1. 25 – 26 March 2013
University of Oxford
Intubation or CPAP ?
Applying Evidence-Based Medicine to extremely preterm infant respiratory management: a critical review
Dimitrios Charalampopoulos, MD
The Practice of Evidence-based Health Care, University of Oxford
Background
Mechanical Ventilation (MV) has been the standard treatment for respiratory support in very preterm infants as it allowed the administration of surfactant via a tracheal tube.
Bronchopulmonary Dysplasia (BPD), a chronic lung disease in which MV is a recognized contributing factor, constitutes a major cause of morbidity & mortality in extremely preterm infants.
Speculation about the damaging effects of MV on the developing lungs of preterm infants has shifted the focus of neonatologists to less invasive means of respiratory support, including nasal Continuous Positive Airway Pressure (n-CPAP)
Results
Key Points
COIN trial retained a robust design but extrapolation of its findings is limited
SUPPORT study had a rigorous design with good external validity; however allocation process was not adequately specified
Both trials found no evidence for a clear benefit from early CPAP Vs intubation, although SUPPORT study found some evidence for benefit in terms of the duration of ventilation
Findings of COIN trial for a slightly increased risk of pneumothorax in the CPAP group were not supported by the larger SUPPORT study
COIN trial (2008)
SUPPORT study (2010)
Participants
610 preterm infants weeks GA spontaneously breathing
1316 preterm infants weeks GA, irrespective of their breathing status
Intervention & Control
CPAP at 8cm H2O Vs intubation and ventilation at 5 minutes after birth
CPAP at 5cm H2O Vs intubation and surfactant within one hour
Outcomes
Primary: death or BPD (need for O2 at 36 weeks GA)
Secondary: outcomes of neonatal morbidity
Primary: death or BPD (need for >30% O2 at 36 weeks GA or need for any O2 at 36 weeks after a withdrawal attempt)
Results
No significant difference between the groups in the primary outcome -RR: 0.87 (95% CI: ), ARR: 5%, NNT: 20 (95% CI: 39 to 8)
*At 28 days of life, the difference in the outcome becomes significant -RR:0.83 (95% CI: ), ARR:10.9%, NNT:10 (95% CI: 6-32)
Incidence of pneumothorax was higher in the CPAP group (p<0.001)
CPAP group required fewer days of ventilation and intubation (p<0.001)
No significant difference between the groups in the primary outcome -RR: 0.95 (95% CI: ), ARR: 3.2% ,
NNT: 32 (95% CI: 46 to 12)
No difference in the incidence of pneumothorax between the groups
CPAP group required fewer days of ventilation (p=0.03)
Design
Allocation concealment
Blinding
Follow-up
Multicenter, international RCT
Sealed, opaque envelops No
less than 1% of neonates were lost
Double-sealed envelops
Complete
Appraisal
Validity
Clinical importance
Applicability
Major criteria satisfied
No evidence for benefit
Problematic
Major criteria satisfied, allocation process not specified
Good applicability to everyday neonatal settings ?
Clinical Question (PICO)
In extremely preterm infants -born between 24 to 28 weeks gestation (Population)- would early treatment with CPAP (Intervention) reduce the risk of death or Bronchopulmonary Dysplasia (Outcome) compared to intubation and early surfactant treatment (Control) ?
Search Strategy
Ovid Medline was searched using suitable keywords & MeSH terms
Of the 57 studies, 45 were excluded due to lack of relevance.
No systematic reviews identified. Four literature reviews obtained but excluded due to low methodological quality
Two RCTs were included in the review
Secondary searches (Embase, Cochrane & Trip database) identified no additional articles
Conclusions - Clinical Bottom Line
There is no evidence to suggest that early CPAP reduces the risk of death or BPD in extremely preterm infants, however there is some evidence for benefit in terms of the duration of ventilation or/and intubation
There is a need for more high-quality RCTs & resources at a higher level in the 6S hierarchy (systematic reviews, meta-analyses)
Commencing CPAP immediately after birth seems to be a feasible and safe practice but strength of evidence is not enough to recommend management
* picture in title was reproduced with the kind permission of Simpson Memorial Maternity, UK