Weight loss and 2,4-dinitrophenol poisoning

Editor—There are only a few cases in the literature of 2,4-dinitrophenol (DNP) poisoning in adults resulting in death.¹ We describe the first case of multiorgan failure and widespread rigidity secondary to DNP poisoning 8 h after presentation.

The prevalence of non-prescription weight loss measures is increasing.² The internet is commonly being used as a low cost alternative of acquiring advice and prescriptions. DNP (C₆H₄N₂O₅) first gained popularity for weight loss in the 1930s with studies showing that a daily dose of 300–400 mg for 2 weeks resulted in 36–95% increase in an individual's basal metabolic rate.³ It was soon taken off the market due to adverse effects including cataracts, liver failure, agranulocytosis, and death. DNP has also been used as a herbicide and also as a photographic developing chemical. Its use has now resurfaced via the internet.

A 27-yr-old lady was admitted to accident and emergency complaining of fatigue, nausea, and excessive sweating. She admitted to starting a new diet tablet (bought over the internet) a week before her admission. She had doubled the recommended dose for faster results. Past medical history was negative. She was a non-smoker, non-drinker, and had no known allergies. Initial examination revealed an agitated overweight female (BMI 33) with a GCS of 15. Her airway was clear, respiratory rate (RR) 60, oxygen saturation 100% (Fi_o2 40%), blood pressure (BP) 122/86, and heart rate 140 beats min⁻¹. Temperature was 38°C. There were no other significant clinical findings.

Toxbase was consulted and she received 2 litre of normal saline i.v. over 2 h and diazepam 35 mg orally. Initial arterial blood gas revealed pH 7.46, Pco₂ 3.9 kPa, Po₂ 13.2 kPa, and base excess (BE) of −5.0. Initial laboratory results including full blood count, electrolytes, amylase, and liver function tests were normal. Creatinine kinase level was 1042. The patient had a further litre of normal saline i.v. over 2 h and 2 mg lorazepam i.v. The intensive care unit was informed. Six hours after admission, GCS was 14 (eyes opening to command), RR 44, BP 146/110, heart rate 150 beats min⁻¹, and temperature of 38°C. Her urine output over 5 h was 146 ml. Repeat arterial blood gas showed pH 7.46, Pco₂ 2.36 kPa, Po₂ 13.8 kPa, BE −11.8, and bicarbonate 16.8. An hour later, she desaturated to <90% and became asystolic. Cardiopulmonary resuscitation was started. Despite suxamethonium 100 mg and vecuronium 10 mg (i.v.), it was not possible to ventilate her due to widespread sustained muscle rigidity. After 14 cycles with epinephrine and atropine, she remained asystolic and was declared dead.

DNP causes a hyper-metabolic state by uncoupling oxidative phosphorylation. Energy is released in the mitochondria as heat. The body attempts to compensate by gluconeogenesis, glycolysis, and lipolysis. Toxic doses will result in uncontrolled thermogenesis leading to hyperthermia and systemic responses to elevated body temperature.⁴ Profuse yellow-tinted perspiration may be observed and is pathonomonic of DNP poisoning. Renal, hepatic, and neurological sequelae can occur. In cases of severe toxicity, death may be followed by prompt rigor mortis.

Management involves aggressive supportive measures and use of benzodiazepines, but because of a large volume of distribution, DNP is not amenable to dialysis or haemoperfusion.⁵ It uncouples oxidative phosphorylation, causing release of calcium from mitochondrial stores. Raised free intracellular calcium causes muscle contraction and hyperthermia. Successful use of dantrolene has been described.⁶ By inhibiting calcium release from the sarcoplasmic reticulum, dantrolene reduces intracellular calcium. This is thought to help to facilitate heat dissipation in uncontrolled DNP-related hyperthermia. We stress importance of early aggressive supportive care and level 2 involvement in cases of DNP poisoning. We also propose the early use of dantrolene.