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Psychological Considerations in Perioperative Acute Pain Management 243
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Pain Management in Children
Leah Margalit Winters Webb, Erin Adams, Billy McElroy, Ashley Reid,
and Kim M. Strupp
Abstract Until the 1980s, it was a widely held belief that premature infants and
newborns did not feel pain. In the decades since, research supports that these patients
do, in fact, feel pain and moreover that there are deleterious effects of poorly
controlled or untreated pain in patients from newborn to adolescence. Pain assess-
ment and treatment in the pediatric population is complicated by changes in mental,
emotional, behavioral, and physical development and physiology that vary with age.
This chapter broadly covers considerations and techniques for assessing and treating
pediatric pain, while highlighting differences in the pediatric population compared
to adults.
Keywords Pediatrics
· Pain management · Pain · Anesthesia and Analgesia ·
Regional Anesthesia
L. M. W. Webb (
B
) · E. Adams · B. McElroy · K. M. Strupp
Division of Pediatric Anesthesiology, Department of Anesthesiology, University of Colorado/
Children’s Hospital Colorado, Aurora, USA
e-mail: Leah.Webb@childrenscolorado.org
E. Adams
e-mail: erin.adams@childrenscolorado.org
B. McElroy
e-mail: billy.mcelroy@childrenscolorado.org
K. M. Strupp
e-mail: kim.strupp@childrenscolorado.org
A. Reid
Department of Pediatric Pharmacy Services, Children’s Hospital Colorado, Aurora, USA
e-mail: ashley.reid@childrenscolorado.org
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A. Abd-Elsayed and K. Schroeder (eds.), Perioperative Pain Management,
https://doi.org/10.1007/978-3-031-67648-2_16
247
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248 L. M. W. Webb et al.
1 Introduction
This chapter will focus on the fundamentals of pediatric pain management—its own
multi-book topic—by highlighting both the differences between children and adults
and the special considerations specific to pediatric pain. While the definition of pain is
the same in pediatrics and adults, pediatric pain assessment and treatment are affected
by developmental, physiologic, and anatomic variations with age. For example, path-
ways for distinguishing and processing nociceptive and non-nociceptive stimuli are
not fully developed at birth, such that neonates, especially those born prematurely,
experience pain differently from adults and can suffer worse pain, due to enhanced
excitability with reduced inhibitory neurotransmission [1]. Distinguishing factors in
pediatric pain do not stop here. Below, the topics of pediatric pharmacokinetics and
pharmacodynamics, pain assessment, and pain treatment—from pharmacologic to
interventional to integrative—and complications will be addressed.
2 Developmental Pharmacokinetics
and Pharmacodynamics
Children have variable drug pharmacokinetics and pharmacodynamics that affect
appropriate medication administration. Dosing is generally based on body weight,
body surface area, age, or a combination thereof. Volume of distribution, drug clear-
ance, and other pharmacodynamic factors—all of which change with age—influence
ideal medication regimens [2]. Body composition, renal function, and liver function
vary as the body ages, contributing to the changing medication pharmacokinetics as
children progress from neonate to adult.
Pediatric dosing guidelines are largely extrapolated from adult studies due to a
lack of targeted studies in children, with 70–90% of medications used in the US pedi-
atric population being considered “off-label” [3]. While vital to caring for pediatric
patients, off-label use puts children at risk for adverse effects and over- and under-
dosing [3]. Health care professionals are hampered by limited evidence to support
drug choice and dose selection [3].
Many factors affect gastro-enteral transit time i n children and therefore absorption,
onset of action and duration, bioavailability, and drug binding. Infants have higher
gastric pH due to decreased acid production leading to increased absorption of acid
labile medications and reduced absorption of drugs requiring acid for absorption [4].
Bacterial colonization of the colon occurs in the first days of life. Over the first year of
life the gut microbiome changes significantly, affecting bacteria-produced enzymes
in the gut that can alter bioavailability [4]. In the first week of life, gastric emptying
time is significantly prolonged and continues to be delayed and irregular until six to
eight months of age. Relative to adults, transit time remains reduced in older infants
(even up to age three) such that onset of action may be faster with shorter duration of
action of medications [4, 5]. Infants have reduced drug-metabolizing enzymes and
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Pain Management in Children 249
drug transporters in the gut that increase to levels at or above adult activity in the
first few years of life [6].
Body composition affects drug distribution. In infants and children, increased
body water composition increases volume of distribution for water soluble medi-
cations, leading to a longer half-life and potentially higher milligram per kilogram
(mg/kg) dosing [4, 6]. Adipose tissue can serve as a reservoir for lipophilic medi-
cations, which particularly impacts the obese population. Further, in obese patients,
water-solublemedications (like morphine) havemore free-drug available,thus dosing
should be based on ideal body weight [4]. Protein binding can affect free or unbound
drug. For example, reduced protein levels in neonates and infants leads to increased
free drug availability and larger volumes of distribution for highly protein-bound
drugs [4]. Particularly salient to pain management is the decreased production of
alpha-1-acid glycoprotein in infants; consequently, highly protein-bound local anes-
thetics have increased levels of free, unbound drug and thus more availability of
active drug [4]. Adult binding is reached by about 1 year of age.
Most drug metabolism is reduced at birth and this decrement is related to under-
developed drug metabolizing enzymes, transporters, and elimination pathways.
Cytochrome 2C9 activity is very low to absent at birth, exceeds adult activity during
childhood, and then returns to adult activity around 10 years of age [5]. Functional
genetic polymorphisms exist that impact its activity, such that some medications
(including hydrocodone, codeine, and tramadol) are not reliably metabolized [5].
Cytochrome 3A4 activity is very low at birth but rapidly develops in the first month
of life [5]. Further, the kidneys, critical for drug elimination, are immature in both
structure and function at birth, when they receive only 5%–6% of cardiac output (as
compared to 15%–25% in adults) via renal blood flow, which increases during the
first year of life [5].
3 Pain Assessment
Pain is a dynamic process that arises from, and is greatly influenced by, multifacto-
rial components including sensation, cognition, developmental maturity, behavior,
emotion, and culture. Pain is defined by the expression of a discomforting sensory
and emotional experience. The experience of pain is subjective, being built on one’s
perspective of an unpleasant sensation, in the context of the above biopsychosocial
factors, and therefore can be difficult to effectively assess and treat.
The goal of pain assessment is to acquire information about the location, quality,
and intensity of discomfort. Multiple tools have been developed and validated to
assess pain in children, taking into consideration development based on age with
varying verbal or mental capabilities. Self-reporting tools are ideal for characterizing
the patient’s expression of pain; however, they are not applicable to patients who are
non-verbal, cognitively impaired, critically ill, or otherwise unable t o respond given
their medical requirements. In these patients, clinicians can assess for physiologic
responses to pain (heart rate and blood pressure trends), as well as for behavioral
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250 L. M. W. Webb et al.
changes in response to discomfort (facial expression, crying, and body positioning).
A non-exhaustive list of validated self-report and observational pain scales can be
found in Table 1.
These pain assessment tools are useful in scoring an experience that is otherwise
highly subjective to the patient experiencing it. Clinicians, however, must understand
that these scales are influenced by the child’s ability to apply it to their situation. Pain
may be underestimated and/or poorly differentiated from agitation, delirium, and
even patient frustration and understanding. These scales do not fully consider patients
with chronic pain, who may experience normalization of vital signs and altered
mental or behavioral understanding of their situation (such as catastrophizing). As
a result, the scoring may not accurately reflect their pain states. Also, parents play a
significant role in pediatric pain management since they are often highly involved in
the recognition and treatment of their child’s pain. Consequently, parental education
and involvement are essential to children’s pain treatment plans.
Regarding pain assessment after anesthesia and surgery, it may be challenging
to distinguish between pain and emergence agitation or delirium (EA/ED) in the
pediatric recovery room; yet, ensuring adequate pain control in a child exhibiting EA/
ED is crucial. Scoring systems such as the Pediatric Anesthesia Emergence Delirium
Scale (PAEDS) have been shown to be valid and reliable in detecting emergence
delirium [7] and can help in distinguishing EA/ED from pain. EA/ED occurs more
commonly with sevoflurane or desflurane anesthesia and is theorized to occur due
Table 1 Recommended sample list of pain assessment tools that have been validated for use in
children. Please reference Manworren [73] for a comprehensive list and details.
Acronym Patient Age Reference Notes
Behavioral
N-PASS Premature infants
23–40 weeks
gestational age
Hummel
[74]
N-PASS = Neonatal Pain, Agitation, and
Sedation Scale
NIPS Pre-term to term
infants
Lawrence
[75]
NIPS = Neonatal Infant Pain Scale
CRIES Neonate Ahn [76] CRIES = crying, requires oxygen,
increased vital signs, expression, and
sleeplessness
COMFORT
Behavior Scale
Neonate to 3 years Van Dijk
[77]
For patients in intensive care units
rFLACC 4to19years Malviya
[78]
rFLACC = revised Faces, Legs, Activity,
Cry, and Consolability Observational Tool;
for patients with intellectual disabilities
Self-report
FPS-R 4to12years Hicks [79] FPS-R = Faces Pain Scale-Revised
NRS 8 years and up NRS = Numeric Rating Scale; 0 (no pain)
to 10 (worst possible pain) point scale; can
be assessed verbally
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Pain Management in Children 251
to rapid awakening in a strange environment with the faster offset of these volatile
anesthetics [8]. Children demonstrating symptoms of EA/ED appear in a dissociated
state and exhibit inconsolability, thrashing, and incoherence, which could otherwise
be interpreted as pain.
4 Multimodal Pain Treatment: Pharmacologic,
Interventional, Non-pharmacologic
Untreated pain can deleteriously affect children by altering neurocognition,
psychosocial interaction, somatosensory processing, and executive functioning [9,
10], highlighting the critical need for efficacious pain treatment. Moreover, stress
and pain early in life can lead to lifelong changes in pain processing and modulation.
These patients are not only prone to amplified, recurrent, and/or chronic pain but also
an increased risk of developing disease in other organ systems [10]. Minor procedural
pain (like that associated with venipuncture, injections, and intravenous and bladder
catheterization) is often associated with anxiety, and treating both factors is critical
to reducing the sequelae of painful experiences in children and preventing resistance
to future healthcare resource utilization [10, 11].
Multimodal pain therapy in infants and children, just as in adults, is important
for effective treatment of pain and associated stressors [12–14]. (See Table 2 for
simplified medication dosing regimens, as exhaustive regimens are too lengthy for
review in this chapter.) A comprehensive multimodal plan includes pharmacologic
interventions, as well as procedures (including regional anesthesia) and nonpharma-
cologic adjuncts [12, 13]. Mechanism of action is the same across patients and thus
not mentioned in this chapter.
5 Pharmacologic Therapies: Nonopioid and Opioid
Medications
Nonopioid Medications
Acetaminophen is a commonly used, nonopioid analgesic that can be administered
orally,rectally, and intravenously. It has a wide safety margin and can be used without
significant concerns in most pediatric patients. Acetaminophen must be dosed appro-
priately, considering age and weight, given its association with hepatic necrosis; it
is often avoided in patients with decreased liver function [15].
Nonsteroidal analgesics, or nonsteroidal anti-inflammatory drugs (NSAIDs), are
often first choice medications in the treatment of pain. NSAIDs are frequently admin-
istered as adjuvant therapy to reduce opioid use; however,nonsteroidals have a ceiling
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252 L. M. W. Webb et al.
Table 2 Suggested dosing for commonly used medications in pediatric pain management. (Non-exhaustive list, which uses dosing recommendations from
Lexicomp® [77], unless otherwise noted.)
Neuraxial Medication Dosing
Local Anesthetic: Spinal Anesthetic Blockade (SAB) adapted from Kokki [64]
Bupivacaine 0.75%: max 20 mg [80] Ropivacaine 0.75%: max 20 mg [80]
Weight (kg) Dose (mg/kg) Duration (min) Weight (kg) Dose (mg/kg) Duration (min)
<5 0.3–1 65–90 <5 0.5–1 45–80 min
6–10 0.4–0.5 75 6–10 0.5 90 min
11–20 0.3–0.4 80 11–20 0.5 90 min
>20 0.25–0.3 >85 >20 0.5 105 min
Local Anesthetic: Epidural Anesthesia (EA) and Peripheral Nerve Catheter(PNC)
Infusion Starting Dose (mg/kg/hr) Maximum Dose (mg/kg/hr), upper limit 28 mg/hr
Bupivacaine 0.2 0.5
Ropivacaine 0.2 0.5
Chloroprocaine 2 6
Loading Dose Epidural (mg/kg) Peripheral Nerve Catheter (mg/kg)
Ropivacaine 0.3–0.5, max 10–20 cc 0.1–0.5
¤
Bupivacaine 0.3–0.5, max 10–20 cc 0.1–0.5
¤
Adjuvants adapted from Anderson [81]
Additive SAB Dose (mcg/kg) EA Dose (mcg/kg) Effect Side Effect
Epinephrine 3–4 1–5 mcg/ml D
§
None
Clonidine 0.5–1 0.5–2 D
§
,A H, S
Fentanyl* 0.25–0.5 0.2–1 A
‡
N, V, P, S,
RD
¥
(continued)
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Pain Management in Children 253
Table 2 (continued)
Neuraxial Medication Dosing
Morphine* 3–10* 10–30* A N, V, P, S,
RD
¥
,U
Hydromorphone 1–4 3–5 A N, V, P, S,
RD
¥
,U
Pain Medications
Nonopioid Route Dose (mg/kg/dose) Frequency Notes: Dose adjustments may be required
for hepatic or renal impairment
Acetaminophen (age >2
years)
PO
IV
PR
10–15
10–15
20–25 (load 40)
Q4–6H 1. Under 2: limit to 7.5–15 mg/kg Q6H;
max 60 mg/kg/day. 2. Max daily dose:
<50kg= 3,750 mg; >50 kg = 4,000
mg.
Ibuprofen
š
PO 4–10 Q6–8H 1. Max single dose 600 mg. 2. Max daily
dose 2,400 mg.
Naproxen
š
PO 5–7 Q8–12H 1. Max daily dose 600–1000 mg. 2.
Usual adult dose 250–500 mg Q12H.
Celecoxib
š
(≥ 2 years)
PO ≥ 10 kg: 50 mg
≥ 25 kg: 100 mg
BID
BID
1. Max daily dose 200 mg.
Ketorolac
š,
° PO
IV
IM
1
0.5 mg
1
Q6–8H
Q6–8H
Q6–8H
1. Max duration 5 days. 2. Max oral dose
age 2–16 years 40 mg/day. 3. Max IV
dose <50 kg 15 mg, ≥ 50 kg 30 mg.
Gabapentin PO 5 TID (at max) 1. Start 300 mg (max) QHS, increase to
BID day 2, then TID day 3. 2. Usual
dose range 8–35 mg/kg/day split TID;
max daily dose 3,600 mg.
(continued)
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