Analgesia and sedation during mechanical ventilation in neonates

Clinical Therapeutics

Volumn 27, Issue 6, 2005, Pages 877-899

  Aranda, J V ^a,e   Carlo, Waldemar ^b   Hummel, Pat ^c   Thomas, R ^a   Lehr, Vicki Tutag ^a   Anand, K J S ^d  

^a WAYNE STATE UNIVERSITY   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c LOYOLA UNIVERSITY MEDICAL CENTER   (United States)

^d UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^e CHILDREN'S HOSPITAL OF MICHIGAN   (United States)

Author keywords

Mechanical ventilation; Newborn; NSAIDs; Opiates; Pain

Indexed keywords

ANALGESIC AGENT; BENZODIAZEPINE DERIVATIVE; BUPRENORPHINE; CLONIDINE; DIAMORPHINE; FENTANYL; GABAPENTIN; HALOTHANE; HYPNOTIC SEDATIVE AGENT; IBUPROFEN; INDOMETACIN; KETAMINE; KETOBEMIDONE; MEMANTINE; METADRENALIN; METHADONE; MIDAZOLAM; MORPHINE; NALOXONE; NONSTEROID ANTIINFLAMMATORY AGENT; NORMETADRENALIN; OPIATE; PARACETAMOL; PLACEBO; SEDATIVE AGENT; SUFENTANIL;

ACIDOSIS; ANALGESIA; ARTIFICIAL VENTILATION; BRADYCARDIA; CARDIOVASCULAR MALFORMATION; CLINICAL TRIAL; CONFERENCE PAPER; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERANCE; DRUG URINE LEVEL; DYSPNEA; FETUS MORTALITY; GASTROINTESTINAL DISEASE; GASTROINTESTINAL MOTILITY; HUMAN; HYPOTENSION; KIDNEY DISEASE; LARYNX SPASM; LOGISTIC REGRESSION ANALYSIS; META ANALYSIS; MUSCLE RIGIDITY; NEWBORN; NEWBORN MORBIDITY; PAIN; PARALYTIC ILEUS; POSTOPERATIVE PAIN; PROSPECTIVE STUDY; RESPIRATION DEPRESSION; RESPIRATORY DISTRESS SYNDROME; SEDATION; SIDE EFFECT; STRESS; SYSTEMATIC REVIEW; THORAX DEFORMITY; TREATMENT OUTCOME; WITHDRAWAL SYNDROME;

EID: 27744559944     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2005.06.019     Document Type: Conference Paper

References (181)

1. Lee SK, McMillan DD, Ohlsson A, et al. Variations in practice and outcomes in the Canadian NICU network: 1996-1997. Pediatrics. 2000;106:1070-1079.
2. Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: Effects on the stress response [published correction appears in Lancet. 1987;1:234]. Lancet. 1987;1:62-66.
3. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Mett. 1987;317:1321-1329.
4. Anand KJ, Craig KD. New perspectives on the definition of pain. Pain. 1996;67:3-6.
5. Bolivar JM, Gerhardt T, Gonzalez A, et al. Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation. J Pediatr. 1995;127:767-773.
6. Kahn DJ, Richardson DK, Gray JE, et al. Variation among neonatal intensive care units in narcotic administration. Arch Pediatr Adolesc Med. 1998;152:844-851.
7. O'Brodovich HM, Mellins RB. Bronchopulmonary dysplasia. Unresolved neonatal acute lung injury. Am Rev Respir Dis. 1985;132:694-709.
8. Anand KJ. Clinical importance of pain and stress in preterm neonates. Biol Neonate. 1998;73:1-9.
9. . Anand KS. Relationships between stress responses and clinical outcome in newborns, infants, and children. Crit Care Med. 1993;21(Suppl 9):S358-S359.
10. Levene M. Pain relief and sedation during neonatal intensive care. Eur J Pediatr. 1995;154(Suppl 3):S22-S23.
11. Quinn MW, Otoo F, Rushforth JA, et al. Effect of morphine and pancuronium on the stress response in ventilated preterm infants. Early Hum Dev. 1992;30:241-248.
12. Quinn MW, Wild J, Dean HG et al. Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated preterm babies. Lancet. 1993:342:324-327.
13. Orsini AJ, Leef KH, Costarino A, et al. Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome, J Pediatr. 1996;129: 140-145.
14. Anand KJ, Barton BA, Mclntosh N, et al. Analgesia and sedation in preterm neonates who require ventilatory support: Results from the NOPAIN trial [published correction appears in Arch Pediatr Adolesc Med. 1999;153:895]. Arch Pediatr Adolesc Med. 1999;153:331 -338.
15. Barker DP, Rutter N. Stress, severity of illness, and outcome in ventilated preterm infants. Arch Dis Child fetal Neonatal Ed. 1996;75:F187-F190.
16. Evans DJ, MacGregor RJ, Dean HG, Levene MI Neonatal catecholamine levels and neurodevelopmental outcome: A cohort study. Arch Dis in Child Fetal Neonatal Ed. 2001;84: F49-F52.
17. Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992;326:1-9.
18. Graven SN, Bowen FW Jr, Brooten D, et al. The high-risk infant environment. Part 2. The role of caregiving and the social environment. J Perinatol. 1992;12:267-275.
19. Grauer TT. Environmental lighting, behavioral state, and hormonal response in the newborn. Sch Inq Nurs PiaCt. 1989;3:53-66.
20. Als H. Developmental care in the newborn intensive care unit. Curr Opin Pediatr. 1998;10:138-142.
21. Als H, Duffy FH, McAnulty GB, et al. Early experience alters brain function and structure. Pediatrics. 2004:113: 846-857.
22. Als H, Lawhon G, Dufly FH, et al. Individualized developmental care for the very low-birth-weight preterm infant. Medical and neurofunctional effects. JAMA. 1994;272: 853-858.
23. Ariagno RL, Thoman EB, Boeddiker MA, et al. Developmental care does not alter sleep and development of premature infants. Pediatrics. 1997;100:E9.
24. Field T, Goldson E. Pacifying effects of nonnutritive sucking on term and preterm neonates during heelstick procedures. Pediatrics. 1984:74: 1012-1015.
25. Gibbins S, Stevens B. Mechanisms of sucrose and non-nutritive sucking in procedural pain management in infants. Pain Res Manag. 2001;6:21-28.
26. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2004; 3:CD001069.
27. Stevens B, Johnston C, Franck L, et al. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. Nurs Res. 1999:48:35-43.
28. Johnston CC, Stevens B, Pinelli J, et al. Kangaroo care is effective in diminishing pain response in preterm neonates. Arch Pediatr Adolesc Med. 2003;157:1084-1088.
29. Ludington-Hoe SM, Swinth JY. Developmental aspects of kangaroo care. J Obstet Gynecol Neonatal Nurs. 1996:25:691-703.
30. Gray L, Watt L, Blass EM. Skin-to-skin contact is analgesic in healthy newborns. Pediatrics. 2000;105:e14.
31. Bohnhorst B, Heyne T, Peter CS, Poets CF. Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation. J Pediatr. 2001 ;138: 193-197.
32. Fohe K, Kropf S, Avenarius S. Skin-to-skin contact improves gas exchange in premature infants. J Perinatol. 2000:20:311-315.
33. Chang YJ, Anderson GC, Lin CH. Effects of prone and supine positions on sleep state and stress responses in mechanically ventilated preterm infants during the first postnatal week.J Adv Nurs. 2002;40: 161-169.
34. Grunau RE, Linhares MB, Holsti L, et al. Does prone or supine position influence pain responses in preterm infants at 32 weeks gestational age? Clin J Pain. 2004;20:76-82.
35. Whyte S, Birrell G, Wyllie J. Pre-medication before intubation in UK neonatal units. Arch Dis Child Fetal Neonatal Ed. 2000;82:F38-F41.
36. Yaster M. The dose response of fentanyl in neonatal anesthesia. Anesthesiology. 1987;66:433-435.
37. Hickey PR, Hansen DD, Wessel DL, et al. Blunting of stress responses in the pulmonary circulation of infants by fentanyl. Anesth Analg. 1985;64: 1137-1142.
38. Saarenmaa E, Huttunen P, Leppaluoto J, et al. Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: A randomized trial. J Pediatr. 1999;134:144-150.
39. Franck LS, Vilardi J, Durand D, Powers R. Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation. Am J Crit Care. 1998;7:364-369.
40. Arnold JH, Truog RD, Scavone JM, Fenton T. Changes in the pharmaco-dynamic response to fentanyl in neonates during continuous infusion. J Pediatr. 1991;119:639-643.
41. Arnold JH, Truog RD, Orav EJ, et al. Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. Anesthesiology. 1990;73:1136-1140.
42. Guinsburg R, Kopelman BI, Anand KJ, et al. Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates. J Pediatr. 1998;132:954-959.
43. Cordero L, Gardner DK, O'Shaughessy R. Analgesia versus sedation during Broviac catheter placement. Am J Perinatol. 1991;8:284-287.
44. Barrington KJ, Byrne PJ. Premedication for neonatal intubation. Am J Perinatol. 1998;15:213-216.
45. Collins C, Koren G, Crean P, et al. Fentanyl pharmacokinetics and hemodynamic effects in preterm infants during ligation of patent ductus arteriosus. Anesth Analg. 1985;64: 1078-1080.
46. Koehntop DE, Rodman JH, Brundage DM, et al. Pharmacokinetics of fen tanyl in neonates. Anesth Analg. 1986;65:227-232.
47. Gauntlett IS, Fisher DM, Hertzka RE, et al. Pharmacokinetics of fentanyl in neonatal humans and lambs: Effects of age. Anesthesiology. 1988; 69:683-687.
48. Roth B, Schlunder C, Houben F, et al. Analgesia and sedation in neonatal intensive care using fentanyl by continuous infusion. Dev Pharmacol Ther. 1991;17:121-127.
49. Goldstein RF, Brazy JE. Narcotic sedation stabilizes arterial blood pressure fluctuations in sick premature infants. J Perinatol. 1991;11:365-371.
50. Hamon I, Hascoet JM, Debbiche A, Vert P. Effects of fentanyl administration on general and cerebral haemodynamics in sick newborn infants. Acta Paediatr. 1996;85:361-365.
51. Katz R, Kelly HW. Pharmacokinetics of continuous infusions of fentanyl in critically ill children. Crit Care Med. 1993;21:995-1000.
52. MacGregor DA, Bauman LA. Chest wall rigidity during infusion of fentanyl in a two-month-old infant after heart surgery. J Clin Anesth. 1996;8: 251-254.
53. Fahnenstich H, Steffan J, Kau N, Bartmann P. Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants. Crit Care Med. 2000;28:836-839.
54. Muller P, Vogtmann C. Three cases with different presentation of fentanyl-induced muscle rigidity-a rare problem in intensive care of neonates. Am J Perinatol. 2000;17: 23-26.
55. Wells S, Williamson M, Hooker D. Fentanyl-induced chest wall rigidity in a neonate: A case report. Heart Lung .1994;23:196-198.
56. Das UG, Sasidharan P. Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 Case reports. Pediatrics. 2001;108:1012-1015.
57. Irazuzta J, Pascucci R, Perlman N, Wessel D. Effects of fentanyl admin istration on respiratory system compliance in infants. Crit Care Med. 1993;21:1001-1004.
58. Katz R, Kelly HW, Hsi A. Prospective study on the occurrence of withdrawal in critically ill children who receive fentanyl by continuous infusion. Crit Care Med. 1994;22:763-767.
59. Franck L, Vilardi J. Assessment and management of opioid withdrawal in ill neonates [published correction appears in Neonatal Netw. 1995;14: 83]. Neonatal Netw. 1995;14:39-48.
60. Caron E, Maguire DP. Current management of pain, sedation, and narcotic physical dependency of the infant on ECMO. J Perinatal Neonatal Nurs. 1990;4:63-74.
61. Lago P, Benini F, Agosto C, Zacchello F. Randomised controlled trial of low dose fentanyl infusion in pre-term infants with hyaline membrane disease. Arch Dis Child Fetal Neonatal Ed. 1998;79:F194-F197.
62. Menon C, Anand KJ, McIntosh N. Practical approach to analgesia and sedation in the neonatal intensive care unit. Semin Perinatol. 1998;22: 417-424.
63. Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347:1094-1103.
64. Bouwmeester NJ, Hop WC, van Dijk M, et al. Postoperative pain in the neonate: Age-related differences in morphine requirements and metabolism. Intensive Care Med. 2003;29: 2009-2015.
65. Bouwmeester NJ, Anand KJ, van Dijk M, et al. Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: A double-blind, randomized trial comparing the effects of continuous versus intermittent morphine. Br J Anaesth. 2001;87:390-399.
66. Dyke MP, Kohan R, Evans S. Morphine increases synchronous ventilation in preterm infants. J Paediatr Child Health. 1995;31:176-179.
67. Farrington EA, McGuinness GA, Johnson GF, et al. Continuous intravenous morphine infusion in post operative newborn infants. Am J Perinatol. 1993;10:84-87.
68. van Dijk M, Bouwmeester NJ, Duivenvoorden HJ, et al. Efficacy of continuous versus intermittent morphine administration after major surgery in 0-3-year-old infants: A double blind randomized controlled trial. Pain. 2002;98:305-313.
69. Wolf AR, Hughes D. Pain relief for infants undergoing abdominal surgery: Comparison of infusions of i.v. morphine and extradural bupivacaine. Br J Anaesth. 1993;70:10-16.
70. Wood CM, Rushforth JA, Hartley R, et al. Randomised double blind trial of morphine versus diamorphine for sedation of preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1998;79: F34-F39.
71. Simons SH, van Dijk M, van Lingen RA, et al. Routine morphine infusion in preterm newborns who received ventilatory support: A randomized controlled trial. JAMA. 2003;290:2419-2427.
72. Carbajal R, Lenclen R, Jugie M, et al. Morphine does not provide adequate analgesia for acute procedural pain in preterm neonates. Pediatrics. 2005;115:1494-1500.
73. Anand KJ, Hall RW, Desai NS, et al, for the NEOPAIN Trial Investigators Group. Effects of morphine analgesia in ventilated preterm neonates: Primary outcomes from the NEOPAIN randomised trial. Lancet. 2004;363: 1673-1682.
74. Barrett DA, Barker DP, Rutter N, et al. Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions. Br J Clin Pharmacol. 1996;41:531-537.
75. Bhat R, Abu-Harb M, Chari G, Gulati A. Morphine metabolism in acutely ill preterm newborn infants. J Pediatr. 1992;120:795-799.
76. Pezzati M, Bertini G, Chiti G, et al. Paralytic ileus in a mechanically ventilated preterm infant treated with fentanyl. Pediatr Med Chir 2001;23: 201 -202
77. . 77. MacGregor R, Evans D, Sugden D, et al. Outcome at 5-6 years of prematurely born children who received morphine as neonates. Arch Dis Child Fetal Neonatal Ed. 1998;79:F40-F43.
78. Bell SC, Ellis LJ. Use of fentanyl for sedation of mechanically ventilated neonates. Neonatal Netw. 1987;6:27-31.
79. Jacqz-Aigrain E, Daoud P, Burtin P, et al. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. Lancet. 1994;344:646-650.
80. Arya V, Ramji S. Midazolam sedation in mechanically ventilated newborns: A double blind randomized placebo controlled trial. Indian Pediatr. 2001;38:967-972.
81. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Sys Rev. 2003;1:CD002052.
82. Fowlie PW, Davis PG. Prophylactic indomethacin for preterm infants: A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2003;88:F464-F466.
83. van Overmeire B. The use of ibuprofen in neonates in the treatment of patent ductus arteriosus. Int J Clin Piact Suppl. 2003;135:23-27.
84. Lago P, Bettiol T, Salvadori S, et al. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: A randomised controlled trial. Eur J Pediatr. 2002;161:202-207.
85. van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000;343:674-681.
86. Thomas RL, Parker GC, van Overmeire B, Aranda JV. A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pedatr. 2005;164:135-140.
87. Varvarigou A, Bardin CL, Beharry K, et al. Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infancs. JAMA. 1996;275:539-544.
88. Aranda JV, Varvarigou A, Beharry K. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr. 1997;86:289-293.
89. Yaffe SJ, Friedman WF, Rogers D, et al. The disposition of indomethacin in preterm babies. J Pediatr. 1980; 97:1001-1006.
90. 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.
91. Gregoire N, Gualano V, Geneteau A, et al. Population pharmacokinetics of ibuprofen enantiomers in very premature neonates. J Clin Pharmacol. 2004;44:1114-1124.
92. van Overmeire B, Brus F, van Acker KJ, et al. Aspirin versus indomethacin treatment of patent ductus arteriosus in preterm infants with respiratory distress syndrome. Pediatr Res. 1995;38:886-891.
93. Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976;295:530-533.
94. Sakhalkar VS, Merchant RH. Therapy of symptomatic patent ductus arteriosus in preterms using mefenemic acid and indomethacin. Indian Pediatr. 1992;29:313-318.
95. Ng PC, So KW, Fok TF, et al. Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants. J Paediatr Child Health. 1997;33:324-328.
96. Perrott DA, Piira T, Goodenough B, Champion CD. Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever A meta-analysis. Arch Pediatr Adolesc Med. 2004;158:521-526.
97. Ng PC, So KW, Fok TF, et al. Fatal haemorrhagic gastritis associated with oral sulindac treatment for patent ductus arteriosus. Acta Paediatr. 1996;85:884-886.
98. Nahata MC. Pediatric drug formulations: Challenges and potential solutions. Ann Pharmacother. 1999; 33:247-249.
99. Berman W Jr, Whitman V, Marks KH, et al. Inadvertent overadministration of digoxin to low-birth-weight infants. J Pediatr. 1978;92: 1024-1025.
100. Dyer C. GMC clears doctors on accidental morphine overdose. BMJ. 1999;318:1167.
101. Conroy S. Extemporaneous (magistral) preparations of oral medicines for children in European hospitals. Acta Paediatr. 2003;92:408-410.
102. Lucas AJ. Improving medication safety in a neonatal intensive care unit. Am J Health Syst Pharm. 2004; 61:33-37.
103. Nieuwoudt CD. Dilution of intravenous medications for neonates. Am J Health Syst Pharm. 1995;52: 1320-1322.
104. Gershanik J, Boecler B, Ensley H, et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982;307:1384-1388.
105. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products. Pediatrics. 1985;76:635-643.
106. Wheless JW. Pediatric use of intravenous and intramuscular phenytoin: Lessons learned. J Child Neurol. 1998;13(Suppl 1):S11-S114.
107. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: Update (subject review). Pediatrics. 1997;99:268-278.
108. Maone TR, Mattes RD, Bernbaum JC, Beauchamp GK. A new method for delivering a taste without fluids to preterm and term infants. Dev Psychobiol. 1990;23:179-191.
109. Tatzer E, Schubert MT, Timischl W, Simbruner G. Discrimination of taste and preference for sweet in premature babies. Early Hum Dev. 1985;12:23-30.
110. Barr RG, Pantel MS, Young SN, et al. The response of crying new boms to sucrose: Is it a "sweetness" effect? Physiol Behav. 1999;66:409-417.
111. Abad F, Diaz NM, Domenech E, et al. Oral sweet solution reduces pain-related behaviour in preterm infants. Acta Paediatr. 1996;85:854-858.
112. Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": Absorptive mechanism or taste perception? Arch Dis Child Fetal Neonatal Ed. 1999;80: F146-F147.
113. Ramenghi LA, Griffith GC, Wood CM, Levene MI. Effect of non-sucrose sweet tasting solution on neonatal heel prick responses. Arch Dis Child Fetal Neonatal Ed. 1996; 74:F129-F131.
114. Bucher HU, Baumgartner R, Bucher N, et al. Artificial sweetener reduces nociceptive reaction in term newborn infants. Early Hum Dev. 2000; 59:51-60.
115. Dyke T, Kitembing RJ. Mothers' preference for the colour of oral medication for their children in Papua New Guinea. Trop Doct. 1996; 26:184-185.
116. Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of anti-epileptic drugs in paediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine and felbamate. Clin Pharmacokinet. 1995; 29:341-369.
117. Paut O, Camboulives J, Viard L, et al. Pharmacokinetics of transdermal fentanyl in the peri-operative period in young children. Anaesthesia. 2000;55:1202-1207.
118. Barrett DA, Rutter N. Transdermal delivery and the premature neonate. Crit Rev Ther Drug Carrier Sys. 1994; 11:1-30.
119. Barrett DA, Rutter N, Davis SS. An in vitro study of diamorphine permeation through premature human neonatal skin. Pharm Res. 1993;10: 583-587.
120. Larsson BA, Norman M, Bjerring P, et al. Regional variations in skin perfusion and skin thickness may contribute to varying efficacy of topical, local anaesthetics in neonates. Paediatr Anaesth. 1996;6:107-110.
121. McCulloch KM, Ji SA, RaJu TN. Skin blood flow changes during routine nursery procedures. Early Hum Dev. 1995;41:147-156.
122. Cohen SP, Dawson TC. Nebulized morphine as a treatment for dyspnea in a child with cystic fibrosis. Pediatrics. 2002;110:e38.
123. Laptook AR, O'Shea TM, Shan-karan S, Bhaskar B, for the NICHD Neonatal Network. Adverse neuro developmental outcomes among extremely low birth weight infants with a normal head ultrasound: Prevalence and antecedents. Pediatrics. 2005;115:673-680.
124. Evans WE, McLeod HL. Pharmaco-genomics-drug disposition, drug targets, and side effects. N Engl J Med. 2003;348:538-549.
125. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003; 348:529-537.
126. Bond C, LaForge KS, Tian M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: Possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998;95:9608-9613.
127. Zubieta JK, Heitzeg MM,Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain Stressor. Science. 2003;299:1240-1243.
128. Simons S, van der Werf M, van der Marel C. Pharmacogenetics of morphine in neonates and infants: Analyses of two single nucleotide polymorphisms. Pediatr Res. 2004;55: A1566. Abstract.
129. Wang D, Quillan JM, Winans K, et al. Single nucleotide polymorphisms in the human mu opioid receptor gene alter basal G protein coupling and calmodulin binding. J Biol Chem. 2001;276:34624-34630.
130. Liu JG, Prather PL. Chronic exposure to mu-opioid agonists pro duces constitutive activation of mu-opioid receptors in direct proportion to the efficacy of the agonist used for pretreatment. Mol Pharmacol. 2001;60:53-62.
131. Barnhart MD, Hubbell JA, Muir WW, et al. Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs. Am J Vet Res. 2000;61:24-28.
132. van Lingen RA, Deinum JT, Quak JM, et al. Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1999;80:F59-F63.
133. Jacqz-Aigrain E, Burtin P. Clinical pharmacokinetics of sedatives in neonates. Clin Pharmacokinet. 1996; 31:423-443.
134. Olkkola KT, Hamunen K, Maunuksela EL. Clinical pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children. Clin Pharmacokinet. 1995; 28:385-404.
135. Burtin P, Jacqz-Aigrain E, Girard P, et al. Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther. 1994;56:615-625.
136. Harte GJ, Gray PH, Lee TC, et al. Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates. J Paediatr Child Health. 1997; 33:335-338.
137. Lee TC, Charles BG, Harte GJ, et al. Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: Midazolam neonatal pharmacokinetics. Anesthesiology. 1999;90:451-457.
138. Swart EL, Zuideveld KP,de Jongh J, et al. Comparative population pharmacokinetics of lorazepam and midazolam during long-term continuous infusion in critically ill patients. Br J Clin Pharmacol. 2004;57: 135-145.
139. Anderson BJ, Woollard GA, Holford NH. A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children. Br J Clin Pharmacol. 2000;50:125-134.
140. Anderson BJ, Holford NH, Woollard GA, Chan PL. Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children. Br J Clin Pharmacol. 1998;46:237-243.
141. Robertson RC, Darsey E, Fortenberry JD, et al. Evaluation of an opiate-weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care Med. 2000;1:119-123.
142. Crain SM, Shen KF. Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/ dependence liability. Pain. 2000;84: 121-131.
143. Gan TJ, Ginsberg B, Glass PS, et al. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997;87:1075-1081.
144. Levine JD, Gordon NC, Taiwo YO, Coderre TJ. Potentiation of pentazocine analgesia by low-dose naloxone. J Clin Invest. 1988;82:1574-1577.
145. Lehmann KA, Reichling U, Wirtz R. lnfluence of naloxone on the post-operative analgesic and respiratory effects of buprenorphine. Eur J Clin Pharmacol. 1988;34:343-352.
146. Andersen S, Dickenson AH, Kohn M, et al. The opioid ketobemidone has a NMDA blocking effect. Pain. 1996;67:369-374.
147. Ebert B, Thorkildsen C, Andersen S, et al. Opioid analgesics as non-competitive N-methyl-D-aspartate (NMDA) antagonists. Biochem Pharmacol. 1998;56:553-559.
148. Gorman AL, Elliott KJ, Inturrisi CE. The d- and I-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett. 1997; 223:5-8.
149. Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999; 289:1048-1053.
150. Liu JG, Liao XP, Gong ZH, Qin BY. The difference between methadone and morphine in regulation of delta-opioid receptors underlies the antagonistic effect of methadone on morphine-mediated cellular actions. Eur J Pharmacol. 1999; 373:233-239.
151. Liu JG, Liao XP, Gong ZH, Qin BY. Methadone-induced desensitization of the delta-opioid receptor is mediated by uncoupling of receptor from G protein, Eur J Pharmacol. 1999;374:301-308.
152. Highfield DA, Grant S. Ng-nitro-L-arginine, an NOS inhibitor, reduces tolerance to morphine in the rat locus coeruleus. Synapse. 1998;29: 233-239.
153. Lue WM, Su MT, Lin WB, Tao PL. The role of nitric oxide in the development of morphine tolerance in rat hippocampal slices. Eur J Pharmacol. 1999;383:129-135.
154. Vaupel DB, Kimes AS, London ED. Nitric oxide synthase inhibitors. Preclinical studies of potential use for treatment of opioid withdrawal. Neuropsychopharmacology. 1995;13:315-322.
155. Singh VP, Jain NK, Kulkarni SK. Fluoxetine suppresses morphine tolerance and dependence: Modulation of NO-cGMP/DA/serotoninergic pathways. Methods Find Exp Clin Pharmacol. 2003;25:273-280.
156. Tobias JD, Deshpande JK, Gregory DF. Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. Intensive Care Med. 1994;20:504-507.
157. Lugo RA, MacLaren R, Cash J, et al. Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy. 2001;21: 1566-1573.
158. Williams PI, Sarginson RE, Ratcliffe JM. Use of methadone in the morphine-tolerant burned paediatric patient. Br J Anaesth. 1998;80: 92-95.
159. Tobias JD, Schleien CL, Haun SE. Methadone as treatment for iatrogenic narcotic dependency in pediatric intensive care unit patients. Crit Care Med. 1990;18:1292-1293.
160. Siddappa R, Fletcher JE, Heard AM, et al. Methadone dosage for prevention of opioid withdrawal in children. Paediatr Anaesth. 2003;13: 805-810.
161. Olkkola KT, Leijala MA, Maunuksela EL. Paediatric ventilatory effects of morphine and buprenorphine revisited. Paediatr Anaesth. 1995;5:303-305.
162. Hamunen K, Olkkola KT, Maunuksela EL. Comparison of the ventilatory effects of morphine and buprenorphine in children. Acta Anaesthesiol Scand. 1993;37:449-453.
163. Kayemba-Kay's S, Laclyde JP. Buprenorphine withdrawal syndrome in newborns: A report of 13 cases. Addition. 2003:98:1599-1604.
164. Marquet P, Chevrel J, Lavignasse P, et al. Buprenorphine withdrawal syndrome in a newborn. Clin Pharmacol Ther. 1997;62:569-571.
165. Herve F, Quenum S. Buprenorphine (Subutex) and neonatal withdrawal syndrome [in French]. Arch Pediatr. 1998;5:206-207.
166. Lacroix I, Berrebi A, Chaumerliac C, et al. Buprenorphine in pregnant opioid-dependent women: First results of a prospective study. Addiction. 2004;99:209-214.
167. McClain BC, Probst LA, Pinter E, Hartmannsgruber M. Intravenous clonidine use in a neonate experiencing opioid-induced myoclonus. Anesthesiology. 2001;95:549-550.
168. Hoder EL, Leckman JF, Ehrenkranz R, et al. Clonidine in neonatal narcotic-abstinence syndrome. N Entf J Meet. 1981:305: 1284.
169. Hoder EL, Leckman JF, Poulsen J, et al. Clonidine treatment of neonatal narcotic abstinence syndrome. Psychiatry Res. 1984;13:243-251.
170. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524-1534.
171. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology. 2002;59(Suppl 2): S14-S17.
172. Kumar P, Jain MK. Gabapentin in the management of pentazocine dependence: A potent analgesic-anticraving agent. J Assoc Physicians India. 2003;51:673-676.
173. Gustorff B, Kozek-Langenecker S, Kress HG. Gabapentin: The first preemptive anti-hyperalgesic for opioid withdrawal hyperalgesia? Anesthesiology. 2003;98:1520-1521.
174. Andrews N, Loomis S, Blake R, et al. Effect of gabapentin-like compounds on development and maintenance of morphine-induced conditioned place preference. Psychopharmacology (Berl). 2001;157:381-387.
175. Bisaga A, Comer SD, Ward AS, et al. The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans. Psychopharmacology (Bert). 2001;157:1-10.
176. Maldonado C, Cauli O, Rodriguez-Arias M, et al. Memantine presents different effects from MK-801 in motivational and physical signs of morphine withdrawal. Behav Brain Res. 2003;144:25-35.
177. Popik P, Kozela E. Clinically available NMDA antagonist, memantine, attenuates tolerance to analgesic effects of morphine in a mouse tail flick test. Pol J Pharmacol. 1999;51:223-231.
178. Unal CB, Owen MD, Millington WR. Cyclo(Gly-Cln) inhibits the cardiorespiratory depression produced by beta-endorphin and morphine. Brain Res. 1997;747:52-59.
179. Owen MD, Gurun S, Zaloga GP, Millington WR. Glycyl-L-glutamine [beta-endorphin-(30-31)] attenuates hemorrhagic hypotension in conscious rats. Am J Physiol. 1997; 273:R1598-R1606.
180. Simpson CW, Resch GE, Millington WR, Myers RD. Glycyl-L-glutamine injected centrally suppresses alcohol drinking in P rats. Alcohol. 1998; 16:101-107.
181. Unal CB, Owen MD, Millington WR. Beta-endorphin-induced cardiorespiratory depression is inhibited by glycyl-L-glutamine, a dipeptide derived from beta-endorphin processing. J Pharmacol Exp Ther. 1994;271:952-958.