Interaction of a subanaesthetic concentration of isoflurane with midazolam: effects on responsiveness, learning and memory

Abstract

There are situations in which "light" anaesthesia combined with neuromuscular block is the only anaesthetic regimen that can be tolerated safely by the patient. Benzodiazepines have hypnotic and specific amnesic effects. Therefore, we have examined the interaction of midazolam with a subanaesthetic dose of isoflurane (0.2% end-expired concentration) in 28 healthy volunteers. Thereafter, 15 subjects received midazolam 0.03 mg kg-1 i.v. and 13 subjects received midazolam 0.06 mg kg-1 in a random, double-blind manner. Word lists were administered and response to commands was tested before and after administration of midazolam. After 1 h of recovery, memory for word lists was tested by word completion, free recall and forced choice recognition tasks. After administration of midazolam, recall and, to a lesser degree, implicit memory were absent. Recognition was also absent after administration of midazolam 0.06 mg kg-1 and at the 3-min and 15-min assessments after administration of midazolam 0.03 mg kg-1. Responsiveness was more frequent with midazolam 0.03 mg kg-1 than with 0.06 mg kg-1 and increased over time. We conclude that a larger dose of midazolam or isoflurane, or both, may be necessary to abolish responsiveness.