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Pediatric Pain Management
introduction
• Over 20 yr ago, a survey reported:
o 40% → pediatric surgical patients
experienced moderate or severe
postoperative pain
o 75% → insufficient analgesia
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95:
59–68
Neonatal Pain Perception
• structural components –
present at about 25wks gestation
• endogenous descending inhibitory pathways –
not fully developed until mid-infancy
• Opioid and other receptors are much more
widely distributed in fetuses and neonates.
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95:
59–68
Neonatal Pain Perception
• Study of reflexes as proved valuable in
observing the development of pain
mechanisms
• Mechanical skin stimulation → Spinal
reflex response – exaggerated in young
infants than adults
• May be because of incomplete
descending inhibitory connections
(corticospinal tract)
M Fitzgerald and R F Howard, “The Neurobiologic Basis of Pediatric
Pain”, Pain in Infants, Children and Adolescents,
2nd ed., N L Schecter, C B Berde and M Yaster (eds), Philadelphia:
Lippincott Williams & Wilkins, 2003, pp. 19–42.
Neonatal Pain Perception
• Only tells about how neonates& infants
process sensory input at the level of the
spinal cord
• Very little is known about the development
of functional connections at higher level in
the CNS, up to & including the cerebral
cortex
M Fitzgerald and R F Howard, “The Neurobiologic Basis of Pediatric
Pain”, Pain in Infants, Children and Adolescents,
2nd ed., N L Schecter, C B Berde and M Yaster (eds), Philadelphia:
Lippincott Williams & Wilkins, 2003, pp. 19–42.
Neonatal Pain Perception
• Somatosensory evoked potentials(SEPs) –
reliably elicited from 27wks PCA
• Maturation of SEP in human neonate occurs
according to PCA, independent of gestational
age at birth
M Fitzgerald and R F Howard, “The Neurobiologic Basis of Pediatric
Pain”, Pain in Infants, Children and Adolescents,
2nd ed., N L Schecter, C B Berde and M Yaster (eds), Philadelphia:
Lippincott Williams & Wilkins, 2003, pp. 19–42.
Developmental Pharmacology
• Neonates have reduced clearance (normalized to body
weight) of many drugs, as compared with
infants,children,& adults, largely because of the
incomplete maturation of their hepatic-enzyme systems.
• In contrast, children two to six years of age have
greater weight-normalized clearance than adults
for many drugs
→ More rapid drug clearance in children than in adults
may mean that more frequent drug dosing is required
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
Hechler&Zernikow. Deutsches Ärzteblatt International⏐Dtsch
Arztebl Int 2008; 105(28–29): 511–22
Pharmacological Interventions
ACETAMINOPHEN & NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
• Acetaminophen (paracetamol) - most widely used
antipyretic & mild analgesic for children
• plasma concentrations effective for fever control
analgesia - 10 to 20 μg/ml
• Rectal administration produces delayed & variable
uptake; single doses of 35-45 mg/kg generally
produce therapeutic plasma concentrations,with
prolonged clearance.
• Single rectal doses of 20 mg/kg produced safe
plasma concentrations in preterm neonates.
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
ACETAMINOPHEN & NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
• Systematic reviews have found few differences
among NSAIDs for analgesia in adults & little
advantage of injected over oral administration.
• Pharmacokinetic studies of several NSAIDs in
children found weight-normalized clearance and
volumes of distribution greater than those in adults,
but similar elimination half-lives.
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
ACETAMINOPHEN & NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
• Some studies comparing acetaminophen and
NSAIDs have found no difference in analgesic
effectiveness, whereas others have found better
analgesia with NSAIDs.
• Selective cyclooxygenase-2 (COX-2) inhibitors
-designed to retain the analgesic &antiinflammatory
effects of NSAIDs while reducing the risk of gastric
irritation & bleeding.
→few published studies of the pediatric use of
selective COX-2 inhibitors
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
ACETAMINOPHEN & NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
• analgesic effectiveness of acetaminophen+ibuprofen
or acetaminophen+rofecoxib
→addition of ibuprofen although not rofecoxib,
reduced the need for early analgesia following
tonsillectomy by 50% when compared to
acetaminophen alone
• 66 children, aged 3–11 years-of-age, tonsillectomy
→ single preoperative dose of rofecoxib (1 mg/kg)
resulted in less vomiting & lower 24-hour pain
scores in pediatric patients
Verghese & Hannallah. Journal of Pain Research 2010:3
OPIOIDS
• exercise caution when used in neonates & young infants
→ increased susceptibility to apnea because of the
relative imbalance of mu 1 (analgesia) to mu 2
(respiratory depression) receptors
• increased susceptibility to hypoventilation due to
decreased ventilatory response to hypoxia
& hypercapnea
Verghese & Hannallah. Journal of Pain Research 2010:3
OPIOIDS
• The respiratory-reflex responses to airway obstruction,
hypercapnia, & hypoxemia are immature at birth and
mature gradually over the first 2-3mos of life in both
preterm & term neonates.
• immature liver conjugation(glucuronidation, sulfation, &
oxidation) and immature renal filtration
→metabolism & excretion of opioids & their
metabolites are markedly decreased.
Verghese & Hannallah. Journal of Pain Research 2010:3
OPIOIDS
• higher concentration of the drug in the brain
because of an immature blood-brain barrier
• Newborns & young infants less than 4–6 months of
age have increased free fraction of the drug in the
blood because of decreased plasma protein (less
alpha-1 acid glycoprotein and albumin) binding.
Verghese & Hannallah. Journal of Pain Research 2010:3
OPIOIDS
• Morphine infusions between 10-30mg/kg/h provide
adequate analgesia with an acceptable level of sideeffects when administered with the appropriate
level of monitoring.
• Clearance:
o term infants >1mo old = children from 1-17yr old
o neonates aged 1–7 days= 1/3 of older infants,
elimination half-life approximately 1.7 times longer
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005;
95: 59–68
OPIOIDS
• Patient-controlled analgesia (PCA) is now widely
used in children as young as 5 yr and compares
favourably with continuous morphine infusion in the
older child.
• Pediatric opioid PCA requires special logistics
and regular monitoring of vital signs.
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005;
95: 59–68
OPIOIDS
• Tramadol, oxycodone, hydromorphone, &
buprenorphine - alternatives to morphine in the
postoperative period.
• Pethidine (meperidine) is not recommended in
children because of the adverse effects of its main
metabolite, norpethidine.
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005;
95: 59–68
OPIOIDS
• Fentanyl, sufentanil, alfentanil, and remifentanil
may have a role after major surgery & in intensive
care practice.
• In infants 3-6months of age, the analgesic effects of
morphine or fentanyl are similar to, and the
ventilatory depression is no greater than, that seen
in adults with similar plasma concentrations of
morphine or fentanyl
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005;
95: 59–68
OPIOIDS
• Remifentanil -titratable and has a context-insensitive
half time with extremely rapid recovery because
of esterase clearance, but transition to the postoperative
phase is difficult to manage & may be complicated by
acute tolerance.
– It may have a particular role in intraoperative stress
control and in neonatal anaesthesia
P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005;
95: 59–68
OPIOIDS
• Remifentanil seems to be safe &effective, but only
in ICU & in operating theatres in children
• few data are available in pediatric populations but experience
the suggested dose seems to be:
0.5-1 mcg/kg/min in the operating theatre
or 0.05-0.125 mcg/kg/min in the
postoperative period
Ivani, etal. MINERVA ANESTESIOL 2005;71:501-5
Hechler&Zernikow. Deutsches Ärzteblatt International⏐Dtsch
Arztebl Int 2008; 105(28–29): 511–22
Chronic Pain in Children
• Chronic pain can be a burden for children and families& can
impair social functioning & school attendance.
• Prolonged pain after amputation is not rare in children.
• Antidepressants & anticonvulsants are commonly used for
children with neuropathic pain, despite a lack of
controlled studies.
→can be effective in children, as they are
in adults, although they can have side effects
Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14
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