Effects of systemic mild hypercapnia on brain function in a refractory cardiac arrest model treated with extracorporeal cardiopulmonary resuscitation

INTRODUCTION: Cardiac arrest (CA) is a major cause of mortality and neurologic disability. Extracorporeal cardiopulmonary resuscitation (ECPR) may be used in refractory CA to potentially reduce hypoxic-ischemic brain injuries. Currently, no recommendation exists regarding optimal carbon dioxide levels in ECPR patients. METHODS: Twelve pigs were submitted to 5 min of untreated ventricular fibrillation followed by 25 min of CPR; 30 min after CA induction, ECPR was initiated and defibrillations delivered until ROSC. Pigs were randomly assigned to normocapnia (NC; PaCO₂ 35-45 mmHg, n = 6) or hypercapnia (HC; PaCO₂ 50-55 mmHg, n = 6). Animals underwent continuous multimodal neurological and cardiovascular monitoring. The primary outcome of the study was the change of brain tissue oxygen tension (PbtO₂) over time. Other parameters were secondary outcomes. At 12 h post-ROSC, animals were euthanized and brain tissues were harvested for molecular analyses. RESULTS: Mean PbtO₂ tended to be higher in the HC group (49.9 vs 36.4 mmHg in the NC group; p = 0.13), while mean intracranial pressure was similar between the two groups (19.9 vs 22.6 mmHg, respectively - p = 0.42). Cerebral glucose concentrations were significantly higher in the HC group (p = 0.01), without differences in lactate/pyruvate ratio, glycerol or glutamate. Caspase-8 gene expression in the parietal lobe was significantly lower in the HC group, with no differences in EEG cortical activity or serum biomarkers of brain injury. CONCLUSIONS: In this model of ECPR, HC was associated with increased cerebral glucose concentrations and reduced caspase-8 expression, without changes in PbtO₂ levels, intracranial pressure, cortical activity, or neurobiomarkers.