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Erschienen in: Pediatric Drugs 6/2016

01.12.2016 | Systematic Review

Opioid-Sparing Effect of Ketamine in Children: A Meta-Analysis and Trial Sequential Analysis of Published Studies

verfasst von: Daphnée Michelet, Julie Hilly, Alia Skhiri, Rachida Abdat, Thierno Diallo, Christopher Brasher, Souhayl Dahmani

Erschienen in: Pediatric Drugs | Ausgabe 6/2016

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Abstract

Introduction

Reducing postoperative opioid consumption is a priority given its impact upon recovery, and the efficacy of ketamine as an opioid-sparing agent in children is debated. The goal of this study was to update a previous meta-analysis on the postoperative opioid-sparing effect of ketamine, adding trial sequential analysis (TSA) and four new studies.

Materials and Methods

A comprehensive literature search was conducted to identify clinical trials that examined ketamine as a perioperative opioid-sparing agent in children and infants. Outcomes measured were postoperative opioid consumption to 48 h (primary outcome: postoperative opioid consumption to 24 h), postoperative pain intensity, postoperative nausea and vomiting and psychotomimetic symptoms. The data were combined to calculate the pooled mean difference, odds ratios or standard mean differences. In addition to this classical meta-analysis approach, a TSA was performed.

Results

Eleven articles were identified, with four added to seven from the previous meta-analysis. Ketamine did not exhibit a global postoperative opioid-sparing effect to 48 postoperative hours, nor did it decrease postoperative pain intensity. This result was confirmed using TSA, which found a lack of power to draw any conclusion regarding the primary outcome of this meta-analysis (postoperative opioid consumption to 24 h). Ketamine did not increase the prevalence of either postoperative nausea and vomiting or psychotomimetic complications.

Conclusions

This meta-analysis did not find a postoperative opioid-sparing effect of ketamine. According to the TSA, this negative result might involve a lack of power of this meta-analysis. Further studies are needed in order to assess the postoperative opioid-sparing effects of ketamine in children.
Fußnoten
1
http://​www.​cochrane-handbook.​org/​ (Section 9.4.6). Last accessed June 2016.
 
2
http://​www.​cochrane-handbook.​org/​ (Section 9.5.2). Last accessed June 2016.
 
3
http://​www.​cochrane-handbook.​org/​ (Section 10.4.3.1). Last access June 2016.
 
4
http://​www.​cochrane-handbook.​org/​ (Section 10.4.3.1). Last access June 2016.
 
Literatur
1.
Zurück zum Zitat 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. Anesth Analg. 2012;114(2):393–406.CrossRefPubMed 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. Anesth Analg. 2012;114(2):393–406.CrossRefPubMed
2.
Zurück zum Zitat Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052):599–603.CrossRefPubMed Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052):599–603.CrossRefPubMed
3.
Zurück zum Zitat Hohmeister J, Kroll A, Wollgarten-Hadamek I, Zohsel K, Demirakca S, Flor H, et al. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study. Pain. 2010;150(2):257–67.CrossRefPubMed Hohmeister J, Kroll A, Wollgarten-Hadamek I, Zohsel K, Demirakca S, Flor H, et al. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study. Pain. 2010;150(2):257–67.CrossRefPubMed
5.
Zurück zum Zitat Elia N, Tramer MR. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain. 2005;113(1–2):61–70.CrossRefPubMed Elia N, Tramer MR. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain. 2005;113(1–2):61–70.CrossRefPubMed
6.
Zurück zum Zitat Ramasubbu C, Gupta A. Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence. J Pain Palliat Care Pharmacother. 2011;25(3):219–30.CrossRefPubMed Ramasubbu C, Gupta A. Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence. J Pain Palliat Care Pharmacother. 2011;25(3):219–30.CrossRefPubMed
7.
Zurück zum Zitat Tawfic QA. A review of the use of ketamine in pain management. J Opioid Manag. 2013;9(5):379–88.CrossRefPubMed Tawfic QA. A review of the use of ketamine in pain management. J Opioid Manag. 2013;9(5):379–88.CrossRefPubMed
8.
Zurück zum Zitat Weinbroum AA. Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Pharmacol Res. 2012;65(4):411–29.CrossRefPubMed Weinbroum AA. Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Pharmacol Res. 2012;65(4):411–29.CrossRefPubMed
9.
Zurück zum Zitat Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, et al. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatr Anaesth. 2011;21(6):636–52.CrossRefPubMed Dahmani S, Michelet D, Abback PS, Wood C, Brasher C, Nivoche Y, et al. Ketamine for perioperative pain management in children: a meta-analysis of published studies. Paediatr Anaesth. 2011;21(6):636–52.CrossRefPubMed
10.
Zurück zum Zitat Afshari A, Wetterslev J. When may systematic reviews and meta-analyses be considered reliable? 20141224 DCOM- 20150904(1365-2346 (Electronic)). Afshari A, Wetterslev J. When may systematic reviews and meta-analyses be considered reliable? 20141224 DCOM- 20150904(1365-2346 (Electronic)).
11.
Zurück zum Zitat Higgins JP, Whitehead A Fau, Simmonds M, Simmonds M. Sequential methods for random-effects meta-analysis. 20110407 DCOM-20110727(1097-0258 (Electronic)). Higgins JP, Whitehead A Fau, Simmonds M, Simmonds M. Sequential methods for random-effects meta-analysis. 20110407 DCOM-20110727(1097-0258 (Electronic)).
13.
Zurück zum Zitat Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.CrossRefPubMed Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.CrossRefPubMed
14.
Zurück zum Zitat Hannallah RS, Broadman LM, Belman AB, Abramowitz MD, Epstein BS. Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology. 1987;66(6):832–4.CrossRefPubMed Hannallah RS, Broadman LM, Belman AB, Abramowitz MD, Epstein BS. Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology. 1987;66(6):832–4.CrossRefPubMed
15.
Zurück zum Zitat Debillon T, Zupan V, Ravault N, Magny JF, Dehan M. Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001;85(1):F36–41.CrossRefPubMedPubMedCentral Debillon T, Zupan V, Ravault N, Magny JF, Dehan M. Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001;85(1):F36–41.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1):13.CrossRefPubMedPubMedCentral Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1):13.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Chinn S. A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med. 2000;19(22):3127–31.CrossRefPubMed Chinn S. A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med. 2000;19(22):3127–31.CrossRefPubMed
18.
Zurück zum Zitat Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323(7304):101–5.CrossRefPubMedPubMedCentral Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323(7304):101–5.CrossRefPubMedPubMedCentral
19.
20.
21.
Zurück zum Zitat Biggerstaff BJ, Tweedie RL. Incorporating variability in estimates of heterogeneity in the random effects model in meta-analysis. Stat Med. 1997;16(7):753–68.CrossRefPubMed Biggerstaff BJ, Tweedie RL. Incorporating variability in estimates of heterogeneity in the random effects model in meta-analysis. Stat Med. 1997;16(7):753–68.CrossRefPubMed
22.
Zurück zum Zitat Dix P, Martindale S, Stoddart PA. Double-blind randomized placebo-controlled trial of the effect of ketamine on postoperative morphine consumption in children following appendicectomy. Paediatr Anaesth. 2003;13(5):422–6.CrossRefPubMed Dix P, Martindale S, Stoddart PA. Double-blind randomized placebo-controlled trial of the effect of ketamine on postoperative morphine consumption in children following appendicectomy. Paediatr Anaesth. 2003;13(5):422–6.CrossRefPubMed
23.
Zurück zum Zitat O’Flaherty JE, Lin CX. Does ketamine or magnesium affect posttonsillectomy pain in children? Paediatr Anaesth. 2003;13(5):413–21.CrossRefPubMed O’Flaherty JE, Lin CX. Does ketamine or magnesium affect posttonsillectomy pain in children? Paediatr Anaesth. 2003;13(5):413–21.CrossRefPubMed
24.
Zurück zum Zitat Tarkkila P, Viitanen H, Mennander S, Annila P. Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy. Acta Anaesthesiol Belg. 2003;54(3):217–22.PubMed Tarkkila P, Viitanen H, Mennander S, Annila P. Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy. Acta Anaesthesiol Belg. 2003;54(3):217–22.PubMed
25.
Zurück zum Zitat Batra YK, Shamsah M, Al-Khasti MJ, Rawdhan HJ, Al-Qattan AR, Belani KG. Intraoperative small-dose ketamine does not reduce pain or analgesic consumption during perioperative opioid analgesia in children after tonsillectomy. Int J Clin Pharmacol Ther. 2007;45(3):155–60.CrossRefPubMed Batra YK, Shamsah M, Al-Khasti MJ, Rawdhan HJ, Al-Qattan AR, Belani KG. Intraoperative small-dose ketamine does not reduce pain or analgesic consumption during perioperative opioid analgesia in children after tonsillectomy. Int J Clin Pharmacol Ther. 2007;45(3):155–60.CrossRefPubMed
26.
Zurück zum Zitat Engelhardt T, Zaarour C, Naser B, Pehora C, de Ruiter J, Howard A, et al. Intraoperative low-dose ketamine does not prevent a remifentanil-induced increase in morphine requirement after pediatric scoliosis surgery. Anesth Analg. 2008;107(4):1170–5.CrossRefPubMed Engelhardt T, Zaarour C, Naser B, Pehora C, de Ruiter J, Howard A, et al. Intraoperative low-dose ketamine does not prevent a remifentanil-induced increase in morphine requirement after pediatric scoliosis surgery. Anesth Analg. 2008;107(4):1170–5.CrossRefPubMed
27.
Zurück zum Zitat Inanoglu K, Ozbakis Akkurt BC, Turhanoglu S, Okuyucu S, Akoglu E. Intravenous ketamine and local bupivacaine infiltration are effective as part of a multimodal regime for reducing post-tonsillectomy pain. Med Sci Monit. 2009;15(10):CR539–43.PubMed Inanoglu K, Ozbakis Akkurt BC, Turhanoglu S, Okuyucu S, Akoglu E. Intravenous ketamine and local bupivacaine infiltration are effective as part of a multimodal regime for reducing post-tonsillectomy pain. Med Sci Monit. 2009;15(10):CR539–43.PubMed
28.
Zurück zum Zitat Bazin V, Bollot J, Asehnoune K, Roquilly A, Guillaud C, De Windt A, et al. Effects of perioperative intravenous low dose of ketamine on postoperative analgesia in children. Eur J Anaesthesiol. 2010;27(1):47–52.CrossRefPubMed Bazin V, Bollot J, Asehnoune K, Roquilly A, Guillaud C, De Windt A, et al. Effects of perioperative intravenous low dose of ketamine on postoperative analgesia in children. Eur J Anaesthesiol. 2010;27(1):47–52.CrossRefPubMed
29.
Zurück zum Zitat Elshammaa N, Chidambaran V, Housny W, Thomas J, Zhang X, Michael R. Ketamine as an adjunct to fentanyl improves postoperative analgesia and hastens discharge in children following tonsillectomy—a prospective, double-blinded, randomized study. Paediatr Anaesth. 2011;21(10):1009–14.CrossRefPubMed Elshammaa N, Chidambaran V, Housny W, Thomas J, Zhang X, Michael R. Ketamine as an adjunct to fentanyl improves postoperative analgesia and hastens discharge in children following tonsillectomy—a prospective, double-blinded, randomized study. Paediatr Anaesth. 2011;21(10):1009–14.CrossRefPubMed
30.
Zurück zum Zitat Javid MJ, Hajijafari M, Hajipour A, Makarem J, Khazaeipour Z. Evaluation of a low dose ketamine in post tonsillectomy pain relief: a randomized trial comparing intravenous and subcutaneous ketamine in pediatrics. Anesth Pain Med. 2012;2(2):85–9.CrossRefPubMedPubMedCentral Javid MJ, Hajijafari M, Hajipour A, Makarem J, Khazaeipour Z. Evaluation of a low dose ketamine in post tonsillectomy pain relief: a randomized trial comparing intravenous and subcutaneous ketamine in pediatrics. Anesth Pain Med. 2012;2(2):85–9.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Perello M, Artes D, Pascuets C, Esteban E, Ey AM. Prolonged perioperative low-dose ketamine does not improve short and long-term outcomes after pediatric idiopathic scoliosis surgery. Spine (Phila Pa 1976). 2016. (Epub ahead of print) Perello M, Artes D, Pascuets C, Esteban E, Ey AM. Prolonged perioperative low-dose ketamine does not improve short and long-term outcomes after pediatric idiopathic scoliosis surgery. Spine (Phila Pa 1976). 2016. (Epub ahead of print)
32.
Zurück zum Zitat Pestieau SR, Finkel JC, Junqueira MM, Cheng Y, Lovejoy JF, Wang J, et al. Prolonged perioperative infusion of low-dose ketamine does not alter opioid use after pediatric scoliosis surgery. Paediatr Anaesth. 2014;24(6):582–90.CrossRefPubMed Pestieau SR, Finkel JC, Junqueira MM, Cheng Y, Lovejoy JF, Wang J, et al. Prolonged perioperative infusion of low-dose ketamine does not alter opioid use after pediatric scoliosis surgery. Paediatr Anaesth. 2014;24(6):582–90.CrossRefPubMed
33.
Zurück zum Zitat Dallimore D, Anderson BJ, Short TG, Herd DW. Ketamine anesthesia in children–exploring infusion regimens. Paediatr Anaesth. 2008;18(8):708–14.CrossRefPubMed Dallimore D, Anderson BJ, Short TG, Herd DW. Ketamine anesthesia in children–exploring infusion regimens. Paediatr Anaesth. 2008;18(8):708–14.CrossRefPubMed
34.
Zurück zum Zitat Idvall J, Ahlgren I, Aronsen KR, Stenberg P. Ketamine infusions: pharmacokinetics and clinical effects. Br J Anaesth. 1979;51(12):1167–73.CrossRefPubMed Idvall J, Ahlgren I, Aronsen KR, Stenberg P. Ketamine infusions: pharmacokinetics and clinical effects. Br J Anaesth. 1979;51(12):1167–73.CrossRefPubMed
35.
Zurück zum Zitat Grant IS, Nimmo WS, McNicol LR, Clements JA. Ketamine disposition in children and adults. Br J Anaesth. 1983;55(11):1107–11.CrossRefPubMed Grant IS, Nimmo WS, McNicol LR, Clements JA. Ketamine disposition in children and adults. Br J Anaesth. 1983;55(11):1107–11.CrossRefPubMed
36.
Zurück zum Zitat Wang L, Johnston B, Kaushal A, Cheng D, Zhu F, Martin J. Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials. Can J Anaesth. 2016;63(3):311–25.CrossRefPubMed Wang L, Johnston B, Kaushal A, Cheng D, Zhu F, Martin J. Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials. Can J Anaesth. 2016;63(3):311–25.CrossRefPubMed
37.
Zurück zum Zitat Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006;1:CD004603. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006;1:CD004603.
Metadaten
Titel
Opioid-Sparing Effect of Ketamine in Children: A Meta-Analysis and Trial Sequential Analysis of Published Studies
verfasst von
Daphnée Michelet
Julie Hilly
Alia Skhiri
Rachida Abdat
Thierno Diallo
Christopher Brasher
Souhayl Dahmani
Publikationsdatum
01.12.2016
Verlag
Springer International Publishing
Erschienen in
Pediatric Drugs / Ausgabe 6/2016
Print ISSN: 1174-5878
Elektronische ISSN: 1179-2019
DOI
https://doi.org/10.1007/s40272-016-0196-y

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