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Year: 2010

Total invtravenous anesthesia with , ketamine, and or detomidine following induction with tiletamine, , and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery

Auer, U ; Wenger, S ; Beigelböck, C ; Zenker, W ; Mosing, M

Abstract: Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 µg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg and 8.7±1.21 µg/kg given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.

DOI: https://doi.org/10.7589/0090-3558-46.4.1196

Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-36361 Journal Article

Originally published at: Auer, U; Wenger, S; Beigelböck, C; Zenker, W; Mosing, M (2010). Total invtravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery. Journal of Wildlife Diseases, 46(4):1196-1203. DOI: https://doi.org/10.7589/0090-3558-46.4.1196 Journal of Wildlife Diseases, 46(4), 2010, pp. 1196–1203 # Wildlife Disease Association 2010

TOTAL INTRAVENOUS ANESTHESIA WITH MIDAZOLAM, KETAMINE, AND XYLAZINE OR DETOMIDINE FOLLOWING INDUCTION WITH TILETAMINE, ZOLAZEPAM, AND XYLAZINE IN RED DEER (CERVUS ELAPHUS HIPPELAPHUS) UNDERGOING SURGERY

Ulrike Auer,1,6 Sandra Wenger,2 Christoph Beigelbo¨ck,3 Wolfgang Zenker,4 and Martina Mosing5 1 Division of Anaesthesiology and Perioperative Intensive Care, University of Veterinary Medicine, Veterina¨ rplatz 1, 1210 Vienna, Austria 2 Clinicfor Zoo Animals, ExoticPets and Wildlife, Vetsuisse Faculty,Univ ersity of Zurich, Winterthurerstrasse 260, 8057 Zu¨ rich, Switzerland 3 Research Institute of Wildlife Ecology, University of Veterinary Medicine, Savoyenstrasse 1, 1160 Vienna, Austria 4 Praxis fu¨ r Zootiere und Exoten, Kleintierpraxis, Neuwiesenstr. 6, 8610 Uster, Switzerland 5 Equine Hospital, The University of Liverpool, Leahurst, Chester High Road, Neston, South Wirral CH64 7TE, UK 6 Corresponding author (email: [email protected])

ABSTRACT: Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean6SD) 1.7960.29 mg/kg xylazine and 1.7960.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 6962 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.560.055 mg/kg/hr) and group D, detomidine (260.22 mg/kg/ hr), both in combination with ketamine (260.02 mg/kg/hr) and midazolam (0.0360.0033 mg/kg/ hr), as a constant rate infusion. Anesthesia was reversed with 0.0960.01 mg/kg atipamezole and 8.761.21 mg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen. Key words: Detomidine, ketamine, midazolam, red deer, total intravenous anesthesia, xylazine.

INTRODUCTION et al., 2000). For prolonged or invasive procedures, inhalation anesthesia is rec- Approximately five million deer live in ommended (Caulkett, 1997). As inhalation captivity worldwide and interest in farmed anesthesia can be difficult to perform deer is growing exponentially (Hudson, under field conditions, a safe protocol 2001). Procedures such as hoof care, using total intravenous anesthesia (TIVA) treatment of dystocia or amputation of would be valuable. antlers are commonly performed in deer, The aims of this study were to evaluate and an in-depth knowledge about immo- a TIVA protocol using a combination of bilization and anesthesia is necessary. midazolam, ketamine, and xylazine or Many and protocols detomidine to maintain anesthesia in red have been evaluated in various deer deer and to investigate the effects of species during the past two decades. partial antagonization of this combination Numerous reports describe the use of with atipamezole and sarmazenil. injectable alone or in combi- nation with local anesthesia for short MATERIALS AND METHODS surgical procedures. Potent or cyclohexamines (tiletamine, ketamine) in Animals combination with or al- Sixteen female free-ranging red deer (Cer- pha-2 adrenoceptor agonists are common- vus elaphus hippelaphus), living in a 45-ha, forested portion of the Research Institute ly used for immobilization and short-term of Wildlife Ecology in Vienna, Austria anesthesia in red deer (McKelvey and (48u12900N, 16u22900E), were immobilized. Simpson, 1985; Caulkett, 1997; Janovsky Animals had a mean6SD age of 4.161.3 yr

1196 AUER ET AL.—TOTAL INTRAVENOUS ANESTHESIA IN RED DEER 1197

(range,1.5–6 yr) and a body weight of tance, approximately 600 m), where endotra- 120615 kg (range, 90–135 kg). Body weight cheal intubation was performed. Time from was estimated by one person before darting; darting to intubation (intubation time) was after induction, the exact weight was deter- recorded. mined by weighing with an electronic balance. A catheter (Intraflon2, 12 G, Vycon, Surgery was performed to implant a self- Ecoune, France) was placed in the left jugular constructed telemetry system as part of an vein for intravenous (IV) administration of etho-ecologic project. A ventral midline neck 10 ml/kg/hr lactated Ringer’s solution (Ringer incision was made through the skin, and the Lactat ‘‘Fresenius,’’ Fresenius Kabi Austria subcutaneous tissue was separated by blunt GmbH, Graz, Austria) and anesthesia mainte- dissection to form a pouch on the left ventro- nance using CRI. After endotracheal intuba- lateral aspect of the neck. Two incisions were tion, the tube was connected to a circle system made along the caudal ventral midline of the delivering an oxygen/air mixture with an pouch for placement of the electrocardiogram inspiratory oxygen concentration (FIO2)of (ECG) electrodes. Electrodes were pulled 30–50%. Animals breathed spontaneously. from the transmitter pouch through a subcu- The animals were positioned in right lateral taneous tunnel prepared with a sterile cathe- recumbency with the left foreleg pulled ter. The transmitter and electrodes were fixed forward. to the subcutis, and the skin incisions were To prepare the CRI solution, 250 mg closed with absorbable suture material (Gia- xylazine (Xylasol, Dr. E. Gra¨ub AG, Berne, cometti et al., 2001). This study was approved Switzerland) for group X, or 1.4 mg detomi- by the Institutional Ethics Committee of dine (Domosedan, Pfizer, Vienna, Austria) for the Veterinary University of Vienna and group D, plus the 1,000 mg ketamine (10% had governmental approval (reference, GZ Narketan, Vetoquinol Austria GmbH, Vienna, 68.205/88-BvGt/2002). Austria) and 15 mg midazolam (Midazolam Mayrhofer Pharmazeutika, Vienna, Austria) Study design were mixed in 500 ml saline (0.9% NaCl A parallel study design was used, and ‘‘Fresenius,’’ Fresenius Kabi). This resulted in animals were randomly divided into two a concentration of 0.5 mg/ml xylazine or 2.0 mg/ groups. Group X received a TIVA protocol ml detomidine, 2 mg/ml ketamine, and using midazolam, ketamine, and xylazine given 0.03 mg/ml midazolam. For the first 20 min, an infusion rate of 1.2 ml/kg/hr was adminis- as a continuous rate infusion (CRI) after initial TM immobilization with tiletamine, zolazepam, tered via an infusion pump (Asena , Alaris and xylazine. In group D, anesthesia was Medical UK Ltd, Basingstoke, Hampshire, maintained using a CRI with midazolam, UK). Thereafter, CRI rate was reduced ketamine, and detomidine. stepwise in 10% increments every 10 min. The duration of CRI administration and the Anesthesia total volume given were noted. After surgery, the animals were brought back Two days before surgery the deer were to the restricted area. Twenty minutes after the brought into a 1-ha, restricted area. Food, but end of anesthesia, a combination of 10 mg not water, was withheld for 24 hr. Lyophilized atipamezole (Antisedan, Pfizer) and 1 mg sar- powder of 500 mg tiletamine-zolazepam (Zo- mazenil (Sarmasol, Dr. E. Gra¨ub AG, Bern, letil, Virbac, Carros, France) and 500 mg of Switzerland) was administered by IV. The lyophilized xylazine powder (Rompun TS, catheter and endotracheal tube were removed. Bayer, Leverkusen, Germany) were dissolved Time from administration of the antagonists to in 5 ml water for injection. This resulted in a sternal recumbency (sternal time) and standing concentration of 50 mg tiletamine, 50 mg (up time) were recorded. Quality of recovery zolazepam, and 100 mg xylazine per milliliter was evaluated as excellent (standing on first of solution. The body weight of the animal was attempt, normal gait without ataxia), good estimated, and a 3-ml, plastic dart (Telinject (standing on first attempt with minimal ataxia, G.U.T., Roemerberg, Germany) was prepared. moving with unsteady gait) or poor (requiring The animal was darted with 2 to 2.5 ml of the more than one attempt to standing, moderate to solution intramuscularly in the upper hind leg severe ataxia, and falling over). Animals were or shoulder area using a CO2-pressurized dart observed for 4 hr after surgery. gun (Daninject, Selerup, Denmark). Time (in minutes) from darting to initial effect with Monitoring head on the ground (onset time) was recorded. Thereafter, the animals were transported from A catheter (Vasocan Braunu¨le, 0.9 3 25 mm, the enclosure to the operating theater (dis- B. Braun, Melsungen, Germany) was placed in 1198 JOURNAL OF WILDLIFE DISEASES, VOL. 46, NO. 4, OCTOBER 2010 the auricular artery for invasive measurement 6962 min, respectively. Mean infusion of arterial blood pressure (Combitrans Mon- rate was 160.1ml/kg/hrwithatotal itoring-Set Arteriell, Fa., Braun). The blood volume of 138618.9 ml. Mean dose of pressure transducer was positioned and cali- 6 brated to atmospheric pressure at the level of xylazine and detomidine was 0.54 the sternum. An arterial blood sample for 0.03 mg/kg/hr and 1.5560.6 mcg/kg/hr, blood gas analysis was taken in four deer in respectively, and was 2.160.2 mg/kg/hr each group before the endotracheal tube was for ketamine and 3.260.4 mg/kg/hr for connected to the circle system and 20 and 40 min after connection to the circle system. midazolam. There were no significant The blood samples were analyzed immediately differences between groups. Total time after sampling using a portable blood gas of anesthesia from darting to end of analyzer (I-STAT Portable Clinical Analyzer; recovery period was 116615 min. I-STAT Corporation, East Windsor, New Heart rate, mean blood pressure, RR, Jersey, USA). An oxygen partial pressure and PECO2 were higher in group X than (PaO2) of lower than 60 mmHg (8 kPa) at the second blood gas analysis was seen as the group D, but this was not statistically % % cutoff point to increase FIO2 from 30 to 50 significant. Tidal volume was significantly to 100%. Heart rate (HR) was determined lower in group X at time points 25, 35, 45, from the ECG in a base-apex lead (HP CMS 55, and 65 min (Table 1). Depth of Monitor M1001A, Hewlett Packard, Boeblin- gen, Germany). Respiratory rate (RR) and anesthesia was easy to adapt in both end-tidal carbon dioxide tension (PECO2) were groups. evaluated using a side stream capnograph Results of blood gas analyses are (Nellcor, Hayward, California, USA). The summarized in Table 2. Both groups same device was used to evaluate hemoglobin showed hypercapnia, respiratory acidosis, oxygen saturation (SpO2) by placing the probe of the pulse oximeter on the tongue. Tidal and decreased PaO2. No significant differ- volume (VT) was measured using a Wright ences were seen for PaO2 between groups. spirometer (Dra¨ger, Lu¨beck, Germany), posi- Mean PaO2 before oxygen supplementa- tioned in the expiratory limb of the circle tion was 82619.7 mmHg (10.862.6 kPa) system. For measuring core body temperature and, after connection to the anesthetic (T), an esophageal temperature probe was 6 used (HPM1008P, HP CMS Monitor, Hewlett circle system, was 105 18.5 mmHg 6 Packard). All parameters were manually re- (14 2.4 kPa). In both groups, PaO2 corded at 10-min intervals. Any side effects increased significantly over time. The throughout the time under anesthesia were partial pressure of carbon dioxide (PaCO2) recorded. was significantly higher at all time points , Statistical analyses in group X (P 0.001) than in group D. 6 The mean doses of sarmazenil and Results are expressed as mean SD. Differ- atipamezole were 8.761.2 mg/kg and ences in HR, RR, PECO2, and T between the 6 two groups were analyzed using an unpaired 0.09 0.01 mg/kg, respectively. Times to Student’s t-test for normally distributed data reach sternal recumbency and to standing and the Wilcoxon rank-sum test for nonpara- after antagonization were 0.960.6 min metric data. One-way analysis of variance and 1.961.6 min, respectively. Mean (ANOVA) was used to compare repeatedly duration of recovery was 21.762.6 min. measured parameters within a group. Statisti- cal significance was determined at P,0.05. No differences were seen between groups. Quality of recovery was excellent in 15 RESULTS deer. One deer in group X received no reversal because it recovered spontane- The mean dose for initial immobiliza- ously 14 min after the end of anesthesia. tion with xylazine and tiletamine/zola- Another deer in group X became recum- zepam was 1.7960.29 mg/kg and bent again 20 min after reversal and, 1.7960.29 mg/kg, respectively. Onset therefore, received an additional bolus of time, intubation time, and duration of 10 mg atipamezole and 1 mg sarmazenil CRI were 8.263.6 min, 30619 min, and IV. Heart rates recorded from the telem- AUER ET AL.—TOTAL INTRAVENOUS ANESTHESIA IN RED DEER 1199

TABLE 1. Physiologic variables of red deer maintained anesthetized with a continuous rate infusion of midazolam, ketamine and xylazine or detomidine. Numbers are mean6SD.

Time (min)

Variablea 5 15253545 55 65

HR X (beats/min) 50615 4465.5 4665.9 4866.8 5068.2 4763.9 4566.7 HR D (Beats/min) 4365.2 4263.9 4466.1 4468.3 46611 45612 47615 SAP X (mmHg) 104613.8 109615.8 107614.9 10612.8 104613.5 101614.1 97615.5 SAP D (mmHg) 117612.8 115615.6 113617.1 108621.1 113618.6 113619.5 111619.6 RR X (breaths/min) 23613.4 28611.9 32610.8 3169.8 28610.9 26611.5 22610.9 RR D (breaths/min) 18615.6 17612.6 19614.9 19612.1 22613.4 21610.7 1868.7

PECO2 X mmHg 63614.6 6368.7 65613.1 6569.4 70610.5 7269.6 80615.9 kPa 8.4 61.9 8.461.2 8.661.7 8.661.3 9.361.4 9.661.3 10.66 2.1

PECO2 D mmHg 55615.4 59614.3 6368.7 6369.9 61615.5 6669.1 6569.3 kPa 7.362.1 7.861.9 8.461.2 8.461.3 8.162.1 8.861.2 8.661.2 VT X (ml/breath) 450694 5136155 469665* 506690* 494677* 4576109* 383676* VT D (ml/breath) 5866237 6696188 6816171 7316148 6886168 6956130 728686 T X (C) 3860.6 3860.5 3960.5 3960.5 3860.5 3960.4 3960.5 T D (C) 3861.1 3960.9 3960.7 3960.7 3960.7 3960.7 3960.5

* Significant difference (P,0.001) between xylazine and detomidine. a 5 5 5 5 5 5 X xylazine; D detomidine; HR heart rate; SAP systolic arterial blood pressure; RR respiratory rate; PECO2 end expiratory carbon dioxide; VT 5 tidal volume; T 5 temperature. etry systems varied from 44620 to 77623 thesia for a surgical procedure lasting in the first 24 hr after end of anesthesia, longer than 1 hr and can easily be applied and no significant differences were seen under field conditions. The major side between the two groups. effect seen in this study was respiratory depression causing hypercapnia and mild DISCUSSION hypoxemia. Therefore, oxygen supplemen- tation is highly recommended. Nasal Inhalation anesthesia is recommended insufflation of oxygen at 10 l/min has been for prolonged or invasive procedures in proven to reduce hypoxemia under field cervids (Caulkett, 1997). Expensive and conditions (Read et al., 2001, Mich et al., bulky equipment is necessary to main- 2008). tain inhalation anesthesia under field Blood gas analyses revealed hypercap- conditions. The TIVA protocol used in nia, respiratory acidosis, and decreased our deer provided a good level of anes- PaO2 in both groups. However, higher

TABLE 2. Blood gas values of four red deer in group xylazine and four in group detomidine that were maintained anesthetized with a continuous rate infusion of midazolam, ketamine, and xylazine or detomidine.a

Group Sampling interval PaO2 (mmHg) PaCO2 (mmHg) Base excess HCO3 pH Lactate

Xylazine 1 82.7619.7 75.166.8* 463.4 3263.4 7.260.1 0.960.4 (n54) 2 88.564.5 79.1611.2* 4.5633263.5 7.260.1 160.6 3 105.5618.2 76.3612.2* 3.861.3 3261.2 7.260.1 0.760.3 Detomidine 1 58.2611.8 59.469.3 3.163.2 29.663.4 7.360.1 1.661.4 (n54) 2 79.5617.9 6769.6 5.462.4 31.563.3 7.360.1 1.360.9 3 107.7667.6 67.968.5 6.162.7 31.864 7.360.1 0.860.5

* Significant differences (P,0.001) between xylazine and detomidine. a 5 5 5 PaO2 oxygen partial pressure; PaCO2 partial pressure of carbon dioxide; HCO3 bicarbonate. 1200 JOURNAL OF WILDLIFE DISEASES, VOL. 46, NO. 4, OCTOBER 2010

PaCO2 and PECO2 levels were seen in the Unlike , midazolam is water xylazine group. This indicates that the soluble and can, therefore, be mixed with combination that included xylazine caused other drugs in a CRI solution. The use of more respiratory depression than the midazolam in combination with ketamine detomidine combination did. Along with for induction in wild ruminants is limited the higher CO2 levels, higher PaO2 levels to one case report in a buffalo (Syncerus were seen in the xylazine group. Similar caffer; Stegmann, 2004). Midazolam, ke- findings were reported with a xylazine- tamine, and three different alpha-2 adre- tiletamine-zolazepam mixture in wapiti noceptor agonists (xylazine, detomidine, (Cervus canadensis; Read et al., 2001). and medetomidine) in combination with a The most likely explanation for this finding low dose of was used for is a higher ventilation/perfusion mismatch maintenance in horses (Equus caballus; and intrapulmonary shunt volume in Mosing et al., 2007). Xylazine and deto- group D leading to lower PaO2 values midine were preferred over medetomi- compared with those for group X. How- dine as the former two alpha-2 adreno- ever, because Pa/PaO2 differences were ceptor agonists are licensed for ruminants not evaluated because the inspiratory in the European Union (European Com- oxygen concentration was not measured, mission, 2009). This is an important issue this remains an assumption. Ventilation/ in the case of deer farmed for meat perfusion mismatch and intrapulmonary production within the European Union. shunt volume are not directly correlated to Using medetomidine as part of the main- pulmonary ventilation, which was better tenance protocol, instead of xylazine or maintained in group D, resulting in lower detomidine, for wildlife captures (in which PaCO2 levels. case, the cascade must not be considered) Combinations of tiletamine-zolazepam might result in quicker onset times, less and xylazine and prolongation of anesthe- stressful responses, more cardiovascular sia with ketamine are widely used for the stability, and quicker recovery when using immobilization of cervids (Caulkett, 1997; atipamezole (Jalanka and Roeken, 1990; Galka et al., 1999; Fernandez-Moran et Caulkett et al., 2000; Ferna´ndez-Mora´net al., 2000; Janovsky et al., 2000; Read et al., al. 2000; Mich et al., 2008) 2001). These combinations can lead to When continuous-rate infusions are prolonged recovery because of the accu- used to provide long-term anesthesia, mulation of ketamine and norketamine, its drugs with a short-elimination half-life first metabolite. An overhang with keta- are preferable to avoid accumulation. mine or norketamine can lead to increased Midazolam has a relatively short elimina- muscle tone and increased oxygen con- tion half-life, which makes it a valuable sumption during recovery. Therefore, drug that can be given via CRI (Hall et al., alternative protocols, combining ketamine 1988; Fragen, 1997). As already men- with muscle relaxants and , could tioned, the limitation of the benzodiaze- be useful because the ketamine dose can pine-ketamine CRI is the ketamine com- be reduced. A TIVA protocol, including ponent. Pharmacokinetic studies done in guaifenesin, can be used in cattle and horses revealed no cumulative effect after small ruminants, but cervids seem to be administration of ketamine CRI lasting particularly sensitive to toxic side effects of 60 min. Norketamine, the active metabo- guaifenesin, including extensor rigidity lite of ketamine was detected throughout and opisthotonus (Lin et al., 1993; Rie- the study period. Recovery was smooth in bold, 1996; Caulkett, 1997). The adminis- all animals (Nolan et al., 1996). In another tration of the midazolam study, two of six ponies showed some for central muscle relaxation, instead of excitement and ataxia after 120 min of guaifenesin, is a relatively new technique. ketamine- CRI (Bettschart- AUER ET AL.—TOTAL INTRAVENOUS ANESTHESIA IN RED DEER 1201

Wolfensberger et al., 1996). The reason antagonize detomidine after continuous for these poor-quality recoveries is dis- rate infusion of up to 110 min, has been cussed as being an accumulation of evaluated in horses (van Dijk et al., 2003). norketamine. However, no ketamine-asso- After atipamezole, all horses could walk ciated side effects were noted during without ataxia, and no relapse into seda- recovery for our red deer. The antagonists tion occurred for 1 hr after antagonization. were given only 20 min after termination Atipamezole is also recommended in deer of ketamine infusion in our red deer, and after the use of detomidine (Hall et al., this might have reduced possible halluci- 2001). In our study, no deer in group D nogenic side effects of ketamine. showed excitement or relapse into seda- Regurgitation and aspiration can occur tion during the observation period. when protective airway reflexes are abol- The effectiveness of atipamezole to ished in ruminants. This is an important antagonize xylazine has been shown in factor because cervids are difficult to white-tailed deer, Arabian oryx (Oryx intubate, compared with small animals leucoryx), grey duikers (Sylvicapra grim- and horses. Protective reflexes are mostly mia), and axis deer (Axis axis; Arnemo et maintained with ketamine and are abol- al., 1993; Ancrenaz, 1994; Nicholls et al., ished under inhalation anesthesia. No 1996; Miller et al., 2004). Reversal was not regurgitation was observed in this study constant in all species, and some animals using midazolam, ketamine and xylazine, showed incomplete reversal or resedation or detomidine anesthesia. We would still after 2 to 5 hr (Ancrenaz, 1994; Nicholls et recommend intubating deer for prolonged al., 1996; Miller et al., 2004). On the other procedures, even under field conditions, hand, one of eight axis deer sedated with to maintain airway patency and avoid xylazine alone showed signs of overalert- aspiration. ness after reversal with atipamezole IV, Side effects of xylazine described in and no cases of resedation were observed cervids, besides respiratory and cardiovas- (Arnemo et al., 1993). One animal from cular depression, include ruminal tympa- group X showed resedation 20 min after ny, regurgitation, and decreased thermo- reversal, and an additional bolus of regulation ability (Caulkett, 1997). In atipamezole and sarmazenil had to be wapiti, dose recommendations for xylazine given by IV. are 1 mg/kg. For white-tailed deer (Odo- Sarmazenil is a partial inverse benzodi- coileus virginianus) and mule deer (Odo- azepine receptor agonist and was used to coileus hemionus) higher doses (2 mg/kg) antagonize the effects of midazolam. are recommended (Caulkett, 1997). The Benzodiazepines bind to a specific benzo- xylazine dose used in our study falls within diazepine receptor site on c-aminobutyric this range. No regurgitation or tympany acid A receptors (GABAA) in the brain. was observed. Genuine antagonists, like , bind Prolonged recoveries might lead to to the same site as benzodiazepines, decreased survival of deer in the wild. without affecting the GABA-binding. Free-ranging animals have to respond Therefore, the only pharmacological effect quickly to dangerous environmental situ- is that benzodiazepine agonists are dis- ations. For this reason, reversible proto- placed from the receptor site. Flumazenil cols are preferred for immobilization of has been used in many species in veter- wildlife. In this study, a mixture of inary anesthesia. One report in white- atipamezole and sarmazenil IV was used tailed deer did not affect recovery time for antagonization. Atipamezole is the (Miller et al., 2004). Sarmazenil, on the most potent and selective alpha-2 adreno- other hand, interacts with the benzodiaz- ceptor antagonist, and is primarily used for epine binding site on the receptor and the reversal of medetomidine. Its use, to reduces GABA binding and GABA-in- 1202 JOURNAL OF WILDLIFE DISEASES, VOL. 46, NO. 4, OCTOBER 2010 duced chloride flux (Haefely, 1983). Sar- Journal of the European Union, L15/1, mazenil is the specific antagonist of 20.1.2010, 1–72. FERNANDEZ-MORAN, J., J. PALOMEQUE, AND V. I. climazolam and is mainly used in horses PEINADO. 2000. Medetomidine/tiletamine/zolaze- (Bettschart-Wolfensberger et al., 1996). pam and xylazine/tiletamine/zolazepam combi- Both sarmazenil and flumazenil have nations for immobilization of fallow deer (Cer- stimulatory effects on locomotion and on vus dama). Journal of Zoo and Wildlife Medicine exploratory behavior in mice (Mus mus- 31: 62–64. FRAGEN, R. J. 1997. and pharma- culus) and therefore might reverse the codynamics of midazolam given via continuous sedative effect of other drugs as well intravenous infusion in intensive care units. (Jackson and Nutt, 1992). In our study, Clinical Therapeutics 19: 405–419, discussion: sarmazenil, given together with atipame- 367–408. zole, provided rapid and complete reversal GALKA, M. E., J. M. AGUILAR,M.A.QUEVEDO,J.M. SANTISTEBAN, AND R. J. GOMEZ-VILLAMANDOS. without causing excitation or obvious 1999. Alpha-2 agonist anesthetic hypermotility. combinations in fallow deer (Cervus dama). In conclusion, we describe two feasible Journal of Zoo and Wildlife Medicine 30: 451– TIVA protocols for red deer to perform 453. prolonged procedures under field condi- GIACOMETTI, M., M. JANOVSKY,G.FLUCH,W.ARNOLD, AND F. SCHOBER. 2001. A technique to implant tions. No adverse effects like tympany or heart-rate transmitter in red deer. 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