Reversible chemical restraint of free-range cattle with a concentrated combination of tiletamine-zolazepam, ketamine, and detomidine.

The aim of this study was to determine the efficacy of a concentrated combination of tiletamine-zolazepam [TZ, 0.53 mg/kg body weight (BW)], ketamine (Ket, 0.53 mg/kg BW), and detomidine (Det, 0.04 mg/kg BW) in the immobilization of free-range cattle for clinical procedures. The combination was administered intramuscularly to 53 animals. Anesthesia was reversed with the α2-adrenoceptor antagonist atipamezole. Locoregional anesthesia was provided with lidocaine when required. The TZKD combination induced suitable immobilization for minor surgical procedures or medical treatments. Anesthetic onset was rapid, taking a mean of 6.1 min [standard deviation (SD) 2.8 min]. The duration of anesthesia depended on the time of administration of the antagonist; the animals recovered in the standing position in 12.9 ± 8.9 min after the administration of atipamezole. The quality of anesthesia and analgesia were satisfactory. In conclusion, this TZKD combination can be used for both immobilization and minor surgical procedures in free-range cattle.

L'objectif de la présente étude était de déterminer l'efficacité d'une combinaison concentrée de tiletamine-zolazepan [TZ, 0,53 mg/kg de poids corporel (BW)], kétamine (Ket, 0,53 mg/kg de BW), et detomidine (Det, 0,04 mg/kg BW) pour l'immobilisation de bovins libres au pâturage aux fins de procédures cliniques. La combinaison fut administrée à 53 animaux par voie intramusculaire. L'anesthésie a été renversée avec l'atipamézole, antagoniste des adrénocepteurs-α2. Au besoin, l'anesthésie locorégionale a été induite avec de la lidocaïne. La combinaison TZKD a induit une immobilisation adéquate pour des procédures chirurgicales mineures ou des traitements médicaux. L'initiation de l'anesthésie était rapide, avec une moyenne de 6,1 minutes [écart-type (SD) 2,8 min]. La durée de l'anesthésie dépendait du temps de l'administration de l'antagoniste; les animaux récupérant en position debout en 12,9 ± 8,9 min après l'administration de l'atipamézole. La qualité de l'anesthésie et de l'analgésie était satisfaisante. En conclusion, la combinaison TZKD peut être utilisée pour l'immobilisation et la réalisation de procédures chirurgicales mineures chez les bovins au pâturage.(Traduit par Docteur Serge Messier).

[New aspects of common antagonists used in the perioperative period: preface and comments].

Anesthesia is a state made by multiple pharmacological agents that affect the functions of central, peripheral and autonomic nervous systems. Antagonists are often used to reverse the effects of anesthetic agents, muscle relaxants, and so forth. Antagonists often have side effects other than their specific antagonistic effect. Some side effects may be clinically useful. Ketamine was found to be a NMDA receptor antagonist. Ketamine potentially has neuroprotective, and anti-tumor effect. Local anesthetic agent also has been known to have anti-NMDA receptor effect. Although the mechanisms of local anesthetics to prevent or treat chronic pain have not been clearly elucidated, local anesthetics may have a place in the treatment of chronic pain. Naloxone may have spinal protective effects when used during thoracic aortic aneurysm surgery and stent placement. Peripherally and centrally active anticholinesterase agents have unique effects. Centrally active anticholinesterase agents such as donepezil and revastigmine, and galantamine have been used to treat patients with Alzheimer's disease. These agents may antagonize the effects of non-depolarizing muscle relaxants. Flumazenil may have adverse effects in patients on chronic benzodiazepines and tricyclic or tetracyclic antidepressants. Because sugammadex has little adverse effects, it has become a popular agent to reverse muscle relaxation by rocuronium in Japan.

Antagonistic effect of atipamezole, flumazenil and naloxone following anaesthesia with xylazine, tramadol and tiletamine/zolazepam combinations in pigs.

OBJECTIVE: To evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine-zolazepam-xylazine-tramadol. STUDY DESIGN: Prospective, experimental, randomized cross-over study. ANIMALS: Eight Chinese miniature pigs (three females and five males) mean age 8 (range 7-10) months and bodyweight 57.5 (52.4-62.1) kg. METHODS: All animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg(-1)), xylazine (1.2 mg kg(-1)) and tramadol (1.6 mg kg(-1)) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg(-1)), FLU (0.1 mg kg(-1)), NAL (0.03 mg kg(-1)), ATI-FLU, FLU-NAL, ATI-NAL or ATI-FLU-NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey's test to compare differences between means, or by Kruskal-Wallis test as appropriate. RESULTS: FLU, NAL alone, or FLU-NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam-xylazine-tramadol. ATI, ATI-FLU, ATI-NAL and ATI-FLU-NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study. CONCLUSION AND CLINICAL RELEVANCE: ATI-FLU-NAL is the most effective combination for antagonizing tiletamine/zolazepam-xylazine-tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.

Human exposures to immobilising agents: results of an online survey.

Cases of human exposure to veterinary injectable anaesthetics were reviewed following a literature search and completion of an online questionnaire in an attempt to provide an objective approach to the problem. The modified Glasgow Coma Scale was used to rank cases according to their severity. From the cases examined, results showed that intoxication with potent opioids, such as etorphine, carfentanil and thiafentanil, need to be treated with antagonists such as naloxone, nalmefene or naltrexone, and not with antagonists with agonistic properties, such as diprenorphine. With regard to the alpha(2)-agonists xylazine, detomidine, medetomidine and romifidine, no antagonist is currently accredited for human use. Atipamezole, a specific alpha(2)-antagonist, is widely used in veterinary medicine and has been used experimentally to reverse dexmetomidine in a study in human medicine. The high concentrations of alpha(2)-agonists being used in zoo and wildlife medicine warrant the accreditation of atipamezole for use in cases of human exposure. Knowledge and availability of the appropriate antagonist are essential in cases of human intoxication with injectable anaesthetics. Preventive measures, such as wearing gloves and eye protection, need to be used more regularly to reduce the risk of exposure.

Action of a Novel PDE4 inhibitor ZL-n-91 on lipopolysaccharide-induced acute lung injury.

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.5 mg kg(-1), ip). After the 6h of instilling intratracheally with LPS in mice, total leukocyte number, neutrophil number and protein content in BALF increased rapidly, a large number of neutrophil infiltration around the pulmonary vessel and airway, the lung wet weight/dry weight (w/d)ratio raised significantly. MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate raised significantly. P(a)O(2), P(a)CO(2) and PH value in peripheral arterial blood also changed obviously, P(a)O(2) and PH value dropped slightly and P(a)CO(2) increased significantly in LPS group. ZL-n-91 (3 microg, 10 microg, 30 microg kg(-1)) dose-dependently reduced the total leukocyte number, neutrophil number and total protein content in BALF, MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate, but the effect of ZL-n-91 in pathological changes and lung wet w/d ratio is slight; Rol and Dex significantly reduced lung wet w/d ratio and improved pathological changes, neutrophil around the pulmonary vessel and airway significantly reduced, symptoms of lung edema relieved; The PH value, P(a)O(2) and P(a)CO(2) in ZL-n-91 high dosage group and Rol group had changes, but there was no significant difference compared with LPS group or saline group; After the administration, the righting reflex recovery time significantly shorten in every group of ZL-n-91. the righting reflex recovery time of Rol group was similar with ZL-n-91 30 microg kg(-1) group, while Dex group was similar with saline group. The present study confirms that the inhibitory effect of ZL-n-91(30 microg kg(-1)) on the inflammatory reactivity, including inhibition of inflammatory cell and protein exudation, MPO and PDE4 activity, improvement of the blood gas, those effects were equivalent with rolipram 1 mg kg(-1), and suggested that ZL-n-91 was stronger than rolipram in PDE4 inhibition. So we speculated that ZL-n-91 may have stronger therapeutic potential for treatment of inflammatory disease than rolipram, meantime have stronger nervous system effect than rolipram.

Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats.

The interaction of isoallopregnanolone (3 beta-OH-5 alpha-pregnan-20-one) on allopregnanolone (3 alpha-OH-5 alpha-pregnan-20-one) induced anaesthesia was studied in male rats using burst suppression of 1 s ("silent second") with an electroencephalographic-threshold method. The i.v. administration of isoallopregnanolone was varied in relation to induction of "silent second". Pre-treatment with isoallopregnanolone (12.5-50 mg/kg iv) 2 min prior to the threshold test gave an increase in the threshold dose of allopregnanolone (ANOVA df(3;36), F=13.61, P<0.001), which was dose dependent (r=0.73, b [slope]=0.08, df=38, P<0.001). After isoallopregnanolone pre-treatment, but not in the controls, anaesthesia time was positively related to the dose of allopregnanolone (r=0.52, b=1.72, df=28, P<0.01). Anaesthesia times were not influenced by a corresponding administration of isoallopregnanolone immediately after induction of "silent second". When allopregnanolone and isoallopregnanolone were infused together at molar ratios of 1:1, 1:1.23, 1:1.43, a linear increase of the threshold doses of allopregnanolone was seen in relation to the dose of isoallopregnanolone (r=0.86, b=0.40, df=8, P<0.01). Thus isoallopregnanolone can antagonise the anaesthetic action of allopregnanolone.

Effectiveness of antagonists for tiletamine-zolazepam/xylazine immobilization in female white-tailed deer.

A combination of tiletamine-zolazepam/xylazine (TZ/X) is effective in the chemical immobilization of white-tailed deer (Odocoileus virginianus); however, the lengthy duration of immobilization may limit its usefulness. From October to November 2002, 21 captive female deer were assigned randomly to an alpha(2) antagonist treatment to reverse xylazine-induced sedation (seven does per group). All deer were given 220 mg of TZ (4.5+/-0.4 mg/kg) and 110 mg of X (2.2+/-0.2 mg/kg) intramuscularly (IM). Antagonist treatments were either 200 mg of tolazoline (4.0+/-0.4 mg/kg), 11 mg of atipamezole (0.23+/-0.02 mg/kg), or 15 mg of yohimbine (0.30+/-0.02 mg/kg) injected, half intravenously and half subcutaneously, 45 min after the IM TZ/X injection. In addition, 10 other deer (five per group) were immobilized as before and then given tolazoline (200 mg) after 45 min, with either a carrier (dimethyl sulfoxide [DMSO]) or carrier (DMSO) plus flumazenil (5 mg) to reverse the zolazepam portion of TZ. Mean times from antagonist injection until a deer raised its head were different for alpha(2) antagonist treatments (P=0.02). Times were longer for yohimbine (62.3+/-42.7 min) than for either atipamezole (24.3+/-17.1 min) or tolazoline (21.3+/-14.3 min). Mean times from antagonist injection until standing were not different (P=0.15) among yohimbine (112.0+/-56.4 min), atipamezole (89.7+/-62.8 min), or tolazoline (52.6+/-37.2 min). A sedation score based on behavioral criteria was assigned to each deer every 30 min for 5 hr. On the basis of sedation scores, tolazoline resulted in a faster and more complete reversal of immobilization. Flumazenil treatment did not affect recovery.

A comparison of carfentanil/xylazine and Telazol/xylazine for immobilization of white-tailed deer.

October 2001 to January 2002, captive free-ranging white-tailed deer (Odocoileus virginianus) were immobilized with a combination of carfentanil citrate and xylazine hydrochloride. From this study, we selected a dose of carfentanil/xylazine for the purpose of comparing immobilization parameters and physiologic effects with those of a combination of tiletamine and zolazepam (Telazol) and xylazine. Animals were initially given intramuscular injections of 10 mg xylazine and one of four doses of carfentanil (i.e., 0.5, 1.0, 1.5, and 2.0 mg). A carfentanil dose of 1.2 mg (x +/- SD = 23.5 +/- 3.2 microg/kg) and 10 mg xylazine (0.2 +/- 0.03 mg/kg) were selected, based on induction times and previously published reports, to compare with a combination of 230 mg of Telazol (4.5 +/- 0.6 mg/kg) and 120 mg xylazine (2.3 +/- 0.3 mg/kg). Time to first observable drug effects and to induction were significantly longer for deer treated with carfentanil/xylazine than with Telazol/xylazine (P < 0.01). Hyperthermia was common in deer immobilized with carfentanil/xylazine, but heart rate, respiration rate, and hemoglobin saturation were within acceptable levels. Degree of anesthesia of deer immobilized with Telazol/xylazine was superior to deer immobilized with carfentanil/xylazine. The combination of 120 mg of naltrexone hydrochloride and 6.5 mg of yohimbine hydrochloride provided rapid and complete reversal (1.9 +/- 1.1 min) of carfentanil/xylazine immobilization. Animals immobilized with Telazol/xylazine had long recovery times with occasional resedation after antagonism with 6.5 mg of yohimbine. The combination of carfentanil and xylazine at the doses tested did not provide reliable induction or immobilization of white-tailel (leer even though drug reversal was rapid and safe using naltrexone and yohimbine.

[Fatty acid-induced reversal of general anesthesia: chain length-dependence of antagonizing potencies of fatty acids].

Anesthesia is always antagonized by high pressure in the range of 100 atm. The pressure reversal means that the volume of the macromolecule in the anesthetized state is larger than the awake state. Long-chain fatty acids tightened the structure of firefly luciferase whereas anesthetics unfolded the enzyme structure. As expected from these findings, myristate (C 14 fatty acid) at 40 microM increased the EC50 values of volatile anesthetics 250% in goldfish. This study was performed to test the hypothesis that anesthesia antagonism by fatty acid in goldfish was caused by nonspecific action on proteins. We therefore studied the chain length-dependence of the antagonizing potencies of fatty acids. The chain length of 6, 8, 10, 12, and 14 was studied. Ten goldfish were placed in a tub containing 3200 ml distilled water without (control) or with fatty acids. After 30 min of bubbling with halothane vaporized with oxygen into the tub, goldfish were electrically stimulated by constant voltage 20 V for 0.2 sec. Those did not respond to the stimuli were counted as anesthetized. All fatty acids except C 10 increased EC50 of halothane by 50-100% compared to the control (1.13% atm). However, the fatty acid concentrations required for antagonizing halothane increased as the chain length decreased, 300 microM in C 6 30-fold higher than 10 microM in C 14. Because water solubility of short-chain fatty acid is higher than long-chain fatty acid, the antagonizing potencies of fatty acids were thus determined not by their concentrations but by their thermodynamic activities (Ferguson's rule). These results suggest that fatty acid-induced anesthesia antagonism may be caused by physical and nonspecific actions on proteins.

Nonimaging detectors in drug development and approval.

Regulatory applications for imaging biomarkers will expand in proportion to the validation of specific parameters as they apply to individual questions in the management of disease. This validation is likely to be applicable only to a particular class of drug or a single mechanism of action. Awareness among the world's regulatory authorities of the potential for these emerging technologies is high, but so is the cost to the sponsor (including the logistics of including images in a dossier), and therefore the pharmaceutical industry must evaluate carefully the potential benefit of each technology for its drug development programs, just as the authorities must consider carefully the extent to which the method is valid for the use to which the applicant has put it. For well-characterized tracer systems, it may be possible to design inexpensive cameras that make rapid assessments.

Antinociceptive properties of neurosteroids II. Experiments with Saffan and its components alphaxalone and alphadolone to reveal separation of anaesthetic and antinociceptive effects and the involvement of spinal cord GABA(A) receptors.

Studies have shown that the steroid anaesthetic alphaxalone positively modulates gamma-aminobutyric acid (GABA) receptors in vitro. It has also been reported that positive modulation of GABA(A) receptors in the rat spinal cord can produce antinociception in vivo. This present study looks at the interaction of an intraperitoneal injection (i.p.) of the steroid anaesthetic combination Saffan (alphaxalone 9 mg/ml, alphadolone acetate 3 mg/ml) with GABA(A) receptors in the spinal cord. Full recovery from anaesthesia induced by Saffan 2 ml/kg i.p., as assessed by the rotarod test, occurred after 28.78 +/- 0.86 min. Residual antinociceptive effects were assessed by application of electrical current at two skin sites (neck and tail) and also tail withdrawal from noxious heat. Residual antinociception was observed at both skin sites assessed by the electrical test but not when assessed by noxious heat. The antinociceptive effects in the tail but not the neck were suppressed by intrathecal administration of GABA(A) antagonists (bicuculline and SR-95531). In a separate group of experiments alphaxalone and alphadolone were given i.p. individually at the same doses that were given when formulated in Saffan. Alphaxalone produced sedative and anaesthetic effects with no antinociception. Alphadolone caused no sedation but it did cause antinociceptive effects equal in magnitude to those produced by Saffan. We conclude that Saffan produces antinociception in rats when given i.p. by an interaction with spinal GABA(A) receptors. Furthermore, this antinociception is due to the alphadolone content of the neurosteroid anaesthetic and not the alphaxalone.

Health evaluation of free-ranging guanaco (Lama guanicoe).

Twenty free-ranging guanaco (Lama guanicoe) in Chubut Province, Argentina, were immobilized for health evaluations. All but two animals appeared to be in good condition. Hematology, serum chemistry, and vitamin and mineral levels were measured, and feces were evaluated for parasites. Serology tests included bluetongue, brucellosis, bovine respiratory syncitial virus, bovine viral diarrhea/mucosal disease, equine herpesvirus 1, infectious bovine rhinotracheitis, Johne's disease (Mycobacterium paratuberculosis), foot and mouth disease, leptospirosis (17 serovars), parainfluenza-3, and vesicular stomatitis. Blood samples from 20 domestic sheep (Ovis aries) maintained in the same reserve with the guanaco were also collected at the same time for serology tests. No guanaco had positive serologic tests. Sheep were found to have antibody titers to bovine respiratory syncytial virus, Johne's disease, leptospirosis, and parainfluenza-3. There was no apparent difference in external appearance or condition, or statistical difference in blood test values, between the animals that were positive or negative for parasite ova.

Use of yohimbine to reverse prolonged effects of xylazine hydrochloride in a horse being treated with chloramphenicol.

A 1-year-old Standardbred gelding had received xylazine hydrochloride (0.75 to 1.00 mg/kg [0.34 to 0.45 mg/lb] of body weight, IV) during 2 surgeries for debridement of a wound. The horse was given chloramphenicol (55 mg/kg [25 mg/lb], PO, q 6 h) for 5 days, and was anesthetized a third time with xylazine (0.75 mg/kg, IM). Five hours after administration of xylazine, the horse remained markedly sedated and had clinical signs of gaseous distention of the large bowel (bloat) requiring trocharization. Administration of yohimbine (0.03 mg/kg [0.01 mg/lb], i.v.) eliminated signs of sedation within 5 minutes. Moderate flatulence developed, and gastrointestinal sounds could be heard within all 4 abdominal quadrants within 15 minutes of yohimbine administration. The remainder of recovery was unremarkable. Xylazine induces bradycardia and decreases gastrointestinal motility in addition to causing sedation, muscle relaxation, and analgesia. Chloramphenicol can inhibit oxidase activity of cytochrome P-450 and inhibit metabolism and elimination of drugs such as xylazine.

Effects of intravenous phenylephrine on blood pressure, nociception, and neural activity in the rostral ventral medulla in rats.

Acute or chronic increases in arterial blood pressure are associated with decreases in nociception. In addition, acute increases in arterial blood pressure inhibit ON cells and excite OFF cells of the rostral ventral medulla (RVM). The current study tested whether the antinociception produced by increases in blood pressure is dependent on changes in the activity of ON and/or OFF cells. Single unit activity of ON or OFF cells was recorded in the RVM during increases in blood pressure produced by intravenous infusion of phenylephrine (1, 2.5, or 10 micrograms/min for 21 min) in lightly anesthetized rats. Nociception was measured using the tail flick test. Phenylephrine dose-dependently increased mean arterial pressure and tail flick latency, but had inconsistent effects on neural activity in the RVM. In a second study, the effects of phenylephrine infusion on tail flick latency was determined before and after saline or lidocaine microinjections into the RVM. Lidocaine had no effect on the ability of phenylephrine to inhibit the tail flick reflex. These data suggest that the RVM, and therefore ON and OFF cells, is not required for phenylephrine-induced antinociception.

The anti-anesthetic action of idazoxan.

A possible anti-anesthetic effect of idazoxan using the depth versus latency of cortical cellular response and somatosensory evoked potentials as indices of anesthesia was studied. With the administration of 10 mg/kg (i.p.) idazoxan, a potent and selective alpha 2-adrenoceptor antagonist, to an anesthetized rat with 1.25-1.5 g/kg (i.p.) urethane, the modal latency of somatosensory cortical responses to electrical stimulation of the forepaw (0-90 V, 1 Hz) was shortened to 87 +/- 3.6% (mean +/- S.D.; n = 3) of the baseline value. The number of units firing increased by 259 +/- 98.5% (n = 3). The combined parameter (1/L x Pi; L, latency; Pi, initial positive wave) of the somatosensory evoked potentials was enhanced to 125.0 +/- 16.2% (n = 19) versus saline (98.9 +/- 25.6%; n = 18) during the desynchronized electroencephalogram (EEG). The initial negative component (Ni) of the somatosensory cortical response was increased to 192.0 +/- 83.1% (n = 19) and 134.8 +/- 36.9% (n = 19) during the synchronized and desynchronized EEG, respectively. Thus idazoxan appears to produce effects resembling a "lightening of anesthesia." This may provide the impetus for further studies on the possibility of using alpha 2-adrenoceptor antagonists in the recovery from certain types of anesthetic agents.

[Antagonists in anesthesia]. / Antagonisten in der Anästhesie.

In modern anaesthesia various antagonists are used. They provide efficient tools to facilitate better control of pharmacological effects and side effects of drugs routinely used in anaesthesia. Naloxone is a competitive antagonist of opioids without any intrinsic activity. It counteracts respiratory depression, pruritus, sedation and analgesia caused by opioids. It is fast-acting with a duration of action of 45 to 90 min. Several investigators have reported severe side effects of naloxone including hypertension, tachyarrhythmias, left heart failure and cardiac arrest, and hence the use of naloxone must be carefully considered in every single patient. Flumazenil is a competitive antagonist of benzodiazepines. It is a remarkably safe drug and very effective to terminate all benzodiazepine effects in anaesthesia and intensive-care patients. Serious complications caused by flumazenil have been reported in patients receiving benzodiazepines in the treatment of seizure disorders and in patients with mixed intoxications. Neostigmine is one of several antagonists of neuromuscular blocking agents. Its side effects include bradycardia, increased bronchial secretions and increased peristalsis. Indication depends on the results of neuromuscular monitoring. Physostigmine is an unspecific antagonist of the central anticholinergic syndrome, an acute psychosis that may be caused by numerous drugs used in anaesthesia. Generally, antagonists should be carefully titrated. In emergency medicine the use of these antagonists is not recommended; the primary goal is to restore vital functions.

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.

Immobilization of Rocky Mountain elk with Telazol and xylazine hydrochloride, and antagonism by yohimbine hydrochloride.

Ten trapped Rocky Mountain elk (Cervus elaphus nelsoni) were successfully immobilized with a combination of 500 mg Telazol and 60 mg xylazine hydrochloride (HCl) from 9 July to 25 August 1993 in Custer State Park, South Dakota (USA). Mean (SD) dosages of 2.5 (0.6) mg/kg Telazol and 0.3 (0.1) mg/kg xylazine HCl, respectively, were administered, resulting in a mean (SD) induction time of 4.6 (0.8) min. Induction time varied with weight and dosage. Respiratory rate (breaths/min) increased following injection of Telazol and xylazine HCl and remained elevated or continued to increase through 10 min post-injection and then declined. There were no mortalities in this study. Forty mg of yohimbine HCl was used as an antagonist in eight elk, resulting in a mean (SD) recovery time of 14.0 (9.9) min when administered intravenously (n = 6), and 124.7 (9.5) min when given intramuscularly (n = 2). Recovery time varied with weight and dosage of yohimbine. Elk given 2.1 to 2.6 mg/kg Telazol and 0.1 to 0.3 mg/kg xylazine HCl responded to yohimbine HCl when administered intravenously.