Abstract T P350: Phase I Clinical Feasibility &Safety Trial of Remote Ischemic Conditioning After Aneurysmal Subarachnoid Hemorrhage

Abstract

Objective: Remote ischemic conditioning (RIC) is a phenomenon by which brief periods of sublethal ischemia in one tissue confers protection from ischemia to distant tissues. The safety and feasibility of RIC must be assessed before testing it in efficacy trials. We report a phase I feasibility and safety trial of RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients. Methods: Patients with aSAH received 2-4 RIC sessions on non-consecutive days. A complete session was defined as four rounds of 5 minutes of one sided lower limb ischemia with a thigh blood pressure cuff followed by 5 minutes of reperfusion (verified by pedal Doppler). Primary end-points were tolerance to the procedure and any complication attributable to RIC. Secondary end-points included cerebral infarction or hemorrhage. Results: Twenty-one patients (67% female, mean age 52, Fisher 3.5, H&H 3.3) were enrolled. Seventeen had evidence of vasospasm during hospitalization. Of 76 RIC sessions performed, 75 (98.7%) were completed and tolerated. One session was incomplete due to poor cooperation secondary to delirium. No patients developed DVTs or other local complications within 2 weeks of their final RIC session. No patients suffered cerebral infarction or hemorrhage throughout the duration of RIC sessions and through 72 hours after their last complete session. Three had infarction confirmed on MRI at 3 and 5 days following the final RIC session. In conscious patients, there was a small increase in the analog pain scale upon inflation of the cuff (deflated: 0.5 inflated: 1.2, p<0.0005), but none requested to stop the session. There was no significant change in other vitals. Conclusions: In aSAH patients, RIC was successfully applied and well tolerated with no procedure-related complications. No patient suffered ischemic stroke within 72 hours of RIC, consistent with our previous studies showing protective cerebral metabolic changes up to 48 hours after sessions. These results demonstrate that application of RIC is safe and feasible and suggest that RIC may be associated with transient tolerance to ischemia during the treatment period. The efficacy of RIC for neuroprotection should be investigated in larger controlled trials.