THE EFFECTS OF MULTIPLE ADMINISTRATIONS OF SEVOFLURANE TO CYNOMOLGUS MONKEYS - CLINICAL-PATHOLOGICAL, HEMATOLOGIC, AND PATHOLOGICAL-STUDY

The effect of multiple administrations of sevoflurane was evaluated by several measures of toxicity. Cynomolgus monkeys assigned to a contro l group and three treatment groups were anesthetized with sevoflurane at 1.0, 1.6, and 2.0 times the minimum alveolar anesthetic concentrati on (MAC) for 3 h/day, 3 days/wk for 8 wk. Reductions in total erythroc yte 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 ba seline by Week 2 for 1.0 MAC. All serum enzyme concentrations had retu rned to baseline by the end of the study. There were no gross patholog ic, histopathologic, or ultrastructural differences found in any of th e four groups of monkeys. At 2.0 MAC, three deaths occurred. The multi ple administrations of 1.0 and 1.6 MAC sevoflurane anesthesia were wel l tolerated by the monkeys. The techniques of this study did not detec t adverse effects from the above enzyme changes.