Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics.
BACKGROUND
Early onset acidosis from mitochondrial toxicity can be observed in massive acetaminophen poisoning prior to the development of hepatotoxicity. In this context, the efficacy of acetylcysteine to reverse mitochondrial toxicity remains unclear and hemodialysis may offer prompt correction of acidosis. Unfortunately, toxicokinetics of acetaminophen and acetylcysteine during extracorporeal treatments hemodialysis have seldom been described.


METHODS
An 18-year-old woman presented to the emergency department 60 minutes after ingestion of 100 g of acetaminophen, and unknown amounts of ibuprofen and ethanol. Initial assessment revealed an agitated patient. Her mental status worsened and she required intubation for airway protection. Investigations showed metabolic acidosis with lactate peaking at 8.6 mmol/L. Liver and coagulation profiles remained normal. Acetaminophen concentration peaked at 981 μg/ml (6496 μmol/L). Pending hemodialysis, the patient received 100 g of activated charcoal and an acetylcysteine infusion at 150 mg/kg over 1 hour, followed by 12.5 mg/kg/h for 4 hours. During hemodialysis, the infusion was maintained at 12.5 mg/kg/h to compensate for expected removal before it was decreased to 6.25 mg/kg for 20 hours after hemodialysis. The patient rapidly improved during hemodialysis and was discharged 48 hours post-admission.


METHODS
The acetaminophen elimination half-life was 5.2 hours prior to hemodialysis, 1.9-hours during hemodialysis and 3.6 hours post hemodialysis. The acetaminophen and acetylcysteine clearances by A-V gradient during hemodialysis were 160.4 ml/min and 190.3 ml/min, respectively. Hemodialysis removed a total of 20.6 g of acetaminophen and 17.9 g of acetylcysteine.


CONCLUSIONS
This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results suggest that the infusion rate of acetylcysteine must be more than double during hemodialysis to compensate for its ongoing removal and provide similar plasma concentrations to the usual acetylcysteine regimen.
a Nephrology Department , Verdun Hospital , Montréal , Québec , Canada ;
Marc
M
Ghannoum
b Department of Emergency Medicine, McGill University Health Centre , Montréal , Québec , Canada ;
Sara
S
Kazim
c Division of Medical Biochemistry, Department of Medicine , McGill University Health Centre , Montréal , Québec , Canada ;
Ami M
AM
Grunbaum
d Department of Pharmacy, McGill University Health Centre , Montréal , Québec , Canada ;
Eric
E
Villeneuve
b Department of Emergency Medicine, McGill University Health Centre , Montréal , Québec , Canada ;|e Centre Antipoison Du Québec , Montréal , Québec , Canada.
Sophie
S
Gosselin
D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000506:poisoning*; D000111:Acetylcysteine / Q000493:pharmacokinetics*; D000140:Acidosis, Lactic / Q000139:chemically induced / Q000628:therapy; D000293:Adolescent; D003128:Coma / Q000139:chemically induced / Q000628:therapy; D062787:Drug Overdose / Q000188:drug therapy*; D004636:Emergency Service, Hospital; D000431:Ethanol / Q000506:poisoning; D005260:Female; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000506:poisoning; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D006435:Renal Dialysis
D019344:Lactic Acid; D000082:Acetaminophen; D000431:Ethanol; D007052:Ibuprofen; D000111:Acetylcysteine
Dialysis; metabolic; paracetamol