Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits

Abstract

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.

Evaluation of a Novel Dry Powder Surfactant Aerosol Delivery System for Use in Premature Infants Supported with Bubble CPAP

“…Experimental nebulizers designed for liquid aerosol of surfactant delivery typically generate a constant output of the drug during the respiratory cycle that may be less efficient for pulmonary drug delivery than breath-synchronized nebulizers designed to time aerosol delivery with the patient's inspiratory phase [31][32][33]. Moreover, constant output aerosol nebulizers have been shown to result in high drug loss in the upper airways (~80%) [31], poor lung delivery, and 99% of aerosolized surfactant depositing in the expiratory tubing [8].…”

Aerosol Delivery of Lung Surfactant and Nasal CPAP in the Treatment of Neonatal Respiratory Distress Syndrome

“…This has led to a shift away from jet nebulizers to VMNs in animal and clinical studies ( Tables 1 , 2 ). Synchronization of aerosol delivery and spontaneous respiration can further enhance lung dose as recently shown in ventilated, surfactant-deficient juvenile rabbits and in a porcine ARDS model using liquid bovine surfactant and a novel breath-actuated small particle VMN with photo-defined aperture plate (PDAP) technology (Aerogen Pharma, San Mateo, CA) placed between the Y- connector of the ventilator circuit and the endotracheal tube ( 63 , 64 ). Synchronization of surfactant delivery was managed by a flow sensor in the inspiratory line of the ventilator and minimized surfactant loss during expiration.…”