Ricci Francesca, Mersanne Arianna, Storti Matteo, Nutini Marcello, Pellicelli Giulia, Carini Angelo, Milesi Ilaria, Lombardini Marta, Dellacà Raffaele L, Thomson Merran A, Murgia Xabier, Lavizzari Anna, Bianco Federico, Salomone Fabrizio
Department of Preclinical Pharmacology, R&D, Chiesi Farmaceutici S.p.A., 15739 Parma, Italy.
TechRes Lab, Dipartimento di Elettronica, Informazione e Bioingegneria (DEIB), Politecnico di Milano University, 20133 Milan, Italy.
Pharmaceutics. 2022 May 20;14(5):1093. doi: 10.3390/pharmaceutics14051093.
High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of ). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.
高流量鼻导管（HFNC）是一种用于治疗呼吸窘迫综合征（RDS）早产儿的无创呼吸支持（NRS）方式。在NRS期间雾化吸入表面活性剂将代表一种真正无创的表面活性剂给药方法，并可降低NRS失败率。然而，HFNC期间雾化表面活性剂的给药效率尚未在体外或呼吸窘迫动物模型中进行评估。因此，我们首先进行了一项基准研究，以比较市售新生儿鼻导管（NCs）和新生儿重症监护病房常用的HFNC回路输送的表面活性剂肺剂量。然后，在诱导呼吸窘迫的自主呼吸兔中研究了通过HFNC输送的雾化表面活性剂的肺部效应。基准研究显示，所测试的两种类型的NCs的表面活性剂肺剂量相对较低（Westmed NCs为标称剂量200mg/kg的0.5±0.45%；Fisher&Paykel NCs为1.8±1.9%）。在基准研究中获得的适度肺剂量与雾化表面活性剂在体内（400mg/kg）缺乏效果一致，在体内动脉氧合和肺力学没有改善，并且明显比气管内滴注表面活性剂差。本研究结果表明，肺表面活性剂剂量相对较低，对动脉氧合和肺力学方面的肺功能影响可忽略不计。这种可忽略不计的影响在很大程度上可以通过HFNC期间使用的高气流导致气溶胶颗粒在通气回路和上呼吸道中的高撞击来解释。
