Intrapulmonary drug administration in neonatal and paediatric critical care: A comprehensive review

European Respiratory Journal

Volumn 37, Issue 3, 2011, Pages 678-689

  De Luca, D ^a   Cogo, P ^b   Zecca, E ^c   Piastra, M ^d   Pietrini, D ^d   Tridente, A ^e   Conti, G ^d   Carnielli, V P ^a  

^a UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

^b UNIVERSITY OF PADOVA   (Italy)

^c Division of Neonatology   (Italy)

^d FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^e SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Critical care; Infant; Inhaled drug

Indexed keywords

ADRENALIN; ANTIINFECTIVE AGENT; ANTIINFLAMMATORY AGENT; ATROPINE; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BRONCHODILATING AGENT; BUDESONIDE; CLARA CELL SECRETORY PROTEIN; CROMOGLYCATE DISODIUM; DORNASE ALFA; ILOPROST; IPRATROPIUM BROMIDE; LIDOCAINE; LUNG SURFACTANT; MUCOLYTIC AGENT; NALOXONE; NITRIC OXIDE; NITROSO DERIVATIVE; O NITROSOETHANOL; PENTOXIFYLLINE; PHOSPHOLIPASE A2 INHIBITOR; PLACEBO; PROSTACYCLIN; SALBUTAMOL; SODIUM CHLORIDE; STEROID; TERBUTALINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASODILATOR AGENT; VASOPRESSIN;

ASTHMA; ATELECTASIS; BRONCHIOLITIS; CHILD; CONGENITAL HEART DISEASE; CONTINUOUS INFUSION; DRUG ADMINISTRATION ROUTE; DRUG EFFICACY; DRUG HALF LIFE; EVIDENCE BASED MEDICINE; HEART RIGHT LEFT SHUNT; HUMAN; HYPERGLYCEMIA; HYPERKALEMIA; IDIOPATHIC RESPIRATORY DISTRESS SYNDROME; INTENSIVE CARE; INTRAPULMONARY DRUG ADMINISTRATION; LUNG DYSPLASIA; MORTALITY; NEONATAL RESPIRATORY DISTRESS SYNDROME; NEWBORN INTENSIVE CARE; PATENT DUCTUS ARTERIOSUS; PREMATURITY; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RESPIRATORY FAILURE; REVIEW; TACHYCARDIA; TACHYPNEA; TREATMENT INDICATION; TREMOR;

ADMINISTRATION, INHALATION; ADRENERGIC BETA-2 RECEPTOR AGONISTS; BRONCHODILATOR AGENTS; CHILD; CHOLINERGIC ANTAGONISTS; CRITICAL CARE; EPINEPHRINE; EVIDENCE-BASED MEDICINE; GASES; HUMANS; INTENSIVE CARE, NEONATAL; NITRIC OXIDE; PROSTAGLANDINS I; RESPIRATORY SYSTEM; S-NITROSOTHIOLS; STEROIDS; SURFACE-ACTIVE AGENTS;

EID: 79953680731     PISSN: 09031936     EISSN: 13993003     Source Type: Journal    
DOI: 10.1183/09031936.00024910     Document Type: Review

References (163)

1. Biron A. Indications of aerosol therapy in pediatrics. Prog Med (Paris) 1951; 79: 603-607.
2. Darlow BA, Mogridge N, Horwood LJ, et al. Admission of all gestations to a regional neonatal unit versus controls: neonatal morbidity. J Paediatr Child Health 2009; 45: 181-186.
3. 2- agonists for recurrent wheeze in children under two years of age. Cochrane Database Syst Rev 2002; 3: CD002873.
4. Denis D, Fayon MJ, Berger P, et al. Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats. Pediatr Res 2001; 50: 515-519.
5. 2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest 2009; 135: 1186-1192.
6. Gadomski AM, Bhasale AL. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2006; 3: CD001266.
7. Gomez-Del Rio M, Gerhardt T, Hehre D, et al. Effect of a β-agonist nebulization on lung function in neonates with increased pulmonary resistance. Pediatr Pulmonol 1986; 2: 287-291.
8. Pantalitschka T, Poets CF. Inhaled drugs for the prevention and treatment of bronchopulmonary dysplasia. Pediatr Pulmonol 2006; 41: 703-708.
9. Ng GY, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev 2001; 3: CD003214.
10. Ballard J, Lugo RA, Salyer JW. A survey of albuterol administration practices in intubated patients in the neonatal intensive care unit. Respir Care 2002; 47: 31-38.
11. Panitch HB, Keklikian EN, Motley RA, et al. Effect of altering smooth muscle tone on maximal expiratory flows in patients with tracheomalacia. Pediatr Pulmonol 1990; 9: 170-176.
12. O'Hare FM, Molloy EJ. What is the best treatment for hyperkalaemia in a preterm infant? Arch Dis Child 2008; 93: 174-176.
13. Singh BS, Sadiq HF, Noguchi A, et al. Efficacy of albuterol inhalation in treatment of hyperkalaemia in premature neonates. J Pediatr 2002; 141: 16-20.
14. Vemgal P, Ohlsson A. Interventions for non-oliguric hyperkalaemia in preterm neonates. Cochrane Database Syst Rev 2007; 24: CD005257.
15. Osmond MH, Klassen TP. Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis. Acad Emerg Med 1995; 2: 651-656.
16. Lord J, Ducharme FM, Stamp RJ, et al. Cost effectiveness analysis of inhaled anticholinergics for acute childhood and adolescent asthma. BMJ 1999; 319: 1470-1471.
17. Goggin N, Macarthur C, Parkin PC. Randomized trial of the addition of ipratropium bromide to albuterol and corticosteroid therapy in children hospitalized because of an acute asthma exacerbation. Arch Pediatr Adolesc Med 2001; 155: 1329-1334.
18. Everard M, Bara A, Kurian M, et al. Anticholinergic drugs for wheeze in children under the age of two years. Cochrane Database Syst Rev 2005; 3: CD001279.
19. Browne GJ, Trieu L, Van Asperen P. Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma in children presenting to an emergency department. Crit Care Med 2002; 30: 448-453.
20. Lee H, Arnon S, Silverman M. Bronchodilator aerosol administered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed 1994; 70: F218-F222.
21. Fayon M, Tayara N, Germain C, et al. Efficacy and tolerance of high-dose inhaled ipratropium bromide vs. terbutaline in intubated premature human neonates. Neonatology 2007; 91: 167-173.
22. Hartling L, Wiebe N, Russel K, et al. A meta-analysis of randomized controlled trials evaluating the efficacy of epinephrine for the treatment of acute viral bronchiolitis. Arch Pediatr Adolesc Med 2003; 157: 957-964.
23. Wainwright C, Altamirano L, Cheney M, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003; 349: 27-35.
24. Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009; 360: 2079-2089.
25. Langley JM, Smith MB, LeBlanc JC, et al. Racemic epinephrine compared to salbutamol in hospitalized young childrenwith bronchiolitis; a randomized controlled clinical trial (ISRCTN46561076). BMC Pediatrics 2005; 5: 7.
26. Mull CC, Scarfone RJ, Ferri LR, et al. A randomized trial of nebulized epinephrine versus albuterol in the emergency departement treatment of bronchiolitis. Arch Pediatr Adolesc Med 2004; 158: 113-118.
27. Walsh P, Caldwell J, McQuillan KK, et al. Comparison of nebulized epinephrine to albuterol in bronchiolitis. Acad Emerg Med 2008; 15: 305-313.
28. Barr FE, Patel NR, Newth CJ. The pharmacologic mechanism by which inhaled epinephrine reduces airway obstruction in respiratory syncytial virus-associated bronchiolitis. J Pediatr 2000; 136: 699-700.
29. Wohl ME, Chernick V. State of the art: bronchiolitis. Am Rev Respir Dis 1978; 118: 759-781.
30. Levin DL, Garg A, Hall LJ, et al. A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation. Pediatr Crit Care Med 2008; 9: 598-604.
31. Argent AC, Hatherill M, Newth CJ, et al. The effect of epinephrine by nebulisation on measures of airway obstruction in patients with acute severe croup. Intensive Care Med 2008; 34: 138-147.
32. Kao B, Stewart de Ramirez SA, Belfort MB, et al. Inhaled epinephrine for the treatment of transient tachypnea of the newborn. J Perinatol 2008; 28: 205-210.
33. Courtney SE, Wachtl JP, Hopson JF, et al. Effect of racemic epinephrine on ventilatory function in the neonate postextubation. Pediatr Res 1987; 21: 381-385.
34. Davies MW, Davis PG. Nebulized racemic epinephrine for extubation of newborn infants. Cochrane Database Syst Rev 2002; 1: CD000506.
35. Kanesh Gonduri K. New approaches for persistent pulmonary hypertension of newborn. Clin Perinatol 2004; 31: 591-611.
36. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2006; 4: CD000399.
37. American Academy of Pediatrics Committee on Fetus and Newborn. Use of inhaled nitric oxide. Pediatrics 2000; 106: 344-345.
38. Kinsella JP, Truog WE, Walsh WF, et al. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn. J Pediatr 1997; 131: 55-62.
39. Kinsella JP, Dunbar Ivy D, Abman SH. Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension. Semin Perinatol 2005; 29: 123-128.
40. Greenough A, Ketriwal B. Pulmonary hypertension in the newborn. Pediatr Resp Rev 2005; 6: 111-116.
41. Cannon BC, Feltes TF, Fraley JK, et al. Nitric oxide in the evaluation of congenital heart disease with pulmonary hypertension: factors related to nitric oxide response. Pediatr Cardiol 2005; 26: 565-569.
42. González A, Fabres J, D'Apremont I, et al. Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension. J Perinatol 2010; 30: 420-424.
43. Konduri Ganesh G, Solimano A, Sokol GM, et al. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Pediatrics 2004; 113: 559-564.
44. Demirakca S, Dotsch J, Knothe C, et al. Inhaled nitric oxide in neonatal and pediatric acute respiratory distress syndrome: dose response, prolonged inhalation and weaning. Crit Care Med 1996; 24: 1913-1919.
45. Macrae DJ, Field D, Mercier JC, et al. Inhaled nitric oxide therapy in neonates and children: reaching a European consensus. Intensive Care Med 2004; 30: 372-380.
46. Barrington KJ, Finer NN. Inhaled nitric oxide for preterm infants: a systematic review. Pediatrics 2007; 120: 1088-1099.
47. Mercier JC, Hummler H, Durrmeyer X, et al. The effects of inhaled nitric oxide on the development of bronchopulmonary dysplasia in preterm infants: the EUNO clinical trial. Arch Dis Child 2008; 93: Suppl. 2, espr22.
48. Watson RS, Clermont G, Kinsella JP, et al. Clinical and economics effect of iNO in premature newborns with respiratory failure at 1 year. Pediatrics 2009; 124: 1333-1343.
49. Dellinger RP, Zimmerman JL, Taylor RW, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Crit Care Med 1998; 26: 15-23.
50. Miller OI, Tang SF, Keech A, et al. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double blind study. Lancet 2000; 356: 1464-1469.
51. Patel NR, Hammer J, Nichani S, et al. Effect of inhaled nitric oxide on respiratory mechanics in ventilated infants with RSV bronchiolitis. Intensive Care Med 1999; 25: 81-87.
52. Howard LS, Morrell NW. New therapeutic agents for pulmonary vascular diseases. Pediatr Respir Rev 2005; 6: 285-291.
53. Schermuly RT, Inholte C, Ardeschir Ghofrani H, et al. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors. Respir Res 2005; 6: 76.
54. Soditt V, Aring C, Groneck P. Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn. Intensive Care Med 1997; 23: 1275-1278.
55. De Jaegere AP, van den Anker JN. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir J 1998; 12: 932-934.
56. Kelly LK, Porta NF, Goodman DM, et al. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002; 141: 830-832.
57. De Luca D, Zecca E, Piastra M, et al. Iloprost as "rescue" therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007; 17: 394-395.
58. Sood BG, Delaney-Black V, Aranda JV, et al. Aerosolized PGE1: a selective pulmonary vasodilator in neonatal hypoxemic respiratory failure: results of a phase I/II open label clinical trial. Pediatr Res 2004; 56: 579-585.
59. Lowson SM. Inhaled alternatives to nitric oxide. Crit Care Med 2005; 33: Suppl. 3, S188-S195.
60. Eifinger F, Sreeram N, Mehler K, et al. Aerosolized iloprost in the treatment of pulmonary hypertension in extremely preterm infants: a pilot study. Klin Padiatr 2008; 220: 66-69.
61. Rimensberger PC, Spahr-Schopfer I, Berner M, et al. Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease. Vasodilator capacity and cellular mechanisms. Circulation 2001; 103: 544-548.
62. Rashid A, Ivy D. Severe paediatric pulmonary hypertension: new management strategies. Arch Dis Child 2005; 90: 92-98.
63. Dahlem P, van Aalderen VM, de Neef M, et al. Randomised controlled trial of aerosolized prostacycline therapy in children with acute lung injury. Crit Care Med 2004; 32: 1055-1060.
64. Moya MP, Gow AJ, Califf RM, et al. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet 2002; 360: 141-143.
65. Gaston B, Reilly J, Drazen JM, et al. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA 1993; 90: 10957-10961.
66. Lauterbach R, Szymura-Oleksiak J. Nebulized pentoxiphylline in successful treatment of five premature neonates with bronchopulmonary dysplasia. Eur J Pediatr 1999; 158: 607-610.
67. Lauterbach R, Pawlik D, Kowalczyk D, et al. Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial. Crit Care Med 1999; 27: 807-814.
68. ter Horst SAJ, Wagenaar GTM, de Boer E, et al. Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury. J Appl Physiol 2004; 97: 2014-2019.
69. Lauterbach R, Szymura-Oleksiak J, Pawlik D, et al. Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: a pilot clinical study. J Matern Fetal Neonatal Med 2006; 19: 433-438.
70. Haque K, Mohan P. Pentoxifylline for neonatal sepsis. Cochrane Database Syst Rev 2003; 4: CD004205.
71. Patole S. Prevention and treatment of necrotising enterocolitis in preterm neonates. Early Hum Dev 2007; 83: 635-642.
72. Shah V, Ohlsson A, Halliday HL, et al. Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev 2007; 4: CD001969.
73. Shah SS, Ohlsson A, Halliday H, et al. Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants. Cochrane Database Syst Rev 2007; 6: CD002057.
74. Bassler D, Halliday HL, Plavka R, et al. The Neonatal European Study of Inhaled Steroids (NEUROSIS): an EU-funded international randomised controlled trial in preterm infants. Neonatology 2009; 97: 52-55.
75. Yeh TF, Lin HC, Chang C, et al. Early intratracheal instillation of budesonide using surfactant as vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics 2008; 121: e1310-1318.
76. Tripathi S, Saili A, Dutta R. Inflammatory markers in meconium induced lung injury in neonates and effect of steroids on their levels: a randomized controlled trial. Indian J Med Microbiol 2007; 25: 103-107.
77. Tripathi S, Saili A. The effect of steroids on the clinical course and outcome of neonates with meconium aspiration syndrome. J Trop Pediatr 2007; 53: 8-12.
78. Basu S, Kumar A, BhatiaBD, et al. Role of steroids on the clinical course and outcome of meconium aspiration syndrome-a randomized controlled trial. J Trop Pediatr 2007; 53: 331-337.
79. Fok TF. Adjunctive pharmacotherapy in neonates with respiratory failure. Semin Fetal Neonat Med 2009; 14: 49-55.
80. Viscardi RM, Hasday JD, Gumpper KF, et al. Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 1997; 156: 1523-1529.
81. Watterberg KL, Murphy S. Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group. Pediatrics 1993; 91: 803-806.
82. Ng GY, Ohlsson A. Cromolyn sodium for the prevention of chronic lung disease in preterm infants. Cochrane Database Syst Rev 2001; 2: CD003059.
83. De Luca D, Minucci A, Cogo P, et al. Secretory phospholipase A2 pathway during pediatric ARDS: a preliminary study. Pediatr Crit Care Med 2010; [Epub ahead of print DOI: 10.1097/pcc.0b013e3181dbe95e].
84. Ramsay PL, DeMayo FJ, Hegemier SE, et al. Clara Cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 164: 155-161.
85. Johansson S, Kristjánsson S, Bjarnarson SP, et al. Clara cell protein 16 (CC16) serum levels in infants during respiratory syncytial virus infection. Acta Paediatr 2009; 98: 579-581.
86. Sengler C, Heinzmann A, Jerkic SP, et al. Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children. J Allergy Clin Immunol 2003; 111: 515-519.
87. Jorens PG, Sibille Y, Goulding NJ, et al. Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury. Eur Respir J 1995; 8: 1647-1653.
88. Levine CR, Gewolb IH, Allen K, et al. The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. Pediatr Res 2005; 58: 15-21.
89. American Heart Association, American Academy of Pediatrics. 2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of pediatric and neonatal patients: Pediatric Advanced Life Support. Pediatrics 2006; 117: e1005-e1028.
90. The International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) Consensus on science with treatment recommendations for pediatric and neonatal patients: neonatal resuscitation. Pediatrics 2006; 117: e978-e988.
91. Choong K, Bohn D, Fraser DD, et al. Vasopressin in pediatric vasodilatory shock. A multicenter randomized controlled trial. Am J Resp Crit Care Med 2009; 180: 632-639.
92. Kleinman ME, Oh W, Stonestreet BS. Comparison of intravenous and endotracheal epinephrine during cardiopulmonary resuscitation in newborn piglets. Crit Care Med 1999; 27: 2748-2754.
93. Mandelberg A, Tal G, Witzling M, et al. Nebulized hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis. Chest 2003; 123: 481-487.
94. Zhang L, Mendoza-Sassi RA, Wainwright C, et al. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2008; 4: CD006458.
95. Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2009; 2: CD001506.
96. Riethmueller J, Borth-Bruhns T, Kumpf M, et al. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol 2006; 41: 61-66.
97. Riethmueller J, Kumpf M, Borth-Bruhns T, et al. Clinical and in vitro effect of dornase alfa in mechanically ventilated pediatric non-cystic fibrosis patients with atelectases. Cell Physiol Biochem 2009; 23: 205-210.
98. Prodhan P, GreenbergB, Bhutta AT, et al. Recombinant human deoxyribonuclease improves atelectasis in mechanically ventilated children with cardiac disease. Congenit Heart Dis 2009; 4: 166-173.
99. Patel A, Harrison E, Durward A, et al. Intratracheal human deoxyribonuclease in acute life-threatening asthma refractory to conventional treatment. Br J Anaesth 2000; 84: 505-507.
100. Puterman AS, Weinberg EG. rhDNase in acute asthma. Paediatr Pulmonol 1997; 23: 316-331.
101. Greally P. Human recombinant DNase for mucous plugging in status asthmaticus. Lancet 1995; 346: 1423-1424.
102. Durward A, Forte V, Shemie S. Resolution of mucous plugging and atelectasis after intratracheal rhDNase therapy in a mechanically ventilated child with refractory status asthmaticus. Crit Care Med 2000; 27: 560-562.
103. El Hassan NO, Chess PR, Huysman MWA, et al. Rescue use of DNase in critical lung atelectasis and mucus retention in premature neonates. Pediatrics 2001;108; 468-470.
104. Erdeve O, Uras N, Atasay B, et al. Efficacy and safety of nebulized recombinant human DNAase as rescue treatment for persistent atelectasis in newborns: case-series. Croat Med J 2007; 48: 234-129.
105. Desai MH, Mlcak R, Richardson J, et al. Reduction in mortality in pediatric patients with inhalation injury with aerosolized heparin/N- acetylcystine [correction of acetylcystine] therapy. J Burn Care Rehabil 1998; 19: 210-212.
106. Bibi H, Seifert B, Oullette M, et al. Intratracheal N-acetylcysteine use in infants with chronic lung disease. Acta Paediatr 1992; 81: 335-339.
107. Purcell K, Fergie J. Driscoll Children's Hospital respiratory syncytial virus database: risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002. Pediatr Infect Dis J 2004; 23: 418-423.
108. Davison C, Ventre KM, Luchetti M, et al. Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis. Pediatr Crit Care Med 2004; 5: 482-489.
109. Ventre K, Randolph AG. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2007; 1: CD000181.
110. Chávez-Bueno S, Mejías A, Merryman RA, et al. Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients. Pediatr Infect Dis J 2007; 26: 1089-1093.
111. Hiddens T. Inhaled antibiotics. Pediatr Pulmonoldel, 2004: Suppl. 26, 92-94.
112. Michalopoulos A, Papadakis E. Inhaled anti-infective agents: emphasis on colistin. Infection 2010; 38: 81-88.
113. Chuchalin A, Eszter C, Gyurkovics K, et al. A formulation of aerosolized tobramycin (Bramitob) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Drugs 2007; 9: Suppl. 1, 21-31.
114. Ratjen F, Munck A, Kho P, et al. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax 2010; 65: 286-291.
115. O'Sullivan BP, Yasothan U, Kirkpatrick P. Inhaled aztreonam. Nat Rev Drug Discov 2010; 9: 357-358.
116. Elborn JS, Henig NR. Optimal airway antimicrobial therapy for cystic fibrosis: the role of inhaled aztreonam lysine. Expert Opin Pharmacother 2010; 11: 1373-1385.
117. Gibson RL, Emerson J, Mayer-Hamblett N, et al. Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis. Pediatr Pulmonol 2007; 42: 610-623.
118. Noah TL, Ivins SS, Abode KA, et al. Inhaled versus systemic antibiotics and airway inflammation in children with cystic fibrosis and Pseudomonas. Pediatr Pulmonol 2010; 45: 281-290.
119. Yang Y, Tsifansky MD, Wu CJ, et al. Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis. Pharm Res 2010; 27: 151-160.
120. Doring G, Hoiby N. Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cystic Fibrosis 2004; 3: 67-91.
121. Wood DM, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2006; 1: CD004197.
122. Muttil P, Wang C, Hickey AJ. Inhaled drug delivery for tuberculosis therapy. Pharm Res 2009; 26: 2401-2416.
123. Falagas ME, Siempos II, Bliziotis IA, et al. Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care 2006; 10: R123.
124. Robinson BRH, Athota KP, Branson RD. Inhalational therapies for the ICU. Curr Opin Crit Care 2009; 15: 1-9.
125. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care 2009; 15: 413-418.
126. Kuiper L, Ruijgrok EJ. Review on the clinical use of inhaled amphotericin B. J Aerosol Med Pulm Drug Del 2009; 22: 213-227.
127. Sanmartín E, Morales P, Monte E, et al. A comparision of several formats of amphotericin B as an inhaled antifungal prophylaxis. Transplant Proc 2009; 41: 2225-2226.
128. Morales P, Galán G, Sanmartín E, et al. Intrabronchial instillation of amphotericin B lipid complex: a case report. Transplant Proc 2009; 41: 2223-2224.
129. Eiland LS, Eiland EH. Zanamivir for the prevention of influenza in adults and children age 5 years and older. Therap Clin Risk Manag 2007; 3: 461-465.
130. Imuta F, Toyoda M, Toyoda T. New application method of zanamivir with a straw. Pediatr Int 2003; 45: 366-367.
131. Engle WA, the Committee on Fetus and Newborn. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121;419-432.
132. Sweet D, Bevilacqua G, Carnielli VP, et al. European consensus guidelines on the management of neonatal respiratory distress sindrome. J Perinat Med 2007; 35: 175-186.
133. Soll R, Özek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2006; 1: CD001694.
134. El Shahed AI, Dargaville PA, Ohlsson A, et al. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007; 3: CD002054.
135. Dargaville PA, Mills JF, Copnell B, et al. Therapeutic lung lavage in meconium aspiration syndrome: a preliminary report. J Paediatr Child Health 2007; 43: 539-545.
136. Dargaville PA, Copnell B, Mills JF, et al. Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. J Pediatr 2010; [Epub ahead of print DOI: 10.1016/j.jpeds.2010.08.044].
137. Cogo PE, Zimmermann LJ, Rosso F, et al. Surfactant synthesis and kinetics in infants with congenital diaphragmatic hernia. Am J Respir Crit Care Med 2002; 166: 154-158.
138. Duffett M, Choong K, Ng V, et al. Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis. Critical Care 2007; 11: R66.
139. Ventre K, Haroon M, Davison C. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev 2006; 3: CD005150.
140. Marraro GA, Luchetti M, Spada C, et al. Selective medicated (normal saline and exogenous surfactant) bronchoalveolar lavage in severe aspiration syndrome in children. Pediatr Crit Care Med 2007; 8: 476-481.
141. Gupta VK, Cheifetz IM. Heliox administration in the pediatric intensive care unit: an evidence-based review. Pediatr Crit Care Med 2005; 6: 204-211.
142. Kneyber MC, van Heerde M, Twisk JW, et al. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure. Crit Care 2009; 13: R71.
143. Martinón-Torres F, Rodríguez-Núñez A, Martinón-Sánchez JM. Nasal continuous positive airway pressure with heliox versus air/oxygen in infants with acute bronchiolitis: a crossover study. Pediatrics 2008; 121: e1190-e1195.
144. Yanney M, Vyas H. The treatment of bronchiolitis. Arch Dis Child 2008; 93: 793-798.
145. Vorwerk C, Coats TJ. Use of helium-oxygen mixtures in the treatment of croup: a systematic review. Emerg Med J 2008; 25: 547-550.
146. Vorwerk C, Coats T. Best evidence topic reports: heliox in croup. Emerg Med J 2008; 25: 365-366.
147. Myers TR. Therapeutic gases for neonatal and pediatric respiratory care. Respir Care 2003; 48: 399-422.
148. Garner SS, Wiest DB, Stevens CE, et al. Effect of heliox on albuterol delivery by metered-dose inhaler in pediatric in vitro models of mechanical ventilation. Pharmacotherapy 2006; 26: 1396-1402.
149. Rodrigo G, Pollack C, Rodrigo C, et al. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev 2006; 4: CD002884.
150. Tsai MH, Wong KS, Lien R, et al. Heliox as the rescue therapy for a neonate with congenital tracheal stenosis, pulmonary artery sling, and intracardiac anomalies. Am J Perinatol 2009; 26: 357-360.
151. Castelló Muñoz A, Carreira Sande N, Bouzón Alejandro M, et al. [Usefulness of Heliox in the management of a serious airway obstruction caused by a subglottic hemangioma.] An Pediatr (Barc) 2007; 67: 61-64.
152. Bigham MT, Nowak JE, Wheeler DS. Therapeutic application of helium-oxygen and mechanical ventilation in a child with acute myelogenous leukemia and airway obstruction. Pediatr Emerg Care 2009; 25: 469-472.
153. Kemper KJ, Ritz RH, Benson MS, et al. Helium-oxygen mixture in the treatment of postextubation stridor in pediatric trauma patients. Crit Care Med 1991; 19: 356-359.
154. Phatak RS, Pairaudeau CF, Smith CJ, et al. Heliox with inhaled nitric oxide: a novel strategy for severe localized interstitial pulmonary emphysema in preterm neonatal ventilation. Respir Care 2008; 53: 1731-1738.
155. Migliori C, Gancia P, Garzoli E, et al. The Effects of helium/oxygen mixture (heliox) before and after extubation in long-term mechanically ventilated very low birth weight infants. Pediatrics 2009; 123: 1524-1528.
156. Rastogi A, Luayon M, Ajayi OA, et al. Nebulized furosemide in infants with bronchopulmonary dysplasia. J Pediatr 1994; 125: 976-979.
157. Kugelman A, Durand M, Garg M. Pulmonary effect of inhaled furosemide in ventilated infants with severe bronchopulmonary dysplasia. Pediatrics 1997; 99: 71-75.
158. Prabhu VG, Keszler M, Dhanireddy R. Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants. Arch Dis Child Fetal Neonatal Ed 1997; 77: F32-F35.
159. Brion LP, Primhak RA, Yong W. Aerosolized diuretics for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev 2006; 3: CD001694.
160. Suresh GK, Davis JM, Soll RF. Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants. Cochrane Database Syst Rev 2001; 1: CD001968.
161. Davis JM, Parad RB, Michele T, et al. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn Superoxide Dismutase. Pediatrics 2003; 111; 469-476.
162. Dhand R. Inhalation therapy in invasive and noninvasive mechanical ventilation. Curr Opin in Crit Care 2007; 13: 27-38.
163. Scottish Intercollegiate Guidelines Network. SIGN50: a guideline developer's handbook. www.sign.ac.uk/guidelines/fulltext/50/ Date last accessed: February 13, 2010. Date last updated: January 2008.