydrochloride (2–4 mg), acepromazine (8 mg), and xylazine hydrochloride (30 or 50 mg) to perform physical examination and blood sample collection for disease diagnostics. Physiological parameters including heart rate, respiratory rate, body temperature, and hemoglobin oxygen saturation were recorded. All zebras exhibited satisfactory anesthesia and fully recovered without re-narcotization. The results suggest that etorphine hydrochloride-acepromazine-xylazine hydrochloride combination for plains zebra immobilization is a safe and sufficient regimen for short procedures such as wellness examinations and sample collection.     

A balanced anesthesia with a combination of xylazine, ketamine and butorphanol and its antagonism by yohimbine in pigs.

The effects of intramuscular injections of xylazine (2 mg/kg)-ketamine (15 mg/kg) [X-K15], and xylazine (2 mg/kg)-ketamine (5 mg/kg)-butorphanol (0.22 mg/kg) [X-K5-B] were compared in atropinized (0.05 mg/kg) miniature pigs (pigs). Both combinations induced the anesthesia for more than 1 hr, however X-K5-B induced the more potent and well balanced anesthesia as compared with X-K15, although the amount of ketamine was reduced to one third. The duration of loss of pedal reflex, an indicator of surgical anesthesia, in X-K5-B (62 +/- 13 min) was significantly (P less than 0.05) longer than in X-K15 (28 +/- 19 min). In addition, X-K5-B was accompanied by loss of laryngeal reflex in all pigs. Recovery from anesthesia in X-K5-B was much smoother than in X-K15, and the administration of yohimbine (0.05 mg/kg) could rapidly and smoothly reverse the anesthesia induced by X-K5-B, although it was accompanied by a transient fall in blood pressure and tachycardia. The combination of xylazine, ketamine and butorphanol appears to be a relatively safe and widely available anesthesia for the period of one hour in pigs.     

Sedative effects of midazolam and xylazine with or without ketamine and detomidine alone following intranasal administration in Ring-necked Parakeets

OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and xylazine (with or without ketamine) and detomidine and their specific antagonists in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination administered intranasally that resulted in adequate sedation (ie, unrestrained dorsal recumbency maintained for >or=5 minutes) was determined; the onset of action, duration of dorsal recumbency, and duration of sedation associated with these treatments were evaluated. The efficacy of the reversal agents flumazenil, yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively. Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55 mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved adequate sedation. Compared with detomidine, duration of dorsal recumbency was significantly longer with midazolam. Intranasal administration of flumazenil (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency time. Compared with the xylazineketamine combination, duration of dorsal recumbency was longer after midazolam-ketamine administration. Intranasal administration of flumazenil, yohimbine, or atipamezole significantly decreased the duration of sedation induced by midazolam, xylazine, or detomidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of sedative drugs appears to be an acceptable method of drug delivery in Ring-necked Parakeets. Reversal agents are also effective when administered via this route.     

Antagonism of xylazine and ketamine anesthesia by 4-aminopyridine and yohimbine in geldings

Thirty-six fasted, mixed horse breed geldings (6 groups of 6 animals each) were anesthetized with xylazine and ketamine, and when maximally sedated, were given 1 of the following antagonists: saline solution, 4-aminopyridine (4-AP), small-dose yohimbine, large-dose yohimbine, 4-AP plus low-dose yohimbine, or 4-AP plus high-dose yohimbine. Measured data included mean standing time (MST), heart rate, respiratory rate, rectal temperature, and mean total recovery time ( MTRT ). Emergence phenomena were also observed and recorded as smooth, fairly smooth, fairly rough, or rough. Groups given 4-AP alone, small-dose yohimbine alone, or large-dose yohimbine alone produced a significant (P less than 0.05) decrease in MST (9.9 +/- 1.6 minutes, 11.3 +/- 1.7 minutes, and 10.6 +/- 2.3 minutes, respectively) compared with that in the saline control group (24.3 +/- 9.2 minutes). The MTRT were not significantly (P greater than 0.05) different (47.2 +/- 10 minutes, 90.4 +/- 15.1 minutes, and 83.2 +/- 23 minutes, respectively) from control values (66.2 +/- 13.4 minutes). When the antagonists were combined, 4-AP plus small-dose yohimbine and 4-AP plus large-dose yohimbine produced significant (P less than 0.05) decreases (10.3 +/- 2 minutes and 8.3 +/- 2.6 minutes, respectively) in MST compared with that of saline controls. The MTRT was significantly longer in the combined antagonist group (4-AP + small-dose yohimbine--131.8 +/- 28.9 minutes; 4-AP + large-dose yohimbine--131.3 +/- 19.4 minutes) compared with that of control or any antagonist alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of optimal immobilizing doses of a medetomidine hydrochloride and ketamine hydrochloride combination in captive reindeer

OBJECTIVE: To establish optimal immobilizing doses of medetomidine hydrochloride (MED) with ketamine hydrochloride (KET) for hand- and dart-administered injections in captive reindeer. ANIMALS: 12 healthy 6- to 9-month-old reindeer (Rangifer tarandus tarandus). Procedure An optimal dose was defined as a dose resulting in an induction time of 150 to 210 seconds, measured from the time of IM injection until recumbency. Initially, each stalled reindeer was immobilized by hand-administered injection. If the induction time was > 210 seconds, the dose was doubled for the next immobilization procedure. If it was < 150 seconds, the dose was halved for the next immobilization procedure. This iteration procedure was continued for each reindeer until an optimal dose was found. Later the reindeer was placed in a paddock and darted with its optimal dose as determined by hand-administered injection. Adjusting to a linear relationship between dose and induction time, optimal darting doses for each reindeer were predicted and later verified. RESULTS: The established mean optimal hand- and dart-administered doses were 0.10 mg of MED/kg of body mass with 0.50 mg of KET/kg, and 0.15 mg of MED/kg with 0.75 mg of KET/kg, producing mean induction times of 171 seconds and 215 seconds, respectively. The mean induction time after darting was 5 seconds greater than the upper limit of the predefined time interval. CONCLUSIONS AND CLINICAL RELEVANCE: The higher dose requirement of MED-KET administration outdoors, compared with indoors, was explained by factors inherent in the darting technique and the different confinements. The iteration and the prediction methods seem applicable for determination of optimal doses of MED-KET in reindeer. The iteration and the prediction procedures may be used to reduce the number of experimental animals in dose-response studies in other species.     

Effects of ketamine, xylazine, and a combination of ketamine and xylazine in Pekin ducks

Effects of ketamine, xylazine, and a combination of ketamine and xylazine were studied in 12 male Pekin ducks (7 to 12 weeks old; mean [+/- SD] body weight, 3.1 +/- 0.3 kg). After venous and arterial catheterization and fixation of a temperature probe in the cloaca, each awake duck was confined, but not restrained, in an open box in a dimly lit room. Blood pressure and lead-II ECG were recorded. Three arterial blood samples were collected every 15 minutes over a 45-minute period (control period) and were analyzed for pHa, PaCO2 and PaO2. After the control period, each duck was assigned at random to 1 of 3 drug groups: (1) ketamine (KET; 20 mg/kg of body weight, IV), (2) xylazine (XYL; 1 mg/kg, IV), and (3) KET + XYL (KET 20 mg/kg and XYL, 1 mg/kg; IV). Measurements were made at 1, 5, 10, 15, 30, 45, 60, and 90 minutes after drug administration. All ducks survived the drug study. Cloacal temperature was significantly (P less than or equal to 0.05) increased above control cloacal temperature at 90 minutes after the administration of ketamine, and from 10 through 90 minutes after administration of ketamine plus xylazine. In ducks of the KET group, pHa, PaCO2, and PaO2, remained unchanged after administration of the drug. In ducks of the XYL group, pHa and PaO2 decreased significantly (P less than or equal to 0.05) from control values for all time points up to and including 15 minutes after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2 mg/kg) or S-ketamine (1.1 mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13 min after ketamine administration. Arterial blood gases were evaluated 5 min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.     

Immobilization of babirusa (Babyrousa babyrussa) with xylazine and tiletamine/zolazepam and reversal with yohimbine and flumazenil.

Twelve babirusa (Babyrousa babyrussa) (four females/eight males) were immobilized 30 times during a 4-yr interval. Significantly higher premedication and immobilizing doses were needed for females than for males (P < 0.05). An i.m. preanesthetic xylazine dose of 1.88 +/- 0.37 mg/kg (range = 1.20-2.12 mg/kg) was used for females and 1.22 +/- 0.16 mg/kg (range = 0.82-1.43 mg/kg) for males. After xylazine, the animals were induced with i.m. tiletamine/zolazepam; females received 2.20 +/- 0.47 mg/kg (range = 1.78-3.33 mg/kg) and males received 1.71 +/- 0.34 mg/kg (range = 1.08-2.05 mg/kg). Anesthesia was reversed with yohimbine (0.14 +/- 0.03 mg/kg; range = 0.07-0.20 mg/kg) and flumazenil (1 mg flumazenil/20 mg zolazepam) either i.m. or i.v. This anesthetic combination produced smooth induction, good relaxation, and sufficient immobilization to perform routine diagnostic and therapeutic procedures (venipuncture, hoof and tusk trims, transportation, radiographs, ultrasound examination, weight determinations, and skin biopsies). Supplemental ketamine HCl or isoflurane was administered to two animals to effectively deepen or prolong the anesthetic plane, with no resultant adverse effects.     

Comparison of yohimbine, 4-aminopyridine and doxapram antagonism of xylazine sedation in deer (Cervus elaphus)

Trials were conducted to test the ability of yohimbine, 4-aminopyridine and doxapram given by intravenous injection to antagonise xylazine sedation in red deer (Cervus elaphus). Yohimbine produced the best and most consistent result. The mean time taken for 34 animals to stand spontaneously after receiving yohimbine (0.2 to 0.25 mg/kg) was 2 minutes 25 seconds and this occurred, on average, 33 minutes after the initial doze of xylazine. Control deer took 67 and 104 minutes on average to stand after receiving intravenous (0.64-0.96 mg/kg) and intramuscular (1.0-1.5 mg/kg) injections of xylazine respectively. Two deer which received an overdose of xylazine (4 mg/kg) recovered 3 and 9 minutes respectively after receiving yohimbine. Two deer given a high intravenous dose of yohimbine (1.0 mg/kg) became mildly nervous and anxious, but returned to normal within an hour. 4-aminopyridine (0.3 mg/kg) alone produced some arousal from xylazine sedation (0.6-1.0 mg/kg) but was inconsistent. In combination with yohimbine (0.125 mg/kg) it produced rapid recovery in two deer but caused convulsions in two other deer. Doxapram (1 mg/kg) produced respiratory stimulation and some arousal from xylazine sedation (0.6-1.0 mg/kg) in the majority of deer but the effect was transitory. Animals relapsed into moderate sedation and recumbency within 10 minutes and required vigorous stimulation to arouse them again. Yohimbine, administered by intravenous injection at a dose rate of 0.2 to 0.25 mg/kg, appears to be a safe and reliable drug for the reversal of xylazine sedation in deer.     

Neospora caninum is a cause of perinatal mortality in axis deer (Axis axis)

Neospora caninum is a worldwide distributed protozoan that may cause neuromuscular disease in dogs and reproductive failure in domestic and wild ruminants. One axis fawn (Axis axis) and four neonates from the same deer herd died at a zoo in Argentina within a four-month period. The fawn presented with dilatation of the anal sphincter at birth and incontinence, developed weakness and ataxia and died at 14 days of age. At necropsy, a mega formation of the distal large intestine was observed. Microscopically, non-suppurative encephalitis, suppurative bronchopneumonia, fibrin necrotic enteritis and degenerative changes in the liver were observed in hematoxilin and eosin-stained tissue sections, and thick-walled N. caninum-like cysts were observed in fresh brain samples. Serologic studies for N. caninum revealed an IFAT titer of 1:6400 in the fawn and 1:25, 1:400, 1:3200 and 1:6400 in the neonates. N. caninum DNA was detected in brain samples from the fawn and from one neonate by PCR, and the parasite was isolated in vitro from the fawn’ brain after passage through gerbils (Meriones unguiculatus) and gamma-interferon knock-out mice. N. caninum DNA obtained from the fawn, neonate and isolated parasites showed the same microsatellite pattern. This suggests a common infection source for both animals.The diagnosis of N. caninum infection was confirmed, suggesting its association with perinatal mortality in captive axis deer. To the best of our knowledge, this is the first report of clinical disease associated to N. caninum infection in axis deer and of isolation of the parasite from this wild ruminant species.