Abstract Introduction Hyperthermia with altered mental status can have a life-threatening presentation leading to complications and multiorgan dysfunction. Hyperthermic syndromes, such as heat stroke, malignant hyperthermia, and neuroleptic malignant syndrome (NMS), share overlapping presentations, resulting in diagnostic challenges. We present a case highlighting the importance of systemic evaluation in complex hyperthermia conditions. Description A 40-year-old male with an unknown past medical history was found outdoors in the extreme heat, confused and unresponsive. On ED arrival, he had a Tmax of 104.8 °F, tachycardia (170 beats/min), and developed ventricular tachycardia requiring synchronized cardioversion and amiodarone. Initial labs had creatine kinase (CK) greater than 22,000 U/L, elevated creatinine (2.7 mg/dL), AST (128 U/L), and ALT (100 U/L). He was intubated in the ICU for heat stroke with multiorgan failure requiring vasopressors and continuous renal replacement therapy (CRRT). However, his muscle rigidity, elevated CK, and persistent hyperthermia raised concern for the rare possibility of malignant hyperthermia; therefore, dantrolene was initiated. Later, a conversation with family revealed his history of schizophrenia with multiple psychiatric admissions and use of multiple psychotropics, including haloperidol and valproate. Therefore, a diagnosis of neuroleptic malignant syndrome was best supported. Antipsychotics were discontinued, and Ativan was added to the ongoing dantrolene. The CK continued to rise before declining, consistent with NMS. After improvement of rigidity, mental status, and CK, he was weaned off ventilator support and CRRT. Discussion This case underscores the importance of maintaining a broad differential diagnosis for severe hyperthermia in ICU patients, especially when history is limited and the course is atypical. In patients with altered mental status, distinguishing environmentally driven heat stroke from drug-induced causes can pose a diagnostic challenge. Given his exposure to extreme heat, it was reasonable to suspect heat stroke. However, with his persistent hyperthermia with rigidity and elevated CK, malignant hyperthermia (MH) could not be excluded. MH and NMS share overlapping presentations such as altered mental status, hyperthermia, and rhabdomyolysis. However, MH follows exposure to anesthetics, whereas NMS follows excessive use of antipsychotics. NMS is a rare disease occurring in 0.01% to 3.2% of patients. Therefore, despite his use of haloperidol, NMS is rare. Risk factors such as concurrent valproate use and dehydration may increase risk. In this case, after a holistic assessment, neuroleptic malignant syndrome was best supported, showcasing that recognition of multisystem involvement and prompt intervention are critical in improving clinical outcomes. This abstract is funded by: None
Kottukkal et al. (2026) studied this question.