Propofol and midazolam act synergistically in combination

Abstract

We have studied interactions between i.v. propofol and midazolam for induction of anaesthesia in 200 unpremedicated female patients undergoing elective gynaecological surgery. Using end-points of "hypnosis" (loss of response to verbal command) and "anaesthesia" (loss of response to a 5-s transcutaneous tetanic stimulus), we determined dose-response curves for propofol and midazolam alone and in combination. For hypnosis, synergistic interaction was found (P less than 0.01), the combination having 1.44 times the potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of propofol required to produce anaesthesia was reduced by 52% in the presence of midazolam (P less than 0.01). The reduction in arterial pressure at induction was the same for the combination as for the individual agents. The cause of the synergism was not clear, but may have been interaction at CNS GABAA receptors.