Improving survival of newborn infants required cardiopulmonary resuscitation.

Professor Graeme Polglase, Monash University

Vanguard Grant

Years funded: 2026 - 2027

Approximately 2-3 million newborn infants require cardiopulmonary resuscitation (CPR - defined as chest compressions + Epinephrine) at birth each year. The mortality rates for infants who receive CPR in the delivery room remains alarmingly high, with approximately 1 million newborns dying annually. Survivors face significant short-term neurological morbidities including hypoxic-ischemic encephalopathy (brain damage) and seizures, and 3/4 suffer from long-term moderate to severe disabilities.

A major cause of the devastating brain injury is severe cerebral haemorrhage. Our previous studies have shown that this is caused by a post-asphyxial overshoot in blood pressure and flow to the brain, resulting in break-down of the blood-brain barrier and cerebrovascular haemorrhage. We have demonstrate that the recommended vasopressor used during neonatal CPR, Epinephrine, is responsible for a more rapid and increased severity of the cerebral overshoot, increasing the risk and severity of cerebral haemorrhage. Therefore, there is a critical need to identify other vasopressors which are effective at restoring spontaneous circulation but reduces the post-asphyxial overshoot in cerebral pressure and flow, thus reducing devastating cerebral haemorrhages.

We have identified that Vasopressin restores circulation and reduces the post-asphyxial overshoot in a paediatric model (piglets) compared to Epinephrine. In this study, we will test the utility of Vasopressin in a neonatal transition model, more reflective of newborn advanced CPR. We will instrument near-term fetal sheep for measurements of pulmonary, cardiovascular and cerebral blood pressures and flows. We will induce asphyxia until they are asystolic (no blood pressure or heart rate), then provide advanced CPR following current neonatal resuscitation guidelines. We will compare intravenous epinephrine with vasopressin for time to ROSC and cerebrovascular injury, using molecular and histological assessments that we developed. Further, we will assess the utility of Vasopressin for intraosseous and endotracheal routes of administration - both are approved alternative routes when intravenous administration is delayed or not possible, which is the case in resource limited settings.

Our studies will provide the fundamental knowledge to support large clinical trials, led by our team, to determine whether vasopressin will improve survival, and reduce disability, in infants requiring CPR at birth. We will translate our findings rapidly into guidelines, given our team are members of the International Liaison Committee on Resuscitation, and disseminate widely through our networks and conference presentations.