Anesthetic Management Using Remimazolam for Dental Treatment in a Pediatric Patient With Dravet Syndrome

Dravet syndrome (DS) is a severe form of epilepsy characterized by frequent or prolonged seizures commonly triggered by hyperthermia (ie, increased body temperature secondary to fever or other nonfebrile causes like bathing in hot water) or visual stimuli (eg, flashing lights). Many different types of seizures can occur with DS, although convulsive or tonic-clonic seizures are common. The seizures in DS may be intractable and are often refractory to treatment with antiepileptic drugs. In patients with DS who are undergoing dental care, perioperative seizure control is a major focus of patient management and sometimes requires concurrent use of sedation or general anesthesia. Here, we report our experience using remimazolam (RMZ) during the anesthetic management for a pediatric dental patient with DS.

CASE PRESENTATION

A girl aged 3 years 5 months (height, 90 cm; weight, 13.8 kg; body mass index, 17.0 kg/m²) presented to our institution for dental care having been diagnosed with DS based on genetic testing at 1 year of age. She was being treated with the antiepileptic drugs topiramate 20 mg, sodium valproate 100 mg, clobazam 2 mg, and stiripentol 200 mg but had occasional focal seizures that occurred approximately 2 to 3 times a month. Additionally, she had been admitted emergently for convulsive seizures twice previously. The planned dental treatment included several composite resin restorations, pulpotomies/pulpectomies, and crowns.

On the day of surgery, a slow mask induction was performed with nitrous oxide 3 L/min, oxygen 3 L/min, and sevoflurane 2.4%, after which peripheral intravenous (IV) access was secured with a 22-gauge IV catheter placed in her right great saphenous vein. Thereafter, we administered a continuous IV infusion of remifentanil 0.35 μg/kg/min and IV boluses of RMZ 2.8 mg and rocuronium 10 mg and then performed oral intubation without difficulty. General anesthesia was maintained with air 2 L/min, oxygen 1 L/min, and continuous infusions of RMZ 1 mg/kg/h and remifentanil 0.35 μg/kg/min under bispectral index monitoring to assess anesthetic depth. A total of 1 mL of 2% lidocaine with 1:80,000 epinephrine was used for local anesthesia intraoperatively.

After completion of the surgery in 1 hour, 20 minutes, and anesthesia for 1 hour, 45 minutes, sugammadex 30 mg was administered, and the patient was extubated after adequate spontaneous ventilation was confirmed (Figure). There were no signs of emergence delirium noted postoperatively. The patient’s intraoperative temperature and other vital signs were stable throughout the case. No signs of hyperthermia, fever, or seizure activity were observed during the perioperative period, and she was allowed to go home after confirming the absence of any abnormalities in her recovery.

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DISCUSSION

DS is thought to be caused by dysfunction of gamma-aminobutyric acid (GABA) interneurons, specifically GABA-A, because of an inborn error in the Na⁺ ion channel gene SCN1A. This GABAergic dysfunction has an estimated prevalence of 1 in 20,000 to 1 in 40,000.¹ In DS patients, benzodiazepines (eg, midazolam) can be useful because of their inherent anticonvulsant effects via positive allosteric modulation of GABA-A receptors.² However, midazolam is metabolized by CYP3A4, a cytochrome P450 enzyme found in the liver, and produces an active metabolite with an affinity for benzodiazepine receptors of approximately one-eighth its parent compound, which may contribute to delayed awaking following use. In contrast, RMZ is rapidly metabolized by tissue carboxylesterases, mainly CES1, which is predominantly found in the liver, and its metabolite has a receptor affinity of approximately 1/400th of its parent compound, which is extremely low and can facilitate a rapid recovery.³ Therefore, we opted to use the new ultrashort-acting benzodiazepine RMZ in combination with remifentanil and rocuronium for the general anesthetic management in this case.

The pharmacokinetic properties of RMZ in pediatric patients are reported to be similar to those of adults.³ Antagonism of RMZ by flumazenil may affect the risk of emergence delirium and seizure.⁴ Therefore, we opted to use the minimum dose of RMZ required to facilitate general anesthesia to avoid the need to use flumazenil postoperatively. If signs of intraoperative awareness were observed, like fluctuations in vital signs or body movements, the RMZ dose rate was planned to be increased up to 2 mg/kg/h. However, this case was managed without any signs of intraoperative awareness, so the RMZ infusion rate was not changed.

Perioperative temperature management is also important for the prevention of induced seizures in patients with DS. There are reports that the incidence of emergence delirium⁵ and postoperative nausea and vomiting (PONV)⁶ are decreased with the use of RMZ. These reports suggest that RMZ may prevent the temperature elevation caused by excitement and the dehydration caused by PONV. Furthermore, RMZ may be useful in patients with DS because emergence delirium, postoperative agitation, and PONV can be stressful and may directly induce seizure activity.

RMZ is an ultrashort-acting benzodiazepine that may be useful for the anesthetic management of pediatric patients with DS because of its potential to prevent seizures as well as reduce the risks of emergence delirium and PONV.

This research was originally published in the Journal of the Japanese Dental Society of Anesthesiology. 2024;52(3):145-149.