The effects of multiple administrations of sevoflurane to cynomolgus monkeys: clinical pathologic, hematologic, and pathologic study.
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.
Soma
L R
LR
University of Pennsylvania School of Veterinary Medicine, Kennett Square 19348-1692, USA.
Tierney
W J
WJ
Hogan
G K
GK
Satoh
N
N
D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001780:Blood Coagulation Tests; D002245:Carbon Dioxide / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004906:Erythrocyte Count / Q000187:drug effects; D004987:Ethers / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007679:Kidney Medulla / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008252:Macaca fascicularis; D008297:Male; D008738:Methyl Ethers; D000077149:Sevoflurane; D013950:Thymus Gland / Q000187:drug effects; D013990:Tidal Volume
D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D002245:Carbon Dioxide; D000077149:Sevoflurane; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase