Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics

Abstract

The analgesic effectiveness and safety of oral tramadol were compared with standard analgesics using a meta-analysis of individual patient data from randomised controlled trials in patients with moderate or severe pain after surgery or dental extraction. Calculation of %maxTOTPAR from individual patient data, and the use of >50%maxTOTPAR defined clinically acceptable pain relief. Number-needed-to-treat (NNT) for one patient to have >50%maxTOTPAR compared with placebo was used to examine the effectiveness of different single oral doses of tramadol and comparator drugs. Eighteen randomised, double-blind, parallel-group single-dose trials with 3453 patients using categorical pain relief scales allowed the calculation of %maxTOTPAR. The use of >50%maxTOTPAR was a sensitive measure to discriminate between analgesics. Tramadol and comparator drugs gave significantly more analgesia than placebo. In postsurgical pain tramadol 50, 100 and 150 mg had NNTs for >50%maxTOTPAR of 7.1 (95% confidence intervals 4.6–18), 4.8 (3.4–8.2) and 2.4 (2.0–3.1), comparable with aspirin 650 mg plus codeine 60 mg (NNT 3.6 (2.5–6.3)) and acetaminophen 650 mg plus propoxyphene 100 mg (NNT 4.0 (3.0–5.7)). With the same dose of drug postsurgical patients had more pain relief than those having dental surgery. Tramadol showed a dose-response for analgesia in both postsurgical and dental pain patients. With the same dose of drug postsurgical pain patients had fewer adverse events than those having dental surgery. Adverse events (headache, nausea, vomiting, dizziness, somnolence) with tramadol 50 mg and 100 mg had a similar incidence to comparator drugs. There was a dose response with tramadol, tending towards higher incidences at higher doses. Single-patient meta-analysis using more than half pain relief provides a sensitive description of the analgesic properties of a drug, and NNT calculations allow comparisons to be made with standard analgesics. Absolute ranking of analgesic performance should be done separately for postsurgical and dental pain.