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British Journal of Anaesthesia, 1992, Vol. 69, No. 2 162-167
© 1992 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

HYPNOTIC AND ANAESTHETIC INTERACTIONS BETWEEN MIDAZOLAM, PROPOFOL AND ALFENTANIL

T. G. SHORT, M.B., CH.B., F.F.A.R.A.C.S, F.H.K.C.A.1, J. L. PLUMMER, PH.D., P. T. CHUI, M.B., B.S., F.F.A.R.A.C.S., F.H.K.C.A.* and P. T. CHUI, M.B., B.S., F.F.A.R.A.C.S., F.H.K.C.A.1

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong Shatin, N.T., Hong Kong

1Correspondence to T.G.S.

We have examined interactions between mid-azolam, propofol and alfentanil using two end-points of light sedation (hypnosis) and anaesthesia. Quantal dose-response curves were determined in 400 female patients for the drugs individually and in combination. At the hypnotic end-point, interactions were analysed by fitting the data to a mathematical model where the response depended on the doses of the three drugs with additional terms included to describe non-additive interactions of the various combinations of the three drugs. There were significant interactions for hypnosis; the decrease in expected ED50 for the various combinations were: midazolam-propofol = 37%, midazolam-alfentanil = 46% propofol-alfentanil = 20% midazolam-propofol-alfentanil = 42% Whilst all responses to the two-drug combinations were synergistic, the three-drug combination led to a response that was less than that expected from the effects of the individual agents and their two drug interactions. For anaesthesia, dose-related effects could not be demonstrated for midazolam or alfentanil when used alone. The decrease in ED50 of propofol in the presence of the other compounds was propofol-midazolam = 52%, propofol-alfentanil = 73%, propofol-midazolam-alfentanil = 82%. When comparing the different combinations, the responses varied markedly at each end-point assessed and could not be predicted from the responses of the individual agents.

* Present address: Pain Management Unit, Flinders Medical Centre, Adelaide, Australia.


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