Neuroleptic malignant syndrome (NMS) is a rare condition experienced by patients taking typical and/or atypical antipsychotic medications. There are well-established diagnostic criteria for NMS. However, differentiating it from serotonin syndrome and malignant hyperthermia—particularly in the intensive care setting--is problematic and thus remains a diagnosis of exclusion. A case report of a patient with atypical NMS in intensive care is described and the subsequent learning points gleaned from the patient are presented.

A 28 year-old female was admitted to the intensive care unit (ITU) following a self-inflicted traumatic injury. The patient was known to local mental health services and her medical history includes personality disorder, anxiety and depression. Regular psychiatric medications prior to hospitalization included flupentixol and quetiapine. Remifentanil was administered in a continuous infusion for sedation as the patient was intubated and ventilated. Valproic acid and levetiracetam were given for seizures.

Repeated spikes in temperature, rigidity and slightly elevated creatine kinase (CPK) were observed in the patient. Autonomic dysfunction was also noted; the patient experienced bradycardic episodes that increased in frequency and duration. On two occasions, this resulted in asystole and cardiopulmonary resuscitation (CPR) had to be commenced with return of spontaneous circulation following CPR. Mental status changes were unable to be assessed due to ongoing sedation of the patient. On the advice of the clinical pharmacist, remifentanil was switched to fentanyl. Quetiapine and flupentixol were also discontinued after consulting with the psychiatric team. In addition, the patient responded quickly to dantrolene administration and to active cooling.

Main diagnostic criteria for NMS include hyperthermia, rigidity, mental status changes and autonomic dysfunction. The definition of atypical NMS includes three of these four criteria. Serotonin syndrome was ruled out as the patient was not taking any selective serotonin reuptake inhibitors (SSRI) nor selective serotonin-norepinephrine reuptake inhibitors (SNRI). Malignant hyperthermia was also considered as the patient had received a volatile anaesthetic gas, isoflurane, for sedation purposes; however, symptoms persisted long after it was stopped.

Atypical NMS is a diagnosis of exclusion that must be considered in patients in an intensive care setting who experience refractory hyperthermia. A multidisciplinary team is essential in caring for critical care patients who exhibit symptoms of NMS, including psychiatry, neurology, and clinical pharmacy.