Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure

Abstract

<b><i>Introduction:</i></b> The ideal body position during surfactant nebulization is not known. <b><i>Objective:</i></b> The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. <b><i>Methods:</i></b> Twenty-four 12- to 36-h-old full-term<b><i></i></b>piglets (1.3–2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (<i>n</i> = 6 each). All animals received 200 mg kg<sup>–1</sup> of poractant alfa mixed with 200 MBq of <sup>99m</sup>technetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. <b><i>Results:</i></b> Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, <i>p</i> = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, <i>p</i> = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, <i>p</i> = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, <i>p</i> = 0.04). <b><i>Conclusions:</i></b> In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned

“…However, animal 1 was positioned with the right side up and animal 2 with the left side up. Interestingly, even though total lung deposition was 38.6% and 47.8% in animal 1 and 2, respectively, surfactant deposition in the dependent lungs accounted for 33.4% and 43.7% in each case, suggesting the formation of a surfactant film within the airways after nebulization which distributes preferentially to the dependent lung [122,130]. Nevertheless, animal 2 and animal 4 were both positioned with the left side up but the difference in lung deposition was evident: total lung deposition in animal 4 was just 3.3%, whereas deposition in the nasopharynx (18.4%) and stomach (20.6%) accounted for 39% of the nominal surfactant dose.…”

“…However, position changes alter the upper respiratory tract angles and may therefore influence the fate of a nebulized drug. A recent scintigraphy study by Cunha-Goncalves et al in newborn piglets ventilated with nCPAP investigated the impact of body positioning on the lung distribution of nebulized surfactant [130]. In this study, all animals received 200 mg/kg of nebulized, radiolabelled surfactant using a customized eFlow Neos vibrating-membrane nebulizer placed between the Y piece and the nCPAP interface (customized nasal prongs).…”

“…Most importantly, the pulmonary distribution of the nebulized drug can be analysed. Figure 7 shows an example of gamma scintigraphy images of different piglets after inhalation of radiolabelled surfactant via nasal prongs [130]. Figure 7 illustrates the variability in terms of both radiolabelled surfactant lung deposition and distribution.…”

“…7 Gamma scintigraphy of newborn piglets obtained after nebulization of 99 m-technetium ( 99m Tc)-labelled surfactant. These images belong to the recent study conducted by Cunha-Goncalves et al [130] and distribution studies also have a number of limitations that must be considered. Firstly, there is a difference between the nasal anatomy of animals and humans.…”

A systematic review of surfactant delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization: Methods, limitations, and outcomes

“…Animal studies on piglets showed mean lung phospholipids of 100 mg/kg was achieved with higher dosages of nebulized surfactant, 41,42 that mean lung deposition was significantly higher when nebulization was performed in the prone position 43 and that lung deposition was significant irrespective of the type of noninvasive respiratory support used during nebulized SRT 44 …”