Drug-associated non-pyrogenic hyperthermia: A narrative review

Purpose: Hyperthermia occurs when heat accumulation surpasses the body’s ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia. Methods: A comprehensive search was performed across 5 databases covering the period of inception to March 2019, for publications that reported hyperthermia associated with drug use. Studies that reported potential drug association with hyperthermia due to altered thermoregulatory mechanisms were included. Case reports of less than 3 cases were excluded, as well as hyperthermia due to other causes, such as hypersensitivity, malignant hyperthermia and neuroleptic malignant syndrome. The primary outcomes of interest were hospitalisation and mortality. Results: The literature search initially identified a total of 2609 records. Based on full-text analysis, 11 articles met the inclusion criteria, of which there were 5 case-control studies, 2 case series and 4 retrospective analyses. Studies reported heat-related hospitalisations or emergency department presentations associated with the use of psychotropics (antipsychotics, antidepressants and anxiolytics), anticholinergics, antihistamines, diuretics, cardiovascular agents, non-steroidal anti-inflammatory drugs and anticoagulants. Psychotropic drugs were reported to be associated with increased heat-related mortality, other than through neuroleptic malignant syndrome, but findings varied among the studies. Conclusion: Given the relative lack of publications, more research is necessary to study specific effects of drugs on body temperature and the likelihood of inducing non-pyrogenic hyperthermia. In particular, psychotropics, anticholinergics, diuretics and cardiovascular agents are of interest for future studies.