Abstract
BACKGROUND: Arterial carbon dioxide tension (PaCO(2)), oxygen tension (PaO(2)), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists. METHODS: The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low- or high-normal PaCO(2), PaO(2), and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 2(3) factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO(2), PaO(2), and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest. DISCUSSION: The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low- or high-normal PaCO(2), PaO(2), and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.