Preclinical Assessment of Nebulized Surfactant Delivered through Neonatal High Flow Nasal Cannula Respiratory Support

Abstract

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

Positive end‐expiratory pressure and surfactant administration mode influence function in ex‐vivo premature sheep lungs

“…Also, the device used to deliver aerosolised surfactant was challenging and therefore not used as a method of surfactant delivery in clinical routine. [11][12][13]26,28 We speculate that in a non-aerated ex vivo immature lung without pulmonary circulation, surfactant but not PEEP is responsible for improving the tidal volume of spontaneous breaths. This study highlights the significant impact of surfactant administration on tidal volume during spontaneous breathing in nonaerated preterm sheep lungs.…”

“…Further, they add to previous discussions that aerosolised surfactant delivery was either similar or inferior to bolus surfactant. Also, the device used to deliver aerosolised surfactant was challenging and therefore not used as a method of surfactant delivery in clinical routine 11–13,26,28 …”

“…In addition, the study compared the efficiency of various nasal cannulas and identified limitations in surfactant deposition, primarily due to particle impaction within the narrow tubing and air leaks. As a result, the study discouraged the use of high flow nasal cannulas as a delivery method for nebulised surfactant in this configuration 13 …”

“…7 Trials published over the past 5 years by Minnocchieri et al and Cummings et al, reported positive effects of nebulised surfactant during non-invasive respiratory support; however, these effects were mostly seen in more mature premature infants. [11][12][13] In addition, the study compared the efficiency of various nasal cannulas and identified limitations in surfactant deposition, primarily due to particle impaction within the narrow tubing and air leaks. As a result, the study discouraged the use of high flow nasal cannulas as a delivery method for nebulised surfactant in this configuration.…”

“…As a result, the study discouraged the use of high flow nasal cannulas as a delivery method for nebulised surfactant in this configuration. 13 Moreover, lung simulators that closely mimic human physiological conditions and thus, enable innovative study designs, have been described by Montigaud et al, Perinel et al, and Pasteka et al [14][15][16] Perinel et al developed and validated an ex vivo respiratory tract model, suitable for pre-clinical trial with results comparable to in vivo human data in aerosol delivery research. The model involved a plastinated human head connected to an ex vivo porcine lung, which was artificially ventilated.…”