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


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.
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France.|Paris Diderot University, Paris, France.
Daphnée
D
Michelet
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France.|Paris Diderot University, Paris, France.
Julie
J
Hilly
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France.|Paris Diderot University, Paris, France.
Alia
A
Skhiri
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France.|Paris Diderot University, Paris, France.
Rachida
R
Abdat
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France.|Paris Diderot University, Paris, France.
Thierno
T
Diallo
Department of Anaesthesia and Pain Management, Royal Children's Hospital, Melbourne, Australia.
Christopher
C
Brasher
Department of Anesthesia and Intensive Care, Robert Debre University Hospital, Paris, France. souhayl.dahmani@rdb.aphp.fr.|Paris Diderot University, Paris, France. souhayl.dahmani@rdb.aphp.fr.|DHU PROTECT, INSERM U1141, Robert Debre University Hospital, Paris, France. souhayl.dahmani@rdb.aphp.fr.|Department of Anesthesiology, Intensive Care and Pain Management, Robert Debre Hospital, 48 Bd Sérurier, 75019, Paris, France. souhayl.dahmani@rdb.aphp.fr.
Souhayl
S
Dahmani
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002648:Child; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000188:drug therapy*; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology
D000701:Analgesics, Opioid; D007649:Ketamine
Stat Med. 1997 Apr 15;16(7):753-68
9131763
Int J Clin Pharmacol Ther. 2007 Mar;45(3):155-60
17416110
Eur J Anaesthesiol. 2015 Feb;32(2):85-7
25536187
J Opioid Manag. 2013 Sep-Oct;9(5):379-88
24353050
Paediatr Anaesth. 2003 Jun;13(5):413-21
12791115
Lancet. 1997 Mar 1;349(9052):599-603
9057731
Eur J Anaesthesiol. 2010 Jan;27(1):47-52
19535988
BMJ. 2001 Jul 14;323(7304):101-5
11451790
Anesth Analg. 2012 Feb;114(2):393-406
22104069
Anesth Pain Med. 2012 Fall;2(2):85-9
24223344
Paediatr Anaesth. 2008 Aug;18(8):708-14
18613930
Anesthesiology. 1987 Jun;66(6):832-4
2884900
Arch Dis Child Fetal Neonatal Ed. 2001 Jul;85(1):F36-41
11420320
Br J Anaesth. 1983 Nov;55(11):1107-11
6639827
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004603
16437490
Acta Anaesthesiol Belg. 2003;54(3):217-22
14598618
Curr Opin Anaesthesiol. 2006 Oct;19(5):556-61
16960491
Can J Anaesth. 2016 Mar;63(3):311-25
26659198
Paediatr Anaesth. 2003 Jun;13(5):422-6
12791116
Br J Anaesth. 1979 Dec;51(12):1167-73
526385
Stat Med. 2000 Nov 30;19(22):3127-31
11113947
Pharmacol Res. 2012 Apr;65(4):411-29
22311381
Paediatr Anaesth. 2011 Oct;21(10):1009-14
21575100
Pain. 2005 Jan;113(1-2):61-70
15621365
Paediatr Anaesth. 2014 Jun;24(6):582-90
24809838
Paediatr Anaesth. 2011 Jun;21(6):636-52
21447047
J Clin Epidemiol. 2009 Oct;62(10):e1-34
19631507
Spine (Phila Pa 1976). 2017 Mar;42(5):E304-E312
27398889
BMC Med Res Methodol. 2005 Apr 20;5:13
15840177
BMJ. 1997 Sep 13;315(7109):629-34
9310563
J Pain Palliat Care Pharmacother. 2011;25(3):219-30
21834699
Pain. 2010 Aug;150(2):257-67
20471751
Anesth Analg. 2008 Oct;107(4):1170-5
18806023
Med Sci Monit. 2009 Oct;15(10):CR539-543
19789514
Stat Med. 2008 Feb 28;27(5):625-50
17590884