Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis

Ke Peng, Shao-ru Wu, Fu-hai Ji, Jian Li, Ke Peng, Shao-ru Wu, Fu-hai Ji, Jian Li

Abstract

Premedication is important in pediatric anesthesia. This meta-analysis aimed to investigate the role of dexmedetomidine as a premedicant for pediatric patients. A systematic literature search was conducted to identify randomized controlled trials comparing dexmedetomidine premedication with midazolam or ketamine premedication or placebo in children. Two reviewers independently performed the study selection, quality assessment and data extraction. The original data were pooled for the meta-analysis with Review Manager 5. The main parameters investigated included satisfactory separation from parents, satisfactory mask induction, postoperative rescue analgesia, emergence agitation and postoperative nausea and vomiting. Thirteen randomized controlled trials involving 1190 patients were included. When compared with midazolam, premedication with dexmedetomidine resulted in an increase in satisfactory separation from parents (RD = 0.18, 95% CI: 0.06 to 0.30, p = 0.003) and a decrease in the use of postoperative rescue analgesia (RD = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003). Children treated with dexmedetomidine had a lower heart rate before induction. The incidence of satisfactory mask induction, emergence agitation and PONV did not differ between the groups. Dexmedetomidine was superior in providing satisfactory intravenous cannulation compared to placebo. This meta-analysis suggests that dexmedetomidine is superior to midazolam premedication because it resulted in enhanced preoperative sedation and decreased postoperative pain. Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia.

Conflict of interest statement

No potential conflict of interest was reported.

Figures

Figure 1
Figure 1
Flow chart of retrieved, excluded and included trials.
Figure 2
Figure 2
Meta-analysis of satisfactory separation from parents in children treated with dexmedetomidine vs. midazolam.
Figure 3
Figure 3
Meta-analysis of satisfactory mask induction in children treated with dexmedetomidine vs. midazolam.
Figure 4
Figure 4
Meta-analysis of postoperative rescue analgesia in children treated with dexmedetomidine vs. midazolam.
Figure 5
Figure 5
Meta-analysis of EA in children treated with dexmedetomidine vs. midazolam. EA: emergence agitation.
Figure 6
Figure 6
Meta-analysis of PONV in children treated with dexmedetomidine vs. midazolam. PONV: postoperative nausea and vomiting.

References

    1. Kain ZN, Mayes LC, O′Connor TZ, Cicchetti DV. Preoperative anxiety in children. Predictors and outcomes. Arch Pediatr Adolesc Med. 1996;150(12):1238–45.
    1. Yuki K, Daaboul DG. Postoperative maladaptive behavioral changes in children. Middle East J Anesthesiol. 2011;21(2):183–9.
    1. Aydin T, Sahin L, Algin C, Kabay S, Yucel M, Hacioglu A, et al. Do not mask the mask: use it as a premedicant. Paediatric Anaesth. 2008;18(2):107–12.
    1. Karling M, Stenlund H, Hagglof B. Child behaviour after anaesthesia: associated risk factors. Acta Paediatr. 2007;96(5):740–7.
    1. Kain ZN, Caldwell-Andrews AA, Maranets I, McClain B, Gaal D, Mayes LC, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg. 2004;99(6):1648–54.
    1. Kain ZN, Wang SM, Mayes LC, Caramico LA, Hofstadter MB. Distress during the induction of anesthesia and postoperative behavioral outcomes. Anesth Analg. 1999;88(5):1042–7.
    1. Palermo TM, Drotar D. Prediction of children's postoperative pain: the role of presurgical expectations and anticipatory emotions. J Pediatr Psychol. 1996;21(5):683–98.
    1. Strom S. Preoperative evaluation, premedication, and induction of anesthesia in infants and children. Curr Opin Anaesthesiol. 2012;25(3):321–5.
    1. Bozkurt P. Premedication of the pediatric patient - anesthesia for the uncooperative child. Curr Opin Anaesthesiol. 2007;20(3):211–5.
    1. Almenrader N, Passariello M, Coccetti B, Haiberger R, Pietropaoli P. Premedication in children: a comparison of oral midazolam and oral clonidine. Paediatr Anaesth. 2007;17(12):1143–9.
    1. Kain ZN, Caldwell-Andrews AA, Krivutza DM, Weinberg ME, Wang SM, Gaal D. Trends in the practice of parental presence during induction of anesthesia and the use of preoperative sedative premedication in the United States, 1995-2002: results of a follow-up national survey. Anesth Analg. 2004;98(5):1252–9.
    1. Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: a comparison of four routes of administration. Paediatr Anaesth. 2002;12(8):685–9.
    1. Davis PJ, Tome JA, McGowan FX, Jr, Cohen IT, Latta K, Felder H. Preanesthetic medication with intranasal midazolam for brief pediatric surgical procedures. Effect on recovery and hospital discharge times. Anesthesiology. 1995;82(1):2–5.
    1. Wilton NC, Leigh J, Rosen DR, Pandit UA. Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology. 1988;69(6):972–5.
    1. Marshall J, Rodarte A, Blumer J, Khoo KC, Akbari B, Kearns G. Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network. J Clin Pharmacol. 2000;40(6):578–89.
    1. Kain ZN, Hofstadter MB, Mayes LC, Krivutza DM, Alexander G, Wang SM, et al. Midazolam: effects on amnesia and anxiety in children. Anesthesiology. 2000;93(3):676–84.
    1. Splinter WM, MacNeill HB, Menard EA, Rhine EJ, Roberts DJ, Gould MH. Midazolam reduces vomiting after tonsillectomy in children. Can J Anaesth. 1995;42(3):201–3.
    1. Kupietzky A, Houpt MI. Midazolam: a review of its use for conscious sedation of children. Pediatri Dent. 1993;15(4):237–41.
    1. Bergendahl H, Lonnqvist PA, Eksborg S. Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication. Acta Anaesthesiol Scand. 2006;50(2):135–43.
    1. Lonnqvist PA, Habre W. Midazolam as premedication: is the emperor naked or just half-dressed. Paediatr Anaesth. 2005;15(4):263–5.
    1. McGraw T, Kendrick A. Oral midazolam premedication and postoperative behaviour in children. Paediatr Anaesth. 1998;8(2):117–21.
    1. Turhanoglu S, Kararmaz A, Ozyilmaz MA, Kaya S, Tok D. Effects of different doses of oral ketamine for premedication of children. Eur J Anaesthesiol. 2003;20(1):56–60.
    1. Sekerci C, Donmez A, Ates Y, Okten F. Oral ketamine premedication in children (placebo controlled double-blind study) Eur J Anaesthesiol. 1996;13(6):606–11.
    1. Bowdle TA, Radant AD, Cowley DS, Kharasch ED, Strassman RJ, Roy-Byrne PP. Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology. 1998;88(1):82–8.
    1. Gingrich BK. Difficulties encountered in a comparative study of orally administered midazolam and ketamine. Anesthesiology. 1994;80(6):1414–5.
    1. Donahue PJ, Dineen PS. Emergence delirium following oral ketamine. Anesthesiology. 1992;77(3):604–5.
    1. Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000;59(2):263–8. discussion 9-70.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
    1. Cochrane Handbook for Systematic Reviews of Interventions Chapter 16.5.4 How to include multiple groups from one study. [].
    1. Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. Br J Anaesth. 2013;110(6):915–25.
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary. Control Clin Trials. 1996;17(1):1–12.
    1. Linares Segovia B, García Cuevas MA, Ramírez Casillas IL, Guerrero Romero JF, Botello Buenrostro I, Monroy Torres R, et al. Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial. An Pediatr (Barc) 2014 Jan 25 pii: S1695- 4033(13)00525-0.
    1. Sheta SA, Al-Sarheed MA, Abdelhalim AA. Intranasal dexmedetomidine vs midazolam for premedication in children undergoing complete dental rehabilitation: a double-blinded randomized controlled trial. Paediat Anaesth. 2014;24(2):181–9.
    1. Pant D, Sethi N, Sood J. Comparison of sublingual midazolam and dexmedetomidine for premedication in children. Minerva Anestesiol. 2014;80(2):167–75.
    1. Mostafa MG, Morsy KM. Premedication with intranasal dexmedetomidine, midazolam and ketamine for children undergoing bone marrow biopsy and aspirate. Egyptian J Anaesth. 2013;29(2):131–5.
    1. Gyanesh P, Haldar R, Srivastava D, Agrawal PM, Tiwari AK, Singh PK. Comparison between intranasal dexmedetomidine and intranasal ketamine as premedication for procedural sedation in children undergoing MRI: a double-blind, randomized, placebo-controlled trial. J Anesth. 2014;28(1):12–8.
    1. Akin A, Bayram A, Esmaoglu A, Tosun Z, Aksu R, Altuntas R, et al. Dexmedetomidine vs midazolam for premedication of pediatric patients undergoing anesthesia. Paediatr Anaesthes. 2012;22(9):871–6.
    1. Ozcengiz D, Gunes Y, Ozmete O. Oral melatonin, dexmedetomidine, and midazolam for prevention of postoperative agitation in children. J Anesth. 2011;25(2):184–8.
    1. Mountain BW, Smithson L, Cramolini M, Wyatt TH, Newman M. Dexmedetomidine as a pediatric anesthetic premedication to reduce anxiety and to deter emergence delirium. AANA J. 2011;79(3):219–24.
    1. Ghali AM, Mahfouz AK, Al-Bahrani M. Preanesthetic medication in children: A comparison of intranasal dexmedetomidine versus oral midazolam. Saudi J Anaesth. 2011;5(4):387–91.
    1. Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK. Optimal timing for the administration of intranasal dexmedetomidine for premedication in children. Anaesthesia. 2010;65(9):922–9.
    1. Talon MD, Woodson LC, Sherwood ER, Aarsland A, McRae L, Benham T. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. Journal of burn care & research: official publication of the American Burn Assoc. 2009;30(4):599–605.
    1. Yuen VM, Hui TW, Irwin MG, Yuen MK. A comparison of intranasal dexmedetomidine and oral midazolam for premedication in pediatric anesthesia: a double-blinded randomized controlled trial. Anesth Analg. 2008;106(6):1715–21.
    1. Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simoes CM, Auler JO., Jr Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatr Aanaesth. 2007;17(7):667–74.
    1. Davidson A, McKenzie I. Distress at induction: prevention and consequences. Curr Opin Anaesthesiol. 2011;24(3):301–6.
    1. Reed MD, Rodarte A, Blumer JL, Khoo KC, Akbari B, Pou S, et al. The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration. J Clin Pharmacol. 2001;41(12):1359–69.
    1. Malinovsky JM, Lejus C, Servin F, Lepage JY, Le Normand Y, Testa S, et al. Plasma concentrations of midazolam after i.v., nasal or rectal administration in children. Br J Anaesth. 1993;70(6):617–20.
    1. Primosch RE, Bender F. Factors associated with administration route when using midazolam for pediatric conscious sedation. ASDC J Dent Child. 2001;68(4):233–8.
    1. Khalil SN, Vije HN, Kee SS, Farag A, Hanna E, Chuang AZ. A paediatric trial comparing midazolam/Syrpalta mixture with premixed midazolam syrup (Roche) Paediatric Anaesth. 2003;13(3):205–9.
    1. Su F, Nicolson SC, Gastonguay MR, Barrett JS, Adamson PC, Kang DS, et al. Population pharmacokinetics of dexmedetomidine in infants after open heart surgery. Anesth Analg. 2010;110(5):1383–92.
    1. Potts AL, Anderson BJ, Holford NH, Vu TC, Warman GR. Dexmedetomidine hemodynamics in children after cardiac surgery. Paediatr Anaesth. 2010;20(5):425–33.
    1. Potts AL, Anderson BJ, Warman GR, Lerman J, Diaz SM, Vilo S. Dexmedetomidine pharmacokinetics in pediatric intensive care–a pooled analysis. Paediatr Anaesth. 2009;19(11):1119–29.
    1. Vilo S, Rautiainen P, Kaisti K, Aantaa R, Scheinin M, Manner T, et al. Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. Br J Anaesth. 2008;100(5):697–700.
    1. Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, et al. A phase I, two-center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology. 2006;105(6):1098–110.
    1. Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003;98(2):428–36.
    1. Dahmani S, Brasher C, Stany I, Golmard J, Skhiri A, Bruneau B, et al. Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies. Acta Anaesthesiol Scand. 2010;54(4):397–402.
    1. Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G, et al. Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol. 2004;16(2):126–35.
    1. Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, et al. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg. 2000;90(4):834–9.
    1. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000;90(3):699–705.
    1. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.
    1. Blaudszun G, Lysakowski C, Elia N, Tramer MR. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012;116(6):1312–22.
    1. Schnabel A, Meyer-Friessem CH, Reichl SU, Zahn PK, Pogatzki-Zahn EM. Is intraoperative dexmedetomidine a new option for postoperative pain treatment. A meta-analysis of randomized controlled trials. Pain. 2013;154(7):1140–9.
    1. Schnabel A, Reichl SU, Poepping DM, Kranke P, Pogatzki-Zahn EM, Zahn PK. Efficacy and safety of intraoperative dexmedetomidine for acute postoperative pain in children: a meta-analysis of randomized controlled trials. Paediatr Anaesth. 2013;23(2):170–9.
    1. Silva LM, Braz LG, Modolo NS. Emergence agitation in pediatric anesthesia: current features. J Pediatr (Rio J) 2008;84(2):107–13.
    1. Jia JE, Chen JY, Hu X, Li WX. A randomised study of intranasal dexmedetomidine and oral ketamine for premedication in children. Anaesthesia. 2013;68(9):944–9.
    1. Daabiss MA, Hashish M. Dexmedetomidine versus ketamine combined with midazolam; a comparison of anxiolytic and sedative premedication in children. Brit J Med Pract. 2011;4(4):4.
    1. Stewart KG, Rowbottom SJ, Aitken AW, Rajendram S, Sudhaman DA. Oral ketamine premedication for paediatric cardiac surgery–a comparison with intramuscular morphine (both after oral trimeprazine) Anaesth Intensive Care. 1990;18(1):11–4.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe