Overdose with acetaminophen is more deadly divided over a day than all at once
Summary: great care must be taken to avoid overdose when using acetaminophen (Tylenol®, Paracetamol®), especially for pain relief. Doses staggered over a day are more harmful than downing the whole amount at once.Acetaminophen overdose is a leading cause of severe liver injury. It might seem that more than 4000 mg of acetaminophen taken all at once would be more toxic than the same amount divided over the course of a day, but a paper just published in the British Journal of Clinical Pharmacology presents evidence that the opposite is true. The authors state:
"Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose."
They investigated the cases of 663 patients admitted to hospital with acetaminophen-induced severe liver injury between 1992 and 2008. 161 of them (24.3%) had taken a staggered overdose, most commonly for relief of pain. These tragic events led to a compelling observation:
"Despite lower total ingested paracetamol doses, and lower admission serum alanine aminotransferase levels, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation, and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%)..."
In other words, spacing out the dosage of Tylenol® is not only an ineffective strategy for avoiding overdose, it is more likely to lead to liver failure, kidney failure and death. Additionally, going to the hospital more than 24 hours after ingestion of a single time overdose was associated with worse outcomes. What is the first-line therapy for acetaminophen overdose?
"Patients presenting with these overdose patterns should be treated as high-risk for progression to acute liver failure, and should receive N-acetyl cysteine in their presenting hospital whilst awaiting serial alanine aminotransferase (ALT) and prothrombin time levels."
Over-the-counter pain medication, including both non-steroidal antiinflammatory drugs (NSAIDs) and acetaminophen, can do severe harm and must be handled with respect. My practice has included patients whose autoimmune disease was triggered or aggravated by the effect of too enthusiastic NSAID use on the intestinal epithelial lining that functions as a barrier between the intestinal contents and the immune lymphoid tissue. The authors conclude:
"Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multiorgan failure and should be considered for early transfer to specialist liver centres."