Dose and timing effect of etomidate on motor evoked potentials elicited by transcranial electric or magnetic stimulation in the monkey and baboon

Abstract

Etomidate has been shown to both enhance and depress the cortical amplitude of somatosensory evoked potentials (SSEP) depending on the dose used. Similar amplitude increases with etomidate and motor evoked potentials resulting from cortical magnetic (tcMMEP) and electric (tcEMEP) stimulation have not been consistent. We used a primate model to elucidate the time and dose characteristics of the effect. tcMMEP and tcEMEP were characterized during bolus injections of 0.1-1.8 mg/kg etomidate in 10 adult cynomologous monkeys during a baseline anesthesia with a continuous ketamine infusion. Responses were assessed by measuring the amplitude and onset latency of the hypothenar compound action potential response. In a second experiment the epidural and hypothenar response to tcEMEP was recorded under 0.3% isoflurane anesthesia and following intravenous injection of 0.05-0.35 mg/kg etomidate. Cortical stimulation was accomplished using a Cadwell MES-10 (tcMMEP) and Digitimer D180 (tcEMEP). The amplitude of the hypothenar muscle response was increased for tcEMEP and tcMMEP at 20 min following 0.1 mg/kg etomidate in the monkey. The amplification of the tcMMEP response was significantly greater than the tcEMEP response (1.95 + 0.62 SD vs. 1.43 + 0.68 SD, P = 0.023). Responses at higher doses were all below baseline. The tcMMEP response was significantly smaller than the tcEMEP at doses above 0.9 mg/kg (all P<0.001). The onset latency values were not significantly increased at any dose or time. The epidural recording demonstrated a large increase in the number of I waves compared to the isoflurane baseline. This study demonstrates that a low dose (0.1 mg/kg) of etomidate increases the com- pound muscle action potential (CMAP) amplitude for tcEMEP and tcMMEP in the monkey whereas higher doses decrease the amplitude. Epidural recordings demonstrate a marked increase in the number of I waves consistent with a cortical effect similar to the postulated effect that results in amplification of the cortical SSEP. This suggests the amplitude loss in the hypothenar muscles may be due to depression of the spinal cord by etomidate. The CMAP response amplification at low doses was greater in tcMMEP than tcEMEP and the depression at higher doses was more with the tcMMEP technique consistent with the greater dependence of the tcMMEP technique on synaptic activation.