From the Guidelines
Non-infective causes of hyperthermia include heat stroke, malignant hyperthermia, neuroleptic malignant syndrome, serotonin syndrome, thyroid storm, adrenal crisis, and drug-induced hyperthermia, with the most recent guidelines from 2024 emphasizing the importance of prompt recognition and treatment of these conditions to prevent morbidity and mortality 1.
Causes of Non-Infective Hyperthermia
- Heat stroke: occurs when the body's temperature regulation fails due to environmental heat exposure or excessive exertion, with a high risk of organ dysfunction and mental status alteration 1.
- Malignant hyperthermia: a rare genetic disorder triggered by certain anesthetic agents like halothane and succinylcholine, causing rapid temperature elevation and muscle rigidity, with a mortality rate of approximately 4% in the UK 1.
- Neuroleptic malignant syndrome: results from antipsychotic medications such as haloperidol or risperidone, while serotonin syndrome stems from excessive serotonergic activity, often due to combinations of SSRIs, MAOIs, or other serotonergic drugs 1.
- Endocrine emergencies like thyroid storm (severe hyperthyroidism) and adrenal crisis can present with hyperthermia, requiring prompt recognition and treatment to prevent complications 1.
- Various medications including stimulants (cocaine, amphetamines), anticholinergics, and sympathomimetics can directly cause temperature elevation, and certain neurological conditions like hypothalamic damage, status epilepticus, and stroke can disrupt temperature regulation 1.
Treatment and Management
Treatment depends on the specific cause but generally includes cooling measures, stopping causative medications, and addressing the underlying condition with specific interventions like dantrolene for malignant hyperthermia or benzodiazepines for certain drug-induced syndromes 1. Prompt recognition and treatment of non-infective causes of hyperthermia are crucial to prevent morbidity and mortality, with the most recent guidelines from 2024 providing updated recommendations for first aid and emergency management 1.
From the FDA Drug Label
In addition to the parent compound, dantrolene, which is found in measurable amounts in blood and urine, the major metabolites noted in body fluids are the 5-hydroxy analog and the acetamido analog. Clinical experience in the management of fulminant human malignant hyperthermia, as well as experiments conducted in malignant hyperthermia susceptible swine, have revealed that the administration of intravenous dantrolene, combined with indicated supportive measures, is effective in reversing the hypermetabolic process of malignant hyperthermia Known differences between human and swine malignant hyperthermia are minor. The prophylactic administration of oral or intravenous dantrolene to malignant hyperthermia susceptible swine will attenuate or prevent the development of signs of malignant hyperthermia in a manner dependent upon the dosage of dantrolene administered and the intensity of the malignant hyperthermia triggering stimulus Limited clinical experience with the administration of oral dantrolene to patients judged malignant hyperthermia susceptible, when combined with clinical experience in the use of intravenous dantrolene for the treatment of malignant hyperthermia and data derived from the above cited animal model experiments, suggests that oral dantrolene will also attenuate or prevent the development of signs of human malignant hyperthermia, provided that currently accepted practices in the management of such patients are adhered to
The non-infective causes of hyperthermia include:
- Malignant hyperthermia 2, which is a rare but life-threatening medical emergency triggered by certain medications used for general anesthesia, particularly volatile anesthetics and succinylcholine.
- Hypermetabolic processes 2, which can be reversed with the administration of intravenous dantrolene and supportive measures. Note that the provided drug labels do not provide an exhaustive list of non-infective causes of hyperthermia, and other causes may exist.
From the Research
Non-Infective Causes of Hyperthermia
The non-infective causes of hyperthermia can be attributed to various factors, including:
- Drug-induced hyperthermia, which can be caused by a range of medications, such as inhalation anaesthetics, sympathomimetic agents, serotonin antagonists, antipsychotic agents, and compounds with anticholinergic properties 3
- Certain medical conditions, such as lethal catatonia, thyrotoxic storm, and pheochromocytoma 3
- Exposure to extreme environmental temperatures, which can lead to exertional heat stroke (EHS) 4
- Drug-induced hyperthermic syndromes, including malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS) 4, 5, 6
Drug-Induced Hyperthermia
Drug-induced hyperthermia can occur due to the disruption of body temperature homeostasis, leading to a syndrome similar to EHS 4. Various drugs and drug classes have been implicated in this condition, including:
- Amphetamines
- Diuretics
- Cocaine
- Antipsychotics
- Metoclopramide
- Selective serotonin reuptake inhibitors (SSRIs)
- Tricyclic antidepressants (TCAs) 4
Other Non-Infective Causes
Other non-infective causes of hyperthermia include: