Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate

Abstract

There has been a resurgence in the use of 2,4-dinitrophenol, C6H4N2O5 (DNP) recently as an illegal weight loss drug. We present a case of a healthy 25-year-old girl who took two tablets of DNP, purchased from an overseas online retailer. She was managed with aggressive, invasive cooling measures and 2.5 mg kg–1 dantrolene. Despite this, her temperature continued to rise exponentially to 41.5°C. Cardiac arrest occurred and resuscitation was unsuccessful. To our knowledge, this is the first reported case of the ineffective use of dantrolene in acute DNP poisoning. We review the pathophysiology of DNP toxicity and argue that the use of dantrolene therapy is biochemically implausible, based on poor evidence and likely to be futile. We have contacted the UK National Poisons Information Service (NPIS/TOXBASE) to propose changes to the management of acute DNP toxicity.

Intoxicación letal por dinitrofenol

“…Se ha rerportado el caso de una paciente que sobrevivió sólo con el manejo de soporte y dantroleno, este último actúa disminuyendo la liberación de calcio del retículo sarcoplásmico, y en esta intoxicación hay un aumento de calcio intracelular que provoca la hipertonía y agrava la hipertermia, por lo que se ha sugerido su uso, aunque es controversial. [33][34][35][36] Hasta ahora se habían visto intoxicaciones por anfetaminas, hormona tiroidea y diuréticos en pacientes que intentan bajar de peso, este es el primer caso de intoxicación por DNF reportado en el país. En conclusión, deberíamos sospechar intoxicación por dinitrofenol en cualquier paciente que ha ingerido productos para perder peso y que acude con signos que indiquen desacople de la fosforilación oxidativa, como hipertermia, taquicardia, taquipnea, sudoración e hipertonía.…”

Analysis of 2,4‐Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography–Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States

“…2,4-DNP is also used as a pesticide in the agriculture industry, resulting in some occupational intoxications (2,15). However, its use for weight loss has been more frequently reported in medical literature in the past few years (3,5,6,12,19).…”

“…A recent study reported that in 14.3% of bodybuilding supplements tested, 2,4-DNP was present as contaminant or adulterant, and around 44% of the products being sold on the internet were contaminated with 2,4-DNP (17). The attractiveness of 2,4-DNP as a fast and effective weight-loss drug, online marketing, media reports of its effectiveness and dangerousness, and its availability on the internet has resulted in increased reports of 2,4-DNP intoxications and deaths (2,18,19). Laboratory confirmation of the ingestion of this chemical is frequently requested, but it is typically not detected in routine drug screening methodologies.…”

Drug-induced Hyperthermic Syndromes in Psychiatry

“…Dintrophenol can cause an MH-like syndrome with severe hyperthermia, rigidity, rhabdomyolysis, acidosis, and abnormal vital signs leading to multiple organ failure and death [ 63 , 64 ]. In addition to intensive care, dantrolene has been recommended as a treatment though evidence is conflicting [ 65 , 66 ].…”