Nitrous oxide and isoflurane are synergistic with respect to amplitude and latency effects on sensory evoked potentials

Objective: Combinations of anesthetic agents are frequently employed to produce the desired clinical effect. No systematic study has been conducted on the effect of the combination of nitrous oxide with a potent inhalational agent such as isoflurane on sensory evoked responses. Methods: Median nerve somatosensory evoked responses from the cervical and cortical regions (SSEP), auditory brainstem responses (ABR) and flash visual evoked responses (VEP) were tested in baboons. The latency and amplitude of the major response peaks were recorded at five proportionate mixtures of isoflurane (I) and nitrous oxide (N₂O) (0.8% I only, 0.6% I/20% N₂O, 0.4% I/40% N ₂O, 0.2% I/60% N₂O, and 79% N₂O only). A similar set of experiments were also conducted with 0.8% isoflurane and 0.6% halothane. All data were normalized to 0.8% isoflurane only and Dunnett's method of analysis used to determine which mixtures deviated from the reference values with 0.8% isoflurane. Results: Several combinations of isoflurane with nitrous oxide produced increases in latency (ABR: wave V, VEP, SSEP cervical and cortical) and decreases in amplitude (ABR: amplitude ratio V/I, VEP, cortical SSEP) from that expected if the effects were additive. No deviations were observed with combinations of isoflurane and halothane. Conclusions: These studies are consistent with drug synergy when isoflurane is mixed with nitrous oxide. This suggests that if these agents are considered for anesthesia when sensory evoked responses are to be monitored that the combination of these agents may produce more amplitude and latency changes than expected from a proportionate mixture of the individual agents.