DOCSLIB.ORG

Synthetic Surfactants: Where Are We? Evidence from Randomized, Controlled Clinical Trials

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthetic Surfactants: Where Are We? Evidence from Randomized, Controlled Clinical Trials Journal of Perinatology (2009) 29, S23–S28 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp REVIEW Synthetic surfactants: where are we? Evidence from randomized, controlled clinical trials F Moya1,2 1Department of Neonatology, New Hanover Regional Medical Center, Wilmington, NC, USA and 2Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA were shown in that meta-analysis or in any individual trials The benefits of exogenous synthetic or animal-derived surfactants for comparing these surfactants. None of these surfactant comparison prevention or treatment of respiratory distress syndrome (RDS) are well trials reported outcomes beyond the initial stay in the neonatal established. Data from head-to-head trials comparing animal-derived intensive care unit (NICU). surfactants primarily with the synthetic surfactant colfosceril suggest that Multiple studies have shown that synthetic surfactants lacking the major clinical advantages afforded by the presence of surfactant protein SP-B and SP-C fail to lower surface tension in vitro, whereas (SP)-B and SP-C in animal-derived preparations relate to faster onset of animal-derived surfactants can reduce it to an extent somewhat action, a reduction in the incidence of RDS when used prophylactically, and directly related to their SP content.3,4 The absence of SP-B seems to a lower incidence of air leaks and RDS-related deaths. However, no benefits be particularly important as animals or humans lacking SP-B in terms of overall mortality or BPD have been shown in these head-to-head because of a genetic mutation develop a fatal form of respiratory comparisons. Findings from trials of a new-generation synthetic surfactant failure during the neonatal period.5,6 In contrast, individuals with containing a peptide that mimics SP-B, as well as their follow-up study mutations in SP-C develop interstitial lung disease as adults rather suggest that its administration improves short-term clinical outcomes than respiratory disease during the neonatal period.7 compared with colfosceril and results in survival through 1 year of age, The purpose of this review is to summarize the results from which is at least comparable, if not perhaps superior, to that seen with published randomized trials comparing animal-derived with animal-derived surfactants. synthetic surfactants devoid of proteins and to review the evidence Journal of Perinatology (2009) 29, S23–S28; doi:10.1038/jp.2009.26 from clinical trials of a new-generation synthetic surfactant that 8 Keywords: surfactant; respiratory distress syndrome; bronchopulmonary contains phospholipids and a peptide that mimics SP-B. For a dysplasia; infant/newborn summary of all published head-to-head comparison trials of surfactants, including comparisons between animal-derived surfactants, the reader is referred to the recent review by Moya and Maturana.9 Introduction Animal-derived surfactants from bovine or porcine sources currently in clinical use contain various phospholipids and variable quantities of surfactant proteins (SP)-B and -C, whereas currently Composition of commonly used surfactants available synthetic surfactants contain only phospholipids and no The main characteristics and components of the most studied and surfactant proteins.1 Although synthetic surfactants have potential used synthetic and animal-derived surfactants are found in safety advantages over animal-derived products, they seem to be Table 1. The amount of phospholipids administered per dose of clinically inferior to animal-derived surfactants. This assertion is surfactant is quite variable and ranges from 50 to 200 mg kg–1. based primarily on the results of a meta-analysis of 11 controlled The volume of each dose and interval for administration trials comparing these two classes of surfactants, which showed a recommended by the various manufacturers are also different. marginally significant lower mortality and a lower risk of Colfosceril and pumactant contain no SPs. Animal-derived pneumothorax plus more rapid weaning with animal-derived surfactants differ in their contents of SP-B and SP-C.3 Calfactant surfactants compared with synthetic surfactants.2 However, no (Infasurf, Forest Laboratories, Inc., St Louis, MO, USA) contains the reductions in the incidence of bronchopulmonary dysplasia (BPD) highest concentration of SP-B on a weight basis, followed by poractant (Curosurf, Chiesi Farmaceutici, Parma, Italy). Beractant Correspondence: Dr F Moya, Department of Neonatology, New Hanover Regional Medical Center, 2131 South 17th Street, Wilmington, NC 28402-9025, USA. (Survanta, Ross Products Division, Abbott Laboratories, Columbus, E-mail: [email protected] OH, USA) has the lowest content of SP-B of these animal-derived Synthetic surfactants F Moya S24 Table 1 Main characteristics of surfactants commonly used or studied in neonates Surfactant Family Main Proteins Phospholipid Suggested dose Phospholipid phospholipids concentration (mg mlÀ1) (ml kgÀ1) per dose (mg kgÀ1) Colfosceril Synthetic DPPC No 13.5 5 67.5 Pumactant Synthetic DPPC, PG No 40 1.2 100 Beractant Animal-derived (bovine) DPPC, PG SP-B/SP-C 25 4 100 Calfactant Animal-derived (bovine) DPPC, PG SP-B/SP-C 35 3 105 Poractant Animal-derived (porcine) DPPC, PG SP-B/SP-C 80 1.25/2.5 100/200 Lucinactant Peptide-containing DPPC, POPG KL4 as SP-B 30 5.8 175 synthetic Abbreviations: DPPC, dipalmitoylphosphatidylcholine; PG, phosphatidylglycerol; POPG, palmitoyloleylphosphatidylglycerol; SP-B, surfactant protein B; SP-C, surfactant protein C. surfactants. The content of the SP-B mimic in lucinactant recent lucinactant prophylaxis trial comparing this surfactant with (Surfaxin, Discovery Laboratories, Warrington, PA, USA) is colfosceril, in which infants were also randomized to beractant in a discussed later. 2:2:1 scheme.10–15 A major advantage of these studies lies in the fact that several thousand infants have been included. A major limitation in the design of these studies is that none of them were Controlled trials comparing non-protein-containing masked, except for the comparison included within the lucinactant synthetic with animal-derived surfactants trial. Moreover, the use of antenatal steroids in all but the Since the advent of exogenous surfactant therapy, several lucinactant trials was <40%, reflecting the time when they were animal-derived but only two synthetic surfactants devoid of SPs have conducted. The cumulative results show that overall mortality was been used clinically, namely colfosceril (Exosurf, GlaxoSmithKline, 18.4% for beractant and 20.9% for colfosceril (relative risk (RR) Brentford, UK) and pumactant (artificial lung expanding 0.89, 95% CI 0.75 to 1.05). Only the incidence of pneumothorax compound, Britannia Pharmaceuticals Ltd, Redhill, Surrey, was reduced using beractant versus colfosceril when used for England). Over the past decade and a half, there have been many treatment of RDS (RR 0.61, 95% CI 0.47 to 0.78) with a number randomized trials comparing these two major classes of surfactants, needed to treat (NNT) of 21, but not for prophylaxis of RDS. No although most have used a treatment rather than a prophylactic changes in need for supplemental oxygen at 36 weeks were noted approach. Soll and Blanco2 conducted a widely quoted systematic (23.5 versus 25.6%, respectively). Nonetheless, those trials for review of 11 trials comparing animal-derived surfactants with treatment of RDS in which ventilatory settings were reported synthetic surfactants. Seven of ten of the trials included in that showed more rapid reductions of supplemental oxygen and review compared colfosceril with beractant, two trials compared it ventilatory pressures among infants given beractant, which with calfactant and one trial with poractant alfa. Only one trial averaged about 7% lower FiO2 and 0.7 cm H2O lower mean airway compared the only other synthetic surfactant used clinically, pressure over the first 48 h. It should be noted that, when pumactant, with poractant. These authors concluded that both types colfosceril was compared with beractant using a prophylactic of surfactants are effective in the treatment and prevention of approach, a secondary comparison in one of the lucinactant trials, respiratory distress syndrome (RDS). However, they also concluded beractant reduced the incidence of RDS at 24 h (33.3 versus 47.2%, that, when taken together, use of animal-derived surfactants respectively), but did not result in less overall deaths, deaths due to 15 resulted in fewer deaths, greater early improvement in the RDS or other complications. requirement for ventilatory support and a lower overall incidence of Collectively, these data show that beractant has clinical pneumothorax than synthetic products containing only advantages such as less pneumothorax and more rapid weaning phospholipids. No advantages in terms of reduction in the incidence over colfosceril mainly when used for treatment of RDS, although of BPD were described in this systematic review or in any of the it is also more effective in prevention of RDS than colfosceril. individual trials included in it. In addition, a small but significant No benefits in terms of overall mortality or BPD have been shown. increase in the incidence of intraventricular hemorrhage (IVH) among infants treated with animal-derived surfactants was reported. Colfosceril versus calfactant There have been only two trials comparing colfosceril and Colfosceril versus beractant calfactant, one for prophylaxis and one for
Load more

Recommended publications
  • Lucinactant Attenuates Pulmonary Inflammatory Response, Preserves Lung Structure, and Improves Physiologic Outcomes in a Preterm Lamb Model of RDS
    nature publishing group Translational Investigation Articles Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS Marla R. Wolfson1–4, Jichuan Wu1,4, Terrence L. Hubert1, Timothy J. Gregory5, Jan Mazela5,6 and Thomas H. Shaffer1,3,7 BACKGROUND: Acute inflammatory responses to supple­ (2). Theoretically, a reduction in the lung inflammatory load mental oxygen and mechanical ventilation have been impli­ related to RDS may not only equate to an improvement in cated in the pathophysiological sequelae of respiratory distress pulmonary outcome but also to a potential improvement in syndrome (RDS). Although surfactant replacement therapy other neonatal morbidities such as necrotizing enterocoli- (SRT) has contributed to lung stability, the effect on lung tis, retinopathy of prematurity, and cerebral palsy. Although inflammation is inconclusive. Lucinactant contains sinapultide more classical forms of anti-inflammatory agents such as early (KL4), a novel synthetic peptide that functionally mimics sur­ postnatal steroids have demonstrated acute improvements in factant protein B, a protein with anti-inflammatory proper­ oxygenation and pulmonary mechanics in preterm infants, ties. We tested the hypothesis that lucinactant may modulate because of significant adverse effects these agents are not con- lung inflammatory response to mechanical ventilation in the sidered safe for routine use in critically ill preterm infants (3). management of RDS and may confer greater protection than New therapies are urgently needed and being explored that animal-derived surfactants. specifically target the acute inflammatory responses in the METHODS: Preterm lambs (126.8 ± 0.2 SD d gestation) were lung (4–7). randomized to receive lucinactant, poractant alfa, beractant, or Events leading to inflammation in the lung and subsequent no surfactant and studied for 4 h.
    [Show full text]
  • Miscibility of Egg Yolk Lecithin with Palmitic Acid and Hexadecanol At
    Journal of Oleo Science Copyright ©2013 by Japan Oil Chemists’ Society J. Oleo Sci. 62, (7) 471-480 (2013) Miscibility of Egg Yolk Lecithin with Palmitic Acid and Hexadecanol at the Air-Water Interface Hiromichi Nakahara and Osamu Shibata＊ Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University; 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan Abstract: The miscibility of Langmuir monolayers of egg yolk lecithin (eggPC) with n-hexadecanoic acid (PA), 1-hexadecanol (HD), and their equimolar mixture (PA/HD) was investigated thermodynamically and morphologically. Surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms for the binary and ternary systems were measured, employing the Wilhelmy method and the ionizing 241Am electrode method, respectively. From the thermodynamic perspective, eggPC was partially miscible with PA, HD, and PA/HD within the monolayer state, in terms of an excess Gibbs free energy of mixing calculated from the π-A isotherms and a two-dimensional phase diagram based on a monolayer collapse pressure. This was also directly supported by phase behavior observations using fluorescence microscopy (FM). EggPC formed a typical liquid-expanded (LE) monolayer, and the others formed liquid-condensed (LC) monolayers. The FM images exhibited miscible modes at middle molar fractions of PA, HD, and PA/ HD, and immiscible patterns at large molar fractions for all the systems examined. A new finding in the present study was that the eggPC/PA, eggPC/HD, and eggPC/(PA/HD) systems exhibited partial miscibility, although the systems were made of both LE (eggPC) and LC monolayers (the others).
    [Show full text]
  • What's New in Surfactant?
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Eur J Pediatr (2007) 166:889–899 DOI 10.1007/s00431-007-0501-4 REVIEW What’s new in surfactant? A clinical view on recent developments in neonatology and paediatrics Jasper V. Been & Luc J. I. Zimmermann Received: 26 March 2007 /Accepted: 18 April 2007 / Published online: 22 May 2007 # Springer-Verlag 2007 Abstract Surfactant therapy has significantly changed evolving and recent developments include further evolution clinical practice in neonatology over the last 25 years. of synthetic surfactants, evaluation of surfactant as a Recent trials in infants with respiratory distress syndrome therapeutic option in lung diseases other than RDS and (RDS) have not shown superiority of any natural surfactant the discovery of genetic disorders of surfactant metabolism. over another. Advancements in the development of syn- Ongoing research is essential to continue to improve thetic surfactants are promising, yet to date none has been therapeutic prospects for children with serious respiratory shown to be superior to natural preparations. Ideally, disease involving disturbances in surfactant. surfactant would be administered without requiring mechanical ventilation. An increasing number of studies Keywords Surfactant . Lung disease . investigate the roles of alternative modes of administration Respiratory distress syndrome . Preterm . Therapy and the use of nasal continuous positive airway pressure to minimise the need for mechanical
    [Show full text]
  • 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.
    [Show full text]
  • Animal-Derived Surfactants for the Treatment and Prevention of Neonatal Respiratory Distress Syndrome: Summary of Clinical Trials
    REVIEW Animal-derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials J Wells Logan Introduction: Available literature suggests that the advantage of animal-derived surfactants Fernando R Moya over fi rst-generation synthetic agents derives from the presence of surface-active proteins and their phospholipid content. Here we summarize the results of clinical trials comparing animal- Department of Neonatology, derived surfactant preparations with other animal-derived surfactants and with both fi rst- and Southeast Area Health Educational second-generation synthetic surfactants. Center, New Hanover Regional Medical Center, Wilmington, NC, USA Methods: Published clinical trials of comparisons of animal-derived surfactants were sum- marized and compared. Comparisons emphasized differences in (1) key surfactant components attributed with effi cacy and (2) differences in published outcomes. Results: For the most important outcomes, mortality and chronic lung disease, currently avail- able natural surfactants are essentially similar in effi cacy. When examining secondary outcomes (pneumothorax, ventilator weaning, and need for supplemental oxygen), it appears that both calfactant and poractant have an advantage over beractant. The weight of the evidence, especially For personal use only. for study design and secondary outcomes, favors the use of calfactant. However, the superiority of poractant over beractant, when the higher initial dose of poractant is used, strengthens the case for use of poractant as well. Conclusions: Clinical trials suggest that the higher surfactant protein-B content in calfactant, and perhaps the higher phospholipid content in poractant (at higher initial dose), are the factors that most likely confer the observed advantage over other surfactant preparations.
    [Show full text]
  • Windtree Therapeutics Company Overview August 20, 2020 OTCQB:(NASDAQ: WINT) WINT Forward-Looking Statements
    Windtree Therapeutics Company Overview August 20, 2020 OTCQB:(NASDAQ: WINT) WINT Forward-looking Statements This presentation includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements, among other things, include statements about the Company's clinical development programs, business strategy, outlook, objectives, plans, intentions, goals, future financial conditions, future collaboration agreements, the success of the Company's product development activities, or otherwise as to future events. The forward-looking statements provide our current expectations or forecasts of future events and financial performance and may be identified by the use of forward-looking terminology, including such terms as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “will,” “should,” “could,” “targets,” “projects,” “contemplates,” “predicts,” “potential” or “continues” or, in each case, their negative, or other variations or comparable terminology, though the absence of these words does not necessarily mean that a statement is not forward-looking. We intend that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. These risks and uncertainties are further described in the Company's periodic filings with the Securities and Exchange Commission (“SEC”), including the most recent reports on Form 10-K, Form 10-Q and Form 8-K, and any amendments thereto (“Company Filings”).
    [Show full text]
  • Comparative Efficacy of Pulmonary Surfactant in Respiratory Distress Syndrome in Preterm Infants: a Bayesian Network Meta-Analysis
    Systematic review/Meta-analysis Comparative efficacy of pulmonary surfactant in respiratory distress syndrome in preterm infants: a Bayesian network meta-analysis Caihong Qiu, Cui Ma, Nana Fan, Xiaoyu Zhang, Guofeng Zheng Maternity and Child Health Care of Zaozhuang, China Corresponding author: Guofeng Zheng PhD Submitted: 4 April 2020 Maternity and Child Accepted: 18 June 2020 Health Care of Zaozhuang China Arch Med Sci E-mail: zheng__guofeng@ DOI: https://doi.org/10.5114/aoms.2020.97065 sina.com Copyright © 2020 Termedia & Banach Abstract Introduction: The comparative efficacy of pulmonary surfactant in the treat- ment of respiratory distress syndrome in preterm infants remains unclear. We aimed to evaluate the effectiveness of different pulmonary surfactant in the treatment of respiratory distress syndrome in preterm infants and to provide an evidence-based reference for clinical use. Material and methods: MEDLINE, Embase, The Cochrane Library, and Clini- cal Trials databases were electronically searched from inception to January 2019. Two reviewers independently screened literature and extracted data, and then R and RevMan 5.3 software packages were used to perform net- work meta-analysis. Results: The relative risk of respiratory distress syndrome in preterm infants associated with six different pulmonary surfactant was analysed, including beractant (Survanta), surfactant A (Alveofact), calfactant (Infasurf), porac- tant (Curosurf), lucinactant (Surfaxin), and colfosceril (Exosurf). Patients with the following drugs appeared to have significantly reduced mortality of respiratory distress syndrome compare with beractant: surfactant A (OR = 0.53, 95% CI: 0.31–0.90), calfactant (OR = 0.91, 95% CI: 0.85–0.97), porac- tant (OR = 0.72, 95% CI: 0.67–0.77), lucinactant (OR = 0.80, 95% CI: 0.71– 0.90), and colfosceril (OR = 0.93, 95% CI: 0.87–0.99).
    [Show full text]
  • Surfactant Replacement Therapy: 2013
    AARC Clinical Practice Guideline. Surfactant Replacement Therapy: 2013 Brian K Walsh RRT-NPS RPFT FAARC, Brandon Daigle RRT-NPS, Robert M DiBlasi RRT-NPS FAARC, and Ruben D Restrepo MD RRT FAARC We searched the MEDLINE, CINAHL, and Cochrane Library databases for English-language randomized controlled trials, systematic reviews, and articles investigating surfactant replacement therapy published between January 1990 and July 2012. By inspection of titles, references having no relevance to the clinical practice guideline were eliminated. The update of this clinical practice guideline is based on 253 clinical trials and systematic reviews, and 12 articles investigating sur- factant replacement therapy. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation scoring system: 1: Administration of surfactant replacement therapy is strongly recommended in a clinical setting where properly trained personnel and equipment for intubation and resuscitation are readily available. 2: Prophylactic surfactant administration is recommended for neonatal respiratory distress syndrome (RDS) in which surfactant deficiency is suspected. 3: Rescue or therapeutic administration of surfactant after the initiation of mechanical ventilation in infants with clinically confirmed RDS is strongly recom- mended. 4: A multiple surfactant dose strategy is recommended over a single dose strategy. 5: Nat- ural exogenous surfactant preparations are recommended over laboratory derived synthetic suspen- sions at this time. 6: We suggest that aerosolized delivery of surfactant not be utilized at this time. Key words: exogenous surfactant administration; intratracheal administration; prematurity; neonatal respiratory distress syndrome; surfactant. [Respir Care 2013;58(2):367–375. © 2013 Daedalus Enterprises] SRT 1.0 PROCEDURE forms a layer between the terminal airways/alveolar sur- faces and the alveolar gas.
    [Show full text]
  • An Overview of Acute Lung Injury in General and in Particular Viral
    Journal of Respiratory Diseases and Medicine Review Article ISSN: 2633-1063 An overview of acute lung injury in general and in particular viral infections with specific reference to nebulized surfactant and anticoagulation Johan Smith1, Andre R Coetzee2 and Johann M van Zyl3* 1Department of Paediatrics and Child Health, Tygerberg Children’s Hospital, Stellenbosch University and Tygerberg Hospital, South Africa 2Emeritus Professor of Anaesthesiology and Critical Care, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa 3Emeritus Professor of Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa Abstract The coronavirus 2 (SARS-CoV-2) has resulted in an international pandemic. The SARS-CoV-2 affects cardiovascular, digestive and urogenital systems. In an attempt to develop a multimodal and targeted approach to the pathophysiology associated with viral lung injury, we reviewed lung histopathology, inflammation, surfactant biology and pathophysiology related to viral associated acute lung injury (ALI / ARDS). Histopathology of viral pneumonia/ARDS cases of the past 100 years has revealed that lung parenchymal and vascular pathologic changes described in the 1918 influenza pandemic, are no different from the histopathology observed in other viral pandemics. Given the inflammatory storm which can occur in COVID-19 infection, the patient is a candidate to develop the classic multi-organ dysfunction and / or failure (MOD/F) which may well include ALI and ARDS. Because there is a well described temporal change in the pathophysiology associated with ALI /ARDS, a “one size fit al” remedy will not suffice, hence our attempt at a targeted functional approach. For instance, variable results in adults treated with surfactant have relegated the use of surfactant in adult ARDS to an uncertainty.
    [Show full text]
  • Comparison of Poractant Alfa and Lyophilized Lucinactant in a Preterm Lamb Model of Acute Respiratory Distress
    nature publishing group Articles Translational Investigation Comparison of poractant alfa and lyophilized lucinactant in a preterm lamb model of acute respiratory distress Jan Mazela1, T. Allen Merritt2, Michael H. Terry3, Timothy J. Gregory4 and Arlin B. Blood2 INTRODUCTiON: A lyophilized formulation of lucinactant of neonatal RDS. All of these surfactants, including porac- has been developed to simplify preparation and dosing. tant alfa, beractant, calfactant, and surfactant-TA, are derived Endotracheal administration of surfactant can be associated from animals. These products contain both hydrophobic sur- with potentially harmful transient hemodynamic changes factant proteins (SPs) B and C in various quantities and pro- including decreases in cerebral blood flow and delivery of O2 portions. The critical importance of SP-B was demonstrated to the brain. Efficacy and peri-dosing effects of poractant alfa by Clark et al., who showed respiratory failure occurring and a lyophilized form of lucinactant were compared in this soon after birth in an SP-B gene knockout mouse model (7). study. Synthetic surfactants such as colfosceril palmitate and pumac- METHODS: Premature lambs (126–129 d gestation) were tant did not contain any SPs (8) and are no longer used for the delivered by c-section, tracheostomized, ventilated, and instru- treatment of RDS. A meta-analysis by the Cochrane Library mented with cerebral laser Doppler flowmetry and tissue showed that animal-derived surfactants, when used to treat PO2 probes. Pulmonary compliance and tidal volumes were RDS, provide a significant benefit over synthetic surfactants by monitored continuously and surfactant lung distribution was decreasing the incidences of pulmonary air leaks and all-cause assessed.
    [Show full text]
  • Exogenous Surfactant Therapy in Pediatrics
    0021-7557/03/79-Supl.2/S205 Jornal de Pediatria Copyright © 2003 by Sociedade Brasileira de Pediatria ARTIGO DE REVISÃO Terapia com surfactante pulmonar exógeno em pediatria Exogenous surfactant therapy in pediatrics Norberto A. Freddi1, José Oliva Proença Filho2, Humberto Holmer Fiori3 Resumo Abstract Objetivo: Revisar o estágio atual do conhecimento sobre a Objective: To review current knowledge about the use of utilização do surfactante exógeno nas diferentes doenças pulmona- exogenous surfactants in the treatment of different lung diseases res que levam à insuficiência respiratória aguda em crianças. causing acute respiratory failure in children. Fontes dos dados: Este manuscrito baseia-se na experiência Source of data: This review is based on the authors’ experience clínica dos autores sobre o assunto e na revisão da literatura recente and on recent data retrieved from ONIA, Mdconsult, Medline and através de consulta aos bancos de dados ONIA, Mdconsult, Medline the Cochrane Database Library. e Cochrane Database Library. Summary of the findings: In spite of the success of the use of Síntese dos dados: Apesar do sucesso obtido com a utilização exogenous surfactants in Respiratory Distress Syndrome (RDS) of do surfactante exógeno na síndrome de desconforto respiratório do the newborn, some questions remain unanswered, such as the optimal recém-nascido, questões permanecem indefinidas, como o momento administration timing - either very early (prophylactic), based on do seu emprego, muito precoce (profilático), baseado na idade gestational age or on quick tests of lung maturity, or later, when the gestacional ou em testes rápidos de maturidade pulmonar, ou então clinical picture becomes unequivocal. In other severe diseases mais tardiamente, após o quadro clínico instalado.
    [Show full text]
  • Label Portion of the Trial (Part A) and 102 Patients Participated in a Subsequent Randomized Controlled Portion (Part B)
    HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------CONTRAINDICATIONS------------------------------ None. (4) These highlights do not include all the information needed to use SURFAXIN® safely and effectively. See full prescribing information for -----------------------WARNINGS AND PRECAUTIONS-----------------------­ SURFAXIN. • Acute Changes in Lung Compliance: Infants receiving SURFAXIN should receive frequent clinical assessments so that oxygen and SURFAXIN (lucinactant) Intratracheal Suspension ventilatory support can be modified to respond to changes in respiratory Initial U.S. Approval: [year] status. (5.1) • Administration-Related Adverse Reactions: If adverse reactions ----------------------------INDICATIONS AND USAGE--------------------------- including bradycardia, oxygen desaturation, reflux of SURFAXIN into SURFAXIN is indicated for the prevention of respiratory distress syndrome the endotracheal tube (ETT), and airway/ETT obstruction occur during (RDS) in premature infants at high risk for RDS. (1) administration of SURFAXIN, dosing should be interrupted and the infant’s clinical condition assessed and stabilized. Suctioning of the ETT ----------------------DOSAGE AND ADMINISTRATION----------------------- or reintubation may be required if airway obstruction persists or is • The recommended dose of SURFAXIN is 5.8 mL per kg birth weight severe. (5.2) administered by intratracheal administration. (2.1) • Increased Serious Adverse Reactions in Adults with Acute Respiratory • Up to 4 doses of SURFAXIN can be administered in the first 48 hours of Distress Syndrome (ARDS): Adults with ARDS who received life. (2.1) lucinactant via segmental bronchoscopic lavage had an increased • Doses should be given no more frequently than every 6 hours. (2.1) incidence of death, multi-organ failure, sepsis, anoxic encephalopathy, renal failure, hypoxia, pneumothorax, hypotension, and pulmonary ---------------------DOSAGE FORMS AND STRENGTHS---------------------- embolism. SURFAXIN is not indicated for use in ARDS.
    [Show full text]