On-scene selective brain cooling in ventricular fibrillation cardiac arrest: pilot results from the PRINCESS2 randomised trial

BACKGROUND: Although ischemia-reperfusion brain injury represents a major clinical problem after cardiac arrest, no neuroprotective treatment currently exists. The PRINCESS2 trial is designed to confirm previous findings, indicating that on-scene selective brain cooling using a portable trans-nasal cooling method improves complete neurological recovery after out-of-hospital cardiac arrest (OHCA) with initial shockable rhythms (e.g. ventricular fibrillation). This prespecified pilot phase aimed to assess protocol adherence and safety aspects for this early cooling strategy. METHODS: The prespecified pilot phase includes the first 100 patients in the main PRINCESS2 trial, an ongoing European multicentre trial enrolling 1,022 OHCA patients with initial shockable rhythm. Patients are randomised to intervention; trans-nasal cooling initiated at the scene of arrest followed by systemic hypothermia (33 ± 0.5 °C for 24 h) in the intensive care unit, or control; normothermia with fever control. Neuroprognostication and criteria for withdrawal of life-sustaining treatment are protocolised. Pilot outcomes were adherence to treatment allocation and protocol in the prehospital and in-hospital stages, and safety aspects, including 72-hour survival, prehospital re-arrest, device-related adverse events, and adverse events within 7 days such as bleeding, sepsis, arrhythmias with hemodynamic compromise, or need for circulatory support. RESULTS: In total, 100 patients were randomised (median age 64 years, 91% male) to intervention (n = 50) or control (n = 50). All intervention patients received allocated treatment. Four had minor trans-nasal cooling interruptions, and two had systemic cooling interruptions. Among controls, 48/50 received allocated treatment, while two crossed over to cooling. One control was lost to follow-up. Overall, adherence to allocation and treatment protocol was 92%. Survival to 72 h was similar (intervention: 32/50 [64%], control: 31/49 [63%]) as well as prehospital re-arrest rates (11/49 [22%] vs. 9/40 [23%]). No device-related serious adverse events occurred. Adverse event rates within 7 days were similar. CONCLUSION: In this pilot phase of the PRINCESS2 trial, on-scene trans-nasal cooling in OHCA patients with shockable rhythms was performed with high protocol adherence without safety concerns. The main trial will continue as planned. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06025123, registered Feb 1, 2023.