Curr Allergy Asthma Rep. 2020 Sep 11;20(11):70. doi: 10.1007/s11882-020-00968-8. Exogenous Surfactant Therapy in Acute Lung Injury/Acute Respiratory Distress Syndrome: The Need for a Revised Paradigm Approach A. Dushianthan LETTERS TO THE EDITOR Exogenous Surfactant Therapy in may need to be adopted with modifications of surfactant Acute Lung Injury/Acute Respiratory preparations to overcome such issues. We employed exogenous bovine surfactant (Survanta beractant) as a carrier vehicle for pulmonary delivery of a recombinant adenovirus expressing β-galactosidase (β-Gal . Due to surfactant inactivation, multiple doses of surfactant may lead to improved outcome. Ongoing clinical trials of surfactant therapy to treat COVID-19 patients. Initial preliminary reports, mainly phase-II multicentre trials, have shown that exogenous artificial surfactant (Exosurf®) 18 or bovine surfactant (Survanta®) 19 in ARDS can improve oxygenation and lung mechanics. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Exogenous surfactant therapy for acute respiratory distress in infancy. (E,n . Table 1. In infants at high risk of respiratory distress, a policy of multiple doses of synthetic surfactant resulted in greater improvements regarding oxygenation and ventilatory requirements, a decreased risk of NEC and decreased mortality. However, as nasal continuous positive airway pressure(nCPAP) is becoming increasingly the preferred first line therapy for RDS, the less invasive approaches of respiratory support along with early selective surfactant administration (e.g. A number of conditions, such as pneumonia, trauma, or systemic sepsis arising from the gut, may result in the acute respiratory distress syndrome (ARDS). Pediatr Res. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. Los autores pretendie-ron evaluar el efecto del tratamiento con surfactante natural exógeno en procesos con consumo de surfactante. This volume of Clinics in Perinatology will examine the latest techniques in mechanical ventilation, including both conventional and high frequency ventilation. Prophylactic vs early or rescue administration Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. We tested the effects of synthetic surfactants with 1 or 2% dSP-B(1-25) and 1% SP-Cfc on lung function in surfactant-deficient rats. This new edition also features an increased focus on evidence-based practice, new CAMTS and AAMS guidelines, new techniques for PICC placement, and changes to the Neonatal Resuscitation Program. Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome - where do we go from here? Found insideHowever, there is essential care that must be included in all centers that care for high-risk babies. This book includes important topics related to neonatal care grouped into four sections. Se compararon los índices de oxigenación antes y después del tratamiento y la evolución clínica y radiológica. 2012 Nov 22;16(6):238. doi: 10.1186/cc11512. Found insideThis book will be invaluable and entertaining for anyone who is involved in the care of patients with cystic fibrosis. Types of Exogenous surfactant (2)-Animal-Synthetic. Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. Predicting the outcomes of preterm neonates beyond the neonatal intensive care unit: What are we missing? The principal surface-active material in surfactant is di-palmatoyl phosphatidylcholine (DPPC). Exogenous surfactant therapy in thirty-eight hour lung graft preservation for transplantation Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). ResearchGate has not been able to resolve any references for this publication. Infants of very low gestational ages are now surviving. This book provides detailed and up-to-date information on imaging of the neonatal chest. The mean duration of need for oxygen and hospitalization of patients in group A and B were 17.73+/-22.25 vs 19.14+/-17.85 days (p=0.67) and 24.89+/-26.41 vs 29.14+/-23.54 days (p= 0.32), respectively. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of . Initial preliminary reports, mainly phase-II multicentre trials, have shown that exogenous artificial surfactant (Exosurf®) 18 or bovine surfactant (Survanta®) 19 in ARDS can improve oxygenation and lung mechanics. The debate over which surfactant to be used, when and what is the best mode of delivery is still raging. This review of trials found that multiple doses, rather than a single dose, further improved babies' outcomes. Qaqish R, Watanabe Y, Galasso M, Summers C, Ali AA, Takahashi M, Gazzalle A, Liu M, Keshavjee S, Cypel M, Del Sorbo L. Intensive Care Med Exp. The most authoritative advice available from world-class neonatologists who share their knowledge of new trends and developments in neonatal care. Purchase each volume individually, or get the entire 7-volume set! PMC Neu-monía congénita. This book presents a concise, evidence-based review of extracorporeal life support (ECLS) for adult diseases. Treatment with exogenous surfactant improves gas exchange and optimizes survival in newborn babies with RDS (Jobe 1993;Mercier and Soll 1993;Suresh and Soll 2002). The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Biophysical behavior of lung surfactant: implications for respiratory physiology and pathophysiology. 2021 Feb;89(3):426-445. doi: 10.1038/s41390-020-0968-5. Two studies were randomized controlled trials of multiple vs. single dose animal derived surfactant extract in infants with established respiratory distress syndrome. We investigated the effect of surfactant deficiency on airway patency and the effectiveness of surfactant replacement as either an instilled liquid bolus, a non-hygroscopic aerosol or a hygroscopic aerosol. Recently, some interesting clinical observations and several animal studies involving transgenic and gene knockout models have further demonstrated the essential role of the various surfactant components, specifically the surfactant proteins for normal lung function [7]. Found inside – Page iThis volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987. Because surfactant dysfunction plays a role in the pathogenesis of pneumonia, beneficial effects can be expected from exogenous surfactant therapy. Methods We performed a retrospective analysis of the evolution of 15 newborn infants treated with natural exogenous sur-factant. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. Soll R, Özek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Veno-venous ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS. Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Professor Pediatrics * Evolution of Exogenous Surfactant Replacement Therapy IRDS=RDS=HMD=SDS Evolution of Exogenous Surfactant Replacement Therapy 1950's Surfactants demonstrated in mammalian lung; deficiency implicated in pathophysiology of respiratory distress syndrome (RDS) 1960's Clinical studies of surfactant replacement . Disclaimer, National Library of Medicine 2017 Jun 24;2(2):1-9. doi: 10.1159/000475877. Dysfunction of pulmonary surfactant is one of the key pathogenic features in meconium aspiration syndrome. Semin Respir Crit Care Med. Meta-analysis of these trials suggests a reduction in the risk of pneumothorax (typical relative risk 0.51, 95% CI 0.30, 0.88; typical risk difference-0.09, 95% CI -0.15, -0.02) and a trend towards a reduction in the risk of mortality (typical relative risk 0.63, 95% CI 0.39, 1.02; typical risk difference -0.07, 95% CI -0.14, 00.00). This text includes illustrations to explain the procedural stages of LMA insertion and describes anatomical, physiological and pathophysiological implications. Abstract Exogenous surfactant therapy has been part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since the beginning of the 1990s. Median values (range): birth weight, 960 g (595 to 4045); age at pulmonary hemorrhage, 24.4 hours (0.3 to 62); and interval between pulmonary hemorrhage and surfactant therapy, 10 hours (3.7 to 46.5). Así, el déficit o la inactivación de surfactante que puede estar presente en varios cuadros de insuficiencia respiratoria como SAM, neumonía congénita, SDRA, hipoplasia pulmonar, entre otros, actualmente se consideran potenciales indicaciones para su uso [1][2][3][4], ... Al contrario del SDR neonatal, resultante de un déficit primario de surfactante endógeno, en las enfermedades pulmonares en recién nacido a término, la principal alteración parece ser la inactivación de las proteínas del surfactante por inhibidores presentes en el líquido del edema pulmonar 2,4,7 . Furthermore, clinical and laboratory evidence suggests that this therapy may be most effective in patients with a direct lung infection, and when . A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the alpha-helix. Comparison of Polymyxin E and Polymyxin B as an Additive to Pulmonary Surfactant in Escherichia coli Pneumonia of Ventilated Neonatal Rabbits. This decreased surface tension is most easily normalized by . In addition, myo-inositol has been found able to decrease the levels of IL-6 in several experimental settings, due to an effect on the inositol-requiring enzyme 1 (IRE1)-X-box-binding protein 1 (XBP1) and on the signal transducer and activator of transcription 3 (STAT3) pathways. The success of exogenous surfactant therapy for COVID-19 and other pulmonary diseases can potentially be enhanced by utilizing it in combination with other drugs and therapies. Three patients with meconium aspiration syndrome died. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. in their management, Meconium aspiration syndrome (MAS) and congenital pneumonia are two worthy These studies are demonstrating a generally favourable influence on lung function by improving . Small airway patency was assessed in isolated piglet lungs by passing a continuous flow of gas though a cannulated airway. If the use of this medication becomes standard care, a greater variety of packaging sizes could lead to decreased acquisition costs and increase the number of patients for whom this treatment is cost-effective. Based on available data, the severity of ARDS and serum levels of IL-6 are key determinants for the prognosis. Compared with other aerosol delivery devices, this process utilizes low air flow (range 0.01–0.2 L min⁻¹) that is ideal for limiting potential barotrauma to the premature newborn lung. The primary outcome measure was mortality 28-30 days after . In the past two decades, exogenous surfactant therapy has been a cornerstone of therapy for preterm infants, and is known to be effective when given prophylactically in the delivery room, or as a rescue therapy to infants with established respiratory distress syndrome (RDS) [1]. M. Moreno 1, J. López-Herce 1, C. Merello 1, A. Alcaraz 1 & A. Carrillo 1 Intensive Care Medicine volume 22, page 87 (1996)Cite this article Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Respiratory distress syndrome (RDS) is a common consequence of pulmonary immaturity in the lungs of neonates. Síndrome de distrés respiratorio del adulto. Its use for this indication should be further investigated by a randomized controlled trial. Although neonatal RDS is still the main indication of surfactant therapy, other pathological processes Found insideThe present book covers contemporary topics of community, hospital, and health care-related bacterial and viral pneumonia in the setting of drug resistance, environmental exposures, climate change, hormonal influences, and gender. Related Papers. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). INSURE) appears to provide a better option. No data on long-term neurological or pulmonary outcome were reported. A novel aerosol generator (Microjet™) is evaluated herein for intrapulmonary aerosol generation within an endotracheal tube and tested with Curosurf and Infasurf surfactants. Natural surfactant is extracted from animal sources such as bovine or porcine. In this study, infants who received poractant had shorter duration of intubation than infants treated with beractant, without any difference in the duration of oxygen therapy or hospitalization. It is hoped that with further improvements, they will outperform their natural counterparts in terms of reliability and cost-effectiveness. Twenty patients were prospectively identified. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Multiple doses decreased the need for mechanical ventilation (machine-assisted breathing). Occlusion was assessed by measuring increases in pressure in the cannula that resulted from airway obstruction. Integrating basic and clinical research on the biophysical and physiological functions of pulmonary surfactants, this practical reference presents thorough, cutting-edge coverage on surfactant-related lung disease. However, Lu et al. Found insideIn this book, you'll learn multiple new aspects of respiratory management of the newborn. These results support the therapeutic use of exogenous surfactant in severe respiratory diseases of the newborn causing secondary surfactant deficiency. Surfactant replacement therapy is thus, being widely used these days in all hospitals throughout the western world [8. Crit Care Clin. There is also a growing body of evidence suggesting that exogenous surfactant may be more effective when combined with pulmonary vasodilators, anti-inflammatory and antioxidant treatment. Multiple doses of surfactant have more benefit than a single dose. We further discovered that there was no improved oxygenation after surfactant supply. Role of inositol to improve surfactant functions and reduce IL-6 levels: A potential adjuvant strategy for SARS-CoV-2 pneumonia? MeSH Respiratory distress syndrome (RDS) is caused by a lack of, or dysfunction in, surfactant. Surfactant Deficiency Syndrome C. Antonio Jesurun, M.D. (C,n10) did not receive TA, early Grp. Exogenous lung surfactants are among the most studied drugs in medicine. It represents 60% of surfactant by weight and accounts for 80% of the phospholipids. After failure of standard therapy the use of alternative approaches is possible, e.g. The preference is generally to give steroids if there is time, and to treat the neonate with exogenous surfactant therapy early after birth. Therapeutic protocols usually include airway suctioning, ventilator support or artificial ventilation, in severe cases also administration of exogenous surfactant, inhaled NO, partial liquid ventilation, or anti-inflammatory treatment. first trial of exogenous surfactant therapy in Malaysia. R01 HL094641/HL/NHLBI NIH HHS/United States. Surfactants used in this manner are typically instilled directly into the trachea. Independent of the cause, in ARDS there is a disturbed permeability of the alveolo-capillary membrane with influx of plasma proteins. There is every reason to Los autores pretendieron evaluar el efecto del tratamiento con surfactante natural exógeno en procesos con consumo de surfactante.MétodosSe efectuó un análisis retrospectivo de 15 recién nacidos con cuadros de síndrome de aspiración meconial (9), neumonía congénita (5) y síndrome de distrés respiratorio del adulto (1), a los cuales se les administró surfactante natural exógeno. Are stem cells the miracle cure? These are just a few of the questions that world experts cover in this book while, at the same time, they take a look at the future of neonatal medicine. Surfactant replacement was established as an effective and safe therapy for immaturity-related surfactant deficiency by the early 1990s. Art. After almost 50 years of intense research, the concerted efforts of basic scientists and clinicians have been rewarded. Eight quantitative waveform parameters were also measured on all patients. The demographic and clinical variables were similar in both groups. However, because haemoglobin and other blood components such as fibrinogen have been shown to have serious adverse effects on surfactant function [31] , surfactant replacement therapy has also been used to treat pulmonary hemorrhage. Found insideIn this book three topics will be discussed: clinical presentation including a general approach to sepsis neonatorum and two distinct diagnoses pneumonia and osteomyelitis diagnostic approaches including C-reactive protein and the immature ... Mean OI improved from 24.6, at 0 to 3 hours presurfactant, to 8.6 at 3 to 6 hours postsurfactant (P < .001). We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. Discoveries that led to its development as a therapeutic agent Stichtenoth G, Haegerstrand-Björkman M, Walter G, Linderholm B, Herting E, Curstedt T. Biomed Hub. Throughout, the text is complemented by numerous illustrations and key information is clearly summarized in tables and lists, providing the reader with clear "take home messages". At one level, the results can be viewed as rather unimpressive: the average improvement in PaO2 was only 49±16 mm Hg, and in three cases this . Due to surfactant inactivation, multiple doses of surfactant may lead to improved outcome. Exogenous surfactant replacement therapy of hyaline membrane disease in premature infants Ran Namgung, 1 Chul Lee, 1 Jin-Suk Suh, 2 Kook-In Park, 1 and Dong-Gwan Han 1 1 Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea. Since the available data are extremely limited, if this potential therapeutic approach will be considered valid in the clinical practice, the necessary future investigations should aim to identify the best dose, administration route (oral, intravenous and/or aerosol nebulization), and cluster(s) of patients which may get beneficial effects from this treatment. The introduction of exogenous surfactant therapy for HMD, in which animal-derived or synthetic surfactant mixtures are instilled into the trachea, has led to a considerable reduction in mortality and risk of pneumothorax. 2021 Feb;44(1):57-67. doi: 10.1007/s10753-020-01266-1. The present article aims at reviewing exogenous surfactant therapy and discussing the current state of research, in which no consensus on the use of exogenous surfactant has been reached yet. No patient deteriorated following surfactant therapy. Introduction. Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. Newborns in the pulmonary group (n=13) (persistent pulmonary hypertension of the newborn/meconium aspiration syndrome, respiratory distress syndrome, pneumonia) and newborns in the control group (n=7) were matched for birth weight, gestational age, and postnatal age. Administration of exogenous surfactant may at least partially alleviate the inactivation of pulmonary surfactant present in meconium aspiration syndrome. Arterial blood gas values and dynamic compliance were measured every 15 min and after 2 h of ventilation, the rats were killed and pressure-volume curves performed. All those with RDS had also received surfactant before their pulmonary hemorrhage. Results from clinical trials, to date, have failed to show an improvement in patient survival after administration of exogenous surfactant; however, ongoing and future research efforts suggest that this therapy may eventually be feasible. 9 Congenital absence of SP-B in humans causes lethal neonatal respiratory distress syndrome 21 and mice who are bred deficient of SP-B die . received considerable attention and major research has been dedicated to explore the role of surfactant To study the effect of exogenous bovine surfactant on oxygen and ventilatory requirements in neonates with respiratory deterioration due to pulmonary hemorrhage. In controlled trials, exogenous surfactant therapy increases the incidence of pulmonary hemorrhage . Novick RJ (1), Veldhuizen RA, Possmayer F, Lee J, Sandler D, Lewis JF. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation. Early reports of exogenous surfactant therapy in patients with the adult respiratory distress syndrome, although promising, remain limited in number. Nine infants had meconium aspiration syndrome, five had congenital pneumonia and one had adult respiratory distress syndrome. Exogenous surfactant therapy has many administration methods. To determine the effect of multiple doses of exogenous surfactant compared to single doses of exogenous surfactant on mortality and complications of prematurity in premature infants at risk for or having respiratory distress syndrome. At 30-32 weeks, the risk of serious RDS is practically eliminated. Murieron 3 pacientes con síndrome de aspiración meconial grave.ConclusionesLos resultados de este estudio sugieren el beneficio de la utilización de surfactante exógeno en el tratamiento de enfermedades pulmonares graves del recién nacido, que cursan con déficit secundario de surfactante. Pulmonary Surfactants: a New Therapeutic Target in Asthma. <32 weeks or low birth weight <1300g) neonates who are intubated, regardless of gestation, and requiring FiO 2 >40%. Aspirated meconium obstructs the airways and subsequently may cause an alveolar atelectasis behind the plug, air-trapping, and air leak. The use of surfactant for the treatment or prophylaxis of neonatal RDS results in a 30% to 65% relative reductio … Abstract Surfactant replacement therapy (SRT) plays a pivotal role in the management of neonates with respiratory distress syndrome (RDS) because it improves survival and reduces respiratory morbidities. The second edition of this best-selling book has been thoroughly revised and expanded to reflect the significant changes and advances made in systematic reviewing. -Exogenous surfactant + steroids added benefit -Without surfactant, steroid therapy is still extremely useful. Found insideThis book compiles the most recent, widespread developments of experimental and clinical research and practice in one comprehensive reference book. Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ARDS than in RDS, where simple deficiency is causative. : Received August 04, 1989; Accepted November 03, 1989. [29,30] The rapid improvement in oxygenation and pulmonary mechanics frequently noted soon after surfactant administration in . For this update additional data were sought on pulmonary hemorrhage, periventricular leukomalacia, neurodevelopmental follow-up, rehospitalization for pulmonary reasons,and reactive airway disease. Synthetic surfactant is manu- The primary respiratory diagnosis was respiratory distress syndrome (RDS) in 8, meconium aspiration syndrome in 3, and isolated pulmonary hemorrhage in 4. However, respiratory morbidity, primarily bronchopulmonary dysplasia, remains unacceptably high. Raghavendran K, Willson D, Notter RH (2011) Surfactant therapy for acute lung injury and acute respiratory distress syndrome. Three trials were identified that met study criteria. Resultados Se verificó una mejoría de la oxigenación después de la administración de surfactante en los 12 recién nacidos que sobrevivieron, acompañada de una mejoría de las altera-ciones radiológicas. However, some patients are non-responders and there is only transient improvement in oxygenation. Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. Surfactant preparation Delivery method Dose Timing PL and Survanta, a bovine lung extract, were controls. To read the full-text of this research, you can request a copy directly from the authors. . 2011 Sep;56(9):1369-86; discussion 1386-8. It has become a nursing responsibility to administer the exogenous surfactant, and care for the premature infant before, during, and after the administration. aspiración meconial (SAM), la neumonía congénita y el síndrome de distrés respiratorio del adulto (SDRA) demostraron mejoría en la oxigenación, reducción de la necesidad de ventilación asistida, así como disminución del tiempo de hospitalización [1][2][3][4], ... Desde 1959, cuando Avery y Mead sugirieron que la dificultad respiratoria de los recién nacidos prematuros se debía al déficit de surfactante, se han realizado numerosos estudios en esta área, habiendo evidencias que apoyan la teoría de que el surfactante tiene un papel pluripotencial, importante en el normal funcionamiento de los pulmones 2,3 . However, administration of exogenous surfactant as an instilled liquid bolus, non-hygroscopic aerosol or a hygroscopic aerosol decreased airway closure such that it was statistically similar to that recorded prior to induction of surfactant deficiency, although the instilled and hygroscopic aerosol surfactant both appeared superior to the non-hygroscopic aerosol. Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. This indication should be further investigated by a randomized controlled trial pulmonary outcome were reported therapeutic use of approaches... ( 11 ):70. doi: 10.1038/s41390-020-0968-5 in both groups be used, when and What is best! Anatomical, physiological and pathophysiological implications SP-D ) is a common consequence of pulmonary surfactant present in meconium syndrome! 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