1. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS AT HIGH RISK OF
RESPIRATORY DISTRESS SYNDROME
Vermont Oxford Network

2. DELIVERY ROOM MANAGEMENT
OF PREMATURE INFANTS
STEERING COMMITTEE
Jeanette M. Conner, PhD, MS Vermont Oxford Network
Alan DeKlerk, MBChB, Maimonides Medical Center
Rose DeKlerk RNC, New York Presbyterian Medical Center
Michael S. Dunn, MD, FRCPC, Sunnybrook & Women’s Hospital
Joseph Kaempf, MD, Providence St. Vincent Medical Center
Maureen Reilly, RRCP, NRCP, Sunnybrook & Women’s Hospital
Roger F. Soll, MD, Chair, Vermont Oxford Network
EXPERT CONSULTANT
Jen-Tien Wung, MD, New York Presbyterian Medical Center

3. DELIVERY ROOM MANAGEMENT
OF PREMATURE INFANTS
PATIENT SAFETY AND DATA COMMITTEE
Steve Block, MD, Chair
Wake Forest University School of Medicine
Walter Ambrosius, PhD
Arthur Kopelman, MD
East Carolina University

4. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS AT HIGH RISK OF
RESPIRATORY DISTRESS SYNDROME:
BACKGROUND and RATIONALE

5. DELIVERY ROOM MANAGEMENT
OF PREMATURE INFANTS
What is the best approach to take in the stabilization of premature infants at high risk of developing respiratory distress syndrome?
delivery room intubation and prophylactic surfactant
administration with continued ventilator support
administration without continued ventilator support
early stabilization on nasal continuous positive
airway pressure (NCPAP)

6. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
What is current practice regarding intubation and surfactant administration for high risk infants (gestational age less than 30 weeks) in centers participating in the Vermont Oxford Network?

7. SURFACTANT TREATMENT AND ENDOTRACHEAL INTUBATION BY GESTATIONAL AGE
< >32
Gestational Age (weeks)
52,397 Infants 401 to 1500 Grams at 335 NICUS in 1998 and 1999

8. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
What is the rationale for early or prophylactic intubation and surfactant administration for high risk infants less than 30 weeks gestation?

9. PROPHYLACTIC SURFACTANT ADMINISTRATION
ADVANTAGES:
improved distribution
decreased barotrauma
need for aggressive
resuscitation practice
increased utilization/cost
DISADVANTAGES:

10. EFFECT ON PNEUMOTHORAX
PROPHYLACTIC vs. SELECTIVE SURFACTANT
EFFECT ON PNEUMOTHORAX
Decreased
Risk
Increased
STUDY
0.2
0.5
1.0
2.0
4.0
Kendig 1991
Dunn 1991
Egberts 1993
Kattwinkel 1993
Walti 1995
Bevilacqua 1996
TYPICAL ESTIMATE
0.2
0.5
1.0
2.0
4.0
Soll 2001
Relative Risk and 95% CI

11. PROPHYLACTIC vs. SELECTIVE SURFACTANT EFFECT ON NEONATAL MORTALITY
Decreased
Risk
Increased
STUDY
0.2
0.5
1.0
2.0
4.0
Kendig 1991
Dunn 1991
Egberts 1993
Kattwinkel 1993
Walti 1995
Bevilacqua 1996
Bevilacqua 1997
TYPICAL ESTIMATE
0.2
0.5
1.0
2.0
4.0
Soll 2001
Relative Risk and 95% CI

12. NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE
What about the early application of
Nasal Continuous Positive Airway Pressure (NCPAP)?

13. NASAL CPAP and OUTCOME OF PRETERM INFANTS
Comparison of clinical outcome before (n=57) and after (n=59) introduction of nasal continuous positive airway pressure
De Klerk AM and De Klerk RK. J Paediatr Child Health 2001

14. PROPHYLACTIC APPLICATION OF NASAL CPAP
RANDOMIZED CONTROLLED TRIAL OF 82 VLBW INFANTS
(HAN AND COWORKERS 1987)
Risk Difference
Decreased
Risk
Increased
OUTCOME
( 95% CI )
0.2
0.5
1.0
2.0
4.0
USE OF IPPV
0.09 (-0.12, 0.29)
PNEUMOTHORAX
-0.01 (-0.14, 0.12)
SEPSIS
-0.04 (-0.21, 0.13)
NECROTIZING ENTEROCOLITIS
-0.14 (-0.30, 0.02)
IVH
0.15 (-0.02, 0.32)
BRONCHOPULMONARY DYSPLASIA
0.13 (-0.03, 0.29)
MORTALITY
0.07 (-0.03, 0.17)
0.2
0.5
1.0
2.0
4.0
HAN 1987
Relative Risk and 95% CI

15. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
What is the rationale for considering early or prophylactic intubation and surfactant administration followed by rapid extubation and stabilization on nasal CPAP?

16. NASAL CPAP AND EARLY SURFACTANT MECHANICAL VENTILATION OR DEATH
VERDER H AND COWORKERS PEDIATRICS 1999

17. NASAL CPAP AND EARLY SURFACTANT
MORTALITY
VERDER H AND COWORKERS PEDIATRICS 1999

18. DELIVERY ROOM MANAGEMENT RESPIRATORY DISTRESS SYNDROME
OF PREMATURE INFANTS
AT HIGH RISK OF
RESPIRATORY DISTRESS SYNDROME
PROTOCOL

19. DELIVERY ROOM MANAGEMENT
OF PREMATURE INFANTS
OBJECTIVE
To compare the effect of three distinct methods of post-delivery stabilization and subsequent respiratory care on chronic lung disease and survival in premature infants at high risk of respiratory distress

20. DELIVERY ROOM MANAGEMENT
OF PREMATURE INFANTS
The three approaches to post-delivery care:
PS Group: Intubation, prophylactic surfactant administration
shortly after delivery, stabilization on ventilator support
NCPAP Group: Early stabilization on nasal continuous positive
airway pressure (NCPAP) with selective intubation and
surfactant administration for clinical indications
ISX Group: Intubation, prophylactic surfactant
administration, and rapid extubation to Nasal CPAP

21. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS : ENROLLMENT CRITERIA
Eligibility: Admission to L & D
high risk of preterm delivery at gestational age 26+0 to 29+6 weeks
Inclusion Criteria:
delivery imminent
no maternal rupture of membranes > 14 days
no potentially life threatening congenital anomaly or genetic syndrome
no known lung maturity
antenatal steroid status known
written informed consent obtained (prior to delivery)
Randomization: Prior to delivery
Exclusion Criteria (s/p delivery):
stillborn (apgar score of 0 at one minute)
potentially life threatening congenital anomaly/genetic syndrome

22. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
STUDY DESIGN
multicenter randomized clinical trial conducted at participating
Vermont Oxford Network Centers

23. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS : TREATMENT GROUPS
Eligible infants will have consent obtained prior to delivery.
At imminent delivery premature infants will be randomized to either:
Intubation, prophylactic surfactant administration, subsequent stabilization on ventilator support
early stabilization on NCPAP and selective intubation and surfactant administration for clinical indications
intubation prophylactic surfactant administration and rapid extubation to NCPAP.
After delivery infants who meet all criteria will be enrolled in the trial.

24. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS: TREATMENT GROUPS
PROPHYLACTIC SURFACTANT ADMINISTRATION
(PS GROUP)
Intubation in the delivery room between five and fifteen minutes of life
Surfactant treatment s/p intubation
Mechanical ventilation
Extubation at anytime after 6 hours of age based on predefined criteria

25. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS: TREATMENT GROUPS
EARLY APPLICATION OF
NASAL CONTINUOUS POSITVE AIRWAY PRESSURE
(NCPAP GROUP)
Stabilization on standardized NCPAP system applied within five to fifteen minutes after delivery
Bubble CPAP system at 5 cm H20
Predefined criteria for respiratory insufficiency requiring intubation and surfactant treatment

26. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS: TREATMENT GROUPS
PROPHYLACTIC SURFACTANT ADMINISTRATION,
RAPID EXTUBATION TO NASAL CONTINUOUS POSITVE AIRWAY PRESSURE
(ISX GROUP)
Intubation in the delivery room between five and fifteen minutes of life
Surfactant treatment s/p intubation
Rapid extubation to standardized nasal CPAP bubble system at 5 cm H20

27. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
CRITERIA FOR SELECTIVE INTUBATION
AND SURFACTANT TREATMENT
Intubation based on clinical status:
apnea
respiratory failure (PCO2 > 65 mmHg)
hypoxemia (supplemental oxygen > 40%-60%
to maintain oxygen saturation > 86%-94%)
severe respiratory distress
Surfactant treatment s/p intubation

28. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
PRIMARY OUTCOME MEASURE:
Chronic Lung Disease or Mortality
at 36 weeks adjusted age
Chronic lung disease is defined as documented
requirement for supplemental oxygen or respiratory
support. Documented oxygen requirement will be
defined as the need for supplemental oxygen to
maintain an oxygen saturation  88%.

29. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
SAMPLE SIZE:
Sample Size is based on:
20% reduction in the number of infants with chronic lung disease/death from 36% to 29% ( 0.05, ß 0.2)
A total of 2106 infants will be enrolled:
702 per study group
Will re-evaluate based on results of pilot study

30. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
SECONDARY OUTCOME MEASURES:
Number of infants receiving surfactant treatment
Number of surfactant doses
Postnatal steroids
Clinical status during first 28 days of life
Clinical status at 36 & 40 weeks adjusted age
Days on assisted ventilation
Days on NCPAP
Days on supplemental oxygen
Growth, day 28 and discharge
Pneumothorax
Pulmonary hemorrhage
Patent ductus arteriosus
Necrotizing enterocolitis
Intraventricular hemorrhage
Steroids for chronic lung disease
Mortality
Duration of hospitalization
Other complications of prematurity
Health and developmental status at 2 years adjusted age

31. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
STUDY TIMELINE
Study to be conducted in three stages
Stage 1: Introduction of Nasal CPAP in routine NICU practice
Stage 2: Pilot study of feasibility of delivery room interventions
Stage 3: Formal enrollment of subjects in large pragmatic trial

32. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
Stage 1: Introduction of Nasal CPAP in routine NICU practice
Build bubble CPAP devices
Educate centers regarding use of bubble NCPAP
Incorporate bubble NCPAP into daily routine of NICU
Evaluate competence of centers in use of bubble CPAP
February through April 2003

33. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
Stage 2: Pilot study of feasibility of delivery room interventions
Educate centers regarding conduct of delivery room management trial
Pilot study of randomization to all three arms of study
May through October 2003
Determine feasibility of launching large pragmatic trial

34. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
Stage 3: Formal enrollment of subjects in large pragmatic trial
In accordance with insights gained from feasibility study
January 2004

35. DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTS
NETWORK CENTER PARTICIPATION
Interested centers must identify a study team comprised of a neonatologist, nurse practitioner or nurse, and a respiratory therapist
Team must commit to participating in a standardized education and training program
Team must implement education and training program within their NICU and unit must establish a level of competency with the bubble CPAP system prior to initiating enrollment in pilot study