Rational Surfactant Therapy

Rational Surfactant Therapy

Ajay Agade

Jawaharlal Nehru Hospital And Research Centre, Steel Plant Bhilai

Thanks m for explaining us the physiology in detailmoving 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 gestationas much as that 80% of babies below gestation 27 weeks may land into rds1

What are the interventions available?OxygenCPAPMechanical VentilationSurfactantDr Ajay Agade

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 mentionedsome will require cpap and some might require advance therapies like surfactant therapythis presentation focuses on the surfactant therapy in rds2

Surfactant Replacement TherapyDoes it work?When to give?Which one to give?How often to give?How to give?Does it cause any problems?Dr Ajay Agade

The first and formost question is does it workwhat is the proper timing to give ..which type whether natural or synthetic.how many dosesthen we will be discussing what is the methodology3

Does Surfactant Replacement Therapy Work?

Dr Ajay Agade

So the first question is does it wotksbeing 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 databse4

Most widely researched with maximum RCT s in neonatology

Dr Ajay Agade

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 slide5

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 1994Dr Ajay Agade

In may 1994 NEJM published a very significant data which concluded that6

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

Dr Ajay Agade

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.7

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

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. 8

What is Surfactant?

Dr Ajay Agade

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

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TYPES OF SURFACTANT

SYNTHETIC MODIFIED NATURAL (Exosurf, Surfact) (Survanta, Curosurf)

Phospholipids DPPC Animal lung extract

Spreading Cetyl alcholol Surfactant proteins agents + (SP-B, SP-C) Tyloxapol

Dr Ajay Agade

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 slidesThe natural ones are prepared from variety of animals..from bovine its called as survantacalflung its called exosurf and porcine called as curosurf.10

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 2005Dr Ajay Agade

Lets see what the databse says about tisIn 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 superior11

Recommendation

Natural surfactants should be used in preference to anyof the synthetic surfactants available (grade A).

Cochrane 2005Dr Ajay Agade

So cochrane came with final conclusion that 12

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

Dr Ajay Agade

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..13

Absence of Surfactant

High Distending Pressures

Airway Stretch / Distortion

Cellular Membrane Disruption

Edema / Hyaline Membrane Formation

Higher FIO2 / Pressures

Barotrauma, BPD

What happens ? Dr Ajay Agade

14Before proceding further Lets us briefly understand what happens in rds

SURFACTANT : DEFICIENCY

Dr Ajay Agade

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 dont know its visible properlycoin is floating over water because of surface tension..now if we administer surfthe air liquid interface breaks and coin sinks..15

PRESSURE VOLUME LOOPDr Ajay Agade

If we try to understand this on respiratory mechanics it will look like thisThis is pressure volume loop showing difference between rd lung and normal lungif we see the lower opening pressure in rds its 15..its less than 10 somewhere hereif 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..16

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 pathwaysDr Ajay Agade

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 surfin fact not only surf has postive effect on lung mechanics it also gets recycled in making of natural surf17

Timing

Prophylactic or RescueDr Ajay Agade

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.18

The meta-analysis (50) indicated that there would be two fewer pneumothoraces and five fewer deaths for every 100 babies treated prophylactically with surfactant.

Dr Ajay Agade

So what the database has to asy about thisThe 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 se19

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.

Dr Ajay Agade

What are the facts regarding ..We had the twins one developed rds another remained stable20

ARE MULTIPLE DOSES MORE BENEFICIAL ?Dr Ajay Agade

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 1991Dr Ajay Agade

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Antenatal steroid and Surfactant goes hand in hand

Dr Ajay Agade

Before we procede to actual procedure I want to emhasis the importence of antenatal steroidseventhogh 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 position23

Antenatal steroids & surfSynergistic effectPrenatal steroids + Surfactant is better than either alone neonatal mortality air leaks severe IVH

Give bothAm J Obst Gynec Suppl, 1995Dr Ajay Agade

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

the established facts are

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How Do We Do Ithttp://www.youtube.com/watch?v=86OA4to66hQ

http://www.youtube.com/watch?v=j9z3fb3dV1A&feature=related

Dr Ajay Agade

Start videopause focusing subjectgive details bout history no antinatal steroids gestation symptopms .show xary start video again.take pauses when reqd.B/0 priyankaborn 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 surfI want to emphasise here that they did not received an steroids..26

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 2005Dr Ajay Agade

What was done next on this baby was something called as INSURE protocol..it says.so we follows exactly the same..27

HOW SHOULD VENTILATORY MANAGEMENTAFTER SURFACTANT THERAPY BEAPPROACHED?

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

Lets see what the evidence has to say.it says that28

Ventilatory strategy-INSURE

Dr Ajay Agade

This is our baby which was extubated within 4 hours of surf therapybaby 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 life29

WHAT ARE THE RISKS OF EXOGENOUS SURFACTANT THERAPY?

Dr Ajay Agade

Coming to the last part of discussionits time to duscuss the problems of surfactant administartion30

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.

Dr Ajay Agade

Increase in ph as compares to normal term subjects.If u compare wit incidence of ph in preterm itself its very lesson the contrary by preventing the complication of prematurity its actually reduces the incidence of ph31

Is Surfactant beyond the reach of the common man?

Dr Ajay Agade

Cost implicationsSurfactant is expensive22% reduction in hospital charges per survivor52 % Reduction in ancillary chargesDr Ajay Agade

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 narang33

Does surfactant fail?Extremely preterm infants with structurally lung immaturityPneumonia or pulmonary hypoplasiaPerinatal asphyxiaPulmonary edema from lung damage or fluid overloadPulmonary edema from L-R shunting through PDACongenital B protein deficiencyDr Ajay Agade

Yes first and foremost thing is the skillsmonitoring ventilatory strategy and supportive therAPY.most important in surf therapy is insurewhat are the other things 34

Got Surfactant!

Dr Ajay Agade

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