SYNERGISTIC INTERACTION BETWEEN MIDAZOLAM AND PROPOFOL

We gave either midazolam or propofol for induction of anaesthesia to 140 ASA I or II female patients (18–60 yr). ED50, values were obtained by probit analysis for three clinical end-points: loss of response to command; loss of eyelash reflex; failure to respond to application of an anaesthetic face mask delivering 1 % isoflurane. Propofol ED50 values (95% confidence intervals) were 1.25 (0.99–1.48) mgkg−1, 1.61 (1.29–1.94) mg kg−1 and1.51 (1.20–1.82) mg kg−1, respectively. ED50 values for midazolam were 0.26 (0.20–0.37) mg kg−1, 0.29 (0.23–0.47) mgkg−1 and 0.25 (0.20–0.32) mg kg−1, respectively. An additional 92 similar patients received one of nine dose combinations of midazolam and propofol for induction of anaesthesia, propofol being administered 2 min after midazolam. Success of induction was based on the clinical end-point of loss of response to command. Administration of 25% of the ED50 of midazolam followed by 50% of the ED50 of propofol resulted in loss of response to command in 50 % of patients, while 50 % of the ED50 of midazolam, followed by 25% of the ED50 of propofol had the same effect. A probit regression model specifying a synergistic interaction between midazolam and propofol fitted the data significantly better than a model specifying no interaction.