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Surfactant therapy
- 1. Dr Rakesh Kumar Asst. Professor N.M.C.H, Patna
- 2. Antenatal steroid Oxygen CPAP Mechanical Ventilation Surfactant
- 3. Does it work? When to give? Which one to give? How often to give? How much to give? How to give? Does it cause any problems?
- 4. 1a-Systematic review (with homogeneity) of randomized controlled trials 1b-Individual randomized controlled trial (with narrow CI) 2a-Systematic review (with homogeneity) of cohort studies 2b-Individual cohort study (or low-quality randomized controlled trial, eg, <80% follow-up) 3a-Systematic review (with homogeneity) of case-control studies 3b-Individual case-control study 4-Case-series (and poor quality cohort and case-control studies) 5-Expert opinion without explicit critical appraisal, or based on physiology, bench research or ‘first principles’
- 5. Grade A-Consistent level 1 studies Grade B-Consistent level 2 or 3 studies Grade C-Level 4 studies Grade D-Level 5 evidence or troublingly inconsistent or inconclusive studies of any level
- 6. Surfactant is most widely researched with maximum RCT’ s in neonatology
- 7. 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
- 8. Exogenous surfactant replacement has been established as an appropriate preventive and treatment therapy for prematurity-related surfactant deficiency (AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn March 1999, pp 684-685)
- 9. 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
- 11. TYPES OF SURFACTANT SYNTHETIC (Exosurf, Surfact) Curosurf,neosurf) Phospholipids Spreading agents DPPC MODIFIED NATURAL (Survanta, Animal lung extract Cetyl alcholol + Tyloxapol Surfactant proteins (SP-B, SP-C)
- 12. •Comparative trials demonstrate greater early improvement in the requirement for ventilator support, fewer pneumothoraces, & deaths associated with natural surfactant. •Natural surfactant may be associated with an increase in IVH, though the more serious hemorrhages (Grade 3 and 4) are not increased. • Despite these concerns, natural surfactant extracts would seem to be the more desirable choice when compared to currently available synthetic surfactants. Cochrane 2005
- 13. Recommendation Natural surfactants should be used in preference to any of the synthetic surfactants available (grade A). Cochrane 2005
- 14. •The animal surfactants have phospholipid compositions similar to that of natural surfactant; they contain some SP-B and SP-C, but no SP-A. • The surfactant approved for use in the United States is Survanta (beractant, Ross Laboratories, Columbus, Ohio) prepared by mincing bovine lungs in saline and extracting the lipids, SP-B, and SP-C with organic solvents. Dipalmitoylphosphatidylcholine, palmitic acid, and triglyceride are then added to improve the surface properties of the extract •. The surface properties of organic-solvent extracts of lung tissue also can be improved by removing neutral lipids by chromatography, as is done with Curosurf
- 15. Absence of Surfactant High Distending Pressures What happens ? Airway Stretch / Distortion Cellular Membrane Disruption Edema / Hyaline Membrane Formation Higher FIO2 / Pressures Barotrauma, BPD
- 19. •There is no indication that exogenously administered surfactant inhibits the synthesis and secretion of endogenous surfactant •Two 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
- 21. The meta-analysis (50 RCT) indicated that there would be two fewer pneumothoraces and five fewer deaths for every 100 babies treated prophylactically with surfactant.
- 22. •Prophylactic treatment during the first 15 minutes of life appears to be more effective •BUT not all infants that would appear to be at risk of developing RDS, actually develop the condition. •May lead to some infants being over treated, and possibly being exposed to adverse effects, unnecessarily.
- 23. Trade name Active ingredient Source dosing Survanta Beractant Bovine lung extract 4ml/kg, maximum upto 4 times 6 hrly Infasurf Calfactant Calf lung lavage 3ml/kg, maximum up to 3 doses 12 hrly Curosurf Poractant alfa Porcine lung extract 2.5ml/ kg 1st dose maximum upto 1.25ml//kg up to 2 doses 12hrly Neosurf Beractant Bovine lung lavage 5ml/kg 1st dose maximum upto 3 doses 12hrly
- 24. ARE MULTIPLE DOSES MORE BENEFICIAL ?
- 25. •Multiple doses of surfactant have been given in most trials because the response to an individual dose is often transient. • In preterm animals, exogenously administered surfactant is can be inhibited by soluble proteins and other factors in the small airways and alveoli. Multiple doses are thought to be useful because they can overcome this functional inactivation of surfactant. Pediatrics 1991
- 27. Synergistic effect Prenatal steroids + Surfactant is better than either alone ↓ neonatal mortality ↓ air leaks Give both ↓ severe IVH Am J Obst Gynec Suppl, 1995
- 28. 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).
- 29. INSURE procedure Early surfactant replacement therapy with extubation to N CPAP compared with continued mechanical ventilation with extubation is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. COCHRANE 2005
- 30. “ Options for ventilatory management that are to be considered after surfactant therapy include very rapid weaning and extubation to CPAP (grade B evidence).”
- 31. Intubate Give Surfactant Extubate Put on Ncpap
- 34. Infant of diabetic mother Meconium Aspiration Syndrome Congenital Diaphragmatic Hernia
- 35. WHAT ARE THE RISKS OF EXOGENOUS SURFACTANT THERAPY?
- 36. The short-term risks of surfactant replacement therapy • Bradycardia and hypoxemia during instillation, • Blockage of the endotracheal tube • Increase in pulmonary hemorrhage following surfactant treatment • However, mortality ascribed to pulmonary hemorrhage is not increased and overall mortality is lower after surfactant therapy.
- 37. Is Surfactant beyond the reach of the common man?
- 38. Surfactant is expensive 22% reduction in hospital charges per survivor 52 % Reduction in ancillary charges
- 39. 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
Editor's Notes
- 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
- 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 def..in 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% Proteins12% (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…..
- Before proceding further Lets us briefly understand what happens in rds
- 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 tension..now 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…..as 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
- What was done next on this baby was something called as INSURE protocol…..it 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 ……