Alveolar Recruitment Promotes Homogeneous Surfactant Distribution in a Piglet Model of Lung Injury

Abstract

Uneven distribution of exogenous surfactant contributes to a poor clinical response in animal models of respiratory distress syndrome. Alveolar recruitment at the time of surfactant administration may lead to more homogeneous distribution within the lungs and result in a superior clinical response. To investigate the effects of three different volume recruitment maneuvers on gas exchange, lung function, and homogeneity of surfactant distribution, we studied 35 newborn piglets made surfactant deficient by repeated airway lavage with warm saline. Volume recruitment was achieved by either a temporal increase in tidal volume or an increase in end-expiratory pressure during surfactant administration, yielding an increase in dynamic compliance of the respiratory system of 77% in the first group and an increase in functional residual capacity of 108% in the second group. A third group of piglets (all n ϭ 7) received a combination of both volume recruitment maneuvers, with increases in dynamic compliance of the respiratory system of 100% and in functional residual capacity of 192%. Those animals subjected to increased tidal volume showed an improved surfactant response in terms of oxygenation, ventilation, lung volumes, lung mechanics, and homogeneity of surfactant distribution. Increased end-expiratory volume augmented the surfactant effect only to some extent. The combination of both volume recruitment maneuvers, however, needed lung volumes beyond total lung capacity (approximately 56 mL/kg), thus probably inducing early sequelae of ventilatorinduced lung injury. We conclude that volume recruitment by means of increased tidal volumes at the time of surfactant administration leads to a superior surfactant effect owing to more homogeneous surfactant distribution within a collapsed lung. Surfactant treatment has reduced mortality and morbidity in infants with RDS (1). However, detrimental factors affecting response to therapy are numerous, such as uneven distribution of exogenous surfactant, insufficient dosage, inability of exogenous surfactant to enter the metabolic pathways, inhibition of surface activity by plasma-derived proteins, or respiratory failure caused by factors other than surfactant deficiency (2).Two clinical studies (3, 4) have identified patent ductus arteriosus, gas accumulation outside the alveolar level, and pulmonary infection as the main reasons for nonresponse in neonates with RDS, leading to an increased mortality as high as 40% of affected infants. Poor response, however, is thought to be predominantly caused by uneven surfactant distribution. Animal studies have shown that the distribution of exogenous surfactant is often nonuniform, and that nonuniform distribution patterns are associated with poor clinical response (5-7).The immediate increase in FRC after surfactant administration to infants with RDS (8 -10) can be considered to be the result of two mechanisms: stabilization of previously collapsing alveoli at end-expiration, and stabilization of alveoli already being ventilated at higher e...

Severe airway obstruction during surfactant administration using a standardized protocol: a prospective, observational study

“…21,22 Our protocol did not include the routine use of these maneuvers before surfactant administration. During the monitoring process, we did not record the time intervals between patient deterioration and changes in ventilator settings and/or initiation of bagging.…”

The Future of Exogenous Surfactant Therapy

“…This model has been studied in several mammalian species, and the response to instilled active exogenous surfactant has been consistently positive. 22,39,[128][129][130][131][132][133][134][135][136][137] However, lung lavage primarily induces surfactant deficiency resembling RDS rather than ALI/ARDS, although superimposed injury from in vivo lavage and mechanical ventilation is also present. Other animal models of direct pulmonary ALI/ARDS have also responded favorably to active exogenous surfactant.…”

“…Using an alveolar recruitment maneuver (eg, manual bagging or a larger tidal volume) during instillation may facilitate surfactant distribution and reduce the degree or duration of hypoxia and hypotension. Studies by Krause et al 136,137 in young rabbits and piglets with lung injury induced by in vivo lavage found that several methods of volume recruitment (increased ventilator peak inspiratory pressure, tidal volume, and/or PEEP) at the time of instillation significantly improved the pulmonary efficacy of surfactant therapy.…”

“…The recruitment of alveoli by bagging or other recruitment maneuvers during surfactant drug delivery may open otherwise inaccessible areas of injured lung, and these may then remain open if exogenous surfactant has reached them effectively. 136,137 Also, if surfactant delivery via aerosolization can be perfected, it might avoid the transient hypoxia, hypertension, and ETT obstruction associated with instillation. However, studies have shown that, despite the drawbacks, instillation benefits patients with several forms of ARDS.…”

Surfactant for Respiratory Distress Syndrome: New Ideas on a Familiar Drug with Innovative Applications

“…In addition to the pool size, positive end expiratory pressure improves pulmonary distribution and augments the surface tension-lowering effects of surfactant [5,6,7]. …”