Abstract

Alpha₂-agonists produce profound sedation and analgesia by virtue of their ability to modulate neurotransmitter release throughout the brain and spinal cord. The highly selective alpha₂-agonist, medetomidine, has recently become available for use in the United States. Medetomidine alone has been used effectively as a sedative-analgesic in a variety of species, but has proven inadequate as a complete immobilization agent. The combination of medetomidine (30–100 µg/kg) and ketamine (1–8 mg/kg depending on species) has proven to be quite effective in a variety of nondomestic mammals.^1,2 In addition to their central nervous system (CNS) effects, alpha₂-agonists have significant effects on the cardiovascular system, particularly in carnivores. In the dog, intramuscular medetomidine results in rapid and intense vasoconstriction followed by a profound compensatory bradycardia. A 50–75% decrease in heart rate is not uncommon and may be accompanied by severe hypotension and respiratory depression. The addition of ketamine does not necessarily prevent these effects.₃ Little is known about the physiological effects of medetomidine-ketamine in nondomestic species.

The purpose of our study was to determine the cardiopulmonary effects of intramuscular medetomidine (40 µg/kg) and ketamine (2 mg/kg) when used as an induction combination prior to isoflurane anesthesia in gorillas and chimpanzees. A previous report had indicated that in chimpanzees medetomidine-ketamine provided rapid induction, stable immobilization, excellent relaxation, and calm recovery.⁴ We chose to extend these findings by monitoring blood pressure, hemoglobin saturation, and end-tidal CO₂ during medetomidine-ketamine-isoflurane anesthesia.

Six chimpanzees and six gorillas undergoing routine physical exams at the North Carolina Zoological Park were included in the study. Medetomidine (10 mg/ml) and ketamine (200 mg/ml) were purchased separately (Wildlife Laboratories, Fort Collins, CO, USA) and mixed in the same syringe prior to injection. The combination was administered either by hand syringe or by dart (Telinject USA, Inc., Saugus, CA, USA) and allowed at least 10 minutes to take effect. Animals were then masked with 2–3% isoflurane (Aerrane, Anaquest, Madison, WI, USA) in 100% oxygen to permit endotracheal intubation. Following intubation, animals were maintained on a non-rebreathing circuit with 0.5–1.5% isoflurane for the duration of the exam (approximately 1 hour). To assess the cardiovascular effects of anesthesia, indirect arterial blood pressure and heart rate were measured oscillometrically (Dinamap Model 8300, Critikon, Tampa, FL, USA) at 3-minute intervals beginning at the point where animals lost their righting reflexes. To assess respiratory effects, hemoglobin saturation was measured indirectly by pulse oximetry (Model N20, Nellcor, Hayward, CA, USA), and end-tidal CO₂ and respiratory rate were measured by mainstream capnography (Model 1260, Novametrix, Wallingford, CT, USA). Arterial blood gases were measured with a pH and blood gas analyzer (StatPal SP2-A, PPG Ind., La Jolla, CA, USA). At the end of the procedure, isoflurane was discontinued, and either a full dose of atipamezole (Antisedan, Pfizer, Exton, PA, USA) was injected IM or a partial dose was given IV and the remainder IM.

Medetomidine-ketamine provided sedation within 3–5 minutes and complete immobilization within 10–15 minutes of initial injection in both chimpanzees and gorillas. We found it to be very important that animals be left alone for the initial 10 minutes, as attempts to move them prior to this could result in rapid arousal. Once the medetomidine-ketamine had taken effect, only 3–5 minutes of 2–3% isoflurane by mask was required for intubation. Once intubated, an adequate plane of anesthesia was readily maintained with 0.5–1.0% (chimpanzees) or 1.0–1.5% (gorillas) isoflurane. Both chimpanzees and gorillas had elevated blood pressures immediately following induction. Average systolic, mean, and diastolic blood pressures were 154, 121, and 87 mm Hg, respectively. Heart rates immediately after induction ranged between 60 and 90 beats/minute and remained steady throughout the procedure. Blood pressure decreased steadily over the first 10–15 minutes and generally stabilized to systolic, mean, and diastolic pressures of 125, 95, and 75 mm Hg, respectively. Beyond the first 15 minutes, blood pressures remained within normal limits, varying only with the depth of isoflurane anesthesia. Spontaneous respiratory rates ranged between 20–40 breaths/minute for both chimpanzees and gorillas. Hemoglobin saturation levels were consistently between 95–100%, and end-tidal CO₂ levels ranged between 30–50 mm Hg. Arterial blood gas values were within normal limits in those animals tested (2 chimpanzees and 2 gorillas). After atipamezole injection, first signs of recovery occurred within 8–10 minutes following injection and all animals were fully recovered (standing, vocalizing, climbing) within 10–13 minutes.

Our results suggest that intramuscular medetomidine and ketamine provides a rapid and safe method of induction in both chimpanzees and gorillas, and allows for a smooth transition to inhalation anesthesia. Of particular benefit was the decreased volume of drug required for initial injection and the decreased concentration of inhalation anesthetic required for maintenance. Cardiovascular effects of the combination proved to be minimal. Modest increases in blood pressure soon after induction were not accompanied by significant decreases in heart rate as has been reported in some carnivores. The transient nature of the increase in blood pressure suggests that this may be an effect of the ketamine. Maintenance of hemoglobin saturation and end tidal CO₂ partial pressures within normal limits indicate that the combination does not significantly depress ventilation. The increased respiratory rates that we observed were most likely the result of using a non-rebreathing system. The prolonged effect of medetomidine allowed for a smooth transition from inhalation anesthesia to recovery, as the animals remained heavily sedated until given the reversal agent. Reversal in all cases was rapid, smooth, and complete.

Acknowledgment

We thank Bill Lance of Wildlife Laboratories for supplying us with concentrated medetomidine and ketamine solutions.

Literature Cited

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