Mechanism of Cocaine-Induced Hyperthermia in Humans

4 June 2002 | Volume 136 Issue 11 | Pages 785-791

Background: The lethal effects of cocaine are unique among those of other illicit drugs because cocaine has the propensity to cause hyperthermia. The traditional view is that cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregulatory adjustments that mediate heat dissipation.

Objective: To test the effects of cocaine on body temperature regulation in humans.

Design: Randomized, double-blind, placebo-controlled crossover trial.

Setting: A cardiovascular physiology laboratory in Dallas, Texas.

Participants: 7 healthy, cocaine-naive volunteers.

Intervention: Progressive passive heat stress, during which each participant received intranasal cocaine (2 mg/kg of body weight) or placebo (lidocaine, 2 mg/kg).

Measurements: Esophageal temperature, skin blood flow, sweat rate, and perceived thermal sensation.

Results: Three major new findings were noted. First, cocaine substantially augmented the progressive increase in esophageal temperature during heat stress (P < 0.001). Second, this augmentation was explained by a rightward shift in the esophageal temperature threshold for the onset of both cutaneous vasodilation (37.37 ± 0.09 °C for cocaine vs. 37.06 ± 0.07 °C for lidocaine; P = 0.01) and sweating (37.38 ± 0.09 °C for cocaine vs. 37.07 ± 0.06 °C for lidocaine; P = 0.002). Third, cocaine paradoxically impaired the perception of heating by attenuating the progressive increase in thermal discomfort associated with heat stress.

Conclusions: In humans, impaired heat dissipation is a major mechanism by which cocaine elevates body temperature. When healthy, cocaine-naive persons are subjected to passive heating, pretreatment with even a small dose of intranasal cocaine impairs sweating and cutaneous vasodilation (the major autonomic adjustments to thermal stress) and heat perception (the key trigger for behavioral adjustments).

Editors' Notes Context The cause of hyperthermia in cocaine abuse is not well understood. Both excess heat generation and defective heat dissipation are potential causes of fatal hyperthermia. Contribution Nasal administration of cocaine causes greater increase in core body temperature, decrease in heat perception, and greater impairment of sweating and skin blood flow compared with nasal lidocaine administration. Implications Excessive heat production, impaired heat dissipation, and alteration of behavioral responses to increased body temperature may lead to fatal hyperthermia in cocaine abusers. –The Editors

 

Author and Article Information

From University of Texas Southwestern Medical Center and Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, Texas.

Grant Support: By the National Institutes of Health (HL-61388) (Dr. Crandall); the American Heart Association, Texas Affiliate (0060010Y) (Dr. Vongpatanasin); and the National Institute on Drug Abuse (RO-1 DA10064) (Dr. Victor).

Requests for Single Reprints: Craig G. Crandall, PhD, Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Avenue, Dallas, TX 75231; e-mail, CraigCrandall{at}texashealth.org.

Potential Financial Conflicts of Interest: None disclosed.

Current Author Addresses: Dr. Crandall: Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Avenue, Dallas, TX 75231.

Drs. Vongpatanasin and Victor: Divisions of Hypertension and Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, J4.134, Dallas, TX 75390-8586.

Author Contributions: Conception and design: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Analysis and interpretation of the data: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Drafting of the article: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Critical revision of the article for important intellectual content: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Final approval of the article: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Provision of study materials or patients: C.G. Crandall, W. Vongpatanasin.

Statistical expertise: C.G. Crandall.

Obtaining of funding: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Administrative, technical, or logistic support: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

Collection and assembly of data: C.G. Crandall.