Paracetamol plus tramadol for acute pain

Clinical bottom line
Based on somewhat limited information, a combination of paracetamol plus tramadol is an effective analgesic in acute postoperative pain. The NNT compared with placebo over six hours was about 2.7.

The combination of tramadol with paracetamol is not commonly available for prescription, but has recently (2002) become available in the USA. The exact dosage strengths in the combinations may vary from country to country, so affecting its efficacy.

SYSTEMATIC REVIEW

JE Edwards et al. Combination analgesic efficacy: Individual patient data meta-analysis of single dose oral tramadol plus acetaminophen in acute postoperative pain. Journal of Pain and Symptom Management 2002 23:121-30.

Date review completed: 2001
Number of trials included: 7
Number of patients: various, because different combination strengths
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). Duration of analgesia through time to remedication.

Inclusion criteria were single oral dose, randomised, placebo-controlled, double-blind trials of paracetamol plus 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 six and eight hour TOTPAR was calculated for each patient (this was an individual patient analysis), 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.

Findings

Paracetamol plus tramadol was an effective analgesic in dental and postsurgical pain, based on limited information (Table 1), with NNTs between 2 and 3. NNTs over eight hours were similar to those over six hours

Table 1: NNTs for paracetamol plus tramadol for half pain relief over six hours compared with placebo

	At least half pain relief, number/total (%)
Pain model/dosage	Paracetamol plus tramadol	Placebo	NNT (95% CI)
Dental pain: Paracetamol 650 mg + tramadol 75 mg	145/340 (43)	14/339 (4)	2.6 (2.3 to 3.0)
Postsurgical pain: Paracetamol 975 mg + tramadol 112.5 mg	61/101 (60)	25/100 (25)	2.8 (2.1 to 4.4)

Adverse events

More patients reported adverse events with paracetamol plus tramadol than with placebo in an analysis of dental pain patients. There were more patients experiencing any adverse effect (NNH 5.4), and dizziness (NNH 23), nausea (NNH 7) and vomiting (NNH 6) with paracetamol plus tramadol.

Comment

The paper calculates results based on pain intensity, pain relief and patient global evaluation of treatment, based on individual patient data. All produced very similar NNTs, confirming findings from other studies, and underpinning the methods used in meta-analysis in acute pain.