Hemodialysis for Acetaminophen Detoxification

Abstract

The effect of an artificial kidney on the removal of acetaminophen and its metabolites (glucuronide and sulfate) was investigated in six chronic hemodialysis patients. Acetaminophen 650 mg was given orally 2 h prior to hemodialysis. Plasma and dialysate samples were collected periodically over 3 h and analyzed by hplc for acetaminophen content. Dialysis clearance was calculated by arterial-venous difference and simultaneous dialysate measurement. The extraction efficiency of the hollow-fiber dialyzers averaged 47.5 and 43% for the parent compound and the total metabolites, respectively. The mean dialysis clearance of 112 mL/min for acetaminophen measured with blood as the body fluid of reference was confirmed by calculation of clearance using dialysate measurement. A comparable dialysis clearance value of 105.8 mL/min was obtained for the total metabolites. A mean of 70.5 mg of acetaminophen of 11% of the administered dose was removed during the 3-h dialysis period. However, the total metabolites were removed at a much faster rate of 374.7 mg/3 h or approximately 58% of the administered dose. The beta phase had a mean half-life of 1.6 h in our patients on hemodialysis compared with 2.0 h reported for both normal patients and uremic patients. Despite the favorable extraction ratio and dialyzer clearance, the artificial kidney is not very effective in competing with the liver for removal of the parent compound acetaminophen because of the drug's short half-life and rapid hepatic metabolism. Hence the chronic hemodialysis patient may not need a dosage adjustment during or following hemodialysis. However, hemodialysis may have a significant application to acetaminophen overdose because of its effectiveness in removing the total metabolites.