Dr Rakesh KumarAsst. Professor

N.M.C.H, Patna

Antenatal steroid Oxygen CPAP Mechanical Ventilation Surfactant

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?

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’

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

Surfactant is most widely researched with maximum RCT’ s in neonatology

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

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)

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

TYPES OF SURFACTANT

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

Phospholipids DPPC Animal lung extract

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

Tyloxapol

•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

Recommendation

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

Cochrane 2005

•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

Absence of Surfactant

High Distending Pressures

Airway Stretch / Distortion

Cellular Membrane Disruption

Edema / Hyaline Membrane Formation

Higher FIO2 / Pressures

Barotrauma, BPD

What happens ?

SURFACTANT : DEFICIENCY

PRESSURE VOLUME LOOP

•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

Timing

Prophylactic or Rescue

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.

•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.

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

ARE MULTIPLE DOSES MORE BENEFICIAL ?

•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

Synergistic effectPrenatal steroids + Surfactant is better than either alone

neonatal mortality air leaks severe IVH

Give both

Am J Obst Gynec Suppl, 1995

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).

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

“ Options for ventilatory management that are to be considered after surfactant therapy include very rapid weaning and extubation to CPAP (grade B evidence).”

Intubate Give Surfactant Extubate Put on Ncpap

Infant of diabetic mother Meconium Aspiration Syndrome Congenital Diaphragmatic Hernia

WHAT ARE THE RISKS OF EXOGENOUS SURFACTANT THERAPY?

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.

Is Surfactant

beyond the

reach of the

common

man?

Surfactant is expensive 22% reduction in hospital charges per

survivor 52 % Reduction in ancillary charges

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