Intraoperative MEP monitoring during spine surgery is used to detect neurologic deficits that occur due to surgical maneuvers, vascular injury, or spinal cord ischemia. General anesthetics, especially volatile anesthetics, induce suppression of MEP amplitude, mainly by affecting synaptic transmission [5]. Volatile anesthetics appear to suppress both synaptic activity in the brain and spinal motor neuron excitability [6, 7]. Intravenous anesthetics, including propofol and benzodiazepine, produce inhibitory effect of interneuron activity through GABA(A) receptor with minimal suppression of spinal motor neuron excitability [8, 9]. Therefore, intravenous anesthetics are preferred over volatile anesthetics for the purpose of MEP monitoring. Remimazolam is a novel short-acting benzodiazepine that has higher affinity for the GABA(A) receptor and is metabolized into a lower-affinity carboxylic acid metabolite than the conventional benzodiazepine midazolam [10]. Midazolam can produce marked depression of MEP responses [11], whereas the impact of remimazolam on MEP responses is not well-known.
In the cases described here, no significant MEP changes were observed throughout operations performed under general anesthesia using remimazolam and remifentanil. Long duration of operation or prolonged exposure to anesthetics can cause MEP responses to deteriorate, a phenomenon called “anesthetic fade” [12]. In case 1, there were no significant changes in MEP signals under general anesthesia using a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. Although the optimal dose of remimazolam during the maintenance phase of general anesthesia is 1 mg/kg/h [13], maintenance dose of remimazolam in this case was lower than previously reported. Remifentanil appears to synergize with the anesthetic effect of remimazolam [13]; thus, using remifentanil in combination with remimazolam enables a reduction in the required amount of remimazolam without interfering with MEP monitoring. In case 2, increasing the dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. Intravenous anesthetics can affect MEP responses in a dose-dependent fashion [14]. During continuous infusion of midazolam, progressive suppression of MEP signals has been observed with increasing doses [15]; in this case, however, increasing the dose of remimazolam did not affect MEP signals. Although we could not clarify the mechanism of the differences between midazolam and remimazolam on MEP monitoring, the difference in dosage may cause different effect on MEPs. Electroencephalogram (EEG) monitoring can obtain good arousal and avoid overuse of anesthetics by assessing the depth of anesthesia [16]. In these cases, it is possible that the MEP responses did not change during the operation because the amount of remimazolam was minimized by using the EEG value as an index of remimazolam dose.
This report has some limitations. First, it is unclear whether remimazolam suppresses MEP because there are no control data without it. Second, this is only an observational finding with two cases; thus, further studies are needed to consider about the indication of remimazolam for operations using MEP monitoring.
In summary, here we have reported our experience with two cases of intraoperative MEP responses during spine surgery under anesthesia with remimazolam and remifentanil. In both cases, MEP monitoring was successfully performed by either fixed or increasing doses of remimazolam. Thus, anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring using an EEG monitor to assess the optimal dose.