Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome

DiBlasi, Robert M; Kajimoto, Masaki; Poli, Jonathan A; Deutsch, Gail H.; Pfeiffer, Juergen; Zimmerman, Joseph D.; Crotwell, David N; Malone, Patrik; Fink, James B.; Ringer, Coral; Uthamanthil, Rajesh; Ledee, Dolena R.; Portman, Michael A.

doi:10.1097/cce.0000000000000338

Cited by 6 publications

(9 citation statements)

References 48 publications

(29 reference statements)

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“…Results were compared with historic healthy control data ( 4 ). Surfactant was nebulized by an investigational vibrating mesh breath-actuated aerosol system (Aerogen Pharma), controlled by a flow sensor in the inspiratory limb of the ventilation circuit ( 3 ). Six patients were randomly allocated to receive three doses of 1,080 mg of Alveofact, a bovine surfactant widely used in preterm neonates ( 5 ), at T = 0, 8, and 24 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Several clinical trials of surfactant for COVID-19 ARDS are ongoing, but there is a critical need to optimize dose concentration, dose frequency and duration, and mode of delivery of therapeutic surfactant administration. In this pilot study, we evaluated the effectiveness of a prototype breath-synchronized vibrating mesh nebulizer to deliver exogenous surfactant to patients ventilated for severe COVID-19 infection ( 2 , 3 ) and report here endogenous surfactant status, turnover, and half-life of administered surfactant. These results have not been previously reported in abstract form.…”

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confidence: 99%

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Rapid Phospholipid Turnover after Surfactant Nebulization in Severe COVID-19 Infection: A Randomized Clinical Trial

Postle

Clark

Fink³

et al. 2022

Am J Respir Crit Care Med

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The Bill & Melinda Gates Foundation funded the study, grant number INV-016631. The NIHR Southampton Biomedical Research Centre provided mass spectrometry facilities and salary support for GK and MP. The NIHR Southampton Biomedical Research Centre provided mass spectrometry facilities and salary support for GK and MP. MPWG receives part of his funding through the NIHR Senior Investigator Scheme. RD and MPWG received part of their funding through the NIHR Southampton Biomedical Research Centre. H.W.C. and D.B. received part of their funding through the

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Rapid Phospholipid Turnover after Surfactant Nebulization in Severe COVID-19 Infection: A Randomized Clinical Trial

Postle

Clark

Fink³

et al. 2022

Am J Respir Crit Care Med

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“…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.…”

Section: Nebulizationmentioning

confidence: 99%

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

Walther

Waring²

2022

Front. Pediatr.

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After shifting away from invasive mechanical ventilation and intratracheal instillation of surfactant toward non-invasive ventilation with nasal CPAP and less invasive surfactant administration in order to prevent bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome, fully non-invasive surfactant nebulization is the next Holy Grail in neonatology. Here we review the characteristics of animal-derived (clinical) and new advanced synthetic lung surfactants and improvements in nebulization technology required to secure optimal lung deposition and effectivity of non-invasive lung surfactant administration. Studies in surfactant-deficient animals and preterm infants have demonstrated the safety and potential of non-invasive surfactant administration, but also provide new directions for the development of synthetic lung surfactant destined for aerosol delivery, implementation of breath-actuated nebulization and optimization of nasal CPAP, nebulizer circuit and nasal interface. Surfactant nebulization may offer a truly non-invasive option for surfactant delivery to preterm infants in the near future.

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“…We included a limited number of controls (n = 2) to provide descriptive data to show rate of endogenous surfactant repletion and recovery against treatment groups. Unlike other studies [23,36], that also showed lavage maintains surfactant-deficiency over several hours of continued ventilator support, Controls were underpowered to do a comparative statistical analysis with treatment groups. Additionally, since these animals were relatively small, sedated, and had severe lung disease, it is difficult to extrapolate from these animal findings to human pre-term newborns with RDS, especially if they are larger, have a milder form of lung disease, or are not sedated.…”

Section: Limitationsmentioning

confidence: 99%

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

et al. 2021

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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.

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Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome

Abstract: Supplemental Digital Content is available in the text.

Cited by 6 publications

References 48 publications

Rapid Phospholipid Turnover after Surfactant Nebulization in Severe COVID-19 Infection: A Randomized Clinical Trial

Rapid Phospholipid Turnover after Surfactant Nebulization in Severe COVID-19 Infection: A Randomized Clinical Trial

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

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

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