title: Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study.
abstract: BACKGROUND
  Although the King's College Hospital (KCH) selection criteria for emergency liver transplantation in paracetamol-induced acute liver failure are widely used, strategies to improve sensitivity and facilitate earlier transplantation are required. We investigated the use of arterial blood lactate measurement for the identification of transplantation candidates.
  
  
  METHODS
  In a single-centre study, we measured arterial blood lactate early (median 4 h) and after fluid resuscitation (median 12 h) in patients admitted to a tertiary-referral intensive-care unit. Threshold values that best identified individuals likely to die without transplantation were derived in a retrospective initial sample of 103 patients with paracetamol-induced acute liver failure and applied to a prospective validation sample of 107 patients. Predictive value and speed of identification were compared with those of KCH criteria.
  
  
  RESULTS
  In the initial sample, median lactate was significantly higher in non-surviving patients than in survivors both in the early samples (8.5 [range 1.7--21.0] vs 1.4 [0.53--7.9] mmol/L, p<0.0001) and after fluid resuscitation (5.5 [1.3--18.6] vs 1.3 [0.26--3.2], p<0.0001). Applied to the validation sample, a threshold value of 3.5 mmol/L early after admission had sensitivity 67%, specificity 95%, positive likelihood ratio 13, and negative likelihood ratio 0.35; the corresponding values for a threshold of 3.0 mmol/L after fluid resuscitation were 76%, 97%, 30, and 0.24. Combined early and postresuscitation lactate concentrations had similar predictive ability to KCH criteria but identified non-surviving patients earlier (4 [3--13] vs 10 [3.5--19.5] h, p=0.01). Addition of postresuscitation lactate concentration to KCH criteria increased sensitivity from 76% to 91% and lowered negative likelihood ratio from 0.25 to 0.10.
  
  
  CONCLUSIONS
  Arterial blood lactate measurement rapidly and accurately identifies patients who will die from paracetamol-induced acute liver failure. Its use could improve the speed and accuracy of selection of appropriate candidates for transplantation.
authors.affiliation: Institute of Liver Studies, King's College Hospital, Guy's, King's, and St Thomas's School of Medicine, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Nora
authors.initials: N
authors.lastname: Donaldson
authors.forename: Duncan
authors.initials: D
authors.lastname: Wyncoll
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007773:Lactates / Q000097:blood*; D017114:Liver Failure, Acute / Q000097:blood* / Q000139:chemically induced / Q000401:mortality; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D018712:Analgesics, Non-Narcotic; D007773:Lactates; D000082:Acetaminophen