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

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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.

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Funding

This study was supported by the Baltimore VAMC—Maryland Exercise and Robotics Center of Excellence (NB). Investing in Clinical Neurocritical Care Research (INCLINE) grant from the Neurocritical Care Society (NB). VA RR&D Senior Research Career Scientist Award (ASR), National Institutes of Health P30AG028747 and P30DK072488. The NMES device (L300 Plus® system) used in this study was given at no cost to the investigators by Bioness, Inc (Valencia, CA).

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Authors and Affiliations

  1. Program in Trauma, University of Maryland School of Medicine, 22 S. Greene Street G7K19, Baltimore, MD, 21201, USA

    Neeraj Badjatia, Melissa Motta, Gunjan Parikh, Wendy Chang & Nicholas Morris

  2. Departments of Neurology, University of Maryland School of Medicine, Baltimore, USA

    Neeraj Badjatia, Stephanie Sanchez, Melissa Motta, Gunjan Parikh, Nicholas Morris & George F. Wittenberg

  3. Department of Clinical Nutrition, University of Maryland Medical Center, Baltimore, USA

    Gabriella Judd

  4. Advanced Practice Provider Program, Neurocritical Care Unit, University of Maryland Medical Center, Baltimore, USA

    Rachel Hausladen & David Hering

  5. Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, USA

    Wendy Chang

  6. Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, USA

    J. Marc Simard

  7. Department of Medicine, University of Maryland School of Medicine, Baltimore, USA

    John Sorkin & Alice S. Ryan

  8. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, USA

    George F. Wittenberg

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  1. Neeraj Badjatia
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  8. Wendy Chang
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  9. Nicholas Morris
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Contributions

All authors provided substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the version to be published.

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Correspondence to Neeraj Badjatia.

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All authors declare that they have no confict of interest.

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The conduct of this study was approved by the University of Maryland, Baltimore Institutional Review Board, and was registered on clinicaltrials.gov (NCT03201094).

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Badjatia, N., Sanchez, S., Judd, G. et al. Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial. Neurocrit Care 35, 46–55 (2021). https://doi.org/10.1007/s12028-020-01138-4

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