Prophylactic Remote Ischemic Preconditioning for Cerebral Vasospasm Following Subarachnoid Hemorrhage

Phase I prospective clinical study to evaluate: the tolerance of clinical subjects with Subarachnoid Hemorrhage (SAH) to the maneuvers involved in the generation of Remote Ischemic Preconditioning (RIPC), the immediate and delayed hemodynamic effects of the RIPC in the cerebral vasculature, in terms of Transcranial Doppler (TCD) velocities, pulsatility index variations, Cerebral Blood Flow (CBF) measures, and cerebral arterial flow measurements using Magnetic Resonance Imaging with flow measurement capabilities (MRI NOVA). As a secondary goal, we will be valuating the impact of RIPC in the incidence of vasospasm, delayed neurological deficits, development of ischemic lesions in MRI and clinical outcome.

Patient Enrollment: Patients who are admitted to the University of California Los Angeles (UCLA) Ronald Reagan Medical Center with a diagnosis of aneurysmal subarachnoid hemorrhage will be considered for inclusion in this study. As is standard of care for this condition, following admission patients' aneurysms are generally treated by one of two methods, surgical clipping or endovascular coiling. Following this definitive treatment of the aneurysm, generally performed emergently in the first 24 to 48 hours following hemorrhage, patients will be consented and enrolled in the study. No patients with unprotected (untreated) aneurysms will be enrolled. Patients with a known history of lower limb vascular disease or lower limb vascular bypass surgery will be excluded.

Remote Ischemic Preconditioning (RIPC) Procedure: Following enrollment, patients will receive four rounds of lower limb remote ischemic preconditioning, starting at the earliest post-hemorrhage day possible following definitive treatment of their aneurysm. The remote ischemic preconditioning will typically take place on post-hemorrhage day 2, 3, 6 and 9. Each cycle of RIPC will consist of four 5-minute cycles of lower limb ischemia following by 5-minute periods of reperfusion. A large blood pressure cuff will be wrapped around the upper thigh of one leg. The cuff will be inflated to a pressure 20 mm Hg greater than the systolic arterial blood pressure measured by the patient's arterial line or upper limb blood pressure cuff. The adequate level of inflation will be confirmed by the absence of pulse in the ipsilateral pedal artery as detected by Doppler. The cuff will remain inflated for 5 minutes. The cuff will then be deflated and the limb will be allowed to re-perfuse for at least 5 minutes. After the cuff is deflated, the same procedure will then be repeated three times for a total of four cycles.

Evaluation of Tolerance to the RIPC Maneuvers: The patient will be continuously monitored for pain and discomfort during the RIPC session. If the patient pain is more than 6 in the traditional 1-10 scale or if the patient expresses their desire to stop the maneuver, the procedure will be stopped, and the data regarding number and duration of the maneuvers will be recorded. A down-escalation of the treatment will be proposed, by reducing the number of cuff inflations to 3 or 2, as tolerated.

Hemodynamic evaluation of the effect of RIPC Maneuvers: Transcranial Doppler (TCD) measurements will be performed during the RIPC session. TCD and Cerebral Blood Flow (CBF) measurements will be performed at 24 hours and 72 hours after treatment.