Surfactant journey,nnk,oct 2017 - Dr Karthik Nagesh

1. Dr Karthik Nagesh
The Surfactant Journey Started in Karnataka!!

2. Manipal Hospital,Bangalore, 1992

3. Multi Centre Porcine Surfactant (Curosurf) trail
(UK,1990 /1992)
• Study was going on at
Queen Charlotte’s &
Chelsea Hospital,
London
• Learnt surfactant
therapy
• Saw its usefulness
Prof. David Harvey

4. Surfactant Replacement Therapy…Early Data
• Need for Oxygen /
ventilatory support is
reduced
• Pneumo thorax, IVH
risk reduced
• Mortality reduced (by
30 - 40 % in VLBW

5. Surfactant Replacement Therapy Established in
Neonatal RDS
• Access to latest journals was difficult (But literature
search through index medicus confirmed early data
proving surfactant usefulness)
• ‘Survanta’ introduced commercially elsewhere
• But not available in India
• Tried desperately to procure through various sources -
need for substantial use
• Wrote to company, no response
• No Internet/Email

6. 28 Weeks POG…Stormy Course! 1993
• Baby S, outborn -28 weeks, 1.1kg.
• No Surfactant
• RDS from Birth: blow by oxygen given
and shifted
• Intubated at our NICU. Hypoxia,
acidosis
• Ventilated,(Pressure Mode,IMV)
for severe RDS for
4weeksSignificant PDA ligated
in OT > weaned off IMV
• Sepsis with DIC
• NEC perforated  Resection >
colostomy > re-anastamosis
• ROP CryoSurgery done in OT.
• Day 86 discharged home
• CLD Dr Neena Modi-Visit to Manipal Hospital NICU

7. Next Opportunity!...
Case 1: Baby of G
• 34 weeks, Infertility
treatment, Precious,
Outborn, Severe RDS
• Ventilated, Pressure
limited, Time Cycled, PIP-
36,a-A(DO2-542)
a/A Ratio 0.1
• What next?
RDS (HMD)
RDS (HMD)

8. • Survanta Available Commercially !!
• In Singapore, Hong Kong, UK, USA
• Contacted KK Women & Children’s Hospital Pharmacy,
Singapore
• Procured 4 vials ‘Survanta’ through help of local
Neonatologist there
• Vials Flown to Bangalore by ‘’Air- Chartered Flight’’
• Ist Dose Given to baby at 28 hours age (Too late) !!
• Unfortunately baby succumbed

9. Subsequent Use of Surfactant
Case 2: Baby of N
• 34 weeks, 2.1Kg, Outborn, Severe RDS. (IMV,PIP-32,FiO2-
1,PaO2/pAO2-0.15,A-a(DO2)-529,Total ‘White Out’ Lungs
• ‘Survanta’ available readily…. given endotracheally
through side port adapter
• Significant improvement, child survived,d/s D-17
• Today healthy & helping in father’s business

10. Surfactant Administered – Good Response!

11. Brief Reports
Surfactant Therapy in Neonatal
Respiratory Distress Syndrome
Karthik Nagesh
V. Bhat
S. Kunikullaya
N. Rajesh
Respiratory distress syndrome (RDS) is
the leading cause of neonatal respiratory
distress in our country and is the commonest
disorder requiring assisted ventilation all
over the world(l,2), Exogenous surfactant
administration is now an established mode
of therapy in neonatal RDS (hyaline mem-
brane disease, HMD). Ever since the first
report of successful surfactant replacement
therapy in neonates with established
RDS(3), numerous clinical trials conducted
worldwide have shown exogenous surfac-
tant therapy to reduce the mortality rate,
requirements for mechanical ventilation
and air leak complications in RDS(4). Four
From the Neonatal Division, Department of
Pediatrics, Manipal Hospital, Bangalore
560 017.
Reprint requests: Dr. N. Karthik Nagesh,
Consultant Neonatologist, Department of
Pediatrics, Manipal Hospital, Airport Road,
Bangalore 560 017.
Received for publication: March 12, 1994;
Accepted: April 30, 1994
surfactant preparations are now available
commercially. Of these, two have been nat-
urally extracted (SURVANTA-bovine lung
source and CUROSURF-porcine lung
source) and two are synthetic (Colfosceril
palmitate-EXOSURF and artificial lung
expanding compound-ALEC). Not many
centres in India have tertiary level care
neonatal units with facilities for ventilation.
Experience with ventilation for neonatal
RDS is limited to a few centres only(5).
However, there is as yet no report of any
experience using established surfactant
replacement therapy for RDS in the Indian
literature. We report here 'exogenous sur-
factant replacement treatment' in addition
to mechanical ventilation and other inten-
sive care measures. This is probably the
first such report from India, of having suc-
cessfully used surfactant replacement
therapy for neonatal RDS.
Case Report
A male baby was born at 34-35 weeks
of gestation to a multiparous woman (gra-
vida six and parity four) in a nursing home.
The mother had an uneventful antenatal
period. The baby was delivered by a Cesa-
rean section. The mother had received two
doses of betamethasone intramuscularly
twelve hours apart prior to the delivery.
The baby cried normally at birth and the
Apgar score was reported to be normal by
the attending Pediatrician. Within half an
hour after birth, the baby was noted to
have respiratory distress with grunting,
alae nasi flaring, subscostal and intercostal
recessions and cyanosis (in air). Progres-
sive worsening in the respiratory distress
occured over the next 2-3 hours inspite of
giving the baby humidified oxygen through
971

12. Following this…
• Many inquiries from Pediatrician’s -about
how/where to procure Surfactant?
• Many thought it was a ‘’Panacea’’ for Neonatal RDS
• Ignoring that more important is well developed
NICU / ventilatory care and monitoring and that
Surfactant is only an Adjunct Therapy!

13. Need for CME / Out reach education hence felt
• Ventilatory & Surfactant workshops conducted
(Multiple) all over Karnataka ( NNF-K) & elsewhere
• Surfactant therapy & administration technique
taught
• Other faculty from hospitals in Bangalore (SJMCH,
MSRMCH) actively involved

15. Surfactant Indications
• Clinical / Radiological
evidence of RDS(HMD)
• Age less than 24 Hours
Preferably
• Baby to be receiving
Ventilation
• paO2/pAO2 Ratio <
0.22

16. All Measures used to procure surfactant
• Importing (Singapore, Dubai, UK)
• Grey Market (Medical Drug Suppliers)
• Patient Relatives
• Wrote multiple times to the company & DCGI to help
to bring the product to Indian Market

17. ‘’EXOSURF’’(Burroughs=Welcome)
• Prof.Walker Long - visited us
• ‘’Exosurf’’ ( Colfosceril Palmitate) first introduced in
India
• Used extensively by us (after post marketing study)
and others in Bangalore, Mumbai, Chennai

18. NIH
CONSENSUS STATEMENT
ON
ANTENATAL STEROIDS (1994)
• Prevents RDS (HMD)
• Reduces RDS Severity
• Reduces Risk Of IVH / NEC
• Betamethasone Better
• Upto 34 Weeks G.Age

19. Single dose surfactant -? Effective
• DNB Thesis Study Manipal
Hospital, Bangalore 1994 –
1997 even ‘Single Dose
Works’ (NNF Award) (2nd
Prize, Vellore)
• Anuradha H S, N.Karthik
Nagesh
• Started using this Single
Dose and helped many
more babies

20. Subsequent use by others
• Synthetic “Surfact”-Sun Pharma” available after a PMS
study done by few centres including us at MH
• Officially ‘’Survanta’’ became available in India in 1999
• Extensive usage of ‘Survanta’ in many tertiary care units
in the country following this

21. • Sanghvi KP, Merchant RH, Indian Pediatrics. ’98
• Narang A et al, Indian Pediatrics, ‘01
• Karthik Nagesh N, Jl. Neonatology,India,’03
• Karthik Nagesh N, Indian Jl. Prac.Pediatrics, ‘05
Improved survival (1000-1249 g)
Reduced sepsis risk,PDA,IVH,CLD
Lesser ventilation need by 44.1 hrs
Lesser hospital stay by 4.37 days
Costs reduced by 25-52%
Initial Surfactant Usage Data from Data

22. Porcine Surfactant - Curosurf
• Available from 2001
• Not as much used till the 2004 data comparing
‘Curosurf’ and ‘Survanta’ was published

23. Clinical Trials on Surfactant -Evidence from Cochrane
systematic meta-analysis (2000-2003)
• S v/s Placebo: Reduced risk of PTX,Mortality.
• Combined AN steroids & PN S: Risk of
PTX,RDS,PDA,mortality reduced.
• Early vs Delayed rescue S t/t : Reduced risk of PTX,CLD.
• High vs Low dose S : Reduced dur. Of IMV/O2, risk of IVH,CLD,PIE.
• Multiple doses : Reduced IMV , risk of PTX/mortality. 2 doses as good as 4.
• Natural vs Synthetic ; Reduced risk of PTX/mortality, early IMV reduction.
• Porcine vs Bovine ;Porcine (curosurf ) better.

24. Approved Surfactants*
1990
2006
FDA approval- 2012
Exosurf Survanta Infasurf Curosurf
1991 1998 1999
Surfaxin-
Lucinactant
Animal derived protein
containing surfactants
*After Extensive Trials & Data
bLes-Neosurf

25. Large Scale Use of Surfactant-2003 onwards
• Easy availability
• More NICUs came up
• Even in tier 2 cities
• More Neonatologists
• Affodability increased
• Insurance/Reimbursement
• Standard Practice guideline
• Government Hospitals

26. Karthik Nagesh N, Abdul
Razak,2016;0:F1–F5. doi:10.1136/
Arch. Dis.Child-2016-308169;F1

27. Advances in Neo.Respiratory Care
• 1970s
• Ventilatory Care
• 1980s
• Surfactant Replacement
Therapy
• ECMO
• 1990s
• HFOV,Nitric Oxide Therapy,
• Liquid Ventilation
• 2000s
• NIV, CPAP , INSURE
• 2011-2012
• Early CPAP alone +/- Surfactant
• 2013
• HHHFNC