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

Background: We studied the effect of variable doses of ketamine on the endpoints of hypnosis, e.g., unresponsiveness to verbal commands (UVC), loss of eyelash reflex (LER), and inhibition of body movement response with or without sneezing to nasal membrane stimulation (INBMR), and processed EEG variables, 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 ketamine 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. BIS, 95% SEF and MF values were monitored and recorded at the endpoints of hypnosis. Propofol and ketamine concentrations were measured at INBMR. Results: Propofol infusion, 30 mg · kg−1 · h−1, induced UVC, LER and INBMR 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 ketamine (Groups PK0.5 and PK0.75), the hypnotic endpoints were achieved at higher BIS and 95% SEF values and lower propofol doses and concentrations as compared to Groups P and PK0.25 (9.9±5.8 and 9.4±3.4 vs. 13.4±4.5 and 14±5.8 μg · ml−1). Conclusions: Our results suggest additive interaction between propofol and ketamine (Groups PK0.5 and PK0.75) for achieving the hypnotic endpoints; however, ketamine did not depress the EEG variables in proportion to its hypnotic effect. The paradoxically higher BIS and 95% SEF values at the hypnotic endpoints may be due to lower propofol concentrations and/or no effect of ketamine on the EEG variables.