The effect of ketamine on clinical endpoints of hypnosis and EEG variablesduring propofol infusion

Background: We studied the effect of variable doses of ketamine on the endp oints of hypnosis, e.g., unresponsiveness to verbal commands (UVC), loss of eyelash reflex (LER), and inhibition of body movement response with or wit hout sneezing to nasal membrane stimulation (INBMR), and processed EEG vari ables, e.g., bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) during propofol infusion. Methods: Forty-eight patients received either propofol infusion, 30 mg . kg (-1) . h(-1) (Group P; n=12) or ketamine bolus, 0.25, 0.5 or 0.75 mg i.v., followed by propofol infusion, 30 mg . kg(-1) . h(-1) +variable dose ketami ne infusion, 0.25, 0.5 or 0.75 mg . kg(-1) . h(-1) Groups PK0.25, PK0.5 and PK0.75; n=12 each) until UVC, LER and INBMR. BTS, 95% SEF and MF values we re monitored and recorded at the endpoints of hypnosis. Propofol and ketami ne concentrations were measured at INBMR. Results: Propofol infusion, 30 mg . kg(-1) . h(-1), induced UVC, LER and IN BMR at BIS: 65+/-2, 63+/-9 and 33+/-7; 95% SEF: 17+/-3, 17+/-4 and 14+/-3; and MF values of 5+/-2, 5+/-3 and 3+/-2 respectively. With adjunctive ketam ine (Groups PK0.5 and PK0.75), the hypnotic endpoints were achieved at high er BIS and 95% SEF values and lower propofol doses and concentrations as co mpared to Groups P and PK0.25 (9.9+/-5.8 and 9.4+/-3.4 vs. 13.4+/-4.5 and 1 4+/-5.8 mu g . ml(-1)). Conclusions: Our results suggest additive interaction between propofol and ketamine (Groups PK0.5 and PK0.75) for achieving the hypnotic endpoints; ho wever, ketamine did not depress the EEG variables in proportion to its hypn otic effect. The paradoxically higher BIS and 95% SEF values at the hypnoti c endpoints may be due to lower propofol concentrations and/or no effect of ketamine on the EEG variables.