B48-19 Serotonin Syndrome in an Intubated Patient: An Underrecognized Cause of ICU Agitation, Fever, and Rhabdomyolysis

Introduction Serotonin syndrome (SS) is a life-threatening condition caused by excess serotonergic activity. In intubated patients, features such as hypertension, tachycardia, clonus, and alteration in mental status may be obscured by intensive care unit (ICU) interventions such as sedation or neuromuscular blockade, leading to delayed diagnosis, prolonged agitation, and failure of spontaneous awakening/breathing trials. We present a case of ventilator and sedation weaning failure in an intubated patient with agitation, prolonged fever, and ventilator dyssynchrony, highlighting the importance of SS recognition in the ICU. Case Presentation A 56-year-old male with a history of alcohol use disorder and depression was admitted to the ICU following cardiac arrest. Prior medications included amlodipine, furosemide, bumetanide, atorvastatin, escitalopram, and aripiprazole, with recent methadone use. Initial management included propofol and fentanyl for sedation with Artic Sun cooling. His course was complicated by ventilator-associated pneumonia and acute respiratory distress syndrome (ARDS) managed with cefepime, corticosteroids, and cisatracurium neuromuscular blockade. Upon discontinuation of temperature management, the patient became febrile with elevation in creatine kinase, agitation, ventilator dyssynchrony, autonomic instability, and diaphoresis despite antipyretics. Repeat infectious workup, electroencephalogram, and computed tomography imaging were grossly unrevealing. Examination revealed inducible, non-fatigable clonus in the lower extremities, hyperreflexia, diaphoresis, and hyperthermia, meeting Hunter criteria for SS, prompting fentanyl discontinuation. Midazolam was initiated for symptomatic management. A tracheostomy was performed with gradual weaning from sedation. Agitation, autonomic instability, and fever resolved. Clonus disappeared completely after two weeks. Discussion This case illustrates the diagnostic challenge of SS in the critically ill, especially in mechanically ventilated patients. Exposure to multiple serotonergic agents, including SSRIs, atypical antipsychotics, methadone, and fentanyl likely precipitated toxicity. Fentanyl is a well-known ICU medication that can potentiate serotonin toxicity. Recognition based on examination and autonomic instability prompted cessation of all serotonergic agents. This case highlights a prolonged form of SS, likely from recent overlap of long-acting serotonergic medications. Initiation of benzodiazepine therapy with midazolam provided supportive management in preparation for tracheostomy and recovery. Recent literature illustrates that supportive care, including benzodiazepines and withdrawal of offending agents, remains first-line management. This case emphasizes the importance of prompt recognition of SS as a possible cause of unexplained and challenging ICU agitation and ventilator dyssynchrony. Conclusion Serotonin syndrome should be suspected in intubated ICU patients with unexplained agitation, hyperthermia, and clonus, especially in the setting of serotonergic drug combinations. Recognition and supportive management are necessary to improve agitation, outcomes, and facilitate ventilator weaning.