Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model.

O’Callaghan, Christopher; Hardy, J. G.; Stammers, J; Stephenson, Terence; Hull, Diana

doi:10.1136/adc.67.1_spec_no.20

Cited by 60 publications

(25 citation statements)

References 15 publications

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“…MDIs and jet nebulizers, currently the most frequently used aerosol delivery devices in these patients, have been extensively evaluated in in vitro neonatal filter studies, animal models and in ventilated infants. All results showed a relatively small lung deposition of 0.5-2% of the nominal dose [10][11][12][13][14][15][16][17][18]. There is, however, little information on their use in nonventilated infants.…”

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confidence: 97%

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer

Fok¹,

Lam²,

Ng³

et al. 1998

Eur Respir J

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To identify the most efficient device for the delivery of bronchodilator aerosol to nonventilated preterm infants with chronic lung disease, we compared the metered dose inhaler (MDI) used in conjunction with a non-valved spacer, an ultrasonic nebulizer with a small medication cup, and two jet nebulizers. The subjects were enrolled in two double-blind randomized crossover studies. In study A (n=10), each infant was given a nominal dose of 200 microg of salbutamol by a MDI (Ventolin) at 4 h intervals, and in random sequence via an Aerochamber (Neonatal Aerochamber) with its one-way valve removed, an ultrasonic nebulizer with a small cone-shaped medication cup (Siemens Electronics), and a jet nebulizer (Side-stream). Their functional residual capacity (FRC) and static respiratory system mechanics were measured before, and at 15, 30, 60, and 120 min after aerosol delivery. Study B (n=10) was carried out in an identical manner, but with a different jet nebulizer (Hudson). In both studies, administration of salbutamol aerosol via the MDI Aerochamber or ultrasonic nebulizer resulted in a significantly greater reduction in respiratory system resistance than via jet nebulizers. Furthermore, the use of MDI Aerochamber or ultrasonic nebulizer was associated with a greater degree of post-treatment tachycardia and improvement in FRC. The bronchodilating effect of salbutamol delivered via the ultrasonic nebulizer appeared to be slightly greater than that via the MDI-Aerochamber, receiving significance only in Study B. We conclude that both the metered-dose inhaler used with a nonvalved Aerochamber and the ultrasonic nebulizer with a small medication cup are both more efficient than the jet nebulizers in preterm infants.

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confidence: 97%

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer

Fok¹,

Lam²,

Ng³

et al. 1998

Eur Respir J

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“…Nonetheless, lung deposition has been consistently found to be low in these studies. In a model of anesthetized rabbits that were intubated with a 3.0-mm ETT, deposition of an aerosol administered via a spacer placed on the ventilator's inspiratory line or directly into the ETT ranged from 0.2 to 0.4% of the emitted dose (6,7). In conditions of uncontrolled ventilation in nonparalyzed rabbits, deposition reached a maximum of 5% of the emitted dose (7,9).…”

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confidence: 99%

Aerosol Deposition in Neonatal Ventilation

et al. 2005

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“…Thus, performance is often projected from in vitro experiments (8 -10) or in vitro lung models (11,12), with data obtained at lower inspiratory flow rates and higher tidal volumes through the spacer devices than what would be encountered in clinical practice. Animal "infant" models (13,14) may be suitable alternatives to assess pulmonary deposition of labeled drugs. Usually, rabbits are tracheotomized, mechanically ventilated, and killed, but this animal model poorly reflects the lung deposition of drug administered through spacer devices in spontaneously breathing children.…”

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Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

et al. 2001

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Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles Ͻ5.8 m in diameter (NES-spacer ϭ Babyhaler Ͼ Aerochamber-Infant; p Ͻ 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52-5.40% of the delivered dose) but greater with the NESspacer than with the Aerochamber-Infant or the Babyhaler (5.40 Ϯ 2.40%, 2.91 Ϯ 0.86%, 0.52 Ϯ 0.46%, respectively; p ϭ 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants. Small-volume spacer devices fitted with a face mask and inspiratory/expiratory valves have been developed for delivering pressurized metered-dose inhaler drugs to infants and newborns with various respiratory diseases (1-4). However, little is known about the ability of these spacer devices to deliver a significant amount of drug to the lungs of spontaneous breathing infants and a fortiori in intubated and mechanically ventilated infants and newborns.The radiotracer technique is the only method available for direct estimation of aerosol deposition in vivo. This technique is commonly used in adults, and has been used in several studies in infants (5-7). However, the exposure of small infants to radioisotopes remains a concern. Thus, performance is often projected from in vitro experiments (8 -10) or in vitro lung models (11,12), with data obtained at lower inspiratory flow rates and higher tidal volumes through the spacer devices than what would be encountered in clinical practice. Animal "infant" models (13, 14) may be suitable alternatives to assess pulmonary deposition of labeled drugs. Usually, rabbits are tracheotomized, mechanically ventilated, and killed, but this animal model poorly reflects the lung deposition of drug administered through spacer devices in spontaneously breathing children. Because oropharyngeal ...

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Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model.

Cited by 60 publications

References 15 publications

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer

Aerosol Deposition in Neonatal Ventilation

Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

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