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Is There a Difference in Surfactant Treatment

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Is There a Difference in Surfactant Treatment y & R ar esp on ir m a l to u r y Ramanthan et al., J Pulmon Resp Med 2013, S13 P f M o e l Journal of Pulmonary & Respiratory d a i DOI: 10.4172/2161-105X.S13-004 n c r i n u e o J ISSN: 2161-105X Medicine Review Article Open Access Is there a Difference in Surfactant Treatment of Respiratory Distress Syndrome in Premature Neonates? A Review Rangasamy Ramanthan1, Karen Kamholz2 and Alan M Fujii3* 1LAC+USC Medical center and Children’s Hospital of Los Angeles, University of Southern California, Keck School of Medicine, USA 2Department of Pediatrics, MedStar Georgetown University Hospital, USA 3Department of Pediatrics, Boston Medical Center, Boston University School of Medicine, USA Abstract Exogenous surfactant treatment of premature infants with Respiratory Distress Syndrome (RDS) has been the standard of care for more than two decades. There are now many studies comparing various surfactant preparations. Data are clear that the synthetic surfactants without surfactant proteins are inferior to animal derived surfactant preparations. In the United States, commercially available surfactants are beractant, calfactant, poractant alfa, and lucinactant. Relative efficacy of the various available animal derived surfactants in the United States appear to favor poractant alfa, the surfactant preparation with the highest concentrations of phospholipids and high concentration of surfactant proteins, allowing a higher initial dose of phospholipids in preterm infants less than 32 weeks. A new synthetic surfactant with a surfactant protein analog, lucinactant, has been recently been approved for use in the United States. Synthetic surfactants hold the possibility of surfactant treatments without potential animal-born infectious agents or animal proteins that could induce an immune response in fragile premature infants with multiple medical problems. New surfactant administration strategies are described, complimenting new respiratory support strategies, designed to minimize invasive mechanical ventilation and decrease the frequency of chronic lung disease. Minimally invasive surfactant administration strategies are being developed to accommodate these new respiratory support strategies. The goal of this manuscript is to review the available surfactant preparations and their administration strategies. Introduction infants are segregated into synthetic vs. animal derived surfactant preparations. The older synthetic surfactants, such as colfosceril RDS was first characterized as surfactant deficiency disease of palmitate (Exosurf®, Glaxo Wellcome, UK) and pumactant (ALEC®, the newborn by Avery and Mead in 1959 [1]. The first clinical use of artificial lung expanding compound, Britannia Pharmaceuticals, UK) exogenous surfactant to treat RDS was by Fujiwara and colleagues are composed of phospholipids, with no surfactant proteins (Table in 1980 [2]. These sentinel reports lead to our current strategies for the surfactant treatment of RDS in premature infants that began in 1). Animal derived surfactant preparations are extracted from either 1989, with the Food and Drug Administration (FDA) approval of the bovine or porcine lungs by mincing or lavaging surfactant from the synthetic surfactant colfosceril palmitate suspension (Exosurf®), closely animal lungs. Specifically, animal-derived surfactant preparations followed by approval of beractant (Survanta®), the first animal derived have surfactant proteins, SP-B and SP-C, responsible for spreading surfactant. These were the first commercially available surfactant and adsorption of phospholipids at the alveolar air-liquid interface preparations in the United States and were associated with a greater [11,12]. Animal derived surfactants with surfactant proteins induce a decline in mortality in premature infants with RDS than in any other more rapid improvement in lung function than synthetic surfactants years in recent decades [3,4]. Since 1989, several animal derived that lack surfactant proteins [13-19]. While synthetic surfactants surfactant preparations have been developed, each surfactant being without surfactant proteins are still being manufactured, the animal more concentrated and tending to have a more rapid onset and longer derived surfactants have become the standard of care. Animal derived duration of action. The animal derived surfactant preparations contain surfactants have become progressively more concentrated, with surfactant protein B and C (SP-B and SP-C) and are superior to the higher concentrations of phospholipids and surfactant proteins, and a early synthetic surfactants without surfactant protein. Nonetheless, concomitant decrease in the volume of administration and increase in RDS continues to be a leading cause of infant morbidity and mortality the rapidity of onset and duration of action (Table 2). Development of in the United States. Reviews on this topic are available from Logan and newer synthetic surfactants, such as lucinactant and rSP-C surfactant Moya [5], Pfister et al. [6], Ramanathan et al. [7], Seger and Soll [8], (Venticute®, ALTANA Pharma AG, Konstanz, Germany, not approved and Fujii and Carillo [9]. There is also a compelling review by Bassler for use in the United States) have synthetic or recombinant polypeptides and Poets [10] advocating for the inclusion of surfactants in the World that may function similarly to that of animal derived surfactant Health Organization (WHO) model list of essential medicines. In the current review, we summarize the current state of the art, concentrating preparations. on the comparison of various animal derived surfactant preparations from a clinician’s perspective. We briefly review what is known of the comparison between animal derived surfactants vs. the newer synthetic *Corresponding author: Alan Fujii, MD, Boston Medical Center, Boston University surfactant, lucinactant (Surfaxin®, Discovery Labs, Warrington, PA), School of Medicine, One Boston Medical Center Place, Boston, MA 02118, USA, approved by the FDA for use in the United States in 2012, and a brief Tel: 617-414-5461; Fax: 617-414-7297; E-mail: [email protected] discussion of the cost-benefit analysis of surfactant use. In addition, we Received February 18, 2013; Accepted July 04, 2013; Published July 08, 2013 discuss some of the novel surfactant administration strategies that are Citation: Ramanthan R, Kamholz K, Fujii AM (2013) Is there a Difference in being used to support newer strategies of Minimally Invasive ventilation Surfactant Treatment of Respiratory Distress Syndrome in Premature Neonates? and Surfactant Therapy (MIST) in these fragile premature infants. A Review. J Pulmon Resp Med S13: 004. doi:10.4172/2161-105X.S13-004 Copyright: © 2013 Ramanthan R, et al. This is an open-access article distributed Background under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the Surfactant preparations for the treatment of RDS in premature original author and source are credited. Controversies in the Management of Respiratory J Pulmon Resp Med ISSN: 2161-105X JPRM, an open access journal Distress Syndrome in Premature Neonate Citation: Ramanthan R, Kamholz K, Fujii AM (2013) Is there a Difference in Surfactant Treatment of Respiratory Distress Syndrome in Premature Neonates? A Review. J Pulmon Resp Med S13: 004. doi:10.4172/2161-105X.S13-004 Page 2 of 7 PHOSPHOLIPID PHOSPHOLIPIDS Protein Mimicking Molecules DOSE VOLUME SURFACTANT COMPOSITION (mg/mL) (mg/mL) (mL/kg) Pumactant DPPC + PG 83.3 0 1.2 (ALEC®) [19,20] Colfosceril palmitate DPPC + Hexadecanol + Tyloxapol 13.5 0 5 (Exosurf®) [21] DPPC + 21 Synthetic aminoacids 0.862 {5 Lysines (K) + 30 5.8 Lucinactant (Surfaxin®) [22] (KL-4) 16 Leucines (L)} DPPC (phospholipid dipalmitoylphosphatidylcholine) PG (Phosphatidylglycerol) Table 1: Synthetic surfactants. PHOSPHO-LIPIDS DSPC Total Proteins SP-B PLMGN SURFACTANT PREPARATION (mg/mL) (mg/mL) (mg/mL) (mg/mL) (mol% total PL) Beractant Minced bovine lung extract 25 11-15.5 <1 Not specified 1.5 ± 0.226 (Survanta®) [23] +DPPC, Palmitic Acid, Tripalmitin Calfactant (Infasurf®) [23] Bovine Lung Lavage/DPPC, Cholesterol 35 16 0.7 0.26 Not specified Poractant alfa (Curosurf®) [25] Minced porcine lung extract-purified via Liquid 3.4 ± 0.126 76 30 1 0.45 Gel chromatography DPPC (phospholipid dipalmitoylphosphatidylcholine) DSPC (Disaturated Phosphotidylcholine) SP-B (Surfactant Protein B) PLMGN (plasmalogens) PL (Phospholipids) Table 2: Animal-derived surfactants. Overview of Surfactant Treatment of Rds or porcine extracts or lung lavage are beractant (Survanta®), calfactant (Infasurf®), poractant alfa (Curosurf®), and bovactant (Alveofact®)[16- Human surfactant is composed of lipids and surfactant proteins 30]. These surfactants differ in their concentration of phospholipids, that act to reduce surface tension in the terminal bronchioles and plasmalogens and the surfactant-proteins, SP-B and SP-C (Table 2). alveoli. The majority of the lipid component is phosphatidylcholine, Beractant, a bovine minced lung extract, has added DPPC. Calfactant, 50% of which is the phospholipid, Dipalmitoylphosphatidylcholine a lavaged calf lung extract, has a higher concentration of SP-B than (DPPC). DPPC enables the surfactant layer to change its configuration beractant. Poractant alfa, a porcine minced lung extract, has the highest during inspiration and expiration, reducing surface tension of the concentration of phospholipids and plasmalogens. Poractant alfa has alveoli [12]. There are
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