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British Journal of Anaesthesia, 2003, Vol. 91, No. 3 357-362
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia

Clinical Investigations

Propacetamol augments inhibition of platelet function by diclofenac in volunteers

E. Munsterhjelm*,1, T. T. Niemi1, M. T. Syrjälä2, O. Ylikorkala3 and P. H. Rosenberg1

1 Department of Anaesthesiology and Intensive Care Medicine, 2 Department of Clinical Chemistry and 3 Department of Obstetrics and Gynaecology, Helsinki University Hospital, Finland

Corresponding author: PO Box 340 (P-floor), FIN-00029 HUS, Finland. E-mail: edward.munsterhjelm@hus.fi

Background. Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects.

Methods. Ten healthy male volunteers (21–30 yr) were given diclofenac 1.1 mg kg–1 alone, a combination of propacetamol 30 mg kg–1 (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg–1 or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22–24 h by photometric aggregometry, platelet function analyser (PFA-100TM) and by measuring the release of thromboxane B2 (TxB2). Analgesia was assessed with the cold pressor test.

Results. Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22–24 h, platelet function had fully recovered. TxB2 release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100TM detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test.

Conclusions. The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.

Br J Anaesth 2003; 91: 357–62


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