Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets

Rey-Santano, Carmen; Mielgo, Victoria; Gomez-Solaetxe, Miguel Angel; Bianco, Federico; Salomone, Fabrizio; Loureiro, Begoña

doi:10.1097/ccm.0000000000004318

Cited by 13 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 The same authors administered 400 mg/kg of nebulized poractant alfa to surfactant-deficient piglets and found a sustained improvement on oxygenation, compliance, and lung histology at 72 hours after treatment. 25 In our study, 10 to 15% of the nebulized surfactant remained in the larger suprapulmonary airways, especially the nasopharynx. It is possible that with continued nCPAP for 48 to 72 hours, some of this suprapulmonary surfactant would migrate down the airways and further increase the lung surfactant pool.…”

Section: Discussionsupporting

confidence: 44%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 44%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In newborn piglets, respiratory distress can be generated by either instilling HCl intratracheally [171,172], which inactivates the endogenous surfactant and creates a diffuse lung injury, or by repeated broncho-alveolar lavages that deplete the intrapulmonary surfactant pools [173]. Rey-Santano et al recently described a spontaneously-breathing, surfactantdepleted piglet model supported with NIV in which they nebulized undiluted surfactant (Poractant alfa, 80 mg/ mL) with an eFlow Neos nebulizer customized to neonatal standards [174]. Interestingly, they expanded the follow up period up to 72 h and in addition to the pulmonary effects, they also investigated the hemodynamic response and the cerebral effects after delivery of nebulized surfactant [174].…”

Section: Table 4 Comparison Of the Parameters Required By Compendial mentioning

confidence: 99%

“…Rey-Santano et al recently described a spontaneously-breathing, surfactantdepleted piglet model supported with NIV in which they nebulized undiluted surfactant (Poractant alfa, 80 mg/ mL) with an eFlow Neos nebulizer customized to neonatal standards [174]. Interestingly, they expanded the follow up period up to 72 h and in addition to the pulmonary effects, they also investigated the hemodynamic response and the cerebral effects after delivery of nebulized surfactant [174].…”

Section: Table 4 Comparison Of the Parameters Required By Compendial mentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

Delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as the intrinsic factors that affect lung deposition. However, there are a number of extrinsic factors that also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.

show abstract

“…It is possible that, with CPAP adjustments and longer observation times, blood gases would have improved. In surfactant-depleted piglets, Rey-Santano et al [25] observed a dose-response curve for improvements in lung injury scores and oxygenation indices with increasing doses of nebulized surfactant (dose range 200-400 mg kg -1 ). However, higher doses showed delayed recovery of oxygenation and shunt parameters.…”

Section: Cunha-goncalves Et Almentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction: The ideal body position during surfactant nebulization is not known. Objective: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. Methods: Twenty-four 12- to 36-h-old full-termpiglets (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 (n = 6 each). All animals received 200 mg kg–1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. Results: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 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%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). Conclusions: 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.

show abstract

Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets

Cited by 13 publications

References 35 publications

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

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

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

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

Contact Info

Product

Resources

About