DiBlasi Robert M, Kajimoto Masaki, Poli Jonathan A, Deutsch Gail, Pfeiffer Juergen, Zimmerman Joseph, Crotwell David N, Malone Patrik, Fink James B, Ringer Coral, Uthamanthil Rajesh, Ledee Dolena, Portman Michael A
Department of Respiratory Care Therapy, Seattle Children's Hospital and Regional Medical Center, Seattle, WA.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA.
Crit Care Explor. 2021 Feb 15;3(2):e0338. doi: 10.1097/CCE.0000000000000338. eCollection 2021 Feb.
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.
Preclinical study.
Research laboratory.
Anesthetized pigs.
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 (Pao/Fio <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.
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 ( = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao/Fio (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects ( = 3) maintained Pao/Fio 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.
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.
急性呼吸窘迫综合征和2019冠状病毒病中表面活性剂治疗的有效方案尚未确立。在已建立的急性呼吸窘迫综合征模型中，使用呼吸同步雾化给药系统进行体外和体内临床前研究，以评估吸入性表面活性剂的效率、粒径、剂量、安全性和疗效。
临床前研究。
研究实验室。
麻醉猪。
体外分析包括使用新型呼吸同步雾化器在模拟通气期间的粒径分布和吸入剂量。在成年猪（体重34.3±0.6kg）严重急性呼吸窘迫综合征（Pao/Fio<100）伴肺灌洗和有创通气期间呼吸机诱导性肺损伤的模型中，将吸入雾化表面活性剂（治疗组）的生理效应与雾化生理盐水（对照组）进行比较。
质量中位气溶胶直径为2.8µm。机械通气期间气管插管远端递送的体外剂量为85%±5%。雾化器在使用高达20剂108mg表面活性剂时仍可正常工作。表面活性剂治疗的动物（n=4）氧合迅速改善，Pao/Fio（~300）和呼气末肺容积几乎完全恢复，表面活性剂名义剂量小于30mg/kg，而对照组（n=3）在4.5小时内Pao/Fio维持在100以下，呼气末肺容积减少。与对照组相比，表面活性剂治疗的猪肺中表面活性剂磷脂含量明显更高，肺炎症和病理性肺损伤指标更低。雾化表面活性剂未出现与给药相关的并发症，但表面活性剂治疗的动物治疗后气道阻力逐渐高于对照组，两组通气效果无差异。
呼吸同步雾化牛肺表面活性剂似乎是用于2019冠状病毒病和其他严重形式急性呼吸窘迫综合征的一种安全可行的治疗选择。
