REVIEW
Pediatrics Sciences Journal (PedScij) 2023, Volume 4, Number 2: 71-79
P-ISSN: 2722-0427, E-ISSN: 2722-1474

The Effectiveness of Analgesics in Pain Treatment in
Critically Ill Children: a Literature Review
Published by
Pediatrics Sciences Journal

Department of Pediatrics, Faculty of
Medicine, Universitas Brawijaya,Saiful
Anwar General Hospital, Malang;
2
Department of Pharmacology, Faculty
of Medicine, Universitas Brawijaya,Saiful
Anwar General Hospital, Malang.
1

*Corresponding to:
Kurniawan Taufiq Kadafi;
Department of Pediatrics, Faculty of
Medicine, Universitas Brawijaya,Saiful
Anwar General Hospital, Malang;
kadafi12.fk@ub.ac.id
Received: 2022-10-08
Accepted: 2023-11-28
Published: 2023-12-15

Kurniawan Taufiq Kadafi1*, Saptadi Yuliarto1, Astika Jihan Ruhi Said1,
Takhta Khalasha2
ABSTRACT
Adequate pain management is an important and common requirement in health care in pediatric intensive care units. There
are many pain assessment scales in children based on the literature, but the guidelines for using pain scales as a guide in
pain management have not been widely discussed. One of the most common pain interventions is to provide opioid or nonopioid analgesics. Analgesic drugs given to critically ill children can provide different anti-pain outcomes when measured by
a pain scale. Therefore, this literature review will compare the effectiveness of analgesics in pain management in critically ill
children.
Keywords: Analgesics, opioid, non-opioid, pain measurement, PICU.
Cite This Article: Kadafi, K.T., Yuliarto, S., Said, A.J.R., Khalasha, T. 2023. The Effectiveness of Analgesics in Pain Treatment in
Critically Ill Children: a Literature Review. Pediatrics Sciences Journal 4(2): 71-79. DOI: 10.51559/pedscij.v4i2.71

INTRODUCTION
Pain management is important in the
pediatric intensive care unit. Critically
ill children tend to experience more
severe pain due to their illness as well
as procedures to be performed in both
surgical and medical nursing units.1 When
compared to pain in children in general
medical surgical floors, critically ill
children have significantly more cases of
moderate to severe pain and have higher
pain scores.2 Patients with critical illness
often experience uncontrolled pain and
the use of analgesic drugs can actually
prevent this. Pain can elicit an immediate
physiological response, including an
increase in intracranial pressure, heart
rate, respiratory rate, blood pressure,
blood glucose, and hormonal stress as
well as a decrease in oxygen saturation.
Furthermore, pain experienced by
children is often associated with changes
in sensory perception, stress response,
cognition, and immune function which
can later increase the risk of diseases of
the nervous system and affective disorders
in the future.1,3 The perception of pain
becomes highly subjective depending on
a person's emotional state and emotional
experience.3,4 Therefore, minimizing
pain in pediatric intensive care units can
improve the quality of a child's health in

both the short and long term.1,3
The scale of pain assessment in
children based on literature is quite a
lot, but the guidelines for using the pain
scale as a guide in pain management have
not been widely discussed, because the
population in the Pediatric Intensive Care
Unit (PICU) is so complex, ranging from
diverse ages, different levels of cognitive
development of children, and the number
of diagnoses of diseases that each child may
be able to suffer from.3,5 One way to deal
with pain is to give opioid or non-opioid
analgesics. Opioids are currently an option
that has long been used to treat pain, and
has proven to be more effective than
non-opioids. A meta-analysis examining
various opioid drugs (compared to placebo
and nonsteroidal anti-inflammatory drugs
[NSAIDs]) in chronic non-cancerous pain
found that, all patients with Chronic NonCancer Pain (CNCP) did not respond to
opioids, only 30-50% of screened subjects
reported experiencing a decrease in pain
with opioids.6,7
Based on the above review, a literature
review is needed that discusses the
effectiveness of analgesic drugs used in
critically ill children in intensive care unit,
including the relationship between pain
scores and analgesic administration in
critically ill children, length of ventilator

use, length of
extubation time.

hospitalization,

and

METHOD
This study is a literature review without
statistical analysis and process of literature
review method. The search is done using
AND to search for literature containing all
keywords and OR to search for literature
that contains alternative keywords. The
search strategy is carried out with search
keywords namely (Analgesics OR Opioid
OR Non-Narcotic OR Pain management)
AND (Pediatric Intensive Care Unit) AND
(Length of stay OR Pain Measurement OR
intubation OR mechanical ventilation).
This research database comes from a
literature search in :
1. PubMed
2. The Cochrane Library
The limitation of literature search in
this study is only the English literature
used and the limit of the last 10 years,
children aged >1 month and <18 years
of publication from literature. From
the literature search, 1302 articles were
obtained, of which 10 articles were
identified as relevant to the topic and
met the inclusion criteria. The article
consists of retrospective, observational
and RCT research in 2012-2022. In this
study, the outputs that are often reported

Published
by Pediatrics
Sciences Journal | Pediatrics Sciences Journal 2023; 4(2): 71-79 | 10.51559/pedscij.v4i2.71
Open access:
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71

REVIEW

are the length of ventilator use, length of
hospitalization, extubation time, and pain
score.
Pain assessment in children
Pain assessment in children is the
most important component of pain
management, sometimes difficult to do,
because there is no one standard method
that can measure pain in children in
various conditions. Self-report by children
is a reliable indicator in measuring the
scale of pain in children.3 However,
this only applies to childrenith good
cognitive and communication skills, but
cannot be applied to all age groups. In
infants and children with cognitive and
communication abilities that are not
optimal in their development, self-report
is not possible, so pain observation can be
based on observations of physiology and
behavior in children. One way to assess
pain is to use the QUESTT method, which
is: Question the child, Use a pain rating
scale, Evaluate the patient’s behavior and
physiologic changes (secure the parent’s
involvement), Take the cause of pain into
account, and Take action and evaluate
results.3,6
a. Measurement pain by giving questions
to children
The statement and description of pain
is an important factor in assessing pain.
Children aged less than 2 years can
convey and localize pain, although at
this age the child has not been able to
describe the quantity of the intensity of
the pain he feels. When giving questions
to the child should be patient and use
words that are commonly used daily
in the family. One of the difficulties
in identifying pain in a child is that if
the examiner is an unknown person,
the child tends to deny the pain, or the
child feels afraid to express the pain.8
b. Measurement pain by using a pain
scale
Pain assessment is important to know
the intensity and determine which
therapy is effective. The intensity of
pain should be assessed as early as
possible and good communication
with the patient is needed. Some of the
scales that can be done to assess the
degree of pain in a child are:

72

• Visual analog scale (VAS)
This scale is ideally used in children
aged >8 years. The VAS scale is
a scale in the form of a linear line
that visually describes the degree of
pain that a person may experience.
The pain range is represented as
a line 10 cm long, with one end
representing no pain, while the
other end representing the heaviest
pain. Usage is very easy and simple.
However, VAS has a disadvantage,
namely in postoperative cases,
VAS is difficult to apply because
VAS requires visual and motor
coordination and concentration
ability. There are studies that state
that the use of VAS can be done in
younger children, namely the age of
≥ 3 years when combined with FPS
(Faces Pain Scale).9
• Numeric Rating Scale (NRS)
This scale can be applied to children
aged ≥ 8 years. This scale uses
the numbers 0 to 10 to describe
the degree of pain. The use of
NRS is better than VAS especially
when assessing acute pain, as it
is considered simple and easy to
understand. However, NRS has
limited word options to describe the
taste of pain that can be represented.
The use of NRS to assess the degree
of pain can only be used in children
who are able to count at least up to
10 and understand the sequence of
numbers.10
• Verbal Rating Scale (VRS)
The Verbal Rating Scale (VRS) is
more beneficial for assessing pain
in surgical patients since verbal/
wording does not rely on visual
and motor coordination. VRS
uses words to assess the degree
of pain, not lines, or numbers in
assessing pain, so VRS can be used
in children aged ≥5 years, who in
general the child can already speak
and understand oral speech, but it
also depends on the child’s cognitive
ability to describe the degree of
pain.11
• Wong Baker Pain Rating Scale
This scale is used in children aged
>3 years who cannot describe
the intensity of their pain with

numbers. On this scale the degree
of pain is represented by an image
of facial expressions that the child
can choose from when assessing
the pain he feels. The advantages
of using this scale are Ease of
administration (fast and easy to
use, requires minimal instruction)
and cost-effectiveness). Research
conducted by stinson et al, found
that children at the age of 4-5
years showed a tendency to choose
the face on a more extreme scale
in pain associated with medical
procedures.9
c. Measurement of pain by evaluating
behavioral and physiological changes
The stress that occurs in children can be
described through changes in voice, facial
expressions and body movements. This
is often related to pain and can be used
to evaluate pain, especially in children
who have limitations in communication.
Changes in behavior in children as a way
to assess pain have weakness, which is
difficult to distinguish from other causes,
such as hunger, thirst and anxiety. This is in
line with research conducted by Dorfman
et al, where in critically ill infant patients
there are limitations in evaluating facial
expressions for pain and normal infant
behavior, such as the baby’s discomfort to
change diapers.12 The FLACC scale (face,
legs, activity, cry and consolability) is a
scale that is often used to assess changes
in behavior in children. The FLACC scale
was originally used to assess postoperative
pain in children aged 2 months - 12 years.
This scale was created as a simple method
that nurses use to identify, document, and
evaluate pain in children who are unable
to verbally express pain and intensintas of
pain. A review conducted by maria beatz
in 2019 stated that, this scale is good for
use in children aged 2 months – 7 years.
The study also found that this scale can be
used in children with disabilities or special
needs, but there is a lack of evidence to
apply to all age groups of children.13 This
scale includes face, legs, activity, cry and
consolability assessments. Each such
component is assigned a value of 0-2, so
the total value is 0-10 (Table 1).8
In chronic pain such as postoperative
pain, the scale for assessing the degree of
pain based on behavioral changes used is

Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023; 4(2): 71-79 | 10.51559/pedscij.v4i2.71

REVIEW

Table 1.

FLACC Scale (face, legs, activity, cry dan consolability)
Categories

Face

0
No particular expression or
smile

Scoring
1
Occasional grimace/frown; withdrawn
or disinterested; appears sad or
worried

Legs

Normal position or relaxed;
usual tone and motion to limbs

Uneasy, restless, tense; occasional
tremors

Activity

Lying quietly, normal position,
moves
easily;
Regular,
rhythmic respirations

Squirming, shifting back and forth;
tense or guarded movements; mildly
agitated (eg. head back and forth,
aggression);
shallow,
splinting
respirations, intermittent sighs
Moans or whimpers; occasional
complaint; occasional verbal outburst
or grunt

No cry/verbalisation
Cry

Consolability

Content and relaxed

Reassured by occasional touching,
hugging, or being talked to; distractible

2
Consistent grimace or frown;
frequent/constant quivering chin,
clenched jaw; distressed-looking
face; expression of fright or panic
Kicking, or legs drawn up; marked
increase in spasticity, constant
tremors or jerking
Arched, rigid, or jerking; severe
agitation, head banging, shivering
(not
rigors);
breath-holding,
gasping or sharp intake of breaths;
severe splinting
Crying steadily, screams or
sobs,
frequent
complaints;
repeated
outbursts,
constant
grunting
Difficult to console or comfort;
pushing away caregiver, resisting
care or comfort measures

Each category is scored on the 0-2 scale, which results in a total score of 0-10
0 = Relaxed and comfortable
1-3 = Mild discomfort
4-6 = Moderate pain
7-10 = Severe discomfort / pain

Table 2.

Modified Children Hospital of Eastern Ontario Pain Scale (CHEOPS)
Score
Cry
Facial
Verbal
Torso
Legs
Touch

the Modified Children’s Hospital of Eastern
Ontario Pain Scale (CHEOPS) (Table 2).
On this scale, the examiner observed 6
types of behavior changes, namely crying,
facial expressions, verbal expressions,
body position, reactions to touch and limb
position. The disadvantage of this scale is
that its application in a narrow age group,
can only be used in children aged 1 – 5
years, but has the advantage of a simple
and fast application.14 The CHEOPS pain
score is the sum of the values of the six
parameters of behavior change. If the total
score of 8 or more indicates that the child
is in a state of pain / pain.
Assessment of pain can also be carried
out by observing the physiological changes
of the child. The difficulty of assessing
pain based on a child’s physiological
changes is that it is difficult to distinguish

0
No cry
Smilling
Positive
Neutral
Neutral
Not touching

1
Crying, moaning
Composed
None or other complaints
Shifting, tense, upright
Kicks, squirm, drawn up
Reach, touch, grab

physiological changes due to pain or other
forms of stress. In some studies, pain
assessment based on physiological changes
is more widely used and more effective
for assessing acute pain than persistent
pain. In patients with intensive care, the
COMFORT pain scale is a pain scale that
is often used to assess the degree of pain
and sedation given to pediatric patients
treated in intensive rooms that cannot be
assessed using the Visual Analog Scale.
The administration of sedation aims
to reduce agitation, eliminate anxiety
and align breathing with a mechanical
ventilator. This scale is used at various
ages, there are several studies conducted
using this scale with different age ranges,
namely, research by Lauren et al in the
age range of 12 months – 3 years, Maria
beatz research in the neonatal age range –

2
Scream
Grimace
Pain complaint
Restrained
Restrained
Restrained

3 years, research Here et al at the age of
0-10 years and research of Harris et al in
the range of 0-16 years, of the four studies
concluded that, this scale is validated for
postoperative settings and is suitable for
anesthetized or unconscious patients.
This scale has the disadvantage that the
assessment takes a long time, which is 2 to
3 minutes of observation and accuracy is
not proven for conscious patients.13,15–17
On the COMFORT Behavior scale
(Figure 1), there are 7 categories that are
assessed, with each category having a
score of 1-5 so that the total score is 35.
The intepretation on the COMFORT scale
is: <12 value: deep sedation, value 13-18:
adequate sedation and analgesia, value
>18: inadept sedation.
Ceeli et al’s study using the Randomized
Controlled Trial method in 71 infants

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73

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under the age of 1 year who underwent
major thoracic surgery (non-cardiac) or
abdominal obtained COMFORT-B scores
with pain scores of 13 and 13.2 included
in the category of optimally working
analgesics.18 Another study conducted
by Neunhoeffer F et al using pre- and
post-implementation standard therapy
consisting of continuous IV infusion of
opioids and fentanyl obtained an average
COMFORT-B score of 14.72 including
the category of analgesics worked
optimally with a percentage of 70% of all
observations, while 12% had oversedation
and undersedation of 18% with the same
dose of morphine analgesics.19
Research conducted by Hanser A et al
in 2020 obtained a median COMFORT-B
score of 13.8 showing analgesics and
sedation working optimally at 71% of
all observations, oversedation occurred
at 25% and undersedation at 4%.20 In
a study conducted by Dreyfus et al in
2017 with the Randomized Controlled
Trial method on 200 children aged 2 - 3
years using opioid sufentanil the average
COMFORT-B score per patient was 8
during the period preimplementation
and 9.5 during the post-implementation
period. Both periods of <12 scores showed
oversedation with a value of p=0.002
indicating the number of scores increased
significantly after implementation.21
Optimal sedation is described as a
patient under sedation who can be easily
awakened and can undergo medical
treatments and procedures. On both
sides of this optimal state are the states
of “oversedation” and “undersedation”.
Excessive sedation is associated with a poor
prognosis such as prolonged mechanical
ventilation,
longer
hospitalizations,
nosocomial infections, and more frequent
withdrawal
symptoms.
Inadequate
sedation involves the risk of agitation
and complications, such as unplanned
extubation.21
Pain measurements using the FLACC
scale were performed by Barnes T.A et
al in 2020 with a retrospective study of
140 postoperative heart patients getting
higher maximum FLACC scores in the
postoperative period of 2017 compared to
2018 (5 to 3 each), but the rate of decline
in FLACC scores in 2017 was statistically
faster and significantly compared to 2018
74

(P < 0.001).22 Honarmand et al in 2012 with
the Randomized Clinical Trial method
obtained pain scores Using the CHEOPS
scale in tonsillectomy surgery patients, it
was significantly lower in the group whose
combined use provided a better and longer
analgesic effect compared to the use of
each drug alone.23
Analgesics used in pediatric intensive
care rooms
Opioid analgesics
a. Morphine
Morphine was discovered more than
200 years ago. Morphine is the oldest
opioid and the only hydrophilic opioid
that is still commonly used. Bolus
administration of morphine can reach
the peak effect in 10-20 minutes and
has a working duration of about 2-4
hours. Morphine is metabolized by
the liver through glucuronidation and
its metabolites are excreted through
the kidneys. The dose of morphine
should be carefully titrated to avoid
excessive sedation and the occurrence
of respiratory depression. Morphine
doses are administered taking into
account the age, physiology and
medical condition of the child, since the
pharmacokinetics of morphine differs
from premature babies to childhood.
Initial administration of morphine in
children with intermittent doses was
0.03-0.2 mg / kg intravenously and
0.01-0.04 mg / kg / hour in continuous
intravenous infusion. Morphine doses
for neonates aged <10 days are less
than half the dose of morphine for
children.17 Morphine is still the most
commonly used opiod in intensive care
rooms and has risks and side effects
such as vasodilation, hypotension,
bronchospasm, and pruritus, but is
usually not clinically significant.24
b. Fentanyl
Fentanyl is a synthetic morphine that
is highly lipophilic and fat-soluble.
Fentanyl has an anti-pain effect a
hundred times stronger than morphine
and shows a very fast onset (<1 to 2
minutes) and has a duration of up
to 60 minutes when administered at
intermittent doses.16 Intermittent
doses of fentanyl in children, namely
1-2 mcg/kg intranasal and 0.5-3 mcg/

kg intravenously, and 0.5-2 mcg/kg/
hour intravenously. With continuous
and
prolonged
administration,
fentanyl can accumulate in peripheral
compartments, increasing half-life and
prolonging sedation. In contrast to
fentanyl and morphine, fentanyl has an
inactive metabolite, norfentanyl, and
does not cause the release of histamine.
Fentanyl can suppress the heart rate
response, this has a negative effect on
children who physiologically rely on
heart rate and increased heart rate to
increase cardiac output. In contrast,
fentanyl has advantages, especially
for reducing the heart rate response
when intubation is performed using
a laryngoscope. Although rare, the
use of fentanyl has a risk of chest wall
stiffness. This usually occurs at large
doses administered rapidly (>5 mcg/
kg) so it is not uncommon to trigger
respiratory failure.25
c. Remifentanyl
Remifentanyl is a new synthetic opioid
equivalent to fentanyl and has a very
short half-life of about 3-4 minutes.
Remifentanyl is metabolized by plasma
esterase, does not accumulate and
shows a small volume distribution
(Vd).17 Remifentanyl may be optimally
administered in patients with renal or
hepatic dysfunction. The strategy to
avoid the risk of accumulation of active
metabolites is to extend the half-life
as well as the duration of work. The
rapid onset and offset of remifentanyl,
making it widely used in pediatric
intensive care rooms. Remifentanyl
has the same effects as other opioids
namely respiratory depression and
myocardial depression, therefore it
must be anticipated and managed
appropriately. Remifentanyl causes
opioid hyperalgesia (Opioid-Induced
Hyperalgesia/OIH)
side
effects,
prolonged postoperative recovery,
increased length of treatment and
significant discomfort.26
d. Hydromorphones
Hydromorphones are semi-synthetic
opioids (hydrogenated ketones from
morphine) that selectively bind to μ
receptors (mu).27 Hydromorphones
are hydrophilic and have 7-10
times greater potential compared to

Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023; 4(2): 71-79 | 10.51559/pedscij.v4i2.71

REVIEW

of adult doses to children equivalent to
23.7 mg of oral morphine to 1 mg of oral
methadone.30

Figure 1. COMFORT Behavior Scale and Scoring Form.
morphine. Hydromorphones have an
onset of 5-10 minutes and a working
length of 3-4 hours. Hydromorphones
are
metabolized
by
liver
glucuronidation into hydromorphon3-glucuronides and excreted in the
urine. Hydromorphones have fewer
unfavorable effects, such as nausea, and
pruritus than morphine.24 Continuous
Intravenous Infusion has been shown
to be effective for prolonged sedation
(>24 hours) in pediatric intensive
care rooms. The initial dose of
hydromorphone averaged 0.024 mg/
kg/hour and the maximum mean dose
was 0.05 mg/kg/hour.
e. Methadone
Methadone is a synthetic opioid μ
receptor agonist (mu) that has a rapid

onset (5-10 minutes in iv and 30-60
minutes orally). Methadone has the
longest duration of action of all opioids
(4-24 hours). Methadone is used to
prevent opioid withdrawal in pediatric
patients receiving morphine or
fentanyl continuously for >5 days, due
to the lack of active metabolites, high
oral bioavailability, as well as a long
duration of action. Enteral methadone
administration has been shown to
accelerate opioid cessation and reduce
the risk of withdrawal in critically ill
children who have a very high risk for
opioid abstinence syndrome.28
Methadone doses equivalent to 2.5
times the daily dose of fentanyl have
demonstrated therapeutic success.29 with
standard guidelines for the conversion

Non-Opioid Analgesics
a. Acetaminophen
Acetaminophen is a synthetic non
opioid that works centrally as an
analgesic and antipyretic derived from
p-aminophenol. Acetaminophen is
widely used for single or combination
treatment with other types of analgesia
in pediatric intensive care rooms to
relieve symptoms of mild to severe
pain and fever, because acetaminophen
has a broad therapeutic index and
efficacy to safety ratio. Acetaminophen
does not affect platelet function
or kidney function and has no
gastrointestinal
and
respiratory
effects. Acetaminophen iv achieves
an analgesic effect within 5 minutes
after administration and reaches
a higher maximum concentration
(Cmax) at an earlier time (Tmax) than
the equivalent dose administered by
oral or rectal route. Acetaminophen
is metabolized by the liver through
glucuronidation,
oxidation,
and
sulfation.31 The limitations of the use of
acetaminophen iv are often due to its
high cost. Acetaminophen iv tops the
list of the most expensive drugs used
in pediatric intensive care rooms, along
with dexmedetomidine, eculizumab,
and immunoglobulin botulism.32
b. Nonsteridal anti-inflammatory drug
(NSAID)
NSAIDs work by blocking the
production of prostaglandins to reduce
pain and inflammation. There are
two types of NSAIDs: Non-Selective
NSAIDs
(ibuprofen,
naproxen,
ketorolac, and acetylsalicylic acid)
work to block two enzymes involved
in the inflammatory process, namely
the enzymes cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX-2), and
selective COX-2 (celecoxib). These nonselective NSAIDs are most widely used
in pediatric intensive care rooms. The
COX enzyme catalyzes the conversion
of arachidonic acid to prostaglandins
and regulates the cellular processes
of platelet aggregation, vasodilation
of afferent arterioles in the kidneys,

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REVIEW

and protection of the gastric mucosa.
COX-2 enzyme is an enzyme that
can be induced and increased during
the inflammatory process, the COX2 enzyme is present in the brain,
kidneys, bones, and reproductive
tract. NSAIDs are widely used due
to their analgesic, anti-inflammatory
and antipyretic properties. Ibuprofen
being the NSAIDs of choice for enteral
administration, preferred for its
efficacy profile and tolerability without
the risk of Reye’s syndrome.33,34
Intravenous ketorolac is not commonly
used for pediatric patients, but is a frequent
option for postoperative analgesics in
pediatric intensive care rooms. NSAIDs
are preferred over opioids, due to the lack
of side effects such as nausea, vomiting,
pruritus, respiratory depression, sedation,
and urinary retention that can occur in
opioids. NSAIDs are metabolized in the
liver into inactive metabolites through
oxidation and conjugation processes.
The administration of NSAIDs should
be carried out carefully in patients at
risk of acute renal failure, post-surgical
bleeding, or gastrointestinal toxicity. In
pediatric populations, NSAIDs have not
been shown to increase the risk of kidney
complications and bleeding for postcardiac and non-cardiac care.34

DISCUSSION
The assessment of pain in a child is very
complex and involves physiological,
psychological, behavioral, social and
developmental factors. In the pediatric
intensive care room, we must consider
the severity of the disease and the child’s
ability to participate in the assessment
of pain.35–38 Verbal reports of pain can
be considered the most effective way to
communicate the subjective emotional
and sensory experiences of the individual.
In infants and children with cognitive
and communication abilities that are
not yet optimal in their development,
pain observations can be based on
observations of physiology and behavior
in children. Pain can be caused by many
factors, namely, complex child conditions,
the administration of pharmacological
agents, such as the use of sedatives and
neuromuscular inhibitory agents that
affect the ability to react to the disease as
76

well as the use of mechanical ventilation
necessary to maintain vital functions.35,38–40
There are two validated pain
assessment scales most commonly used
in pediatric intensive care rooms, namely
the COMFORT and FLACC (Face,
Legs, Activity, Cry, and Consolability)
scales for use in young children and
children who cannot self-report their
pain.35,38,41,42 The COMFORT-B score is
a customized version of the COMFORT
score, based on observation items such
as alertness, calmness, respiratory
response in ventilated or crying patients
in unventilated patients, muscle tone,
physical movement, and facial tension.
This scale has been introduced and
validated for pain assessment as well as
for sedation management in pediatric
intensive care rooms. A COMFORT-B
score of 12-18 is assumed to be the optimal
range of analgesics and sedatives.43–45
The FLACC scale has been used in a
variety of populations and ages including,
children who cannot speak yet, children
with cognitive impairment and also
as a postoperative pain assessment.8
Analgesics are given taking into account
the assessment of the degree of pain.
Most children in intensive care rooms
experience moderate to severe pain as a
result of different sources of pain, namely
underlying disease, surgery, trauma, and
invasive procedures. Opioid analgesics
are used to score pain with moderate
to severe categories.35,46 Morphine and
fentanyl are the most widely used opioid
analgesics in terms of dosage effectiveness,
method of administration, and side
effects. This widespread use of opioids
is in line with the recommendations of
the World Health Organization (WHO),
which recommends administering opioid
analgesics to children with moderate to
severe pain levels.
Non-opioid analgesics such as ketorolac
are effective for treating moderate to
severe pain, but some children who
receive ketorolac experience side effects
in the form of nausea and vomiting.
Acetaminophen has been shown to reduce
pain in pediatric intensive care rooms
after surgery with mild to moderate pain
and unventilated children. Intravenous
administration is more effective than oral
or rectally. Existing recommendations do

not support the use of acetaminophen as a
single drug for the therapy of moderate or
severe pain in children.17
From several studies conducted to
assess the effectiveness of analgesics on
the pain scale in children, a significant
decrease in the pain scale was found after
administration of analgesic agents, in a
study conducted by Neunhoeffer F et al
with the Randomized Controlled Trial
method on 337 children aged 1-24 months
with analgesic post-sedation pain, it was
found that the average COMFORT-B
score was 14.72. COMFORT-B scores
showed optimal analgesics & sedation at
70% of all observations (CF-B 12-18) with
a morphine infusion dose of 10 mcg/kg/
hour and fentanyl infusion of 0.5 mcg/kg/
hour, oversedation at 12% (CF-B <12) and
undersedation at 18% (CF-B >18).19
The study with the same method
as postoperative pain obtained an
average COMFORT-B score per patient
was 8 (range 6-19) during the preimplementation period and 9.5 (range
6-15.5) during the post-implementation
period. The difference between these
two periods is significant (p=0.002). The
average number of adequate sedation
and analgesic levels (scores 11-17) was
significantly greater after implementation
(22.2 vs 31.7%), while the average number
of excessive sedation and analgesic levels
(score <11) decreased significantly from
73.3% in pre-implementation to 60.7%
in the post-implementation period by
sufentanil 0.1 g/kg/h.21
Research conducted by Welzing
L et al in 2012 with the Randomized
Controlled Trial method comparing the
effectiveness of analgesics and sedation
of remifentanil/midazolam and fentanyl/
midazolam obtained results that the need
for mechanical ventilation was longer in
the remifentanyl group at a dose of 6–30
mcg/kg/hour compared to the phenytanyl
group dose 2-10 mcg/kg/hour (average
difference of 25 hours).47 Furthermore in
2013 a study from Ceeli at al in 71 infants
under the age of 1 year who undergoing
major thoracic surgery (non-cardiac)
or abdominal showed that the average
duration of mechanical ventilator use was
34 days in the paracetamol group of 30
mg/kg/day in 4 doses and decreased to 23
days in the morphine group with a dose

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REVIEW

age of ≤10 days 2.5 mcg/kg/hour; Patients
aged 11 days to 1 year 5 mcg/kg/hour
(p=0.43).18
Research conducted by Neunhoeffer
F et al using standard pre- and postimplementation
therapy
consisting
of continuous iv infusion of opioids
(morphine [5-100 mcg/kg/hour, initial
dose 30 mcg/kg/hour] ≤ 2 years and
fentanyl [0.1–6.0 mcg/kg/hour; initial
dose 0.5 mcg/kg/hour] > 2 years) stated
that the average length of mechanical
ventilator use in the preimplementation
group was 2.02 days and 1.71 days postimplementation.19 The same results were
also shown by the study from Dreyfus
et al in with sufentanil opioid therapy
started at 0.2-0.3 mcg/kg/h concluded
that the duration of mechanical ventilator
use in the preimplementation group was
significantly longer when compared to the
post-implamentation group of 5.6 days
and 4.8 days.21 Another study by Magner
C et al in 2020 with a retrospective study
concluded, the amount of morphine
administered during the first 72 hours
after surgery between the pre- and postimplementation groups found that the
median length of mechanical ventilator
use became shorter post-implementation
from 30.5 hours to 25.7 hours.48
A study conducted by Hanser A et al
in 2020 with a retrospective study method.
The results were obtained that, after the
implementation of the analgesic and
sedation protocol, the average duration of
mechanical ventilator use was shorter than
72 hours to 49 hours with a value of p=0.407
but this value was not significant in both
groups.20 Although from all the above
studies, the two groups had insignificant
differences, the preimplantation group
required a longer ventilator use time
compared to the post-implament group.
Research conducted by Khalili et
al in 2012 with the Cross Sectional
Retrospective method concluded that no
significant changes were shown in the
length of hospitalization in PACU for
the use of 0.2 mg/kg of dexamethasone
intravenously for 54.71 minutes and 20
mg/kg of oral codeine-acetaminophen
syrup for 55.14 minutes with a value of
p=0.33.49 Neunhoeffer F et al in 2015 with
the Randomized Controlled Trial method
using pre- and post-implementation

standard therapy consisting of Infusion
IV continuous opioids (morphine [5–100
mcg/kg/h, initial dose 30 mcg/kg/h] ≤
2 years and fentanyl [0.1–6.0 mcg/kg/h;
initial dose 0.5 mcg/kg/h] > 2 years) stated
that the average length of hospitalization
was 5.8 days in the preimplementation
group and 5.0 days post-implementation.19
Then, a study from Magner C et al in 2020
with a retrospective study stated that, the
amount of morphine administered during
the first 72 hours after surgery between
the pre- and post-implementation groups
median length of hospitalization decreased
from 3.5 days in pre-implementation and
to 2.8 days post-implementation with a
value.48
A retrospective study by Barnes et
al of 140 postoperative cardiac patients
using morphine dose range of 0-5 mg/
kg/day also showed that the length of
stay at the PICU was from 6 days to 5
days.22 With the same method, Hanser A
et al in 2020 were treated using morphine
continuous iv-infusion opioid analgesics:
5–100 mcg/kg/h, initial dose: 30 mcg/
kg/h proved that the length of treatment
at the PICU was significantly reduced in
the preimplementation group compared
to the post-implementation group from 7
days to 5 days with a p value = 0.017.20
Different results were shown from
a study conducted by Dreyfus et al in
2017 with the Randomized Controlled
Trial method concluded that the median
length of hospitalization of the preimplementation group of 9 days and 9.8
days post-implementation with a value
of p=0.767 however, was not significantly
meaningful.21 The longer the treatment
period will increase the costs incurred and
decrease the quality of life of the patient.
Sedation and analgesia also affect the
patient’s extubation time. Extubation is
the act of removing the endotracheal pipe.
Extubation is carried out at the right time
for the patient to avoid the occurrence of
reintubation and other complications. A
study conducted by Khalili et al in 2012 with
the Cross Sectional Retrospective method
concluded that there was no significant
difference in the time of extubation.49
Research conducted by Welzing L et al in
2012 stated that the median extubation
time in the remifentanil group at a dose of
6-30 mcg / kg / hour was 80.0 minutes and

the fentanyl group dose was 2-10 mcg/kg/
hour which was 782.5 minutes (p = 0.005)
so that there was a significant difference.47
In the same year Honarmand et al with
post-tonsillectomy pain obtained results
that there was a significant difference in
extubation time, namely the ketamine iv
group 0.5 mg/kg 10.7±24 minutes and the
ketamine iv group 0.5 mg / kg + tramadol
peritonsil 2 mg / kg which was 13.8±21.5
min.23 Another study conducted by
Dreyfus et al using opioid sufentanil dose
range 0.2-0.3 mcg/kg/ hour obtained
results that there was no significant change
between pre and post implementation.21
Another
study
conducted
by
Neunhoeffer F et al in 2015 using pre- and
post-implementation standard therapy
consisting of continuous iv infusion
of opioids at the age of ≤ 2 years and
fentanyl at the age of > 2 years showed
that there was no significant difference
in the unplanned extubation rate, which
was 0.54 in preimplementation and 0.71
post-implementation per 100 days of
ventilator.19 Then, a study from Barnes et
al in 2020 with retrospective studies using
morphine dose range of 0-5 mg/kg/day
concluded that the extubation time was
consistent in the 2017 group and the 2018
group with the median time of extubation
in each group was 1 day.22
Limitations of this study included
factors such as most included studies
had concerns related to risk of bias. We
were unable to thoroughly explore the
influence of potential effect modifiers
such as treatment duration and route of
administration because of the limited
data and poor network structure. Further
research is needed, particularly highquality trials comparing analgesics to
placebo. In future trials, we encourage
investigators to report the number of
participants who had any adverse event, as
well as type and severity of those adverse
events.

CONCLUSION
Critically ill pediatric patients should
be assessed for pain and comfort. Many
scores have been validated to assess the
pain and comfort of critically ill patients
in the PICU. Adequate administration
of sedation and analgesics will shorten
hospital stay, shorten ventilator use, and

Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023; 4(2): 71-79 | 10.51559/pedscij.v4i2.71

77

REVIEW

shorten patient extubation time. When
deciding whether to give analgesics or
sedation, it should be based on the patient’s
clinical condition and can use pain scores
to determine pain and discomfort in
critically ill pediatric patients.

10.

11.

FUNDINGS
No sponsors were included in the funding
of this study.

12.

CONFLICT OF INTERESET
The authors have no competing interests
to declare
13.

AUTHOR CONTRIBUTION
All authors have contributed to all
processes in this research, including
preparation, data gathering, analysis,
drafting, and approval for publication of
this manuscript.

14.

15.

REFERENCE
1.

2.

3.

4.

5.
6.

7.

8.

9.

78

Friedrichsdorf SJ, Postier A, Eull D, Weidner C,
Foster L, Gilbert M, et al. Pain Outcomes in a
US Children’s Hospital: A Prospective CrossSectional Survey. Hosp Pediatr. 2015;5(1):18–
26.
Groenewald CB, Rabbitts JA, Schroeder DR,
Harrison TE. Prevalence of moderate-severe
pain in hospitalized children. Paediatr Anaesth.
2012;22(7):661–8. Available from: https://
pubmed.ncbi.nlm.nih.gov/22332912/
LaFond CM, Hanrahan KS, Pierce NL,
Perkhounkova Y, Laures EL, McCarthy AM.
Pain in the Pediatric Intensive Care Unit: How
and What Are We Doing? American Journal of
Critical Care. 2019;28(4):265–73.
Treede R-D. The International Association for
the Study of Pain definition of pain: as valid
in 2018 as in 1979, but in need of regularly
updated footnotes. Pain Rep. 2018;3(2):e643.
Yudiyanta NK, Novitasari RW. Penilaian Nyeri.
Jurnal Kesehatan. 2015;42(3).
van Dijk M, Peters JWB, van Deventer P,
Tibboel DM. The COMFORT Behavior Scale.
American Journal of Nursing. 2005;105(1):33–
6.
Sehgal N, Colson J, Smith HS. Chronic pain
treatment with opioid analgesics: benefits
versus harms of long-term therapy. Expert Rev
Neurother. 2013;13(11):1201–20.
Misiołek H, Cettler M, Woroń J, Wordliczek
J, Dobrogowski J, Mayzner-Zawadzka E.
Zalecenia postępowania w bólu pooperacyjnym
— 2014. Anestezjol Intens Ter. 2014;46(4):221–
44.
Stinson JN, Kavanagh T, Yamada J, Gill N,
Stevens B. Systematic review of the psychometric
properties, interpretability and feasibility of
self-report pain intensity measures for use in

16.

17.

18.

19.

20.

21.

22.

clinical trials in children and adolescents. Pain.
2006;125(1):143–57.
Bailey B, Daoust R, Doyon-Trottier E, DauphinPierre S, Gravel J. Validation and properties of
the verbal numeric scale in children with acute
pain. Pain. 2010;149(2):216–21.
Joestlein L. Pain, Pain, Go Away! EvidenceBased Review of Developmentally Appropriate
Pain Assessment for Children in a Postoperative
Setting. Orthopaedic Nursing. 2015;34(5):252–
9.
Dorfman TL, Sumamo Schellenberg E, Rempel
GR, Scott SD, Hartling L. An evaluation of
instruments for scoring physiological and
behavioral cues of pain, non-pain related
distress, and adequacy of analgesia and
sedation in pediatric mechanically ventilated
patients: A systematic review. Int J Nurs Stud.
2014;51(4):654–76.
Marques B, JM C, MJ S. Postoperative Pain
Assessment Methods for Infants and Young
Children: A Review. Journal of Clinical Research
in Pain and Anaesthesia. 2019;1(1):180004.
Laures E, LaFond C, Hanrahan K, Pierce N, Min
H, McCarthy AM. Pain Assessment Practices
in the Pediatric Intensive Care Unit. J Pediatr
Nurs. 2019;48:55–62.
Herr K, Coyne PJ, McCaffery M, Manworren R,
Merkel S. Pain Assessment in the Patient Unable
to Self-Report: Position Statement with Clinical
Practice Recommendations. Pain Management
Nursing. 2011;12(4):230–50.
Harris J, Ramelet A-S, van Dijk M, Pokorna
P, Wielenga J, Tume L, et al. Clinical
recommendations
for
pain,
sedation,
withdrawal and delirium assessment in
critically ill infants and children: an ESPNIC
position statement for healthcare professionals.
Intensive Care Med. 2016;42(6):972–86.
Playfor S, Jenkins I, Boyles C, Choonara I, Davies
G, Haywood T, et al. Consensus guidelines on
sedation and analgesia in critically ill children.
Intensive Care Med. 2006;32(8):1125–36.
Ceelie I, de Wildt SN, van Dijk M, van den
Berg MMJ, van den Bosch GE, Duivenvoorden
HJ, et al. Effect of Intravenous Paracetamol
on Postoperative Morphine Requirements
in Neonates and Infants Undergoing Major
Noncardiac Surgery. JAMA. 2013;309(2):149.
Neunhoeffer F, Kumpf M, Renk H, Hanelt
M, Berneck N, Bosk A, et al. Nurse-driven
pediatric analgesia and sedation protocol
reduces withdrawal symptoms in critically ill
medical pediatric patients. Pediatric Anesthesia.
2015;25(8):786–94.
Hanser A, Neunhoeffer F, Hayer T, Hofbeck
M, Schlensak C, Mustafi M, et al. A nurse‐
driven analgesia and sedation protocol reduces
length of PICU stay and cumulative dose of
benzodiazepines after corrective surgery for
tetralogy of Fallot. Journal for Specialists in
Pediatric Nursing. 2020;25(3).
Dreyfus L, Javouhey E, Denis A, Touzet S,
Bordet F. Implementation and evaluation of a
paediatric nurse-driven sedation protocol in
a paediatric intensive care unit. Ann Intensive
Care. 2017;7(1):36.
Barnes TA, Feng HX, Herrera NA, Leathers LA.
The impact of intravenous opioid shortages on

23.

24.

25.
26.

27.

28.

29.
30.

31.
32.

33.

34.
35.

36.

37.
38.

postoperative pain control in a pediatric cardiac
intensive care unit. J Card Surg. 2020;35(4):840–
4.
Honarmand A, Safavi M, Kashefi P, Hosseini B,
Badiei S. Comparison of effect of intravenous
ketamine,
peritonsillar
infiltration
of
tramadol and their combination on pediatric
post-tonsillectomy pain: A double-blinded
randomized placebo-controlled clinical trial. .
Res Pharm Sci. 2013;177–83.
Beckman EJ. Analgesia and sedation in
hospitalized children. In: PedSAP 2017 Book
3: Sedation and Analgesia. Lenexa, USA: The
American College of Clinical Pharmacy; 2017.
p. 7–30.
Vet NJ, Kleiber N, Ista E, de Hoog M, de Wildt
SN. Sedation in Critically Ill Children with
Respiratory Failure. Front Pediatr. 2016;4.
Santonocito C, Noto A, Crimi C, Sanfilippo
F.
Remifentanil-induced
postoperative
hyperalgesia:
current
perspectives
on
mechanisms and therapeutic strategies. Local
Reg Anesth. 2018;Volume 11:15–23.
Quigley C. Hydromorphone for acute and
chronic pain. In: Hobson A, editor. Cochrane
Database of Systematic Reviews. Chichester,
UK: John Wiley & Sons, Ltd; 2002.
Jeffries SA, McGloin R, Pitfield AF, Carr RR.
Use of Methadone for Prevention of Opioid
Withdrawal in Critically Ill Children. Can J
Hosp Pharm. 2012;65(1).
Çoruh B, Tonelli MR, Park DR. FentanylInduced Chest Wall Rigidity. Chest.
2013;143(4):1145–6.
Fife PA, Postier MA, Flood PA, Friedrichsdorf
MFSJ. Methadone conversion in infants
and children: Retrospective cohort study of
199 pediatric inpatients. J Opioid Manag.
2016;12(2):123–30.
Jahr JS, Lee VK. Intravenous Acetaminophen.
Anesthesiol Clin. 2010;28(4):619–45.
Howell KA, Ruggles CA, Thompson M, Metzger
KZ, Christopher JA, Bigham MT. Using Quality
Improvement to Reduce IV Acetaminophen
Use in a PICU. Pediatric Critical Care Medicine.
2020;21(6):550–6.
de Martino M, Chiarugi A, Boner A, Montini
G, de’ Angelis GL. Working Towards an
Appropriate Use of Ibuprofen in Children:
An
Evidence-Based
Appraisal.
Drugs.
2017;77(12):1295–311.
Gaid E, Mehta R, Waller J. The routine use of
post-operative NSAIDs in the pediatric patient
is effective and safe. Pediatrics. 2020;146:165–6.
Ismail A. The Challenges of Providing Effective
Pain Management for Children in the Pediatric
Intensive Care Unit. Pain Management Nursing.
2016;17(6):372–83.
Ramelet A-S, Abu-Saad HH, Rees N, McDonald
S. The challenges of pain measurement in
critically ill young children: A comprehensive
review. Australian Critical Care. 2004;17(1):33–
45.
Srouji R, Ratnapalan S, Schneeweiss S. Pain in
Children: Assessment and Nonpharmacological
Management. Int J Pediatr. 2010;2010:1–11.
Oakes LL. Compact Clinical Guide to Infant
and Child Pain Management. D’Arcy Y, editor.
New York: Springer Publishing; 2011.

Published by Pediatrics Sciences Journal | Pediatrics Sciences Journal 2023; 4(2): 71-79 | 10.51559/pedscij.v4i2.71

REVIEW

39. Gélinas C, Fortier M, Viens C, Fillion L,
Puntillo K. Pain assessment and management in
critically ill intubated patients: a retrospective
study. Am J Crit Care. 2004;13(2):126–35.
40. Turner HN. Complex Pain Consultations in the
Pediatric Intensive Care Unit. AACN Clinical
Issues: Advanced Practice in Acute and Critical
Care. 2005;16(3):388–95.
41. Johansson M, Kokinsky E. The COMFORT
behavioural scale and the modified FLACC
scale in paediatric intensive care. Nurs Crit
Care. 2009;14(3):122–30.
42. Voepel-Lewis T, Zanotti J, Dammeyer JA,
Merkel S. Reliability and Validity of the Face,
Legs, Activity, Cry, Consolability Behavioral
Tool in Assessing Acute Pain in Critically Ill
Patients. American Journal of Critical Care.
2010;19(1):55–61.
43. Ista E, van Dijk M, Tibboel D, de Hoog M.
Assessment of sedation levels in pediatric
intensive care patients can be improved by using

44.

45.

46.

47.

the COMFORT ???behavior??? scale*. Pediatric
Critical Care Medicine. 2005;6(1):58–63.
Ista E, de Hoog M, Tibboel D, van Dijk
M. Implementation of standard sedation
management
in
paediatric
intensive
care: effective and feasible? J Clin Nurs.
2009;18(17):2511–20.
Michel J, Hofbeck M, Gerbig I, Icheva V,
Heimberg E, Jost W, et al. Nurse-driven
analgesia and sedation in pediatric patients with
univentricular hearts requiring extracorporeal
life support after first-stage palliation
surgery: A pilot study. Pediatric Anesthesia.
2017;27(12):1261–70.
Stevens BJ, Abbott LK, Yamada J, Harrison D,
Stinson J, Taddio A, et al. Epidemiology and
management of painful procedures in children
in Canadian hospitals. Can Med Assoc J.
2011;183(7):E403–10.
Welzing L, Oberthuer A, Junghaenel S,
Harnischmacher U, Stützer H, Roth B.
Remifentanil/midazolam versus fentanyl/

midazolam for analgesia and sedation of
mechanically ventilated neonates and young
infants: a randomized controlled trial. Intensive
Care Med. 2012;38(6):1017–24.
48. Magner C, Valkenburg AJ, Doherty D, van Dijk
M, O’Hare B, Segurado R, et al. The impact of
introducing nurse-led analgesia and sedation
guidelines in ventilated infants following
cardiac surgery. Intensive Crit Care Nurs.
2020;60:102879.
49. Khalili G, Sajedi P, Shafa A, Hosseini B,
Seyyedyousefi H. A randomized evaluation
of
intravenous
dexamethasone
versus
oral acetaminophen codeine in pediatric
adenotonsillectomy: emergence agitation
and analgesia. Middle East J Anaesthesiol.
2012;21(4):499–504.

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