Perioperative Anesthetic Considerations for Anti-NMDA Receptor Encephalitis Patients: A Case Report

Abstract

Introduction: Anti-NDMA receptor (anti-NMDA-R) encephalitis is a neurologic autoimmune disease that presents with characteristic psychiatric, neurological, and constitutional symptoms. It is caused by production of anti-NMDA-R antibodies, which in turn cause downregulation of NMDA receptors on central neurons. Detection of anti-NMDA-R antibodies in the serum or cerebrospinal fluid (CSF) confirms the diagnosis. The disease is often associated with an underlying tumor, most commonly an ovarian teratoma. Perioperative anesthetic management of patients with anti-NMDA-R encephalitis is a subject of interest to anesthesiologists because many anesthetic agents interact with the NMDA receptor, and therefore pose a risk of worsening the patient’s encephalitis, especially if surgical removal of the underlying teratoma is required for treatment. Case Description: A 15-year-old male diagnosed with anti-NMDA-R encephalitis in April 2022 was taken to the operating room (OR) for G-tube placement under general anesthesia in June 2022. The procedure followed a month-long hospitalization in the ICU and a month-long stay in the inpatient rehabilitation unit, all at Riley Children’s Hospital in Indianapolis, IN. The procedure was performed with total intravenous (IV) anesthesia with midazolam, dexmedetomidine, and remifentanil. Other medications the patient received during the procedure include cefazolin, dexamethasone, ondansetron, and ketorolac. Neither propofol nor volatile anesthetics were administered during the case. The patient remained hemodynamically stable intraoperatively with an uneventful postoperative course. Discussion: There is currently no definitive consensus on the optimal anesthetic regimen for patients with anti-NMDA-R encephalitis. In the available literature on this subject, both ketamine and nitrous oxide (N2O) have been routinely avoided because they are well-known for their direct NMDA-R antagonist activity. Commonly used agents include propofol, volatile anesthetics (e.g. sevoflurane), opioids, nondepolarizing paralytics, dexmedetomidine, and benzodiazepines (e.g. midazolam). Notably, volatile anesthetics (e.g. sevoflurane) and propofol are known to have some inhibitory activity on NMDA receptors, with volatile anesthetics demonstrating this moreso than propofol. Furthermore, there is some data to suggest that use of volatile anesthetics in these patients is associated with higher rates of postoperative adverse events, namely hypoventilation (potentially requiring reintubation) as well as pneumonia (e.g. aspiration pneumonia and ventilator-associated pneumonia). However, other studies and reviews have also reported no postoperative adverse events in the setting of volatile anesthetic use. A number of authors advocate for the use of midazolam, dexmedetomidine, and opioids, as these agents do not interact with NMDA receptors. Although there are no known reports of IV opioid-induced hypoventilation postoperatively in anti-NMDA-R encephalitis patients (to our knowledge), opioids still ought to be used judiciously in these patients, as they are at elevated risk of hypoventilation due to involvement of the brainstem respiratory center by the primary disease process.