Paracetamol in critical illness: a review

Background: Paracetamol is one of the commonest medications used worldwide. This review was conceived as a consequence of evaluating the literature in the protocol development of two randomised, controlled clinical trials investigating the safety and efficacy of paracetamol in ICU patients (the HEAT [Permissive HyperthErmiA Through Avoidance of Paracetamol in Known or Suspected Infection in the Intensive Care Unit] study; the Paracetamol After traumatic Brain Injury [PARITY] Study). Objective: To provide a historical perspective on the introduction of paracetamol into clinical practice, to present the pharmacology of paracetamol in critical illness, and evaluate the current evidence for its use as an antipyretic and analgesic in intensive care. Design: Literature searches were performed using keywords: "paracetamol", "acetaminophen", "critical illness", "intensive care", "history", "pharmacology", "antipyre*", "analgesi*", "adverse effect*", "administration and dosage", "toxicity", "animals" and "humans". Data sources: Embase, MEDLINE, PubMed (1947/1950 to July 2011). Review methods: The authors examined each article's title and abstract, fully reviewing relevant articles, with searching of reference lists and additional hand-searching. The most recent and highest quality available evidence was included. Results: Limited data are available on the pharmacology of paracetamol in the critically ill. Among patients with sepsis, paracetamol may inhibit the immunological response. Among patients with neurological injury paracetamol can reduce temperature but appears not to improve outcome. When administered with opioids after major surgery, paracetamol does not reduce the incidence of pain or opioidrelated side-effects. Conclusion: Despite the widespread use of paracetamol in critical illness, there is a paucity of data supporting its utility in this setting. Further research is required to determine how paracetamol should be used in the critically ill.