AJA Asian Journal of Anesthesiology

Advancing, Capability, Improving lives

Review Article
Volume 59, Issue 1, Pages 7-21
Chan Josephine 1 , Ina Ismiarti Shariff uddin 1 , Sook Hui Chaw 1 , Kevin Wei Shan Ng 1 , Ka Ting Ng 1
4860 Views


Abstract

Dexmedetomidine is a highly selective α2-adrenoceptor agonist, which is off-labelled use for pediatric sedation. However, the hemodynamic responses of dexmedetomidine remain unclear the pediatric population. The primary objectives of this systematic review and meta-analys were to examine the hemodynamic effects of high-dose and low-dose dexmedetomidine in pediatric patien undergoing surgery. EMBASE, MEDLINE, and CENTRAL were systematically searched from its inception until April 2019. All randomized clinical trials comparing high-dose (> 0.5 mcg/kg) and low-do (≤ 0.5 mcg/ kg) dexmedetomidine in pediatric surgical patients were included, regardless of the types surgeries. Observational studies, case series, and case reports were excluded. Four trials (n = 473) were included in this review. Our review demonstrated that high-dose dexmedetomidine was associated with low heart rate than low-dose dexmedetomidine after intravenous bolus of dexmedetomidine (studies, 3; n = 274; mean difference [MD], –5 [–6 to –4]; P < 0.0001) and during surgical stimulant (studies, 2; n = 153; MD, –11 [–13 to –9]; P < 0.0001). In comparison to the low-dose dexmedetomidine, high-dose dexmedetomidine was al associated with a signifi cant longer recovery time (studies, 3; n = 257; MD, 5.90 [1.56 to 10.23]; P = 0.008) but a lower incidence of emergence agitation (studies, 2; n = 153; odds ratio, 0.17 [0.03 to 0.95]; P = 0.040). In this metaanalysis, low-dose dexmedetomidine demonstrated better hemodynamic stability with shorter recovery time than high-dose dexmedetomidine. However, these fi ndings need to be interpreted with cauti due to limited published studies, a small sample size, and a high degree of heterogeneity.

Keywords

bradycardia, dexmedetomidine, hemodynamic, heart rate, mean arterial pressure, pediatric


Introduction

Dexmedetomidine is a highly selective α2-adrenoceptor agonist, which has the properties of sedation, analgesic, anxiolysis, and sympatholysis.1 In recent years, dexmedetomidine has been approved for sedation of intubated or non-intubated adults before and during surgical and other minimally invasive procedures.2 Although the uses of dexmedetomidine are not labelled for the pediatric population, many studies have widely reported its uses for pediatric sedation or during surgeries.3-10

For children undergoing elective surgery with general anesthesia, any surgical stimulants will trigger the intense stress response and cause fluctuation on hemodynamic parameters, which may affect the quality of closed monitoring anesthesia during surgery.11 The anxiolytic, analgesic, and sympatholytic properties of dexmedetomidine are believed attenuate raised heart rate and blood pressure as a result of the surgical stress response.12 However, one of the main concerns of the uses of dexmedetomidine in pediatric patients is its unpredictable hemodynamic response, which causes bradycardia and hypotension.13-15 Low plasma concentration of dexmedetomidine causes a drop in mean arterial pressure (MAP) and heart rate due to its sympatholytic myocardial depression and reduction of catecholamine.16 In contrast, the high plasma concentration of dexmedetomidine is associated with an increased MAP, but a further reduction in heart rate as a result of the considerable additional vasoconstriction.16

To date, there is no recommended doses of dexmedetomidine for pediatric sedation or during anesthesia. For non-invasive procedural sedation and anesthesia, a loading dose of 1 mcg/kg followed by a continuous infusion of 0.2–1 mcg/kg/h is recommended for spontaneous breathing adults.16 However, the dosing of bolus and continuous infusion of dexmedetomidine varied across all the reported studies in the pediatric population.6-9 Thus, a systematic review is warranted to synthesize the evidence for the hemodynamic effects of high and low doses of dexmedetomidine uses in pediatric patients undergoing surgery. Two studies have defined a single dose of dexmedetomidine less than 0.5 mcg/kg as a low dose without serious adverse events.8,9 Based on the available literature, we defined high and low doses of dexmedetomidine as > 0.5 mcg/kg and ≤ 0.5 mcg/kg, respectively. We hypothesized that the sedation of low doses of dexmedetomidine was associated with better hemodynamic stability than high doses of dexmedetomidine in pediatric patients. The primary objective of this systematic review and meta-analysis was to examine the hemodynamic effects (MAP and heart rate at different time points post-dexmedetomidine bolus, during surgical stimulant, and the end of surgery) of high dose and low dose dexmedetomidine in pediatric patients undergoing surgery. The secondary objective was to investigate the effects of high and low doses of dexmedetomidine on recovery time and emergency agitation.

Methods

This review was conducted and reported according to the Cochrane Handbook of Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analys (PRISMA) guidelines, respectively.17,18 The protocol of this review was published in a public database, PROSPERO (CRD42020132535). The population (pediatric), intervention (high-dose dexmedetomidine), comparison (low-dose dexmedetomidine) and outcomes approach were used to formulate our review questions. The primary outcomes were hemodynamic responses (MAP and heart rate) of high and low doses of dexmedetomidine at different time-points (baseline, post-dexmedetomidine bolus, during surgical stimulant, and the end of surgery) in surgical pediatric patients. The secondary outcomes included the effects of a high and low dose of dexmedetomidine on recovery time and the incidence of emergence agitation.

Search Strategy

Databases of EMBASE (Ovid), MEDLINE (Ovid), and Cochrane Controlled Register of Trials (CENTRAL) were searched from their start date until April 2019. Two trial registries (ClinicalTrials.gov and International Clinical Trials Registry Platform) were searched for any ongoing studies. No restriction was applied to the language of publication. Search terms and search strategy were outlined in the Supplement Table 1. Eligibility criteria were listed as below:

(1) Parallel-arm randomized controlled trials (RCTs).

(2) Comparing high dose of intravenous dexmedetomidine (> 0.5 mcg/kg).

(3) Versus low doses of intravenous dexmedetomidine ≤ 0.5 mcg/kg).

(4) Pediatric patients (age less than 18 years old) undergoing general anesthesia in any types of elective surgery, regardless of reported outcomes.

Studies randomizing dexmedetomidine via the route of intranasal or epidural were not included. Cross-over RCTs, observational studies, case series, editorials, and conference abstracts were excluded in this review. The bibliographies of all relevant RCTs and review papers were manually searched for additional papers.

Study Selection, Data Items, Data Collection, and Assessment of Validity

Our authors, Chan Josephine and Ka Ting Ng, screened the titles and abstracts of articles for eligibility criteria independently. Articles coded as “yes” were included for full-text screening, which were conducted by the two authors independently. Those coded as “no” were excluded whereas studies coded as “maybe” were discussed with our auth (Ina Ismiarti Shariffuddin). All the final included RCTs were discussed and agreed amongst all authors.

An online extraction form was piloted prior to the data extraction. Data extraction was performed by Chan Josephine and Ka Ting Ng independently. Any discrepancies were resolved by the author (Ina Ismiarti Shariffuddin). Apart from all the measured outcomes, other data included authors, the year of publication, study design, sample size, age of the included pediatric population, classification of American Society of Anesthesiologist (ASA), and the types of surgery.

Risk of Bias in Individual Studies, Summary of Findings

The Cochrane Collaboration Risk of Bias Assessment Tool was used to assess the risk of bias for all the included articles by Chan Josephine and Ka Ting Ng independently. Any disagreements were discussed with Ina Ismiarti Shariffuddin until a consensus was achieved. Any conflicts were resolved with Ina Ismiarti Shariffuddin.

Summary Measures and Synthesis of Results

Review Manager version 5.3 (Cochrane, London, UK) was used for data analysis, and a two-sided P-value < 0.05 was considered as statistical significance. All the findings of dichotomous and continuous outcomes were reported as odds ratios (OR) and mean difference (MD), respectively with 95% confidence interval (CI). Statistical heterogeneity of each measured outcome was performed with I-square (I2) test, where I2 < 40, 40–60%, and > 60% were considered as low, moderate, and substantial heterogeneity, respectively. A fixed effect model was used for all the pooled estimates. If substantial heterogeneity (I2 > 60%) was observed, a random-effect model was used.

Results

The PRISMA flow chart was outlined in Figure 1. Our search generated 1,844 articles for titles and abstracts screening. Of all, 49 studies were retrieved for full-text screening. Applying the eligibility criteria, four RCTs6-9 (total sample size, 473 patients) were included for qualitative and quantitative meta-analysis. Searching trial registries identified 3 ongoing studies (Supplement Table 2).

Figure 1.
Download full-size image
Figure 1. PRISMA Diagram
Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The clinical characteristics of all the included RCTs were illustrated in Table 1.6-9 All the included RCTs were published in 2017 and 2018 with the sample size ranging from 977 to 156.9 The ASA for all the included population from class I to II across all the studies. Of all, three RCTs6,7,9 were elective hernia repair surgery and one8 was non-specific elective surgery. The dose of dexmedetomidine varied (0.25–2.5 mcg/kg) across all the trials. Based on the literature, our review classified high-dose and lowdose dexmedetomidine as > 0.5 mcg/kg and ≤ 0.5 mcg/kg for data pooling. In the overall risk of bias assessment (Supplement Table 3),6-9 two RCTs6,9 were graded as unclear risk due to inadequate information provided for allocation concealment and blinding of participants, personnel and, outcome assessor. Zhou et al.’s study8 was the high risk of bias in the domains of sequence generation, allocation concealment, and blinding. The PRISMA checklist was illustrated in the Supplement Table 4. The findings of the primary and the secondary outcomes were demonstrated in Table 2. Forest plots of all measured outcomes were included in the Supplement Figure 1.

Table 1. Clinical Characteristics of Included Studies
Table 1.
Download full-size image
Table 2. Data Analysis of Primary and Secondary Outcomes
Table 2.
Download full-size image

Primary Outcomes: MAP and Heart Rate (Baseline, Post-Dexmedetomidine Bolus, During Surgical Stimulant, and the End of Surgery)

All the included RCTs recorded the readings of MAP at different time points. For the baseline of MAP (Table 2), no significant difference was noted based on the combined data of three RCTs6,7,9 (studies, 3; n = 257; MD, 0 [–1 to 2]; P = 0.50). No heterogeneity (I2 = 0%) was observed in this measured outcome. The pooled data of post-dexmedetomidine bolus (studies, 3; n = 274; MD, 1 [–3 to 4], P = 0.75), during surgical stimulant (studies, 2; n = 153; MD, 4 [–5 to 13], P = 0.38), and at the end of surgery (studies, 3; n = 237; MD, –4 [–12 to 5], P = 0.38) demonstrated no significant differences in MAP between high-dose and lowdose dexmedetomidine in pediatrics. However, the statistical heterogeneity was substantial across all the included studies (I2 > 60%). Due to the limited available studies, the small sample size of our included trials may contribute variances to these findings.

Based on the combined data of three RCTs,6,7,9 no significant difference was reported for the baseline of heart rate (Table 2) (studies, 3; n = 257; MD, 0 [–2 to 1]; P = 0.1; I2 = 0%). In the pooled estimate of heart rate after an intravenous bolus of dexmedetomidine (studies, 3; n = 274; MD, –5 [–6 to –4]; P < 0.0001) and during the surgical stimulant (studies, 2; n = 153; MD, –11 [–13 to –9]; P < 0.0001), high dose dexmedetomidine was associated with a significantly lower heart rate as compared to low-dose dexmedetomidine. Statistical heterogeneity was low across the included studies. However, at the end of surgery, our review demonstrated no significant difference in the heart rate between high-dose and low-dose dexmedetomidine with a substantial degree of heterogeneity (studies, 3; n = 267; MD, –3 [–8 to 2]; P = 0.19; I2 = 96%).

Secondary Outcomes: Duration of Recovery Time and Incidence of Emergence Agitation

Two RCTs6,7 examined the incidence of emergence agitation with different emergence agitation scales (Pediatric Anesthesia Emergence Delirium Scale6 and Emergence agitation scale7). In comparison to high dose dexmedetomidine, our review demonstrated that low dose dexmedetomidine was significantly associated with higher incidence of emergence agitation (studies, 2; n = 153; OR, 0.17 [0.03 to 0.95]; P = 0.04) (Table 2). No substantial heterogeneity was observed in this measured outcome (I2 = 0%).

Three RCTs6,7,9 (n = 257) reported the duration of recovery time (minutes) after surgery. Our pooled analysis showed that the recovery time was significantly shorter in the low-dose dexmedetomidine group than the high-dose dexmedetomidine group (MD, 5.90 [1.56 to 10.23]; P = 0.008; I2 = 97%) (Table 2). However, the definition of the recovery time varied across the included RCTs. Two studies7,9 defin the recovery time as the time to spontaneous eye-opening after extubation; whereas one study6 included time stay at a post-anesthesia care unit in the recovery time. A sensitivity analysis was performed by excluding Chen et al.’s study6 to investigate for the high heterogeneity. The pooled estimate showed no significant difference in the recovery time with a similar high degree of heterogeneity based on the combined two studies7,9 (n = 177; MD, 1.88 [–1.12 to 4.88], P = 0.22; I2 = 95%).

Discussion

To the best of our knowledge, this is the first systematic review and meta-analysis assessing the hemodynamic responses of high-dose and low-dose dexmedetomidine in the pediatric population. Our meta-analysis of four RCTs demonstrated that highdose dexmedetomidine was associated with a lower heart rate than low-dose dexmedetomidine after an intravenous bolus of dexmedetomidine and during the surgical stimulant. In comparison to low-dose dexmedetomidine, high-dose dexmedetomidine was also associated with a significantly longer recovery time but a lower incidence of emergence agitation. However, our findings need to be interpreted with caution as there were only limited published studies of the small sample size in the literature.

Several systematic reviews and meta-analyses19-21 reported no significant adverse events of bradycardia and hypotension in adults who was randomized to dexmedetomidine. However, the body physiology of pediatrics is different from adults, in which pediatrics are more susceptible to those adverse effects of dexmedetomidine.22 Dexmedetomidine is believed to inhibit the release of norepinephrine by agonizing the presynaptic membrane α2-receptor, resulting in central sympatholytic effects with hypotension and bradycardia, especially during the infusion or higher doses of dexmedetomidine.12 Both the incidence of hypotension and bradycardia were also reported in several pediatric studies.5,15,16,23,24 Although hypotension and bradycardia were commonly resolved by dose reduction or intravenous fluid bolus, several case reports documented severe bradycardia, which caused cardiac arrest in the high-dose use of dexmedetomidine.23,24 Although dexmedetomidine is not labelled for pediatric use, our literature search identified many applications of dexmedetomidine in pediatric over the last few years as it causes minimal respiratory depression as compared to other sedative agents.3-10 Thus, the doses of dexmedetomidine for pediatric patients must be judicious to ensure the benefits outweigh its adverse effects namely hypotension and bradycardia. Our current meta-analysis provides evidence on the hemodynamic responses of high and low doses of dexmedetomidine in the pediatric population, which will provide valuable findings to clinicians.

Mason and Lerman described that the hemodynamic responses (MAP and heart rate) of dexmedetomidine are influenced by the dosage of dexmedetomidine and its rate of infusion.12 In comparison to low-dose dexmedetomidine, our review demonstrated that high-dose dexmedetomidine was associated with a significantly lowered heart rate after the intravenous bolus dexmedetomidine and during the surgical stimulant. However, none of the patients required any additional treatment for bradycardia. In term of MAP, both high-dose and low-dose dexmedetomidine groups had no significant differences in the different time-points of baseline, post-dexmedetomidine bolus, during the surgical stimulant, and at the end of surgery. Thus, low dose dexmedetomidine is believed to have better hemodynamic stability than high dose dexmedetomidine.

A high degree of heterogeneity and a small sample size may introduce bias to our findings. There was also potential sampling bias in the included studies as the readings of hemodynamic parameters were only taken at several time-points. In an observational study of 747 children,10 although good sedation was achieved with high-dose dexmedetomidine (loading doses 2–3 mcg/kg + infusions of 1–2 mcg/kg/hr.), the incidence of bradycardia was 16%, which was 5-folds to the reported incidence of bradycardia (3%) in a meta-analysis by Gong and colleagues25 based on 21 studies (2,835 pediatric patients). Thus, high-dose dexmedetomidine should be used with extra cautions, especially in those with left ventricular dysfunction, volume-depleted, or severe heart block.12,26

Our review demonstrated that high-dose dexmedetomidine significantly reduced the incidence of emergence agitation than those receiving low-dose dexmedetomidine. Emergence agitation is defined as a temporary state of disorientation, irritability, and dissociation during the early stage of recovery from anesthesia in children.27 Although it is self-limiting, it triggered significant emotional disturbance and distress to caretakers and family members.28 The reported incidence of emergence agitation varied between 18%29 to 80%,30-32 depending on different types of scoring systems with different sensitivity and specificity, the types of surgery, and the choices of anesthetic agents (benzodiazepam, ketamine, propofol, and fentanyl). In this review, the overall incidence of emergence agitation for high-dose dexmedetomidine and low-dose dexmedetomidine was 1.5% and 13.6%, respectively. Although high-dose dexmedetomidine was associated with a lesser incidence of emergence agitation, it came with the expenses of a longer duration of recovery time and higher risk for bradycardia. However, two of the included RCTs utilized different scoring systems (Emergence Agitation Scale,7 and Pediatric Anesthesia Emergence Delirium6), which may introduce variances to the findings. Of all the different scoring systems for emergence agitation, the Pediatric Anesthesia Emergence Delirium score is the most validated and comprehensive system, which incorporates the domains of cognitive and agitation in the assessment of emergence agitation.33-36 Other confounding factors, namely preoperative anxiety and the types of anesthetic agents may also introduce bias to the findings.37,38 Pradeep and co-workers demonstrated an increased incidence of emergence agitation in those with the sevoflurane-anesthesia group than the isoflurane- anesthesia group.39 However, a Cochrane review by Costi and colleagues based on 158 studies comprising of 14,045 children found no clear evidence of the risk of emergence agitation between isoflurane, sevoflurane, and desflurane.40

In our review, the high-dose dexmedetomidine group required a longer recovery time than the lowdose dexmedetomidine group, which was consistent with other studies.2-4,6,14 Our findings need to be interpreted with caveats as one of the RCTs6 included the duration of stay in the post-anesthesia care unit in the recovery time. In a sensitivity analysis by removing this study,6 the pooled analysis showed no significant difference in recovery time between the high- and low-dose dexmedetomidine groups. In contrast, Sun and his team reported that high dose dexmedetomidine infusion of 1.0 mcg/kg significantly increased the time between the end of anesthesia and laryngeal mask removal and time to spontaneous eye opening after extubation as compared to the dose of 0.5 mcg/kg.7 Varied primary outcomes and small sample size across all the included studies introduced variances as most of the studies were not powered to detect the significance of this measured outcome.

One of the biggest limitations was that none of the included studies were adequately powered to compare the hemodynamic outcomes of high-dose and low-dose dexmedetomidine in pediatrics. In this review, data from different doses of dexmedetomidine were combined based on the threshold of 0.5 mcg/kg to synthesize the evidence on the hemodynamic responses of high-dose versus low-dose dexmedetomidine in the pediatric population. A future pharmacodynamics clinical dose-response study is required to provide further clarity on our findings. In addition, three out of four included RCTs were assessed as unclear or high risk of bias due to the lack of sequence generation, allocation concealment, and blinding of participants, personnel, and outcome assessors. Future trials could standardize on the doses of dexmedetomidine, the types of anesthetic agents, time points of hemodynamic response observation, the definition of recovery time, and the scoring systems for emergence delirium to minimize the degree of heterogeneity.

In this meta-analysis, the low-dose dexmedetomidine (≤ 0.5 mcg/kg) demonstrated better hemodynamic stability with shorter recovery time than the high-dose dexmedetomidine (> 0.5 mcg/kg). However, these findings need to be interpreted with caution due to limited published studies of small sample size and the high degree of heterogeneity.

Author Contributions

Chan Josephine: protocol/ project management, data collection or management, data analysis, manuscript writing/editing; Ina Ismiarti Shariffuddin: protocol/ project management, data collection or management, data analysis, manuscript writing/editing; Sook Hui Chaw: protocol/ project management, data collection or management, data analysis, manuscript writing/editing; Kevin Wei Shan Ng: protocol/ project management, data collection or management, data analysis, manuscript writing/editing; Ka Ting Ng: protocol/ project management, data collection or management, data analysis, manuscript writing/editing.

Conflict of Interest

All authors have declared that they do not have any conflicts of interest in this review.

Funding

No funding was received in support of this project.

PROSPERO Registration

CRD42020132535.


References

1
Scott-Warren VL, Sebastian J.
Dexmedetomidine: its use in intensive care medicine and anaesthesia.
Br J Anaesth. 2016;16(7):242-246.
2
Kaygusuz K, Gokce G, Gursoy S, Ayan S, Mimaroglu C, Gultekin Y.
A comparison of sedation with dexmedetomidine or propofol during shockwave lithotripsy: a randomized controlled trial.
Anesth Analg. 2008;106(1):114-119.
3
Erdil F, Demirbilek S, Begec Z, Ozturk E, Ulger MH, Ersoy MO.
The effects of dexmedetomidine and fentanyl on emergence characteristics after adenoidectomy in children.
Anaesth Intensive Care. 2009;37(4):571-576.
4
Mahmoud M, Gunter J, Donnelly LF, Wang Y, Nick TG, Sadhasivam S.
A comparison of dexmedetomidine with propofol for magnetic resonance imaging sleep studies in children.
Anesth Analg. 2009;109(3):745-753.
5
Mason KP, Zgleszewski SE, Prescilla R, Fontaine PJ, Zurakowski D.
Hemodynamic effects of dexmedetomidine sedation for CT imaging studies.
Paediatr Anaesth. 2008;18(5):393-402.
6
Chen F, Wang C, Lu Y, Huang M, Fu Z.
Efficacy of different doses of dexmedetomidine as a rapid bolus for children: a double-blind, prospective, randomized study.
BMC Anesthesiol. 2018;18(1):103.
7
Sun Y, Li Y, Sun Y, Wang X, Ye H, Yuan X.
Dexmedetomidine effect on emergence agitation and delirium in children undergoing laparoscopic hernia repair: a preliminary study.
J Int Med Res. 2017;45(3):973-983.
8
Zhou M, Wang Q, Zhang Q, Liu Y, Zhan L, Shu A.
Application of pre-injection of dexmedetomidine of different doses in pediatric intravenous general anesthesia without tracheal intubation.
Exp Ther Med. 2018;15(3):2973-2977.
9
Xie Y, Du Y, Shi H, Sun J, Duan H, Yu J.
Different doses of dexmedetomidine in children with non-tracheal intubation intravenous general anesthesia.
nt J Clin Exp Med. 2018;11(6):6215-6221.
10
Mason KP, Zurakowski D, Zgleszewski SE, et al.
High dose dexmedetomidine as the sole sedative for pediatric MRI.
Paediatr Anaesth. 2008;18(5):403-411.
11
Mir Ghassemi A, Neira V, Ufholz LA, et al.
A systematic review and meta‐analysis of acute severe complications of pediatric anesthesia.
Paediatr Anaesth. 2015;25(11):1093- 1102.
12
Mason KP, Lerman J.
Review article: dexmedetomidine in children: current knowledge and future applications.
Anesth Analg. 2011;113(5):1129-1142.
13
Talke P, Richardson CA, Scheinin M, Fisher DM.
Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine.
Anesth Analg. 1997;85(5):1136-1142.
14
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- 394.
15
Arain SR, Ebert TJ.
The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation.
Anesth Analg. 2002;95(2):461-466.
16
Snapir A, Posti J, Kentala E, et al.
Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects.
Anesthesiology. 2006;105:902-910.
17
Higgins JPT, Green S (editors).
Cochrane handbook for systematic reviews of interventions.
Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Accessed March 31, 2019
18
Shamseer L, Moher D, Clarke M, et al.
Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.
BMJ. 2015;350:g7647.
19
Sun Q, Liu S, Wu H, et al.
Dexmedetomidine as an adjuvant to local anesthetics in transversus abdominis plane block: a systematic review and meta-analysis.
Clin J Pain. 2019;35(4):375-384.
20
Feng M, Chen X, Liu T, Zhang C, Wan L, Yao W.
Dexmedetomidine and sufentanil combination versus sufentanil alone for postoperative intravenous patient-controlled analgesia: a systematic review and meta-analysis of randomized controlled trials.
BMC Anesthesiol. 2019;19(1):81.
21
Duan X, Coburn M, Rossaint R, Sanders RD, Waesberghe JV, Kowark A.
Efficacy of perioperative dexmedetomidine on postoperative delirium: systematic review and meta- analysis with trial sequential analysis of randomised controlled trials.
Br J Anaesth. 2018;121(2):384-397.
22
Macfarlane F.
Paediatric anatomy, physiology and the basics of paediatric anaesthesia.
Anaesthesia UK. Accessed April 9, 2020.
23
Videira RL, Ferreira RM.
Dexmedetomidine and asystole.
Anesthesiology. 2004;101(6):1479.
24
Ingersoll-Weng E, Manecke GR Jr, Thistlethwaite PA.
Dexmedetomidine and cardiac arrest.
Anesthesiology. 2004;100(3):738-739.
25
Gong M, Man Y, Fu Q.
Incidence of bradycardia in pediatric patients receiving dexmedetomidine anesthesia: a meta-analysis.
Int J Clin Pharm. 2017;39(1):139-147.
26
Afonso J, Reis F.
Dexmedetomidine: current role in anesthesia and intensive care.
Rev Bras Anestesiol. 2012;62(1):118-133.
27
Dahmani S, Stany I, Brasher C, et al.
Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies.
Br J Anaesth. 2010;104(2):216-223.
28
Ng KT, Sarode D, Lai YS, Teoh WY, Wang CY.
The effect of ketamine on emergence agitation in children: a systematic review and meta‐analysis.
Paediatr Anaesth. 2019;29(12):1163-1172.
29
Voepel-Lewis T, Malviya S, Tait AR.
A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit.
Anesth Analg. 2003;96(6):1625-1630.
30
Chandler JR, Myers D, Mehta D, et al./div>
Emergence delirium in children: a randomized trial to compare total intravenous anaesthesia with propofol and remifentanil to inhalational sevoflurane anaesthesia.
Paediatr Anaesth. 2013;23(4):309-315.
31
Locatelli BG, Ingelmo PM, Emre S, et al.
Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale.
Paediatr Anaesth. 2013;23(4):301- 308.
32
Jöhr M, Berger TM.
Paediatric anaesthesia and inhalation agents.
Best Pract Res Clin Anaesthesiol. 2005;19(3):501-522.
33
Bong CL, Ng AS.
Evaluation of emergence delirium in Asian children using the Pediatric Anesthesia Emergence Delirium Scale.
Paediatr Anaesth. 2009;19(6):593-600.
34
Wong DD, Bailey CR.
Emergence delirium in children.
Anaesthesia. 2015;70(4):383-387.
35
Janssen NJ, Tan EY, Staal M, et al.
On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, the Delirium Rating Scale-revised R-98.
Intensive Care Med. 2011;37(8):1331-1337.
36
Lee CA.
Paediatric emergence delirium: an approach to diagnosis and management in the postanaesthesia care unit.
J Perioper Crit Intensive Care Nurs. 2017;3(2):140.
37
Mason KP.
Paediatric emergence delirium: a comprehensive review and interpretation of the literature.
Br J Anaesth. 2017;118(3):335-343.
38
Ng KT, Shubash CJ, Chong JS.
The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta‐analysis with trial sequential analysis.
Anaesthesia. 2019;74(3):380-392.
39
Pradeep T, Manissery JJ, Upadya M.
Emergence agitation in paediatric patients using sevoflurane and isoflurane anaesthesia: a randomised controlled study.
S Afr J Anaesth Analg. 2017;23(2):32-35.
40
Costi D, Cyna AM, Ahmed S, et al.
Effects of sevoflurane versus other general anaesthesia on emergence agitation in children.
Cochrane Database Syst Rev. 2014;9:CD007084.

Supplement

Supplement Table 1. Search Strategy for EMBASE and MEDLINE Databases (Its Inception Until April 2019)a
Supplement Table 1.
Download full-size image
Supplement Table 2. Characteristics of Ongoing Studies
Supplement Table 2.
Download full-size image
Supplement Table 3. Risk of Bias Assessment of All the Included Studies
Supplement Table 3.
Download full-size image
Supplement Table 4. PRISMA Checklist
Supplement Table 4.
Download full-size image
Supplemenet Figure 1.
Download full-size image
Figure 1. Forest Plots of All Measured Outcomes
Abbreviations: CI, confi dence interval; HR, heart rate; IV, interval variable; MAP, mean arterial pressure; SD, standard deviation.

References

Close