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) 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.
McClune
S
S
Department of Anaesthetics, Queen's University of Belfast, N. Ireland.
McKay
A C
AC
Wright
P M
PM
Patterson
C C
CC
Clarke
R S
RS
D000293:Adolescent; D000328:Adult; D000771:Anesthesia, Intravenous; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008874:Midazolam / Q000494:pharmacology*; D008875:Middle Aged; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation
D008874:Midazolam; D015742:Propofol