Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial

Abstract

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization.

Methods: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m² were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90.

Results: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = - 0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90.

Conclusions: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.

Keywords: Clinical trial; Muscle atrophy; Neuromuscular electrical; Nutrition; Stimulation; Subarachnoid hemorrhage.

Figure 1.. Study Flow diagram.

Schematic representation of number of patients screened, excluded and randomized during study period.

Figure 2.. Comparison of Caloric Intake, Protein Intake and Nitrogen Balance between Intervention Groups.

Comparison between HPRO+NMES and SOC groups of daily caloric intake(A.) and protein intake(B.) shown as mean +/− 95% CI throughout study period. (C). Comparison between HPRO+NMES and SOC groups of mean +/− standard error of nitrogen balance at three specified post bleed days(PBD), PBD 2–4, PBD 7–9, and PBD 12 −14.

Figure 3.. Comparison of Quadriceps Muscle Atrophy between Intervention Groups.

Comparison of mean +/− standard error percent atrophy of quadriceps muscle between NMES+HPRO and SOC groups.