Surfactant therapy


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  • Thanks m for explaining us the physiology in detail…moving on to the next part of presentation….as already introduced rds is a big prob in preterm babies and the risk exponentially rise with decreasing gestation…as much as that 80% of babies below gestation 27 weeks may land into rds…
  • So what are the interventions avaible….starting with basics of essential newborn care including the the temp management fluid and elctrolyte calculation along with managing oxygenation and ventilation constitutes the management of respiratory destress syndrome previously called as hmd….many of them will do fine with simple intervention mentioned…some will require cpap and some might require advance therapies like surfactant therapy………this presentation focuses on the surfactant therapy in rds…
  • The first and formost question is does it work…what is the proper timing to give …..which type whether natural or synthetic….how many doses…then we will be discussing what is the methodology
  • So the first question is does it wotks…being a novel therapy many of us are not comfortabel with surfactant therapy..the critics qustion its usefullness and those who are convinced raise the question of being costly and its cost effectiveness….this presentation is based upon the evidences collected from databse…
  • If we search neonatal databases maximum rcts in neonatalogy are attributed to surfactant therapy ….most of the systemic reviews and metaanylysises gives us good strength in answering the questions I put in the first slide
  • In may 1994 NEJM published a very significant data which concluded that
  • Within 5 years of the previous publication aap labaled exogenous surf therapy as standard preventive and therpeutic modality of management in case of prematurity related surf front of u on the screen is the statement issued by commete on fetus and newborn….
  • So what is the indian status the first case controll study came in 2001 by narang which concluded that both the duration of ventilation and hospital stay reduced significantly in treated patients,…..secondly the complication which are in fact more with prematurity where also found to be reduced which was attributed to the overall respiratory well being of these patients…..this was one of the first kind of studies which prooved cost effectiveness of surfctant despite the critisism in our country….
  • Phospholipids 80% Saturated phosphatidyl choline Unsaturated phosphatidyl choline Phosphatidyl glycerol Phosphadityl inositol Neutral lipids 8% Proteins 12% (SP - A, SP - B, SP- C, SP - D) formation secretion and regulation
  • Pramarily of two types the natural ones these are the Animal lungs extracts and the sunthetic one..what intersts us here is the natural one.. I ll be discussing this over next few slides…The natural ones are prepared from variety of animals..from bovine its called as survanta…calflung its called exosurf and porcine called as curosurf….
  • Lets see what the databse says about tis…In 2005 cochrane stated that natural surfactant decreases ventialtoty requirement and also other complication….. Although it increases chance of IVH but if compared to the currently available synthetic product they are all the way superior
  • So cochrane came with final conclusion that ……
  • Lets try to underastand this on pv loop If we compare the efficacy of available surfactants here on this pv curve it clearly seems that the lower opening pressure required are much less with natural surfactant …further if we compare the opening pressures amongst natural one sheep extract scores highest in efficacy….we in our unit use cursosurf whose efficacy lies between sheep extract and survanta…..
  • This is simple digram depicting alveoli with deficient surfactant because the surface tension working inside the alveoli, the alveoli tend to collapse….because of surfactant in alveoli the collapsibility decreases….This small video explain the physiology..i don’t know its visible properly…coin is floating over water because of surface if we administer surf…the air liquid interface breaks and coin sinks…..
  • If we try to understand this on respiratory mechanics it will look like this…This is pressure volume loop showing difference between rd lung and normal lung…if we see the lower opening pressure in rds its 15..its less than 10 somewhere here…if u see the change in volume with pressure there is exponential rise and exponential decay in normal lung while its very very poor in hMD… we all know minute ventilation is a basic of respiratory function…..
  • Now the last querry which chalanges the usefullness is whether surf interfers with the normal physiology answer is no….surf do not inhibit the synthesis of endogenous surf……in fact not only surf has postive effect on lung mechanics it also gets recycled in making of natural surf
  • Timing of surf administration emerged as single most important factor as for as the outcome of rds is concerned….administering the surfactant within two hours of birth as a matter of fact in labour room itself is called as prophylactic therapy…….these patients are identified as at risk of RDS depending on gestation and then selected for prohylactic therapy (jusifiable in 27 weeker where incidence is very very high)…another form is administering surf once the signs and symp develop or after radiological cinfirmation this is called as rescue therapy…….this is further divided in early and late rescue depending upon the timin after disgnosis….
  • So what the database has to asy about this…The metanalysis done from pooled data of 5o rct revealed that there will be less comlication and less death with prohylactic therpy….although this is an establisted fact that prophylaxis is better than rescue I want to bring to an attention some practical problems with prophylaxis therapy…..lets se
  • What are the facts regarding ……..We had the twins one developed rds another remained stable
  • Before we procede to actual procedure I want to emhasis the importence of antenatal steroids…eventhogh we have a novel drug with us now we should never forget the importence of an steroids as cornerstone in preventing occurrence and severity of rds. Its been 100 year eve more an steroid still hold their position
  • ……the established facts are
  • Start video…pause focusing subject…give details bout history no antinatal steroids… gestation symptopms ….show xary …start video again….take pauses when reqd….B/0 priyanka…born to a primi mother with gestation of 31 weeks weighing 1990 grams..developed sign syp of rds within 2 hours and we decided to treat this baby wid surf…I want to emphasise here that they did not received an steroids…..
  • What was done next on this baby was something called as INSURE protocol… says….so we follows exactly the same…..
  • Lets see what the evidence has to say….it says that
  • This is our baby which was extubated within 4 hours of surf therapy…baby was put on buble CPAP and then further weaned to oxygen by hood and with good supportive therapy we were able to discharge this baby on …day of her life
  • Coming to the last part of discussion…its time to duscuss the problems of surfactant administartion
  • Increase in ph as compares to normal term subjects….If u compare wit incidence of ph in preterm itself its very less…on the contrary by preventing the complication of prematurity its actually reduces the incidence of ph
  • Surf is expensive yes its true….1.5 ml of surf cost arround 12000 however it should alwys be kept in mind that This was already prooved in mumbai based study of narang
  • Yes first and foremost thing is the skills…monitoring ventilatory strategy and supportive therAPY….most important in surf therapy is insure…what are the other things ……
  • Surfactant therapy

    1. 1. Rational Surfactant Therapy Ajay Agade Jawaharlal Nehru Hospital And Research Centre, Steel Plant Bhilai
    2. 2. What are the interventions available?• Oxygen• CPAP• Mechanical Ventilation• Surfactant Dr Ajay Agade
    3. 3. Surfactant Replacement Therapy • Does it work? • When to give? • Which one to give? • How often to give? • How to give? • Does it cause any problems? Dr Ajay Agade
    4. 4. Does Surfactant Replacement Therapy Work? Dr Ajay Agade
    5. 5. Most widely researched with maximumRCT’ s in neonatology Dr Ajay Agade
    6. 6. • Odds of death in hospital for VLBW infants were reduced by 30 % after surfactant was introduced.• 80% of decline in the U.S. neonatal mortality rate between 1989 & 1990 could be attributed solely to the use of surfactant. NEJM May 1994 Dr Ajay Agade
    7. 7. Exogenous surfactant replacement has beenestablished as an appropriate preventive andtreatment therapy for prematurity-relatedsurfactant deficiency AMERICAN ACADEMY OF PEDIATRICSCommittee on Fetus and Newborn March 1999, pp 684-685 Dr Ajay Agade
    8. 8. Indian Experience• The mean duration of ventilation 44.1 hours lesser, and the hospital stay 4.37 days lesser in babies who received surfactant.• The incidence of sepsis, pneumonia, PDA, IVH and CLD was lower in babies who received surfactant. Narang et al Indian Pediatrics 2001 Dr Ajay Agade
    9. 9. What is Surfactant? Dr Ajay Agade
    10. 10. TYPES OF SURFACTANT SYNTHETIC MODIFIED NATURAL (Exosurf, Surfact) (Survanta, Curosurf)Phospholipids DPPC Animal lung extractSpreading Cetyl alcholol Surfactant proteinsagents + (SP-B, SP-C) Tyloxapol Dr Ajay Agade
    11. 11. Comparative trials demonstrate greater earlyimprovement in the requirement for ventilatorsupport, fewer pneumothoraces, & deathsassociated with natural surfactant.Natural surfactant may be associated with anincrease in IVH, though the more serioushemorrhages (Grade 3 and 4) are not increased. Despite these concerns, natural surfactant extractswould seem to be the more desirable choice whencompared to currently available syntheticsurfactants. Cochrane 2005 Dr Ajay Agade
    12. 12. RecommendationNatural surfactants should be used inpreference to anyof the synthetic surfactants available(grade A). Cochrane 2005 Dr Ajay Agade
    13. 13. •The animal surfactants have phospholipid compositions similar tothat of natural surfactant; they contain some SP-B and SP-C, butno SP-A.• The surfactant approved for use in the United States is Survanta(beractant, Ross Laboratories, Columbus, Ohio) prepared bymincing bovine lungs in saline and extracting the lipids, SP-B, andSP-C with organic solvents.Dipalmitoylphosphatidylcholine, palmitic acid, and triglyceride arethen added to improve the surface properties of the extract•. The surface properties of organic-solvent extracts of lung tissuealso can be improved by removing neutral lipids bychromatography, as is done with Curosurf Dr Ajay Agade
    14. 14. Absence of Surfactant High Distending Pressures Airway Stretch / DistortionWhat happens ? Cellular Membrane Disruption Edema / Hyaline Membrane Formation Higher FIO2 / Pressures Barotrauma, BPD Dr Ajay Agade
    15. 15. SURFACTANT : DEFICIENCY Dr Ajay Agade
    16. 16. PRESSURE VOLUME LOOP Dr Ajay Agade
    17. 17. There is no indication that exogenously administeredsurfactant inhibits the synthesis and secretion ofendogenous surfactantTwo major benefits result from surfactant treatment: The biophysical effects of the surfactant on the surfactant-deficient lungs And the provision of phospholipids as substrate for recycling pathways Dr Ajay Agade
    18. 18. Timing Prophylactic or Rescue Dr Ajay Agade
    19. 19. The meta-analysis (50) indicated that therewould be two fewer pneumothoraces andfive fewer deaths for every 100 babiestreated prophylactically with surfactant. Dr Ajay Agade
    20. 20. •Prophylactic treatment during the first 15 minutes of lifeappears to be more effectiveBUT not all infants that would appear to be at risk ofdeveloping RDS, actually develop the condition.May lead to some infants being over treated, and possiblybeing exposed to adverse effects, unnecessarily. Dr Ajay Agade
    22. 22. Multiple doses of surfactant have been given in mosttrials because the response to an individual dose is oftentransient.In preterm animals, exogenously administered surfactantis can be inhibited by soluble proteins and other factors inthe small airways and alveoli.Multiple doses are thought to be useful because they canovercome this functional inactivation of surfactant. Pediatrics 1991 Dr Ajay Agade
    23. 23. Antenatal steroid and Surfactant goes hand in hand Dr Ajay Agade
    24. 24. Antenatal steroids & surf• Synergistic effect Prenatal steroids + Surfactant is better than either alone•  neonatal mortality•  air leaks Give both•  severe IVH Am J Obst Gynec Suppl, 1995 Dr Ajay Agade
    25. 25. • A secondary analysis of data from surfactant trials also indicates a greater reduction in disease severity in babies who received antenatal steroids (evidence level 4).• Combination of antenatal steroids is more effective than exogenous surfactant alone (evidence level 2b). Dr Ajay Agade
    26. 26. How Do We Do It Dr Ajay Agade
    27. 27. INSURE procedureEarly surfactant replacement therapy withextubation to N CPAP compared with continuedmechanical ventilation with extubation isassociated with a reduced need for mechanicalventilation and increased utilization of exogenoussurfactant therapy. COCHRANE 2005 Dr Ajay Agade
    28. 28. HOW SHOULD VENTILATORY MANAGEMENT AFTER SURFACTANT THERAPY BE APPROACHED? “ Options for ventilatory management that are to be considered after surfactant therapy include very rapid weaning and extubation to CPAP (grade B evidence).” Dr Ajay Agade
    29. 29. Ventilatory strategy-INSURE Dr Ajay Agade
    31. 31. The short-term risks of surfactant replacement therapy• Bradycardia and hypoxemia during instillation,• Blockage of the endotracheal tube• Increase in pulmonary hemorrhage following surfactanttreatment• However, mortality ascribed to pulmonary hemorrhage is not increased and overall mortality is lower after surfactant therapy. Dr Ajay Agade
    32. 32. Is Surfactantbeyond thereach of thecommonman? Dr Ajay Agade
    33. 33. Cost implications• Surfactant is expensive• 22% reduction in hospital charges per survivor• 52 % Reduction in ancillary charges Dr Ajay Agade
    34. 34. Does surfactant fail?• Extremely preterm infants with structurally lung immaturity• Pneumonia or pulmonary hypoplasia• Perinatal asphyxia• Pulmonary edema from lung damage or fluid overload• Pulmonary edema from L-R shunting through PDA• Congenital B protein deficiency Dr Ajay Agade
    35. 35. Got Surfactant! Dr Ajay Agade