Effect of remote ischemic preconditioning on cerebral vasospasm and biomarkers of cerebral ischemia in aneurysmal subarachnoid hemorrhage (ERVAS): A protocol for a randomized, controlled pilot trial

Abstract

Introduction: Cerebral vasospasm is a dreaded complication of aneurysmal subarachnoid hemorrhage (aSAH) predisposing to delayed cerebral ischemia. We intend to study the cerebroprotective effects of remote ischemic preconditioning (RIPC) in patients with aSAH.

Materials and methods: This is a single-center, prospective, parallel group, randomized, pilot trial, approved by the Institutional Ethics Committee. Patients with aSAH admitted to our hospital for surgical clipping; fulfilling the trial inclusion criteria will be randomized to true RIPC (n = 12) (inflating upper extremity blood pressure cuff thrice for 5 min to 30 mmHg above systolic blood pressure) or sham RIPC (n = 12) (inflating blood pressure cuff thrice for 5 min to 30 mmHg) in 1:1 allocation ratio using a computerized random allocation sequence and block randomization.

Results: Our primary outcome measure is vasospasm on cerebral angiography and transcranial Doppler study, and concentration of serum S100B and neuron-specific enolase at 24 h after RIPC and on day 7 of ictus. Our secondary outcomes are safety of RIPC, cerebral oxygen saturation, and Glasgow coma score, and extended Glasgow outcome scale scores at discharge and at 1, 3, and 6 months following discharge. Outcome measures will be assessed by an observer blinded to the study intervention.

Conclusion: If our preliminary results demonstrate a beneficial effect of RIPC, this would serve as a clinically applicable and safe preemptive method of protection against cerebral ischemia.

Keywords: Biomarkers of cerebral ischemia; cerebral oxygen saturation; cerebral vasospasm; delayed cerebral ischemia; ischemic preconditioning; transcranial Doppler.

Figure 1

Flowchart of the ERVAS trial methodology. DSA: Digital subtraction angiography, S100B: calcium-binding protein S100beta, NSE: neuron-specific enolase, RIPC: remote ischemic preconditioning, TCD: transcranial Doppler, NIRS: near-infrared spectroscopy, CBFV: Cerebral blood flow velocity, rScO2: Regional cerebral oxygen saturation, GCS: Glasgow coma scale, GOSE: Glasgow outcome scale extended