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Nienke J. Vet
Erwin Ista
Saskia N. de Wildt
Monique van Dijk
Dick Tibboel
Matthijs de Hoog
Optimal sedation in pediatric intensive care
patients: a systematic review
Received: 12 March 2013
Accepted: 18 May 2013
Ó Springer-Verlag Berlin Heidelberg and
ESICM 2013
N. J. Vet (
)
) E. Ista S. N. de Wildt
M. van Dijk D. Tibboel M. de Hoog
Intensive Care, Erasmus MC, Sophia
Children’s Hospital, Dr. Molewaterplein 60,
3015 GJ Rotterdam, The Netherlands
e-mail: n.vet@erasmusmc.nl
Tel.: ?31-10-7036922
N. J. Vet E. Ista M. de Hoog
Department of Pediatrics, Erasmus MC,
Sophia Children’s Hospital, Dr.
Molewaterplein 60, 3015 GJ Rotterdam,
The Netherlands
S. N. de Wildt M. van Dijk D. Tibboel
Department of Pediatric Surgery, Erasmus
MC, Sophia Children’s Hospital, Dr.
Molewaterplein 60, 3015 GJ Rotterdam,
The Netherlands
Abstract Purpose: Sedatives
administered to critically ill children
should be titrated to effect, because
both under- and oversedation may
have negative effects. We conducted
a systematic review to examine
reported incidences of under-, opti-
mal, and oversedation in critically ill
children receiving intensive care.
Methods: A systematic literature
search using predefined criteria was
performed in PubMed and Embase to
identify all articles evaluating level of
sedation in PICU patients receiving
continuous sedation. Two authors
independently recorded: study objec-
tive, study design, sample size, age
range, details of study intervention (if
applicable), sedatives used, length of
sedation, sedation scale used, and
incidences of optimal, under-, and
oversedation as defined in the studies.
Results: Twenty-five studies were
included. Two studies evaluated
sedation level as primary study out-
come; the other 23 as secondary
outcomes. Together, these studies
investigated 1,163 children; age
range, 0–18 years. Across studies,
children received many different
sedative agents and sedation level
was assessed with 12 different seda-
tion scales. Optimal sedation was
ascertained in 57.6 % of the obser-
vations, under sedation in 10.6 %,
and oversedation in 31.8 %. Conclu-
sions: This study suggests that
sedation in the PICU is often subop-
timal and seldom systematically
evaluated. Oversedation is more
common than undersedation. As
oversedation may lead to longer hos-
pitalization, tolerance, and
withdrawal, preventing oversedation
in pediatric intensive care deserves
greater attention.
Keywords Pediatrics
Intensive care Sedation
Clinical pharmacology
Introduction
The provision of adequate sedation and analgesia to
critically ill children is an important aspect of care in
the pediatric intensive care unit. Sedatives and analge-
sics reduce anxiety, pain, and agitation, enhance
synchronization with mechanical ventilation, and enable
invasive procedures to be performed. Adequate sedation
is defined as the level of sedation at which patients are
asleep but easily arousable [1]. Oversedation delays
recovery, as greater sedatives consumption is associated
with longer duration of ventilation as well as extubation
failure [2]. Oversedation also induces tolerance and
withdrawal syndrome [3, 4]. Undersedation, on the
other hand, may lead to increased distress and adverse
events such as unintentional extubation or displacement
of catheters. All this may also lead to a longer ICU
stay.
Intensive Care Med
DOI 10.1007/s00134-013-2971-3
SYSTEMATIC REVIEW
Children are usually sedated through a combination
of hypnotics (e.g., midazolam) and analgesics (e.g.,
morphine or fentanyl) [5–7]. Regrettably, there is little
evidence from randomized trials on the efficacy of
these drugs for sedation in critically ill children [8].
Nevertheless, efforts are being made to improve seda-
tion management, for example with the use of sedation
algorithms and standardized sedation management [9,
10].
To achieve the optimal level of sedation in individual
patients, doses of sedatives are individually titrated to
effect. This process is guided by scores on a variety of
observational sedation scales [5]. The COMFORT score
or COMFORT behavior scale and the Hartwig sedation
scale are widely used and validated for this setting [11,
12]. Other scales used are the Ramsay scale [13], Rich-
mond Agitation Sedation Scale (RASS) [14], State
Behavior Scale (SBS) [15], and the University of Mich-
igan Sedation Scale (UMSS) [16]. In addition, methods
derived from the electro-encephalogram (EEG), such as
the Bispectral Index (BIS) and middle latency auditory-
evoked potential index (AEP), are applied, although their
use is not validated in young children [17].
The aim of this systematic literature review is to
evaluate the reported incidences of under-, optimal, and
oversedation in pediatric intensive care patients and to
determine to what extent the goal of adequate sedation is
met [18].
Methods
Search strategy
A systematic literature search was performed in the
PubMed and Embase databases from inception to July
2012, using the terms sedation, child, intensive care unit,
and sedation quality/sedation level. We used a compre-
hensive search strategy to identify all published articles
evaluating the level of sedation, measured with an
observational scale, in pediatric intensive care patients.
For Embase, appropriate search terms were applied. Full
details of the search strategy are presented in Appendix 1.
Furthermore, reference lists of retrieved articles were
searched to identify other relevant papers that complied
with the inclusion criteria.
Selection criteria
We used the following inclusion criteria:
1. Study population of PICU patients (0–18 years) on
mechanical ventilation and receiving continuous
sedation.
2. Reporting level of sedation and/or the incidence of
under-, over-, and optimal sedation, as defined in the
study.
Studies published in any language with an English-
language abstract were eligible for review.
Exclusion criteria were:
1. Procedural sedation
2. Preterm patients
3. Patients treated with muscle relaxants, which preclude
the use of sedation scores
4. Studies using only the BIS monitor in children aged
\1 year, since this method is not validated for this
patient group [17].
Two authors (NV, EI) independently reviewed titles
and abstracts of all retrieved citations to identify eligible
studies. Of all included studies, the full-text articles were
again reviewed to ensure that they met inclusion criteria.
Disagreements between reviewers were resolved by
consensus.
Data extraction
Two authors (NV, EI) each independently recorded the
following data: country of origin, study objective, study
design, study population, age of patients, sample size,
details of study intervention (if applicable), sedatives used
(drug, dose), length of sedation, sedation scale used, and
the incidence of optimal sedation, and under- and over-
sedation. We used the definitions for optimal sedation as
used by the researchers in the individual studies (as per-
centage of number of observations, patients or time) to be
able to pool the data, despite different sedation assess-
ment methods (Table 1).
Quality assessment
Study quality was determined with the ‘‘Quality Assess-
ment Tool for Quantitative Studies’’ by the McMaster
University, School of Nursing [19] as strong, moderate, or
weak.
Statistical analysis
We analyzed studies separately on study design, sedation
scale used, and proportion of under-, over-, and optimal
sedation. Proportion was expressed as percentage of
number of observations, patients or time (h). If similar
outcome measures were used, the results of individual
studies were quantitatively pooled to calculate a weighted
mean, using descriptive statistics. The large heterogeneity
Table 1 Summary of included studies reporting the incidence of optimal, under-, and oversedation
Authors Country Study design Study population n Sedatives used Sedation scale Definition
optimal
sedation
Incidence of
optimal
sedation
Incidence of
under-
sedation
Incidence of
over-
sedation
Comments
Parkinson et al.
[34]
UK RCT of sedative
drugs
Critically ill
children 1 day–
15 years
44 Midazolam vs.
chloral hydrate
and promethazine
Clinical sedation
scale
2–4, depending on
patients
condition
96 and 90 %
(413/432 and
332/367 obs)
4 and 9 %
(19/432 and
32/367 obs)
0 and 1 %
(0/432 and 3/367 obs)
Amigoni et al.
[22]
Italy Observational study
of sedation scales
Critically ill
children
1 month–
18 years
46 Not reported Comfort behavior
scale nurse
(and BIS)
COMFORT-B
11–22
(BIS 40–80)
34.8 %
(16/46 pts)
73.9 %
(34/46 pts)
0%
(0/46 pts)
4.3 %
(2/46 pts)
65.2 %
(30/46 pts)
21.7 %
(10/46 pts)
Ista et al. [9] The Netherlands Observational study,
before-after
introduction of
sedation protocol
Critically ill
children
0–3 years
131 Midazolam,
morphine
COMFORT behavior
scale and NISS
COMFORT-B
11–22 with a
NISS of 2
64 %
(2273/3573 obs)
12.9 %
(461/3573 obs)
19.7 %
(704/3573 obs)
Ista et al. [11] The Netherlands Observational study
of sedation scale
Critically ill
children
0–18 years
78 Midazolam,
morphine,
ketamine,
fentanyl
COMFORT behavior
scale and NISS
COMFORT-B
11–22 with a
NISS of 2
48.8 %
(411/843 obs)
11.2 %
(94/843 obs)
40.1 %
(338/843 obs)
Froom
et al. [23]
UK Observational study
of sedation scales
Critically ill
children
0–16 years
19 Midazolam,
morphine, chloral
hydrate
COMFORT score 17–26 14.8 %
(4/27 obs)
3.7 %
(1/27 obs)
81.5 %
(22/27 obs)
Triltsch et al.
[24]
Germany Observational study
of sedation scales
Critically ill
children
\18 years
40 Benzodiazepines,
opioids, propofol,
ketamine
COMFORT score 17–26 27.5 %
(11/40 pts)
0 % 72.5 %
(29/40 pts)
de Wildt et al.
[40]
The Netherlands Observational PKPD
study
Critically ill
children
2 days–17 years
21 Midazolam COMFORT score 17–26 46.1 %
(244/497 obs)
6%
(30/497 obs)
44.9 %
(223/497 obs)
Arenas-Lopez
et al. [35]
UK Observational study
of sedative drug
Critically ill
children
\5 years
14 Morphine and
clonidine
COMFORT score 13–23 81.9 %
(837/1022 h)
10.8 %
(110/1022 h)
7.3 %
(75/1022 h)
Marx et al. [20] USA Observational study
of sedation scale
Critically ill
children
1–102 months
85 Opiates,
benzodiazepines,
barbiturates
COMFORT score 17–26 57.1 %
(32/56 obs)
12.5 %
(7/56 obs)
30.4 %
(17/56 obs)
Brunow de
Carvalho
et al. [12]
Brazil Observational study
of sedation scales
Critically ill
children
16 days–5 years
18 Opiates,
benzodiazepines,
barbiturates
COMFORT score
Hartwig sedation
scale
COMFORT 17–26
Hartwig 15–18
CF 60 %
(18/30 obs)
Hartwig 56.7 %
(17/30 obs)
CF 6.7 %
(2/30 obs)
Hartwig 16.7 %
(5/30 obs)
CF 33.3 %
(10/30 obs)
Hartwig 26.7 %
(8/30 obs)
Aneja et al. [25] USA Observational study
of sedation scales
Critically ill
children
3 months–
18 years
24 Opioids,
benzodiazepines,
propofol
Ramsay 2–3 33.8 %
(155/458 obs)
9.2 %
(42/458 obs)
Deeply 38.8 %
(179/458 obs)
Oversedated 18.2 %
(82/458 obs)
Berkenbosch
et al. [26]
USA Observational study
of sedation scales
Critically ill
children
1 month–
20 years
24 Midazolam,
fentanyl, propofol
Ramsay 2–4 50.9 %
(217/426 obs)
8.7 %
(37/426 obs)
40.4 %
(172/426 obs)
Curley et al.
[15]
USA Observational study
of sedation scales
Critically ill
children
6 weeks–
6 years
91 Opioids,
benzodiazepines
State Behavioral
Scale
0 and -1 42.9 %
(85/198 obs)
4%
(8/198 obs)
53 %
(105/198 obs)
Johansson et al.
[27]
Sweden Observational study
of sedation scales
Postoperative
patients
0–10 years
40 Midazolam,
morphine
NISS NISS of 2 70 % 17 % 13 %
Ambrose et al.
[36]
UK Observational study
of sedative drug
Critically ill
children
\10 years
20 Midazolam and
clonidine
Clinical sedation
score
2–7 89 % – –
Playfor et al.
[21]
UK Observational study
of sedation scale
Critically ill
children
1 month–
16 years
28 Midazolam,
morphine, chloral
hydrate,
antihistamines
Clinical sedation
score (response to
tracheal suction)
1, 2, or 4 79 % ideal
11 % acceptable
(64/81 obs and
9/81 obs)
10 %
(8/81 obs)
–
Hartwig et al.
[37]
Germany Observational PKPD
study
Critically ill
children
26 days–5 years
24 Midazolam, fentanyl Clinical sedation
score
15–18 60 %
(9/15 points)
6.7 %
(1/15 points)
33.3 %
(5/15 points)
Table 1 continued
Authors Country Study design Study population n Sedatives used Sedation scale Definition
optimal
sedation
Incidence of
optimal
sedation
Incidence of
under-
sedation
Incidence of
over-
sedation
Comments
Lamas et al.
[28]
Spain Observational study
of sedation scales
Postoperative
cardiac and non-
cardiac surgery
patients
\14 years
50 Midazolam, fentanyl
(vecuronium)
BIS monitor
MLAEPs
Ramsay score
COMFORT score
BIS C 60
MLAEPs C 30
Ramsay B 5
COMFORT C 18
8%
(4/50 pts)
– BIS 56 %
MLAEPs 73.3 %
Ramsay 83.9 %
COMFORT 92.9 %
40 % of the obs in
paralyzed
patients
Lamas et al.
[29]
Spain Observational study
of sedation scales
Critically ill
children
6 months–
19 years
50 Opioids,
benzodiazepines
BIS
MLAEPs
BIS C 60
MLAEPs C 30
44 %
(62/141 obs)
–56%
(79/141 obs)
39 % of the obs in
paralyzed
patients
Lamas et al.
[30]
Spain Observational study
of sedation scales
Critically ill
children
\19 years
77 Midazolam, fentanyl
(vecuronium)
BIS monitor
AEPs
Ramsay score
COMFORT score
BIS C 60
AEPs C 30
Ramsay 1–5
COMFORT 18–40
BIS 35 %
AEPs 32.5 %
Ramsay 27 %
COMFORT 18 %
– BIS 65 %
AEPs 67.5 %
Ramsay 73 %
COMFORT 82 %
40 % of the obs in
paralyzed
patients
Twite et al. [31] USA Observational study
of sedation scales
Critically ill
children
1 month–
13 years
75 Fentanyl, midazolam BIS BIS 61–80 26.5 %
(230/869 obs)
9.5 %
(83/869 obs)
64 %
(556/869 obs)
Courtman et al.
[32]
UK Observational study
of sedation scales
Critically ill
children
1 month–
16 years
40 Midazolam,
morphine
BIS BIS 60–80 63 % – 24 %
Crain et al. [33] USA Observational study
of sedation scales
Critically ill
children
31 Opioids,
benzodiazepines,
propofol
BIS BIS 61–80 27.4 %
(17/62 obs)
22.6 %
(14/62 obs)
50 %
(31/62 obs)
Chrysostomou
et al. [38]
USA Retrospective study
of sedative drug
Postoperative
cardiothoracic
surgery patients
38 Dexmedetomidine Sedation scale 0–2 93 % – – 33 patients not on
MV
Rosen et al. [39] USA Retrospective study
of sedative drug
Critically ill
children
55 Midazolam Five-point activity
scale for sedation
3 ±90 % \10 % –
Studies are categorized by study design and sedation scale used
Obs observations, pts patients, h hours
in study aims and study designs precluded further statis-
tical analysis.
Results
Study selection
After filtering out duplicate studies, our search yielded
392 potentially relevant articles. Of these studies, 348
were excluded on the grounds of information in title and
abstract (Fig. 1). Of the remaining 44 articles, the full-text
was retrieved and assessed for eligibility. Nineteen stud-
ies were excluded for lack of quantitative data on sedation
level or incidence of optimal-, under-, or oversedation, or
for absence of a definition of optimal sedation. Details of
the remaining 25 studies are presented in Table 1.
Study characteristics
One study was a randomized controlled trial (comparing
two sedative regimens); 22 studies were prospective
observational studies; and two were retrospective studies
on a sedative drug. Of all 25 studies, only two determined
the level of sedation as primary study outcome [20, 21].
Fifteen studies investigated one or more sedation scales or
sedation monitoring systems (such as the BIS) [11, 12, 15,
22–33]; six studies investigated a sedative drug [34–39];
one was a pharmacokinetic-pharmacodynamic study [40];
and one study described the effect of implementation of a
sedation protocol on amount of sedatives administered
[9]. Although assessment of level of sedation was not the
primary objective in the latter 23 studies, they reported
incidences of under-, optimal-, and oversedation.
Since sedation practices may differ between countries,
we also looked at the country of origin. Of the 25 studies,
eight were conducted in the United States, 16 in six
European countries, and one in Brazil.
All studies together investigated a total of 1,163 crit-
ically ill children. The most frequently used drugs were
benzodiazepines (midazolam, in 22 studies) and opioids
(morphine, in 14 studies). Other drugs used were fentanyl,
ketamine, clonidine, propofol, barbiturates, chloral
hydrate, first-generation antihistamines, and dexmede-
tomidine in different combinations.
Quality assessment
Only two studies had level of sedation as their primary
outcome, all other studies varied by aim and study design.
Therefore, assessment of study quality with the ‘‘Quality
Assessment Tool for Quantitative Studies’’ was not
possible, and this makes direct comparison between the
studies difficult.
Sedation scales
Across all studies, 12 different observational sedation
scores were used, of which four were validated for the
PICU setting, i.e., the COMFORT-score, the COMFORT-
B scale, the Hartwig sedation scale, and the State
Behavior Scale. Most frequently (11/25) used were the
COMFORT-score and COMFORT-behavior scale
(COMFORT-B), followed by the Ramsay score, the State
Behavioral Scale, and the Hartwig sedation scale. Six
studies (23 %) used the BIS monitor. In 13 studies two or
more sedation scales or monitors were used.
All studies defined optimal sedation in terms of cut-off
values (Table 1). The definition of optimal sedation dif-
fered between studies, even when the same sedation scale
was used. For example, a COMFORT score between 17
and 26 is thought to indicate adequate sedation [20].
However, one study applied the 13–23 range to define
adequate sedation [35]. This range was chosen a priori to
target a level of sedation that would produce a patient
who was under analgesics, calm, with minimal risk of
self-extubation, but able to maintain an appropriate cough
reflex and spontaneous respiratory effort to achieve ven-
tilator synchrony. Furthermore, different cut-off values
for the Ramsay score were used: i.e., 2–3 [25]; 2–4 [26];
and 1–5 [28, 30]. Assessment frequency also varied
considerably between studies; from once daily to hourly.
Level of sedation
Reported incidences of optimal, under-, and oversedation
are presented in Table 1.
Studies varied in the way incidence was reported (as a
proportion of observations, patients or hours). Fifteen
studies reported the incidence as a proportion of obser-
vations, as summarized in Fig. 2. Optimal sedation was
ascertained in 15–93 % of observations, undersedation in
0–22 %, and oversedation in 0–82 % of observations. In
these 15 studies, patients were optimally sedated in
57.6 % of the observations, undersedated in 10.6 % of the
observations, and oversedated in 31.8 % of the
observations.
Two studies reported proportions of patients; in these
two studies together, 68.6 % of patients were oversedated
at any time during admission (Fig. 3).
The two studies that used both an observational score
and the BIS score reported considerably different results
[28, 30]. The incidence of oversedation measured with the
BIS was lower than that measured with a validated
observational scale (56 vs. 92.9 % and 65 vs. 82 %).
Discussion
This review shows that the level of sedation in critically
ill children is often suboptimal during their ICU stay, at
least in ICUs that apply sedation assessment in daily
practice. Patients are optimally sedated in only 60 % of
assessments. Under- and oversedation occur in 10 and
30 % of the assessments, respectively. However, across
all studies, there is a large variation in incidence of
oversedation, i.e., from 0 to 82 % of assessments. Most
studies, however, report incidence in the range of 40 to
65 %, which corresponds to that reported in adult ICU
patients [41–43].
Our results indicate that in critically ill children
oversedation is more common than undersedation. We
suggest several reasons for the relatively high incidence
of oversedation. First, there may be a tendency to avoid
undersedation at all cost, as this may lead to discomfort
and potential adverse effects as self-extubation and
Fig. 1 Flowchart search results
removal of lines and catheters. Since children, especially
preverbal infants, cannot clearly communicate their well-
being and are often bewildered by the ICU setting, nurses
and doctors may also tend to avoid undersedation. Sec-
ond, nurses believe that mechanical ventilation is
uncomfortable and stressful, and this perception might
lead to higher sedation level than necessary [42, 44].
Third, sedation protocols are not fully adhered to, so that
sedatives are not tapered off when possible [45]. These
tendencies are unwanted, as oversedation may be even
more detrimental to patients.
Continuous sedation as such is an independent pre-
dictor of prolonged mechanical ventilation in adults, and
consequently leads to longer ICU and hospital stay [46].
Oversedation, in addition, is also associated with toler-
ance, withdrawal, and delirium. Especially longer
duration of use and high drug doses are risk factors for
development of withdrawal symptoms in children [4].
Moreover, longer use of sedatives has been associated
with symptoms of depression and post-traumatic stress
symptoms in adults [47]. In a study in children, almost
one-third of children reported delusional memories, and
these were the children with the longest duration of
administration of opiates/benzodiazepines and the highest
risk of posttraumatic stress [48]. The administration of
sedatives to children may also be associated with adverse
neurodevelopmental outcomes at later age, probably by
inducing neuroapoptosis [49–51].
Fig. 2 Incidence of under-, optimal, and oversedation (% of observations)
Fig. 3 Incidence of under-, optimal, and oversedation (% of patients)
The implementation of sedation algorithms aimed at
less sedation has led to shorter duration of mechanical
ventilation, ICU stay, and hospital stay in adults [52].
Also, daily sedation interruption significantly improved
short- and long-term outcomes in adults [53]. A more
recent ‘‘no-sedation’’ protocol is even more promising in
this respect [54]. All evidence indicates that the use of
sedative drugs should be reduced. In children, daily
sedation interruption seems feasible and safe, but effec-
tiveness needs to be demonstrated in large trials [55].
This review also shows a great variety of assessment
instruments used in clinical practice. No more than four of
the 12 observational sedation scores have been validated
for PICU patients, i.e., the COMFORT-score, the COM-
FORT-B scale, the Hartwig sedation scale, and the State
Behavior Scale. This is remarkable, as there is consensus
that the level of sedation should be assessed and docu-
mented using a validated sedation assessment scale [5].
The reliability of the other scales is questionable. Fur-
thermore, six studies used the BIS monitor. There is
insufficient evidence, however, to support the use of the
BIS monitor, or any other neurophysiological sedation
scoring technique, such as auditory evoked potentials, in
children below the age of 6 months [56]. The suitability
of the adult-derived EEG algorithm to assess children’s
BIS values is doubted. Furthermore, pre-awakening BIS
values in children aged \1 year are lower than in older
children [57]. This could explain why in some pediatric
studies BIS monitoring resulted in a lower incidence of
oversedation than did application of the COMFORT score
[28, 30].
In all studies the authors defined optimal level of
sedation. Remarkably, different studies applied different
cut-off values of the COMFORT score and Ramsay score
[25, 26, 28, 30]. This variation may be explained by the
uncertainty in what constitutes optimal sedation, but may
also be the result of patient-specific factors. For example,
a deeper level of sedation is often aimed for in patients
with pulmonary hypertension, traumatic brain injury or
difficult airway. Playfor et al. [21] used a clinical sedation
score based on the response to tracheal suction, catego-
rizing the response on a five-point scale. A score of 1 (no
response to tracheal suction) was considered as the
desired level of sedation for children with severe head
injury; a score of 2 for children receiving a high level of
intensive care with frequent invasive procedures, and a
score of 4 for children prior to extubation.
In addition, the relatively high incidence of suboptimal
sedation shown in this review reflects the fact that titrat-
ing the correct amount of sedation for each child can be
complex. There may be several reasons for this. First,
PICU populations are quite heterogeneous with respect to
disease type and severity, age, and neurodevelopmental
stage, so optimal sedation management may differ widely.
Second, pharmacokinetics and pharmacodynamics, lar-
gely insufficiently studied, may be unpredictable,
particularly in patients with multiorgan failure [58].
Dosing regimens are often based on healthy adult vol-
unteers and do not take into account factors such as
altered protein binding, distribution, and clearance in
critically ill children. Also, sedation requirements may
change over the course of illness [59].
With the risks of oversedation and the difficulties of
reaching adequate sedation in mind, a critical appraisal of
sedation strategies in critically ill children is needed.
Optimal sedation could perhaps be achieved with the use
of validated sedation scales and standard sedation proto-
cols and by studying promising interventions such as
daily sedation interruption. These studies are needed in
pediatric intensive care.
Conclusions
This review shows that optimal sedation for critically ill
children remains challenging for health professionals.
These children are often oversedated and consequently
run the risk of adverse outcomes. It is high time to find
conclusive evidence on optimal sedation strategies in the
PICU setting.
Acknowledgments The authors declare that they have no conflicts
of interest. This research was supported by ZonMw Priority Med-
icines Kinderen (project number 113202002), ZonMw AGIKO
Stipendium (project number 92003549), and Erasmus MC
Doelmatigheidsonderzoek.
Appendix 1. Search strategy
PubMed
(child*[tw] OR infan*[tw] OR pediatr*[tw] OR
paediatr*[tw])
AND
(intensive car*[tw] OR critical car*[tw] OR critically
ill*[tw] OR ICU[tw] OR PICU[tw])
AND
(sedat*[tw] OR midazolam[tw] OR lorazepam[tw] OR
diazepam[tw] OR benzodiazepin*[tw] OR fentanyl[tw]
OR remifentanyl[tw] OR morphine[tw] OR ketamine[tw]
OR clonidine[tw] OR pentobarbital[tw] OR opioid*[tw]
OR propofol[tw])
AND
(sedation qualit*[tw] OR quality of sedation[tw] OR
sedation level*[tw] OR level of sedation[tw] OR sedation
score*[tw] OR sedation scale*[tw] OR sedation
assess*[tw] OR assessing of sedation[tw] OR sedation
protocol*[tw] OR sedation guideline*[tw] OR sedation
algorithm*[tw] OR assessment tool*[tw] OR conscious
sedation/standards[mesh] OR conscious sedation/meth-
ods[mesh] OR nursing assessment[mesh] OR nursing
assess*[tw] OR nursing diagn*[tw] OR COMFORT
score*[tw] OR COMFORT scale*[tw] OR COMFORT
behavio*[tw] OR bispectral inde*[tw] OR state Behavior
Scale*[tw] OR state behaviour scale*[tw] OR
pharmacodynamic*[tiab])
Embase
(child*:ti,ab,de OR infan*:ti,ab,de OR pediatr*:ti,ab,de OR
paediatr*:ti,ab,de) AND (((intensive OR critical*) NEAR/
2 (car* OR ill*)):ti,ab,de OR ICU:ti,ab,de OR PICU:-
ti,ab,de) AND (sedat*:ti,ab,de OR midazolam:
ti,ab,de OR lorazepam:ti,ab,de OR diazepam:ti,ab,de OR
benzodiazepin*:ti,ab,de OR fentanyl:ti,ab,de OR
remifentanyl:ti,ab,de OR morphine:ti,ab,de OR keta-
mine:ti,ab,de OR clonidine:ti,ab,de OR
pentobarbital:ti,ab,de OR opioid*:ti,ab,de OR propo-
fol:ti,ab,de) AND ((sedation NEAR/2 (qualit* OR level*
OR score* OR scale* OR assess* OR protocol* OR
guideline* OR algorithm*)):ti,ab,de OR (assess* NEAR/2
tool*):ti,ab,de OR ‘conscious sedation’:de OR ‘nursing
assessment’/exp OR (nurs* NEAR/2 (assess* OR di-
agn*)):ti,ab,de OR (COMFORT NEAR/1 (score* OR
scale* OR behavio*)):ti,ab,de OR (bispectral NEAR/1
inde*):ti,ab,de OR ((‘state Behavior’ OR ‘state behaviour’)
NEAR/1 scale*):ti,ab,de OR pharmacodynamic*:ti,ab)
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