Surfactant: agents utilized to lower surface tension.
Clinical Indications for Exogenous Surfactants
Exogenous surfactants are clinically indicated for the treatment or prevention of RDS in the newborn. This may be done as a prophylactic or rescue treatment. The use of surfactants in ARDS has been studied, but continues to be a topic of discussion. Currently, there is no U.S. Food and Drug Administration (FDA) approved surfactant agent to treat ARDS
The term exogenous, used to describe this class of drugs, refers to the fact that these are surfactant preparations from outside the patient's own body. These preparations may be obtained from other humans, from animals, or by laboratory synthesis. The clinical use of exogenous surfactants has been to replace the missing pulmonary surfactant of the premature or immature lung in RDS of the newborn. The results of literature for treatment of ARDS have been inconsistent.
Types of Exogenous Surfactant Preparations
Exogenous surfactant preparations can be placed into three categories: Natural/Modified Natural, Synthetic, and Synthetic/Natural.
Natural/Modified Natural Surfactant - Natural surfactant is an apt descriptive term for the category of surfactants obtained from animals or humans by alveolar wash or from amniotic fluid. The large surface-active aggregates of natural surfactant are recovered from the fluid by centrifugation or simple filtration. Because these are natural surfactants, the ingredients necessary for effective function to regulate surface tension are present. Examples of natural surfactant include Beractant (Survanta), Poractant Alfa (Curosurf), and Clafactant (Infasurf)
Synthetic Surfactant - Synthetic surfactants are mixtures of synthetic components. The characteristic feature of artificial surfactants is that none of the ingredients are obtained from natural sources, such as human, cow, or pig lung. Synthetic surfactants do not contain any of the surfactant proteins, including SP-B or SP-C, that are found in the natural preparations. A major advantage of this class of surfactant is its freedom from contaminating infectious agents and additional foreign proteins that may be antigenic to the recipient. A possible disadvantage is the lack of equivalent performance between the organic chemicals substituted for the naturally occurring surfactant proteins, such as SP-A, -B, or -C. At present, no synthetic surfactant is available. Exosurf (colfosceril palmitate), which was the only synthetic surfactant on the market, has been removed. However, a new synthetic surfactant, Surfaxin (lucinactant) is currently being considered by the FDA. In a study conducted by Moya and colleagues they found that Surfaxin was better at reducing RDS and bronchopulmonary dysplasia than Exosurf, but not less than those administered Survanta. Another study it found no difference between Surfaxin and Curosurf. The interesting make-up of Surfaxin it that it appears to have a chemical replication of surfactant protein B, which has never been created in synthetic agents. The use of lucinactant is being created as an aerosolized agent. This agent, Aerosurf being developed by the same manufactured would be aerosolized to the airway instead of direct instillation. This agent is currently in phase two trials and will not be available or reviewed for a number of years.
Synthetic Natural Surfactant - An ideal solution to the problems of Concern in both naturaland artificial surfactants would be genetically engineered surfactant produced by recombinant DNA technology. However, there is not literature describing this type of surfactant agent.
Mode of Action
The mode of action of exogenous surfactants is to replace and replenish a deficient endogenous surfactant pool in neonatal RDS. Endogenous surfactant is normally secreted by alveolar type II cells, which leaves the alveolar space and reenters the type II cells in the form of small vesicles. In the intracellular space, surfactant components are recycled. Exogenously administered surfactant that reaches the alveolar space can be recycled into the type II cells and form a surfactant pool to regulate surface tension.
Specific Exogenous Surfactant Preparations
Beractant (Survanta) is considered a modified natural surfactant. It is a natural bovine lung extract mixed with colfosceril palmitate (DPPC), palmitic acid, and tripalmitin. These last three ingredients are used to standardize the composition of the drug preparation, as well as to reproduce the surface tension-lowering properties of natural surfactant
Calfactant is another modified natural surfactant preparation from calf lung (bovine). It is an organic solvent extract of calf lung surfactant obtained by cell-free bronchoalveolar lavage. The extract contains phospholipids, neutral lipids, and hydrophobic proteins SP-B and SP-C.
Poractant alfa is a natural surfactant obtained as an extract of porcine lung. It is a suspension consisting of approximately 99% phospholipids and about 1% surfactant-associated proteins, including surfactant protein B.
Future Directions of Surfactant
In addition to RDS of the newborn, surfactant replacement therapy has been considered in meconium aspiration syndrome. In a meta-analysis, Soll and Dargaville report that surfactant therapy may be beneficial in reducing respiratory illness severity and reducing infants' need for extracorporeal membrane oxygenation (ECMO). Surfactant therapy had been studied for a variety of adult respiratory disorders. This topic is comprehensively reviewed by Hamm and colleagues. Acute respiratory distress syndrome (ARDS) in the adult is a potential target for surfactant therapy. In RDS of the newborn, the primary abnormality of lung function is related to surfactant deficiency. In ARDS with adults, the surfactant deficiency is secondary to lung injury with complex inflammatory responses. This would suggest a difference in clinical response to surfactant therapy between premature infants and adults with ARDS. In addition, dose amount and administration techniques may need to be modified for therapy in adults, who have large lung volumes compared with infants. If lung injury in ARDS is nonuniform in distribution, exogenous surfactant, especially if aerosolized, may distribute unevenly to more compliant lung areas instead of to areas needing surfactant the most.
Other adult respiratory disorders in which either surfactant replacement therapy or abnormal surfactant regulation may occur include pneumonia, lung transplants, sarcoidosis, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, alveolar proteinosis, obstructive lung disease including asthma, radiation pneumonitis, and drug-induced pulmonary disease.
By Douglas Gardenhire MS, RRT-NPS
Douglas Gardenhire is a veteran therapist, author, educator and the Director of Clinical Education in the RC Program at GA State University.
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|Title Annotation:||RESPIRATORY PHARMACOLOGY|
|Publication:||FOCUS: Journal for Respiratory Care & Sleep Medicine|
|Date:||Sep 1, 2009|
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