Surfactant replacement therapy.

Abstract

In 1959 Avery and Mead discovered that the lungs of infants who died of hyaline membrane disease (HMD) were deficient in surfactant.1 Surfactant reduces surface tension and stabilises alveoli at low lung volumes and may act as an "anti-stick" or lubricant allowing the alveolar walls to remain open.2" HMD is characterised by progressive atelectasis and respiratory failure in premature infants and is a major cause of morbidity and mortality in the neonatal period.56 Numerous studies of the development of the pulmonary surfactant system have led to the clinical use of phospholipid composition ofhuman amniotic fluid to predict lung maturity and to the use of antenatal hormones to accelerate lung maturation. Recently, this research has culminated in successful attempts to treat HMD in premature infants with surfactant replacement therapy (SRT).We will begin this article with a brief review of the pulmonary surfactant system and the various types ofsurfactants used in replacement therapy. This will be followed by a review of the animal and clinical studies investigating SRT 10-15% protein.278 The major phospholipid in surfactant is phosphatidylcholine of which approximately 70-75% is present as dipalmitoyl phosphatidylcholine (DPPC), the major surface active component in surfactant. The second most abundant phospholipid is phosphatidylglycerol (PG) which comprises 7-10% of total surfactant. These lipids are important in the formation of the monolayer on the alveolar-air interface, and PG is important in the spreadability over a large surface area. (Curosurf) has been used in Europe. In addition to containing the phospholipids of surfactant, these modified natural surfactants also contain the hydrophobic surfactant proteins SP-B and SP-C, but they do not contain the hydrophilic proteins, SP-A and SP-D. Synthetic surfactants have been designed and one preparation contains surface active phospholipids as well as agents which improve spreadability and stability of the preparation. The first synthetic surfactant preparation that was approved for use by the FDA in 1990 was Exosurf which contains DPPC, PG, and the stabilisers tyloxapol and hexadecanol. Another synthetic surfactant that has been used in both animal research and clinical trials is called artificial lung expanding compound (ALEC) which is a mixture of DPPC and phosphatidylglycerol in a ratio of 7:3 by weight.65 The synthetic preparations do not contain the surfactant proteins. There are efforts currently underway, however, to develop engineered surfactants which contain synthetic phospholipids and recombinantly synthesised human surfactant proteins. The advantages of these surfactants are that they would not be from animal sources and they would contain the human surfactant proteins which may have important physiological roles in the function and metabolism of exogenously administered surfactant without the potential for antigenic stimulation of proteins derived from animal sources.Animal studies of surfactant replacement therapy Studies of SRT in anima...

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation

“…At 32 weeks' gestation the majority of pregnancies have mature lecithin/sphingomyelin ratios following prophylactic corticosteroids29, 30, and in our institution neonatal survival at 32 weeks is similar to that at term. The incidence of RDS at 32 weeks' gestation has been estimated to be 5% with surfactant use31 and mortality to be less than 1% for non‐anomalous fetuses32. In keeping with this, there were no neonatal deaths in our study group, and only a minority developed RDS.…”

Perinatal outcomes in monoamniotic gestations

“…This finding calls into question the validity of delaying delivery. The incidence of significant respiratory distress syndrome at 32 completed weeks of gestation has been estimated to be 5% with surfactant use 79 , and mortality to be less than 1% for non-anomalous fetuses 80 .…”

Continuous neonatal blood gas monitoring using a multiparameter intra-arterial sensor

“…The need to avoid hyperoxia as well as hypoxia has similar implications for PaO 2 . Moreover, rapid changes in ABG can occur after surfactant administration, especially natural surfactants,14 and during high frequency oscillatory ventilation. Indeed, some workers have suggested patients receiving the latter should always have continuous PCO 2 monitoring 15…”