title: Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.
abstract: Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure.
authors.affiliation: Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, Great Maze Pond, London, UK. anoop.shah@gstt.nhs.uk
authors.forename: Anoop D
authors.initials: AD
authors.lastname: Shah
authors.forename: David M
authors.initials: DM
authors.lastname: Wood
authors.forename: Paul I
authors.initials: PI
authors.lastname: Dargan
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000628:therapy; D062787:Drug Overdose; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008297:Male; D011379:Prognosis
chemical_list: D000082:Acetaminophen