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Review
. 2014 Sep 12;2014(9):CD007084.
doi: 10.1002/14651858.CD007084.pub2.

Effects of sevoflurane versus other general anaesthesia on emergence agitation in children

David Costi  1 , Allan M Cyna, Samira Ahmed, Kate Stephens, Penny Strickland, James Ellwood, Jessica N Larsson, Cheryl Chooi, Laura L Burgoyne, Philippa Middleton
Affiliations
Review

Effects of sevoflurane versus other general anaesthesia on emergence agitation in children

David Costi et al. Cochrane Database Syst Rev. .

Abstract

Background: Sevoflurane is an inhaled volatile anaesthetic that is widely used in paediatric anaesthetic practice. Since its introduction, postoperative behavioural disturbance known as emergence agitation (EA) or emergence delirium (ED) has been recognized as a problem that may occur during recovery from sevoflurane anaesthesia. For the purpose of this systematic review, EA has been used to describe this clinical entity. A child with EA may be restless, may cause self-injury or may disrupt the dressing, surgical site or indwelling devices, leading to the potential for parents to be dissatisfied with their child's anaesthetic. To prevent such outcomes, the child may require pharmacological or physical restraint. Sevoflurane may be a major contributing factor in the development of EA. Therefore, an evidence-based understanding of the risk/benefit profile regarding sevoflurane compared with other general anaesthetic agents and adjuncts would facilitate its rational and optimal use.

Objectives: To compare sevoflurane with other general anaesthetic (GA) agents, with or without pharmacological or non-pharmacological adjuncts, with regard to risk of EA in children during emergence from anaesthesia. The primary outcome was risk of EA; secondary outcome was agitation score.

Search methods: We searched the following databases from the date of inception to 19 January 2013: CENTRAL, Ovid MEDLINE, Ovid EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost), Evidence-Based Medicine Reviews (EBMR) and the Web of Science, as well as the reference lists of other relevant articles and online trial registers.

Selection criteria: We included all randomized (or quasi-randomized) controlled trials investigating children < 18 years of age presenting for general anaesthesia with or without surgical intervention. We included any study in which a sevoflurane anaesthetic was compared with any other GA, and any study in which researchers investigated adjuncts (pharmacological or non-pharmacological) to sevoflurane anaesthesia compared with no adjunct or placebo.

Data collection and analysis: Two review authors independently searched the databases, decided on inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved differences between their results by discussion. Data were entered into RevMan 5.2 for analyses and presentation. Comparisons of the risk of EA were presented as risk ratios (RRs) with 95% confidence intervals (CIs). Sevoflurane is treated as the control anaesthesia in this review. Sensitivity analyses were performed as appropriate, to exclude studies with a high risk of bias and to investigate heterogeneity.

Main results: We included 158 studies involving 14,045 children. Interventions to prevent EA fell into two broad groups. First, alternative GA compared with sevoflurane anaesthesia (69 studies), and second, use of an adjunct with sevoflurane anaesthesia versus sevoflurane without an adjunct (100 studies). The overall risk of bias in included studies was low. The overall Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) assessment of the quality of the evidence was moderate to high. A wide range of EA scales were used, as were different levels of cutoff, to determine the presence or absence of EA. Some studies involved children receiving potentially inadequate or no analgesia intraoperatively during painful procedures.Halothane (RR 0.51, 95% CI 0.41 to 0.63, 3534 participants, high quality of evidence) and propofol anaesthesia were associated with a lower risk of EA than sevoflurane anaesthesia. Propofol was effective when used throughout anaesthesia (RR 0.35, 95% CI 0.25 to 0.51, 1098 participants, high quality of evidence) and when used only during the maintenance phase of anaesthesia after sevoflurane induction (RR 0.59, 95% CI 0.46 to 0.76, 738 participants, high quality of evidence). No clear evidence was found of an effect on risk of EA of desflurane (RR 1.46, 95% CI 0.92 to 2.31, 408 participants, moderate quality of evidence) or isoflurane (RR 0.76, 95% CI 0.46 to 1.23, 379 participants, moderate quality of evidence) versus sevoflurane.Compared with no adjunct, effective adjuncts for reducing the risk of EA during sevoflurane anaesthesia included dexmedetomidine (RR 0.37, 95% CI 0.29 to 0.47, 851 participants, high quality of evidence), clonidine (RR 0.45, 95% CI 0.31 to 0.66, 739 participants, high quality of evidence), opioids, in particular fentanyl (RR 0.37, 95% CI 0.27 to 0.50, 1247 participants, high quality of evidence) and a bolus of propofol (RR 0.58, 95% CI 0.38 to 0.89, 394 participants, moderate quality of evidence), ketamine (RR 0.30, 95% CI 0.13 to 0.69, 231 participants, moderate quality of evidence) or midazolam (RR 0.57, 95% CI 0.41 to 0.81, 116 participants, moderate quality of evidence) at the end of anaesthesia. Midazolam oral premedication (RR 0.81, 95% CI 0.59 to 1.12, 370 participants, moderate quality of evidence) and parental presence at emergence (RR 0.91, 95% CI 0.51 to 1.60, 180 participants, moderate quality of evidence) did not reduce the risk of EA.One or more factors designated as high risk of bias were noted in less than 10% of the included studies. Sensitivity analyses of these studies showed no clinically relevant changes in the risk of EA. Heterogeneity was significant with respect to these comparisons: halothane; clonidine; fentanyl; midazolam premedication; propofol 1 mg/kg bolus at end; and ketamine 0.25 mg/kg bolus at end of anaesthesia. With investigation of heterogeneity, the only clinically relevant changes to findings were seen in the context of potential pain, namely, the setting of adenoidectomy/adenotonsillectomy (propofol bolus; midazolam premedication) and the absence of a regional block (clonidine).

Authors' conclusions: Propofol, halothane, alpha-2 agonists (dexmedetomidine, clonidine), opioids (e.g. fentanyl) and ketamine reduce the risk of EA compared with sevoflurane anaesthesia, whereas no clear evidence shows an effect for desflurane, isoflurane, midazolam premedication and parental presence at emergence. Therefore anaesthetists can consider several effective strategies to reduce the risk of EA in their clinical practice. Future studies should ensure adequate analgesia in the control group, for which pain may be a contributing or confounding factor in the diagnosis of EA. Regardless of the EA scale used, it would be helpful for study authors to report the risk of EA, so that this might be included in future meta-analyses. Researchers should also consider combining effective interventions as a multi-modal approach to further reduce the risk of EA.

PubMed Disclaimer

Conflict of interest statement

David Costi: received a SPANZA research grant (The Society for Paediatric Anaesthesia in New Zealand and Australia) for a randomized controlled study of EA in 2010.

Allan M Cyna: received travel and accommodation expenses for speaking at the New Zealand Society of Hypnosis ASM in 2013.

Samira Ahmed: none known.

Kate Stephens: none known.

Penny Strickland: none known.

James Ellwood: none known.

Jessica N Larsson: none known.

Cheryl Chooi: none known.

Laura L Burgoyne: none known.

Philippa Middleton: none known.

Figures

1
1
Study flow diagram. We reran the search in April 2014. We found a further 29 studies of interest, which we will assess for eligibility when we update the review.*
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.
4
4
Funnel plot of comparison: 1 Any other GA versus sevoflurane anaesthesia, outcome: 1.1 Emergence agitation.
5
5
Funnel plot of comparison: 2 Adjunct versus placebo/No adjunct during sevoflurane anaesthesia, outcome: 2.1 Emergence agitation.
1.1
1.1. Analysis
Comparison 1 Any other GA versus sevoflurane anaesthesia, Outcome 1 Emergence agitation.
2.1
2.1. Analysis
Comparison 2 Adjunct versus placebo/No adjunct during sevoflurane anaesthesia, Outcome 1 Emergence agitation.
See this image and copyright information in PMC

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Ibacache 2004 {published data only}
    1. Ibacache ME, Muñoz HR, Brandes V, Morales AL. Single‐dose dexmedetomidine reduces agitation after sevoflurane anesthesia in children. Anesthesia and Analgesia 2004;98(1):60‐3. [PUBMED: 14693585] - PubMed
Im 2004 {published data only}
    1. Im MJ, Kim DY, Kim CH, Kim YJ. The effect of ketorolac and fentanyl on the emergence characteristics after sevoflurane anesthesia in children undergoing tonsillectomy and adenoidectomy. Korean Journal of Anesthesiology 2004;46:29‐34.
Inomata 2010 {published and unpublished data}
    1. Inomata S, Maeda, T Shimizu T, Satsumae T, Tanaka M. Effects of fentanyl infusion on tracheal intubation and emergence agitation in preschool children anaesthetized with sevoflurane. British Journal of Anaesthesia 2010;105(3):361‐7. [PUBMED: 20627877] - PubMed
Isik 2005 {published data only}
    1. Isik B, Arslan M, Dogan AT, Kurtipek O. The effect of fentanyl administration at different periods on emergence agitation [Farkli zamanlarda uygulanan fentanilin derlenme ajitasyonu uzerine etkisi]. Turk Anesteziyoloji ve Reanimasyon Dernegi Dergisi 2005;33:311‐7.
Isik 2006a {published data only}
    1. Isik B, Arslan M, Tunga AD, Kurtipek O. Dexmedetomidine decreases emergence agitation in pediatric patients after sevoflurane anesthesia without surgery. Pediatric Anaesthesia 2006;16(7):748‐53. [PUBMED: 16879517] - PubMed
Jacob 2012 {published data only}
    1. Jacob Z, Li H, Zhang S, Jambawalikar S, Makaryus R, Benveniste H. Brain metabolites discriminate sevoflurane from propofol anesthesia in children. Anesthesia and Analgesia 2011;112(Suppl):S351.
Jiang 2010 {published data only}
    1. Jiang XY, Li TZ, Li L. Premedication with oral midazolam in children receive sevoflurane general anesthesia. National Medical Journal of China 2010;90(37):2633‐5. [PUBMED: 21162931] - PubMed
Johannesson 1995 {published data only}
    1. Johannesson GP, Florén M, Lindahl SGE. Sevoflurane for ENT‐surgery in children. A comparison with halothane. Acta Anaesthesiologica Scandinavica 1995;39(4):546‐50. [PUBMED: 7676795] - PubMed
Jung 2010 {published data only}
    1. Jung HJ, Kim JB, Im KS, Oh SH, Lee JM. Effect of ketamine versus thiopental sodium anesthetic induction and a small dose of fentanyl on emergence agitation after sevoflurane anesthesia in children undergoing brief ophthalmic surgery. Korean Journal of Anesthesiology 2010;58(2):148‐52. [PUBMED: 20498793] - PMC - PubMed
Kain 2005 {published data only}
    1. Kain ZN, Caldwell‐Andrews AA, Weinberg ME, Mayes LC, Wang SM, Gaal D, et al. Sevoflurane versus halothane: postoperative maladaptive behavioral changes: a randomized, controlled trial. Anesthesiology 2005;102(4):720‐6. [PUBMED: 15791099] - PubMed
Kataria 1996 {published data only}
    1. Kataria B, Epstein R, Bailey A, Schmitz M, Backus WW, Schoeck D, et al. A comparison of sevoflurane to halothane in paediatric surgical patients: results of a multicentre international study. Paediatric Anaesthesia 1996;6(4):283‐92. [PUBMED: 8827744] - PubMed
Kazak 2010 {published data only}
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Keaney 2004 {published data only}
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Khattab 2009 {published data only}
    1. Khattab AM, El‐Seify ZA. Sevoflurane‐emergence agitation: effect of supplementary low‐dose oral ketamine premedication in preschool children undergoing dental surgery. Saudi Journal of Anaesthesia 2009;3(2):61‐6. [PUBMED: 20532105] - PMC - PubMed
    1. Khattab AM, El‐Seify ZA, Shaaban A, Radojevic D, Jankovic I. Sevoflurane‐emergence agitation: effect of supplementary low‐dose oral ketamine premedication in preschool children undergoing dental surgery. European Journal of Anaesthesiology 2010;27(4):353‐8. [PUBMED: 20035226] - PubMed
Kim 2009 {published data only}
    1. Kim JY, Chang YJ, Lee JY, Park HY, Kwak HJ. Post‐induction alfentanil reduces sevoflurane‐associated emergence agitation in children undergoing an adenotonsillectomy. Acta Anaesthesiologica Scandinavica 2009;53(5):678‐81. [PUBMED: 19419364] - PubMed
Kim 2011 {published data only}
    1. Kim YH, Yoon SZ, Lim HJ, Yoon SM. Prophylactic use of midazolam or propofol at the end of surgery may reduce the incidence of emergence agitation after sevoflurane anaesthesia. Anaesthesia and Intensive Care 2011;39(5):904‐08. [PUBMED: 21970137] - PubMed
Ko 2001 {published and unpublished data}
    1. Ko YP, Huang CJ, Hung YC, Su NY, Tsai PS, Chen CC, et al. Premedication with low‐dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurane anesthesia. Acta Anaesthesiologica Sinica 2001;39(4):169‐77. [PUBMED: 11840583] - PubMed
Kobylarz 2001 {published data only}
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Kol 2008 {published data only}
    1. Kol IO, Egilmez H, Kaygusuz K, Gursoy S, Mimaroglu C. Open‐label, prospective, randomized comparison of propofol and sevoflurane for laryngeal mask anesthesia for magnetic resonance imaging in pediatric patients. Clinical Therapeutics 2008;30(1):175‐81. [PUBMED: 18343254] - PubMed
Koner 2011 {published data only}
    1. Koner O, Ture H, Mercan A, Menda F, Sozubir S. Effects of hydroxyzine‐midazolam premedication on sevoflurane‐induced paediatric emergence agitation: a prospective randomised clinical trial. European Journal of Anaesthesiology 2011;28(9):640‐5. [PUBMED: 21822077] - PubMed
Konig 2009 {published data only}
    1. König MW, Varughese AM, Brennen KA, Barclay S, Shackleford TM, Samuels PJ, et al. Quality of recovery from two types of general anesthesia for ambulatory dental surgery in children: a double‐blind, randomized trial. Pediatric Anesthesia 2009;19(8):748‐55. [PUBMED: 19538532] - PubMed
Kubo 2001 {published data only}
    1. Kubo S, Kinouchi K, Taniguchi A, Fukumitsu K, Kitamura S. Recovery characteristics of propofol anesthesia in pediatric outpatients; comparison with sevoflurane anesthesia. Japanese Journal of Anesthesiology [Masui] 2001;50(4):371‐7. [PUBMED: 11345748] - PubMed
Kulka 2001a {published data only}
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Kulka 2001b {published data only}
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Lankinen 2006 {published data only}
    1. Lankinen U, Avela R, Tarkkila P. The prevention of emergence agitation with tropisetron or clonidine after sevoflurane anesthesia in small children undergoing adenoidectomy. Anesthesia and Analgesia 2006;102(5):1383‐6. [PUBMED: 16632814] - PubMed
Lapin 1999 {published data only}
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Le Berre 2001 {published and unpublished data}
    1. Berre PY, Wodey E, Joly A, Carré P, Ecoffey C. Comparison of recovery after intermediate duration of anaesthesia with sevoflurane and isoflurane. Paediatric Anaesthesia 2001;11(4):443‐8. [PUBMED: 11442862] - PubMed
Lee 2010a {published data only}
    1. Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park YC. The effect of ketamine on the incidence of emergence agitation in children undergoing tonsillectomy and adenoidectomy under sevoflurane general anesthesia. Korean Journal of Anesthesiology 2010;58(5):440‐5. [PUBMED: 20532051] - PMC - PubMed
Lee 2010b {published data only}
    1. Lee CJ, Lee SE, Oh MK, Shin CM, Kim YJ, Choe YK, et al. The effect of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy. Korean Journal of Anesthesiology 2010;59(2):75‐81. [PUBMED: 20740210] - PMC - PubMed
Lee 2011 {published data only}
    1. Lee YC, Kim JM, Ko HB, Lee SR. Use of laryngeal mask airway and its removal in a deeply anaesthetized state reduces emergence agitation after sevoflurane anaesthesia in children. The Journal of International Medical Research 2011;39(6):2385‐92. [PUBMED: 22289558] - PubMed
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    1. Lerman J, Davis PJ, Welborn LG, Orr RJ, Rabb M, Carpenter R, et al. Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane. Anesthesiology 1996;84(6):1332‐40. [PUBMED: 8669674] - PubMed
Li 2011 {published data only}
    1. Li J, Huang ZL, Zhang XT, Luo K, Zhang ZQ, Mao Y, et al. Sufentanil reduces emergence agitation in children receiving sevoflurane anesthesia for adenotonsillectomy compared with fentanyl. Chinese Medical Journal 2011;124:3682‐5. [PUBMED: 22340224] - PubMed
Liao 2010 {published data only}
    1. Liao R, Li JY, Liu GY. Comparison of sevoflurane volatile induction/maintenance anaesthesia and propofol‐remifentanil total intravenous anaesthesia for rigid bronchoscopy under spontaneous breathing for tracheal/bronchial foreign body removal in children. European Journal of Anaesthesiology 2010;27(11):930‐4. [PUBMED: 20683333] - PubMed
Liao 2011 {published data only}
    1. Liao WW, Wang JJ, Wu GJ, Kuo CD. The effect of cerebral monitoring on recovery after sevoflurane anesthesia in ambulatory setting in children: a comparison among bispectral index, A‐line autoregressive index, and standard practice. Journal of the Chinese Medical Association 2011;74(1):28‐36. [PUBMED: 21292200] - PubMed
Lili 2012 {published data only}
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Lin 2009 {published data only}
    1. Lin YC, Tassone RF, Jahng S, Rahbar R, Holzman RS, Zurakowski D, et al. Acupuncture management of pain and emergence agitation in children after bilateral myringotomy and tympanostomy tube insertion. Paediatric Anaesthesia 2009;19(11):1096‐101. [PUBMED: 19709377] - PubMed
Lopez Gil 1999 {published data only}
    1. Lopéz Gil ML, Brimacombe J, Clar B. Sevoflurane versus propofol for induction and maintenance of anaesthesia with the laryngeal mask airway in children. Paediatric Anaesthesia 1999;9(6):485‐90. [PUBMED: 10597550] - PubMed
Makharita 2009 {published data only}
    1. Makharita MY, Ahmady M, El‐Morsy G, El‐Emam H, Raouf AA, Eldeek BS. Prevention of pediatric emergence agitation after sevoflurane anaesthesia using preoperative rectal acetaminophen and intraoperative IV fentanyl. Egyptian Journal of Anaesthesia 2009;25:319‐25.
Malviya 2006 {published data only}
    1. Malviya S, Voepel‐Lewis T, Ramamurthi RJ, Burke C, Tait AR. Clonidine for the prevention of emergence agitation in young children: efficacy and recovery profile. Paediatric Anaesthesia 2006;16(5):554‐9. [PUBMED: 16677266] - PubMed
Meena 2009 {published data only}
    1. Meena K, Pandy M, Jain A. Comparison of induction and recovery characteristics of sevoflurane versus halothane in pre‐school children undergoing cleft lip palate repair. Journal of Anaesthesiology and Clinical Pharmacology 2009;25(2):171‐4.
Meng 2012 {published data only}
    1. Meng QT, Xia ZY, Luo T, Wu Y, Tang LH, Zhao B, et al. Dexmedetomidine reduces emergence agitation after tonsillectomy in children by sevoflurane anesthesia: a case‐control study. International Journal of Pediatric Otorhinolaryngology 2012;76(7):1036‐41. [PUBMED: 22537843] - PubMed
Meyer 2007 {published data only}
    1. Meyer RR, Münster P, Werner C, Brambrink AM. Isoflurane is associated with a similar incidence of emergence agitation/delirium as sevoflurane in young children‐a randomized controlled study. Paediatric Anaesthesia 2007;17(1):56‐60. [PUBMED: 17184433] - PubMed
Michalek‐Sauberer 1998 {published data only}
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Mikawa 2002 {published data only}
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    1. Milic M, Goranovic T, Knezevic P. Complications of sevoflurane‐fentanyl versus midazolam‐fentanyl anesthesia in pediatric cleft lip and palate surgery: a randomized comparison study. International Journal of Oral and Maxillofacial Surgery 2010;39(1):5‐9. [PUBMED: 19854614] - PubMed
Mizrak 2013 {published data only}
    1. Mizrak A, Karatas E, Saruhan R, Kara F, Oner U, Saricicek V, et al. Does dexmedetomidine affect intraoperative blood loss and clotting tests in pediatric adenotonsillectomy patients?. The Journal of Surgical Research 2013;179(1):94‐8. [PUBMED: 23122669] - PubMed
Moore 2003 {published data only}
    1. Moore JK, Moore EW, Elliott RA, Leger AS, Payne K, Kerr J. Propofol and halothane versus sevoflurane in paediatric day‐case surgery: induction and recovery characteristics. British Journal of Anaesthesia 2003;90(4):461‐6. [PUBMED: 12644418] - PubMed
Murray 2002 {published data only}
    1. Murray DJ, Cole JW, Shrock CD, Snider RJ, Martini JA. Sevoflurane versus halothane: effect of oxycodone premedication on emergence behaviour in children. Paediatric Anaesthesia 2002;12(4):308‐12. [PUBMED: 11982836] - PubMed
Na 2013 {published data only}
    1. Na HS, Song IA, Hwang JW, Do SH, Oh AY. Emergence agitation in children undergoing adenotonsillectomy: a comparison of sevoflurane vs. sevoflurane‐remifentanil administration. Acta Anaesthesiologica Scandinavica 2013;57:100‐5. [PUBMED: 23110746] - PubMed
Naito 1991 {published data only}
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Nakayama 2007 {published data only}
    1. Nakayama S, Furukawa H, Yanai H. Propofol reduces the incidence of emergence agitation in preschool‐aged children as well as in school‐aged children: a comparison with sevoflurane. Journal of Anesthesia 2007;21(1):19‐23. [PUBMED: 17285408] - PubMed
Oh 2005 {published data only}
    1. Oh AY, Seo KS, Kim SD, Kim CS, Kim HS. Delayed emergence process does not result in a lower incidence of emergence agitation after sevoflurane anesthesia in children. Acta Anaesthesiologica Scandinavica 2005;49(3):297‐9. [PUBMED: 15752391] - PubMed
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Ozcengiz 2011 {published data only}
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Ozer Kocak 2001 {published data only}
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Ozturk 2009 {published data only}
    1. Ozturk T, Erbuyun K, Keles GT, Ozer M, Yuksel H, Tok D. The effect of remifentanil on the emergence characteristics of children undergoing FBO for bronchoalveolar lavage with sevoflurane anaesthesia. European Journal of Anaesthesiology 2009 Apr;26(4):338‐42. [PUBMED: 19401665] - PubMed
Patel 2010 {published data only}
    1. Patel A, Davidson M, Tran MCJ, Quraishi H, Schoenberg C, Sant M, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesthesia and Analgesia 2010;111(4):1004‐10. [PUBMED: 20705788] - PubMed
Picard 2000 {published data only}
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Pieters 2010 {published data only}
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Rampersad 2010 {published data only}
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Saadawy 2009 {published data only}
    1. Saadawy I, Boker A, Elshahawy MA, Almazrooa A, Melibary S, Abdellatif AA, et al. Effect of dexmedetomidine on the characteristics of bupivacaine in a caudal block in pediatrics. Acta Anaesthesiologica Scandinavica 2009;53(2):251‐6. [PUBMED: 19076110] - PubMed
Salik 2011 {published data only}
    1. Salik I, Narang J, Brous P. Dexmedetomidine in emergence agitation in children undergoing general anesthesia for interventional radiology. Journal of Neurosurgical Anesthesiology 2011;23(4):436.
Sato 2010 {published data only}
    1. Sato M, Shirakami G, Tazuke‐Nishimura M, Matsuura S, Tanimoto K, Fukuda K. Effect of single‐dose dexmedetomidine on emergence agitation and recovery profiles after sevoflurane anesthesia in pediatric ambulatory surgery. Journal of Anesthesia 2010;24(5):675‐82. [PUBMED: 20585813] - PubMed
Seo 2011 {published data only}
    1. Seo IS, Seong CR, Jung G, Park SJ, Kim SY, Kim MM. The effect of sub‐tenon lidocaine injection on emergence agitation after general anaesthesia in paediatric strabismus surgery. European Journal of Anaesthesiology. 2011;28(5):334‐9. [PUBMED: 21206277] - PubMed
Shen 2012 {published data only}
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Shibata 2005 {published data only}
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Shin 2001 {published data only}
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Shukry 2005 {published data only}
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Singh 2009 {published data only}
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Sun 2010 {published data only}
    1. Sun Y, Hu J, Xu W‐Y, Bai J, Zhang M‐Z. Combination effect of tramadol and low dose propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure. Journal of Shanghai Jiaotong University (Medical Science) 2010;30:73‐5.
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Tang 2009 {published data only}
    1. Tang YF, Chen F, Wang BF, Li HF, Fuzaylov G, Li J, et al. Analgesic and sedative effects of multimodal analgesia in stage of emergence after general anesthesia for cleft lip and/or palate prosthesis [Article in Chinese]. National Medical Journal of China 2009;89(13):906‐8. [PUBMED: 19671292] - PubMed
Tazeroualti 2007 {published data only}
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Tesoro 2005 {published data only}
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Tsai 2008 {published data only}
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Valley 1999 {published data only}
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Viitanen 1999b {published data only}
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Viitanen 1999c {published data only}
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    1. Welborn LG, Hannallah RS, Norden JM, Ruttimann UE, Callan CM. Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesthesia and Analgesia 1996;83(5):917‐20. [PUBMED: 8895263] - PubMed
Weldon 2004 {published data only}
    1. Weldon BC, Abele A, Simeon R, Erkman C, Kosa J, Roth P, et al. Postoperative agitation: sevoflurane vs halothane. Anesthesiology 1997;87(3A):A1057.
    1. Weldon BC, Bell M, Craddock T. The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anesthesia. Anesthesia and Analgesia 2004;98(2):321‐6. [PUBMED: 14742362] - PubMed
Yucel 2012 {published data only}
    1. Yucel A, Begec Z, Ozgul U, Aydogan MS, Gulhas N, Ersoy MO. The effect of magnesium on emergence agitation in children undergoing adenotonsillectomy under sevoflurane general anesthesia: a prospective randomised clinical trial. HealthMED 2012;6:1605‐10.
Zand 2011 {published data only}
    1. Zand F, Allahyary E, Hamidi AR. Postoperative agitation in preschool children following emergence from sevoflurane or halothane anesthesia: a randomized study on the forestalling effect of midazolam premedication versus parental presence at induction of anesthesia. Acta Anaesthesiologica Taiwanica 2011;49:96‐9. [PUBMED: 21982170] - PubMed

References to studies excluded from this review

Akinci 2008 {published data only}
    1. Akinci SB, Kose EA, Ocal T, Aypar U. The effects of maternal presence during anesthesia induction on the mother's anxiety and changes in children's behavior. Turkish Journal of Pediatrics 2008;50(6):566‐71. [PUBMED: 19227421] - PubMed
Almenrader 2007 {published data only}
    1. Almenrader N, Passariello M, Coccetti B, Haiberger R, Pietropaoli P. Premedication in children: a comparison of oral midazolam and oral clonidine. Pediatric Anaesthesia 2007;17(12):1143‐9. [PUBMED: 17986032] - PubMed
Ariffin 1997 {published data only}
    1. Ariffin SA, Whyte A, Malins AF, Cooper GM. Comparison of induction and recovery between sevoflurane and halothane supplementation of anaesthesia in children undergoing outpatient dental extractions. British Journal of Anaesthesia 1997;78:157‐9. [PUBMED: 9068332] - PubMed
Chen 2010 {published data only}
    1. Chen J, Li W, Hu X, Wang D. Emergence agitation after cataract surgery in children: a comparison of midazolam, propofol and ketamine. Pediatric Anesthesia 2010;20(9):873‐9. [PUBMED: 20716081] - PubMed
Choi 2011 {published data only}
    1. Choi HR, Cho JK, Lee S, Yoo BH, Yon JH, Kim KM. The effect of remifentanil versus N2O on postoperative pain and emergence agitation after pediatric tonsillectomy/adenoidectomy. Korean Journal of Anesthesiology 2011;61(2):148‐53. [PUBMED: 21927686] - PMC - PubMed
Cole 2002 {published data only}
    1. Cole JW, Murray DJ, McAllister JD, Hirschberg GE. Emergence behaviour in children: defining the incidence of excitement and agitation following anaesthesia. Paediatric Anaesthesia 2002;12:442‐7. [PUBMED: 12060332] - PubMed
Delvi 2007 {published data only}
    1. Delvi MB, Samarkandi A, Zahrani T, Faden A. Recovery profile for magnetic resonance imaging in pediatric daycase‐‐sevoflurane vs. isoflurane. Middle East Journal of Anesthesiology 2007;19(1):205‐11. [PUBMED: 17511194] - PubMed
El‐Hennawy 2009 {published data only}
    1. El‐Hennawy AM, Abd‐Elwahab AM, Abd‐Elmaksoud AM, El‐Ozairy HS, Boulis SR. Addition of clonidine or dexmedetomidine to bupivacaine prolongs caudal analgesia in children. British Journal of Anaesthesia 2009 Aug;103(2):268‐74. [PUBMED: 19541679] - 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. The Journal of International Medical Research 2006;34(6):648‐54. [PUBMED: 17294997] - PubMed
Funk 2000 {published data only}
    1. Funk W, Jakob W, Riedl T, Taeger K. Oral preanaesthetic medication for children: double‐blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone. British Journal of Anaesthesia 2000;84(3):335‐40. [PUBMED: 10793592] - PubMed
Greenspun 1995 {published data only}
    1. Greenspun JCF, Hannallah RS, Welborn LG, Norden JM. Comparison of sevoflurane and halothane anesthesia in children undergoing outpatient ear, nose and throat surgery. Journal of Clinical Anesthesia 1995;7:398‐402. [PUBMED: 7576676] - PubMed
Hung 2005 {published data only}
    1. Hung WT, Chen CC, Liou CM, Tsai WY. The effects of low‐dose fentanyl on emergence agitation and quality of life in patients with moderate developmental disabilities. Journal of Clinical Anaesthesia 2005;17:494‐8. [PUBMED: 16297747] - PubMed
Ibrahim 2001 {published data only}
    1. Ibrahim AE, Ghoneim MM, Kharasch ED, Epstein RH, Groudine SB, Ebert TJ, et al. Speed of recovery and side‐effect profile of sevoflurane sedation compared with midazolam. Anesthesiology 2001;94(1):87‐94. [PUBMED: 11135727] - PubMed
Ingelmo 2007 {published data only}
    1. Ingelmo PM, Bendall EJ, Frawley G, Locatelli BG, Milan B, Lodetti D, et al. Bupivacaine caudal epidural anesthesia: assessing the effect of general anesthetic technique on block onset. Pediatric Anesthesia 2007;17(3):255‐62. [PUBMED: 17263741] - PubMed
Isik 2006b {published data only}
    1. Isik Y, Goksu S, Kocoglu H, Oner U. Low flow desflurane and sevoflurane anaesthesia in children. European Journal of Anaesthesiology 2006;23:60‐4. [PUBMED: 16390568] - PubMed
Kain 1999 {published data only}
    1. Kain ZN, Mayes LC, Wang SM, Hofstander MB. Postoperative behavioural outcomes in children: effects of sedative premedication. Anesthesiology 1999;90(3):758‐65. [PUBMED: 10078677] - PubMed
Kain 2007 {published data only}
    1. Kain ZN, Caldwell‐Andrews AA, Mayes LC, Weinberg ME, Wang SM, MacLaren JE, et al. Family‐centered preparation for surgery improves perioperative outcomes in children: a randomized controlled trial. Anesthesiology 2007;106(1):65‐74. [PUBMED: 17197846] - PubMed
Kawaai 2008 {published data only}
    1. Kawaai H, Sato J, Watanabe M, Ito H, Ogawa S, Shimamura K, et al. Dexmedetomidine for postoperative management after sevoflurane anesthesia in children. Journal of Japanese Dental Society of Anesthesiology 2008;36:269‐77.
Kawaraguchi 2002 {published data only}
    1. Kawaraguchi Y, Miyamoto Y, Fukumitsu K, Taniguchi A, Hirao O, Kitamura S, et al. The effect of ketamine on reducing postoperative agitation after sevoflurane anesthesia in pediatric strabismus surgery. Japanese Journal of Anesthesiology [Masui] 2002;51(12):1343‐8. [PUBMED: 12607270] - PubMed
Malmgren 2004 {published data only}
    1. Malmgren W, Akeson J. Similar excitation after sevoflurane anaesthesia in young children given rectal morphine or midazolam as premedication. Acta Anaesthesiologica Scandinavica 2004;48(10):1277‐82. [PUBMED: 15504188] - PubMed
Mayer 2006 {published data only}
    1. Mayer J, Boldt J, Röhm KD, Scheuermann K, Suttner SW. Desflurane anesthesia after sevoflurane inhaled induction reduces severity of emergence agitation in children undergoing minor ear‐nose‐throat surgery compared with sevoflurane induction and maintenance. Anesthesia and Analgesia 2006;102(2):400‐4. [PUBMED: 16428532] - PubMed
Mckay 2011 {published data only}
    1. Mckay WP, Derdall K, Brahmania M, Nagle CL, Hamilton I, Teekasingh MA. Three adjuncts to anesthesia to prevent emergence agitation in pediatric dentistry; a pilot study. Internet Journal of Anesthesiology 2011;29(1):1.
Mizrak 2011 {published data only}
    1. Mizrak A, Erbagci I, Arici T, Avci N, Ganidagli S, Oner U. Dexmedetomidine use during strabismus surgery in agitated children. Medical Principles and Practice 2011;20(5):427‐32. [PUBMED: 21757931] - 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;20(11):920‐4. [PUBMED: 14649346] - PubMed
Piat 1994 {published data only}
    1. Piat V, Dubois MC, Johanet S, Murat I. Induction and recovery characteristics and hemodynamic responses to sevoflurane and halothane in children. Anesthesia and Analgesia 1994;79:840‐4. [PUBMED: 7978397] - PubMed
Sarner 1995 {published data only}
    1. Sarner JB, Levine M, Davis PJ, Lerman J, Cook R, Motoyama EK. Clinical characteristics of sevoflurane in children—a comparison with halothane. Anesthesiology 1995;82(1):38‐46. [PUBMED: 7832332] - PubMed
Shaban 2008 {published data only}
    1. Shaban MM, Asida SM. Oral midazolam with low dose ketamine, fentanyl, or ketoprofen for the prevention of emergence agitation after pediatric ambulatory surgery. Egyptian Journal of Anaesthesia 2008;24(1):27‐33.
Steinmetz 2007 {published data only}
    1. Steinmetz J, Holm‐Knudsen R, Sorensen MK, Eriksen K, Rasmussen LS. Hemodynamic differences between propofol‐remifentanil and sevoflurane anesthesia for repair of cleft lip and palate in infants. Pediatric Anesthesia 2007;17(1):32‐7. [PUBMED: 17184429] - PubMed
Uysal 2011 {published data only}
    1. Uysal HY, Takmaz SA, Yaman F, Baltaci B, Basar H. The efficacy of intravenous paracetamol versus tramadol for postoperative analgesia after adenotonsillectomy in children. Journal of Clinical Anesthesia 2011;23(1):53‐7. [PUBMED: 21296248] - PubMed
Wagner 2003 {published data only}
    1. Wagner D, Pandit U, Voepel‐Lewis T, Weber M. Dolasetron for the prevention of postoperative vomiting in children undergoing strabismus surgery. Paediatric Anaesthesia 2003;13(6):522‐6. [PUBMED: 12846709] - PubMed

References to studies awaiting assessment

Abdelhalim 2013 {published data only}
    1. Abdelhalim AA, Alarfaj AM. The effect of ketamine versus fentanyl on the incidence of emergence agitation after sevoflurane anesthesia in pediatric patients undergoing tonsillectomy with or without adenoidectomy. Saudi Journal of Anaesthesia 2013;7:392‐8. - PMC - PubMed
Abdulatif 2013 {published data only}
    1. Abdulatif M, Ahmed A, Mukhtar A, Badawy S. The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Anaesthesia 2013;68:1045‐52. - PubMed
Ali 2013 {published data only}
    1. Ali MA, Abdellatif AA. Prevention of sevoflurane related emergence agitation in children undergoing adenotonsillectomy: a comparison of dexmedetomidine and propofol. Saudi Journal of Anaesthesia 2013;7:296‐300. - PMC - PubMed
Aydin 2013 {published data only}
    1. Aydin G, Apan A, Kose EA, Oz G. Pre‐ versus postoperative tramadol instillation: both are effective for decreasing pain and/or agitation in pediatric adenotonsillectomy. Turkish Journal of Medical Sciences 2013;43:899‐904.
Celebi 2013 {published data only}
    1. Celebi S, Topak M, Develioglu ON, Caglar E, Yalcin E, Unsel M, et al. Effect of thermal welding tonsillectomy on emergence agitation. Journal of Craniofacial Surgery 2013;24:1844‐8. - PubMed
Chandler 2013 {published data only}
    1. Chandler JR, Myers D, Mehta D, Whyte E, Groberman MK, Montgomery CJ, et al. Emergence delirium in children: a randomized trial to compare total intravenous anesthesia with propofol and remifentanil to inhalational sevoflurane anesthesia. Pediatric Anesthesia 2013;23:309‐15. - PubMed
Chen 2013a {published data only}
    1. Chen J‐Y, Jia J‐E, Liu T‐J, Qin M‐J, Li W‐X. Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children. Canadian Journal of Anesthesia 2013;60:385‐92. - PubMed
Chen 2013b {published data only}
    1. Chen L, Yu L, Fan Y, Manyande A. A comparison between total intravenous anaesthesia using propofol plus remifentanil and volatile induction/maintenance of anaesthesia using sevoflurane in children undergoing flexible fibreoptic bronchoscopy. Anaesthesia and Intensive Care 2013;41:742‐9. - PubMed
Cheng 2014 {published data only}
    1. Cheng X, Huang Y, Zhao Q, Gu E. Comparison of the effects of dexmedetomidine‐ketamine and sevoflurane‐sufentanil anesthesia in children with obstructive sleep apnea after uvulopalatopharyngoplasty: an observational study. Journal of Anaesthesiology and Clinical Pharmacology 2014;30:31‐5. - PMC - PubMed
Elgebaly 2013 {published data only}
    1. Elgebaly AS. Subtenon's lidocaine injection improves emergence agitation after general anaesthesia in paediatric ocular surgery. Southern African Journal of Anaesthesia and Analgesia 2013;19:114‐9.
Gai 2013 {published data only}
    1. Gai C‐A, Zhu Z‐R, Hu Z‐Y, Jiang Y‐L. Clinical comparison of sevoflurane and propofol anesthesia with propofol and remifentanil anesthesia for children with cleft lip and palate repair surgery. National Medical Journal of China 2013;93:1819‐21. - PubMed
Gupta 2013 {published data only}
    1. Gupta N, Rath GP, Prabhakar H, Dash HH. Effect of intraoperative dexmedetomidine on postoperative recovery profile of children undergoing surgery for spinal dysraphism. Journal of Neurosurgical Anesthesiology 2013;25:271‐8. - PubMed
Hasanein 2013 {published data only}
    1. Hasanein R, El‐Sayed W. The effect of nebulized lidocaine hydrochloride on emergence from sevoflurane anesthesia in children undergoing tonsillectomy. Egyptian Journal of Anaesthesia 2013;29:351‐6.
Hasani 2013 {published data only}
    1. Hasani A, Gecaj‐Gashi A, Llullaku S, Jashari H. Postoperative analgesia in children after propofol versus sevoflurane anesthesia. Pain Medicine 2013;14:442‐6. - PubMed
He 2013 {published data only}
    1. He L, Wang X, Zheng S, Shi Y. Effects of dexmedetomidine infusion on laryngeal mask airway removal and postoperative recovery in children anaesthetised with sevoflurane. Anaesthesia and Intensive Care 2013;41:328‐33. - PubMed
Khalifa 2013 {published data only}
    1. Khalifa OSM, Hassanin AAM. Melatonin, ketamine and their combination in half doses for management of sevoflurane agitation in children undergoing adenotonsillectomy. Egyptian Journal of Anaesthesia 2013;29:337‐41.
Kim 2013a {published data only}
    1. Kim D, Doo AR, Lim H, Son J‐S, Lee J‐R, Han Y‐J, et al. Effect of ketorolac on the prevention of emergence agitation in children after sevoflurane anesthesia. Korean Journal of Anesthesiology 2013;64:240‐5. - PMC - PubMed
Kim 2013b {published data only}
    1. Kim MS, Moon B‐E, Kim H, Lee J‐R, Hemmings HC. Comparison of propofol and fentanyl administered at the end of anaesthesia for prevention of emergence agitation after sevoflurane anaesthesia in children. British Journal of Anaesthesia 2013;110:274‐80. - PubMed
Kim 2014 {published data only}
    1. Kim NY, Kim SY, Yoon HJ, Kil HK. Effect of dexmedetomidine on sevoflurane requirements and emergence agitation in children undergoing ambulatory surgery. Yonsei Medical Journal 2014;55:209‐15. - PMC - PubMed
Kodra 2013 {published data only}
    1. Kodra N, Gani H, Beqiri V, Bedalli F, Naco M, Doko P. Comparison of oral premedication between midazolam and clonidine on children that undergo urology surgery. European Journal of Anaesthesiology 2013;30:157.
Li 2013 {published data only}
    1. Li X, Zhang Y, Zhou M, Xia Q, Li W, Lu Q. The effect of small dose sufentanil on emergence agitation in preschool children following sevoflurane anesthesia for elective repair of unilateral inguinal hernia. Saudi Medical Journal 2013;34:40‐5. - PubMed
Locatelli 2013 {published data only}
    1. Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, et al. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Pediatric Anesthesia 2013;23:301‐8. - PubMed
Oofuvong 2014 {published data only}
    1. Oofuvong M, Siripruekpong S, Naklongdee J, Hnookong R, Lakateb C. Comparison of the incidence of emergence agitation between sevoflurane and desflurane after pediatric ambulatory urologic surgery. Journal of the Medical Association of Thailand 2013;96:1470‐5. - PubMed
Park 2014 {published data only}
    1. Park JH, Lim BG, Kim HZ, Kong MH, Lim SH, Kim NS, et al. Comparison of emergence agitation between sevoflurane/nitrous oxide administration and sevoflurane administration alone in children undergoing adenotonsillectomy with preemptive ketorolac. Korean Journal of Anesthesiology 2014;66:34‐8. - PMC - PubMed
Pedersen 2013 {published data only}
    1. Pedersen NA, Jensen AG, Kilmose L, Olsen KS. Propofol‐remifentanil or sevoflurane for children undergoing magnetic resonance imaging? A randomised study. Acta Anaesthesiologica Scandinavica 2013;57:988‐95. - PubMed
Rashad 2014 {published data only}
    1. Rashad MM, Soud DEM. The effect of different drugs on sevoflurane emergence agitation in pediatric patients undergoing hypospadias repair surgery. Egyptian Journal of Anaesthesia 2014;30:123‐7.
Rizk 2014 {published data only}
    1. Rizk SN, Samir EM. Use of ketofol to control emergence agitation in children undergoing adenotonsillectomy. Egyptian Journal of Anaesthesia 2014;30:13‐9.
Sethi 2013 {published data only}
    1. Sethi S, Ghai B, Ram J, Wig J. Postoperative emergence delirium in pediatric patients undergoing cataract surgery—A comparison of desflurane and sevoflurane. Pediatric Anesthesia 2013;23:1131‐7. - PubMed
Sheta 2014 {published data only}
    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. Pediatric Anesthesia 2014;24:181‐9. - PubMed

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References to other published versions of this review

Stephens 2008
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