Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

We have studied the effects of midazolam premedication on multiple anaesthe tic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulati on (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg(-1) h(-1). Patients recei ved midazolam 0.05 mg kg(-1) i.v. (group TM, n = 12) or no midazolam (group TO, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantl y thiopental ED50 and ED95 values at all endpoints (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infus ion bag (DF)) (ED95 + 52%, ED50 +23%, median +39%), and smallest for painfu l stimulation (LRP) (median +18%; ED50 +13%) For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LV C or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our da ta suggest that the mechanism of interaction between midazolam premedicatio n and thiopental was different for motor effects or analgesia (DF, LRP) com pared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these dist inct anaesthetic end-points.