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Acute Pain | Chronic Pain | General

Aspirin plus codeine in postoperative pain

Clinical bottom line:

Aspirin 650 mg plus codeine 60 mg is an effective analgesic in postoperative pain. A single oral dose had an NNT of 5.3 (4.1-7.4) for at least 50% pain relief over 4-6 hours in patients with moderate to severe pain compared with placebo. However, based on eight trials, this appears to be less effective than a 650 mg dose of aspirin alone [NNT 4.4 (4.0-4.9)].

Adverse effects were mild and transient, mainly nausea and somnolence.

Aspirin (Acetylsalicylic Acid) is an important analgesic. Prescriptions of 300 mg tablets total approximately 3/4 million annually in England alone (1996). Codeine is an opium alkaloid, with activity similar to, but weaker than morphine. It is often prepared 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.

Inclusion criteria were full journal publication, single oral dose, randomised, placebo-controlled, double-blind trials of aspirin plus codeine in acute postoperative pain, baseline pain moderate to severe. Mean TOTPAR and SPID values for each trial were converted to %maxTOTPAR and %maxSPID, and then the proportion of patients achieving at least 50%maxTOTPAR were calculated. This information was used to calculate NNT and relative benefit. Adverse effects frequency data were used to calculate numbers-needed-to-harm and relative risk.


The meta-analysis was carried out on two postsurgical pain trials and six dental extraction trials.

Aspirin 650 mg plus codeine 60 mg had an NNT of 5.3 (4.1-7.4) for at least 50% pain relief. This dose of aspirin plus codeine was significantly more effective than placebo.

Adverse effects

Aspirin 650 mg plus codeine 60 mg was associated with significantly more dizziness, drowsiness/somnolence and nausea than with placebo (Table).

Table: Adverse effects for aspirin 650 mg plus codeine 60 mg compared with placebo

Adverse effect Harmed on Active Harmed on Control Relative risk (95%CI) NNH (95%CI)
Dizziness 18/309 15/714 2.8 (1.4 to 5.4) 25 (15 to 110)
Drowsiness/somnolence 58/309 48/714 2.8 (2.0 to 4.0) 8.3 (6 to 14)
Headache 18/309 41/714 1.0 (0.5 to 1.7) not calculated
Nausea 35/309 31/714 2.6 (1.6 to 4.2) 14 (9 to 32)
Vomiting 3/309 6/714 1.2 (0.3 to 4.6) not calculated

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