• M Silvanto, E Munsterhjelm, S Savolainen, P Tiainen, T Niemi, O Ylikorkala, H Scheinin, and K T Olkkola.
• Research Institute of Military Medicine, Helsinki, Finland. martti.silvanto@hus.fi
• Acta Anaesthesiol Scand. 2007 Oct 1;51(9):1147-54.

BackgroundParacetamol is often given as an adjunctive analgesic to reduce opioid-related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3-g intravenous (i.v.) dose of paracetamol in adults.MethodsOne hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post-operative morphine using a patient-controlled analgesia-device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1-1 (GSTA1-1) and thromboxane B(2) were measured.ResultsDuring the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6-h cumulative consumption of morphine in patients given paracetamol (18.7 +/- 13.8 mg), diclofenac (16.1 +/- 9.9 mg) and placebo (22.0 +/- 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B(2) at 1 h but they did not affect serum aminotransferase and GSTA1-1 levels. One patient given paracetamol displayed a transient increase in GSTA1-1 and liver aminotransferases.ConclusionDuring the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B(2) from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.

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