Introduction: Sudden cardiac arrest is a significant cause of mortality, with an estimated annual incidence of 84 cases per 100,000 individuals in Europe. Effective cardiopulmonary resuscitation (CPR), including proper ventilation, is crucial for survival. However, the interplay between ventilation and circulation during CPR is complex and not fully understood. While ventilation is necessary for oxygenation, excessive hyperventilation and high intrathoracic pressures can be detrimental. Positive End-Expiratory Pressure (PEEP) may improve oxygenation and ventilation by maintaining alveolar patency and improving oxygenation. Previous observational studies have suggested that PEEP might enhance the rate of Return of Spontaneous Circulation (ROSC) and improve short-term outcomes. However, no prospective randomised clinical trials have been conducted to confirm these findings. The Lazarus-PEEP trial aims to address this gap by evaluating the efficacy and safety of PEEP during CPR for out-of-hospital cardiac arrest (OHCA) patients.

Methodology: The study will be conducted at Ghent University Hospital and three non-university hospitals in Belgium, enrolling adult patients who experience non-traumatic OHCA and are intubated and ventilated during resuscitation efforts by an advanced life support (MUG) team. Participants will be randomised to receive either PEEP at 5 cm H2O or no PEEP (0 cm H2O) during CPR. Custom-built sensors will measure tracheal airflow and pressure, while additional data on CPR quality and patient outcomes will be collected. The trial's primary outcome measure is the rate of ROSC, with secondary outcomes including survival to hospital admission and discharge, as well as neurological outcomes at discharge.

Outcome: The study will evaluate the effectiveness of PEEP in improving ROSC rates, short-term survival, and neurological outcomes. Safety profiles will also be examined, focusing on adverse effects such as barotrauma and increased intrathoracic pressures. Comprehensive data collection will provide insights into the physiological impact of PEEP during CPR and its feasibility in a pre-hospital setting.

Conclusion: The Lazarus-PEEP trial aims to gather strong evidence on the potential advantages and risks of utilizing PEEP during CPR for OHCA patients. The results will inform evidence-based guidelines and enhance resuscitation practices, potentially leading to improved patient outcomes. The findings will be disseminated through influential journals, major scientific conferences, and public data- sharing platforms to ensure widespread accessibility and impact.