Oral codeine in acute postoperative pain

Clinical bottom line:

Codeine 60 mg orally is not an effective analgesic for postoperative pain.

A 60 mg oral dose of codeine had an NNT of 16.7 (11-48) for at least 50% pain relief over 4 to 6 hours compared with placebo in pain of moderate to severe intensity.

Oral codeine in postoperative pain

Codeine is an opium alkaloid, with activity similar to, but weaker than morphine. It is also widely available in combination with aspirin or paracetamol.

Systematic review

Moore RA, McQuay HJ. Single-patient data meta-analysis of 3453 postoperative patients: Oral tramadol versus placebo, codeine and combination analgesics. Pain 1997; 69:287-294.

Date review completed: 1995
Number of trials included: 17
Number of patients: 1305 (649 codeine/656 placebo)
Control group: oral placebo
Main outcomes: pain relief at 6 hours (TOTPAR), Number-needed-to-treat (NNT) (with 95% confidence intervals) and relative benefit with 95% confidence intervals).

Inclusion criteria were single oral dose, randomised, placebo-controlled, double-blind trials of codeine in acute postoperative pain with sufficient data to calculate the area under the curve for pain relief (TOTPAR). Baseline pain was moderate to severe. The 6 hour TOTPAR was calculated for each patient, and the data were converted to the percent of maximum total pain relief from categorical pain scales (%maxTOTPAR), and then to dichotomous information to generate a number-needed-to-treat for at least 50% pain relief. Relative benefit was calculated to provide an assessment of how much more likely an individual given a particular treatment is to have at least 50% pain relief than someone given no treatment. Adverse effects frequency data were used to calculate numbers-needed-to-harm and relative risk.

Dental trials and postsurgical trials were also analysed separately to establish whether this had an effect on the NNTs and relative benefits of the drug conditions.

Findings

The meta-analysis was carried out on eight postsurgical pain trials and nine dental extraction trials.

Codeine 60 mg generated an NNT of 16.7 (11-48).

Adverse effects

Dizziness and drowsiness/somnolence were significantly more frequent with codeine 60 mg (Table). Headache, nausea and vomiting were not.

Table: Adverse effects with codeine 60 mg compared with placebo