In this case, general anesthesia with desflurane and nitrous oxide facilitated early emergence in a patient with NKH, contrasting with her previous experience of delayed emergence following sevoflurane and remifentanil anesthesia. The patient’s almost flat EEG observed on the BIS monitor post-induction with propofol and fentanyl suggests a heightened sensitivity to anesthetic agents in NKH patients.

Previous reports have suggested that sevoflurane may cause delayed emergence in patients with NKH [9, 10], as seen in the patient’s history. Although desflurane has not been extensively studied in this patient population, the rapid recovery observed in this case supports its use as a potentially preferable anesthetic agent. Given that glycine is an inhibitory neurotransmitter in the spinal cord and brainstem, it can cause apnea and hiccups in NKH patients. However, NKH is thought to be neurotoxic owing to excessive activation of NMDA receptors produced by accumulated glycine which acts as a co-transmitter of glutamate [11]. However, we found no reports indicating a significant difference between the effects of sevoflurane and desflurane on glycine and NMDA receptors [12]. Therefore, we hypothesized that the delayed emergence produced by sevoflurane may be owing to its pharmacokinetic properties rather than to differences in the action of the drug itself.

The favorable pharmacological profile of desflurane, including its low blood-gas solubility coefficient, may also have contributed to the quicker emergence. The severe suppression on the BIS monitor observed in this case also suggests that patients with NKH may be more sensitive to sedative drugs, and we presume that the difference in the pharmacokinetic profile between sevoflurane and desflurane may have been expressed as a significant clinical difference.

Remifentanil, an ultra-short-acting opioid, is generally considered appropriate for NKH patients due to its rapid clearance [9]. However, the glycine present in clinical formulations of remifentanil posed a potential risk for this patient, given her condition’s underlying defect in glycine metabolism. This concern led us to avoid remifentanil, although there is no direct evidence to suggest that its use would be harmful in NKH patients.

Nitrous oxide, which has NMDA receptor antagonistic properties similar to ketamine [11, 13,14,15], was included in the anesthetic plan due to its potential to provide neuroprotective effects in NKH [16]. Although ketamine could theoretically alleviate symptoms related to NKH, its impact on the speed of emergence is unclear, and thus it was not used in this case.

After induction of general anesthesia with propofol and fentanyl, severe suppression of EEG signals was observed on the BIS monitor for approximately 60 min. Delayed emergence from sedation or anesthesia has been reported in patients with NKH [8,9,10]. Although the relationship between anesthetic sensitivity and preoperative EEG findings is unclear, abnormal EEG patterns, including burst suppression and hypsarrhythmia without the administration of sedatives, have been reported in neonatal and infantile cases of NKH [17]. The patient in the present case also exhibited burst suppression during the neonatal period and hypsarrhythmia at 5 months of age. In addition, although the concentrations of desflurane and nitrous oxide remained constant throughout the surgery, the suppression ratio decreased over time. The severe EEG suppression observed in this case may be due to the propofol used at the induction of anesthesia, indicating that NKH patients might be particularly sensitive to anesthetic agents. Ideally, we should compare the intraoperative EEG patterns with the preoperative ones. Unfortunately, preoperative EEG findings are unknown because an EEG recording had not been performed recently. Although we could confirm the EEG patterns before the induction of anesthesia, we regrettably attached the BIS sensor after the induction of general anesthesia. Therefore, it was difficult to conclude that the EEG patterns observed in the present case reflected the effect of general anesthetics including desflurane or propofol. However, the patients showed time-dependent recovery of the BIS value without any changes in desflurane concentration, suggesting that the effect of propofol could cause severe suppression of the EEG. However, in a previous report of a patient with NKH, the BIS value was 41 before anesthesia induction and varied from 32 to 55 under the administration of propofol, remifentanil, and nitrous oxide [9]. Although the symptoms, severity, and dosage of propofol in that case were similar to those in the present case, it is noteworthy that the intraoperative EEG findings differed. According to our study, we suggest that an anesthesiologist should monitor EEG before induction of general anesthesia and pay attention to the findings when a patient has a possibility of unpredictable sensitivity to general anesthetics.

In conclusion, this case suggests that desflurane and nitrous oxide, owing to their favorable pharmacological profiles, may be preferable anesthetic agents in patients with NKH, particularly those with a history of delayed emergence from sevoflurane anesthesia. The observed EEG suppression may reflect an increased sensitivity to anesthetics in patients with NKH.