Rapid Recovery and Short Duration Anesthesia after Low Dose Ketamine and High Dose Dexmedetomidine in Rhesus Macaques (Macaca mulatta)

Abstract

Anesthesia in rhesus macaques is required for many procedures. Although ketamine is the backbone of most anesthetic protocols, tolerance to the drug can develop, resulting in the need for higher doses to provide sufficient restraint. Combination with other drugs, such as α-agonists, can be ketamine-sparing, providing for sufficient restraint at lower ketamine doses. In addition, because α-agonists are reversible, recovery from anesthesia has the potential to be much shorter. We hypothesized that use of a low dose of ketamine with a high dose of dexmedetomidine, an α2 receptor selective agonist, in male and female rhesus macaques less than 15 y of age would provide adequate anesthesia for short procedures and that recovery would be faster than in macaques given a higher dose of ketamine (10 mg/kg) alone. We found that the combination, in conjunction with atipamezole for reversal, provided smooth induction of anesthesia and significantly shorter recovery time than did ketamine alone, with no significant effects of sex. The combination of low dose ketamine and high dose dexmedetomidine also provided a 30-min window of anesthesia with analgesia sufficient for mild to moderately painful procedures.

Figure 1.

(A) Time to sedation (min) was compared between ketamine and ketamine plus dexmedetomidine-treated rhesus macaques. No significant difference was found between the 2 groups (P = 0.239). (B) The impact of sex on median time to sedation was compared between male and female animals. No significant effect of sex was found on median time to sedation (P = 0.489). Horizontal black lines within boxes represent the median value. Numbered open circles above boxes represent outlier animals.

Figure 2.

(A) Time to recovery (min) was compared between ketamine and ketamine plus dexmedetomidine-treated rhesus macaques. Macaques treated with ketamine plus dexmedetomidine recovered significantly faster than macaques sedated with ketamine alone (P < 0.005). (B) The impact of sex on time to recovery was compared between male and female rhesus macaques. There was no significant effect of sex on median time to recovery (P = 0.730). Horizontal black lines within boxes represent the median value. Numbered open circles above boxes represent outlier animals.