Effect of 3 g of intravenous paracetamol on post-operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia.
BACKGROUND
Paracetamol 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.


METHODS
One 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.


RESULTS
During 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.


CONCLUSIONS
During 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.
Silvanto
M
M
Research Institute of Military Medicine, Helsinki, Finland. martti.silvanto@hus.fi
Munsterhjelm
E
E
Savolainen
S
S
Tiainen
P
P
Niemi
T
T
Ylikorkala
O
O
Scheinin
H
H
Olkkola
K T
KT
D000082:Acetaminophen / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000494:pharmacology; D000772:Anesthesia, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004008:Diclofenac / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005982:Glutathione Transferase / Q000097:blood; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000517:prevention & control*; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014068:Tonsillectomy
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D000082:Acetaminophen; D013929:Thromboxane B2; D005982:Glutathione Transferase