1. Novel Approaches to Surfactant Administration
Dr.Sh.Noripour
Neonatologis
Semnan Medical Sciences University

2. RDS - Treatment Oxygen CPAP Mechanical ventilation
Surfactant replacement
Supportive Care
The standard treatments we are all familiar with, including oxygen supplementation, Respiratory support with CPAP of mechanical ventilation and surfactant replacement therapy whilst at the same time providing good supportive care with careful fluid and nutritional management and temperature control. However within each of these areas controversies still exist. How much oxygen should we give? Who should get CPAP and who should be ventilated? When should you intubate to give surfactant etc.

3. Information about HMD in Late 1960’s
Normal lungs contained surfactant (Clements – 1957)
HMD lungs were surfactant deficient (Avery and Mead – 1959)
Intubation of HMD infants abolished grunting and decreased oxygenation (Harrison, et al., 1968)

4. ( Goran Enhorning (obstetrician).
(b) Bengt Robertson (perinatal pathologist).

5. Goran Enhorning, an obstetrician, and Bengt Robertson, a pediatric pathologist, showed that preterm rabbits treated with natural surfactant did not die as expected soon after birth.
After one year later, in 1973, they showed that pharyngeal deposition rather than tracheal instillation of natural surfactant was also effective

6. Historical Perspectives –cont.
In 1973 CPAP using nasal catheters positioned in the midnares was used on infants weighing >1500gms who had RDS requiring >60% oxygen to maintain a PaO2 of mmHg.
These early interventions increased survival of preterm infants.

7. VIENNA-09

8. 20 - Required 100% or had Apnea 1 - Ventilated from Birth
20 Infants Treated with CPAP over 16 Months
51 Infants with IRDS
UA lines, O2 for Pao2 of mmHg
20 - Required 100% or had Apnea
5 - Apnic at Birth
1 - Ventilated from Birth
25 - Increased O2 Only
All Survived
Bag & Mask Ventilation
Ventilated
1 Survived
CPAP
All Died
16 Survived
Data from Gregory NEJM, 1971
VIENNA-09

9. CPAP Device for use with Endotracheal Tube
Gregory, et al., NEJM, 1971
VIENNA-09

10. Head Box for CPAP without Endotracheal Tube
VIENNA-09
Gregory, et al., NEJM, 1971

11. CPAP Provided by G. Gregory
This is a trash bag with gas inflow. It was closed loosely about the neck and pressure could be maintained easily and constantly. This was about the 5th or 6th patient we treated.
Provided by G. Gregory

12. George Gregory

13. Fujiwara in 1980 published a seminal article in the Lancet giving the results of administration of a modified bovine surfactant (Surfactant-TA) to 10 preterm infants.

14. Verder et al. tested a novel approach, INSURE (intubation, surfactant administration, and extubation). This technique provides the benefits of surfactant administration but also eliminates continued mechanical ventilation.
This approach, still requires skills for intubation and has the potential for trauma to the glottis and airway during intubation as well as the risks of surfactant administration enumerated above.
H. Verder, B. Robertson, G. Greisen et al., “Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome,” New England Journal of Medicine, vol. 331, no. 16, pp. 1051–1055, 1994. 

15. Infants randomly assigned to treatment with surfactant were treated with morphine (0.1 mg per kilogram intravenously) and atropine (10 μg per kilogram intravenously) before intubation.
Treatment with naloxone (10 μg per kilogram intravenously) before extubation was optional

16. Current recommendations vary from use in infants who are intubated and have an aAPo2 <0.22 to use in infants receiving ≥40% oxygen administered in a hood when the Pao2 is <80 TORR (aAPo2 approximately <0.36).

17. Guidelines for Surfactant Treatment of RDS
< 28 wk
29-31 wk
> 32 wk
NIPPV in DR, Early Rescue (<30’) in DR or NICU with 200 mg/kg of Poractant Alfa
Early CPAP/NIPPV
Surfactant if intubated for resuscitation
Observe
CPAP/NIPPV if respiratory
distress
Extubate to NIPPV as soon as possible (> 24 wk).
Start Caffeine
Early Rescue with
mg/kg if FiO2 > white CXR.
Delayed Rescue with
100 mg/kg if FiO2 > 0.40
+ white CXR
Caffeine if symptomatic
Redosing:
FiO2 > 0.30
How soon: 2-12 hrs from the 1st dose
FiO2 > 0.35
How soon: 12 hrs from the 1st dose
FiO2 > 0.40 17

22. Downes’ Scoring system
0   1 2
 Cyanosis
None
In room air
 In 40% FIO2
 Retractions
Mild
Severe
Grunting
Audible with stethoscope
Audible without stethoscope
Air entry
Clear
Decreased or delayed
Barely audible
Respiratory rate
<60
60-80
>80 or apnea
 Score:  > 4 = Clinical respiratory distress; monitor arterial blood gases > 8 = Impending respiratory failure

23. Failure of InSurE was associated with severity of RDS and extremely low birth weight < 750g

24. MISurf: Minimally invasive intratracheal surfactant application without mechanical ventilation by feeding tube device
InSurE: Surfactant application by InSurE strategy (Intubation - surfactant - extubation sequence).

25. Minimally invasive surfactant application (MISurf) via feeding tube or IV cannula device is a recently described innovative method of surfactant administration without the need for positive pressure ventilation

26. Several techniques, collectively labeled “minimally invasive surfactant therapy” (MIST), have been described in which surfactant is delivered without tracheal intubation.

27. strategies include (1)intra-amniotic instillation
(2)pharyngeal instillation
(3)administration via laryngeal mask airway
(4)administration via thin endotracheal catheter without IPPV
(5)aerosolized/nebulized surfactant administration in spontaneously breathing infants.

28. Intra-Amniotic Instillation of Surfactant
There is only one feasibility report describing endoscopic delivery of surfactant directly to the fetus during active preterm labor
Using this approach the investigators injected surfactant into the mouths of 3 preterm fetuses through a catheter placed through the biopsy channel of the fiberscope
it has not been incorporated into clinical practice.

29. Pharyngeal Instillation of Surfactant
The pharyngeal instillation of surfactant before delivery has the potential to replicate the physiologic process.
While the chest remains compressed in the birth canal, fetal lung fluid can be suctioned from the upper airway and replaced with a surfactant-containing solution.
Then, as the chest expands, the baby is stimulated to aspirate the surfactant-containing solution providing surfactant at the advancing air-fluid interface.
This process can be further facilitated by the application of mask CPAP.

30. Surfactant administered within the nasopharynx before delivery of the shoulders after suctioning of the nasopharynx.
Newborns received CPAP at 10 cm H2O by mask as they initiated breathing, and this was continued at 6 cm H2O for at least 48 hours
this approach requires a cephalic delivery and a spontaneously breathing infant.
Cesarean section, malpresentation (breech or transverse), or perinatal compromise limit the application of this approach.

31. Administering via Laryngeal Mask Airway (LMA)
A protocol for LMA surfactant administration suggested by Trevisanuto
involves positioning the LMA, followed by instilling the surfactant in two to four aliquots via the LMA.
Each aliquot is usually followed by brief IPPV until the surfactant disappears from the LMA.
the LMA is removed and the baby is placed on CPAP for subsequent management.

33. The limitations of surfactant administration using LMA are related to the nonavailability of smaller LMA sizes for use in extremely premature infants
The technique is relatively simple and seems promising, but well-designed studies are needed to confer safety and efficacy.

34. aerosolized/nebulized surfactant administration
Use of nebulized surfactant seems to be the most sophisticated and minimally invasive technique
Multiple factors are reported to influence aerosol surfactant dose delivery, including patient weight or size, minute ventilation , aerosol flow and patient peak inspiratory flow, aerosol particle size

35. It is classified as a “MIST” technique.
Administration via Thin Endotracheal Catheter/Feeding Tube without IPPV
This method of surfactant administration delivers exogenous surfactant using a thin intravascular catheter or feeding tube inserted below the vocal cords.
It is classified as a “MIST” technique.

36. MIST/LIST – Minimally/Less Invasive Surfactant Therapy
Dargaville and Gopel described the use of rescue surfactant administered in spontaneously
breathing infants, via a fine tube placed into the trachea without the use of sedative or paralysing
drugs

40. Indication for MIST
worsening hyaline membrane disease in a baby on non-invasive support
increased work of breathing (WOB – respiratory rate,recession, apnoea, cardiovascular stability)
Increasing oxygen requirement (FiO2) (normally over 50%)

41. Equipment (1) Laryngoscope with appropriate sized blade
(2) Surfactant administration pack – syringe, needle and
administration tube
(3) Magill forceps
(4) 5ml syringe
(5) Warmed surfactant (rub vial in hands to ensure not chilled), prescribed on drug chart