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Anesth Analg 2000;90:431
© 2000 International Anesthesia Research Society

REGIONAL ANESTHESIA AND PAIN MANAGEMENT

The Pharmacokinetics and Analgesic Efficacy of Larger Dose Rectal Acetaminophen (40 mg/kg) in Adults: A Double-Blinded, Randomized Study

Dieter H. Beck, MD, DEAA, EDIC, DA, DTM&H, Michael R. Schenk, MD, Kerstin Hagemann, Ulrich R. Doepfmer, MD, FRCA, DEAA, and Wolfgang J. Kox, MD, PhD, FRCP

Department of Anesthesiology and Intensive Care Medicine, Charité University Hospital, Humboldt University, Berlin, Germany

Address correspondence and reprint requests to Dieter H. Beck, MD, Charité Klinik für Anaesthesiologie und Operative Intensivmedizin, Schumannstrasse 20-21, D-10117 Berlin, Germany.

Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg · kg-1) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10–20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.

Implications: Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2000 by the International Anesthesia Research Society.