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Pediatric Anesthesia ISSN 1155-5645
SYSTEMATIC REVIEW
Outcomes of dexmedetomidine treatment in pediatric
patients undergoing congenital heart disease surgery:
a meta-analysis
Wanying Pan, Yueting Wang, Lin Lin, Ge Zhou, Xiaoxiao Hua & Liqiu Mo
Department of Anaesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
What is already known
• Dexmedetomidine is a safe and efficacious sedative agent, and can offer some benefit for adult patients undergoing cardiac surgery.
What this article adds
• Perioperative dexmedetomidine treatment improves the outcomes in children undergoing congenital heart dis-
ease surgery, including more stable hemodynamics, shorter ventilation duration, and lesser incidence of postoperative agitation, and rescue analgesia.
Keywords
congenital heart disease; dexmedetomidine;
meta-analysis; pediatric
Correspondence
Prof. L.Q. Mo, Department of
Anaesthesiology, The First Affiliated
Hospital, Sun Yat-sen University, No. 58,
Zhongshan 2nd Road, Guangzhou 510080,
China
Email: [email protected]
Section Editor: Mark Thomas
Accepted 18 October 2015
doi:10.1111/pan.12820
Summary
Background: Dexmedetomidine decreases cardiac complications in adults
undergoing cardiovascular surgery. This systematic review assessed whether
perioperative dexmedetomidine improves congenital heart disease (CHD)
surgery outcomes in children.
Methods: The PubMed, Embase, and Cochrane Library databases were
searched for randomized controlled trials (RCTs) or observational studies
that were published until 16 April 2015 and compared dexmedetomidine with
placebo or an alternative anesthetic agent during pediatric CHD surgery. The
assessed outcomes included hemodynamics, ventilation length, intensive care
unit (ICU) and hospital stays, blood glucose and serum cortisol levels, postoperative analgesia requirements, and postoperative delirium.
Results: Five RCTs and nine observational studies involving 2229 patients
were included. In pooled analyses, dexmedetomidine was associated with
shorter length of mechanical ventilation (mean difference: 93.36, 95% CI:
137.45, 49.27), lower postoperative fentanyl (mean difference: 24.11,
95% CI: 36.98, 11.24) and morphine (mean difference: 0.07, 95% CI:
0.14, 0.00) requirements, reduced stress response (i.e., lower blood glucose
and serum cortisol levels), and lower risk of delirium (OR: 0.39, 95% CI:
0.21, 0.74). The hemodynamics of dexmedetomidine-treated patients
appeared more stable, but there were no significant differences in the ICU or
hospital stay durations. Dexmedetomidine may increase the bradycardia and
hypotension risk (OR: 3.14, 95% CI: 1.47, 6.69).
Conclusions: Current evidence indicates that dexmedetomidine improves outcomes in children undergoing CHD surgery. However, this finding largely
relies on data from observational studies; high-quality RCTs are warranted
because of the potential for subject selection bias.
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Pediatric Anesthesia 26 (2016) 239–248
239
Dex for cardiac surgery in children
Background
Congenital cardiovascular defects represent the most
common cause of infant death due to birth defects (1).
Every year, approximately 10 000 children require anesthesia for congenital heart disease (CHD) surgery during
their first year of life (1,2). Surgical injury may be followed by stress-induced catabolism, which can lead to
delayed convalescence and increased morbidity and
mortality (3,4). Furthermore, postoperative mortality is
high in patients with delirium after surgery (5), and
recovery is slower than in those without delirium such
that intensive care unit (ICU) stays are prolonged and
hospital costs are higher (5,6).
Dexmedetomidine, a potent and highly selective a2
adrenoreceptor agonist, is widely used in ICUs and
operating rooms. In addition to analgesia, sedation, and
anxiolysis, dexmedetomidine possesses numerous other
desirable properties with respect to the treatment of
adult patients, including reduced catecholamine release
(7), a decreased incidence of postoperative delirium
(8,9), and anesthetic-sparing effects (10,11). There is
strong evidence that dexmedetomidine can reduce cardiac complications after cardiovascular surgery in adults
(12–14). Although not currently approved by the Food
and Drug Administration for use in pediatric populations, the clinical use of dexmedetomidine continues to
increase in numerous pediatric contexts, including as an
adjunctive anesthetic agent during CHD surgery.
However, because of their generally small sample
sizes, the value of previous studies that assessed the
effects of dexmedetomidine on outcomes in pediatric
patients undergoing CHD surgery is limited. We aimed
to provide more recent and convincing evidence of the
effects and safety of dexmedetomidine in pediatric
patients undergoing CHD surgery by systematically
reviewing the currently available literature.
Methods
This systematic review and meta-analysis was conducted
and reported in adherence to PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-Analyses) (15).
W. Pan et al.
cation language restriction was imposed. The final
search was run on 16 April 2015. Two investigators
independently carried out the initial search, deleted
duplicate records, screened titles and abstracts for relevance, and decided whether articles should be excluded
or required further assessment; we then reviewed the
full-text articles.
Studies that met all of the following inclusion criteria
were included: (i) population: pediatric patients undergoing CHD surgery; (ii) intervention: dexmedetomidine;
(iii) comparison: other anesthetics or placebo; (iv) outcome parameters: blood pressure, heart rate, duration of
ventilation, ICU and hospital stays, requirement for
postoperative fentanyl and morphine, perioperative
blood glucose and serum cortisol levels, and incidence of
postoperative delirium, bradycardia, and hypotension;
and (v) study design: randomized controlled trials
(RCTs) and observational studies (prospective or retrospective cohort studies).
Data abstraction and quality assessment
Data extraction was performed by Y.T.W. and confirmed independently by X.X.H. The following information was extracted from each paper and tabulated: first
author, year of publication, study design, patient characteristics, number of patients enrolled, surgery time,
cardiopulmonary bypass time, and dexmedetomidine
and control agent doses. Information on the following
outcomes was extracted if reported: blood pressure,
heart rate, duration of mechanical ventilation, length of
ICU and hospital stays, requirement for postoperative
morphine and fentanyl, blood glucose and cortisol
levels, risk of delirium, and bradycardia or hypotension
requiring intervention. In instances where the same
patients were included in several publications, we
retained only the largest study to avoid information
duplication.
The Jadad scale was used to assess the methodological quality of each RCT (16). The methodological
quality of observational studies was assessed using the
Newcastle–Ottawa Scale (17). Differences were
resolved by discussion and consensus; if disagreement
persisted, the opinions of all members of the research
team were sought.
Literature search and selection criteria
The PubMed, Embase, and Cochrane Library databases were searched for studies on the effects of
dexmedetomidine on CHD surgery outcomes in pediatric patients. The following search keywords were
used: ‘dexmedetomidine’ AND ‘cardiac surgery or
heart surgery’ AND ‘children or pediatric’. No publi240
Statistical analysis
The meta-analysis was performed and forest plots were
produced using the REVIEW MANAGER software package
(ver. 5.2; Cochrane Collaboration, Oxford, UK). Mean
differences (MD) and odds ratios (OR) were calculated
to compare continuous and dichotomous variables,
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
W. Pan et al.
Dex for cardiac surgery in children
respectively. All results were reported with 95% confidence intervals (CIs). For studies that presented continuous data as median and range values, standard
deviations were calculated using the technique described
by Hozo et al. (18). Statistical heterogeneity between
studies was assessed using the chi-squared test with the
significance level set at P < 0.10; heterogeneity was
quantified using the I2 statistic. The random-effects
model was used if there was heterogeneity between studies; otherwise, the fixed-effects model was used (19).
Results
midine group, n = 1055; control group, n = 1174). Five
of the included studies were RCTs (20–24), one was a
post hoc analysis of RCTs (25), and the remaining eight
were cohort studies (26–33): four retrospective
(26,29,30,33) and four prospective (27,28,31,32).
To our best knowledge, children with cardiac disease
are considered as a single diagnosis. The heterogeneity
and physiologic disparity of the subgroups of children
with congenital heart disease can be vast. Therefore, the
anatomical defect types among the included studies are
organized to take advantage of these informations
(Table S1).
Literature search and study selection
Quality of the included studies
In total, 353 studies were identified during the initial
database search, including 110 articles in PubMed, 207
articles in Embase, and 36 articles in the Cochrane
Library. Eighty-eight records with duplicate data were
excluded; a further 237 records were excluded on the
basis of their titles and abstracts. Of the remaining 28
eligible studies, 14 were removed because they reported
on other outcomes, they were not full-text, or two publications used the same patients. Fourteen studies were
included in the final meta-analysis (20–33). The selection
process is detailed in Figure 1.
The quality of the included studies was generally low.
True randomization and blinding was applied in only
four and three RCTs, respectively. None of the observational studies mentioned the length of follow-up, and
they all provided only perioperative data (Table 1).
Article characteristics
The main characteristics of the included studies are
listed in Table 1. All of the studies were published from
2006 to 2015; the sample sizes ranged from 14 to 1088,
and the total number of patients was 2229 (dexmedetoPubMed: n = 110
Embase: n = 207
Cochrane: n = 36
Studies identified through initial
searches of electronic databases:
n = 353
Duplications: n = 88
Titles and abstracts screened:
n = 265
Excluded studies:
n = 237
Full-text articles screened:
n = 28
Effects on hemodynamics
Mean blood pressure (MBP) was investigated in five
studies (356 children) (20,21,27,28,33), and systolic
blood pressure (SBP) was investigated in five studies
(227 children) (22–24,27,31). Heart rate data were presented in nine studies (526 children) (20–24,27,28,31,33).
All of the hemodynamic values were obtained at the
point of skin incision or sternotomy, when the maximal
increase in heart rate and blood pressure occurred. The
collective data from the RCTs and observational studies
indicated that dexmedetomidine significantly reduced
the heart rate (MD 13.62; 95% CI 20.37, 6.86;
P < 0.0001). The heart rate of the dexmedetomidine
group remained >90 bmin 1, which is preferable for
children (Figure 2). Moreover, dexmedetomidine stabilized the blood pressure at the time of surgical stimulation, such that fluctuations were smaller relative to the
control group (Figure 3). In addition, the children treated with dexmedetomidine seemed to be far less vulnerable to tachycardia (OR 0.07; 95% CI 0.02, 0.22;
P < 0.0001) (Table 2 and Figure S1a). When the data
were pooled, dexmedetomidine was found to significantly increase the risk of bradycardia and hypotension
(OR 3.14; 95% CI 1.47, 6.69; P = 0.003) (Table 2 and
Figure S1b).
Excluded studies:
n = 14
Included studies
n = 14
Figure 1 Flow diagram of the identified, included, and excluded
studies.
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
Effects on stress response
Treatment with dexmedetomidine was associated with a
blunting of the sympathetic stress response, evidenced
by lower blood glucose (MD 49.80; 95% CI 66.74,
241
242
2011
2010
2009
Chrysostomou
et al. (31)
Hosokawa
et al. (32)
Tokuhira
et al. (33)
5
5
7
6
Retrospective
Prospective
Prospective
Retrospective
Retrospective
Prospective
Prospective
Post hoc
analysis
of RCT
Retrospective
RCT
RCT
RCT
RCT
RCT
Study design
14 (9/5)
141 (56/85)
52 (32/20)
269 (89/180)
1088 (544/544)
25 (15/10)
57 (29/28)
174 (77/97)
31 (15/16)
30 (15/15)
28 (14/14)
60 (30/30)
40 (20/20)
220 (110/110)
No.of patients
(DEX/control)
1.3Y (14M–11Y)/
1.8Y (13M–15Y)
1 (0.5–3.0)/
1 (0.8–4.0) Y
13.7 (3–215)/
14.7 (1–265) M
4.8 (0.16–198)/
2.6 (0.13–158) M
0.45 (0.29–0.95)/
0.48 (0.31–1.10) Y
Postoperative
17.7 11.4/
20.2 11.8 M
6.6 2.1/
6.3 1.5 M
11.9 3.9/
11.5 2.6 M
Postoperative
Intraoperative
and
postoperative
Postoperative
Intraoperative
and
postoperative
Intraoperative
and
postoperative
Postoperative
Intraoperative
Intraoperative
Intraoperative
Intraoperative
Intraoperative
Intraoperative
and
postoperative
Postoperative
Medication time
5 (2–21)/4
(3–7) M
2.3 1.3/
2.5 1.6 Y
23.2 10.6/
26.5 8.5 M
6.07 3.94/
5.67 3.34 Y
10.8 21.6/
24.4 31.6 M
2.77 1.57/
2.71 1.44 Y
Age (DEX/control)
Chlorpromazine,
midazolam,
fentayl
Midazolam,
propofol,
buprenorphine,
pentazocine
Midazolam,
fentanyl
Fentanyl
Not given
Midazolam,
fentanyl
Propofol
Midazolam
Saline
Saline
Midazolam
Fentanyl
Fentanyl
Saline
Comparison
0.3–0.4
lgkg 1h
0.4–0.6
lgkg 1h
1
1
0.3–0.7
lgkg 1h 1
0.76 0.04
lgkg 1h 1
0.3 lgkg 1,
then 0.2–
0.3 lgkg 1h
Not given
1
1 lgkg 1 over
10 min, then
0.5 lgkg 1h 1
0.25–0.75
lgkg 1h 1
0.5–0.7 lgkg 1h
1 lgkg 1h 1
for 1 h, then
0.5 lgkg 1h 1
0.5 lgkg 1
over 10 min, then
0.5 lgkg 1h 1
1
1
0.1 mgkg 1h 1;
0.1 mgkg 1h 1;
or 0.2 lgkg 1h 1
Not given
Not given
0.1 mgkg 1h 1;
1 lgkg 1h 1
1–4 lgkg 1h 1
Not given
293 109/
274 124
Not given
Not given
141 29/
155 33
Not given
Not given
Not given
Not given
166.5 15/
170.6 18
256 16.43/
242 15.38
Not given
167.62 35.84/
167.23 30.99
Surgery
time (min)
Not given
Not given
A similar
volume
of saline
0.5–3
lgkg 1min 1
6–8 mgkg 1h 1
0.2 mgkg 1h 1
for 1 h, then
0.1 mgkg 1h 1
A similar
volume of
saline
1 lgkg 1h
0.5 lgkg 1h
1
A similar
volume
of saline
1 lgkg 1
Control
0.5 lgkg 1 over
10 min, then
0.5 lgkg 1h 1
0.5 lgkg 1
Dexmedetomidine
Infusion rate
DEX, dexmedetomidine; Y, year; M, month; RCT, randomized controlled trial; CPB, cardiopulmonary bypass; NOS, Newcastle-Ottawa Scale.
Values are presented as median (interquartile range) or mean standard deviation unless indicated otherwise.
2011
Le et al. (30)
6
5
2014
2014
7
4
2014
2015
Moffett
et al. (29)
Jiang
et al. (26)
Cheng
et al. (27)
Chen
et al. (28)
6
Observational study
Naguib
2013
et al. (25)
3
2010
2
4
2012
2006
Mukhtar
et al. (24)
5
5
2013
2014
RCT
Rajput
et al. (20)
Nasr
et al. (21)
Prasad
et al. (22)
Klamt
et al. (23)
Year
Study
Jadad or
NOS
score
Table 1 Characteristics of the included studies
Not given
118 72/
114 86
120 (33–406)/
114 (14–402)
93 7/79 9
Not given
56.8 16.1/
61.6 19.4
82 27/
71 26
51.9 6.2/
52.9 5.3
124 (83–173)/
113 (74–225)
50 4.9/
49 5.6
45.2 6.1/
47.9 5.6
83 (80–110)/
76 (76–103)
117.6 44.2/
101.9 41.5
85.48 26.11/
86.59 19.49
CPB time (min)
Dex for cardiac surgery in children
W. Pan et al.
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
W. Pan et al.
Dex for cardiac surgery in children
Mean difference
Mean difference
subgroup
τ
χ
τ
τ
χ
χ
χ
Figure 2 Comparison between dexmedetomidine-treated and control patients with respect to heart rate. The meta-analysis indicated that
dexmedetomidine was associated with a more stable heart rate during surgical stimulation.
32.86; P < 0.00001; Figure 4a) and serum cortisol
(MD 59.17; 95% CI 111.83, 6.52; P < 0.00001;
Figure 4b) levels.
Effects on early recovery
After pooling data from eight studies (20–
22,25,26,29,30,32,33) that assessed postoperative
mechanical ventilation in 2037 patients, it was found
that dexmedetomidine significantly reduced the length
of mechanical ventilation (MD
93.36; 95% CI
137.45, 49.27; P < 0.0001; Table 2). Our data also
revealed no difference between the dexmedetomidinetreated and control patients in the length of ICU (MD
0.18; 95% CI 0.49, 0.13; P = 0.25) and hospital (MD
0.39; 95% CI 0.22, 1.01; P = 0.15) stays.
Effects on postoperative rescue analgesia
Four trials (526 patients) compared dexmedetomidinetreated and control participants with respect to postoperative rescue analgesia (25,26,30,31). The meta-analysis
revealed that children treated with dexmedetomidine
required less rescue analgesia (fentanyl [MD 24.11;
95% CI 36.98, 11.24] or morphine [MD 0.07; 95%
CI 0.14, 0.00]). All the details is shown in Table 2.
Effects on delirium
Dexmedetomidine reduced the incidence risk of agitation or delirium following CHD surgery (OR 0.39; 95%
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
CI 0.21, 0.74; P = 0.004) (Table 2 and Figure S1a).
Meanwhile, the methods to judge whether the preverbal
subjects are delirium or not in the included studies are
addressed in Data S1. On visual inspection, the funnel
plots did not exhibit a skewed or asymmetrical shape
(Figure S2).
Discussion
This systematic review and meta-analysis indicates that
perioperative use of dexmedetomidine is associated with
better outcomes in pediatric patients undergoing CHD,
including more stable intraoperative hemodynamics,
shorter length of postoperative mechanical ventilation,
and reduced stress responses, postoperative analgesia
requirements, and postoperative delirium. Notably, the
incidence of bradycardia and hypotension was higher in
the dexmedetomidine-treated patients.
The hemodynamic values in this meta-analysis were
obtained at the time of surgical trauma, including skin
incision, sternotomy, and bypass termination. We also
found that the blood pressure and heart rate of children
treated with dexmedetomidine appeared to be more
stable, which is consistent with a previous meta-analysis
that focused on the use of dexmedetomidine as a
premedication in children (34). The underlying mechanism of action of dexmedetomidine may be related to its
sympatholytic effects, which attenuate the stress
response to various noxious stimuli (35,36). In our analysis, dexmedetomidine use was associated with an
almost three-fold increase in the risk of bradycardia or
243
Dex for cardiac surgery in children
(a)
W. Pan et al.
Mean difference
Mean difference
Mean difference
Mean difference
Study or subgroup
τ2
τ2
τ2
χ2
χ2
χ2
χ2
(b)
Study or subgroup
τ2
χ2
τ2
χ2
τ2
χ2
χ2
Figure 3 Comparison between dexmedetomidine-treated and control patients with respect to MAP (a) and SBP (b).
hypotension, which is consistent with another recent
meta-analysis (37) in which the incidence of bradycardia
and hypotension among dexmedetomidine-treated
patients was higher than that in controls (pooled ORs:
5.14 and 3.00, respectively; adult patients). Although no
severe complications related to bradycardia or hypotension were reported in these studies, particular attention
should be paid to patients with a transduction block and
those who are in shock.
Whether dexmedetomidine reduces postoperative ventilation remains controversial. In one retrospective study
with a large sample (14), perioperative dexmedetomidine
did not reduce postoperative ventilation times in adults
after cardiac surgery. However, a meta-analysis (8)
supports the notion that dexmedetomidine can
decrease postoperative mechanical ventilation times in
244
adults. Our review offers moderate evidence that
dexmedetomidine can also shorten the length of postoperative mechanical ventilation in children after CAD
surgery. Consistently, we always use dexmedetomidine
when we are planning an early extubation, and we rarely
use it when we are not planning an early extubation.
The mechanism underlying this ventilation-shortening
effect may in turn relate to an anesthetic-sparing effect
(10,11,36), in addition to the minimal amount of respiratory depression (36,38) produced by dexmedetomidine.
Therefore, dexmedetomidine appears to facilitate
decreases in the adverse effects induced by narcotics
and more rapidly restores spontaneous breathing.
A decreased extubation time may protect patients from
ventilator-associated pneumonia and contribute to a
reduction in the length of ICU stays and hospital costs
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
W. Pan et al.
Dex for cardiac surgery in children
Table 2 Results of the meta-analysis comparing dexmedetomidine-treated and control patients
Outcomes of interest
Studies, no.
Dexmedetomidine
patients, no.
Control
patients,
no.
Heart rate
Mean arterial pressure
Systolic blood pressure
Ventilator
ICU stay
Hospital stay
Fentanyl
Morphine
Glucose
Cortisol
Delirium
Bradycardia or hypotension
Tachycardia
9
5
5
8
8
5
3
3
3
3
2
3
2
274
183
120
950
932
757
136
198
50
50
133
97
142
252
173
107
1087
1057
857
216
297
51
51
182
110
130
Odds ratio or weighted
mean (95%
confidence interval)
13.62 ( 20.37, 6.86)
3.78 ( 13.19, 5.63)
11.80 ( 20.06, 3.53)
93.36 ( 137.45, 49.27)
0.18 ( 0.49, 0.13)
0.39 ( 0.22, 1.01)
24.11 ( 36.98, 11.24)
0.07 ( 0.14, 0.00)
49.80 ( 66.74, 32.86)
59.17 ( 111.83, 6.52)
0.39 (0.21, 0.74)
3.14 (1.47, 6.69)
0.07 (0.02, 0.22)
Study
heterogeneity
P-value
P-value
I2 test
0.0001
0.43
0.005
0.0001
0.25
0.21
0.0002
0.07
0.00001
0.03
0.004
0.003
0.00001
0.00001
0.00001
0.00001
0.00001
0.02
0.15
0.004
0.00001
0.00001
0.00001
0.33
0.43
0.92
95%
96%
95%
97%
58%
41%
82%
94%
93%
95.80%
0%
0%
0%
Statistically significant results are shown in bold.
(a)
Mean difference
Mean difference
Mean difference
Mean difference
Study or subgroup
τ2
τ2
χ2
χ2
χ2
(b)
Study or subgroup
τ2
τ2
χ2
χ2
χ2
Figure 4 Comparison between dexmedetomidine-treated and control patients with respected to blood glucose (a) and serum cortisol (b).
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
245
Dex for cardiac surgery in children
(39,40). Similar to adults, no reduction in the duration
of ICU or hospital stays was observed in children (8).
There are other factors, in addition to ventilation time,
that influence ICU and hospital stay lengths, including
medical and sociodemographic variables, self-rated
health and happiness, postoperative cardiac failure, and
postoperative complications (41).
Patients undergoing cardiac surgery are exposed to
specific risk factors for delirium, such as cardiopulmonary bypass and circulatory arrest, and appear at
high risk of delirium (42). Our results showed that
dexmedetomidine reduced the risk of delirium, which is
important in pediatric patients after CHD surgery to
avoid poor outcomes, such as prolonged ICU and hospital stays, slower recovery from cognitive impairment,
higher risk of mortality, and increased healthcare costs
(43–45). Although an increasing number of studies support the notion that dexmedetomidine can effectively
prevent delirium (8,46), recent (2013) American College
of Critical Care medicine guidelines for the management of pain, agitation, and delirium in adult patients
in ICUs suggested that there is no compelling evidence
for this effect and provided no recommendations for
the use of dexmedetomidine to prevent delirium (47).
Therefore, more high-quality RCTs on this subject are
required.
Surgical procedures and cardiopulmonary bypass
during cardiac surgery produce a neuroendocrine stress
response that plays an important role in the pathogenesis of perioperative cardiac complications and increases
morbidity and mortality (48). Blood levels of glucose
and cortisol are regarded as predictors of this stress
response; as expected, our analysis convincingly demonstrates that dexmedetomidine can inhibit increased
blood glucose and cortisol levels in patients undergoing
cardiac surgery.
A previous meta-analysis confirmed that perioperative dexmedetomidine can decrease postoperative morphine consumption and pain intensity (49). Our analysis
provides further evidence that dexmedetomidine reduces
postoperative morphine and fentanyl consumption
effectively in children after CHD surgery; a reduced
requirement for analgesia may in turn reduce the incidence of opioid-related adverse effects, such as nausea
and vomiting.
Several potential limitations should be taken into
account when interpreting the results. First, among
the 14 included studies, only five studies were RCTs
with small sample sizes, whereas the other nine were
observational studies. Inadequate blinding tended to
increase the risk of bias, and observational studies
were highly subject to selection bias and confounding
by indication. Second, this meta-analysis was
246
W. Pan et al.
influenced by significant heterogeneity that was introduced by multiple factors that included different
study design, age group, dosage, dosing regimens,
and disease severity. Third, several clinical end
points, such as blood glucose, serum cortisol, and
adverse events, were reported in only three studies
and the population was not large. Nevertheless, this
meta-analysis was conducted at an appropriate time,
and provided the most up-to-date information for
dexmedetomidine utilization in children undergoing
CHD surgery.
Conclusions
In conclusion, the present systematic review and
meta-analysis offers convincing evidence that dexmedetomidine can be recommended for use in children
undergoing CHD surgery. The advantages of using
this agent include more stable intraoperative hemodynamics, reduced mechanical ventilation times and
analgesia requirements, a lower incidence of agitation and delirium, and an attenuated stress response.
However, particular attention should be paid to perioperative bradycardia and hypotension induced by
dexmedetomidine.
Author contributions
W.Y.P.: study design, data analysis, and first draft of
manuscript. L.L. and G.Z.: literature search and identification. Y.T.W and X.X.H.: data extraction. L.Q.M.:
study design, supervision, and reviewed manuscript.
Funding
This work was supported by departmental funding.
Conflicts of interest
The authors report no conflict of interest.
Supporting information
Additional Supporting Information may be found in the
online version of this article:
Figure S1 Forest plot for incidence of tachycardia (a),
bradycardia (b), and postoperative delirium (c).
Figure S2 Forrest plot for intraoperative heart rate (a)
and postoperative mechanical ventilation (b).
Table S1 The anatomical defect types among the
included studies.
Data S1 The methods to measure the children delirium or not.
© 2015 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.
Pediatric Anesthesia 26 (2016) 239–248
W. Pan et al.
Dex for cardiac surgery in children
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