Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination.

This study examined the interaction between i.v. administered midazolam and thiopentone on the loss of response to verbal command ("hypnosis") and the loss of response to transcutaneous electrical stimulation of the ulnar nerve ("anaesthesia") in patients presenting for minor elective surgery. Dose-response curves for thiopentone and midazolam individually and in combination were determined using the two end-points in 300 unpremedicated patients. For hypnosis a highly significant (P less than 0.001) supra-addictive (synergistic) interaction was found, the combination having 1.8 times the expected potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of thiopentone required to produce anaesthesia was reduced by 50% in the presence of midazolam. The mechanism of interaction and the potential role of benzodiazepine-barbiturate combinations are discussed and the observed synergistic anaesthesia interaction is used to explain the potentially dangerous combination of benzodiazepines with other potent CNS depressants such as barbiturates and alcohol.