The Effects of Multiple Administrations of Sevoflurane to Cynomolgus Monkeys

Abstract

The effect of multiple administrations of sevoflurane was evaluated by several measures of toxicity. Cynomolgus monkeys assigned to a control group and three treatment groups were anesthetized with sevoflurane at 1.0, 1.6, and 2.0 times the minimum alveolar anesthetic concentration (MAC) for 3 h/day, 3 days/wk for 8 wk. Reductions in total erythrocyte and leukocyte counts and increases in serum enzymes were the only changes noted. The increases in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and creatinine kinase (CK), occurred at Week 1 at all three concentrations of sevoflurane. These increases were dose-related, and returned to baseline by Week 2 for 1.0 MAC. All serum enzyme concentrations had returned to baseline by the end of the study. There were no gross pathologic, histopathologic, or ultrastructural differences found in any of the four groups of monkeys. At 2.0 MAC, three deaths occurred. The multiple administrations of 1.0 and 1.6 MAC sevoflurane anesthesia were well tolerated by the monkeys. The techniques of this study did not detect adverse effects from the above enzyme changes.

Sevoflurane-a long-awaited volatile anaesthetic

“…Although subtle increases in hepatic enzymes were detected, these were less marked than the increase caused by multiple exposures to other volatile anaesthetics. No evidence of histopathological toxicity was detected after 24 exposures to 3-5 MAC-h of sevoflurane in cynomolgus monkeys [77]. Thus the toxicity of sevoflurane would appear to be more of a theoretical than a clinical problem.…”

“…In addition, no evidence of renal injury or impairment has been detected in any of the published studies of sevoflurane anaesthesia in humans [10,24,28,50,53,75,76]. The effects of multiple exposures to sevoflurane anaesthesia have been evaluated recently in primates [77]. Although subtle increases in hepatic enzymes were detected, these were less marked than the increase caused by multiple exposures to other volatile anaesthetics.…”

Effects of repeat exposure to inhalation anesthetics on liver and renal function

“…[17] In monkeys, multiple administration of sevoflurane increased serum concentration of liver enzymes at 1 week and it returned to the baseline at 2 weeks without any pathological liver damages. [18] Moreover, repeated low flow sevoflurane anesthesia with the interval of 7 days in beagles did not affect liver and renal function. [19] In the prospective human study of repeated sevoflurane anesthesia, the multiple administration of sevoflurane anesthesia was not related to adverse effects of liver and renal damage.…”

The minimum alveolar concentration of sevoflurane in ring-tailed lemurs (Lemur catta) and aye-ayes (Daubentonia madagascariensis)

“…The MAC of sevoflurane is 2.0% in cynomolgus macaques ( Macaca fascicularis ) (Soma et al. ) and 1.8% in humans (Katoh & Ikeda ). The authors are not aware of any study describing MAC in prosimians.…”