Abstract
Lung deposition of inhaled drugs in ventilated neonates has been studied in models of questionable relevance. With conventional nebulizers, pulmonary deposition has been limited to 1% of the total dose. The objective of this study was to assess lung delivery of aerosols in a model of neonatal ventilation using a conventional and novel electronic micropump nebulizer. Aerosol deposition studies with 99mTc diethylenetriamine pentaacetate (99mTc-DTPA) were performed in four macaques (2.6 kg) that were ventilated through a 3.0-mm endotracheal tube (with neonatal settings (peak inspiratory pressure 12–14 mbar, positive end-expiratory pressure 2 mbar, I/E ratio 1/2, respiratory rate 40/min), comparing a jet-nebulizer MistyNeb (3-mL charge, 4.8 μm), an electronic micropump nebulizer operating continuously [Aeroneb Professional Nebulizer (APN-C); 0.5-mL charge, 4.6 μm], and another synchronized with inspiration [Aeroneb Professional Nebulizer Synchronized (APN-S); 0.5-mL charge, 2.8 μm]. The amount of radioactivity deposited into lungs and connections and remaining in the nebulizer was measured by a gamma counter. Despite similar amounts of 99mTc-DTPA in the respiratory circuit with all nebulizers, both APN-S and APN-C delivered more drug to the lungs than MistyNeb (14.0, 12.6, and 0.5% in terms of percentage of nebulizer charge, respectively; p = 0.006). Duration of delivery was shorter with APN-C than with the two other nebulizers (2 versus 6 and 10 min for the APN-S and the MistyNeb, respectively; p < 0.001). Electronic micropump nebulizers are more efficient to administer aerosols in an animal model of ventilated neonates. Availability of Aerogen's electronic micropump nebulizers offers new opportunities to study clinical efficacy and risks of aerosol therapy in ventilated neonates.
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Abbreviations
- APN-C:
-
Aeroneb Professional Nebulizer operating continuously
- APN-S:
-
Aeroneb Professional Nebulizer Synchronized
- ETT:
-
endotracheal tube
- PCA:
-
principal components of analysis
- 99mTC-DTPA:
-
99mTc diethylenetriamine pentaacetate
References
Ahrens RC, Ries RA, Popendorf W, Wiese JA 1986 The delivery of therapeutic aerosols through endotracheal tubes. Pediatr Pulmonol 2: 19–26
Cole CH 2000 Special problems in aerosol delivery: neonatal and pediatric considerations. Respir Care 45: 646–651
Fok TF, Monkman S, Dolovich M, Gray S, Coates G, Paes B, Rashid F, Newhouse M, Kirpalani H 1996 Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia. Pediatr Pulmonol 21: 301–309
Flavin M, MacDonald M, Dolovich M, Coates G, O'Brodovich H 1986 Aerosol delivery to the rabbit lung with an infant ventilator. Pediatr Pulmonol 2: 35–39
Cameron D, Arnot R, Clay M, Silverman M 1991 Aerosol delivery in neonatal ventilator circuits: a rabbit lung model. Pediatr Pulmonol 10: 208–213
O'Callaghan C, Hardy J, Stammers J, Stephenson TJ, Hull D 1992 Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model. Arch Dis Child 67: 20–24
Fok TF, al-Essa M, Monkman S, Dolovich M, Girard L, Coates G, Kirpalani H 1997 Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits. Crit Care Med 25: 140–144
Fok TF, al-Essa M, Monkman S, Dolovich M, Girard L, Coates G, Kirpalani H 1997 Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits. Pediatr Res 42: 721–727
Dubus JC, Rhem R, Dolovich M 2001 Delivery of salbutamol pressurized metered-dose inhaler administered via small-volume spacer devices in intubated, spontaneously breathing rabbits. Pediatr Res 50: 384–389
Turpeinen M, Nikander K 2001 Nebulization of a suspension of budesonide and a solution of terbutaline into a neonatal ventilator circuit. Respir Care 46: 43–48
Smart JR 2002 A brief overview of novel liquid-based inhalation technologies. Drug Deliv Syst Sci 2: 67–71
Coleman DM, Kelly HW, McWilliams BC 1996 Determinants of aerosolized albuterol delivery to mechanically ventilated infants. Chest 109: 1607–1613
Kelly HW, Keim KA, McWilliams BC 2003 Comparison of two methods of delivering continuously nebulized albuterol. Ann Pharmacother 37: 23–26
Martonen TB, Katz IM, Musante CJ 2001 A nonhuman primate aerosol deposition model for toxicological and pharmaceutical studies. Inhal Toxicol 13: 307–324
Diot P, Galinier E, Grimbert D, Bugeon S, Valat C, Lemarié E, Diot E, Baulieu JL, Besnard JC, Guilloteau D 2001 Characterization of 99m Tc-DTPA aerosols for lung permeability studies. Respiration 68: 313–317
Lister P, Iles R, Shaw B, Ducharme F 2000 Inhaled steroids for neonatal chronic lung disease. Cochrane Database Syst Rev CD002311
Arnon S, Grigg J, Nikander K, Silverman M 1992 Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit. Pediatr Pulmonol 13: 172–175
Lugo RA, Kenney JK, Keenan J, Salyer JW, Ballard J, Ward RM 2001 Albuterol delivery in a neonatal ventilated lung model: nebulization versus chlorofluorocarbon and hydrofluoroalkane-pressurized metered dose inhalers. Pediatr Pulmonol 31: 247–254
Fink JB Aerosol delivery to ventilated infant and pediatric patients. Respir Care 49: 653–665 2004
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This study was funded in part by Aerogen, Inc. (Mountain View, CA).
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Dubus, J., Vecellio, L., De Monte, M. et al. Aerosol Deposition in Neonatal Ventilation. Pediatr Res 58, 10–14 (2005). https://doi.org/10.1203/01.PDR.0000156244.84422.55
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DOI: https://doi.org/10.1203/01.PDR.0000156244.84422.55
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