Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses

The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients. The analgesic effect of alfentanil was studied by measuring the threshold for pain caused by pressure on the trapezius muscle with the use of a dolorimeter in 21 patients. The study was randomized, double-blind, and performed on the unpremedicated patients with ASA physical status I or II. Alfentanil was found to reduce the midazolam ED50 value for the induction of anesthesia in a dose-dependent fashion. The smallest dose of alfentanil (3 micrograms/kg) that caused a marked shift of the midazolam dose-response curve to the left along the dose axis (from the ED50 of 270 micrograms/kg to the ED50 of 142 micrograms/kg, P less than 0.0005) represents approximately 2% of the alfentanil ED50 for induction of unconsciousness (130 micrograms/kg). Alfentanil (10 micrograms/kg) caused only a tendency for increase in the pain threshold, whereas a dose of 15 micrograms/kg significantly increased the pain threshold by 37% (P less than 0.05). The results demonstrate that alfentanil potentiates the hypnotic effect of midazolam in very small doses. The high potency of alfentanil in this respect, as compared to its analgesic potency, suggests a very specific mechanism of alfentanil-midazolam hypnotic interaction, one that most likely is based on a functional relationship between the GABA receptor-benzodiazepine receptor system and the opioid receptor system in mediation of hypnosis.