Surfactant: where it comes from and where it's going.
The genesis of the pulmonary tree and its branches--the mainstem, lobar, segmental and bronchiolar airways--are defined by periods of lung development. The period of development has time-specific phases of lung tissue development in utero, suggesting that the lung tissue, airways and pneumocytes will mature and develop at a certain speed, and that this speed is directly related to the maturity and survivability of the infant.
Using this model, the infant's lungs and airways begin developing in the Embryonic period, from 21 intrauterine days to about five weeks of life. The baby will then progress into the Fetal period that includes lung tissue development in the Pseudoglandular Stage from six weeks to 16 weeks, the Canalicular stage from 16 weeks to 26 weeks, and the Terminal saccular stage from 26 weeks to the infant's birth at 38 to 40 weeks of normal gestation.
It is interesting to note that the Alveolar stage, where alveolar buds ripen and grow on the distal respiratory bronchial tree limb, will continue the process of alveolar growth from 32 weeks until the child is 8 to 10 years of age. Murray noted that, likewise, the evolution of the pulmonary circulation isn't complete until somewhere in the 15th to 19th year of the child's life. At maturity, about 470 million alveoli will be formed, with about 300 million alveoli per lung.
While there are well-documented exceptions to the rule, theoretically, we in the field look on the 24th week of gestation as the first point of successful extrauterine life. However, extrauterine survival at this point will require aggressive life support systems with a lot of related risks and hazards, and this aggressive care will challenge the long-term quality of life for critically ill babies, especially those weighing less than 486g (<1 Ib).
That said, the improvements in prenatal follow-up care and the miracle of exogenous surfactant therapy have improved the prognosis for millions of babies over the past 30 years. Hall id ay noted that in 1929, Kurt von Neergaard suggested the presence of pulmonary surfactant and described its relevance to the newborn's first breath.
One historical point taken from Halliday's paper was that the 1963 death from respiratory distress syndrome of Patrick B. Kennedy served to focus the American public's attention to infant mortality, and may have spurred research in that direction.
Endogenous surfactants, those which occur naturally in the lungs of the baby, are a product of the alveolar type II cell, the granular pneumocyte, and that natural surfactant consists of 85 to 90 percent lipids and 10 percent proteins, jointly comprising surfactant as we know it, dipalmitoylphosphatidylcholine (DPPC), or lecithin. Respiratory therapists have always been taught that the L/S (lecithin/sphyngomyelin) ratio of 2:1 in amniotic fluid provided some evidence of Type 2 cell maturity.
Gardenhire's 7th edition of Rau noted that alveolar type II cells also secrete other proteins such as cytokines, growth factors and antibacterial proteins into the alveolar space. Surfactant protein A (SP-A) may regulate the secretion and exocytosis of surfactant from the type II cell, as well as the re-uptake of surfactant for recycling and re-use. SP-A and other proteins, SP-B and SP-C, may hold the key to improved types of surfactant for therapy or other indications such as adult acute respiratory distress syndrome (ARDS), which has proven refractory to surfactant instillation therapy in adult patients.
The problems that impact the surfactant production in the small for dates, premature or high-risk neonate are multitudinous. Today, babies who meet the inclusion criteria set for the administration of exogenous surfactant preparations may receive one of several surfactant preparations. Much of the initial interest in surfactant dealt with the use of natural DPPC from human amniotic fluid, but most of the later research focused on artificial and biological preparations that were compatible with human patients, and marketable to physicians.
The published indications for the use of artificial surfactant preparations and dosages, both for prophylaxis and rescue criteria, were generated from controlled clinical trials. Infants were generally intubated and were receiving gentle, low-pressure manual positive pressure ventilation with low continuous distending airway pressure. The babies are placed in physical positions that advanced the surfactant using the gravity dependence of each targeted bronchopulmonary lobe and its segments. I explain here to students that we essentially use an oppositional postural drainage positioning strategy to allow the surfactant to flow and spread through the bronchial tree and into the alveoli.
One of the first available protein-free, artificial surfactant preparations was Exosurf, or colfosceril palmitate plus cetyl alcohol and tyloxapol. A 1991 paper by Dechant and Faulds noted that in a large clinical trial, babies diagnosed with respiratory distress syndrome who were treated with Exosurf had fewer pneumothoraces, and survivors had less incidence of bronchopulmonary dysplasia.
Although Exosurf was one of the important early protein-free non-biological surfactant preparations of the 1980s, it was later withdrawn from the U.S. market. Other protein-free, artificial surfactants were Pumactant and Turfsurf. Newer protein analogue artificial surfactants are Surtax in (lucinactant) and Venticute.
Biological surfactants were derived from minced lung or lunglavage extracts. Survanta (beractant) is derived from minced bovine lung extracts with DPPC added to the preparation. Indications for prophylaxis and rescue use in at-risk babies were generated from controlled clinical trials. Survanta was given 100 mg/kg (4mL/kg) in four divided doses and was indicated if the infant weighed < 1,250 g, had suspected surfactant deficiency, the risk of RDS or the physician opted to rescue an infant with RDS.
The biological surfactant preparation Infasurf (calfactant) was a natural lung-ravage surfactant derived from calf lung that required no reconstitution. Infasurf was considered indicated if the baby was < 29 weeks of gestation, had a high risk for RDS, was < 72 hours of age or developed RDS with intubation. Infasurf was given as 3 mL/kg in two 1.5 mL/kg doses.
The biological surfactant preparation Curosurf (poractant alfa) was derived from minced porcine lung extracts, and its indications followed similar risk profiles as noted in the biologicals above. Curosurf was given 2.5 mL/kg as 200mg/kg in two separate doses.
Surfactant should theoretically decrease the alveolar surface tension, allowing for alveolar recruitment, less positive and distending pressure to achieve critical alveolar opening pressures, and improved pulmonary compliance. The risks associated with surfactant therapy are primarily due to the critical condition of the patient, and the technique of instillation.
Airway occlusion, arterial desaturation, bradycardia, hyperoxygenation, overventilation and hypocarbia, apnea and pulmonary hemorrhage have been reported. Thorough patient assessment, team member communication and timing of surfactant doses may impact patient outcomes and quality of patient care.
Horbar and associates established an intervention hospital education program. They found that, compared with control hospitals, infants in intervention hospitals were more likely to receive surfactant in the delivery room, were less likely to receive the first dose more than two hours after birth, and received the first dose of surfactant sooner after birth.
Researchers continue to explore new types of surfactants, in particular surfactants that mimic or copy the biochemistry and proteins of human surfactant. This work will continue to improve the indications, safety and efficacy of surfactant therapy.
Douglas Masini is the Department Head/Chair of the Respiratory Therapy Program at Armstrong Atlantic State University in Savannah, CA. He can be reached at firstname.lastname@example.org.
by Douglas Masini, EdD, RPFT, RRT-NPS, AE-C, FAARC
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|Title Annotation:||PEDIATRIC/NEONATAL RESPIRATORY CARE|
|Publication:||FOCUS: Journal for Respiratory Care & Sleep Medicine|
|Date:||Jan 1, 2010|
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