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 25-28 weeks GA spontaneously breathing 1316 preterm infants 24-27 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: 0.7-1.07), 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: 0.73 -0.95), 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: 0.85-1.05), 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