Timing of midazolam and propofol administration for co-induction of anaesthesia

We aimed to determine the optimum timing of midazolam administration prior to propofol to achieve the maximal reduction in the dose of propofol required to induce anaesthesia. Female (ASA 1-2) patients, aged 18 to 45 years, weighing 40 to 75 kg and scheduled for gynaecological surgery were eligible for the study. Consenting patients were randomly assigned to six groups. Group 1 received saline and Groups 2 to 6 received midazolam 3 mg at 1, 2, 4, 6 or 10 minutes respectively prior to propofol (n =20 to 22 per group) in a blinded manner. Propofol was administered IV over 10 seconds and flushed in with saline 5 ml. Two minutes later, the patient's response to pressure applied to the finger was determined as an index of loss of consciousness. The ED50 of propofol in each group was determined by the up-and-down method. Propofol ED50 was reduced to 34 to 67% (P<0.001) in the midazolam treated groups. There was no significant (P=0.14) difference in propofol ED50 among the five groups which received midazolam. Patients who received midazolam had less recollection of events surrounding induction (P <0.001) and recalled the induction experience as being more pleasant (P=0.03) than those who did not receive midazolam. These results indicate that midazolam may be given up to 10 minutes prior to propofol and still achieve a substantial dose reduction.