Review Article

Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis

Corresponding Author

Georgia G. Tsaousi MD, MSc, PhD

tsaousig@otenet.gr

orcid.org/0000-0003-3806-837X

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

Address correspondence and reprint requests to: Georgia G. Tsaousi, MD, MSc, PhD, Maiandrou 32, GR 56224 Thessaloniki, Greece. E-mail: tsaousig@otenet.gr.

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Anastasia Chatzistravou MSc,

Anastasia Chatzistravou MSc

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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George Papazisis MD, PhD,

George Papazisis MD, PhD

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Vasilios Grosomanidis MD, PhD,

Vasilios Grosomanidis MD, PhD

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Dimitrios Kouvelas MD, PhD,

Dimitrios Kouvelas MD, PhD

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Chryssa Pourzitaki MD, MSc, PhD,

Chryssa Pourzitaki MD, MSc, PhD

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Georgia G. Tsaousi MD, MSc, PhD,

Corresponding Author

Georgia G. Tsaousi MD, MSc, PhD

tsaousig@otenet.gr

orcid.org/0000-0003-3806-837X

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

Address correspondence and reprint requests to: Georgia G. Tsaousi, MD, MSc, PhD, Maiandrou 32, GR 56224 Thessaloniki, Greece. E-mail: tsaousig@otenet.gr.

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Anastasia Chatzistravou MSc,

Anastasia Chatzistravou MSc

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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George Papazisis MD, PhD,

George Papazisis MD, PhD

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Vasilios Grosomanidis MD, PhD,

Vasilios Grosomanidis MD, PhD

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Dimitrios Kouvelas MD, PhD,

Dimitrios Kouvelas MD, PhD

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Chryssa Pourzitaki MD, MSc, PhD,

Chryssa Pourzitaki MD, MSc, PhD

Department of Anesthesiology and ICU, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

Department of Clinical Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

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First published: 03 February 2020

https://doi.org/10.1111/papr.12874

Citations: 7

Trial registration: PROSPERO CRD42019131995.

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Abstract

Objectives

The aim of this systematic review and meta-analysis was to appraise clinical evidence of the impact of peritonsillar infiltration of tramadol, on postoperative pain control and the occurrence of adverse effects in children undergoing tonsillectomy.

Methods

A database search was conducted to identify randomized controlled trials (RCTs) pertinent to peritonsillar infiltration of tramadol compared to no treatment (placebo) or other analgesic regimens. The outcomes of interest were postoperative pain intensity, time to first analgesic demand, rescue analgesic consumption up to 24 hours after intervention, and the occurrence of adverse events.

Results

Twelve RCTs enrolling 972 pediatric patients were selected for qualitative analysis, among which eight were suitable for meta-analysis. Tramadol infiltration induced a significant reduction of pain intensity up to 24 hours post-tonsillectomy (mean difference [MD], −2.31; 95% confidence interval [CI], −3.49 to −1.12; P < 0.001; I² = 97%) and time to first analgesic (MD 180.54; 95% CI, 56.91 to 304.18; P = 0.004; I² = 99%), with no profound impact on postoperative nausea and vomiting (risk ratio [RR] 0.98; 95% CI, 0.73 to 1.32; P = 0.90; I² = 0%) compared to the placebo group. The analgesic efficacy of tramadol infiltration was equivalent to the local or systematic use of ketamine or infiltration with local anesthetics. This effect was further enhanced when tramadol infiltration served as an adjunct to other analgesic interventions. No serious adverse events were reported.

Conclusions

In children undergoing tonsillectomy, peritonsillar infiltration of tramadol is associated with a postoperative analgesic benefit when compared to placebo, with negligible adverse events. Yet, no definite conclusion can be drawn due to the low quality, considerable heterogeneity, and paucity of the available data.

Conflicts of Interest

The authors report no conflicts of interest.

References

1Blacoe DA, Cunning E, Bell G. Paediatric day-case surgery: an audit of unplanned hospital admission Royal Hospital for Sick Children, Glasgow. Anaesthesia. 2008; 63: 610–615.
10.1111/j.1365-2044.2008.05438.x
CASPubMedWeb of Science®Google Scholar
2Ayatollahi V, Behdad S, Hatami M, Moshtaghiun H, Baghianimoghadam B. Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial. Croat Med J. 2012; 53: 155–161.
10.3325/cmj.2012.53.155
PubMedWeb of Science®Google Scholar
3Cho HK, Kim KW, Jeong YM, Lee HS, Lee YJ, Hwang SH. Efficacy of ketamine in improving pain after tonsillectomy in children: meta-analysis. PLoS ONE. 2014; 9:e101259.
10.1371/journal.pone.0101259
PubMedWeb of Science®Google Scholar
4Yenigun A, Et T, Aytac S, Olcay B. Comparison of different administration of ketamine and intravenous tramadol hydrochloride for postoperative pain relief and sedation after pediatric tonsillectomy. J Craniofac Surg. 2015; 26: e21–e24.
10.1097/SCS.0000000000001250
PubMedWeb of Science®Google Scholar
5Li YH, Wang X, Zhou ZJ, Zhuang PJ. Association between fentanyl test results and rescue morphine requirements in children after adenotonsillectomy. J Anesth. 2018; 32: 77–81.
10.1007/s00540-017-2433-0
PubMedWeb of Science®Google Scholar
6Walrave Y, Maschi C, Bailleux S, et al. Pain after tonsillectomy: effectiveness of current guidelines? Eur Arch Otorhinolaryngol. 2018; 275: 281–286.
10.1007/s00405-017-4788-0
CASPubMedWeb of Science®Google Scholar
7Cocelli 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. Int J Pediatr Otorhinolaryngol. 2012; 76: 653–657.
10.1016/j.ijporl.2012.01.031
PubMedWeb of Science®Google Scholar
8Akkaya T, Bedirli N, Ceylan T, et al. Comparison of intravenous and peritonsillar infiltration of tramadol for postoperative pain relief in children following adenotonsillectomy. Eur J Anaesthesiol. 2009; 26: 333–337.
10.1097/EJA.0b013e32831c8988
PubMedWeb of Science®Google Scholar
9Anderson BJ, Thomas J, Ottaway K, Chalkiadis GA. Tramadol: keep calm and carry on. Paediatr Anaesth. 2017; 27: 785–788.
10.1111/pan.13190
PubMedWeb of Science®Google Scholar
10Vlok R, Melhuish TM, Chong C, Ryan T, White LD. Adjuncts to local anaesthetics in tonsillectomy: a systematic review and meta-analysis. J Anesth. 2017; 31: 608–616.
10.1007/s00540-017-2310-x
CASPubMedWeb of Science®Google Scholar
11Hadi BA, Sbeitan SM. Clinical pharmacy intervention post tonsillectomy: a randomized control trial. Int J Clin Pharm. 2015; 37: 133–138.
10.1007/s11096-014-0051-6
CASPubMedWeb of Science®Google Scholar
12Maryam H, Amin J, Sedighe V, Vida A. Comparing the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain. Eur Arch Otorhinolaryngol. 2017; 274: 2521–2527.
10.1007/s00405-017-4477-z
PubMedWeb of Science®Google Scholar
13Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339: b2700.
10.1136/bmj.b2700
PubMedWeb of Science®Google Scholar
14 Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. Vol. 2011. http://www.cochrane-handbook.org (accessed August 2019).
Google Scholar
15Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 17: 1–12.
10.1016/0197-2456(95)00134-4
CASPubMedGoogle Scholar
16Atef A, Fawaz AA. Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Eur Arch Otorhinolaryngol. 2008; 265: 571–574.
10.1007/s00405-007-0479-6
PubMedWeb of Science®Google Scholar
17Heiba MH, Atef A, Mosleh M, Mohamed R, El-Hamamsy M. Comparison of peritonsillar infiltration of tramadol and lidocaine for the relief of post-tonsillectomy pain. J Laryngol Otol. 2012; 126: 1138–1141.
10.1017/S0022215112002058
CASPubMedWeb of Science®Google Scholar
18Honarmand A, Safavi M, Kashefi P, Hosseini B, Badiei S. Comparison of effect of intravenous ketamine, peritonsillar infiltration of tramadol and their combination on pediatric posttonsillectomy pain: A double-blinded randomized placebo-controlled clinical trial. Res Pharm Sci. 2013; 8: 177–183.
CASPubMedGoogle Scholar
19Honarmand A, Safavi M, Naghibi K, et al. Preemptive peritonsillar infiltration with bupivacaine in combination with tramadol improves pediatric post-tonsillectomy pain better than using bupivacaine or tramadol alone: a randomized, placebo-controlled, double blind clinical trial. Adv Biomed Res. 2015; 4: 132.
10.4103/2277-9175.161518
PubMedGoogle Scholar
20Sarafraz M, Derakhshandeh V, Nesioonpour S, Araghi S. Efficacy of peritonsillar infilltration of ketamine, tramadol, and lidocaine for prevention of post tonsillectomy pain. Niger J Med. 2016; 25: 49–52.
10.4103/1115-2613.278252
PubMedGoogle Scholar
21Topal K, Aktan B, Sakat MS, Kilic K, Gozeler MS. Post-operative pain control after tonsillectomy: dexametasone vs tramadol. Acta Otolaryngol. 2017; 137: 618–622.
10.1080/00016489.2016.1269945
CASPubMedWeb of Science®Google Scholar
22Ugur KS, Karabayirli S, Demircioğlu Rİ, et al. The comparison of preincisional peritonsillar infiltration of ketamine and tramadol for postoperative pain relief on children following adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2013; 77: 1825–1829.
10.1016/j.ijporl.2013.08.018
PubMedWeb of Science®Google Scholar
23Ugur MB, Yilmaz M, Altunkaya H, Cinar F, Ozer Y, Beder L. Effects of intramuscular and peritonsillar injection of tramadol before tonsillectomy: a double blind, randomized, placebo-controlled clinical trial. Int J Pediatr Otorhinolaryngol. 2008; 72: 241–248.
10.1016/j.ijporl.2007.11.002
PubMedWeb of Science®Google Scholar
24Dahmani S, Michelet D, Abback PS, et al. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Pediatr Anesth. 2011; 21: 636–652.
10.1111/j.1460-9592.2011.03566.x
PubMedWeb of Science®Google Scholar
25Tolska HK, Hamunen K, Takala A, Kontinen VK. Systematic review on analgesics and dexamethasone for post-tonsillectomy pain in adults. Br J Anaesth. 2019; 123: e397–e411.
10.1016/j.bja.2019.04.063
CASPubMedWeb of Science®Google Scholar
26de Boer HD, Detriche O, Forget P. Opioid-related side effects: Postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature. Best Pract Res Clin Anaesthesiol. 2017; 31: 499–504.
10.1016/j.bpa.2017.07.002
PubMedGoogle Scholar
27Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev. 2013;(7): CD003591.
PubMedWeb of Science®Google Scholar
28Mitra S, Purohit S, Sharma M. Postoperative analgesia after wound infiltration with tramadol and dexmedetomidine as an adjuvant to ropivacaine for lumbar discectomies: a randomized-controlled clinical trial. J Neurosurg Anesthesiol. 2017; 29: 433–438.
10.1097/ANA.0000000000000422
PubMedWeb of Science®Google Scholar
29Demiraran Y, Albayrak M, Yorulmaz IS, Ozdemir I. Tramadol and levobupivacaine wound infiltration at cesarean delivery for postoperative analgesia. J Anesth. 2013; 27: 175–179.
10.1007/s00540-012-1510-7
PubMedWeb of Science®Google Scholar
30Grainger J, Saravanappa N. Local anaesthetic for post-tonsillectomy pain: a systematic review and meta-analysis. Clin Otolaryngol. 2008; 33: 411–419.
10.1111/j.1749-4486.2008.01815.x
CASPubMedWeb of Science®Google Scholar
31Sousa AM, Ashmawi HA. Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats. Rev Bras Anestesiol. 2015; 65: 186–190.
10.1016/j.bjan.2014.06.008
PubMedWeb of Science®Google Scholar
32Bravo L, Mico JA, Berrocoso E. Discovery and development of tramadol for the treatment of pain. Expert Opin Drug Discov. 2017; 12: 1281–1291.
10.1080/17460441.2017.1377697
CASPubMedWeb of Science®Google Scholar
33Mert T, Gunes Y, Gunay I. Local analgesic efficacy of tramadol following intraplantar injection. Eur J Pharmacol. 2007; 858: 68–72.
10.1016/j.ejphar.2006.11.055
Web of Science®Google Scholar
34Lintz W, Beier H, Gerloff J. Bioavailability of tramadol after i.m. injection in comparison to i.v. infusion. Int J Clin Pharmacol Ther. 1999; 37: 175–183.
CASPubMedWeb of Science®Google Scholar
35Sahbaie P, Shi X, Guo TZ, et al. Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision. Pain. 2009; 145: 341–349.
10.1016/j.pain.2009.06.037
CASPubMedWeb of Science®Google Scholar
36Teunkens A, Vermeulen K, Peters M, Fieuws S, Van de Velde M, Rex S. Bupivacaine infiltration in children for postoperative analgesia after tonsillectomy: a randomised controlled trial. Eur J Anaesthesiol. 2019; 36: 206–214.
10.1097/EJA.0000000000000950
CASPubMedWeb of Science®Google Scholar
37Cicekci F, Sizer C, Atici SS, Arican S, Karaibrahimoglu A, Kara I. Comparison of the perioperative and postoperative effects of levobupivacaine and of levobupivacaine + adrenaline in pediatric tonsillectomy: a double-blind randomized study. Pain Res Manag. 2017; 2017: 8431823.
10.1155/2017/8431823
PubMedWeb of Science®Google Scholar
38Tan GX, Tunkel DE. Control of pain after tonsillectomy in children: a review. JAMA Otolaryngol Head Neck Surg. 2017; 143: 937–942.
10.1001/jamaoto.2017.0845
PubMedWeb of Science®Google Scholar
39Tschopp C, Tramèr MR, Schneider A, Zaarour M, Elia N. Benefit and harm of adding epinephrine to a local anesthetic for neuraxial and locoregional anesthesia: a meta-analysis of randomized controlled trials with trial sequential analyses. Anesth Analg. 2018; 127: 228–239.
10.1213/ANE.0000000000003417
CASPubMedWeb of Science®Google Scholar
40Tolska HK, Takala A, Blomgren K, Hamunen K, Kontinen V. Topical ropivacaine in prevention of post-tonsillectomy pain in adults. Anesth Analg. 2017; 124: 1459–1466.
10.1213/ANE.0000000000002015
CASPubMedWeb of Science®Google Scholar
41Kreutzwiser D, Tawfic QA. Expanding role of NMDA receptor antagonists in the management of pain. CNS Drugs. 2019; 33: 347–374.
10.1007/s40263-019-00618-2
CASPubMedWeb of Science®Google Scholar
42Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet. 2016; 55: 1059–1077.
10.1007/s40262-016-0383-6
CASPubMedWeb of Science®Google Scholar
43Zhu A, Benzon HA, Anderson TA. Evidence for the efficacy of systemic opioid-sparing analgesics in pediatric surgical populations: a systematic review. Anesth Analg. 2017; 125: 1569–1587.
10.1213/ANE.0000000000002434
CASPubMedWeb of Science®Google Scholar
44Manworren RC, Stinson J. Pediatric pain measurement, assessment, and evaluation. Semin Pediatr Neurol. 2016; 23: 189–200.
10.1016/j.spen.2016.10.001
PubMedWeb of Science®Google Scholar
45Beltramini A, Milojevic K, Pateron D. Pain assessment in newborns, infants, and children. Pediatr Ann. 2017; 46: e387–e395.
10.3928/19382359-20170921-03
PubMedWeb of Science®Google Scholar

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Volume20, Issue5

June 2020

Pages 550-563

Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis

Abstract

Objectives

Methods

Results

Conclusions

Conflicts of Interest

References

Citing Literature

References

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Analgesic Efficacy and Safety of Local Infiltration of Tramadol in Pediatric Tonsillectomy Pain: A Systematic Review and Meta-Analysis

Abstract

Objectives

Methods

Results

Conclusions

Conflicts of Interest

References

Citing Literature

References

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