delivery room management of premature infants at high risk of at high risk of respiratory distress...

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTSOF PREMATURE INFANTS

AT HIGH RISK OFAT HIGH RISK OFRESPIRATORY DISTRESS RESPIRATORY DISTRESS

SYNDROMESYNDROME

Vermont Oxford NetworkVermont Oxford Network


STEERING COMMITTEESTEERING COMMITTEE

Jeanette M. Conner, PhD, MS Vermont Oxford NetworkJeanette M. Conner, PhD, MS Vermont Oxford NetworkAlan DeKlerk, MBChB, Maimonides Medical CenterAlan DeKlerk, MBChB, Maimonides Medical CenterRose DeKlerk RNC, New York Presbyterian Medical CenterRose DeKlerk RNC, New York Presbyterian Medical CenterMichael S. Dunn, MD, FRCPC, Sunnybrook & Women’s HospitalMichael S. Dunn, MD, FRCPC, Sunnybrook & Women’s HospitalJoseph Kaempf, MD, Providence St. Vincent Medical CenterJoseph Kaempf, MD, Providence St. Vincent Medical CenterMaureen Reilly, RRCP, NRCP, Sunnybrook & Women’s HospitalMaureen Reilly, RRCP, NRCP, Sunnybrook & Women’s HospitalRoger F. Soll, MD, Chair, Vermont Oxford NetworkRoger F. Soll, MD, Chair, Vermont Oxford Network EXPERT CONSULTANTEXPERT CONSULTANT

Jen-Tien Wung, MD, New York Presbyterian Medical CenterJen-Tien Wung, MD, New York Presbyterian Medical Center


PATIENT SAFETY AND DATA COMMITTEEPATIENT SAFETY AND DATA COMMITTEE Steve Block, MD, ChairSteve Block, MD, ChairWake Forest University School of MedicineWake Forest University School of Medicine

Walter Ambrosius, PhDWalter Ambrosius, PhDWake Forest University School of MedicineWake Forest University School of Medicine

Arthur Kopelman, MDArthur Kopelman, MDEast Carolina UniversityEast Carolina University



SYNDROME:SYNDROME:

BACKGROUND and RATIONALEBACKGROUND and RATIONALE


What is the best approach to take in the What is the best approach to take in the stabilization of premature infants at high risk of stabilization of premature infants at high risk of

developing respiratory distress syndrome?developing respiratory distress syndrome?

• delivery room intubation and prophylactic delivery room intubation and prophylactic surfactant surfactant administration with continued ventilator supportadministration with continued ventilator support

• delivery room intubation and prophylactic delivery room intubation and prophylactic surfactant surfactant administration without continued ventilator administration without continued ventilator supportsupport

• early stabilization on nasal continuous positiveearly stabilization on nasal continuous positive airway pressure (NCPAP)airway pressure (NCPAP)

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS OF PREMATURE INFANTS

What is current practice regarding What is current practice regarding intubation and surfactant administration for intubation and surfactant administration for high risk infants (gestational age less than high risk infants (gestational age less than 30 weeks) in centers participating in the 30 weeks) in centers participating in the

Vermont Oxford Network?Vermont Oxford Network?

0%

20%

40%

60%

80%

100%

NO ETT

ETT

SURFACTANT

Gestational Age (weeks)

SURFACTANT TREATMENT AND ENDOTRACHEAL INTUBATION BY GESTATIONAL AGE

52,397 Infants 401 to 1500 Grams at 335 NICUS in 1998 and 1999

<24 24 25 26 27 28 29 30 31 32

>32


What is the rationale for early or What is the rationale for early or prophylactic intubation and surfactant prophylactic intubation and surfactant

administration for high risk infants administration for high risk infants less than 30 weeks gestation?less than 30 weeks gestation?

PROPHYLACTIC SURFACTANT ADMINISTRATIONPROPHYLACTIC SURFACTANT ADMINISTRATION

• improved distributionimproved distribution• decreased barotraumadecreased barotrauma

• need for aggressiveneed for aggressive resuscitation practiceresuscitation practice• increased utilization/costincreased utilization/cost

ADVANTAGES:ADVANTAGES:

DISADVANTAGES:DISADVANTAGES:

Relative Risk and 95% CIRelative Risk and 95% CI

STUDYSTUDY0.50.5 1.01.0 2.02.0 4.04.00.20.2

DecreasedDecreased IncreasedIncreasedRiskRisk

0.50.5 1.01.0 2.02.0 4.04.00.20.2

PROPHYLACTIC vs. SELECTIVE SURFACTANTPROPHYLACTIC vs. SELECTIVE SURFACTANT

Dunn 1991Dunn 1991

EFFECT ON PNEUMOTHORAXEFFECT ON PNEUMOTHORAX

Egberts 1993Egberts 1993

Kattwinkel 1993Kattwinkel 1993

Walti 1995Walti 1995

Bevilacqua 1996Bevilacqua 1996

Soll 2001Soll 2001

TYPICAL ESTIMATETYPICAL ESTIMATE

Kendig 1991Kendig 1991


STUDYSTUDY0.50.5 1.01.0 2.02.0 4.04.00.20.2


0.50.5 1.01.0 2.02.0 4.04.00.20.2

PROPHYLACTIC vs. SELECTIVE SURFACTANTPROPHYLACTIC vs. SELECTIVE SURFACTANT

Dunn 1991Dunn 1991

EFFECT ON NEONATAL MORTALITYEFFECT ON NEONATAL MORTALITY

Egberts 1993Egberts 1993

Kattwinkel 1993Kattwinkel 1993

Walti 1995Walti 1995


Soll 2001Soll 2001

TYPICAL ESTIMATETYPICAL ESTIMATE

Kendig 1991Kendig 1991


NASAL CONTINUOUS POSITIVE AIRWAY PRESSURENASAL CONTINUOUS POSITIVE AIRWAY PRESSURE

What about the early application ofWhat about the early application of

Nasal Continuous Positive Airway Pressure Nasal Continuous Positive Airway Pressure

(NCPAP)?(NCPAP)?

0%

10%

20%

30%

40%

50%

IMV SURF NEC CLD @ 28 CLD/DEATH

% I

NFA

NTS

1000

-149

9 g

BEFORE AFTER

De Klerk AM and De Klerk RK. J Paediatr Child Health 2001De Klerk AM and De Klerk RK. J Paediatr Child Health 2001

NASAL CPAP and OUTCOME OF PRETERM NASAL CPAP and OUTCOME OF PRETERM INFANTSINFANTS

Comparison of clinical outcome before (n=57) and after Comparison of clinical outcome before (n=57) and after (n=59) introduction of nasal continuous positive airway (n=59) introduction of nasal continuous positive airway

pressurepressure


OUTCOME OUTCOME Risk DifferenceRisk Difference( 95% CI )( 95% CI ) 0.50.5 1.01.0 2.02.0 4.04.00.20.2


0.50.5 1.01.0 2.02.0 4.04.00.20.2

PROPHYLACTIC APPLICATION OF NASAL CPAPPROPHYLACTIC APPLICATION OF NASAL CPAP

RANDOMIZED CONTROLLED TRIAL OF 82 VLBW INFANTSRANDOMIZED CONTROLLED TRIAL OF 82 VLBW INFANTS(HAN AND COWORKERS 1987)(HAN AND COWORKERS 1987)

PNEUMOTHORAXPNEUMOTHORAX -0.01 (-0.14, 0.12)-0.01 (-0.14, 0.12)

SEPSISSEPSIS -0.04 (-0.21, 0.13)-0.04 (-0.21, 0.13)

IVHIVH

BRONCHOPULMONARY DYSPLASIABRONCHOPULMONARY DYSPLASIA 0.13 (-0.03, 0.29)0.13 (-0.03, 0.29)

MORTALITY MORTALITY 0.07 (-0.03, 0.17)0.07 (-0.03, 0.17)

USE OF IPPVUSE OF IPPV

NECROTIZING ENTEROCOLITISNECROTIZING ENTEROCOLITIS

0.09 (-0.12, 0.29)0.09 (-0.12, 0.29)

-0.14 (-0.30, 0.02)-0.14 (-0.30, 0.02)

0.15 (-0.02, 0.32)0.15 (-0.02, 0.32)

HAN 1987


What is the rationale for considering What is the rationale for considering early or prophylactic intubation and early or prophylactic intubation and

surfactant administration followed by surfactant administration followed by rapid extubation and stabilization on rapid extubation and stabilization on

nasal CPAP?nasal CPAP?

0%

10%

20%

30%

40%

50%

60%

70%

MECHANICAL VENTILATION/MORTALITY

% C

AS

ES

EARLY TREATMENT LATE TREATMENT

VERDER H AND COWORKERS PEDIATRICS 1999VERDER H AND COWORKERS PEDIATRICS 1999

NASAL CPAP AND EARLY SURFACTANTNASAL CPAP AND EARLY SURFACTANT

MECHANICAL VENTILATION OR DEATHMECHANICAL VENTILATION OR DEATH

0%

10%

20%

30%

40%

MORTALITY

% C

AS

ES

EARLY TREATMENT LATE TREATMENT

VERDER H AND COWORKERS PEDIATRICS 1999VERDER H AND COWORKERS PEDIATRICS 1999

NASAL CPAP AND EARLY SURFACTANTNASAL CPAP AND EARLY SURFACTANT

MORTALITYMORTALITY



SYNDROMESYNDROME

PROTOCOLPROTOCOL


To compare the effect of three distinct To compare the effect of three distinct methods of post-delivery stabilization methods of post-delivery stabilization and subsequent respiratory care on and subsequent respiratory care on chronic lung disease and survival in chronic lung disease and survival in premature infants at high risk of premature infants at high risk of respiratory distressrespiratory distress

OBJECTIVEOBJECTIVE


The three approaches to post-delivery care:The three approaches to post-delivery care:

• PS Group: Intubation, prophylactic surfactant PS Group: Intubation, prophylactic surfactant administrationadministration shortly after delivery, stabilization on ventilator shortly after delivery, stabilization on ventilator supportsupport

• NCPAP Group: Early stabilization on nasal continuous NCPAP Group: Early stabilization on nasal continuous positivepositive airway pressure (NCPAP) with selective intubation airway pressure (NCPAP) with selective intubation andand surfactant administration for clinical indicationssurfactant administration for clinical indications

• ISX Group: ISX Group: Intubation, prophylactic surfactantIntubation, prophylactic surfactant administration, and rapid extubation to Nasal CPAPadministration, and rapid extubation to Nasal CPAP

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS : ENROLLMENT CRITERIAOF PREMATURE INFANTS : ENROLLMENT CRITERIA

Eligibility: Admission to L & D Eligibility: Admission to L & D

• high risk of preterm delivery at gestational age 26+0 to 29+6 high risk of preterm delivery at gestational age 26+0 to 29+6 weeks weeks

Inclusion Criteria: Inclusion Criteria:

• delivery imminentdelivery imminent• no no maternal rupture of membranes > 14 daysmaternal rupture of membranes > 14 days• no potentially life threatening congenital anomaly or genetic no potentially life threatening congenital anomaly or genetic

syndromesyndrome • no known lung maturityno known lung maturity• antenatal steroid status knownantenatal steroid status known• written informed consent obtained (prior to delivery)written informed consent obtained (prior to delivery)

Randomization: Prior to deliveryRandomization: Prior to delivery

Exclusion Criteria (s/p delivery):Exclusion Criteria (s/p delivery):

• stillborn (apgar score of 0 at one minute)stillborn (apgar score of 0 at one minute)• potentially life threatening congenital anomaly/genetic potentially life threatening congenital anomaly/genetic

syndromesyndrome


multicenter randomized clinical multicenter randomized clinical trial conducted at participatingtrial conducted at participating

Vermont Oxford Network CentersVermont Oxford Network Centers

STUDY DESIGNSTUDY DESIGN

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS : TREATMENT OF PREMATURE INFANTS : TREATMENT

GROUPSGROUPSEligible infants will have consent obtained prior to delivery.Eligible infants will have consent obtained prior to delivery.At imminent delivery premature infants will be randomized to either:At imminent delivery premature infants will be randomized to either:

• Intubation, prophylactic surfactant administration, subsequent Intubation, prophylactic surfactant administration, subsequent stabilization on ventilator supportstabilization on ventilator support

• early stabilization on NCPAP and selective intubation and early stabilization on NCPAP and selective intubation and surfactant administration for clinical indicationssurfactant administration for clinical indications

• intubation prophylactic surfactant administration and rapid intubation prophylactic surfactant administration and rapid extubation to NCPAP. extubation to NCPAP.

After delivery infants who meet all criteria will be enrolled in the After delivery infants who meet all criteria will be enrolled in the trial.trial.

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS: TREATMENT OF PREMATURE INFANTS: TREATMENT

GROUPSGROUPS

• Intubation in the delivery room Intubation in the delivery room between five and fifteen minutes of between five and fifteen minutes of lifelife

• Surfactant treatment s/p intubationSurfactant treatment s/p intubation• Mechanical ventilationMechanical ventilation• Extubation at anytime after 6 hours Extubation at anytime after 6 hours

of age based on predefined criteriaof age based on predefined criteria

PROPHYLACTIC SURFACTANT ADMINISTRATION PROPHYLACTIC SURFACTANT ADMINISTRATION (PS GROUP)(PS GROUP)

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS: TREATMENT GROUPSOF PREMATURE INFANTS: TREATMENT GROUPS

• Stabilization on standardized NCPAP system Stabilization on standardized NCPAP system applied within five to fifteen minutes after deliveryapplied within five to fifteen minutes after delivery

• Bubble CPAP system at 5 cm HBubble CPAP system at 5 cm H2200• Predefined criteria for respiratory insufficiency Predefined criteria for respiratory insufficiency

requiring intubation and surfactant treatmentrequiring intubation and surfactant treatment

EARLY APPLICATION OFEARLY APPLICATION OFNASAL CONTINUOUS POSITVE AIRWAY PRESSURE NASAL CONTINUOUS POSITVE AIRWAY PRESSURE

(NCPAP GROUP)(NCPAP GROUP)

DELIVERY ROOM MANAGEMENTDELIVERY ROOM MANAGEMENTOF PREMATURE INFANTS: TREATMENT OF PREMATURE INFANTS: TREATMENT

GROUPSGROUPS

PROPHYLACTIC SURFACTANT ADMINISTRATION,PROPHYLACTIC SURFACTANT ADMINISTRATION,RAPID EXTUBATION TO NASAL CONTINUOUS RAPID EXTUBATION TO NASAL CONTINUOUS

POSITVE AIRWAY PRESSURE POSITVE AIRWAY PRESSURE (ISX GROUP)(ISX GROUP)

• Intubation in the delivery room between five Intubation in the delivery room between five and fifteen minutes of lifeand fifteen minutes of life

• Surfactant treatment s/p intubationSurfactant treatment s/p intubation• Rapid extubation to standardized nasal CPAP Rapid extubation to standardized nasal CPAP

bubble system at 5 cm Hbubble system at 5 cm H2200


• Intubation based on clinical status:Intubation based on clinical status:– apneaapnea– respiratory failure (PCO2 > 65 mmHg)respiratory failure (PCO2 > 65 mmHg)– hypoxemia (supplemental oxygen > 40%-hypoxemia (supplemental oxygen > 40%-

60%60%to maintain oxygen saturation > 86%-94%)to maintain oxygen saturation > 86%-94%)

– severe respiratory distresssevere respiratory distress• Surfactant treatment s/p intubationSurfactant treatment s/p intubation

CRITERIA FOR SELECTIVE INTUBATIONCRITERIA FOR SELECTIVE INTUBATIONAND SURFACTANT TREATMENTAND SURFACTANT TREATMENT


PRIMARY OUTCOME MEASURE:

Chronic Lung Disease or Mortalityat 36 weeks adjusted age

Chronic lung disease is defined as documentedrequirement for supplemental oxygen or

respiratorysupport. Documented oxygen requirement will bedefined as the need for supplemental oxygen tomaintain an oxygen saturation 88%.


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


• Number of infants receiving Number of infants receiving surfactant treatmentsurfactant treatment

• Number of surfactant dosesNumber of surfactant doses• Postnatal steroidsPostnatal steroids• Clinical status during first 28 Clinical status during first 28

days of lifedays of life• Clinical status at 36 & 40 Clinical status at 36 & 40

weeks adjusted ageweeks adjusted age• Days on assisted ventilationDays on assisted ventilation• Days on NCPAP Days on NCPAP • Days on supplemental oxygenDays on supplemental oxygen• Growth, day 28 and dischargeGrowth, day 28 and discharge

• PneumothoraxPneumothorax• Pulmonary hemorrhagePulmonary hemorrhage• Patent ductus arteriosusPatent ductus arteriosus• Necrotizing enterocolitisNecrotizing enterocolitis• Intraventricular hemorrhageIntraventricular hemorrhage• Steroids for chronic lung Steroids for chronic lung

diseasedisease• Mortality Mortality • Duration of hospitalizationDuration of hospitalization• Other complications of Other complications of

prematurityprematurity• Health and developmental Health and developmental

status at 2 years adjusted agestatus at 2 years adjusted age

SECONDARY OUTCOME MEASURES:SECONDARY OUTCOME MEASURES:

DELIVERY ROOM MANAGEMENT OF DELIVERY ROOM MANAGEMENT OF PREMATURE INFANTSPREMATURE INFANTS

STUDY TIMELINESTUDY TIMELINE

Study to be conducted in three stagesStudy to be conducted in three stages

• Stage 1: Introduction of Nasal CPAP in routine NICU Stage 1: Introduction of Nasal CPAP in routine NICU practice practice

• Stage 2: Pilot study of feasibility of delivery room Stage 2: Pilot study of feasibility of delivery room interventionsinterventions

• Stage 3: Formal enrollment of subjects in large Stage 3: Formal enrollment of subjects in large pragmatic trialpragmatic trial


Stage 1: Introduction of Nasal CPAP in routine NICU Stage 1: Introduction of Nasal CPAP in routine NICU practicepractice

• Build bubble CPAP devicesBuild bubble CPAP devices• Educate centers regarding use of bubble NCPAPEducate centers regarding use of bubble NCPAP• Incorporate bubble NCPAP into daily routine of NICUIncorporate bubble NCPAP into daily routine of NICU• Evaluate competence of centers in use of bubble Evaluate competence of centers in use of bubble

CPAPCPAP• February through April 2003 February through April 2003


Stage 2: Pilot study of feasibility of delivery room Stage 2: Pilot study of feasibility of delivery room interventionsinterventions

• Educate centers regarding conduct of delivery room Educate centers regarding conduct of delivery room management trialmanagement trial

• Pilot study of randomization to all three arms of studyPilot study of randomization to all three arms of study• May through October 2003May through October 2003• Determine feasibility of launching large pragmatic trialDetermine feasibility of launching large pragmatic trial


Stage 3: Formal enrollment of subjects in large Stage 3: Formal enrollment of subjects in large pragmatic trialpragmatic trial

• In accordance with insights gained from feasibility In accordance with insights gained from feasibility studystudy

• January 2004January 2004


• Interested centers must identify a study team Interested centers must identify a study team comprised of a neonatologist, nurse comprised of a neonatologist, nurse practitioner or nurse, and a respiratory practitioner or nurse, and a respiratory therapisttherapist

• Team must commit to participating in a Team must commit to participating in a standardized education and training programstandardized education and training program

• Team must implement education and training Team must implement education and training program within their NICU and unit must program within their NICU and unit must establish a level of competency with the establish a level of competency with the bubble CPAP system prior to initiating bubble CPAP system prior to initiating enrollment in pilot studyenrollment in pilot study

NETWORK CENTER PARTICIPATIONNETWORK CENTER PARTICIPATION

delivery room management of premature infants at high risk of at high risk of respiratory distress...

Documents

rationale slide

prophylactic intubation

death slide

relative risk

vlbw infants han

selective surfactant

endotracheal intubation

ci outcome risk difference