Comparing single doses of oral analgesics for acute pain in adults postoperation

All analgesic drugs (painkillers) are tested in standardised clinical studies of people with established pain following surgery, and often after removal of third molar (wisdom) teeth. In all these studies the participants have to have at least moderate pain in order for there to be a sensitive measure of pain-relieving properties. The Cochrane Library has 35 reviews of oral analgesic interventions, with 38 different drugs, at various doses involving 45,000 participants in about 350 studies. This overview sought to bring all this information together, and to report the results for those drugs with reliable evidence about how well they work or any harm they may do in single oral doses.

For some drugs there were no published trials, for some inadequate amounts of information, and for some adequate information but with results that would have been overturned by just a few unpublished studies with no effect. None of these could be regarded as reliable. However, amongst the data there were still 46 drug/dose combinations with reliable evidence.

No drug produced high levels of pain relief in all participants. The range of results with single-dose analgesics in participants with moderate or severe acute pain was from 70% achieving good pain relief with the best drug to about 30% with the worst drug. The period over which pain was relieved also varied, from about two hours to about 20 hours. Typically adverse event rates were no higher with analgesic drugs than with placebo, except often with opioids (for example, codeine, oxycodone) where more participants experienced them.

Commonly used analgesic drugs at the recommended or licensed doses produce good pain relief in some, but not all, patients with pain. The reasons for this are varied, but patients in pain should not be surprised if drugs they are given do not work for them. Alternatives analgesic drugs or procedures should be found that do work.

Authors' conclusions: 

There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

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Background: 

Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data.

Objectives: 

To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone.

Main results: 

The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.

There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions.

NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids.

Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg.

Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours.