Poisonings with Paracetamol: Improving Understanding to Guide Medication Safety Initiatives

Abstract

Paracetamol poisoning is a leading cause of acute liver failure in developed countries and a leading substance reported in calls to Australian Poisons Information Centres (PICs). Paracetamol poisoning is often intentional and higher doses taken in these poisonings carry a greater risk of severe liver injury. However, liver injury and death can also occur from unintentional poisonings. This thesis aims to characterise the nature of paracetamol poisoning in Australia using data from PICs and hospital admissions (with data linkage).

Chapter 1 - Introduction on Australian paracetamol access, Australian PICs and data linkage.

Chapter 2 - Narrative literature review encompassing paracetamol toxicity, treatments, prevention measures and an estimate of global burden from paracetamol poisoning. We estimated that paracetamol was involved in 6% of poisonings worldwide, 56% of severe acute liver injury and acute liver failure and 7% of drug-induced liver injury.

Chapter 3 - Study focusing on therapeutic (dosing) errors with paracetamol in Australians aged ≥12 years old reported to Australia’s largest PIC. Our analysis found that exposures requiring hospitalisation were associated with paracetamol use for dental pain and that these individuals used paracetamol at greater doses for longer durations.

Chapter 4 - Study focusing on therapeutic (dosing) errors with paracetamol in Australians aged <12 years old reported to Australia’s largest PIC. Our analysis found that high strength liquid dosage forms were frequently implicated however exposures in children were unlikely to cause severe outcomes such as liver injury and death.

Chapter 5 - Data linkage study of hospitalised cases of paracetamol poisoning that explores poisoning intent, patient demographics and outcomes. Our analysis found that intentional poisonings had the lowest rates of liver injury compared to other types of poisoning but had a high risk of repeated poisoning and eventual death during the follow up period.