Letter To The Editor: “Comment on “Pediatric Fatality Following Ingestion of Dinitrophenol: Postmortem Identification of a ‘Dietary Supplement’””

To the Editor:

Hsiao et al. reported a pediatric fatality following Dintrophenol overdose (1). The patient developed hyperthermia and was treated with antipyretics, tepid water compresses, and fans. Despite these measures, her body temperature continued to rise to >40°C (>104°F). Mental status declined and she was intubated for airway protection. Five minutes after intubation, the patient developed ventricular tachycardia which rapidly progressed to asystole. She was unable to be resuscitated. Since hyperthermia is frequently reported in dinitrophenol fatalities, effective treatment of hyperthermia may improve patient outcome. Intubation of a patient that has ingested an agent that uncouples oxidative phosphorylation may also affect the outcome. Agents that uncouple oxidative phosphorylation increase the respiratory rate in an attempt to remove increased cellular carbon dioxide. Intubation and fixed (ventilated) respiratory rate may prevent removal of cellular carbon dioxide causing acidosis, cellular death and increased mortality.

We previously reported a patient with dinitrophenol-induced hyperthermia, which improved following dantrolene administration (2). The patient was a thirty year-old male who presented to an emergency department with diaphoresis, beet red skin, and yellow sclera. He initially denied ingestion of any toxic substance, but it was subsequently learned that he was taking dinitophenol for weight loss and body building. While in the emergency department, his mental status deteriorated and he was intubated. His body temperature rose to 108 °F (42.2°C). Cooling blankets, fans, and tepid water soaks decreased his temperature to 104°F (40°). However, within 20 minutes of the administration of dantrolene, his body temperature decreased to 100.8°F (38.2°C). Dantrolene was repeatedly administered over the next 12 hours to maintain body temperature below 100.4°F (38°C). Over the next 12 days he developed rhabdomyolysis and renal failure which resolved. He was extubated on day twelve. He had no known permanent sequelae from the overdose and was discharged from the hospital.

Studies have not found a benefit from administration of dantrolene to treat hyperthermia caused by heatstroke, cocaine, or amphetamines. However the underlying etiology of the hyperthermia may determine if dantrolene administration will decrease temperature. Dinitrophenol uncouples oxidative phosphorylation, causes release of calcium from mitochondrial stores and prevents calcium re-uptake (3). This leads to free intracellular calcium and causes muscle contraction and hyperthermia. Dantrolene inhibits calcium release from the sarcoplasmic reticulum which reduces intracellular calcium. The resulting muscle relaxation allows heat dissipation (4).

There is little risk to dantrolene administration. Since dantrolene may be effective in reducing hyperthermia caused by agents that inhibit oxidative phosphorylation, early administration may improve outcome.