Selective brain cooling via cerebrospinal fluid exchange: Proof of concept in a porcine model

Therapeutic hypothermia is neuroprotective after brain injury, reducing metabolic demand, inflammation, and secondary injury cascades. However, clinical application is limited by systemic side effects, and selective brain cooling without systemic hypothermia has not been demonstrated in large mammals. We aimed to demonstrate the feasibility of selective brain cooling using cerebrospinal fluid (CSF) exchange with cooled saline via a double-lumen external ventricular drain (EVD) system in a porcine model. Using 12 pigs under general anesthesia, we placed a double-lumen EVD in the lateral ventricle and a lumbar spinal drain to enhance CSF outflow. Cooled NaCl (13 °C) was infused at 120, 360, or 720 mL/h while maintaining intracranial pressure. After reperfusion, mean arterial pressure was increased to 140 mmHg. Brain temperatures were recorded bilaterally; core temperature was monitored. Ipsilateral brain temperature decreased by 7.5 °C, contralateral cooled by 3.1 °C. Core temperature remained stable. Target temperature was reached in 1.5 h at 120 mL/h, and within 10-15 min at 360-720 mL/h. Arrhythmias occurred with NaCl but not with Ringer's acetate. We demonstrate that selective brain cooling is feasible in a large mammal model via CSF exchange without systemic hypothermia. This method may offer a safe, controllable approach for neuroprotection.