Acute Postoperative Pain Management
Content
Acute Postoperative Pain Management
in Infants and Children: Size and
Age Do Matter
Patrick K. Birmingham, MD, FAAP
Department of Anesthesiology, Division of Pain Medicine
Ann & Robert H. Lurie Children’s Hospital of Chicago
Northwestern University Feinberg School of Medicine
Chicago, Illinois
time to discharge and decrease unplanned returns to the
hospital.1,2
Much of the discussion in this chapter includes ‘‘offlabel’’ or ‘‘unapproved’’ use of drugs, as this practice remains common in children despite recent laws promoting
the need for more study and inclusive labeling for infants
and children.3 Unapproved use does not imply improper or
illegal use of such drugs.4
An in-depth review of developmental pharmacokinetics
and pharmacodynamics in newborns and infants is beyond
the scope of this discussion, but is available to the interested reader in any of several pediatric anesthesia textbooks.5,6
Learning Objectives:
As a result of completing this activity, the participant
will be able to
Describe evidence-based approaches to pain management in children
Explain the role of parenteral, neuraxial, and oral
analgesics for postoperative analgesia
Discuss the safety and efficacy of analgesic
regimens in children
Author Disclosure Information:
Dr. Birmingham has disclosed that he receives
research funding from Cadence Pharmaceuticals.
nesthesiologists have expertise and experience with
both analgesics and regional anesthetic techniques
that enable them to optimize perioperative pain
relief. This has always been of value to patients and their
families. It is particularly so in the modern era of the
‘‘perioperative surgical home,’’ where what anesthesiologists do in the operating room and beyond may improve
PAIN MEASUREMENT
A
Many tools are developed and in use to measure pain in
infants and children. They rely on physiological, behavioral, or self-report measures singly or in combination. The
scale used depends on the patient’s age, cognitive ability,
willingness to cooperate, and medical condition. Physiological measurements such as blood pressure, heart rate,
and respiratory rate are nonspecific but may have to be
relied upon in infants and in sedated, mechanically ventilated patients. Behavioral measures such as facial expression, body posture, activity, and quality of cry can be
used in infants and children7 (Table 1). Age-appropriate
self-report measures have been developed for children as
young as 3 to 4 years of age8 (Figure 1). Some scales have
Supplemental Digital Content is available for this article. Direct URL
citations appear in the printed text and are available in both the HTML
and PDF versions of this article. Links to the digital files are provided in
the HTML and PDF text of this article on the Journal’s Web site
(www.asa-refresher.com).
42
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
43
Acute Pain Management in Infants and Children
Table 1. The FLACC Scale*
Scoring
Categories
0
Face
1
2
No particular expression or smile
Occasional grimace or frown,
withdrawn, disinterested
Frequent to constant frown,
clenched jaw, quivering chin
Legs
Normal position or relaxed
Uneasy, restless, tense
Kicking, or legs drawn up
Activity
Lying quietly, normal position,
moves easily
Squirming, shifting back and
forth, tense
Arched, rigid, or jerking
Cry
No cry (awake or asleep)
Moans or whimpers, occasional
complaint
Crying steadily, screams or sobs,
frequent complaints
Consolability
Content, relaxed
Reassured by occasional
touching, hugging, or being
talked to, distractible
Difficult to console or comfort
*Copyright r 2002, The Regents of the University of Michigan.
been revised for use and validated in the cognitively impaired child. Behavioral or self-report measures scored on
a 0 to 10 scale, similar to a numeric rating scale used in
older children, allow the convenience of the same scoring
system across all age groups. A simple question to the parents (‘‘Do you think your child is getting enough pain
medicine?’’) can also be very helpful.
PAIN MANAGEMENT
The menu of available pain management modalities is
discussed in the context of patients undergoing commonly
performed surgical procedures. This case-based approach
highlights currently available evidence-based options.
Bilateral Myringotomy and Pressure Equalization
Tube Placement
Bilateral myringotomy and pressure equalization tube
placement (BM&T) is the most common otolaryngology
procedure in children and is routinely performed at outpatient community surgicenters as well as academic medical centers. Yet BM&T is often overlooked in discussions
of pain management. Many studies have been performed
using acetaminophen, nonsteroidal antiinflammatory
drugs (NSAIDs), opioids, and a-2 agonists by various
routes and dosages. One way to evaluate these studies
is to focus on those that use a control group who receive
no preoperative or intraoperative analgesic. From 40 to
70% of these patients will require rescue medication
in the postanesthesia care unit.9,10 This makes an
argument for providing some form of analgesia during the
procedure.
Whereas acetaminophen by the oral or rectal route has
been studied, its efficacy in BM&T has been mixed. Oral or
parenteral ketorolac (study dose 1 mg/kg; current recommended dose 0.5 mg/kg) and nasal fentanyl (2 mg/kg) have
been shown to reduce pain scores, emergence agitation, or
both.9,11,12 One study measuring fentanyl serum concentrations showed rapid uptake when the agent was given nasally with decreasing concentrations by 30 minutes after
administration.12 Nasal dexmedetomidine (1 to 2 mg/kg) has
also been studied but, at the higher dose, resulted in prolonged postanesthesia care unit discharge times.13
There is also a role for regional anesthesia in BM&T.
Blockade of the auricular branch of the vagus nerve (nerve
of Arnold) on the posterior surface of the tragus (Figure 2)
with 0.2 mL of plain 0.25% bupivacaine is as effective as
2 mg/mL nasal fentanyl.14
Interestingly, intravenous access for BM&T has been shown
to prolong postoperative recovery and discharge times, increase
pain scores, and result in lower parental satisfaction.15
Tonsillectomy
Providing comfort in children after tonsillectomy can be
challenging, particularly in the child with sleep disordered
breathing. Up to 3.9% of tonsillectomy patients will require
Figure 1. The Faces Pain Scale-Revised. From Hicks et al.,8 Faces Pain Scale-Revised (FPS-R). www.iasp-pain.org/fpsr. Copyright r 2001, International
Association for the Study of Pains. Reproduced with permission.
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
44
Birmingham
In the evaluation of opioid studies in
tonsillectomy patients, it is worthwhile to note
whether the surgical indication is recurrent
tonsillitis versus obstructive sleep apnea.
Figure 2. Nerve of Arnold block. Using a 30-gauge needle, 0.2 mL of 0.25%
plain bupivacaine is injected into the posterior surface of the tragus.
readmission to the hospital with pain, dehydration, fever,
bleeding, or a combination of these complications,16
with some returning to the operating room for control of
bleeding. These concerns limit, although do not eliminate,
the use of perioperative NSAIDs for pain management. Ketorolac and more recently available intravenous ibuprofen
are parenteral options in addition to oral NSAIDs (Table 2).
A metaanalysis and systematic review reported conflicting
conclusions about whether NSAIDs should be used in tonsillectomy patients (Supplemental Digital Content 1, http://
links.lww.com/ASA/A542).17,18 Current clinical practice
guidelines for otolaryngology recommend that ketorolac be
avoided in the tonsillectomy patient.16
Intravenous acetaminophen has been more commonly
used in the United States since its Food and Drug Administration approval for use in children more than 2 years of
age. If acetaminophen is given by any route, it should be
factored into subsequent postoperative dosing ordered by
the surgeon (Table 2).
Opioids are frequently used during or after surgery, or
both, in the child undergoing tonsillectomy. In the evaluation
of opioid studies in tonsillectomy patients, it is worthwhile
to note whether the surgical indication is recurrent tonsillitis
versus obstructive sleep apnea (sleep disordered breathing).
The child with sleep disordered breathing may have altered
sensitivity to opioids.19 Dosing should be adjusted accordingly. Patients with more severe sleep disordered breathing
may need to be admitted postoperatively for monitoring,
sometimes in an intensive care unit setting.
Single-dose dexamethasone in tonsillectomy patients
has been shown to be safe and effective in decreasing
postoperative nausea and vomiting.16,20–22 It also has an
analgesic benefit, as indicated by earlier return to oral intake and decreased postoperative analgesic requirements.
Doses as low as 0.0625 mg/kg have been shown to be as
effective as 1 mg/kg in this regard.23
Dexmedetomidine at doses of 0.75 to 4 mg/kg with or
without an infusion (0.7 mg/kg/h) have been studied
in tonsillectomy patients.24–26 While prolonging the
opioid-free interval, decreasing emergence agitation
postoperatively, or both, the higher doses studied also
prolonged postanesthesia care unit stay.
Use of N-methyl-D-aspartate receptor antagonists such
as ketamine, magnesium, and dextromethorphan in tonsillectomy patients has been studied with little benefit
shown versus standard opioid administration.27,28 Additional studies may better define a role for these alternatives
in the tonsillectomy patient.
Local anesthetic infiltration of the tonsillar bed is reported by 51.4% of surgeons29 but, interestingly, was not
shown to be of benefit in a recent systematic review.30
The anesthesiologist can also contribute to the postoperative or postdischarge safety of these patients by directing pain management away from the use of codeine.
Codeine’s conversion to its active metabolite, morphine,
can be influenced by genetic variation in the cytochrome
CYP2D6 metabolic pathway. A ‘‘slow’’ metabolizer may
have lower concentrations of morphine and possible ‘‘resistance’’ to a given dose, whereas the ‘‘ultrarapid’’ metabolizer may have higher concentrations. Postoperative
respiratory depression and arrest have been reported with
standard (0.5 to 1 mg/kg) doses of codeine in posttonsillectomy patients.31,32 Codeine is being removed from
pediatric hospital formularies and its use discouraged in
the postoperative tonsillectomy patient for this reason.
Inguinal Hernia Repair
Inguinal hernia repair is among the most common pediatric surgical procedures in infants and children, particularly in the former preterm infant. It is an ideal procedure
for the use of single-injection caudal epidural analgesia,
which can provide excellent perioperative pain control
while minimizing or eliminating the use of opioids (Supplemental Digital Content 2, http://links.lww.com/ASA/
A543, Supplemental Digital Content 3, http://links.
lww.com/ASA/A544). Recent analyses demonstrate the
overwhelming safety of caudal epidural anesthesia33 and
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
45
Acute Pain Management in Infants and Children
Table 2. NSAID General Dosing Guidelines (Age 4 1 year)
NSAID
Route
Dose (mg/kg)
Dose Interval (h)
Max. Dose (mg)
Daily Maximum/Comments
Ketorolac
IV
0.5
6
30 (15 if o 50 kg)
For r5 d
Ibuprofen
PO
5–10
6
400
40 mg/kg (1,200 mg)
Naproxen
PO
5–7.5
8–12
200
10–15 mg/kg (600 mg)
Acetaminophen
PO
10–15
4–6
1,000
75–90 mg/kg (3,000–4,000 mg)
Acetaminophen
PR
40 load, then 20
6
1,000
Acetaminophen
IV
10–15
4–6
10,000
75 mg/kg (4,000 mg)
IV ¼ intravenous; NSAID ¼ nonsteroidal antiinflammatory drug; PO ¼ oral; PR ¼ rectal.
alternatives such as transversus abdominis plane blockade,34 which can be performed under ultrasound guidance
to aid in localization of nerve roots and tissue planes to
optimize blockade.
In the former preterm infant, spinal anesthesia is an alternative to general anesthesia. One of the potential advantages of a primary regional technique, more commonly
subarachnoid blockade but potentially also caudal blockade, is avoidance of general anesthesia and any potential
long-term cognitive effects on the developing central
nervous system. Ongoing prospective trials, such as the
General Anesthesia versus Spinal (GAS) study and the Pediatric Anesthesia and Neurodevelopment Assessment
(PANDA) study, are attempting to clarify animal data and
some retrospective human studies that suggest deleterious
central nervous system effects from exposure to general
anesthesia in early life.
In addition, despite the high initial success rate for spinal
block placement at experienced institutions, more than
20% of patients may require supplemental anesthesia at
some time during surgery.35 Other authors have found no
difference in the incidence of postoperative apnea, regardless of the technique.36 Whether the former preterm
infant undergoes general or regional anesthesia for hernia
repair, the same criteria should be used for postoperative
monitoring for apnea of prematurity.
Neuraxial and peripheral regional blocks, whether single-injection or catheter techniques, are routinely performed during general anesthesia in children. A recent
report from a large multisite registry of regional anesthesia, the Pediatric Regional Anesthesia Network
(PRAN), examined the safety of blocks done during general anesthesia. Their analysis of more than 50,000 blocks
demonstrated that placement of neuraxial and peripheral
regional anesthesia blocks in pediatric patients under
general anesthesia is as safe as placement in sedated and
awake children, and that it should remain the prevailing
standard of care (Supplemental Digital Content 4, http://
links.lww.com/ASA/A545).37
Intravenous supplementation can include acetaminophen and NSAIDs. The pharmacokinetics of ketorolac
has been studied in infants and children, leading to a
dosing recommendation of 0.5 mg/kg in the younger
patient.38,39
One must be aware of the recommended upper limits of
local anesthetic dosing (2.5 to 3 mg/kg for bupivacaine/
ropivacaine) to avoid local anesthetic systemic toxicity.
Because of lower protein binding and reduced clearance in
infancy, the local anesthetic dose should be reduced by 30
to 50% in the first 4 to 6 months of life.
The pharmacokinetics of ketorolac has been
studied in infants and children, leading to a
dosing recommendation of 0.5 mg/kg
in the younger patient.
One should also have prompt access to Intralipid 20%
in the event of systemic toxicity and be prepared to use it in
the resuscitation of an infant or child (Table 3).40 Although
propofol is compounded in a 10% lipid emulsion, it should
not be used for resuscitation from local anesthetic toxicity.
Table 3. Treatment of Local Anesthetic Systemic
Toxicity
20% Lipid Emulsion
Dosing Recommendations
Initial bolus
1.5 mL/kg over 1 min
Repeat bolus
1.5 mL/kg once or twice for persistent
cardiovascular collapse
Maintenance
infusion
0.25 mL/kg/min for Z10 min after attaining
circulatory stability
Double to 0.5 mL/kg/min if blood pressure
remains low
Recommended
upper limit
Approximately 10–12 mL/kg over first 30 min
Derived from Neal JM, Bernards CM, Butterworth JF IV, Di Gregorio G, Drasner
K, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Reg Anesth
Pain Med 2010; 35:152–61, table 4.40
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
46
Birmingham
Table 4. Epidural Dosing Guidelines
Local Anesthetic
Additives
0.1% bupivacaine or
ropivacaine
Clonidine (1 mg/mL)
or
fentanyl (2 mg/mL)
Continuous Infusion
(mL/kg/h)
Bolus Dose
(mL)
Lockout (min)
0.1–0.2
0.5–2
15–30
Posterior Spinal Fusion for Idiopathic Scoliosis
The adolescent undergoing posterior spinal fusion can benefit from multimodal analgesic techniques to optimize postoperative analgesia. The analgesic plan can start before
surgery with administration of the voltage-dependent calcium channel blockers pregabalin or gabapentin, which have
analgesic and sometimes anxiolytic properties. These drugs
can be effective in the management of centrally acting pain,
which may be a component of the postoperative pain in
these patients.41,42 Pregabalin and gabapentin have been
shown to reduce pain scores and opioid consumption in the
early postoperative phase after pediatric spinal fusion.41
Surgical access to the epidural space allows for placement of an epidural catheter under direct visualization after completion of instrumentation and before wound
closure. Upon awakening and surgical confirmation of the
patient’s motor function, a single bolus dose followed by a
continuous infusion of plain local anesthetic or with additives such as clonidine or an opioid is initiated using the
catheter. The most recent metaanalysis of randomized
controlled trials of epidural opioids demonstrated similar
analgesic outcomes between morphine, fentanyl, and sufentanil with a higher incidence of nausea or vomiting and
possibly pruritus with the more hydrophilic opioid morphine.43 In spinal fusion or other major orthopedic procedures (e.g., femoral osteotomy), a demand option can be
added to the epidural catheter. Both epidural patient-controlled analgesia (PCA)44 and epidural analgesia by nurse
or parent proxy45 have been safely used in children undergoing major surgery (Table 4).
Alternatively, a single dose of intrathecal morphine (2 to
15 mg/kg) can be injected by the anesthesiologist before the
incision or by the surgeon under direct vision before closing the incision. This measure has been shown to result in
lower pain scores and opioid consumption in the first 24
hours after surgery.46,47
Intravenous PCA is widely utilized in children and is a
routine component of postoperative pain management for
spinal fusion and many other pediatric surgical procedures
(Table 5). The opioid ‘‘loading dose’’ is frequently administered intraoperatively, and parameters are adjusted
postoperatively as needed to optimize pain relief. Children
as young as 5 to 6 years of age will self-activate their PCA
button. Although safety concerns have been raised about
parent or caregiver ‘‘PCA by proxy’’ and continuous opioid
1 h Limit
(Cont þ Bolus)
(mg/kg/h)
0.4 (lumbar catheter)
0.3 (thoracic catheter)
0.2 (age o 4–6 mo)
infusions, both are utilized and can be done safely (Supplemental Digital Content 5, http://links.lww.com/ASA/
A546).48–50
The use of nonopioid analgesics such as ketorolac
should include input from the surgeon because of concerns
about potential bleeding in the early postoperative period
and surgical nonunion in the months after surgery. The
likelihood of nonunion is lower in the pediatric versus the
adult spinal fusion population. Intravenous acetaminophen is a useful addition in this and other patient populations.
Children as young as 5 to 6 years of age will
self-activate their PCA button.
Tramadol (1 to 2 mg/kg), a serotonin and norepinephrine uptake inhibitor with weak mu-opioid receptor activity, can be a useful transition agent from stronger
intravenous opioids to oral analgesics or an alternative to
the use of oxycodone or hydrocodone.51
MANAGEMENT OF SIDE EFFECTS
An important component of postoperative pain control is
management of related side effects. Nausea and vomiting
are the most common concerns. Risk factors for postoperative vomiting in children include a family history of
postoperative nausea and vomiting, age 3 years or higher,
surgical time 30 minutes or more, and surgical subpopulations such as strabismus surgery. The commonly
used combination therapy of dexamethasone and ondansetron has been shown to be effective in children.52 Lowdose naloxone by intravenous infusion (0.25 to 1 mg/kg/
h)53,54 is effective in the management of opioid-related side
effects such as nausea and vomiting or pruritus. Naloxone
also has a site-specific effect and can be administered orally
or by a nasogastric tube (10 to 20 mg/kg) for opioid-related
ileus. Metaanalyses of acupuncture and acustimulation
have demonstrated their effectiveness in reducing postoperative vomiting in children.55,56 Leg weakness from
continuous epidural infusion can be avoided or minimized
by using lower infusion rates or lower local anesthetic
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
47
Acute Pain Management in Infants and Children
Table 5. Intravenous PCA Parameters
Opioid
Bolus Dose
Lockout (min) (default 8 min)
Continuous Infusion
1 h Limit
Maximum 1 h Limit
Morphine
0.01–0.02 mg/kg
5–15
0.01–0.02 mg/kg/h
0.2 mg/kg
15 mg
Fentanyl
0.2–0.4 mg/kg
5–15
0.2–0.4 mg/kg/h
4 mg/kg
300 mg
2–3 mg/kg
5–15
2–3 mg/kg/h
30–40 mg/kg
3,000 mg
Hydromorphone
PCA ¼ patient-controlled analgesia.
concentrations, or by substitution of ropivacaine for bupivacaine.
Be aware also of the use of herbal medications in children and their potential impact on pain medication and
postoperative side effects, such as bleeding, hypoglycemia,
and prolonged sedation.57,58
CONCLUSIONS
A perioperative evidence-based analgesic strategy combined with daily rounds by an anesthesiologist-directed
pain management service can optimize pain control, avoid
or minimize undesired side effects, and contribute toward
enhanced recovery after surgery. As anesthesiologists move
forward in an evolving health-care environment, patient
and parental satisfaction measures of pain management
and minimization of readmission after discharge will be
important metrics in hospital ratings and reimbursement.
Anesthesiologists are uniquely positioned to provide leadership and value in optimizing such quality outcome
measures.
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41. Ho KY, Gan TJ, Habib AS: Gabapentin and postoperative pain—A
systematic review of randomized controlled trials. Pain 2006;
126:91–101.
42. Rusy LM, Hainsworth KR, Nelson TJ, et al.: Gabapentin use in
pediatric spinal fusion patients: A randomized, double-blind,
controlled trial. Anesth Analg 2010; 110:1393–8.
43. Youssef N, Orlov D, Alie T, et al.: What epidural opioid results in the
best analgesia outcomes and fewest side effects after surgery?:
44.
45.
46.
47.
48.
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52.
53.
54.
55.
56.
57.
58.
A meta-analysis of randomized controlled trials. Anesth Analg
2014; 119:965–77.
Birmingham PK, Wheeler M, Suresh S, et al.: Patient-controlled
epidural analgesia in children: Can they do it? Anesth Analg 2003;
96:686–91.
Birmingham PK, Suresh S, Ambrosy A, Porfyris S: Parent-assisted or
nurse-assisted epidural analgesia: Is this feasible in pediatric patients?
Paediatr Anaesth 2009; 19:1084–9.
Gall O, Aubineau JV, Bernie`re J, Desjeux L, Murat I: Analgesic effect
of low-dose intrathecal morphine after spinal fusion in children.
Anesthesiology 2001; 94:447–52.
Eschertzhuber S, Hohlrieder M, Keller C, et al.: Comparison of highand low-dose intrathecal morphine for spinal fusion in children. Br J
Anaesth 2008; 100:538–43.
Voepel-Lewis T, Marinkovic A, Kostrzewa A, Tait AR, Malviya S:
The prevalence of and risk factors for adverse events in children
receiving patient-controlled analgesia by proxy or patient-controlled
analgesia after surgery. Anesth Analg 2008; 107:70–5.
Monitto CL, Greenberg RS, Kost-Byerly S, et al.: The safety and
efficacy of parent-/nurse-controlled analgesia in patients less than six
years of age. Anesth Analg 2000; 91:573–9.
Krane EJ: Patient-controlled analgesia: Proxy-controlled analgesia?
Anesth Analg 2008; 107:15–7.
Finkel JC, Rose JB, Schmitz ML, et al.: An evaluation of the efficacy
and tolerability of oral tramadol hydrochloride tablets for the
treatment of postsurgical pain in children. Anesth Analg 2002;
94:1469–73.
Gan TJ, Diemunsch P, Habib AS, et al.: Consensus guidelines for the
management of postoperative nausea and vomiting. Anesth Analg
2014; 118:85–113.
Maxwell LG, Kaufmann SC, Bitzer S, et al.: The effects of a smalldose naloxone infusion on opioid-induced side effects and analgesia
in children and adolescents treated with intravenous patientcontrolled analgesia: A double-blind, prospective, randomized,
controlled study. Anesth Analg 2005; 100:953–8.
Monitto CL, Kost-Byerly S, White E, et al.: The optimal dose of
prophylactic intravenous naloxone in ameliorating opioid-induced
side effects in children receiving intravenous patient-controlled
analgesia morphine for moderate to severe pain: A dose
finding study. Anesth Analg 2011; 113:834–42.
Dune LS, Shiao SY: Metaanalysis of acustimulation effects on
postoperative nausea and vomiting in children. Explore (NY) 2006;
2:314–20.
Jindal V, Ge A, Mansky PJ: Safety and efficacy of acupuncture in
children: A review of the evidence. J Pediatr Hematol Oncol 2008;
30:431–42.
Everett LL, Birmingham PK, Williams GD, Brenn BR, Shapiro JH:
Herbal and homeopathic medication use in pediatric surgical
patients. Paediatr Anaesth 2005; 15:455–60.
Ang-Lee MK, Moss J, Yuan CS: Herbal medicines and perioperative
care. JAMA 2001; 286:208–16.
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
in Infants and Children: Size and
Age Do Matter
Patrick K. Birmingham, MD, FAAP
Department of Anesthesiology, Division of Pain Medicine
Ann & Robert H. Lurie Children’s Hospital of Chicago
Northwestern University Feinberg School of Medicine
Chicago, Illinois
time to discharge and decrease unplanned returns to the
hospital.1,2
Much of the discussion in this chapter includes ‘‘offlabel’’ or ‘‘unapproved’’ use of drugs, as this practice remains common in children despite recent laws promoting
the need for more study and inclusive labeling for infants
and children.3 Unapproved use does not imply improper or
illegal use of such drugs.4
An in-depth review of developmental pharmacokinetics
and pharmacodynamics in newborns and infants is beyond
the scope of this discussion, but is available to the interested reader in any of several pediatric anesthesia textbooks.5,6
Learning Objectives:
As a result of completing this activity, the participant
will be able to
Describe evidence-based approaches to pain management in children
Explain the role of parenteral, neuraxial, and oral
analgesics for postoperative analgesia
Discuss the safety and efficacy of analgesic
regimens in children
Author Disclosure Information:
Dr. Birmingham has disclosed that he receives
research funding from Cadence Pharmaceuticals.
nesthesiologists have expertise and experience with
both analgesics and regional anesthetic techniques
that enable them to optimize perioperative pain
relief. This has always been of value to patients and their
families. It is particularly so in the modern era of the
‘‘perioperative surgical home,’’ where what anesthesiologists do in the operating room and beyond may improve
PAIN MEASUREMENT
A
Many tools are developed and in use to measure pain in
infants and children. They rely on physiological, behavioral, or self-report measures singly or in combination. The
scale used depends on the patient’s age, cognitive ability,
willingness to cooperate, and medical condition. Physiological measurements such as blood pressure, heart rate,
and respiratory rate are nonspecific but may have to be
relied upon in infants and in sedated, mechanically ventilated patients. Behavioral measures such as facial expression, body posture, activity, and quality of cry can be
used in infants and children7 (Table 1). Age-appropriate
self-report measures have been developed for children as
young as 3 to 4 years of age8 (Figure 1). Some scales have
Supplemental Digital Content is available for this article. Direct URL
citations appear in the printed text and are available in both the HTML
and PDF versions of this article. Links to the digital files are provided in
the HTML and PDF text of this article on the Journal’s Web site
(www.asa-refresher.com).
42
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
43
Acute Pain Management in Infants and Children
Table 1. The FLACC Scale*
Scoring
Categories
0
Face
1
2
No particular expression or smile
Occasional grimace or frown,
withdrawn, disinterested
Frequent to constant frown,
clenched jaw, quivering chin
Legs
Normal position or relaxed
Uneasy, restless, tense
Kicking, or legs drawn up
Activity
Lying quietly, normal position,
moves easily
Squirming, shifting back and
forth, tense
Arched, rigid, or jerking
Cry
No cry (awake or asleep)
Moans or whimpers, occasional
complaint
Crying steadily, screams or sobs,
frequent complaints
Consolability
Content, relaxed
Reassured by occasional
touching, hugging, or being
talked to, distractible
Difficult to console or comfort
*Copyright r 2002, The Regents of the University of Michigan.
been revised for use and validated in the cognitively impaired child. Behavioral or self-report measures scored on
a 0 to 10 scale, similar to a numeric rating scale used in
older children, allow the convenience of the same scoring
system across all age groups. A simple question to the parents (‘‘Do you think your child is getting enough pain
medicine?’’) can also be very helpful.
PAIN MANAGEMENT
The menu of available pain management modalities is
discussed in the context of patients undergoing commonly
performed surgical procedures. This case-based approach
highlights currently available evidence-based options.
Bilateral Myringotomy and Pressure Equalization
Tube Placement
Bilateral myringotomy and pressure equalization tube
placement (BM&T) is the most common otolaryngology
procedure in children and is routinely performed at outpatient community surgicenters as well as academic medical centers. Yet BM&T is often overlooked in discussions
of pain management. Many studies have been performed
using acetaminophen, nonsteroidal antiinflammatory
drugs (NSAIDs), opioids, and a-2 agonists by various
routes and dosages. One way to evaluate these studies
is to focus on those that use a control group who receive
no preoperative or intraoperative analgesic. From 40 to
70% of these patients will require rescue medication
in the postanesthesia care unit.9,10 This makes an
argument for providing some form of analgesia during the
procedure.
Whereas acetaminophen by the oral or rectal route has
been studied, its efficacy in BM&T has been mixed. Oral or
parenteral ketorolac (study dose 1 mg/kg; current recommended dose 0.5 mg/kg) and nasal fentanyl (2 mg/kg) have
been shown to reduce pain scores, emergence agitation, or
both.9,11,12 One study measuring fentanyl serum concentrations showed rapid uptake when the agent was given nasally with decreasing concentrations by 30 minutes after
administration.12 Nasal dexmedetomidine (1 to 2 mg/kg) has
also been studied but, at the higher dose, resulted in prolonged postanesthesia care unit discharge times.13
There is also a role for regional anesthesia in BM&T.
Blockade of the auricular branch of the vagus nerve (nerve
of Arnold) on the posterior surface of the tragus (Figure 2)
with 0.2 mL of plain 0.25% bupivacaine is as effective as
2 mg/mL nasal fentanyl.14
Interestingly, intravenous access for BM&T has been shown
to prolong postoperative recovery and discharge times, increase
pain scores, and result in lower parental satisfaction.15
Tonsillectomy
Providing comfort in children after tonsillectomy can be
challenging, particularly in the child with sleep disordered
breathing. Up to 3.9% of tonsillectomy patients will require
Figure 1. The Faces Pain Scale-Revised. From Hicks et al.,8 Faces Pain Scale-Revised (FPS-R). www.iasp-pain.org/fpsr. Copyright r 2001, International
Association for the Study of Pains. Reproduced with permission.
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
44
Birmingham
In the evaluation of opioid studies in
tonsillectomy patients, it is worthwhile to note
whether the surgical indication is recurrent
tonsillitis versus obstructive sleep apnea.
Figure 2. Nerve of Arnold block. Using a 30-gauge needle, 0.2 mL of 0.25%
plain bupivacaine is injected into the posterior surface of the tragus.
readmission to the hospital with pain, dehydration, fever,
bleeding, or a combination of these complications,16
with some returning to the operating room for control of
bleeding. These concerns limit, although do not eliminate,
the use of perioperative NSAIDs for pain management. Ketorolac and more recently available intravenous ibuprofen
are parenteral options in addition to oral NSAIDs (Table 2).
A metaanalysis and systematic review reported conflicting
conclusions about whether NSAIDs should be used in tonsillectomy patients (Supplemental Digital Content 1, http://
links.lww.com/ASA/A542).17,18 Current clinical practice
guidelines for otolaryngology recommend that ketorolac be
avoided in the tonsillectomy patient.16
Intravenous acetaminophen has been more commonly
used in the United States since its Food and Drug Administration approval for use in children more than 2 years of
age. If acetaminophen is given by any route, it should be
factored into subsequent postoperative dosing ordered by
the surgeon (Table 2).
Opioids are frequently used during or after surgery, or
both, in the child undergoing tonsillectomy. In the evaluation
of opioid studies in tonsillectomy patients, it is worthwhile
to note whether the surgical indication is recurrent tonsillitis
versus obstructive sleep apnea (sleep disordered breathing).
The child with sleep disordered breathing may have altered
sensitivity to opioids.19 Dosing should be adjusted accordingly. Patients with more severe sleep disordered breathing
may need to be admitted postoperatively for monitoring,
sometimes in an intensive care unit setting.
Single-dose dexamethasone in tonsillectomy patients
has been shown to be safe and effective in decreasing
postoperative nausea and vomiting.16,20–22 It also has an
analgesic benefit, as indicated by earlier return to oral intake and decreased postoperative analgesic requirements.
Doses as low as 0.0625 mg/kg have been shown to be as
effective as 1 mg/kg in this regard.23
Dexmedetomidine at doses of 0.75 to 4 mg/kg with or
without an infusion (0.7 mg/kg/h) have been studied
in tonsillectomy patients.24–26 While prolonging the
opioid-free interval, decreasing emergence agitation
postoperatively, or both, the higher doses studied also
prolonged postanesthesia care unit stay.
Use of N-methyl-D-aspartate receptor antagonists such
as ketamine, magnesium, and dextromethorphan in tonsillectomy patients has been studied with little benefit
shown versus standard opioid administration.27,28 Additional studies may better define a role for these alternatives
in the tonsillectomy patient.
Local anesthetic infiltration of the tonsillar bed is reported by 51.4% of surgeons29 but, interestingly, was not
shown to be of benefit in a recent systematic review.30
The anesthesiologist can also contribute to the postoperative or postdischarge safety of these patients by directing pain management away from the use of codeine.
Codeine’s conversion to its active metabolite, morphine,
can be influenced by genetic variation in the cytochrome
CYP2D6 metabolic pathway. A ‘‘slow’’ metabolizer may
have lower concentrations of morphine and possible ‘‘resistance’’ to a given dose, whereas the ‘‘ultrarapid’’ metabolizer may have higher concentrations. Postoperative
respiratory depression and arrest have been reported with
standard (0.5 to 1 mg/kg) doses of codeine in posttonsillectomy patients.31,32 Codeine is being removed from
pediatric hospital formularies and its use discouraged in
the postoperative tonsillectomy patient for this reason.
Inguinal Hernia Repair
Inguinal hernia repair is among the most common pediatric surgical procedures in infants and children, particularly in the former preterm infant. It is an ideal procedure
for the use of single-injection caudal epidural analgesia,
which can provide excellent perioperative pain control
while minimizing or eliminating the use of opioids (Supplemental Digital Content 2, http://links.lww.com/ASA/
A543, Supplemental Digital Content 3, http://links.
lww.com/ASA/A544). Recent analyses demonstrate the
overwhelming safety of caudal epidural anesthesia33 and
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
45
Acute Pain Management in Infants and Children
Table 2. NSAID General Dosing Guidelines (Age 4 1 year)
NSAID
Route
Dose (mg/kg)
Dose Interval (h)
Max. Dose (mg)
Daily Maximum/Comments
Ketorolac
IV
0.5
6
30 (15 if o 50 kg)
For r5 d
Ibuprofen
PO
5–10
6
400
40 mg/kg (1,200 mg)
Naproxen
PO
5–7.5
8–12
200
10–15 mg/kg (600 mg)
Acetaminophen
PO
10–15
4–6
1,000
75–90 mg/kg (3,000–4,000 mg)
Acetaminophen
PR
40 load, then 20
6
1,000
Acetaminophen
IV
10–15
4–6
10,000
75 mg/kg (4,000 mg)
IV ¼ intravenous; NSAID ¼ nonsteroidal antiinflammatory drug; PO ¼ oral; PR ¼ rectal.
alternatives such as transversus abdominis plane blockade,34 which can be performed under ultrasound guidance
to aid in localization of nerve roots and tissue planes to
optimize blockade.
In the former preterm infant, spinal anesthesia is an alternative to general anesthesia. One of the potential advantages of a primary regional technique, more commonly
subarachnoid blockade but potentially also caudal blockade, is avoidance of general anesthesia and any potential
long-term cognitive effects on the developing central
nervous system. Ongoing prospective trials, such as the
General Anesthesia versus Spinal (GAS) study and the Pediatric Anesthesia and Neurodevelopment Assessment
(PANDA) study, are attempting to clarify animal data and
some retrospective human studies that suggest deleterious
central nervous system effects from exposure to general
anesthesia in early life.
In addition, despite the high initial success rate for spinal
block placement at experienced institutions, more than
20% of patients may require supplemental anesthesia at
some time during surgery.35 Other authors have found no
difference in the incidence of postoperative apnea, regardless of the technique.36 Whether the former preterm
infant undergoes general or regional anesthesia for hernia
repair, the same criteria should be used for postoperative
monitoring for apnea of prematurity.
Neuraxial and peripheral regional blocks, whether single-injection or catheter techniques, are routinely performed during general anesthesia in children. A recent
report from a large multisite registry of regional anesthesia, the Pediatric Regional Anesthesia Network
(PRAN), examined the safety of blocks done during general anesthesia. Their analysis of more than 50,000 blocks
demonstrated that placement of neuraxial and peripheral
regional anesthesia blocks in pediatric patients under
general anesthesia is as safe as placement in sedated and
awake children, and that it should remain the prevailing
standard of care (Supplemental Digital Content 4, http://
links.lww.com/ASA/A545).37
Intravenous supplementation can include acetaminophen and NSAIDs. The pharmacokinetics of ketorolac
has been studied in infants and children, leading to a
dosing recommendation of 0.5 mg/kg in the younger
patient.38,39
One must be aware of the recommended upper limits of
local anesthetic dosing (2.5 to 3 mg/kg for bupivacaine/
ropivacaine) to avoid local anesthetic systemic toxicity.
Because of lower protein binding and reduced clearance in
infancy, the local anesthetic dose should be reduced by 30
to 50% in the first 4 to 6 months of life.
The pharmacokinetics of ketorolac has been
studied in infants and children, leading to a
dosing recommendation of 0.5 mg/kg
in the younger patient.
One should also have prompt access to Intralipid 20%
in the event of systemic toxicity and be prepared to use it in
the resuscitation of an infant or child (Table 3).40 Although
propofol is compounded in a 10% lipid emulsion, it should
not be used for resuscitation from local anesthetic toxicity.
Table 3. Treatment of Local Anesthetic Systemic
Toxicity
20% Lipid Emulsion
Dosing Recommendations
Initial bolus
1.5 mL/kg over 1 min
Repeat bolus
1.5 mL/kg once or twice for persistent
cardiovascular collapse
Maintenance
infusion
0.25 mL/kg/min for Z10 min after attaining
circulatory stability
Double to 0.5 mL/kg/min if blood pressure
remains low
Recommended
upper limit
Approximately 10–12 mL/kg over first 30 min
Derived from Neal JM, Bernards CM, Butterworth JF IV, Di Gregorio G, Drasner
K, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Reg Anesth
Pain Med 2010; 35:152–61, table 4.40
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
46
Birmingham
Table 4. Epidural Dosing Guidelines
Local Anesthetic
Additives
0.1% bupivacaine or
ropivacaine
Clonidine (1 mg/mL)
or
fentanyl (2 mg/mL)
Continuous Infusion
(mL/kg/h)
Bolus Dose
(mL)
Lockout (min)
0.1–0.2
0.5–2
15–30
Posterior Spinal Fusion for Idiopathic Scoliosis
The adolescent undergoing posterior spinal fusion can benefit from multimodal analgesic techniques to optimize postoperative analgesia. The analgesic plan can start before
surgery with administration of the voltage-dependent calcium channel blockers pregabalin or gabapentin, which have
analgesic and sometimes anxiolytic properties. These drugs
can be effective in the management of centrally acting pain,
which may be a component of the postoperative pain in
these patients.41,42 Pregabalin and gabapentin have been
shown to reduce pain scores and opioid consumption in the
early postoperative phase after pediatric spinal fusion.41
Surgical access to the epidural space allows for placement of an epidural catheter under direct visualization after completion of instrumentation and before wound
closure. Upon awakening and surgical confirmation of the
patient’s motor function, a single bolus dose followed by a
continuous infusion of plain local anesthetic or with additives such as clonidine or an opioid is initiated using the
catheter. The most recent metaanalysis of randomized
controlled trials of epidural opioids demonstrated similar
analgesic outcomes between morphine, fentanyl, and sufentanil with a higher incidence of nausea or vomiting and
possibly pruritus with the more hydrophilic opioid morphine.43 In spinal fusion or other major orthopedic procedures (e.g., femoral osteotomy), a demand option can be
added to the epidural catheter. Both epidural patient-controlled analgesia (PCA)44 and epidural analgesia by nurse
or parent proxy45 have been safely used in children undergoing major surgery (Table 4).
Alternatively, a single dose of intrathecal morphine (2 to
15 mg/kg) can be injected by the anesthesiologist before the
incision or by the surgeon under direct vision before closing the incision. This measure has been shown to result in
lower pain scores and opioid consumption in the first 24
hours after surgery.46,47
Intravenous PCA is widely utilized in children and is a
routine component of postoperative pain management for
spinal fusion and many other pediatric surgical procedures
(Table 5). The opioid ‘‘loading dose’’ is frequently administered intraoperatively, and parameters are adjusted
postoperatively as needed to optimize pain relief. Children
as young as 5 to 6 years of age will self-activate their PCA
button. Although safety concerns have been raised about
parent or caregiver ‘‘PCA by proxy’’ and continuous opioid
1 h Limit
(Cont þ Bolus)
(mg/kg/h)
0.4 (lumbar catheter)
0.3 (thoracic catheter)
0.2 (age o 4–6 mo)
infusions, both are utilized and can be done safely (Supplemental Digital Content 5, http://links.lww.com/ASA/
A546).48–50
The use of nonopioid analgesics such as ketorolac
should include input from the surgeon because of concerns
about potential bleeding in the early postoperative period
and surgical nonunion in the months after surgery. The
likelihood of nonunion is lower in the pediatric versus the
adult spinal fusion population. Intravenous acetaminophen is a useful addition in this and other patient populations.
Children as young as 5 to 6 years of age will
self-activate their PCA button.
Tramadol (1 to 2 mg/kg), a serotonin and norepinephrine uptake inhibitor with weak mu-opioid receptor activity, can be a useful transition agent from stronger
intravenous opioids to oral analgesics or an alternative to
the use of oxycodone or hydrocodone.51
MANAGEMENT OF SIDE EFFECTS
An important component of postoperative pain control is
management of related side effects. Nausea and vomiting
are the most common concerns. Risk factors for postoperative vomiting in children include a family history of
postoperative nausea and vomiting, age 3 years or higher,
surgical time 30 minutes or more, and surgical subpopulations such as strabismus surgery. The commonly
used combination therapy of dexamethasone and ondansetron has been shown to be effective in children.52 Lowdose naloxone by intravenous infusion (0.25 to 1 mg/kg/
h)53,54 is effective in the management of opioid-related side
effects such as nausea and vomiting or pruritus. Naloxone
also has a site-specific effect and can be administered orally
or by a nasogastric tube (10 to 20 mg/kg) for opioid-related
ileus. Metaanalyses of acupuncture and acustimulation
have demonstrated their effectiveness in reducing postoperative vomiting in children.55,56 Leg weakness from
continuous epidural infusion can be avoided or minimized
by using lower infusion rates or lower local anesthetic
Copyright r 2015 American Society of Anesthesiologists. All rights reserved.
47
Acute Pain Management in Infants and Children
Table 5. Intravenous PCA Parameters
Opioid
Bolus Dose
Lockout (min) (default 8 min)
Continuous Infusion
1 h Limit
Maximum 1 h Limit
Morphine
0.01–0.02 mg/kg
5–15
0.01–0.02 mg/kg/h
0.2 mg/kg
15 mg
Fentanyl
0.2–0.4 mg/kg
5–15
0.2–0.4 mg/kg/h
4 mg/kg
300 mg
2–3 mg/kg
5–15
2–3 mg/kg/h
30–40 mg/kg
3,000 mg
Hydromorphone
PCA ¼ patient-controlled analgesia.
concentrations, or by substitution of ropivacaine for bupivacaine.
Be aware also of the use of herbal medications in children and their potential impact on pain medication and
postoperative side effects, such as bleeding, hypoglycemia,
and prolonged sedation.57,58
CONCLUSIONS
A perioperative evidence-based analgesic strategy combined with daily rounds by an anesthesiologist-directed
pain management service can optimize pain control, avoid
or minimize undesired side effects, and contribute toward
enhanced recovery after surgery. As anesthesiologists move
forward in an evolving health-care environment, patient
and parental satisfaction measures of pain management
and minimization of readmission after discharge will be
important metrics in hospital ratings and reimbursement.
Anesthesiologists are uniquely positioned to provide leadership and value in optimizing such quality outcome
measures.
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