Dallas 2015

590: CPAP and IPPVIn spontaneously breathing preterm

infants with respiratory distress requiring respiratory support in the delivery room, does the use of CPAP compared with intubation and IPPV

improve outcome ?

TFQO: B Stenson #274EVREV 1: Tetsuya Isayama #113EVREV 2: Ben Stenson #274Taskforce: NRP

Dallas 2015COI Disclosure

B Stenson COI#274Commercial/industry• Nil relevant to this review

Potential intellectual conflicts• nil

Tetsuya Isayama COI#113Commercial/industry• nil

Potential intellectual conflicts• nil

Dallas 2015

2010 CoSTR

“Spontaneously breathing preterm infants who have respiratory distress may be supported with CPAP or intubation and mechanical ventilation. The most appropriate choice may be guided by local expertise and preferences.”

Dallas 2015C2015 PICO

Population:Spontaneously breathing preterm infants with respiratory distress in the delivery roomIntervention:CPAPComparison:Intubation and IPPVOutcomes:

Death or BPD -8, Death -9, BPD-7 Air leak -5, severe IVH-7, NEC -7, severe ROP - 7

Dallas 2015Inclusion/Exclusion& Articles Found

Inclusions/ExclusionsInclusion - Randomized controlled trials with the intervention allocated in the first 15 minutes after birthExclusion – Randomized trials with later treatment allocationLower levels of evidence

Number of Articles initially identified, and number finally Included in Evidence Profile tables

Found in Medline 469, Embase 679, Cochrane 2886 RCTs identified, RCTs - 3 included

• Other 3 RCTs were excluded because they were published only as abstracts.

non-RCTs n/a

Dallas 20152015 Proposed Treatment Recommendations

For spontaneously breathing preterm infants with respiratory distress requiring respiratory support in the delivery room we suggest initial use of CPAP rather than intubation and IPPV (weak recommendation, moderate quality of evidence).

Dallas 2015

Risk of Bias in studies

• No blinding was done in all 3 trials but all outcomes assessed were objective. • Two trials (Finer 2010 and Dunn 2011) included all infants at birth.• Finer 2010 used different extubation criteria between the 2 groups.

Dallas 2015 Key data from key studies

Death or BPD

Death

BPD

Dallas 2015 Key data from key studies

Severe IVH

NEC

Air leak

Dallas 2015

Evidence profile tableQuality assessment Event rates Effect

QualityImporta

nce

Study#&

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other NCPAPIntubate & IPPV

Relative(95% CI)

Absolute(95% CI)

Death or bronchopulmonary dysplasia (BPD)

3 RCTnot

serious1

not serious

not serious

serious2

none 493/1193 (41.3%)

531/1165 (45.6%)

RR 0.91(0.83 to 1)

41 fewer per 1000

(0 fewer−77 fewer)

⨁⨁⨁◯MODER

ATE

CRITICAL(8)

Bronchopulmonary dysplasia (BPD)

3 RCTnot

serious1

not serious

not serious

serious2

none 370/1070 (34.6%)

384/1018 (37.7%)

RR 0.92(0.82 to

1.03)

30 fewer per 1000

(11 more−68 fewer)

⨁⨁⨁◯MODER

ATE

CRITICAL(7)

Death

3 RCTnot

serious1

not serious

not serious

serious2

none 123/1193 (10.3%)

147/1165 (12.6%)

RR 0.82(0.66 to

1.03)

23 fewer per 1000

(4 more−43 fewer)

⨁⨁⨁◯MODER

ATE

CRITICAL(9)

Three RCTs (Morley 2008, Finer 2010, and Dunn 2011) were included.

1.Interventions were not blinded but outcomes were objective.2.The 95%CI included the null or minimal (negligible) harm (RR 1.0-1.03)

Dallas 2015Evidence profile tableQuality assessment Event rates Effect

QualityImportan

ceStudy#

& Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other NCPAPIntubate & IPPV

Relative(95% CI)

Absolute(95% CI)

Severe intraventricular hemorrhage (Severe IVH)

3 RCT not serious1

serious2

not serious

very serious

4none 125/1167

(10.7%)112/1134

(9.9%)RR 1.09(0.86 to

1.39)

9 more per 1000(14 fewer−39

more)

⨁◯◯◯VERY LOW

CRITICAL(7)

Air leak

3 RCT not serious1

serious3

not serious

serious5 none 85/1192

(7.1%)67/1165 (5.8%)

RR 1.24(0.91 to

1.69)

14 more per 1000(5 fewer−40

more)⨁◯◯◯

LOW

IMPORTANT

(5)Severe retinopathy of prematurity (Severe ROP)

2 RCT not serious1

not serious

not serious

very serious

4none 80/703

(11.4%)72/656 (11.0%)

RR 1.03(0.77 to

1.39)

3 more per 1000(25 fewer−43

more)⨁◯◯◯

LOWCRITICAL

(7)

Necrotizing enterocolitis (NEC)

3 RCT not serious1

not serious

not serious

serious5 none 113/1183

(9.6%)92/1148 (8.0%)

RR 1.19(0.92 to

1.55)

15 more per 1000(6 fewer−44

more)

⨁◯◯◯MODER

ATE

CRITICAL(7)

Three RCTs (Morley 2008, Finer 2010, and Dunn 2011) were included, except for severe ROP in which two RCTs (Finer 2010 and Dunn 2011) were included.

1.Interventions were not blinded but outcomes were objective.2.I-square = 52%3.I-squared = 75%. Air leak was increased in the CPAP group in one trial (Morley 2008). In this trial the initial CPAP was at 8cmH2O and the criteria for intubation was an oxygen requirement of 60%.4.The 95% CI were wide and included both clinically important benefit (RR<0.9) and harm (e.g. RR>1.1)5.The 95%CI included the null or minimal (negligible) harm (RR 1.0-1.03)

Dallas 2015Proposed Consensus on Science statements

For the critical composite outcome of “death or bronchopulmonary dysplasia” we have identified moderate quality evidence (downgraded for imprecision) from 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) enrolling 2358 preterm infants born at < 30 weeks gestation in the first 15 minutes after birth showing modest potential benefit to starting treatment with CPAP (R.R. 0.91, 95% CI 0.83 – 1.00). For the critical outcome of “death” we have identified moderate quality evidence (downgraded for imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing modest potential benefit to starting treatment with CPAP (R.R. 0.82, 95% CI 0.66 – 1.03). For the critical outcome of “bronchopulmonary dysplasia” we have identified moderate quality evidence (downgraded for imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing modest potential benefit to starting treatment with CPAP (R.R. 0.92, 95% CI 0.82 – 1.03).  

Dallas 2015Proposed Consensus on Science statements

For the critical outcome of “air leak” we have identified low quality evidence (downgraded for inconsistency and imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing no benefit to starting treatment with CPAP (R.R 1.24, 95% CI 0.91 – 1.69).

 For the critical outcome of “severe intraventricular haemorrhage” we have identified very low quality evidence (downgraded for inconsistency and very serious imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing no benefit to starting treatment with CPAP (R.R 1.09, 95% CI 0.86 – 1.39).

Dallas 2015Proposed Consensus on Science statements

For the important outcome of “necrotizing enterocolitis” we have identified moderate quality evidence (downgraded for imprecision) from the same 3 RCTs (Morley 2008 700, Finer 2010 1970, Dunn 2011 e1069) showing no benefit to starting treatment with CPAP (R.R 1.19 95% CI 0.92 – 1.55).  

For the important outcome of “severe retinopathy of prematurity” we have identified low quality evidence (downgraded for very serious imprecision) from 2 RCTs (Finer 2010 1970, Dunn 2011 e1069) enrolling 1359 infants showing no benefit to starting treatment with CPAP (R.R 1.03 95% CI 0.77-1.39).

Dallas 2015Draft Treatment Recommendations

For spontaneously breathing preterm infants with respiratory distress requiring respiratory support in the delivery room we suggest initial use of CPAP rather than intubation and IPPV (weak recommendation, moderate quality of evidence).

Values and preference statement: In making this suggestion we recognize that the absolute reduction in risk of adverse outcome associated with starting with CPAP is small and that infants recruited to the trials had a high rate of treatment with antenatal steroids but we favor the less invasive approach. The balance of risks and benefits of this approach in infants who have not received antenatal steroids is unknown.

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Knowledge Gaps

A further trial of CPAP versus intubation and IPPV in high risk preterm infants at lower gestations is required to determine the risks and benefits more clearly. It is not clear whether there is a significant effect on mortality. The confidence intervals for the other morbidities of prematurity leave open the possibility that any benefit in relation to bronchopulmonary dysplasia might still be balanced by a small increase in risk of severe intraventricular haemorrhage or necrotizing enterocolitis.

 The utility of using an INSURE approach to facilitate early stabilization on CPAP soon after birth has been compared with CPAP alone in at least 2 trials and this should be the subject of a future worksheet.

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Next Steps

This slide will be completed during Task Force Discussion (not EvRev) and should include:

Consideration of interim statementPerson responsibleDue date

Essential slide (one slide only). Estimated time <30 sec