Recent developments in the pharmacological management of pain in children

Current Opinion in Anaesthesiology

Volumn 19, Issue 3, 2006, Pages 285-292

  Anderson, Brian J ^a   Palmer, Greta M ^b  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b ROYAL CHILDREN'S HOSPITAL   (Australia)

Author keywords

Analgesia; Neonates; Pain; Pediatrics; Pharmacokinetics

Indexed keywords

ACETYLSALICYLIC ACID; ALFENTANIL; ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; ANALGESIC AGENT; CLONIDINE; CODEINE; CYCLOOXYGENASE 2 INHIBITOR; CYSTEINE; DRUG METABOLITE; FENTANYL; IBUPROFEN; INDOMETACIN; KETAMINE; KETOROLAC; LOCAL ANESTHETIC AGENT; MANNITOL; MIDAZOLAM; MORPHINE; MORPHINE 3 GLUCURONIDE; MORPHINE 6 GLUCURONIDE; NARCOTIC ANALGESIC AGENT; NITROXYPARACETAMOL; NONSTEROID ANTIINFLAMMATORY AGENT; NORKETAMINE; OPIATE; PARACETAMOL; PARACETAMOL DERIVATIVE; SODIUM DIHYDROGEN PHOSPHATE; TRAMADOL; UNCLASSIFIED DRUG;

ACCURACY; AMNESIA; ANALGESIA; AROUSAL; ASTHMA; BEHAVIOR THERAPY; BLADDER SPASM; BLEEDING TIME; BRAIN DEVELOPMENT; BRAIN HEMORRHAGE; BRAIN PERFUSION; CHILD CARE; CHRONIC PAIN; COGNITIVE THERAPY; CONSTIPATION; CONTACT DERMATITIS; DISEASE EXACERBATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG POTENCY; DRUG SAFETY; DRUG USE; GLOMERULUS FILTRATION RATE; HUMAN; HYPNOSIS; HYPOTENSION; INJECTION SITE PAIN; LICENSING; LIVER INJURY; MUSCLE SPASM; NAUSEA; PACIFIER; PAIN; PATENT DUCTUS ARTERIOSUS; PERINATAL DEVELOPMENT; PHARMACOGENOMICS; POSTOPERATIVE PAIN; PREMATURITY; PRIORITY JOURNAL; PRURITUS; RESPIRATION DEPRESSION; RESPIRATORY TRACT DISEASE; REVIEW; RISK ASSESSMENT; SCIENCE; SIDE EFFECT; SUPPLEMENTATION; TREATMENT OUTCOME; VEIN PUNCTURE; VOMITING; WITHDRAWAL SYNDROME;

ADOLESCENT; ANALGESICS; CHILD; CHILD, PRESCHOOL; HUMANS; INFANT; INFANT, NEWBORN; PAIN;

EID: 33744993620     PISSN: 09527907     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.aco.0000192802.33291.6f     Document Type: Review

References (90)

1. Lago P, Guadagni A, Merazzi D, et al. Pain management in the neonatal intensive care unit: a national survey in Italy. Paediatr Anaesth 2005; 15:925-931.
2. Walker SM. Management of procedural pain in NICUs remains problematic. Paediatr Anaesth 2005; 15:909-912. This editorial reviews poor management of neonatal procedural pain in neonatal intensive care units. Recognition of the presence of pain, assessment of pain severity and evaluation of the effectiveness of interventions remain poor and are barriers to better management.
3. Anseloni VC, Ren K, Dubner R, et al. A brainstem substrate for analgesia elicited by intraoral sucrose. Neuroscience 2005; 133:231-243. Intraoral sucrose activates neurons in the periaqueductal gray and nucleus raphe magnus - two key brainstem sites critically involved in descending pain modulation.
4. Kracke GR, Uthoff KA, Tobias JD. Sugar solution analgesia: the effects of glucose on expressed mu opioid receptors. Anesth Analg 2005; 101:64-68. Further evidence that glucose does act directly on the mu receptor, but rather indirectly through release of endogenous opioids.
5. Mitchell A, Stevens B, Mungan N, et al. Analgesic effects of oral sucrose and pacifier during eye examinations for retinopathy of prematurity. Pain Manag Nurs 2004; 5:160-168.
6. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2004 (CD001069).
7. Allegaert K, Van der Marel CD, Debeer A, et al. Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age. Arch Dis Child Fetal Neonatal Ed 2004; 89:F25-F28.
8. Anderson BJ, Pons G, Autret-Leca E, et al. Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis. Paediatr Anaesth 2005; 15:282-292. A population pharamacokinetic analysis of propacetamol (acetaminophen) in children postconception age 27 weeks to 14 years. The authors describe the maturation of clearance with age (87% of mature value by 1 year of age) that allows prediction of age-appropriate dosing schedules.
9. Wurthwein G, Koling S, Reich A, et al. Pharmacokinetics of intravenous paracetamol in children and adolescents under major surgery. Eur J Clin Pharmacol 2005; 60:883-888. Similar paracetamol pharmacokinetics parameters were estimated in older children, but very young children were not investigated.
10. Anderson BJ, Woollard GA, Holford NH. Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. Eur J Clin Pharmacol 2001; 57:559-569.
11. Allegaert K, Anderson BJ, Naulaers G, et al. Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates. Eur J Clin Pharmacol 2004; 60:191-197.
12. Murat I, Baujard C, Foussat C, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair. Paediatr Anaesth 2005; 15:663-670. This study confirms less pain at injection site with intravenous paracetamol compared with propacetamol in children. The onset of analgesia is consistent with those postulated by earlier work examining cerebrospinal fluid and pharmacokinetics-pharmacodynamic relationships in children given oral formulations.
13. van der Marel CD, Anderson BJ, Pluim MA, et al. Acetaminophen in cerebrospinal fluid in children. Eur J Clin Pharmacol 2003; 59:297-302.
14. Allegaert K, Verbesselt R, Devlieger H, et al. Cerebrospinal fluid pharmacokinetics of paracetamol after intravenous propacetamol in a former preterm infant. Br J Clin Pharmacol 2004; 57:224-225.
15. Moore PK, Marshall M. Nitric oxide releasing acetaminophen (nitroacetaminophen). Dig Liver Dis 2003; 35 (Suppl 2):S49-S60.
16. Gaitan G, Ahuir FJ, Herrero JF. Enhancement of fentanyl antinociception by subeffective doses of nitroparacetamol (NCX-701) in acute nociception and in carrageenan-induced monoarthritis. Life Sci 2005; 77:85-95. Animal work demonstrating that fentanyl antinociception can be potentiated with subanalgesic doses of nitroparacetamol without the development of acute tolerance.
17. Futter LE, al-Swayeh OA, Moore PK. A comparison of the effect of nitroparacetamol and paracetamol on liver injury. Br J Pharmacol 2001; 132:10-12.
18. Wallace JL. Acetaminophen hepatotoxicity: NO to the rescue. Br J Pharmacol 2004; 143:1-2.
19. Fiorucci S, Antonelli E, Distrutti E, et al. Liver delivery of NO by NCX-1000 protects against acute liver failure and mitochondrial dysfunction induced by APAP in mice. Br J Pharmacol 2004; 143:33-42.
20. Aranda JV, Varvarigou A, Beharry K, et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr 1997; 86:289-293.
21. Van Overmeire B, Touw D, Schepens PJ, et al. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther 2001; 70:336-343.
22. Scott CS, Retsch-Bogart GZ, Kustra RP, et al. The pharmacokinetics of ibuprofen suspension, chewable tablets, and tablets in children with cystic fibrosis. J Pediatr 1999; 134:58-63.
23. Smyth JM, Collier PS, Darwish M, et al. Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study. Br J Clin Pharmacol 2004; 58:249-258.
24. Topic E, Stefanovic M, Samardzija M. Association between the CYP2C9 polymorphism and the drug metabolism phenotype. Clin Chem Lab Med 2004; 42:72-78.
25. Garcia-Martin E, Martinez C, Tabares B, et al. Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin Pharmacol Ther 2004; 76:119-127.
26. Gregoire N, Gualano V, Geneteau A, et al. Population pharmacokinetics of ibuprofen enantiomers in very premature neonates. J Clin Pharmacol 2004; 44:1114-1124.
27. Jackson ID, Heidemann BH, Wilson J, et al. Double-blind, randomized, placebo-controlled trial comparing rofecoxib with dexketoprofen trometamol in surgical dentistry. Br J Anaesth 2004; 92:675-680.
28. Gaitan G, Herrero JF. Subanalgesic doses of dexketoprofen and HCT-2037 (nitrodexketoprofen) enhance fentanyl antinociception in monoarthritic rats. Pharmacol Biochem Behav 2005; 80:327-332.
29. Palmer GM. A teenager with severe asthma exacerbation following ibuprofen. Anaesth Intensive Care 2005; 33:261-265. Aspirin-induced asthma typically affects adults in their third decade of life. This case report and review suggests that the NSAIDs can precipitate asthma, particularly in teenagers with severe asthma and chronic rhinosinusitis or nasal polyps. Conversely, benefit is likely to be seen in younger children with mild episodic asthma.
30. Lesko SM. The safety of ibuprofen suspension in children. Int J Clin Pract Suppl 2003:50-53.
31. Allegaert K, Cossey V, Langhendries JP, et al. Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin in preterm infants during the first days of life. Biol Neonate 2004; 86:207-211.
32. Allegaert K, Cossey V, Debeer A, et al. The impact of ibuprofen on renal clearance in preterm infants is independent of the gestational age. Pediatr Nephrol 2005; 20:740-743.
33. Allegaert K, Anderson BJ, Cossey V, et al. Limited predictability of amikacin clearance in extreme premature neonates at birth. Br J Clin Pharmacol 2005; 61:39-48. This study and that in [32] quantify the effect of a NSAID (either aspirin or ibuprofen) on amikacin clearance (a measure of glomerular filtration rate) in the first day of life in premature neonates. Clearance was reduced by 22% and this effect appears independent of gestational age.
34. Gupta A, Daggett C, Drant S, et al. Prospective randomized trial of ketorolac after congenital heart surgery. J Cardiothorac Vasc Anesth 2004; 18:454-457.
35. Ment LR, Vohr BR, Makuch RW, et al. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr 2004; 145:832-834.
36. Cardwell M, Siviter G, Smith A. Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev 2005 (CD003591). The perioperative use of NSAIDs during tonsillectomy surgery continues to generate debate, despite frequent use in some units. This Cochrane Review concludes NSAIDs did not cause any increase in bleeding requiring a return to theatre. There was significantly less nausea and vomiting when NSAIDs were used compared with alternative analgesics, suggesting that the benefits outweigh the negative aspects of these drugs.
37. Naulaers G, Delanghe G, Allegaert K, et al. Ibuprofen and cerebral oxygenation and circulation. Arch Dis Child Fetal Neonatal Ed 2005; 90:F75-F76. It is encouraging to learn that no significant difference in the change in cerebral blood volume, change in cerebral blood flow or tissue oxygenation index was found between administration of ibuprofen or placebo in premature neonates. These are gross measures, however, and the effects on microcirculation remain unknown.
38. Sheeran PW, Rose JB, Fazi LM, et al. Rofecoxib administration to paediatric patients undergoing adenotonsillectomy. Paediatr Anaesth 2004; 14:579-583.
39. Joshi W, Connelly NR, Reuben SS, et al. An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management. Anesth Analg 2003; 97:35-38.
40. Jones SF, Power I. Editorial I: Postoperative NSAIDs and COX-2 inhibitors: cardiovascular risks and benefits. Br J Anaesth 2005; 95:281-284.
41. Krotz F, Schiele TM, Klauss V, et al. Selective COX-2 inhibitors and risk of myocardial infarction. J Vasc Res 2005; 42:312-324. The COX-2 inhibitors came under fire in 2005 owing to negative adult cardiovascular risks and benefits, culminating in the withdrawal of some of these drugs from the market. This editorial summarizes and reviews the adult literature. Studies of COX-2 inhibitors in children are limited and adult data may stymie further paediatric studies for some years.
42. Levin RI. Theriac found? Nitric oxide-aspirin and the search for the universal cure. J Am Coll Cardiol 2004; 44:642-643.
43. Fredriksson A, Archer T, Aim H, et al. Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration. Behav Brain Res 2004; 153:367-376.
44. Wang C, Sadovova N, Fu X, et al. The role of the N-methyl-D-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture. Neuroscience 2005; 132:967-977. Others have shaken beliefs about the benign nature of anesthesia in the neonate. This paper suggests that upregulation of an NMDA receptor subunit (NR1) promotes ketamine-induced apoptosis.
45. Soriano SG, Anand KJ, Rovnaghi CR, et al. Of mice and men: should we extrapolate rodent experimental data to the care of human neonates? Anesthesiology 2005; 102:866-868. A thoughtful editorial reviewing rodent data concerning ketamine-induced apoptosis and its applicability to humans.
46. Anand KJ, Soriano SG. Anesthetic agents and the immature brain: are these toxic or therapeutic? Anesthesiology 2004; 101:527-530.
47. Davidson A, Soriano S. Does anaesthesia harm the developing brain: evidence or speculation? Paediatr Anaesth 2004; 14:199-200.
48. Young C, Jevtovic-Todorovic V, Qin YQ, et al. Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol 2005; 146:189-197. Anesthetizing infant rats for 6 h with a combination of anesthetic drugs (midazolam, nitrous oxide, isoflurane) caused widespread apoptotic neurodegeneration in the developing brain, followed by lifelong cognitive deficits. The applicability of these experimental rodent findings to the clinical practice of pediatric anaesthesia is hotly debated. The effects of adequate nutrition, hypoxia, hypotension, dose and duration of exposure all modulate effects. This debate has generated international multicenter clinical studies to resolve the question.
49. Lin C, Durieux ME. Ketamine and kids: an update. Paediatr Anaesth 2005; 15:91-97. A timely review of ketamine pharmacokinetics, pharmacodynamics and therapeutics in children.
50. Becke K, Albrecht S, Schmitz B, et al. Intraoperative low-dose S-ketamine has no preventive effects on postoperative pain and morphine consumption after major urological surgery in children. Pediatr Anesth 2005; 15:484-490.
51. Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg 2004; 99:482-495.
52. Tsui BC, Davies D, Desai S, et al. Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with severe cancer pain from metastatic neuroblastoma. J Pediatr Hematol Oncol 2004; 26:678-680.
53. Umuroglu T, Eti Z, Ciftci H, et al. Analgesia for adenotonsillectomy in children: a comparison of morphine, ketamine and tramadol. Paediatr Anaesth 2004; 14:568-573.
54. Gunes Y, Secen M, Ozcengiz D, et al. Comparison of caudal ropivacaine, ropivacaine plus ketamine and ropivacaine plus tramadol administration for postoperative analgesia in children. Paediatr Anaesth 2004; 14:557-563.
55. Zwaveling J, Bubbers S, van Meurs AH, et al. Pharmacokinetics of rectal tramadol in postoperative paediatric patients. Br J Anaesth 2004; 93:224-227.
56. Allegaert K, Anderson BJ, Verbesselt R, et al. Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity. Br J Anaesth 2005; 95:231-239. The first description of tramadol pharmacokinetics in very young children with some age-related dosing suggestions for that cohort. Clearance maturation is rapid and reached 84% of the mature value by 44 weeks PCA. The validity of dosing recommendations is not yet tested. Some of tramadol's effect can be attributed to an active metabolite (O-demethyl tramadol, M1), but the authors were unable to map maturation of CYP2D6 activity.
57. van den Berg AA, Halliday E, Lule EK, et al. The effects of tramadol on post-operative nausea, vomiting and headache after ENT surgery: a placebo-controlled comparison with equipotent doses of nalbuphine and pethidine. Acta Anaesthesiol Scand 1999; 43:28-33.
58. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs 2000; 60:139-176.
59. Bozkurt P. Use of tramadol in children. Pediatric Anesthesia 2005; 15:1041-1047. A review of tramadol use in children suggesting that the drug has an effectiveness somewhere between NSAIDs and morphine, and that its use should be adopted more widely in children.
60. Anand KJ, Barton BA, McIntosh N, et al. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Pediatr Adolesc Med 1999; 153:331-338.
61. Anand KJ, Hall RW, Desai N, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet 2004; 363:1673-1682.
62. Hall RW, Kronsberg SS, Barton BA, et al. Morphine, hypotension, and adverse outcomes among preterm neonates: who's to blame? Secondary results from the NEOPAIN trial. Pediatrics 2005; 115:1351-1359. A secondary data analysis from the NEOPAIN trial that identified the clinical factors associated with hypotension and examined the contributions of morphine treatment or hypotension to severe intraventricular hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1-4) or death. Preemptive morphine infusions, additional morphine and lower gestational age were associated with hypotension among preterm neonates. Severe IVH, any IVH and death were associated with preexisting hypotension, but morphine therapy did not contribute to these outcomes. Morphine infusions, although they cause hypotension, can be used safely for most preterm neonates but should be used cautiously for 23-26-week neonates and those with preexisting hypotension.
63. Bouwmeester NJ, Anderson BJ, Tibboel D, et al. Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children. Br J Anaesth 2004; 92:208-217.
64. Anderson BJ, Meakin GH. Scaling for size: some implications for paediatric anaesthesia dosing. Paediatr Anaesth 2002; 12:205-219.
65. Peters JW, Anderson BJ, Simons SH, et al. Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 2005; 31:257-263. The effects of ECMO therapy on drug disposition are poorly quantified and effects variable. The authors used complex modelling techniques to demonstrate that morphine clearance is reduced in infants requiring ECMO, possibly reflecting severity of illness. Clearance maturation on ECMO is rapid and normalizes within 2 weeks. Initial morphine dosing may be guided by age and weight, but clearance and distribution volume changes (and their variability) during prolonged ECMO suggesting that morphine therapy should be subsequently guided by clinical monitoring.
66. Stamer UM, Bayerer B, Stuber F. Genetics and variability in opioid response. Eur J Pain 2005; 9:101-104. CYP2D6 genetic variability is known to be a factor in response variability and side-effect profile. There are other candidate genes involved in pain perception, pain processing and pain management such as opioid receptors and transporters, and other targets of pharmacotherapy are under investigation. This area of investigation will be of importance for future pain management.
67. Lotsch J, Skarke C, Liefhold J, et al. Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin Pharmacokinet 2004; 43:983-1013.
68. Ikeda K, Ide S, Han W, et al. How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci 2005; 26:311-317. Improved understanding of the relationships between gene polymorphisms and opiate sensitivities will enable more accurate prediction of the opiate sensitivity and opiate requirements in individual patients.
69. Bergendahl HT, Lonnqvist PA, Eksborg S, et al. Clonidine vs. midazolam as premedication in children undergoing adeno-tonsillectomy: a prospective, randomized, controlled clinical trial. Acta Anaesthesiol Scand 2004; 48:1292-1300.
70. Lonnqvist PA, Bergendahl HT, Eksborg S. Pharmacokinetics of clonidine after rectal administration in children. Anesthesiology 1994; 81:1097-1101.
71. Ivani G, Bergendahl HT, Lampugnani E, et al. Plasma levels of clonidine following epidural bolus injection in children. Acta Anaesthesiol Scand 1998; 42:306-311.
72. Eisenach JC, De Kock M, Klimscha W. Alpha(2)-adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984-1995). Anesthesiology 1996; 85:655-674.
73. Munoz R, Berry D. Dexmedetomidine: promising drug for pediatric sedation? Pediatr Crit Care Med 2005; 6:493-494. One of a number of articles (see references [74-77]) outlining dexmedetomidine's usefulness as a sedative. Analgesic potential is not yet reported.
74. Shukry M, Ramadhyani U. Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21-month old child. Paediatr Anaesth 2005; 15:241-242.
75. Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children. Pediatr Crit Care Med 2005; 6:435-439.
76. Nichols DP, Berkenbosch JW, Tobias JD. Rescue sedation with dexmedetomidine for diagnostic imaging: a preliminary report. Paediatr Anaesth 2005; 15:199-203.
77. Hammer GB, Philip BM, Schroeder AR, et al. Prolonged infusion of dexmedetomidine for sedation following tracheal resection. Paediatr Anaesth 2005; 15:616-620.
78. Finkel JC, Johnson YJ, Quezado ZM. The use of dexmedetomidine to facilitate acute discontinuation of opioids after cardiac transplantation in children. Crit Care Med 2005; 33:2110-2112.
79. Chrysostomou C, Zeballos T. Use of dexmedetomidine in a pediatric heart transplant patient. Pediatr Cardiol 2005 (Epub Aug 11).
80. Baddigam K, Russo P, Russo J, et al. Dexmedetomidine in the treatment of withdrawal syndromes in cardiothoracic surgery patients. J Intensive Care Med 2005; 20:118-123.
81. ••], and reviews problems associated with CRPS research in children and the need for further mechanistic study and clinical trials to help clarify which patients should receive which treatments, and in which sequence.
82. McCleane G. Pharmacological strategies in relieving neuropathic pain. Expert Opin Pharmacother 2004; 5:1299-1312.
83. Christie D, Wilson C. CBT in paediatric and adolescent health settings: a review of practice-based evidence. Pediatr Rehabil 2005; 8:241-247. CBT is a valuable tool for management of chronic pain in children, although improvement for many children with CRPS is achieved with a regime of active physical therapy, with or without CBT.
84. Plaghki L, Adriaensen H, Morlion B, et al. Systematic overview of the pharmacological management of postherpetic neuralgia: an evaluation of the clinical value of critically selected drug treatments based on efficacy and safety outcomes from randomized controlled studies. Dermatology 2004; 208:206-216.
85. Wilder RT, Berde CB, Wolohan M, et al. Reflex sympathetic dystrophy in children: clinical characteristics and follow-up of seventy patients. J Bone Joint Surg Am 1992; 74:910-919.
86. Lee BH, Scharff L, Sethna NF, et al. Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr 2002; 141:135-140.
87. Dadure C, Motais F, Ricard C, et al. Continuous peripheral nerve blocks at home for treatment of recurrent complex regional pain syndrome I in children. Anesthesiology 2005; 102:387-391. Controlled studies concerning chronic pain in children are few. This case series reports ambulatory continuous peripheral nerve block associated with an initial Bier block for CRPS I. Results are encouraging for this novel treatment. It allows complete pain relief, early mobilization and rapid return home, representing a psychological advantage for these children. Unfortunately, follow-up was limited.
88. Wiffen RJ, Edwards JE, Barden J, et al. Oral morphine for cancer pain. Cochrane Database Syst Rev 2003:4.
89. Zernikow B, Lindena G. Long-acting morphine for pain control in paediatric oncology. Med Pediatr Oncol 2001; 36:451-458.
90. Drake R, Longworth J, Collins JJ. Opioid rotation in children with cancer. J Palliat Med 2004; 7:419-422.