Adverse drug reactions resulting in hyperthermia in the intensive care unit

Abstract

Hyperthermia is frequently seen in the intensive care setting and is associated with significant morbidity and mortality. It is often initially misdiagnosed as fever associated with infection. Atypical presentations of classic syndromes are common. Clinical suspicion is the key to diagnosis. Adverse drug reactions are a frequent culprit. Syndromes include adrenergic "fever," anticholinergic "fever," antidopaminergic "fever," serotonin syndrome, malignant hyperthermia, uncoupling of oxidative phosphorylation, and withdrawal from baclofen. This review describes the pathophysiology of hyperthermia, as distinct from fever, and the physiology, diagnosis, and treatment of serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia, and baclofen withdrawal. Much of the available evidence regarding the treatment of these disorders is based on single case reports, case series, or animal models. Therapeutic modalities consist of identification/withdrawal of possible offending agent(s), support directed at lowering temperature and preventing/treating complications, as well as targeted pharmacologic therapy directed at the specific cause. Early recognition and treatment using a multidisciplinary approach are essential to achieve the best possible outcome.

Case Scenario: Opioid Association with Serotonin Syndrome

“…4 Many of these can be ruled out by careful, thorough history and physical examination. The clinical mimics include: neuroleptic syndrome, malignant hyperthermia, anticholinergic syndrome, opioid withdrawal, and acute opioid toxicity 31 (table 4). Neuroleptic syndrome can be precipitated by use of antipsychotic medications and may present with similar symptoms, such as hypertension, tachycardia, tachypnea, pallor, stupor, and coma.…”

“…The two entities differ in onset of symptoms, hyporeflexia, decrease or normal bowel sounds, leadpipe rigidity, and hyperthermia of more than 41°C. 14,31 Malignant hyperthermia is differentiated by exposure to inhaled halogenated anesthetics or depolarizing paralytic agents with associated hyperthermia of 42-46°C, hypercarbia, acidosis, muscular rigidity, hyporeflexia, decreased bowel sound along with hypertension, tachycardia, tachypnea, mottled skin, and agitation. 14,31 Anticholinergic syndrome carries a history of tricyclic antidepressant or anticholinergic agent use and is associated with dry mouth, blurred vision, delirium, decreased bowel sounds along with tachycardia, tachypnea, and hyperthermia of 40°C.…”

Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study

“…Several syndromes including malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), serotonin syndrome, anticholinergic poisoning, heat stroke and sympathomimetic poisoning have been reported to be associated with hyperthermia [1]- [4]. Extreme hyperthermia with temperatures as high as >41˚C have been reported in some syndromes [5] [6]. Hyperthermia can be extremely harmful and potentially fatal because it may result in permanent neurologic sequelae like Cerebellar syndrome if not treated properly [7] [8].…”

Acute psychosis in anti-NMDA-receptor encephalitis

“…Anti-NMDA receptor encephalitis may be highly misleading, as it may mimic acute psychosis. Moreover, in treated psychotic patients symptoms such as diaphoresis, fever, confusion, autonomic dysfunction, dyskinesia and movement disorders, seizures and hypoventilation may be ascribed to anti-psychotic therapy toxicity, such as neuroleptic malignant syndrome [6]. Our first patient suffered from fever and rhabdomyolysis, and events chronology strongly suggested neuroleptic syndrome that was confusing.…”