Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome
Objectives:. Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2021-02-01
|
| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000000338 |
| _version_ | 1818436690820202496 |
|---|---|
| author | Robert M. DiBlasi, RRT-NPS, FAARC Masaki Kajimoto, MD, PhD Jonathan A. Poli, MS Gail Deutsch, MD Juergen Pfeiffer, MS Joseph Zimmerman, RRT-NPS David N. Crotwell, MHL, RRT-NPS Patrik Malone, RRT James B. Fink, RRT-NPS, PhD Coral Ringer, RN Rajesh Uthamanthil, DVM, PhD Dolena Ledee, PhD Michael A. Portman, MD |
| author_facet | Robert M. DiBlasi, RRT-NPS, FAARC Masaki Kajimoto, MD, PhD Jonathan A. Poli, MS Gail Deutsch, MD Juergen Pfeiffer, MS Joseph Zimmerman, RRT-NPS David N. Crotwell, MHL, RRT-NPS Patrik Malone, RRT James B. Fink, RRT-NPS, PhD Coral Ringer, RN Rajesh Uthamanthil, DVM, PhD Dolena Ledee, PhD Michael A. Portman, MD |
| author_sort | Robert M. DiBlasi, RRT-NPS, FAARC |
| collection | DOAJ |
| description | Objectives:. Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.
Design:. Preclinical study.
Setting:. Research laboratory.
Subjects:. Anesthetized pigs.
Intervention:. In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.
Measurements and Main Results:. Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.
Conclusions:. Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome. |
| first_indexed | 2024-12-14T17:12:48Z |
| format | Article |
| id | doaj.art-40c5820562d444c88bba89d3ddc037a5 |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-12-14T17:12:48Z |
| publishDate | 2021-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-40c5820562d444c88bba89d3ddc037a52022-12-21T22:53:30ZengWolters KluwerCritical Care Explorations2639-80282021-02-0132e033810.1097/CCE.0000000000000338202102000-00007Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress SyndromeRobert M. DiBlasi, RRT-NPS, FAARC0Masaki Kajimoto, MD, PhD1Jonathan A. Poli, MS2Gail Deutsch, MD3Juergen Pfeiffer, MS4Joseph Zimmerman, RRT-NPS5David N. Crotwell, MHL, RRT-NPS6Patrik Malone, RRT7James B. Fink, RRT-NPS, PhD8Coral Ringer, RN9Rajesh Uthamanthil, DVM, PhD10Dolena Ledee, PhD11Michael A. Portman, MD121 Department of Respiratory Care Therapy, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.2 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA.2 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA.3 Department of Pathology, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.4 Scientific Research Partners, Moss Beach, CA.1 Department of Respiratory Care Therapy, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.1 Department of Respiratory Care Therapy, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.1 Department of Respiratory Care Therapy, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.5 Aerogen Pharma Corporation, San Mateo, CA.1 Department of Respiratory Care Therapy, Seattle Children’s Hospital and Regional Medical Center, Seattle, WA.8 Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA.2 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA.2 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA.Objectives:. Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model. Design:. Preclinical study. Setting:. Research laboratory. Subjects:. Anesthetized pigs. Intervention:. In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation. Measurements and Main Results:. Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups. Conclusions:. Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.http://journals.lww.com/10.1097/CCE.0000000000000338 |
| spellingShingle | Robert M. DiBlasi, RRT-NPS, FAARC Masaki Kajimoto, MD, PhD Jonathan A. Poli, MS Gail Deutsch, MD Juergen Pfeiffer, MS Joseph Zimmerman, RRT-NPS David N. Crotwell, MHL, RRT-NPS Patrik Malone, RRT James B. Fink, RRT-NPS, PhD Coral Ringer, RN Rajesh Uthamanthil, DVM, PhD Dolena Ledee, PhD Michael A. Portman, MD Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome Critical Care Explorations |
| title | Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome |
| title_full | Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome |
| title_fullStr | Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome |
| title_full_unstemmed | Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome |
| title_short | Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome |
| title_sort | breath synchronized nebulized surfactant in a porcine model of acute respiratory distress syndrome |
| url | http://journals.lww.com/10.1097/CCE.0000000000000338 |
| work_keys_str_mv | AT robertmdiblasirrtnpsfaarc breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT masakikajimotomdphd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT jonathanapolims breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT gaildeutschmd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT juergenpfeifferms breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT josephzimmermanrrtnps breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT davidncrotwellmhlrrtnps breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT patrikmalonerrt breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT jamesbfinkrrtnpsphd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT coralringerrn breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT rajeshuthamanthildvmphd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT dolenaledeephd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome AT michaelaportmanmd breathsynchronizednebulizedsurfactantinaporcinemodelofacuterespiratorydistresssyndrome |