title: Tramadol for postoperative pain treatment in children.
abstract: BACKGROUND
  According to current recommendations a multimodal approach is believed to be the gold standard for postoperative pain treatment in children. However, several surveys in the last few years demonstrated that postoperative pain in children is still a serious problem, mainly because opioids are avoided. One of the reasons for this is the fear of severe adverse events following opioid administration. Tramadol is a weak mu-opioid agonist and inhibits reuptake of noradrenaline and serotonin (5HT). Because of a relatively wide therapeutic window and a ceiling effect with a lower risk for severe adverse events (for example respiratory depression) tramadol is a widely used opioid in children. However, the exact efficacy and occurrence of adverse events following tramadol (in comparison with placebo or other opioids) for postoperative pain treatment in children and adolescents are currently not clear.
  
  
  OBJECTIVE
  To assess the effectiveness and side effect profile of tramadol for postoperative pain relief in children and adolescents undergoing different surgical procedures.
  
  
  METHODS
  We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE via PubMed (January 1966 to July 2014) and EMBASE via Ovid (January 1947 to July 2014). There were no restrictions regarding language or date of publication. The reference lists of all included trials were checked for additional studies.
  
  
  METHODS
  All randomised controlled clinical trials investigating the perioperative administration of tramadol compared to placebo or other opioids for postoperative pain treatment in children and adolescents were included.
  
  
  METHODS
  Three review authors independently assessed the study eligibility, performed the data extraction and assessed the risk of bias of included trials.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Oberduerrbacher Str. 6, Würzburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schnabel
authors.forename: Sylvia U
authors.initials: SU
authors.lastname: Reichl
authors.forename: Christine
authors.initials: C
authors.lastname: Meyer-Frießem
authors.forename: Peter K
authors.initials: PK
authors.lastname: Zahn
authors.forename: Esther
authors.initials: E
authors.lastname: Pogatzki-Zahn
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008614:Meperidine / Q000627:therapeutic use; D009020:Morphine / Q000627:therapeutic use; D009266:Nalbuphine / Q000627:therapeutic use; D010149:Postoperative Pain / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014147:Tramadol / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol; D009020:Morphine; D008614:Meperidine; D009266:Nalbuphine; D005283:Fentanyl