Results. Eight studies compared rectal paracetamol with placebo. ... combination of an NSAID and paracetamol showed improved pain relief for the combination.
British Journal of Anaesthesia 88 (2): 215±26 (2002)
Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia J. Rùmsing1*, S. Mùiniche2 and J. B. Dahl2 1
Department of Pharmaceutics, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen, Denmark. 2Department of Anaesthesiology, Herlev University Hospital, Herlev, Denmark. *Corresponding author Background. We have reviewed the analgesic ef®cacies of rectal and parenteral paracetamol and tested the evidence for a possible additive analgesic effect of the combination of paracetamol with a non-steroidal anti-in¯ammatory drug (NSAID) in postoperative pain. Methods. Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia. Results. Eight studies compared rectal paracetamol with placebo. One study of single-dose administration of rectal paracetamol 40±60 mg kg±1 and three studies of repeat dosing with 14±20 mg kg±1 showed signi®cant analgesic ef®cacy, while studies of a single dose of 10±20 mg kg±1 were negative. Ten studies compared parenteral paracetamol with placebo and eight studies showed improved pain relief with paracetamol. Of the nine studies comparing paracetamol with a combination of paracetamol and an NSAID, six studies showed improved pain relief for the combination while only two of the six studies comparing an NSAID with a combination of an NSAID and paracetamol showed improved pain relief for the combination. Conclusions. Considering the few studies available, evidence was found of a clinically relevant analgesic effect of rectal and parenteral paracetamol. Concurrent use of paracetamol and an NSAID was superior to paracetamol alone but no evidence was found of superior analgesic effect of the combination compared with the NSAID alone. Br J Anaesth 2002; 88: 215±26 Keywords: analgesics non-opioid, paracetamol; analgesics anti-in¯ammatory, non-steroidal; pain, postoperative; anaesthesia, audit Accepted for publication: June 12, 2001
Paracetamol is frequently used as a non-opioid analgesic in postoperative pain. Its mechanism of action is not fully understood, but it is generally accepted that paracetamol is a centrally acting drug.1 2 The analgesic effect of paracetamol is probably dependent on the rate and amount of active drug reaching the CNS, where its analgesic effect takes place.3 Paracetamol is available as oral, rectal and injectable formulations. Reports of analgesic ef®cacy and adverse effects of oral paracetamol have been the subject of recent systematic reviews,4±8 but evidence-based estimates of clinical analgesic effects of rectal and parenteral paracetamol in postoperative pain are not available. When pain relief is insuf®cient with paracetamol alone, a non-steroidal anti-in¯ammatory drug (NSAID) may be added in combination. NSAIDs inhibit prostaglandin synthesis in peripheral tissues. Some suggest a peripheral±
central synergistic action of NSAIDs that varies depending on the particular NSAID and on the presence of an in¯ammatory process.9 Concomitant administration of two analgesics with presumably different mechanisms of action may be more effective than the use of either drug alone and may reduce the need for supplementary analgesics after surgery. The combination of paracetamol and NSAIDs is widely used clinically, but consensus on whether such a combination offers a clinically relevant improvement in analgesia is still lacking. The aim of this systematic review was, ®rst, to review the analgesic ef®cacy of rectally or parenterally administered paracetamol for postoperative pain relief, and secondly to test the evidence for a possible additive analgesic effect of the combination of paracetamol and an NSAID compared with either drug alone in postoperative pain.
Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2002
Rùmsing et al. Table 1 Comparisons of rectal paracetamol with placebo and different doses of paracetamol. P
