Eighteen patients with acetaminophen poisoning were studied with magnetic resonance spec- troscopy to measure phosphorus-containing metabolites in their livers. The concentrations of all magnetic resonancdetectable metabolites fell in parallel with a decrease in the synthetic ability of the liver, indicated by the prothrombin time ratio (international normalized ratio). In particular, ATP fell to about 20% of its normal concentration in severely affected patients, as did the phosphodiester signal, which is thought to arise mainly from the endoplasmic reticulum i n the liver. The correlation between ATP levels and international normalized ratio suggests that the international normalized ratio is a more accurate measure of the number of viable hepatocytes than are other biochemical tests. (HEPATOLOGY 1992; 16:943-948.)
Self-poisoning with acetaminophen (paru-acetaminophenol) accounts for many emergency medical hospital admissions. Liver damage after acetaminophen ingestion can lead to death by fulminant liver failure; indeed, of 588 patients admitted to King's College Hospital with acute liver failure between 1976 and 1985, 53% had acetaminophen poisoning. Of these, 34% later died (1).
Acetaminophen is mainly metabolized in the liver, where 60% to 90% of therapeutic doses are glucuronidated or sulfated before being excreted by the kidneys (2). Only 1% to 4% of the drug is excreted unchanged in the urine. The remainder is oxidized by cytochrome P-45Mependent mixed-function oxidases to N-acetyl p-benzoquinoneimine (NAPQI). Overdoses cause cell damage through increased oxidation of the drug as the conjugation pathways are saturated. NAPQI is highly reactive but can be trapped by conjugation with