Contemporary Perspectives in Critical Care of Neuroleptic Malignant Syndrome

Background: Neuroleptic malignant syndrome (NMS) is a psychiatric-neurologic emergency that may require intensive care management. There is a paucity of information about NMS as a critical illness. We reviewed the Mayo Clinic experience.

Methods: A comprehensive data extraction was completed within the Mayo Clinic system diagnosed with NMS using International Classification of Diseases, ninth revision (ICD-9); ICD-9, Clinical Modification; ICD-10; ICD-10, Clinical Modification; and Health Insurance Claim (HIC) codes between the years of 1995 and 2023. Major criteria included fever, rigidity, tachycardia, and exposure to a neuroleptic agent. Minor criteria included rhabdomyolysis and dysautonomia. Criteria for exclusion were Parkinson's disease, abrupt discontinuation of baclofen or levodopa, concomitant selective serotonin reuptake inhibitors use or serotonin syndrome, malignant catatonia, or a classic dystonic reaction.

Results: A total of 332 patients had diagnostic codes of NMS, but only 20 patients fulfilled DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision), diagnostic criteria. The average age was 48.2 years (range 20-93 years). Four patients received antipsychotics following postoperative acute agitation or delirium (20%). Previous psychiatric diagnoses were schizophrenia or schizoaffective disorder in six patients (33%), major depressive disorder in five patients (20%), and bipolar disorder in two patients (10%). Haloperidol was the sole inciting neuroleptic in five patients (25%), but the remainder was associated with atypical or second-generation antipsychotics. A total of nine patients (45%) required mechanical ventilation. The majority of patients had rhabdomyolysis, which led to acute kidney failure in nearly half of them, but none required hemodialysis. Most patients recovered promptly, and no fatalities were directly attributable to NMS; however, four patients (20%) died within 1 month, and four patients died years from diagnosis and unrelated to NMS.

Conclusions: Neuroleptic malignant syndrome can become a critical illness, but there is often rapid recovery. Mortality proximate to NMS was uncommon, but late mortality remained substantial. The overwhelming majority of cases coded as NMS did not meet DSM-5 diagnostic criteria. Stricter criteria should be applied when diagnosing NMS in critical care and emergency medicine settings.