Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion

Repeated supratherapeutic ingestion of acetaminophen is potentially lethal but poorly described. We provide the first prospective description of the characteristics, course, and outcome of patients with repeated supratherapeutic ingestion of acetaminophen.

This was a prospective case series of consecutive patients aged 12 years and older with acetaminophen dosage greater than 4 g per 24 hours referred to our poison center. Acetylcysteine was recommended if serum acetaminophen level exceeded 10 mg/L or aspartate aminotransferase exceeded 50 IU/L. Acetaminophen dosage, demographic factors, treatment, and outcome were recorded using standardized methods. Minimum follow-up was 72 hours.

Of 277 patients eligible, 249 patients were enrolled. At presentation, serum aspartate aminotransferase levels less than 50 IU/L were found in 126 patients, aspartate aminotransferase levels of 50 to 1,000 IU/L were present in 47 patients, and aspartate aminotransferase levels were above 1,000 IU/L in 37 patients. No aspartate aminotransferase data were available for 39 patients. No patient with an aspartate aminotransferase level below 50 IU/L at presentation developed hepatotoxicity (aminotransferase >1,000 IU/L). Seven (15%) patients with aspartate aminotransferase levels of 50 to 1,000 IU/L at presentation subsequently developed hepatotoxicity; 1 patient died. Six (16%) patients with aspartate aminotransferase levels above 1,000 IU/L at presentation died or received liver transplants. Study limitations included recall bias, incomplete patient follow-up, and the assumption that absence of clinical signs indicated insignificant liver injury.

Our results suggest that the injury caused by acetaminophen repeated supratherapeutic ingestion is apparent at presentation and related to dose magnitude and duration. All patients who developed hepatotoxicity presented with aspartate aminotransferase above 50 IU/L. Determination of serum aspartate aminotransferase and acetaminophen concentrations may allow early discharge from the emergency department.