Acute pain occurs as a result of tissue damage either accidentally due to an injury or as a result of surgery. Acute postoperative pain is a manifestation of inflammation due to tissue injury. The management of postoperative pain and inflammation is a critical component of patient care. This is one of a series of reviews whose aim is to increase awareness of the range of analgesics that are potentially available, and present evidence for relative analgesic efficacy through indirect comparisons with placebo, in very similar trials performed in a standard manner, with very similar outcomes, and over the same duration. Such relative analgesic efficacy does not in itself determine choice of drug for any situation or patient, but guides policy‐making at the local level. Recently published reviews include paracetamol (Toms 2008), celecoxib (Derry 2008), naproxen (Derry C 2009a), ibuprofen (Derry C 2009b), diclofenac (Derry P 2009) and etoricoxib (Clarke 2009).

Single dose trials in acute pain are commonly short in duration, rarely lasting longer than 12 hours. The numbers of participants are small, allowing no reliable conclusions to be drawn about safety. To show that the analgesic is working it is necessary to use placebo (McQuay 2005). There are clear ethical considerations in doing this. These ethical considerations are answered by using acute pain situations where the pain is expected to go away, and by providing additional analgesia, commonly called rescue analgesia, if the pain has not diminished after about an hour. This is reasonable, because not all participants given an analgesic will have significant pain relief. Approximately 18% of participants given placebo will have significant pain relief (Moore 2005), and up to 50% may have inadequate analgesia with active medicines. The use of additional or rescue analgesia is hence important for all participants in the trials.

Clinical trials measuring the efficacy of analgesics in acute pain have been standardised over many years. Trials have to be randomised and double blind. Typically, in the first few hours or days after an operation, patients develop pain that is moderate to severe in intensity, and will then be given the test analgesic or placebo. Pain is measured using standard pain intensity scales immediately before the intervention, and then using pain intensity and pain relief scales over the following 4 to 6 hours for shorter acting drugs, and up to 12 or 24 hours for longer acting drugs. Pain relief of half the maximum possible pain relief or better (at least 50% pain relief) is typically regarded as a clinically useful outcome. For patients given rescue medication it is usual for no additional pain measurements to be made, and for all subsequent measures to be recorded as initial pain intensity or baseline (zero) pain relief (baseline observation carried forward). This process ensures that analgesia from the rescue medication is not wrongly ascribed to the test intervention. In some trials the last observation is carried forward, which gives an inflated response for the test intervention compared to placebo, but the effect has been shown to be negligible over 4 to 6 hours (Moore 2005). Patients usually remain in the hospital or clinic for at least the first 6 hours following the intervention, with measurements supervised, although they may then be allowed home to make their own measurements in trials of longer duration.

Codeine is an opioid. Its analgesic effects are attributed to its metabolism in the liver to the active compounds morphine and codeine‐6‐glucuronide. Normally between 5% and 10% is converted to morphine, and a dose of about 30 mg codeine phosphate is considered equivalent to 3 mg morphine. The capacity to metabolise codeine to its active metabolites varies between individuals, however, with up to 10% of Caucasians, 2% of Asians and 1% of Arabs being "poor metabolizers". In these individuals codeine is a relatively ineffective analgesic. A few individuals are "extensive metabolizers" and are able to convert more of the codeine to morphine, putting them at increased risk of toxicity from standard doses. Various medications interfere with the enzymes that catalyse the metabolism of codeine, increasing or decreasing the extent of conversion and hence the analgesic effect. For example, the selective serotonin reuptake inhibitors fluoxetine and paroxetine reduce conversion, while rifampicin and dexamethasone increase it.

As with other opioids, repeated administration of codeine can cause dependence and tolerance, but long term use, or use of high doses, tends to be limited by adverse effects, in particular constipation and drowsiness. In severe or persistent pain, or both, for which large amounts of codeine are required, smaller doses of stronger opioids are thought to be better tolerated. Respiratory depression is dose‐related and may have serious consequences in "extensive metabolizers" and the elderly.

Codeine is administered by mouth (as tablets or syrup) or intramuscular injection, and in some countries as suppositories. In many countries it is a controlled substance, but may be available in small quantities without prescription, in combination analgesics such as paracetamol plus codeine, and in cough syrups. In 2007 in England, there were almost 2.5 million prescriptions for codeine phosphate, mostly as 30 mg and 15 mg tablets, with many more for combination products (PCA 2007).