To evaluate drug delivery to the lungs of nebulized and metered-dose inhalers (MDIs) in an in vitro infant lung model.
METHODS:
An in vitro lung model was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5 L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was used at the following ventilator settings: positive inspiratory pressure 30 cm H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data.
RESULTS:
There was a significantly greater percentage of drug delivery with MDI albuterol (1.96 ± 0.50) as compared with nebulized albuterol (1.26 ± 0.37) (p = 0.002) or beclomethasone diproprionate (0.51 ± 0.24) (p = 0.001).
CONCLUSIONS:
Albuterol MDI provides a more efficient delivery of drug to the lung as compared with nebulized albuterol and MDI beclomethasone diproprionate.
WilkieRABryanMH. Effect of bronchodilators on airway resistance in ventilator-dependent neonates with chronic lung disease. J Pediatr1987;111: 278–82.
2.
PrendivilleAGreenSSilvermanM. Ipratropium bromide and airways function in wheezy infants. Arch Dis Child1987;62: 397–400.
3.
BrundageKLMohsiniKGFroeseABFisherJT. Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia. Am Rev Respir Dis1990;142: 1137–42.
4.
DenjeanAGuimaraesHMigdalMMiramandJLDehanMGaultierC. Dose-related bronchodilator response to aerosolized salbutamol (albuterol) in ventilator-dependent premature infants. J Pediatr1992;120: 974–9.
5.
RotschildASolimanoAPutermanMSmythJSharmaAAlbersheimS. Increased compliance in response to salbutamol in premature infants with developing bronchopulmonary dysplasia. J Pediatr1989;115: 984–91.
6.
WatterbergKLClarkARKellyHWMurphyS. Delivery of aerosolized medication to intubated babies. Pediatr Pulmonol1991;10: 136–41.
7.
NewmanS. Aerosol deposition considerations in inhalation therapy. Chest1985;88 (suppl):152S–60S.
8.
FullerHDDolovichMBPosmituckGPackW WongNewhouseMT. Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Am Rev Respir Dis1990;141: 440–4.
9.
MacIntyreNRSilverRMMillerCWSchulerFColemanRE. Aerosol delivery in intubated, mechanically ventilated patients. Crit Care Med1985;13: 81–4.
10.
FraserIDuVallADolovichMNewhouseMT. Therapeutic aerosol delivery in ventilator systems (abstract). Am Rev Respir Dis1981;123:107.
11.
CameronDArnotRClayMSilvermanM. Aerosol delivery in neonatal ventilator circuits: A rabbit lung model. Pediatr Pulmonol1991;10: 208–13.
12.
O'CallaghanCHardyJStammersJStephensonTJHullD. Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model. Arch Dis Child1992;67: 20–4.
13.
FlavinMMacDonaldMDolovichMCoatesGO'BrodovichH. Aerosol delivery to the rabbit lung with an infant ventilator. Pediatr Pulmonol1986;2: 35–9.
14.
BanksJLevensonHCvetnicWNaglieRZenkKHallmanM. Pulmonary aerosol deposition in the mechanically ventilated newborn piglet (abstract). Clin Res1990;38:201A.
15.
JenkinsSCHeatonRWFultonTJMoxhamJ. Comparison of domiciliary nebulized salbutamol and salbutamol from a metered-dose inhaler in stable chronic airflow limitation. Chest1987;91: 804–7.
16.
SummerWElstonRTharpeLNelsonSHaponikEF. Aerosol bronchodilator delivery methods: Relative impact on pulmonary function and cost of respiratory care. Arch Intern Med1989;149: 618–23.
17.
JasperACMohsenifarZKahanSGoldbergHSKoernerSK. Cost— Benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients. Chest1987;91: 614–9.
18.
TurnerJRCorkeryKJEckmanDGelbAMLipavskyASheppardD. Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Chest1988;93: 476–81.
19.
ChristenssonPArboreliusMLiljaB. Salbutamol inhalation in chronic asthma bronchiale: Dose aerosol versus jet nebulizer. Chest1981;79: 416–9.
20.
GayPCPatelHGNelsonSBGillesBHubmayrRD. Metered dose inhalers for bronchodilator delivery in intubated, mechanically ventilated patients. Chest1991;99: 66–71.
21.
MestitzHCoplandJMMcDonaldCF. Comparison of outpatient nebulized vs metered dose inhaler terbutaline in chronic airflow obstruction. Chest1989;96: 1237–40.
22.
LeeHArnonSSilvermanM. Bronchodilator aerosol administered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome. Arch Dis Child1994;70 (suppl):F218–22.
23.
BensonJMGalPKandrotasRJWatlingSMHansenCJ. The impact of changing ventilator parameters on availability of nebulized drugs in an in vitro neonatal lung system. DICP Ann Pharmacother1991;25: 272–5.
24.
GriggJArnonSJonesTClarkeASilvermanM. Delivery of therapeutic aerosols to intubated babies. Arch Dis Child1992;67: 25–30.
25.
ColemanDMKellyHWMcWilliamsBC. Determinants of aerosolized albuterol delivery to mechanically ventilated infants. Chest1996;109: 1607–13.
26.
DhandRTobinMJ. Bronchodilator delivery with metered-dose inhalers in mechanically-ventilated patients. Eur Respir J1996;9: 585–95.
27.
ManthousCAHallJBSchmidtGAWoodLDH. Metered-dose inhaler versus nebulized albuterol in mechanically ventilated patients. Am Rev Respir Dis1993;148: 1567–70.
28.
RauJLHarwoodRJGroffJL. Evaluation of a reservoir device for metered-dose bronchodilator delivery to intubated adults: An in vitro study. Chest1992;102: 924–30.
29.
EverardMLStammersJHardyJGMilnerAD. New aerosol delivery system for neonatal ventilator circuits. Arch Dis Child1992;67: 826–30.
30.
KraemerRBirrerPModelskaKAebischerCSchöniMH. A new baby-spacer device for aerosolized bronchodilator administration in infants with bronchopulmonary disease. Eur J Pediatr1992;151: 57–60.
31.
EbertJAdamsABGreen-AideB. An evaluation of MDI spacers and adapters: Their effect on the respirable volume of medication. Respir Care1992;37: 862–8.
32.
AventMLGalPRansomJLBrownYLHansenCJ. Comparing the delivery of albuterol metered-dose inhaler via an adapter and spacer device in an in vitro infant ventilator lung model. Ann Pharmacother1999;33: 141–3.
33.
HughesJMSaezJ. Effects of nebulizer mode and position in a mechanical ventilator circuit on dose efficiency. Respir Care1987;32: 1131–5.
34.
O'DohertyMJThomasSHLPageCJTreacherDFNunanTO. Delivery of a nebulized aerosol to a lung model during mechanical ventilation: Effect of ventilator settings and nebulizer type, position, and volume of fill. Am Rev Respir Dis1992;146: 383–8.
35.
MaloneRAHollieMCGlynn-BarnhartANelsonHS. Optimal duration of nebulized albuterol therapy. Chest1993;104: 1114–8.
36.
GarnerSSWiestDBBradleyJWLesherBAHabibDM. Albuterol delivery by metered-dose inhaler in a mechanically ventilated pediatric lung model. Crit Care Med1996;24: 870–4.
37.
O'RiordanTGGrecoMJPerryRJSmaldoneGC. Nebulizer function during mechanical ventilation. Am Rev Respir Dis1992;145: 1117–22.
38.
FinkJBDhandRDuarteAGJenneJWTobinMJ. Aerosol delivery from a metered-dose inhaler during mechanical ventilation. Am J Respir Crit Care Med1996;154: 382–7.
39.
CameronDClayMSilvermanM. Evaluation of nebulizers for use in neonatal ventilator circuits. Crit Care Med1990;18: 866–70.
