The Future of Exogenous Surfactant Therapy

Abstract

Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Key words: surfactant; infant respiratory distress syndrome; RDS; acute lung injury; ALI; acute respiratory distress syndrome; ARDS; neonatal. [Respir Care 2011;56(9):1369 -1386.

Pediatric Acute Respiratory Distress Syndrome

“…17,57,58 Many had hoped that the Calfactant Therapy for Direct Acute Respiratory Distress Syndrome and Direct Acute Lung Injury in Children (CARDS) trial, which involved 30 international centers, would provide definitive guidance for the surfactant management of pediatric patients with direct lung injury; however, the study was recently closed for futility. 59 At this point the clinician is left with his or her own interpretation of the data by Willson et al 17,54,59 Calfactant improved oxygenation and significantly decreased mortality in a heterogeneous group of pediatric patients with ALI. 17 However, there were no significant differences in the duration of ventilation, intensive care unit stay, or hospital stay.…”

The effects of porcine pulmonary surfactant on smoke inhalation injury

“…Despite the encouraging experimental evidence that exogenous surfactant administration was a potential adjunctive therapy in ALI and/or ARDS, the beneficial effects and safety issues of exogenous surfactant supplement in treatment of ALI and/or ARDS patients except neonatal respiratory distress syndrome is controversial [41,42]. These differences of therapeutic effects were dependent on the doses of PPS, approach of medication administration, the severity and stage of ALI and/or ARDS, and the causes of ALI.…”

Comparison of Polymyxin E and Polymyxin B as an Additive to Pulmonary Surfactant in Escherichia coli Pneumonia of Ventilated Neonatal Rabbits

“…For treatment of acute inflammatory lung injury, SF must have the greatest possible activity and resistance to inactivation [10]. Often, repeated high SF doses are needed to overcome inhibition as shown in premature neonates with culture-positive bronchoalveolar lavage [11].…”