Paracetamol overdose: relevance of recent evidence for managing patients in Sri Lanka.

Paracetamol poisoning is the commonest overdose recorded in high income countries [1-4]. In Sri Lanka paracetamol overdose has exponentially increased in urban and rural areas [5, 6]. It is responsible for 50% of admissions due to overdose in the National Hospital of Sri Lanka (National Poisons Information Center data), and on average two patients are admitted every day with paracetamol overdose [7]. In the Kurunegala district primary hospitals, paracetamol was responsible for 18% of overdose admissions in 2012 (South Asian Clinical Toxicology Research Collaboration cohort data). Paracetamol toxicity is mostly due to the toxic intermediate metabolite N-acetyl-p-benzoquinone imine (NAPQI) produced by cyctochrome P450 enzymes. This normally binds to sulfhydral groups in gluthathione to form non toxic metabolites. In overdose, gluthathione stores can become depleted and NAPQI binds to sulfhydral groups in other proteins causing hepatic and renal damage. Early administration of sulfhydral donor antidotes such as methionine or N-acetylcysteine (NAC) significantly reduces the risk of death or hepatic injury [8-10]. Risk factors for death includes late presentations (>8 hours), staggered overdoses or unintentional therapeutic excesses [3,11-14]. In 2012 Sri Lanka spent Rs 41 million on methionine and Rs 126 million for NAC, distributed to both urban and rural areas (Medical Supplies Division data). The international standard for risk assessment following a single ingestion of paracetamol is to plot the paracetamol concentration on a risk nomogram. As a small percentage of patients with paracetamol levels below the nomogram threshold develop some hepatic injury, current research seeks to define optimal treatment thresholds and dose and duration of antidotes [15, 16]. This article focuses on some recent developments and discusses the relevance of the new evidence for managing patients in Sri Lanka.