Surfactant


Article Author:
Hina Khawar


Article Editor:
Komal Marwaha


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
9/12/2019 10:39:37 PM

Indications

Pulmonary surfactant is a lipoprotein complex responsible for preventing the collapse of alveoli and increasing lung compliance.[1]Therapeutically,  exogenous surfactant administration, or surfactant replacement therapy(SRT), is considered in preterm infants with radiographic (small volume lungs, haziness/ ground-glass appearance, air bronchograms and loss of cardiac borders on chest radiographs) and clinical evidence of neonatal respiratory distress syndrome (NRDS).[2] Surfactant administration in preterm infants with NRDS reduces morbidity and mortality. There is a reduced risk of air leak and chronic lung disease. In NRDS, the earlier surfactant is used, the better the outcomes.  Also, the outcome is reported to be better, if early surfactant administration is followed by extubation of preterm infants with RDS as compared to prolonged ventilation after surfactant administration.

Therapeutically, surfactant administration is also indicated in infants who have meconium aspiration syndrome. Surfactant use, in this case, will recover oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO). Also, infants who undergo intubation for any reason, irrespective of their gestational age, or infants who have respiratory failure requiring mechanical ventilation can receive surfactant therapy.

Prophylactic use of surfactant is indicated in the neonates who are predisposed to the development of NRDS. These include those who are born before 32 weeks gestation and those with low birth weights (less than 1300 gm). In premature infants, at risk for developing RDS, the surfactant administration with brief lung-protective ventilation (followed by extubation to nasal CPAP) has been found to lower incidence of mechanical ventilation, air leak syndromes, and result in a lower incidence of pneumothorax, pulmonary interstitial emphysema and improved survival without bronchopulmonary dysplasia. Prophylactic surfactant is also indicated in infants with laboratory evidence of surfactant deficiency (lecithin/sphingomyelin ratio of less than 2 to 1, evidence of lung immaturity on bubble stability test or absence of phosphatidylglycerol). Surfactant replacement therapy may also be a consideration in other situations like worsening pulmonary hemorrhage.[3]

 The use of surfactant may also be beneficial in case of severe respiratory syncytial virus-induced respiratory failure.[3] In this case, there may be an improvement in gas exchange and respiration, contributing to shortened hospital stay and duration of mechanical ventilation.

Mechanism of Action

As mentioned above, pulmonary surfactant is a lipoprotein. Its production begins around 26 weeks gestation and reaches mature levels at approximately 35 weeks. It is produced in the endoplasmic reticulum (ER) of type two pneumocytes and secreted from the lamellar bodies of type two pneumocytes.[4] Other cells in the lung, namely club or Clara cells, also produce surfactant. This lipoprotein mixture enhances lung compliance and aids in lowering the surface tension of the air-liquid interface within alveolar walls, which will ultimately prevent atelectasis.[1] A large portion of the composition of surfactant is phospholipid dipalmitoylphosphatidylcholine (DPPC), which makes up about 50% of its structure.[4] Phosphatidylglycerol is the second most abundant phospholipid in the structure. Other lipid constituents of surfactant include neutral lipids such as cholesterol and other phospholipids such as sphingomyelin (SM). Surfactant proteins comprise about 10% of the structure and interact extensively with phospholipids. They are SP-A, SP-B, SP-C, and SP-D. The SP-A and SP-D proteins are part of the innate immune response. These proteins coat bacteria and viruses, allowing phagocytosis and destruction by macrophages.[5] SP-A is also thought to be a part of a negative feedback mechanism that controls the release of surfactant from type II alveolar cells. SP-B and SP-C are hydrophobic proteins that control the rate at which surfactant covers the surface of alveoli.

Administration

The American Academy of Pediatrics 2014 guidelines recommend immediate management of all preterm infants with nasal continuous positive airway pressure. Subsequently, in selected patients, surfactant administration may be considered as an alternative to intubation with prophylactic or early surfactant administration. The surfactant replacement therapy is administered by trained personnel, in a clinical setting where equipment for intubation and resuscitation are readily available.

Endotracheal installation of surfactant is the most widely accepted technique. Surfactant is administered in liquid form via an endotracheal tube in a single bolus dose as quickly as the neonate tolerates. Some studies recommend the administration of all the surfactant at once while others advocate dividing the bolus into smaller aliquots.

 Another technique of administration known as the INSURE technique is approached with the neonate not already intubated. The INSURE technique uses an in-out intubation procedure to administer the surfactant. This process includes intubation, followed by administration of the drug, and then extubation. Newer methods to limit the invasiveness of older approaches are in practice and targets of research today.[6][7] One such technique is known as the Minimally Invasive Surfactant Therapy or MIST.[8] The MIST method connects the patient to non-invasive respiratory support, and through that, the surfactant administration is with the work of spontaneous breathing. This method is increasingly being used to reduce intubation rates and their associated pathologies. Another method is the less invasive surfactant administration or LISA technique.[9] This method utilizes a thin catheter for surfactant delivery, which serves to reduce the possibility of lung injury as is possible with intubation. At present, five surfactants (Lucinactant, colfosceril palmitate, beractant, calefacient, and protectant alfa) have FDA approval. Colfosceril palmitate is no longer commercially available. Lucinactant is the first U.S. FDA-approved protein-containing synthetic surfactant.

Adverse Effects

The usage of surfactant can lead to bradycardia and hypotension in the neonate. There are also some reports of instances of oxygen desaturation upon administration of the drug. Also, because conventional methods of surfactant administration require an endotracheal tube, certain risks are associated with tubal administration of any drug. Hygiene is of vital importance, especially in neonates as their immunities are underdeveloped. Infections and sepsis can occur if measures are not taken to prevent them. Unless the neonate is already intubated, intubation must take place first, which presents with the risk of injury and air leaks. Intubation also poses the risk of airway obstruction, mechanical damage to the airway, and it may require frequent suctioning. There is a risk of alterations in cerebral flow and hypoxemia. Concomitant administration of oxygen can damage lung tissue from oxygen pressure. Excess oxygenation and subsequent cessation of it leads to diseases like bronchopulmonary dysplasia and retrolental fibroplasia in infants as well.[10][11][12]

Since surfactant extraction is from animal sources, a risk of immune activation exists. Rarely the drug can lead to pneumothorax and/or pulmonary hemorrhage. Other side effects may include intraventricular hemorrhage, patent ductus arteriosus, retinopathy, necrotizing enterocolitis, and/or blockage of the endotracheal tube can cause complications as well.

Contraindications

Contraindications to surfactant administration include congenital anomalies that are uncongenial with life, perfusion failure states, diffuse pulmonary hemorrhagic conditions, and a diagnosis of congenital diaphragmatic hernia. Contraindications also include neonates who display respiratory difficulty, but laboratory evidence suggests lung maturity has already occurred. Usage of surfactant appears to result in a deterioration in newborns with pulmonary hypoplasia, although more clinical trials-based evidence is needed.

Monitoring

Surfactant, especially being a drug administered to neonates, must be carefully monitored when given. Whether the drug administration is as a bolus or in aliquots, monitoring the endotracheal tubing for obstruction is just as essential as administering the drug itself. Because of the risks that accompany such procedures, it is vital to determine the definite necessity of this drug. Lung ultrasonography (LUS) scoring is a bedside technique useful to diagnose respiratory problems in neonates and has now become a tool to monitor lung function and guide surfactant therapy.[13] The LUS score is an excellent indicator of oxygenation status and thus can predict the need to administer surfactant in both term and pre-term babies (those with gestational ages of less than 34 weeks) on continuous positive airway pressure (CPAP). This approach is particularly useful in severe deficiency of surfactant; continuous positive airway pressure can fail, and such failure may pose a risk of lung injury.

Toxicity

Given that surfactant is a substance that is produced in the body and administered only when deficient, there have not been any serious reports of toxicities related to surfactant administration. The prerequisites for administration, namely the endotracheal intubation and CPAP usage, do possess some inherent risks as mentioned above.

Enhancing Healthcare Team Outcomes

New advances in medicine are regularly assisting clinicians and their teams in their practice and enabling them to think creatively and make healthcare increasingly convenient for patients. Management of infants with respiratory distress syndrome is best with an interprofessional team. While the respiratory therapist may administer the surfactant, the NICU nurse (specifically neonate specialty-trained nurses), critical care specialist, and pulmonologist all have to be involved in the monitoring of the neonate. The volume, viscosity, and the mode of ventilation are all vital components for surfactant efficacy. After administration of surfactant, the nurse has to monitor the vital signs and oxygenation. The respiratory therapist must monitor the ventilatory parameters at least for the first 60 minutes after surfactant administration.

The pharmacy will be responsible for ensuring proper preparation of the surfactant, verifying dosing and administration, and serving as a drug information resource to the rest of the team. Only with an interprofessional team approach and open communication can surfactant therapy optimally reduce the morbidity of respiratory distress syndrome in neonates. [Level V]

Research has indicated that surfactant preparations have anti-inflammatory properties and can aid the immune system in cases of acute lung injury (ALI) secondary to LPS (lipopolysaccharide) endotoxin. Because the surfactant proteins play a role in regulating cytokine production by inflammatory cells, animal models have shown that they can effectively limit lung injury caused by LPS endotoxin.[14] Additionally, new methods are persistently being tested and used to ease to delivery of surfactant and make the procedure less invasive,[6][7][15] such as the LISA and MIST techniques mentioned above.[9][8] These newer approaches improve patient safety and enhance team performances by improving care coordination. Not only that, nanotechnology is being tested to determine whether surfactant may serve as a drug delivery system for the administration of alternative medications.[16] Achievements in this regard are significantly enhancing the role of respiratory routes of drug administration using surfactant as a backbone.


  • Image 11423 Not availableImage 11423 Not available
    Image courtesy O.Chaigasame
Attributed To: Image courtesy O.Chaigasame

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Surfactant - Questions

Take a quiz of the questions on this article.

Take Quiz
A 24-year-old pregnant female is involved in a car accident and has a traumatic brain injury. To save the life of her 23-week old fetus, she is taken to the labor and delivery suite for an emergent cesarean section. At birth, the baby is intubated and given dipalmitoylphosphatidylcholine (DPPC) via the endotracheal tube. Regarding the alveoli of the lung, which of the following should be an expected outcome of this therapy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A newborn was born prematurely at 32 weeks gestation with neonatal respiratory distress syndrome (NRDS). The baby was given surfactant along with vigorous oxygen supplementation by an amateur team of clinicians but survived. At the postnatal checkup, the newborn appears cross-eyed and displays abnormal ocular movements. Which of the following most likely explains these findings?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 28-week pregnant woman comes to the clinic with Braxton Hicks contractions that have now resolved. She is reassured about the commonality of them, but she is concerned about something she saw on the internet related to premature babies and respiratory distress syndrome. She wants to know which tests can be done beforehand to determine whether her child is at risk or not, in case she goes into early labor. She is informed about a test that measures the components of a substance, which is essential for lung maturity. Which of the following are the most likely test and the substance?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 32-week pregnant woman with a history of cocaine addiction comes in for prenatal testing. When questioned about her more recent drug status, she says it was challenging, but she has successfully avoided cocaine since she realized she was pregnant five months ago. Along with routines tests, the clinician suggests a test that aids in the assessment of lung maturity by quantifying the surface tension-lowering ability of a substance in the amniotic fluid. Which of the following cells are responsible for the production and secretion of this substance?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient complains of recurrent infections throughout his life. It is determined that his immune cells display defective phagocytosis. The cause of his condition is linked to defects in a substance that is composed of phospholipid dipalmitoylphosphatidylcholine (50%), other lipids (40%), and proteins (10%). A defect in which of the following component of this substance is causing the immune compromise?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
After C-section delivery, a newborn demonstrates difficulty breathing. Peripheral cyanosis can also be seen. The mother has a history of type 2 diabetes mellitus. The newborn is considered for a drug that will lower the surface tension on his alveoli to prevent them from collapse. What is the most critical preparation specific to the administration of this medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A low birth weight newborn displays respiratory distress. The baby has an APGAR score of 6 and uses accessory muscles of respiration. He is rapidly intubated and given appropriate medication. Administration of the medication results in bradycardia and hypotension. In a healthy individual, this medication is naturally produced as a lipoprotein by the endoplasmic reticulum of a particular cell. Which structure within these cells is most likely responsible for the secretion of this lipoprotein?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Surfactant - References

References

Kolomaznik M,Nova Z,Calkovska A, Pulmonary surfactant and bacterial lipopolysaccharide: the interaction and its functional consequences. Physiological research. 2017 Sep 22;     [PubMed]
Sweet DG,Carnielli V,Greisen G,Hallman M,Ozek E,Plavka R,Saugstad OD,Simeoni U,Speer CP,Vento M,Visser GH,Halliday HL, European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;     [PubMed]
Hidalgo A,Cruz A,Pérez-Gil J, Pulmonary surfactant and nanocarriers: Toxicity versus combined nanomedical applications. Biochimica et biophysica acta. Biomembranes. 2017 Sep;     [PubMed]
Aldana-Aguirre JC,Pinto M,Featherstone RM,Kumar M, Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Archives of disease in childhood. Fetal and neonatal edition. 2017 Jan;     [PubMed]
Kribs A, Minimally Invasive Surfactant Therapy and Noninvasive Respiratory Support. Clinics in perinatology. 2016 Dec;     [PubMed]
Nouraeyan N,Lambrinakos-Raymond A,Leone M,Sant'Anna G, Surfactant administration in neonates: A review of delivery methods. Canadian journal of respiratory therapy : CJRT = Revue canadienne de la therapie respiratoire : RCTR. 2014 Fall;     [PubMed]
Brat R,Yousef N,Klifa R,Reynaud S,Shankar Aguilera S,De Luca D, Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA pediatrics. 2015 Aug;     [PubMed]
Foglia EE,Jensen EA,Kirpalani H, Delivery room interventions to prevent bronchopulmonary dysplasia in extremely preterm infants. Journal of perinatology : official journal of the California Perinatal Association. 2017 Nov;     [PubMed]
APPELBAUM A, Retrolental fibroplasia; blindness in infants of low weight at birth. California medicine. 1952 Oct;     [PubMed]
Kalina RE, Treatment of retrolental fibroplasia. Survey of ophthalmology. 1980 Jan-Feb;     [PubMed]
Canals Candela FJ,Vizcaíno Díaz C,Ferrández Berenguer MJ,Serrano Robles MI,Vázquez Gomis C,Quiles Durá JL, [Surfactant replacement therapy with a minimally invasive technique: Experience in a tertiary hospital]. Anales de pediatria (Barcelona, Spain : 2003). 2016 Feb;     [PubMed]
Agassandian M,Mallampalli RK, Surfactant phospholipid metabolism. Biochimica et biophysica acta. 2013 Mar;     [PubMed]
Griese M, Pulmonary surfactant in health and human lung diseases: state of the art. The European respiratory journal. 1999 Jun;     [PubMed]
Polin RA,Carlo WA, Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics. 2014 Jan;     [PubMed]
Lawson PR,Reid KB, The roles of surfactant proteins A and D in innate immunity. Immunological reviews. 2000 Feb;     [PubMed]
Walsh BK,Daigle B,DiBlasi RM,Restrepo RD, AARC Clinical Practice Guideline. Surfactant replacement therapy: 2013. Respiratory care. 2013 Feb     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pediatrics-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pediatrics-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pediatrics-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pediatrics-Medical Student. When it is time for the Pediatrics-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pediatrics-Medical Student.