Pediatric Pain ManagementPediatric Pain Management

introductionintroduction

• 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 PerceptionNeonatal 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

• 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)

Neonatal Pain PerceptionNeonatal Pain Perception

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.

• 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

Neonatal Pain PerceptionNeonatal Pain Perception

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.

• 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

Neonatal Pain PerceptionNeonatal Pain Perception

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 Developmental PharmacologyPharmacology

• 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 Pharmacological InterventionsInterventions

• 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.

ACETAMINOPHEN & NONSTEROIDALANTIINFLAMMATORY DRUGS

Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14

Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14

• 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 & NONSTEROIDALANTIINFLAMMATORY 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

ACETAMINOPHEN & NONSTEROIDALANTIINFLAMMATORY DRUGS

Berde& Sethna. N Engl J Med, 2002.Vol. 347, No. 14

• 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

ACETAMINOPHEN & NONSTEROIDALANTIINFLAMMATORY DRUGS

Verghese & Hannallah. Journal of Pain Research 2010:3

• 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

OPIOIDS

Verghese & Hannallah. Journal of Pain Research 2010:3

• 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.

OPIOIDS

Verghese & Hannallah. Journal of Pain Research 2010:3

• 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.

OPIOIDS

Verghese & Hannallah. Journal of Pain Research 2010:3

• Morphine infusions between 10-30mg/kg/h provide adequate analgesia with an acceptable level of side-effects when administered with the appropriate level of monitoring.

• Clearance:o term infants >1mo old = children from 1-17yr oldo neonates aged 1–7 days= 1/3 of older infants,

elimination half-life approximately 1.7 times longer

OPIOIDS

P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95: 59–68

• 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 logisticsand regular monitoring of vital signs.

OPIOIDS

P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95: 59–68

• 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.

OPIOIDS

P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95: 59–68

• 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

OPIOIDS

P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95: 59–68

• 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

OPIOIDS

P.-A. Lo¨nnqvist & N. S. Morton. Br J Anaesth 2005; 95: 59–68

• 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

OPIOIDS

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 ChildrenChronic 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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