Synergistic Interaction Between Midazolam and Propofol

Abstract

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) mg kg-1, 1.61 (1.29-1.94) mg kg-1 and 1.51 (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) mg kg-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.

Haemodynamic changes and heart rate variability during midazolam‐propofol co‐induction*

“…................................................................................................................................................................................................................ [2] and McClune et al [4] there is no statistical evidence to suggest that propofol and midazolam act synergistically on the arterial blood pressure. McClune et al [4] also noticed a greater increase of the heart rate following midazolam-propofol co-induction than following propofol-alone induction, although the difference between the two groups was not statistically significant. Thus, their findings were consistent with our results.…”

“…Co-induction with midazolam and propofol has been mainly studied in relation to the drugs' synergistic hypnotic actions of the drugs and haemodynamic changes [1][2][3][4] during induction of anaesthesia, but there are no reports to date of the haemodynamic changes occurring during tracheal intubation. Propofol decreases the arterial blood pressure, associated with a decrease of the cardiac output ⁄ index, stroke volume index, and systemic vascular resistance [5]; on the other hand, the cardiac output ⁄ index and ventricular filling pressures are maintained after the administration of midazolam [5,6].…”

Midazolam and awareness with recall during total intravenous anaesthesia

“…Drug combinations which have demonstrated synergistic properties include thiopentone/midazolam, l.2 and propofol/midaz01am. [3][4][5][6][7] Despite the potential advantages of co-induction, reluctance to utilize midazolam or other benzodiazepines for outpatient anaesthesia persists, due to concerns regarding the potential for prolonged recovery. 8 Although recent evidence suggests that propofol/midazolam co-induction does not delay hospital discharge times following very brief propofol anaesthesia,9 doseresponse relationships have not been clarified.…”

Premedication modifies the quality of sedation with propofol during regional anesthesia

“…Moreover, benzodiazepines and propofol act synergistically. 3,7,8 It is possible that preanesthetic diazepam reduces the propofol requirements and decreases the complications. Both drugs are useful for premedication, however, there are few reports to investigate the differences between them when used as premedicants for sedation with propofol.…”

“…[14][15][16][17] Therefore, benzodiazepine reduces propofol requirements probably due to its synergistic action on GABA A -receptor. 3,7,8 Although we maintained the same sedation level in all groups, fewer patients in Group-DZ recalled intraoperative events than in other groups. Benzodiazepines, including diazepam, produce anterograde amnesia, and this may contribute to this reduction of the memories of intraoperative events.…”