Differentiating Malignant Hyperthermia, Neuroleptic Malignant Syndrome, and Serotonin Syndrome: A Clinical Review and Diagnostic Algorithm

Author(s): Brian Gabriel

This review summarizes the clinical presentation, distinguishing clinical features, and underlying pathophysiology of malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). MH results from exposure to inhalational anesthetics or succinylcholine and is due to uncontrolled calcium release in skeletal muscle cells. Hypercarbia and masseter spasms occur early, followed by hyperthermia and rigor-mortis–like rigidity. NMS results from dopamine receptor blockade in the central nervous system. Associated features include altered mental status, dysautonomia, and lead-pipe rigidity, typically developing over several days. SS is produced by medications that prevent serotonin degradation and usually presents abruptly. Characteristic features of SS include clonus and gastrointestinal symptoms.

MH, NMS, and SS share overlapping clinical features, and no definitive diagnostic tests exist for these conditions. A thorough medication history is the most important diagnostic tool, but patients often present with confusion or altered mental status that limit their ability to communicate. When history is unavailable, diagnosis may be aided by recognizing characteristic features associated with each condition. A novel diagnostic algorithm is proposed that combines key findings to assist clinicians in distinguishing MH, NMS, and SS. Improved recognition and earlier diagnosis will help guide treatment and improve patient outcomes.