Chest Compression superimposed with Sustained Inflation – Translating preclinical findings into a neonatal clinical trial
- Apr 17
- 3 min read
From bench to bedside: translating physiology into clinical trials
Cardiopulmonary resuscitation (CPR) at birth remains one of the most critical—and challenging—situations in neonatal care. While only a small proportion of newborns require CPR, the outcomes are sobering: mortality remains high, and survivors often face significant neurological injury.
This blog highlights an important journey in neonatal resuscitation research—the development and translation of chest compressions with sustained inflation (CC+SI) from preclinical discovery to global clinical trials.
Why rethink neonatal CPR?
Current guidelines recommend a 3:1 compression-to-ventilation (C:V) ratio, delivering 90 compressions and 30 inflations per minute. While this approach has been standard for decades, it has important limitations.
Neonatal cardiac arrest is primarily driven by respiratory failure, not primary cardiac disease. This means that:
Effective ventilation is essential
Oxygenation and gas exchange are central
Circulatory support alone is not sufficient
Yet, the 3:1 technique interrupts ventilation and may lead to lung de-recruitment, limiting effective gas exchange during CPR.
The CC+SI concept
Over the past decade, our group has explored an alternative approach:continuous chest compressions superimposed with sustained inflation (CC+SI).
Instead of alternating compressions and breaths, CC+SI:
Delivers continuous chest compressions (90–120/min)
Maintains a constant distending airway pressure (sustained inflation)
Allows passive ventilation during chest recoil
This approach leverages the thoracic pump mechanism, increasing intrathoracic pressure and improving:
Pulmonary blood flow
Carotid blood flow
Venous return and preload
Overall oxygen delivery
At the same time, it promotes lung recruitment and stability, avoiding the tidal volume loss seen with the 3:1 technique.
What have we learned from preclinical studies?
Extensive work in neonatal animal models has shown that CC+SI:
Improves tidal volume delivery
Enhances gas exchange
Maintains more stable hemodynamics
Supports continuous ventilation during CPR
Importantly, concerns about injury—such as pneumothorax or increased brain inflammation—have not been confirmedin these models.
These findings provided the physiological foundation to move toward clinical testing.
Early clinical experience
We have successfully translated this work into two pilot trials in newborn infants:
A single-center feasibility trial demonstrated a significantly shorter time to return of spontaneous circulation (ROSC) with CC+SI
The SURV1VE pilot trial, a cluster crossover study, showed promising trends toward faster ROSC and lower mortality, although limited by small sample size and logistical challenges
A recent meta-analysis of these trials suggests:
Reduced time to ROSC with CC+SI
No increase in adverse outcomes
No clear difference in mortality (likely due to insufficient power)
The next step: SURV1VE-2
While early data are encouraging, definitive answers require a large, well-powered trial.
The SURV1VE-2 Trial, funded in 2025, represents the next critical step. This international, multicenter trial aims to recruit over 550 infants across sites in:
Canada, USA, and Europe
Australia and New Zealand
Asia, Africa, and South America
This will be the largest neonatal CPR trial ever conducted, designed to evaluate:
Survival
Neurodevelopmental outcomes
Safety and effectiveness of CC+SI
Why this matters
CC+SI represents more than a new technique—it reflects a shift in how we think about neonatal CPR:
From interrupted ventilation → continuous ventilation
From fixed protocols → physiology-driven care
From local studies → global collaboration
Most importantly, it focuses on what matters most in neonatal resuscitation:oxygen delivery, lung recruitment, and effective circulation from the very first minutes of life.
Looking ahead
The journey from preclinical discovery to global clinical trial is long—and often challenging. But it is essential if we want to improve outcomes for the most vulnerable patients.
CC+SI is a powerful example of how translational research can reshape clinical practice.
The next few years will be critical as we complete the SURV1VE-2 trial and determine whether this approach can truly change the way we resuscitate newborns worldwide.
Stay tuned.
Comments