Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 Mar 18;2015(3):CD009574.
doi: 10.1002/14651858.CD009574.pub2.

Tramadol for postoperative pain treatment in children

Alexander Schnabel  1 , Sylvia U Reichl, Christine Meyer-Frießem, Peter K Zahn, Esther Pogatzki-Zahn
Affiliations
Meta-Analysis

Tramadol for postoperative pain treatment in children

Alexander Schnabel et al. Cochrane Database Syst Rev. .

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.

Objectives: To assess the effectiveness and side effect profile of tramadol for postoperative pain relief in children and adolescents undergoing different surgical procedures.

Search 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.

Selection criteria: 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.

Data collection and analysis: Three review authors independently assessed the study eligibility, performed the data extraction and assessed the risk of bias of included trials.

Main 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).

Authors' 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.

PubMed Disclaimer

Conflict of interest statement

AS has no relevant conflicts of interests.

SR has no relevant conflicts of interests.

CMF has no relevant conflicts of interests.

PZ has no relevant conflicts of interests.

EPZ has no relevant conflicts of interests.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Tramadol versus placebo, Outcome 1 Number of patients requiring rescue analgesia (PACU).
1.2
1.2. Analysis
Comparison 1 Tramadol versus placebo, Outcome 2 Number of patients requiring rescue analgesia (PACU) (Subgroup: Surgery).
1.3
1.3. Analysis
Comparison 1 Tramadol versus placebo, Outcome 3 Number of patients requiring rescue analgesia (PACU) (Subgroup: Dose).
1.4
1.4. Analysis
Comparison 1 Tramadol versus placebo, Outcome 4 Time to first rescue analgesic (min).
1.5
1.5. Analysis
Comparison 1 Tramadol versus placebo, Outcome 5 Number of patients with PONV (PACU).
1.6
1.6. Analysis
Comparison 1 Tramadol versus placebo, Outcome 6 Number of patients with PONV (24h postop).
1.7
1.7. Analysis
Comparison 1 Tramadol versus placebo, Outcome 7 Number of patients with respiratory depression.
2.1
2.1. Analysis
Comparison 2 Tramadol versus morphine, Outcome 1 Number of patients requiring rescue analgesia (PACU).
2.2
2.2. Analysis
Comparison 2 Tramadol versus morphine, Outcome 2 Number of patients requiring rescue analgesia (24h postop).
2.3
2.3. Analysis
Comparison 2 Tramadol versus morphine, Outcome 3 Number of patients with respiratory depression.
3.1
3.1. Analysis
Comparison 3 Tramadol versus nalbuphine, Outcome 1 Number of patients requiring rescue analgesia (24h postop).
3.2
3.2. Analysis
Comparison 3 Tramadol versus nalbuphine, Outcome 2 Number of patients with PONV (PACU).
3.3
3.3. Analysis
Comparison 3 Tramadol versus nalbuphine, Outcome 3 Number of patients with respiratory depression.
3.4
3.4. Analysis
Comparison 3 Tramadol versus nalbuphine, Outcome 4 Number of patients with bradycardia.
4.1
4.1. Analysis
Comparison 4 Tramadol versus pethidine, Outcome 1 Number of patients requiring rescue analgesia (PACU).
4.2
4.2. Analysis
Comparison 4 Tramadol versus pethidine, Outcome 2 Number of patients with moderate/severe pain (PACU).
4.3
4.3. Analysis
Comparison 4 Tramadol versus pethidine, Outcome 3 Number of patients with PONV (PACU).
4.4
4.4. Analysis
Comparison 4 Tramadol versus pethidine, Outcome 4 Number of patients with respiratory depression.
4.5
4.5. Analysis
Comparison 4 Tramadol versus pethidine, Outcome 5 Number of patients with bradycardia.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009574

References

References to studies included in this review

Ali 2008 {published data only}
    1. Ali SM, Shahrbano S, Ulhaq TS. Tramadol for pain relief in children undergoing adenotonsillectomy a comparison with dextromethorphan. Laryngoscope 2008 Sep;118(9):1547‐9. - PubMed
Antila 2006 {published data only}
    1. Antila H, Manner T, Kuurila K, Salanterä S, Kujala R, Aantaa R. Ketoprofen and tramadol for analgesia during early recovery after tonsillectomy in children. Paediatric Anaesthesia 2006 May;16(5):548‐53. - PubMed
Barsoum 1995 {published data only}
    1. Barsoum MW. Comparison of the efficacy and tolerability of tramadol, pethidine and nalbuphine in children with postoperative pain. Clinical Drug Investigation 1995;9(4):183‐90.
Bösenberg 1998 {published data only}
    1. Bösenberg AT, Ratcliffe S. The respiratory effects of tramadol in children under halothane an anaesthesia. Anaesthesia. 1998 Oct;53(10):960‐4. - PubMed
Chiaretti 2000 {published data only}
    1. Chiaretti A, Viola L, Pietrini D, Piastra M, Savioli A, Tortorolo L, et al. Preemptive analgesia with tramadol and fentanyl in pediatric neurosurgery. Child's Nervous System 2000 Feb;16(2):93‐9. - PubMed
Cocelli 2012 {published data only}
    1. Cocelli LP, Ugur BK, Durucu C, Kul S, Arik H, Mumbuc S. Comparison of pre‐emptive tonsillar lodge infiltration with ropivacaine versus intravenous tramadol in pediatric tonsillectomies a randomized placebo‐controlled study. International Journal of Pediatric Otorhinolaryngology 2012 May;76(5):653‐7. - PubMed
Ekemen 2008 {published data only}
    1. Ekemen S, Yelken B, Ilhan H, Tokar B. A comparison of analgesic efficacy of tramadol and pethidine for management of postoperative pain in children a randomized, controlled study. Pediatric Surgery International 2008 Jun;24(6):695‐8. - PubMed
Engelhardt 2003 {published data only}
    1. Engelhardt T, Steel E, Johnston G, Veitch DY. Tramadol for pain relief in children undergoing tonsillectomy a comparison with morphine. Paediatric Anaesthesia 2003 Mar;13(3):249‐52. - PubMed
Ertugrul 2006 {published data only}
    1. Ertugrul F, Akbas M, Karsli B, Kayacan N, Bulut F, Trakya A. Pain relief for children after adenotonsillectomy. Journal of International Medical Research 2006 Nov‐Dec;34(6):648‐54. - PubMed
Hullett 2006 {published data only}
    1. Hullett BJ, Chambers NA, Pascoe EM, Johnson C. Tramadol vs morphine during adenotonsillectomy for obstructive sleep apnea in children. Paediatric Anaesthesia 2006 Jun;16(6):648‐53. - PubMed
Moyado Garcia 2009 {published data only}
    1. Moyao‐García D, Hernández‐Palacios JC, Ramírez‐Mora JC, Nava‐Ocampo AA. A pilot study of nalbuphine versus tramadol administered through continuous intravenous infusion for postoperative pain control in children. Acta Biomedica 2009 Aug;80(2):124‐30. - PubMed
Ozalevli 2005 {published data only}
    1. Ozalevli M, Unlügenç H, Tuncer U, Güneş Y, Ozcengiz D. Comparison of morphine and tramadol by patient‐controlled analgesia for postoperative analgesia after tonsillectomy in children. Paediatric Anaesthesia 2005 Nov;15(11):979‐84. - PubMed
Ozer 2003 {published data only}
    1. Ozer Z, Görür K, Altunkan AA, Bilgin E, Camdeviren H, Oral U. Efficacy of tramadol versus meperidine for pain relief and safe recovery after adenotonsillectomy. European Journal of Anaesthesiology 2003 Nov;20(11):920‐4. - PubMed
Ozköse 2000 {published data only}
    1. Ozköse Z, Akçabay M, Kemaloğlu YK, Sezenler S. Relief of posttonsillectomy pain with low‐dose tramadol given at induction of anesthesia in children. International Journal of Pediatric Otorhinolaryngology 2000 Jul 14;53(3):207‐14. - PubMed
Payne 1999 {published data only}
    1. Payne KA, Roelofse JA. Tramadol drops in children: analgesic efficacy, lack of respiratory effects, and normal recovery times. Anesthesia Progress 1999 Summer;46(3):91‐6. - PMC - PubMed
Roelofse 1999 {published data only}
    1. Roelofse JA, Payne KA. Oral tramadol analgesic efficacy in children following multiple dental extractions. European Journal of Anaesthesiology 1999 Jul;16(7):441‐7. - PubMed
Schäffer 1986 {published data only}
    1. Schäffer J, Piepenbrock S, Kretz FJ, Schönfeld C. Nalbuphine and tramadol for the control of postoperative pain in children. Anaesthesist 1986 Jul;35(7):408‐13. - PubMed
Umuroglu 2004 {published data only}
    1. Umuroğlu T, Eti Z, Ciftçi H, Yilmaz Göğüş F. Analgesia for adenotonsillectomy in children: a comparison of morphine, ketamine and tramadol. Paediatric Anaesthesia 2004 Jul;14(7):568‐73. - PubMed
van den Berg 1999 {published data only}
    1. Berg AA, Montoya‐Pelaez LF, Halliday EM, Hassan I, Baloch MS. Analgesia for adenotonsillectomy in children and young adults a comparison of tramadol, pethidine and nalbuphine. European Journal of Anaesthesiology 1999 Mar;16(3):186‐94. - PubMed
Viitanen 2001 {published data only}
    1. Viitanen H, Annila P. Analgesic efficacy of tramadol 2 mg kg(‐1) for paediatric day‐case adenoidectomy. British Journal of Anaesthesia 2001 Apr;86(4):572‐5. - PubMed

References to studies excluded from this review

Aguirre Córcoles 2003 {published data only}
    1. Aguirre Córcoles E, Durán González ME, Zambudio GA, González Celdrán R, Castaño Collado I, Cárceles Barón MD, et al. [Post‐surgical paediatric pain Nursing‐ PCA vs continuous I.V. infusion of tramadol]. Cir Pediatria 2003 Jan;16(1):30‐3. - PubMed
Akkaya 2009 {published data only}
    1. Akkaya T, Bedirli N, Ceylan T, Matkap E, Gulen G, Elverici O, et al. Comparison of intravenous and peritonsillar infiltration of tramadol for postoperative pain relief in children following adenotonsillectomy. European Journal of Anaesthesiology 2009 Apr;26(4):333‐7. - PubMed
Alencar 2012 {published data only}
    1. Alencar AJ, Sanudo A, Sampaio VM, Góis RP, Benevides FA, Guinsburg R. Efficacy of tramadol versus fentanyl for postoperative analgesia in neonates. Archives of Diseases in Childhood. Fetal and Neonatal Edition 2012 Jan;97(1):F24‐9. - PubMed
Altunkaya 2003 {published data only}
    1. Altunkaya H, Ozer Y, Kargi E, Babuccu O. Comparison of local anaesthetic effects of tramadol with prilocaine for minor surgical procedures. British Journal of Anaesthesia 2003 Mar;90(3):320‐2. - PubMed
Apiliogullari 2011 {published data only}
    1. Apiliogullari S, Kara I, Senaran H, Duman A, Celik JB. Combined spinal and light general anaesthesia for children undergoing developmental hip dysplasia surgery: Single centre experience. Regional Anesthesia and Pain Medicine 2011.
Bedirli 2011 {published data only}
    1. Bedirli N, Akcabay M, Emik U. The effects of intraoperative single dosage tramadol or dexmedetomidine on postoperative analgesia, sedation and emerge reactions in pediatric patients undergoing adenotonsillectomy. Regional Anesthesia and Pain Medicine 2011.
Borazan 2012 {published data only}
    1. Borazan H, Sahin O, Kececioglu A, Uluer MS, Et T, Otelcioglu S. Prevention of propofol injection pain in children: A comparison of pre‐treatment with tramadol and propofol‐lidocaine mixture. International Journal of Medical Sciences 2012;9(6):492‐7. - PMC - PubMed
Chu 2006 {published data only}
    1. Chu YC, Lin SM, Hsieh YC, Chan KH, Tsou MY. Intraoperative administration of tramadol for postoperative nurse‐controlled analgesia resulted in earlier awakening and less sedation than morphine in children after cardiac surgery.. Anesthesia and Analgesia 2006 Jun;102(6):1668‐73. - PubMed
Courtney 2000 {published data only}
    1. Courtney MJ, Cabraal D. Tramadol vs diclofenac for posttonsillectomy analgesia. Archives of Otolaryngology‐‐Head & Neck Surgery 2001 Apr;127(4):385‐8. - PubMed
Demiraran 2005 {published data only}
    1. Demiraran Y, Kocaman B, Akman RY. A comparison of the postoperative analgesic efficacy of single‐dose epidural tramadol versus morphine in children. British Journal of Anaesthesia 2005 Oct;95(4):510‐3. - PubMed
Finkel 2002 {published data only}
    1. Finkel JC, Rose JB, Schmitz ML, Birmingham PK, Ulma GA, Gunter JB, et al. An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children. Anesthesia and Analgesia 2002 Jun;94(6):1469‐73. - PubMed
Griessinger 1997 {published data only}
    1. Griessinger N, Rösch W, Schott G, Sittl R. Tramadol infusion for pain therapy following bladder exstrophy surgery in pediatric wards. Urologe A 1997 Nov;36(6):552‐6. - PubMed
Günes 2004 {published data only}
    1. Güneş Y, Gündüz M, Unlügenç H, Ozalevli M, Ozcengiz D. Comparison of caudal vs intravenous tramadol administered either preoperatively or postoperatively for pain relief in boys. Paediatric Anaesthesia 2004 Apr;14(4):324‐8. - PubMed
Khosravi 2006 {published data only}
    1. Khosravi MB, Khezri S, Azemati S. Tramadol for pain relief in children undergoing herniotomy: a comparison with ilioinguinal and iliohypogastric blocks. Paediatric Anaesthesia 2006 Jan;16(1):54‐8. - PubMed
Macarone 1998 {published data only}
    1. Macarone Palmieri A, Meglio M, Testa D, Salafia M, Iasiello A. Anesthesiologic and surgical problems in adenotonsillectomy in pediatric patients. Our current trend. Minerva Anestesiologica 1998 Dec;64(12):545‐52. - PubMed
Metodiev 2011 {published data only}
    1. Metodiev Y, Gavrilova N. Analgesic efficacy of ultrasound‐guided transversus abdominis plane block after open appenedectomy in children. Regional Anesthesia and Pain Medicine 2011.
Mikhel'son 2002 {published data only}
    1. Mikhel'son VA, Zhirkova IuV, Beliaeva ID, Stepanenko SM, Manerova AF, Butyleva OIu. [Postoperative analgesia with tramadol in newborn children using the method of continuous intravenous infusion]. Anesteziologiia i Reanimatologiia 2003 Jan‐Feb;1:24‐8. - PubMed
Oliveira 2000 {published data only}
    1. Oliveira EDS, Micheletti LG, Sakata RK, Iwata NM, Do Amaral JLG. A comparative study of postoperative analgesia of tramadol or fentanyl in pediatric patients anesthetic induction. Pediatric Anesthesia 2000;413(1‐2):89‐92.
Osifo 2008 {published data only}
    1. Osifo OD, Aghahowa ES. Safety profile and efficacy of commonly used analgesics in surgical neonates in Benin City, Nigeria. American Journal of Perinatology 2008 Nov;25(10):617‐22. - PubMed
Ostreikov 1993 {published data only}
    1. Ostreĭkov IF, Sen'kov VN, Kurilova ES, Bershinskiĭ VP, Pivovarov SA, Babaev BD. [Use of tramadol during minor surgical interventions in children]. Anesteziologiia i Reanimatologiia 1993 May‐Jun;3:28‐31. - PubMed
Pendeville 2000 {published data only}
    1. Pendeville PE, Montigny S, Dort JP, Veyckemans F. Double‐blind randomized study of tramadol vs. paracetamol in analgesia after day‐case tonsillectomy in children. European Journal of Anaesthesiology 2000 Sep;17(9):576‐82. - PubMed
Sun 2010 {published data only}
    1. Sun Y, Xu W, Hu J, Xu W, Bai J, Zhang M. Combination effect of tramadol and low dose propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure. Journal of Shanghai Jiaotong University 2010;1.

Additional references

Allegaert 2011
    1. Allegaert K, Rochette A, Veyckemans F. Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics and elimination clearance. Paediatric Anaesthesia 2011;21(3):266‐73. [PUBMED: 20723094] - PubMed
Andrews 2002
    1. Andrews K, Fitzgerald M. Wound sensitivity as a measure of analgesic effects following surgery in human neonates and infants. Pain 2002;99(1‐2):185‐95. [PUBMED: 12237196] - PubMed
Awad 2004
    1. Awad IT, Moore M, Rushe C, Elburki A, O'Brien K, Warde D. Unplanned hospital admission in children undergoing day‐case surgery. European Journal of Anaesthesiology 2004;21(5):379‐83. [PUBMED: 15141796] - PubMed
Bamigbade 1998
    1. Bamigbade TA, Langford RM. Tramadol hydrochloride: an overview of current use. Hospital Medicine 1998;59(5):373‐6. [PUBMED: 9722388] - PubMed
Bosenberg 1998
    1. Bosenberg AT, Ratcliffe S. The respiratory effects of tramadol in children under halothane an anaesthesia. Anaesthesia 1998;53(10):960‐4. [PUBMED: 9893539] - PubMed
Bozkurt 2005
    1. Bozkurt P. Use of tramadol in children. Paediatric Anaesthesia 2005;15(12):1041‐7. [PUBMED: 16324021] - PubMed
Dadure 2009
    1. Dadure C, Bringuier S, Raux O, Rochette A, Troncin R, Canaud N, et al. Continuous peripheral nerve blocks for postoperative analgesia in children: feasibility and side effects in a cohort study of 339 catheters. Canadian Journal of Anaesthesia = Journal Canadien d'Anesthesie 2009;56(11):843‐50. [PUBMED: 19697092] - PubMed
Dayer 1994
    1. Dayer P, Collart L, Desmeules J. The pharmacology of tramadol. Drugs 1994;47 Suppl 1:3‐7. [PUBMED: 7517823] - PubMed
Franck 2004
    1. Franck LS, Cox S, Allen A, Winter I. Parental concern and distress about infant pain. Archives of Disease in Childhood. Fetal and Neonatal Edition 2004;89(1):F71‐5. [PUBMED: 14711862] - PMC - PubMed
Glaser 1999
    1. Glaser R, Kiecolt‐Glaser JK, Marucha PT, MacCallum RC, Laskowski BF, Malarkey WB. Stress‐related changes in proinflammatory cytokine production in wounds. Archives of General Psychiatry 1999;56(5):450‐6. [PUBMED: 10232300] - PubMed
Groenewald 2012
    1. Groenewald CB, Rabbitts JA, Schroeder DR, Harrison TE. Prevalence of moderate‐severe pain in hospitalized children. Paediatric Anaesthesia 2012;22(7):661‐8. [PUBMED: 22332912] - PubMed
Hennies 1988
    1. Hennies HH, Friderichs E, Schneider J. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittel‐Forschung 1988;38(7):877‐80. [PUBMED: 2849950] - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration.
Hirschfeld 2013
    1. Hirschfeld G, Zernikow B. Variability of "optimal" cut points for mild, moderate, and severe pain: neglected problems when comparing groups. Pain 2013;154(1):154‐9. [PUBMED: 23182623] - PubMed
Kharasch 2003
    1. Kharasch S, Saxe G, Zuckerman B. Pain treatment: opportunities and challenges. Archives of Pediatrics & Adolescent Medicine 2003;157(11):1054‐6. [PUBMED: 14609892] - PubMed
Lintz 1998
    1. Lintz W, Barth H, Osterloh G, Schmidt‐Bothelt E. Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. Arzneimittel‐Forschung 1998;48(9):889‐99. [PUBMED: 9793614] - PubMed
Michelet 2012
    1. Michelet D, Andreu‐Gallien J, Bensalah T, Hilly J, Wood C, Nivoche Y, et al. A meta‐analysis of the use of nonsteroidal antiinflammatory drugs for pediatric postoperative pain. Anesthesia and Analgesia 2012;114(2):393‐406. [PUBMED: 22104069] - PubMed
Murthy 2000
    1. Murthy BV, Pandya KS, Booker PD, Murray A, Lintz W, Terlinden R. Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration. British Journal of Anaesthesia 2000;84(3):346‐9. [PUBMED: 10793594] - PubMed
Niesters 2013
    1. Niesters M, Overdyk F, Smith T, Aarts L, Dahan A. Opioid‐induced respiratory depression in paediatrics: a review of case reports. British Journal of Anaesthesia 2013;110(2):175‐82. [PUBMED: 23248093] - PubMed
Orliaguet 2015
    1. Orliaguet G, Hamza J, Couloigner V, Denoyelle F, Loriot MA, Broly F, et al. A case of respiratory depression in a child with ultrarapid CYP2D6 metabolism after tramadol. Pediatrics 2015. [PUBMED: 25647677] - PubMed
Page 2013
    1. Page MG, Stinson J, Campbell F, Isaac L, Katz J. Identification of pain‐related psychological risk factors for the development and maintenance of pediatric chronic postsurgical pain. Journal of Pain Research 2013;6:167‐80. [PUBMED: 23503375] - PMC - PubMed
Payne 2002
    1. Payne KA, Roelofse JA, Shipton EA. Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years‐‐a pilot study. Anesthesia Progress 2002;49(4):109‐12. [PUBMED: 12779111] - PMC - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Romsing 1996
    1. Romsing J, Walther‐Larsen S. Postoperative pain in children: a survey of parents' expectations and perceptions of their children's experiences. Paediatric Anaesthesia 1996;6(3):215‐8. [PUBMED: 8732613] - PubMed
Russell 2013
    1. Russell P, Ungern‐Sternberg BS, Schug SA. Perioperative analgesia in pediatric surgery. Current Opinion in Anaesthesiology 2013;26(4):420‐7. [PUBMED: 23756911] - PubMed
Scaife 1988
    1. Scaife JM, Campbell I. A comparison of the outcome of day‐care and inpatient treatment of paediatric surgical cases. Journal of Child Psychology and Psychiatry, and Allied Disciplines 1988;29(2):185‐98. [PUBMED: 3372615] - PubMed
Schnabel 2014
    1. Schnabel A, Reichl SU, Zahn PK, Pogatzki‐Zahn E. Nalbuphine for postoperative pain treatment in children. Cochrane Database of Systematic Reviews 2014;7:CD009583. [PUBMED: 25079857] - PMC - PubMed
Schunemann 2008
    1. Schunemann HJ, Oxman AD, Brozek J, Glasziou P, Bossuyt P, Chang S, et al. GRADE: assessing the quality of evidence for diagnostic recommendations. Evidence‐Based Medicine 2008;13(6):162‐3. [PUBMED: 19043023] - PubMed
Scott 2000
    1. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs 2000;60(1):139‐76. [PUBMED: 10929933] - PubMed
Segerdahl 2008
    1. Segerdahl M, Warren‐Stomberg M, Rawal N, Brattwall M, Jakobsson J. Children in day surgery: clinical practice and routines. The results from a nation‐wide survey. Acta Anaesthesiologica Scandinavica 2008;52(6):821‐8. [PUBMED: 18498436] - PubMed
Standing 2009
    1. Standing JF, Savage I, Pritchard D, Waddington M. Diclofenac for acute pain in children. Cochrane Database of Systematic Reviews 2009, (4):CD005538. [PUBMED: 19821348] - PubMed
Stanko 2013
    1. Stanko D, Bergesio R, Davies K, Hegarty M, Ungern‐Sternberg BS. Postoperative pain, nausea and vomiting following adeno‐tonsillectomy ‐ a long‐term follow‐up. Paediatric Anaesthesia 2013;23(8):690‐6. [PUBMED: 23668258] - PubMed
Subramanyam 2014
    1. Subramanyam R, Chidambaran V, Ding L, Myer CM 3rd, Sadhasivam S. Anesthesia‐ and opioids‐related malpractice claims following tonsillectomy in USA: LexisNexis claims database 1984‐2012. Paediatric Anaesthesia 2014;24(4):412‐20. [PUBMED: 24417679] - PubMed
Tarkkila 1998
    1. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and pethidine. European Journal of Anaesthesiology 1998;15(1):64‐8. [PUBMED: 9522144] - PubMed
Taylor 2008
    1. Taylor EM, Boyer K, Campbell FA. Pain in hospitalized children: a prospective cross‐sectional survey of pain prevalence, intensity, assessment and management in a Canadian pediatric teaching hospital. Pain Research & Management 2008;13(1):25‐32. [PUBMED: 18301813] - PMC - PubMed
Vickers 1992
    1. Vickers MD, O'Flaherty D, Szekely SM, Read M, Yoshizumi J. Tramadol: pain relief by an opioid without depression of respiration. Anaesthesia 1992;47(4):291‐6. [PUBMED: 1519677] - PubMed
Walker 2009
    1. Walker SM, Franck LS, Fitzgerald M, Myles J, Stocks J, Marlow N. Long‐term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain 2009;141(1‐2):79‐87. [PUBMED: 19026489] - PubMed
Weisman 1998
    1. Weisman SJ, Bernstein B, Schechter NL. Consequences of inadequate analgesia during painful procedures in children. Archives of Pediatrics & Adolescent Medicine 1998;152(2):147‐9. [PUBMED: 9491040] - PubMed