Nebulization of High-Dose Poractant Alfa in Newborn Piglets on Nasal Continuous Positive Airway Pressure Yields Therapeutic Lung Doses of Phospholipids

Anders Nord; Federico Bianco; Fabrizio Salomone; Francesca Ricci; Martin Schlun; Rikard Linner; Doris Cunha-Goncalves

doi:10.1055/s-0040-1721392

American Journal of Perinatology, Table of Contents

Am J Perinatol 2022; 39(09): 1001-1007
DOI: 10.1055/s-0040-1721392

Original Article

Nebulization of High-Dose Poractant Alfa in Newborn Piglets on Nasal Continuous Positive Airway Pressure Yields Therapeutic Lung Doses of Phospholipids

Anders Nord

¹Pediatric Anesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden

³Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

,

Federico Bianco

⁴Department of Preclinical Pharmacology, R&D, Chiesi Farmaceutici S.p.A., Parma, Italy

,

Fabrizio Salomone

⁴Department of Preclinical Pharmacology, R&D, Chiesi Farmaceutici S.p.A., Parma, Italy

,

Francesca Ricci

⁴Department of Preclinical Pharmacology, R&D, Chiesi Farmaceutici S.p.A., Parma, Italy

,

Martin Schlun

⁵PARI Pharma GmbH, Starnberg, Germany

,

Rikard Linner

²Cardiothoracic Anesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden

³Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

,

Doris Cunha-Goncalves

¹Pediatric Anesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden

³Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

› Author Affiliations

Abstract

Objective It is not known how much surfactant must be nebulized to reach a lung dose of phospholipids equivalent to that obtained by the instillation of 200 mg/kg of surfactant. We aimed to assess the feasibility of nebulizing a high-dose of poractant alfa with the eFlow-Neos investigational vibrating-membrane nebulizer in newborn piglets on nasal continuous positive airway pressure (nCPAP) and to determine whether this intervention would yield therapeutic lung doses of phospholipids.

Study Design Twelve 1-day-old piglets on nCPAP received 600 mg/kg of poractant alfa admixed with technetium-99m via nebulization. Six piglets receiving 200 mg/kg of instilled synthetic surfactant served as controls. Lung deposition (percentage of the nominal dose) was determined by gamma scintigraphy, and the phospholipids' lung dose was calculated.

Results The lung dose of phospholipids (mean ± standard deviation [SD]) was 138 ± 96 mg/kg with nebulization, and 172 ± 24 mg/kg with instillation (p = 0.42). Nebulization took 58 ± 12 minutes. The arterial partial pressure of carbon dioxide increased from 6.7 ± 1.1 to 7.2 ± 1.1 kPa during nebulization (p = 0.04). Cerebral oximetry remained stable, and there was no hemodynamic instability.

Conclusion Nebulization was well tolerated, and the mean lung dose of phospholipids was above 100 mg/kg, that is, not different from the instillation group. These experimental findings suggest that it may be feasible to reach therapeutic lung doses of phospholipids by surfactant nebulization during nCPAP.

Key Points

It is not known if effective lung doses of surfactant can be delivered by nebulization.
Nebulization of high-dose surfactant in newborn piglets on nCPAP was well tolerated.
A high-dose of nebulized poractant alfa yielded therapeutic lung doses of phospholipids.

Keywords

deposition - aerosolization - noninvasive ventilation - neonatal respiratory distress syndrome - surfactant

Full Text

References

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