Remote Ischemic Limb Preconditioning After Subarachnoid Hemorrhage

Abstract

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

Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke

“…The results of our questionnaire analysis are consistent with other studies. 12,34,35 We could not detect any adverse effect on hematoma volume in patients presenting with PICH, and there were no excess mortality in the group treated with rPerC. Other studies have not reported on bleeding problems caused by or worsened by rPerC.…”

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

“…The BAIPC treatment consisted of 5 cycles of simultaneous bilateral upper arm ischemia for 5 min followed by reperfusion for another 5 min, performed twice daily for 180 consecutive days. The BAIPC procedure was performed using an electric autocontrol device with cuffs that inflated to a pressure of 200 mmHg during the ischemic period (patent number ZL200820123637.X, China) [18,26]. At the end of the BAIPC treatment, all devices were donated to the patients enrolled.…”

“…Control participants (n=28) underwent a sham BAIPC procedure during which bilateral upper arm cuffs were inflated to a pressure of 30 mmHg for 5 min, followed by 5 min of relaxation of the cuffs, for a total of 5 cycles twice daily for 180 consecutive days [18,26]. Aside from the preset cuff pressure during ischemia, the BAIPC and sham BAIPC devices were similar in both appearance and function.…”

“…The following were defined as primary safety end points [26]: 1) Objective signs of tissue or neurovascular injury resulting from BAIPC treatment-inspection by observers blinded to the study protocol included palpation of distal radial pulses, visual inspection for local edema, erythema, and/or skin lesions, and palpation for tenderness; 2) development of symptomatic or asymptomatic upper extremity deep vein thrombosis as detected by a vascular ultrasound; 3) elevation of plasma myoglobin levels beyond normal limits after BAIPC treatment; 4) symptomatic hemorrhagic transformation after cerebral infarction; 5) patients not tolerating BAIPC treatment. Any suspicious BAIPC or sham BAIPC treatment related events were to be reported to the investigators by the observers who were blinded to the study protocol.…”

Ischemic Preconditioning: The Long-Awaited Savior of Neuroprotection. Has It Arrived?

“…Small clinical studies are ongoing to test the role of rIPC in protecting the brain against delayed ischemic injury after subarachnoid hemorrhage [4]. Recently, the value of rIPC as an adjunct therapy to thrombolysis in patients with ischemic stroke was investigated in an open-label, blinded-outcome, proof-of-concept study.…”