title: Antidote removal during haemodialysis for massive acetaminophen overdose.
abstract: BACKGROUND
  Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of "mitochondrial paralysis" (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases.
  
  
  METHODS
  Three adults each presented comatose and acidemic 10 to ~18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 μM (900 μg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ~18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3-4 h of haemodialysis removed 10-20 g of acetaminophen (48-80% of remaining body burden), reduced serum acetaminophen concentrations by 56-84% (total clearance 3.4-7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure.
  
  
  CONCLUSIONS
  When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.
authors.affiliation: Department of Emergency Medicine, Queen's University , Kingston, ON , Canada.
authors.forename: M L A
authors.initials: ML
authors.lastname: Sivilotti
authors.forename: D N
authors.initials: DN
authors.lastname: Juurlink
authors.forename: J S
authors.initials: JS
authors.lastname: Garland
authors.forename: I
authors.initials: I
authors.lastname: Lenga
authors.forename: R
authors.initials: R
authors.lastname: Poley
authors.forename: L N
authors.initials: LN
authors.lastname: Hanly
authors.forename: M
authors.initials: M
authors.lastname: Thompson
mesh_terms: D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000140:Acidosis, Lactic / Q000209:etiology; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000931:Antidotes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003128:Coma / Q000209:etiology; D016903:Drug Monitoring; D062787:Drug Overdose / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D017093:Liver Failure / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine