Oral tramadol in postoperative pain
Clinical bottom line:
Tramadol is an effective analgesic in postoperative pain. A single 100 mg oral dose of tramadol is equivalent to 1000 mg paracetamol. A dose of 100 mg had an NNT of 4.6 (3.6-6.4) for at least 50% pain relief over 4-6 hours in patients with moderate to severe pain compared with placebo.
At doses of 50 and 100 mg incidence of adverse effects (headache, nausea, vomiting, dizziness, somnolence) was similar to comparator drugs. In dental trials there was increased incidence of vomiting, nausea, dizziness and somnolence.
Tramadol (tramadol hydrochloride) has been in use in Europe since the 1970s for a range of pain conditions, and in the US since the late 1980s. It is a weak opioid receptor agonist with a number of other properties including serotonin release and inhibition of noradrenaline uptake. Tramadol is produced as a racemic mixture.
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: 18
- Number of patients: 3453 (1486 tramadol / 695 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 tramadol 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. Comparisons with codeine and combination analgesics were also made.
The meta-analysis was carried out on nine postsurgical pain trials and nine dental extraction trials. All trials showed a significantly superior analgesia to placebo, with a clear dose response for tramadol (higher doses associated with higher benefit and lower NNTs). Tramadol 100 mg had an NNT of 4.6 (3.6-6.4).
|Table: Oral tramadol in acute postoperative pain. Data for all analgesics in the review|
|Improved on Active||Improved on Control||Relative benefit (95%CI)||NNT (95%CI)|
|codeine 60||99/649||63/656||1.6 (1.2 - 2.1)||16.7 (11 - 48)|
|tramadol 50||79/409||26/361||2.7 (1.8 - 4.1)||8.3 (6.0 - 13)|
|tramadol 75||90/281||37/282||2.4 (1.7 - 3.5)||5.3 (3.9 - 8.2)|
|tramadol 100||140/468||35/414||3.5 (2.5 - 5.0)||4.8 (3.8 - 6.1)|
|tramadol 150||135/279||37/282||3.7 (2.7 - 5.1)||2.9 (2.4 - 3.6)|
|paracetamol 650 plus propoxyphene 100||114/316||40/322||2.9 (2.1 - 4.0)||4.2 (3.3 - 5.8)|
|aspirin 650 plus codeine 60||76/305||17/293||4.3 (2.6 - 7.1)||5.3 (4.1 - 7.4)|
With the exception of tramadol 100 mg, NNTs were lower in postsurgical pain than in dental extraction models. This was not due to differences in baseline pain intensity.
The most commonly reported effects were headache, vomiting, nausea, dizziness and somnolence, though predominantly of mild intensity. In dental trials only, this was significantly different to placebo for vomiting, nausea, dizziness and somnolence, and there was a distinct dose-response, particularly in dental patients, with higher doses producing greater incidence of adverse events. Numbers-needed-to-harm for individual adverse effects with dental patients are shown in the Figure (unpublished data).