Selection of general anesthesia method is a concern in patients with mitochondrial disease [1]. Although the risk of malignant hyperthermia from inhalational anesthetics was previously believed to be increased in patients with muscular disease, this does not appear to be the case, even for patients with hereditary muscular disease. Malignant hyperthermia risk is not higher in patients with muscular dystrophy compared with the general population [6], and the same is assumed for patients with mitochondrial disease [7]. In fact, a survey of pediatric anesthesiologists in the USA showed that approximately 80% used sevoflurane to induce and maintain anesthesia in children with mitochondrial disease [7]. Propofol infusion syndrome is another concern because its risk is reportedly high in patients with mitochondrial disease [8]. Opinions vary regarding the selection of inhalational anesthetics or propofol. In our patient, we selected a benzodiazepine to avoid the risks of both. Benzodiazepines have been considered safe for general anesthesia in patients with mitochondrial disease and can be administered intravenously [7]. However, clearance is slow and prolonged effects may occur [9].
Remimazolam is an ultrashort-acting benzodiazepine with an imidazobenzodiazepine structure that exhibits pharmacological effects similar to those of midazolam. It has a side chain with an ester bond that is rapidly inactivated by carboxylesterase hydrolysis in the liver. The pharmacological activity of remimazolam metabolites is low, approximately 1/400th that of remimazolam, which suggests they have negligible pharmacological activity [5]. Furthermore, the effects of remimazolam can be reversed by flumazenil. These features make remimazolam a safe and feasible alternative to inhalational anesthetics and propofol.
The use of muscle relaxants in patients with mitochondrial disease presents potential difficulties. Patients with mitochondrial disease may experience muscle weakness and prolonged muscle relaxation after anesthesia. Muscle relaxant effects may be prolonged in these patients because of increased rocuronium sensitivity [10, 11]. To address this, sugammadex administration to reverse neuromuscular blockade may be useful, but experience is limited and no clear conclusion has yet been reached. In our patient, we did not administer sugammadex because the TOF ratio was ≥ 0.9 [12] and the effects of sugammadex in patients with muscular disease and TOF ratio ≥ 0.9 have not been investigated. Furthermore, sugammadex administration is associated with risks such as difficulty with reintubation and allergic reaction [13]. Therefore, the decision to use sugammadex should be considered carefully. Future studies are warranted.
Hearing impaired patients have difficulty perceiving changes in their environment and communicating, which are relevant to anesthesia recovery. Effective communication between the patient and medical personnel during recovery is crucial. Administration of flumazenil after remimazolam allows rapid psychomotor recovery from sedation [14], even in patients with muscular dystrophy [15]. The administration of flumazenil after remimazolam anesthesia may be useful to assist in achieving good communication with hearing impaired patients.
Remimazolam, remifentanil, and rocuronium can be pharmacologically antagonized, which is a major advantage in their use. The rapid and clear response achieved with flumazenil in our patient may indicate the superiority of remimazolam over other sedatives. However, flumazenil may cause convulsions by antagonizing benzodiazepine effects [16,17,18], and should not be administered casually.
