Comparative Anesthetic Efficacy and Cardiopulmonary Effects of Medetomidine-Ketamine Combinations and Xylazine-Ketamine in Red Wolves (Canis rufus)
The red wolf (Canis rufus), originally endemic to the southeastern United States, is a critically endangered species. Captive propagation and reintroduction efforts undertaken by the U.S. Fish and Wildlife Service (USFWS) in eastern North Carolina have restored this carnivore species to a portion of its former range.2 Because of the endangered status of this species, and the intensive management practices being used to help maintain the health and well-being of the remaining population, the development of a safe, effective, and reversible anesthetic protocol is crucial.
Although immobilization regimens have been described in several wolf species, the red wolf is not among them.3,6-10,12,15 Traditionally, the USFWS has used a xylazine-ketamine combination for immobilizing captive and free-ranging red wolves, but prolonged and rough recoveries have become a concern. Medetomidine, like xylazine, is an alpha2-agonist, but binds with higher affinity, and is more specific for the alpha2-adrenoreceptor.14 When used as a single anesthetic agent, medetomidine causes sedation and analgesia in a variety of species, however, complete anesthesia is rarely achieved.4 In order to induce anesthesia, medetomidine is typically combined with other injectable agents, such ketamine, tiletamine-zolazepam, with or without butorphanol. In addition to providing more effective induction, combinations can provide the benefit of reducing the effective dose of medetomidine. Adverse effects of medetomidine include bradycardia, hypertension, vasoconstriction, respiratory depression, hyperglycemia and hypothermia.11 Rapid and complete reversal of the sedative effects of medetomidine can be achieved by the administration of atipamezole, a specific alpha2-antagonist.
Butorphanol is a synthetic opioid agonist-antagonist, with analgesic and mild sedative properties. In dogs, it has been shown to reduce arterial blood pressure, heart rate and arterial oxygen tension.5,13 Combining butorphanol with medetomidine can reduce the dose of medetomidine required for inducing sedation in dogs, and has the effect of counteracting the hypertension frequently observed with medetomidine combinations.1
The primary objective of this study was to compare cardiopulmonary and behavioral effects associated with anesthesia induced by combinations of medetomidine- (Domitor, Pfizer Animal Health, Exton, Pennsylvania, USA) ketamine (Ketaset, Ft. Dodge Animal Health, Ft. Dodge, Iowa, USA), medetomidine-ketamine-acepromazine, medetomidine-ketamine-butorphanol and xylazine-ketamine. Acepromazine (Butler Co., Columbus, Ohio, USA) and butorphanol (Torbugesic, Ft. Dodge Animal Health, Ft. Dodge, Iowa, USA) were included in the medetomidine combinations for both their sedative and vasodilatory actions, in order to evaluate effects on arterial blood pressure and anesthetic quality. The xylazine- (Butler Co., Columbus, Ohio, USA) ketamine combination, used by the USFWS, provided a useful comparison group.
Thirty-two captive, adult red wolves (19 females and 13 males) were used in a between-subjects experimental design. Each subject was assigned to one of the following four experimental groups:
xylazine (8 mg/kg) + ketamine (2 mg/kg) induction with yohimbine (0.10 mg/kg) reversal
medetomidine (40 µg/kg) + ketamine (2 mg/kg) induction with atipamezole (0.2 mg/kg) reversal
medetomidine (40 µg/kg) + ketamine (2 mg/kg) + acepromazine (0.01 mg/kg) induction with atipamezole (0.2 mg/kg) reversal
medetomidine (20 µg/kg) + ketamine (2 mg/kg) + butorphanol (0.2 mg/kg) induction with atipamezole (0.2 mg/kg) reversal
Each anesthetic combination was administered by hand-injection into the caudal hindlimb muscles. Once induced, a first set of physiologic parameters were collected prior to endotracheal intubation; these included heart rate, rate of respiration, body temperature, indirect arterial blood pressure (systolic, diastolic and mean) measured oscillometrically (Dinamap, Critikon, Tampa, Florida, USA), and indirect hemoglobin saturation measured by pulse oximeter (Vet Ox 4403, Sensor Devices Inc., Waukesha, Wisconsin, USA). Each subject was intubated and maintained on ambient air during the 50-min procedure. It was our objective to simulate field immobilization conditions as much as possible, so although wolves were intubated, they were not maintained on oxygen or gas anesthetics. After intubation, in addition to the above parameters, end tidal CO2 and tidal volume were measured by sidestream capnography (Microcap, Sensor Devices Inc., Waukesha, Wisconsin, USA) and spirometry (Model RM121, Fraser Harlake Co., Orchard Park, New York, USA), respectively. Values were measured at 10-min intervals for the duration of the procedure. At approximately 30 min, a femoral arterial blood sample was collected for immediate blood analysis using a portable iSTAT clinical analyzer (Sensor Devices Inc., Waukesha, Wisconsin, USA). The following blood parameters were analyzed: sodium, potassium, ionized calcium, hematocrit, hemoglobin, pH, PCO2, TCO2, PO2, SO2, HCO3, and base excess. All individuals were weighed prior to anesthetic recovery. At the end of the procedure, either atipamezole (Antisedan, Pfizer Animal Health, Exton, Pennsylvania, USA) or yohimbine (Antagonil, Wildlife Laboratories, Ft. Collins, Colorado, USA) was administered intramuscularly. Data are presented as mean±SD.
All four combinations provided sedation within 5 min and complete immobilization within 8–10 min of initial injection. Intubation was most easily and consistently achieved with the MBK/A group, and these subjects were considered more relaxed compared with subjects in the other groups. Arterial blood pressure was markedly elevated immediately following induction in all treatment groups. The average mean arterial blood pressures taken just after induction were as follows: MK/A=133±42 mm Hg; XK/Y=150±12 mm Hg; MKA/A=149±14 mm Hg; and MBK/A=131±37 mm Hg. Blood pressure remained elevated in all treatment groups except the MBK/A group, in which blood pressure decreased steadily over time. Mean heart and respiration rates were lower at all time points in the MBK/A group relative to the three other treatment groups. Mean end-tidal CO2 was elevated in the MBK/A group relative to the other treatment groups, and in a direct comparison between the MK/A and the MBK/A groups, mean PaCO2 was statistically elevated in the MBK/A group. There were no differences between groups in PaO2 or SaO2. Hemoglobin saturation levels were slightly lower in the MBK/A group during the first 20 min, but were indistinguishable from the other treatment groups for the final 30 min of the procedure. Blood pH decreased slightly in the MBK/A group relative to the other treatment groups. After anesthetic reversal, wolves in the three medetomidine combination groups, generally, were standing within 10–11 min, while the wolves in the xylazine-ketamine group did not consistently remain standing until a mean of 23 min after the reversal agent was administered. The quality of recoveries in the xylazine-ketamine subjects were characterized by prolonged recumbency and ataxia compared with the subjects in the medetomidine combination groups.
Anesthesia of red wolves using all four drug combinations was characterized by marked hypertension. Arterial blood pressure measurements have not been previously reported in other wolf species, and the mechanism underlying this hypertension is unclear. The addition of butorphanol to medetomidine-ketamine attenuated the hypertension, contributed to smooth inductions, and provided excellent muscle relaxation, while reducing the medetomidine dosage by 50%. The mild hypoxemia, hypercapnia, and acidemia observed in the MBK/A group is probably of little clinical significance in a healthy animal, but may become important in a physiologically compromised individual.
We gratefully acknowledge A. Bayer, M. Morse and W. Savage for their assistance.
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