JOURNAL CLUB · LANDMARK TRIAL
Sustained inflations vs standard ventilation at birth in extremely preterm infants (SAIL)
Kirpalani H, Ratcliffe SJ, Keszler M, et al; for the SAIL Site Investigators. JAMA. 2019;321(12):1165-1175. An international, unmasked randomised trial, stopped early.
SUSTAINED
INFLATIONS
No benefit on the primary outcome
Death or BPD: 63.7% (sustained inflation) vs 59.2% (standard). Adjusted risk difference 4.7% (95% CI -3.8 to 13.1).
More early deaths
Death under 48 hours: 7.4% vs 1.4% (risk difference 5.6%, 95% CI 2.1-9.1). Blinded review judged 11 of 16 early deaths possibly resuscitation-related in the sustained inflation group, vs 1 of 3.
More bradycardia
HR under 60 after the first manoeuvre: 23.4% vs 11.4%. 26 of 27 other secondary outcomes showed no difference.
The verdict
No benefit and a possible harm signal. Early stopping limits certainty, but a post hoc Bayesian analysis suggested benefit was unlikely even with full recruitment.
WHY THIS MATTERS
- The preterm lung is fluid-filled at birth; a long inflation should, in theory, aerate it faster
- Animal studies were strongly supportive
- Earlier small trials hinted at less need for ventilation
- Sustained inflation had become routine in parts of Europe
- A classic example of plausible physiology not translating to benefit
STRENGTHS
- The largest trial of sustained inflation, in the most immature babies
- International and pragmatic, across 9 countries
- Prespecified safety monitoring that detected harm
- Blinded adjudication of early deaths
- Clear, practice-changing answer
LIMITATIONS
- Stopped early (460 of 600): possibly underpowered, and truncated trials can exaggerate effects
- Unmasked - performance and detection bias possible
- No detailed delivery-room recordings of what was actually delivered
- Only one sustained inflation regimen (pressure and duration) was tested
- Mixed antenatal and deferred consent across sites
Practice implications
SAIL is the main reason sustained inflations are not part of routine newborn resuscitation. ILCOR and ANZCOR advise against routine sustained inflations in preterm babies, and European consensus guidance restricts them to research. For babies of any gestation who need help at birth: CPAP or PEEP, then effective intermittent breaths with visible chest rise, and reassess the heart rate. Background reading - SAIL studied 23-26 week babies, beyond day-to-day SCN care, but its message applies to every preterm birth.
Why might an intervention that works in animal models fail, or harm, in extremely preterm babies?
How should we interpret a trial stopped early for harm?
What does “effective ventilation” look like at a preterm birth?
Is deferred consent acceptable for delivery-room trials?
JAMA 2019 ANZCOR
Newborn resuscitation PRETERM BIRTH
The Hub page LANDMARK TRIALS
More trials to know
Take-home message: In babies born at 23-26 weeks, sustained inflations at birth did not reduce death or BPD, and were linked to more deaths in the first 48 hours. The trial stopped early, but it moved practice away from sustained inflation. Use PEEP and effective intermittent breaths instead.
For educational purposes only. Journal club appraisal - figures paraphrased from the published trial and later reviews; read the full article for complete data. Always align practice to current ANZCOR/NRP guidelines.