Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation

Abstract

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.

The Contribution of Surface Tension-Dependent Alveolar Septal Stress Concentrations to Ventilation-Induced Lung Injury in the Acute Respiratory Distress Syndrome

“…However, surfactant therapy only improved oxygenation significantly in one of the six trials and marginally in one other and did not improve compliance in either of the two trials in which compliance was assessed ( Weg et al, 1994 ; Anzueto et al, 1996 ; Gregory et al, 1997 ; Spragg et al, 2004 , 2011 ; Kesecioglu et al, 2009 ), suggesting that it is a challenge for exogenous surfactant to lower alveolar T . Problematic surfactant dosage, administration technique, and formulation have been discussed as possible causes of the failure of surfactant therapy in ARDS ( Spragg et al, 2011 ; Kazemi et al, 2019 ). My group has identified two new potential causes for the failure of surfactant therapy.…”

“Optimal surfactant delivery protocol using the bovine lipid extract surfactant: a quality improvement study”

“…The results of our study demonstrate that surfactant administration technique should consider the type of surfactant used and target population, as preparations using much lower administration volumes (2.5 mL/kg) are effective and do not report such adverse events without using all the steps outlined here [ 1 ]. This is probably due to the favorable tridimensional anatomy of the preterm lungs for adequate drug distribution even at lower instillation volumes [ 22 ]. Therefore, neonatal units should implement local evidence-based protocols for surfactant administration including costs analyzes while ensuring optimal care.…”

Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation, and reduces ventilation injury in a respiratory distress model

“…In ARDS, unexpectedly, surfactant therapy has not reduced mortality (3). Surfactant dosage or delivery may be problematic (14,27). An alternative means of lowering T in ARDS is required.…”