Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2 (PRINCESS2)

The aim of this clinical trial is to study the impact of ultra-early transnasal evaporative cooling after cardiac arrest and subsequent hypothermia at hospital, on survival with complete neurologic recovery, compared to currently recommended normothermia. The study population will consist of patients 18-79 years old, with out-of-hospital cardiac arrest with initial shockable rhythm. The main research question it aims to answer is whether there is a difference in survival with complete neurologic recovery at 90 days after cardiac arrest between the group of patients that received ultra-early cooling, compared to the group that was treated with normothermia. Participants will be randomized to two groups. One group (the intervention group) will receive ultra-early trans-nasal evaporative cooling initiated by EMS personnel at the scene of the cardiac arrest, and subsequent systemic hypothermia for 24 hours at hospital arrival. The other group (the control group), will receive standard of care (advanced cardiac life support and normal body temperature (normothermia)).

Therapeutic hypothermia, transnasal cooling, neurologic outcome, ultrafast hypothermia, prehospital, ECPR

Patients will be randomized by EMS personnel at the scene of cardiac arrest to either a) intervention: early transnasal evaporative cooling initiated within 20 minutes from EMS arrival, and subsequent systemic hypothermia at 33°C for 24 h and fever control for 72 h in the ICU, or b) control: standard ACLS (advanced cardiac life support) and fever control (normothermia) for 72 h in the ICU.

Patients in the intervention group will be treated with hypothermia, which makes blinding for care provider and next of kin difficult in the intervention phase (first 36 h). Participants will be informed of which group the were assigned to if they regained consciousness. The study personnel assessing neurologic outcome at discharge and at 90 days will be blinded for which study group the participant belongs to. In addition, the physician performing the prognostication at 72 hours from cardiac arrest will be a neurologist, intensivist or other specialist experienced and will be blinded for group allocation, but not for relevant clinical data.

Early transnasal evaporative cooling initiated during ACLS at the scene of the cardiac arrest within 20 minutes from EMS arrival and subsequent hypothermia at 33ºC for 24 hours and fever control for 72 hours at the ICU

Early prehospital transnasal evaporative cooling followed by systemic hypothermia to 33 degrees Celsius for 24 hours and fever control for 72 hours

Proportion of patients surviving with complete neurologic recovery at 90 days defined as modified Rankin scale (mRs) of 0-1.

The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.

Proportion of patients with sustained ROSC (return of spontaneous circulation) and admitted alive to hospital

The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.

The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.

The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.

The Cerebral Performance Category (CPC) scale is a measure for neurologic function. It ranges from 1-5, where 1 equals no or minimal neurologic disabilities, and 5 equals death.

The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symtoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.

EQ-5D is a a measure of health status and quality of life defined in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels; no problems, some or moderate problems or extreme problems.

INCLUSION CRITERIA: Patients ≥18 years that meet all of the following inclusion criteria: Adult out-of-hospital cardiac arrest patients with initial shockable rhythm Unconsciousness defined as Glasgow Coma Scale < 8 Inclusion within 20 minutes from EMS arrival EXCLUSION CRITERIA: Patients are not eligible if they meet one or more of the following criteria: Age ≥ 80 years Obvious non-cardiac causes to cardiac arrest Obvious already hypothermic Obvious barrier to placing intra nasal catheters Have a known Do Not Attempt to Resuscitate (DNAR) order or other limitations in care Have a known terminal disease Known or clinically apparent pregnancy

Department of Anesthesiology, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico