Abstract: Twenty randomised controlled trials involving 1170 patients were included in this systematic review. The overall risk of bias in included trials was assessed as unclear, because concealment of allocation processes and blinding of outcome assessors were poorly described. Due to inconsistent outcome reporting, data from 17 included trials could be pooled for some endpoints only. Eight trials compared tramadol administration with placebo and five trials found that the need for rescue analgesia in the postoperative care unit (PACU) was reduced in children receiving tramadol (RR 0.40; 95% CI 0.20 to 0.78; low quality evidence). Only one trial investigated the number of patients with moderate to severe pain, but a non-validated pain scale was used (very low quality evidence). Four trials compared morphine with tramadol administration. There was no clear evidence of difference in the need for rescue analgesia in the PACU (RR 1.25; 95% CI 0.83 to 1.89; low quality evidence) with tramadol compared with morphine. No trials could be pooled for the outcome 'number of patients with moderate to severe pain'. Three trials were included for the comparison of tramadol with nalbuphine. There was no clear evidence for the need for rescue analgesia in the PACU (RR 0,63; 95% CI 0.16 to 2.45; low quality evidence). Only one trial reported the number of patients with moderate to severe pain, but used a non-validated pain scale (very low quality evidence). Two out of six included trials, which compared pethidine with tramadol, reported the number of children with a need for rescue analgesia within the PACU and showed no clear evidence (RR 0.93; 95% CI 0.43 to 2.02; very low quality evidence). Two trials reported the number of patients with moderate to severe pain and showed a lower RR in patients treated with tramadol (RR 0.64; 95% CI 0.36 to 1.16; low quality evidence). Only one trial was included, which compared tramadol with fentanyl, reporting the number of patients with the need for rescue analgesia (very low quality evidence). Generally, adverse events were poorly reported. Most data could be pooled for the comparison with placebo focusing on the RR for postoperative nausea and vomiting (PONV) in the postoperative care unit and 24 h postoperation. Children treated with tramadol, compared to placebo, did not show clear evidence of benefit for PONV in the postoperative care unit (RR 0.84; 95% CI 0.28 to 2.52; moderate quality evidence) and 24 h postoperation (RR 0.78; 95% CI 0.54 to 1.12; moderate quality evidence). The overall evidence regarding tramadol for postoperative pain in children is currently low or very low and should be interpreted with caution due to small studies and methodological problems (different validated and non-validated pain scales with different pain triggers, missing sample size calculations and missing intention-to-treat analysis). Nevertheless, we demonstrated that tramadol administration might provide appropriate analgesia when compared to placebo; this is based on results showing reduced rescue analgesia in children treated with tramadol compared to placebo. In contrast, the evidence regarding the comparison with other opioids (for example morphine) was uncertain. Adverse events were only poorly reported, so an accurate risk-benefit analysis was not possible.

Plain-language summary: Children experience pain after surgery (‘postoperative pain’) and according to recently published trials the management of this pain is of major concern. A combination of drugs may be the best way to treat postoperative pain, for example drugs called ‘opioids’, like morphine and codeine. However, there are concerns about severe side effects (adverse events) when using opioids. Tramadol is a weak opioid that is used worldwide to treat children with moderate to severe acute or chronic pain. Tramadol can be given to children before surgery to help reduce pain afterwards. It is believed that tramadol administration might be associated with a lower risk for respiratory or haemodynamic depression and might therefore be the ideal analgesic drug for children in the perioperative period. Our systematic review assessed the efficacy and adverse events of tramadol administration compared to placebo or other opioids. In July 2014 we found 20 small randomised controlled trials involving 1170 patients. These small trials had limited data but tramadol may be better than placebo. In five trials, mostly preschool children undergoing minor surgery (for example tonsillectomy) were treated with tramadol or placebo before the start of surgery. Children needed less rescue medication in the postoperative care unit when given tramadol, indicating better analgesia with tramadol. Due to the low amount of usable data, the evidence focusing on the comparison of tramadol with other opioids (for example morphine, nalbuphine, pethidine, fentanyl) is currently unclear. Adverse events were generally only poorly reported in the trials so that the side effects as a result of tramadol administration were not clear.