Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase Ib study of safety and feasibility

Making a limb transiently ischemic has been shown to induce ischemic tolerance in a distant organ. This phenomenon is known as remote ischemic limb preconditioning. We conducted a Phase IB study of remote ischemic limb preconditioning to determine the safety and feasibility of increasing durations of limb ischemia in patients with subarachnoid hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage underwent limb preconditioning every 24 to 48 hours for 14 days. Limb preconditioning consisted of 3 5-minute inflations of a blood pressure cuff to 200 mm Hg around a limb followed by 5 minutes of reperfusion. In the lead-in phase, we preconditioned the upper extremities, but this proved impractical and we began preconditioning the leg in a similar manner. Ischemia times were then escalated to 7.5 and 10 minutes. After each session, a visual analog scale was obtained and the extremity examined for neurovascular complications.

A total of 33 patients completed the study. Mean age was 53±12 years and mean Hunt Hess score was 2.4±0.9. In the lead-in phase, an average of 7.7±2.4 preconditioning sessions was completed with mean visual analog scale 3.6±3.4. In the dose escalation phase, an average of 8.6±2.1 preconditioning sessions was done with mean visual analog scale 1.8±2.2 and 2.5±2.9 for the 7.5- and 10-minute cohorts, respectively. No session was prematurely terminated due to subject discomfort. No objective signs of neurovascular injury were observed.

We found limb preconditioning to be safe and well tolerated, even at ischemia times of 10 minutes, in critically ill patients with subarachnoid hemorrhage.