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PubMed1993

Influence of anesthetic regimens on the perioperative catecholamine response associated with onychectomy in cats.

Plasma catecholamine concentrations in response to onychectomy were examined in 27 cats receiving different anesthetic regimens. Each cat was anesthetized with a dissociative-tranquilizer combination, and onychectomy was performed on 1 forefoot. One week later, each cat was anesthetized with the same dissociative-tranquilizer combination plus either butorphanol or oxymorphone, and onychectomy was performed on the other forefoot. Four treatment groups were studied: tiletamine-zolazepam and tiletamine-zolazepam-butorphanol combinations were administered to group-1 cats, ketamine-acepromazine and ketamine-acepromazine-butorphanol combinations were administered to group-2 cats, tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone combinations were administered to group-3 cats, and ketamine-acepromazine and ketamine-acepromazine-oxymorphone combinations were administered to group-4 cats. All drug combinations were administered IM. Central venous blood samples were drawn for catecholamine analysis after injection of drug(s), after onychectomy, and 1, 2, and 4 hours after injection. Tiletamine-zolazepam alone or tiletamine-zolazepam-butorphanol prevented epinephrine release for 2 hours after injection of drug(s). Norepinephrine concentration increased significantly (P < 0.05) from baseline after onychectomy for tiletamine-zolazepam-butorphanol and at 4 hours for tiletamine-zolazepam and tiletamine-zolazepam-butorphanol. After onychectomy, there was no difference in epinephrine values between tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone. Ketamine-acepromazine prevented increases in norepinephrine and epinephrine concentrations for up to 2 hours after surgery. Addition of butorphanol to ketamine-acepromazine decreased norepinephrine values immediately after onychectomy. Addition of oxymorphone to ketamine-acepromazine resulted in lower epinephrine values 4 hours after surgery.

Anesthesia, General↗
PubMed1999

Comparative physiologic effects of telazol, medetomidine-ketamine, and medetomidine-telazol in captive polar bears (Ursus maritimus).

The cardiopulmonary effects of three drug combinations in polar bears (Ursus maritimus) were studied. In 1995, five adult polar bears received i.m. injections of either 8.2 +/- 1.3 mg/kg of Telazol or a combination of 159 +/- 34 microg/kg of medetomidine with 4 +/- 0.8 mg/kg of ketamine in a crossover design. Significantly higher mean arterial pressure, lower heart rate, and lower partial pressure of arterial oxygen (Pao2) occurred with medetomidine-ketamine. In 1996, six adult polar bears were immobilized with i.m. injections of either 8.2 +/- 2 mg/kg of zolazepam-tiletamine or a combination of 74.8 +/- 11.8 microg/kg of medetomidine plus 2.2 +/- 0.3 mg/kg of zolazepam-tiletamine in a crossover design. Significantly higher mean arterial pressure and lower heart rate, base excess, and Pao2 occurred with medetomidine-zolazepam-tiletamine compared with zolazepam-tiletamine alone. Hypertension, bradycardia, and decreased Pao2 were observed with both medetomidine-ketamine and medetomidine-zolazepam-tiletamine. Both combinations should be well tolerated by healthy bears, but both have the potential to produce adverse effects in animals with cardiopulmonary disease. Zolazepam-tiletamine produced minimal adverse cardiopulmonary effects, consistent with the wide margin of safety of this combination in bears. The analgesic effect of zolazepam-tiletamine was apparently poor on the basis of the marked increases in pulse rate and mean arterial pressure after noxious stimuli.

Anesthetics, Combined↗
PubMed1999

A fatality related to the veterinary anesthetic telazol.

A 45-year-old male veterinarian was found dead in bed. Police investigation showed no evidence of trauma or other suspicious circumstances. Autopsy was unremarkable except for cardiomegaly and hepatosplenomegaly. Toxicological analysis revealed the presence of Telazol and ketamine. Telazol is a veterinary anesthetic agent that is composed of equal parts of tiletamine and zolazepam. Tiletamine is a disassociative anesthetic similar to ketamine and phencyclidine, and zolazepam is a diazepine derivative tranquilizer used to minimize the muscle hypertonicity and seizures associated with tiletamine. Quantitation of tiletamine and zolazepam was performed using gas chromatography-mass spectrometry in the selected ion monitoring mode following a solid-phase extraction. Postmortem blood, urine, and liver concentrations of tiletamine were 295 ng/mL, 682 ng/mL, and 196 ng/g, respectively, whereas postmortem concentrations of zolazepam for the same tissues were 1.71 microg/mL, 1.33 microg/mL, and 15.5 microg/g, respectively. Blood and urine ketamine levels were 37 ng/mL and 381 ng/mL, respectively. The cause of death was ruled an acute mixed drug intoxication of tiletamine, zolazepam, and ketamine with the manner of death ruled as unclassified.

Anesthetics↗
PubMedDate not supplied

A comparison of injectable anesthetic combinations in horses.

Six combinations of injectable anesthetic agents were administered to six adult horses in a Latin square design. The drug combinations were xylazine-ketamine, xylazine-butorphanol-ketamine, xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, detomidine-ketamine, and detomidine-butorphanol-ketamine. Measured variables were heart rate, respiratory rate, systolic blood pressure, arterial pH (pHa), PaCO2, PaO2, recumbency time, and number of attempts necessary to stand. Quality of induction and recovery, muscle relaxation, and response to stimulus were evaluated subjectively. The horses required significantly more attempts to stand after administration of xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, and detomidine-ketamine than after xylazine-ketamine, xylazine-butorphanol-ketamine, or detomidine-butorphanol-ketamine. Mean recumbency times varied from 23.0 minutes with xylazine-ketamine to 41.3 minutes with xylazine-butorphanol-tiletamine-zolazepam. There were significant differences in mean heart rates at minute 15, mean respiratory rates at minutes 5, 10 and 15, and mean systolic blood pressures at minute 10 of anesthesia. There were no significant differences in pHa, PaCO2 or PaO2.

Acid-Base Equilibrium↗
PubMed2000

Pharmacokinetics and tissue residues of Telazol in free-ranging polar bears.

A pharmacokinetic and tissue residue study was conducted to assess the risks associated with human consumption of polar bears in arctic Canada that have been exposed to the immobilizing drug Telazol, a mixture of tiletamine hydrochloride and zolazepam hydrochloride. Twenty-two bears were remotely injected with about 10 mg/kg of Telazol. Following immobilization, serum samples were collected serially at regular intervals until the bears awakened. Sixteen of the bears were relocated and killed under permit by local hunters at various times from 0.5 to 11 days after dosing. Serum, kidney, muscle and adipose tissue samples were collected immediately after death. All samples were stored at -70 C until analysis by HPLC. The concentration-time data of tiletamine and zolazepam in serum during the immobilization period were fitted to curves by computer and the pharmacokinetic parameters assessed. In addition, the serum and tissue samples collected at the time of death were analyzed for both parent drugs, for one metabolite of tiletamine (CI-398), and for three metabolites of zolazepam (metabolites 1, 2 and 4). A one-compartment model with first-order absorption and elimination best fit the time-series data for the drugs in serum during the immobilization period. This model gave half-lives (mean +/- SE) for tiletamine and zolazepam of 1.8+/-0.2 h and 1.2+/-0.08 h, respectively, clearance values of 2.1+/-0.3 l x h(-1) x kg(-1) and 1.1+/-0.1 l x h(-1) x kg(-1), and volumes of distribution of 5.2+/-0.6 l/kg and 1.8+/-0.2 l/kg. The concentrations of both drugs and their metabolites declined rapidly to trace levels by 24 h post-dosing, although extremely low concentrations of some metabolites were encountered sporadically over the entire sampling period. In particular, zolazepam metabolite 2, remained detectable in fat and muscle tissue at the end of the study, 11 days after dosing. It was concluded that during immobilization, both tiletamine and zolazepam levels decline rapidly in a monoexponential fashion, and their pharmacokinetic parameters in polar bears are similar to those observed in other species. Tissue levels of the drugs and their metabolites declined sufficiently rapidly that individuals eating meat from exposed bears would be unlikely to experience pharmacological effects from the drugs. Nevertheless, slight exposure to the drugs and/or their metabolites might be possible for an indeterminate time after dosing.

Animals↗
PubMed2005

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

Adrenergic alpha-Antagonists↗
PubMed1998

Comparison of five regimens for oral administration of medication to induce sedation in dogs prior to euthanasia.

OBJECTIVE: To compare regimens for oral administration of medication to induce sedation in dogs prior to euthanasia. DESIGN: Prospective randomized clinical study. ANIMALS: 37 dogs. PROCEDURE: Groups and medications were as follows: group 1, acepromazine (n = 8); group 2, tiletamine-zolazepam (8); group 3, tiletamine-zolazepam and acepromazine (8); group 4, tiletamine-zolazepam and butorphanol (6); and group 5, pentobarbital sodium (7). Capsules or tablets were placed in each dog's food. Sedation was scored at 3-minute intervals after consumption of medication for at least 60 minutes. Dogs with signs of persistent or progressive sedation were observed for 90 minutes. RESULTS: Only 2 dogs in group 1 became slightly ataxic. All group-2 dogs were slightly ataxic, and 4 of 8 became laterally recumbent (mean time to lateral recumbency, 62 minutes). Seven of 8 group-3 dogs became sternally recumbent, and 6 of these dogs became laterally recumbent (mean, 48.6 minutes). Four of 6 group-4 dogs were slightly or moderately ataxic, and 1 of these dogs became laterally recumbent (mean, 48 minutes). One dog in group 5 was not affected by the medication, but all other group-5 dogs became laterally recumbent (mean, 59 minutes). CLINICAL IMPLICATIONS: Of the medications evaluated, tiletamine-zolazepam and acepromazine at dosages of approximately 20 mg/kg (9.1 mg/lb) and 2 mg/kg (0.91 mg/lb), respectively, or pentobarbital sodium alone (63.2 +/- 5.1 mg/kg [28.7 +/- 2.3 mg/lb]) most consistently induced profound sedation and lateral recumbency after oral administration to dogs.

Acepromazine↗
PubMed1998

Induction of hepatic cytochrome P450 2B and P450 3A isozymes in rats by zolazepam, a constituent of Telazol.

Telazol, a 1:1 combination of tiletamine HCl and zolazepam HCl, is an anesthetic and immobilizing agent that is capable of inducing cytochrome P450 (CYP) 2B isozymes in rats. The primary goal of the present study was to determine the constituent of Telazol responsible for the enzyme induction. A secondary goal was to compare the effects produced by Telazol and its constituents with those elicited by sodium phenobarbital (PB) using the same dosing regimen. Adult male Long Evans rats were given a single i.p. injection of tiletamine or zolazepam at a dose of 60 mg/kg, Telazol at a dose of 120 mg/kg, PB at a dose of 60 and 120 mg/kg, or vehicle at a dose of 1 mL/kg. Animals were killed 24 hr later, and hepatic microsomes were prepared. Treatment with zolazepam and Telazol increased microsomal benzyloxyresorufin O-dealkylase (BROD) activity by approximately 9- and 15-fold, respectively, and increased microsomal testosterone 16 beta-hydroxylase activity by 5- and 8-fold, respectively. Treatment with tiletamine had a slight, but insignificant, effect on CYP-mediated enzyme activities. In comparison, BROD and testosterone 16 beta-hydroxylase activities were increased by 22- and 13-fold, respectively, after treatment with PB at a dose of 60 mg/kg. Densitometric quantitation of immunoblots revealed that the hepatic CYP2B content was elevated by approximately 15-, 22-, and 25-fold, and the hepatic CYP3A content was increased by 2-, 2-, and 8-fold after treatment with zolazepam, Telazol, and PB, respectively. In contrast, levels of CYP1A1 and CYP2E1 were unaltered after treatment. In summary, the results indicate that zolazepam was the constituent primarily responsible for the inductive effect of Telazol, and the pattern of enzyme induction produced by zolazepam and Telazol was similar to, but weaker than that elicited by PB at a similar dosing regimen.

Animals↗
PubMed2004

Effects of tiletamine/zolazepam-romifidine-atropine in ocelots (Leopardus pardalis).

OBJECTIVES: To evaluate the effects of a combination of tiletamine-zolazepam-romifidine-atropine in ocelots. DESIGN: Prospective experimental trial. ANIMALS: Eight captive adult ocelots (three females and five males). METHODS: Calculated doses of tiletamine-zolazepam (3.75 mg kg(-1)), romifidine (50 microg kg(-1)) and atropine (0.04 mg kg(-1)) were administered intramuscularly. After immobilization, animals were weighed and the real doses determined. Heart rate, respiratory frequency, noninvasive systolic, diastolic, and mean arterial pressure, arterial oxygen hemoglobin saturation, and rectal temperature were measured. Data were analyzed by means of anova for repeated measures, followed by the Tukey test to compare values over time. RESULTS: Doses administered were 3.4 +/- 0.6 mg kg(-1) of tiletamine-zolazepam, 0.04 +/- 7.0 mg kg(-1) of romifidine, and 0.03 +/- 0.007 mg kg(-1) of atropine. The mean time to recumbency and duration of immobilization were 7.0 +/- 4.5 and 109.2 +/- 27.9 minutes, respectively. The median times to standing and walking were 52.3 [0-90] and 2.3 [0-69.3] minutes, respectively. A decrease in heart rate was observed 45 minutes following drug administration. Arterial blood pressure was maintained during the study. CONCLUSIONS AND CLINICAL RELEVANCE: This protocol produced good immobilization in ocelots with minimal changes over time in cardiovascular parameters.

Anesthetics, Dissociative↗
PubMed1995

Antagonism of some cyclohexamine-based drug combinations used for chemical restraint of southern elephant seals (Mirounga leonina).

This study examined the use of 4 antagonists of chemical restraint in mature female southern elephant seals (Mirounga leonina) that were restrained with ketamine and diazepam, ketamine and xylazine, or tiletamine and zolazepam. The antagonists were: 4-aminopyridine, yohimbine, doxapram and sarmazenil. The effects of the antagonists on the animal's time to first movement forward and recovery, heart rate, respiratory rate and venous blood gas and pH values, and level of chemical restraint were recorded. Sarmazenil (1.0 mg/kg) and doxapram (5.0 mg/kg) partially antagonised 50:1 ketamine: diazepam (ketamine = 3.0 mg/kg, diazepam = 0.06 mg/kg) and tiletamine and zolazepam (tiletamine = 0.5 mg/kg, zolazepam = 0.5 mg/kg). However, the rapid recovery after low doses of anaesthetics means that antagonism is usually unnecessary, and it may increase the likelihood of shaking. Routine antagonism of ketamine and xylazine (ketamine = 3.0 mg/kg, xylazine = 0.5 mg/kg) is more useful given its usually delayed recovery time and potential for thermoregulatory problems. For this purpose yohimbine (0.06 mg/kg) offered advantages over doxapram in giving a smoother recovery with less aggression. 4-aminopyridine (0.2 mg/kg) prolonged chemical restraint by 100:1 ketamine:diazepam (ketamine = 3.0 mg/kg, diazepam = 0.03 mg/kg) and ketamine and xylazine, and should be contraindicated. Doxapram (5.0 mg/kg) was the most useful general antagonist for all groups of drugs but shaking was seen and a lower dose is recommended.

4-Aminopyridine↗
PubMed1997

Postanesthetic monitoring of core body temperature using telemetry in North American river otters (Lutra canadensis).

Remote thermal telemetry was performed on North American river otters (Lutra canadensis) during the 1995 North Carolina Wildlife Resources Commission Otter Restoration Project. Otters were anesthetized with either ketamine-midazolam (n = 11) or tiletamine-zolazepam (n = 9) combinations. Based upon initial rectal temperatures, mild to moderate hyperthermia (39.4-40.5 degrees C) developed in five otters given ketamine-midazolam and three otters given tiletamine-zolazepam. Following anesthetic induction, each otter received an ingestible temperature transmitter. Dependent upon gastrointestinal transit time and transmitter battery life, core body temperature was monitored for up to 13.75 hr postanesthesia. Thermal telemetry revealed a gradual decline in core temperature in all otters after anesthetic recovery (30-60 min). Median core temperature stabilized subsequently within 0.3 degrees C of resting temperature (38.4 degrees C) 1.75 hr after initial injection in otters given tiletamine-zolazepam and 2.75 hr in otters given ketamine-midazolam. Minor fluctuations in body temperature (less than 1 degree C) occurred in most otters from 6 to 13.75 hr and were attributed to variations in physical activity.

Anesthesia Recovery Period↗
PubMed2006

Dissociative anaesthesia during field and hospital conditions for castration of colts.

The principal aim of this study was to evaluate dissociative anaesthesia for castration of colts during field conditions. Three dissociative anaesthetic protocols were evaluated during castration of colts in an animal hospital. The protocol considered to be the most suitable was thereafter evaluated during castration of colts under field conditions. Respiratory and haemodynamic parameters and the response to surgery were determined during anaesthesia. All horses breathed air spontaneously during anaesthesia. Under hospital conditions 26 colts were randomised to receive one of three anaesthetic protocols: Romifidine and tiletamine-zolazepam (RZ); acepromazine, romifidine and tiletamine-zolazepam (ARZ); or acepromazine, romifidine, butorphanol and tiletamine-zolazepam (ARBZ). The surgeon was blinded to the anaesthetic protocol used and decided whether supplemental anaesthesia was needed to complete surgery. Under field conditions 31 colts were castrated during anaesthesia with the ARBZ protocol. All inductions, anaesthesia and recoveries were calm and without excitation under both hospital and field conditions. Surgery was performed within 5-20 minutes after the horses had assumed lateral recumbency during both hospital and field castrations. Under hospital conditions some horses needed supplemental anaesthesia with all three anaesthetic protocols to complete surgery. Interestingly, none of the horses castrated with protocol ARBZ under field conditions needed additional anaesthesia. Cardiorespiratory changes were within acceptable limits in these clinically healthy colts.

Anesthesia↗