The administration of N-acetylcysteine causes a decrease in prothrombin time in patients with paracetamol overdose but without evidence of liver impairment.
OBJECTIVE
To explore the effect of intravenous N-acetylcysteine (NAC) on the prothrombin time (PT) in patients with paracetamol overdose and persistent normal liver profile.


METHODS
This retrospective case series study examined all admissions with a diagnosis of paracetamol poisoning in a tertiary hospital between 1989 and 2002. Patients were included if they had ever received NAC infusion, had no biochemical evidence of liver damage, and had more than two measurements of PT. Patients who had also ingested other drugs were excluded.


RESULTS
Of 65 admissions wtih paracetamol poisoning, 18 patients (10 men) met the inclusion criteria. The median age was 29 years, and the median quantity of paracetamol ingested was 186 mg/kg. The mean number of PT measurements per patient was 4.8. The baseline PT (as a percentage) 8.6 h after paracetamol ingestion was 89.6%. During NAC infusion the PT fell in all patients (range, 4.8-53.4% relative to baseline; P < 0.0001) at 14 h. The PT was less than 60% in 28% of the patients. Eight hours after the initiation of NAC there was a 16% fall in PT (range, 4.3-34%; P < 0.0001). At the end of NAC infusion all PTs returned to values close to baseline. Nine patients were hospitalized.


CONCLUSIONS
In patients with paracetamol overdose without evidence of liver damage a marked decrease in PT often occurs, which seems to be due to the overload of NAC infused at the beginning of treatment. This particular feature should be noted in clinical practice guidelines as a potentially misleading indicator of the development of severe liver dysfunction.
Lucena
M Isabel
MI
Clinical Pharmacology Service, Hospital Universitario, School of Medicine, University of Málaga, Málaga, Spain. Lucena@uma.es
López-Torres
Enrique
E
Verge
Carmen
C
Andrade
Raúl J
RJ
Puche
M José
MJ
Seoane
Julia
J
de la Cuesta
Felipe Sánchez
FS
D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000506:poisoning; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D062787:Drug Overdose / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008297:Male; D011379:Prognosis; D011517:Prothrombin Time; D012189:Retrospective Studies
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000082:Acetaminophen; D000111:Acetylcysteine