Using an iteration method, optimal hand-injected immobilization dosages of carfentanil/xylazine (CAR/XYL) were determined for 13 adult white-tailed deer (Odocoileus virginianus). Deer were temporarily restrained in a squeeze chute and were repeatedly immobilized one to four times at 2-5-wk intervals from December 2002 to March 2003. A fixed ratio of 1 mg CAR:10 mg XYL intramuscularly was used, increasing or decreasing the dosage until the optimal dosage (defined by an induction time < 3 min and PaCO(2)< 60 mmHg) was reached for each animal. Inductions were video-recorded and reviewed by observers blinded to drugs and dosages, who rated qualitative aspects of each induction. There were significant (P < 0.05) dosage-dependent decreases in induction time, time to first effect, PaO(2), SaO(2), and arterial pH, and significant dosage-dependent increases in PaCO(2) and quality ratings. The median optimal dosage (mOD) was 0.03 (range, 0.015-0.06) mg/kg CAR+0.3 (range, 0.15-0.6) mg/kg XYL. Induction times using the mOD were rapid (median 3.0 min [range, 1.8-10.0]), but quality ratings were considered undesirable for nine of 13 deer. Increased rectal body temperatures of 40.6+/-0.5 C (mean +/- SD) were noted in all deer and hyperthermia (T > 41 C) was noted in three. There was a positive correlation between body temperature and induction time (r=0.44). Heart rates significantly decreased from 5 to 15 min postinduction and remained decreased at the 20-min reading; there was occasional bradycardia. There was a significant increase in pH from 10 to 20 min postinduction, but metabolic acidemia (pH<7.3) persisted throughout the immobilization periods for all deer. Possible hypoxemia (SaO(2) and SpO(2)<90 mmHg but PaO(2)>60 mmHg) was present after induction, while hypercapnea (PaCO(2) > 60 mmHg) did not occur. Reversal times with naltrexone and yohimbine were rapid (mean 3.7+/-1.5 min) and uneventful, with no evidence of renarcotization. Although the median optimal dosage produced rapid inductions, no respiratory depression, complete reversal after antagonist administration, and no renarcotization, negative attributes included elevated body temperatures, acidemia, and undesirable induction qualities.
From 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 (xϮSDϭ23.5Ϯ3.2 g/kg) and 10 mg xylazine (0.2Ϯ0.03 mg/kg) were selected, based on induction times and previously published reports, to compare with a combination of 230 mg of Telazol (4.5Ϯ0.6 mg/kg) and 120 mg xylazine (2.3Ϯ0.3 mg/kg). Time to first observable drug effects and to induction were significantly longer for deer treated with carfentanil/xylazine than with Telazol /xylazine (PϽ0.01). 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 (1.9Ϯ1.1 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-tailed deer even though drug reversal was rapid and safe using naltrexone and yohimbine.
2Brookfield Zoological Gardens, Brookfield, Illinois 3 Dallas Zoo and Dallas Aquarium, Dallas, TexasThe mediation of nociception with analgesic medications has not been well documented in elasmobranchs. The purpose of this study was to determine effective analgesic doses of the opioid agonist-antagonist, butorphanol, and the non-steroidal anti-inflammatory drug, ketoprofen, in an elasmobranch. This was evaluated by repetitively assessing minimum anesthetic concentrations of the immersion anesthetic, tricaine methanesulfonate (MS-222), required to prevent response to noxious stimuli in chain dogfish (Scyliorhinus retifer) when administered multiple doses of each of the analgesics (0.25, 0.5, 1.0, 2.5, and 5.0 mg/kg butorphanol and 1.0, 1.5, 2.0, and 4.0 mg/kg ketoprofen). Baseline concentrations of MS-222 required to prevent a response to a noxious stimulus were determined for each animal and served as the controls. Although individual animals displayed a reduction in MS-222 concentration with various doses of both analgesics, no statistically significant difference was noted between control animals and animals given analgesics. It is plausible that unique elasmobranch anatomy, lack of appropriate medication dose or timing of administration, and other physiological factors not yet identified may have contributed to the lack of apparent efficacy of the analgesics evaluated in this study.
The objective of this study was to document the pharmacokinetics of ketoprofen following 3 mg/kg intramuscular (IM) and intravenous (IV) injections in rainbow trout ( Oncorhynchus mykiss ) and 8 mg/kg intramuscular (IM) injection in Nile tilapia ( Oreochromis niloticus) . Plasma was collected laterally from the tail vein for drug analysis at various time intervals up to 72 h following the injection of ketoprofen. In trout, area under the curve (AUC) levels were 115.24 μg hr/mL for IM and 135.69 μg hr/mL for IV groups with a half-life of 4.40 and 3.91 h, respectively. In both trout and tilapia, there were detectable ketoprofen concentrations in most fish for 24 h post-injection. In tilapia, there was a large difference between the R- and S-enantiomers, suggesting either chiral inversion from R- to S-enantiomer or more rapid clearance of the R-enantiomer. AUC values of the S- and R-enantiomers were 510 and 194 μg hr/Ml, respectively, corresponding to a faster clearance for the R-enantiomer. This study shows that there were very high plasma concentrations of ketoprofen in trout and tilapia with no adverse effects observed. Future studies on the efficacy, frequency of dosing, analgesia, adverse effects, and route of administration are warranted.
Using a crossover design, the effects of the addition of ketamine to a previously determined optimal hand-injected immobilization dosage of carfentanil/xylazine were evaluated in 11 adult white-tailed deer (Odocoileus virginianus). Two i.m. ketamine dosages were evaluated: 0.15 mg/kg (low ketamine) and 0.30 mg/kg (high ketamine). Each deer was immobilized twice 2 wk apart. Inductions were video recorded and reviewed by observers, who had been blinded to drugs and dosages, who rated qualitative aspects. There were significant (P < 0.05) dosage-dependent decreases in heart rate, SaO2, and arterial pH, and a significant dosage-dependent increase in PaCO2. Induction times with both dosages were more rapid (mean 2.3 +/- 0.9 min for low ketamine and 2.3 +/- 0.6 min for high ketamine) than those reported for the same carfentanil/xylazine dosage used without ketamine. Mean quality ratings, though improved compared to those reported for carfentanil/xylazine alone, were considered "undesirable" for both dosages. Hyperthermia (temperature > 41 degrees C) was noted in 13 of 22 immobilizations. Arterial pH and PaO2 increased significantly from 10 to 20 min postrecumbency, but acidemia (pH < 7.3) was present throughout immobilization periods for all deer. There were ketamine dosage-dependent increases in respiratory components of this acidemia compared with that associated with carfentanil/xylazine alone. Possible hypoxemia was present at both sampling times for both groups, while hypercapnea (PaCO2 > 60 mm Hg) was present for the high-ketamine group only. Reversal times for naltrexone and yohimbine were rapid (mean 2.9 +/- 0.7 min for low ketamine and 3.3 +/- 0.8 min for high ketamine), with no evidence of renarcotization. Although the addition of ketamine to carfentanil/xylazine caused faster inductions and improved induction qualities, it also produced an increased incidence of hyperthermia, acidemia, hypoxemia, and hypercapnea. Supplemental oxygen and close monitoring of body temperature is recommended when using this immobilization regimen.
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