Surfactant agents
After reading this chapter, the reader will be able to:
1. Define key terms that pertain to surfactant agents
2. List all available exogenous surfactant agents used in respiratory therapy
3. Describe the mode of action for exogenous surfactant agents
4. Discuss the route of administration for exogenous surfactant agents
5. Recognize hazards and complications of exogenous surfactant therapy
Chapter 10 reviews pharmacologic agents termed surfactants, which are intended to alter the surface tension of alveoli and the resulting pressures needed for alveolar inflation. The physical principles of surfactants and surface tension forces are reviewed as a basis for introducing agents that have been used or are currently used in respiratory care. The use of current exogenous surfactant agents in the treatment of respiratory distress syndrome (RDS) of the newborn is presented.
Physical principles
Surface tension
Surface tension is the force caused by attraction between like molecules that occurs at liquid-gas interfaces and holds the liquid surface intact. The units of measure for surface tension are usually dynes per centimeter (dyn/cm), indicating the force required to cause a 1-cm rupture in the surface film. Because the molecules in a liquid are more attracted to each other than to the surrounding gas, a droplet or spherical shape usually results (Figure 10-1, A).
Laplace’s law
LaPlace’s law is the physical principle describing and quantifying the relationship between the internal pressure of a drop or bubble, the amount of surface tension, and the radius of the drop or bubble (Figure 10-1, B). For a bubble, which is a liquid film with gas inside and out, LaPlace’s law is as follows:
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In alveoli, there is only a single air-liquid interface, and LaPlace’s law is as follows:
Clinical indications for exogenous surfactants
• Prophylactic treatment: Prevention of RDS in infants with very low birth weight and in infants with higher birth weight but with evidence of immature lungs, who are at risk for developing RDS
• Rescue treatment: Retroactive, or “rescue,” treatment of infants who have developed RDS
The basic problem in RDS is lack of pulmonary surfactant as a result of lung immaturity. This lack of pulmonary surfactant results in high surface tensions in the liquid-lined, gas-filled alveoli. Increased ventilating pressure is required to expand the alveoli during inspiration, which leads to ventilatory and respiratory failure in an infant without ventilatory support. This concept and the effect of exogenous surfactant are shown in Figure 10-2. Exogenous surfactants are also being investigated for efficacy in the treatment of acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and meconium aspiration syndrome (MAS), although MAS is not an approved clinical application at this time.1
Identification of surfactant preparations
Table 10-1 lists surfactant formulations that currently have U.S. Food and Drug Administration (FDA) approval for general clinical use in the United States. Detailed differences between these formulations and details of their dosing and administration are discussed subsequently for each agent in separate sections.
TABLE 10-1
Exogenous Surfactant Preparations Currently Approved for Use in the United States*
| DRUG | BRAND NAME | FORMULATION AND INITIAL DOSE |
| Beractant | Survanta |
*Individual agents are discussed subsequently in a separate section. Detailed information on each agent should be obtained from the manufacturer’s drug insert.
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. These agents have also been investigated for use in ARDS and have been beneficial in improving oxygenation, although results have been inconsistent.2,3
Composition of pulmonary surfactant
Pulmonary surfactant is a complex mixture of lipids and proteins (Box 10-1). The surfactant mixture is produced by alveolar type II cells. Their primary function, although not their only function, is to regulate the surface tension forces of the liquid alveolar lining. Surfactant regulates surface tension by forming a film at the air-liquid interface. Surfactant reduces surface tension as it is compressed during expiration, reducing the amount of pressure and inspiratory effort required to reexpand the alveoli during a succeeding inspiration. The amount of extracellular (i.e., outside the type II cell) surfactant in animals is 10 to 15 mg/kg body weight in adults and 5 to 10 times that in mature newborns.4 Figure 10-3 illustrates the source, basic composition, and regulation of pulmonary surfactant in the alveolus. Each of the major components is described in the following sections.
Lipids
Lipids make up about 85% to 90% of surfactant by weight. The lipid component of surfactant is approximately 90% phospholipids, such as phosphatidylcholine, phosphatidylglycerol, sphingomyelin, and others, and 10% other lipids, most of which is cholesterol.5 Phospholipids have lipophilic and hydrophilic properties and are able to achieve low surface tensions at air-liquid interfaces. Phosphatidylcholine constitutes about 75% to 80% of the phospholipids in surfactant, and about half of this is dipalmitoylphosphatidylcholine (DPPC), which is also known as lecithin. DPPC is the surfactant component predominantly responsible for the reduction of alveolar surface tension. The hydrophilic choline residue of DPPC is associated with the liquid phase in alveoli, whereas the hydrophobic palmitic acid residue projects into the air phase.6
Proteins
The total protein portion of surfactant is about 10% by weight. Approximately 80% of this portion is contaminating serum proteins, and 20% is surfactant-specific proteins. Four surfactant-specific proteins (SPs) have been identified so far: SP-A, SP-B, SP-C, and SP-D.4 Proteins of the surfactant mixture are reviewed by Johansson and associates.7
