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 two 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 minute 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.

Introduction

Many aneurysmal subarachnoid hemorrhage(SAH) survivors live with long term residual physical disability¹, and considerable evidence points to an acute pro-inflammatory response as a major contributor to the development of secondary complications that impact on long term recovery^{2, 3}. Immune-mediated malnutrition, resulting from TNF alpha signaling, leads to elevated energy expenditure coupled with protein energy catabolism and is associated with muscle wasting, a higher incidence of hospital acquired infections, and impaired long term functional recovery^4–7.

Current nutritional standards for SAH patients do not provide adequate protein delivery necessary to overcome the catabolic state⁵, possibly contributing to profound muscle weakness and long-term impairment of neuromotor recovery⁸. Trials evaluating the potential benefit of enhanced protein intake(PI) have failed to consistently demonstrate benefit⁹. Concurrent exercise may be the key in promoting the benefits of a high protein supplementation approach. Exercise appears to improve muscle function after ischemic and hemorrhagic stroke¹⁰ by, in part, modulating the immune-mediated metabolic response^{11, 12}. Recent evidence supports that exercise supplemented with appropriately timed PI may be required to optimize skeletal muscle amino acid uptake and muscle protein synthesis and prevent muscle wasting⁹. Neuromuscular electrical stimulation(NMES) is a noninvasive means of achieving repeated skeletal muscle contraction that is deployable during routine therapy sessions in patients unable to do voluntary exercise, and appears to preserve muscle mass, strength, and blood flow in immobilized and comatose critically ill patients¹¹. It remains unclear whether NMES or HPRO or both interventions in the first two weeks after injury can preferentially impact on muscle wasting and recovery after SAH.

We hypothesized that a combined approach of NMES+HPRO would be safe and feasible to perform in a critically ill population of SAH patients, and may impact acute quadriceps muscle atrophy as compared to standard of care PI and mobilization.

Methods

Subject Enrollment:

Patients admitted to the Neurocritical Care Unit(NCCU), or their legally authorized representatives, were approached for consent with the following inclusion criteria:1).Diagnosis of aneurysmal SAH;2).Aneurysmal repair within 48 hours of ictus;3).Age>18 years old;4).Expected stay in the NCCU>72 hours;5).Admission Hunt Hess Grade >=2;6)modified Fisher score >1. Exclusion criteria were:1).Diagnosis of SAH from trauma, rupture of an arteriovenous malformation, neoplasm, vasculitis, or other secondary causes;2).Unlikely to survive one-week post hemorrhage either due to impending brain death or likely request for withdrawal of care;3).Unlikely to remain in the ICU for more than 7 days;4).Body mass index <15 or >40 kg/m2;5).Allergy to whey protein;6).Evidence of lower extremity paresis or spasticity within 48 hours of injury;7).Pre-morbid modified Rankin Score >1;8).Known pregnancy, malignancy, inflammatory disorder, neuromuscular disorder or renal failure;9).Ongoing seizure activity as assessed clinically or by electrographic detection on continuous electroencephalogram(cEEG) at time of enrollment;10).Prisoner.

Study Procedures(Supplementary Figure 1).

After informed consent, patients were randomized 1:1 to either a standard of care(SOC) group or neuromuscular electrical stimulation and high protein supplementation(NMES + HPRO) group, stratified by clinical severity and age to balance the proportion of high clinical grade(Hunt Hess grade 4 and 5) and older(Age ≥ 55 years old) patients in each group. Once assigned, all patients underwent study interventions up until post bleed day(PBD) 14, and followed up at 90 days at in person for outcome measurements and quality of life assessments.

Clinical Management and Data Collection:

Medical and surgical treatment conformed to AHA/NCS guidelines and consensus statements^{13, 14}. The data collection materials and practices established by the NINDS Common Data Elements for Unruptured Cerebral Aneurysms and Subarachnoid Hemorrhage was utilized for collection of clinical variables. Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at University of Maryland, Baltimore^{15, 16}.

Safety and Feasibility Endpoints:

Adverse events for NMES were considered if there was any sustained muscle soreness (>1day) or skin irritation from hydrogel electrodes. A serious adverse event was considered for any skin breakdown or sustained muscle soreness lasting for >=2 days. Serial measurements of blood urea nitrogen and creatinine levels was done daily as part of routine care and any rise in Cr meeting acute kidney injury criteria¹⁷ was considered a serious adverse event. We also tracked any aspiration, nausea or emesis events attributable to HPRO. Feasibility of the combined intervention was defined a priori as the ability to complete of at least 80% of planned NMES sessions as well as achieve 80% of targeted PI for HPRO supplementation.

Nutritional Measurements and Protein Supplementation:

Baseline nutritional status was assessed by calculating the body mass index(BMI, kg/m²) and administering the Mini Nutritional Assessment(MNA) questionnaire^{18, 19} to all study patients. Nutritional support was prescribed by an ICU-based dietician and standardized to begin enteral or oral nutrition within 24 hours after aneurysmal repair. Target total daily caloric intake(CI) was calculated by a dietician using the Mifflin StJeor(non intubated)²⁰ and Penn State (intubated)^{21, 22} energy expenditure estimation equations. Total daily caloric intake was assessed daily from oral intake, enteral nutrition, dextrose infusions, and sedatives (propofol) using methods previously described^4,5. Parenteral nutrition was not given to SAH patients. All SAH patients underwent 24-hour urine collection for urine urea nitrogen and calculation of nitrogen balance (grams/day) by standard equations on PBD 2–4, PBD 7–9 and PBD 12–14.

Patients enrolled in HPRO+NMES arm were administered HPRO as an enteral bolus of a whey protein powder dissolved in water(8 to 10 ounces) three times daily with a total dose of at least 3 g leucine/feeding to achieve a goal of 1.75 g/kg/day. SOC group patients were prescribed 1.2–1.4 g/kg/day of protein, which was delivered thru enteral nutritional formulas or specific oral diets. No additional supplementation was permitted in SOC group patients.

Mobilization, NMES intervention and Muscle Volume Measurements:

All patients underwent nursing or therapist guided mobilization beginning on the first day after aneurysm securing procedure from bed to chair, and eventual ambulation with assistance, as tolerated, throughout their hospitalization. Mobilization to sitting, standing, and ambulation was tracked daily by the bedside nurses and entered into the electronic medical record. All study participants had equal access to therapists. Skeletal muscle composition was assessed with a helical CT scan(Siemens Somatom Sensation 64 Scanner) at two time points, baseline(PBD 0–2) and PBD 14 for all patients. Thigh CT scans were started at the patella and ended at the femoral head to quantify skeletal muscle volume and muscle attenuation of both thighs. Scans were analyzed using MIPAV(Medical Image Processing,Analysis and Visualization,v.7.0,NIH). The cross-sectional area(CSA;cm²) of the mid-thigh vastus medialis, and the vastus intermedius, were manually outlined as the regions of interest to quantify muscle area (range, 30–80 Hounsfield units [Hu]) by the same observer using a technique previously reported²³. The CSA for each axial CT slice was determined by the same observer. All CT scans were anonymized for blinded analysis by a single rater(AR).

The NMES device used in this study was the L300 Plus® system(Bioness,Inc,Valencia, CA) and was provided by the manufacturer at no cost for this study. Thigh cuffs were applied bilaterally to stimulate with stimulator pads across the quadriceps muscles. A portable, hand-held device communicated wirelessly with the system to select stimulation parameters and make real time adjustments. The NMES intervention consisted of two 30-minute sessions per day (total 1 hour/day), the first between the hours of 0900 and 1100 and the second between 1300 and 1700. At the start of each treatment, the NMES amplitude was titrated to achieve visible contraction of the muscle without causing pain. All sessions were performed in either a supine position with legs partially flexed or sitting in a bedside chair. The SOC group did not receive any NMES stimulations and neither group received any other form of exercise or physical activity during the intervention period.

Outcome Measurements and Quality of Life Assessments:

Outcome assessment scales were measured and administered on PBD (PBD) 14 and 90. Functional outcome was assessed by the modified Rankin Scale (mRS)²⁴ and cognitive functioning evaluated with the Montreal Cognitive Assessment (MoCA) scale²⁵. Quality of life (QoL) measures across physical (lower extremity mobility and fatigue) and cognitive domains were ascertained using the short – form NeuroQoL measurement tool²⁶ at PBD 90. All quality of life assessment instruments were administered to the patient or caregiver if the patient was unable to provide answers. Physical recovery was measured by the Short Performance Physical Battery(SPPB) at PBDs 14 and 90. The SPPB is a validated tool^27–29 to assess lower extremity mobility across three domains: gait speed (timed 8-foot walk), standing balance, and lower extremity strength and endurance. Each domain scored on a scale of 0 to 4 points, with a summary performance score range of 0 to 12 points.

Statistical Analysis:

Categorical variables were summarized by proportions in a specific category and comparisons were made using a Pearson’s Chi-Square or Fisher’s Exact test. Normally distributed numbers were summarized by means and standard deviations and compared with analysis of variance(for three groups) or Student’s t tests(for two groups). Nonnormally distributed numbers(as detected by examination of a histogram and testing with the Kolmogorov-Smirnov distribution) were summarized by medians(range) and compared with the Mann-Whitney U test. Percent atrophy was calculated as a comparative difference in the change quadriceps muscle cross-sectional area from baseline to PBD 14 between SOC and intervention groups. Spearman’s rank correlation(ρ) was utilized to measure association between atrophy and continuous variables. For all analyses, significance was set at P <0.05. The sample size assessed for this study was based on primarily on the ability to recruit patients within the time constraints of the funding provided for this pilot grant. We believed that the results from this study would provide adequate information regarding safety and feasibility as well as impact on muscle atrophy inform future, more definitive studies. The conduct of this study was approved by the University of Maryland, Baltimore Institutional Review Board, and was registered on clinicaltrials.gov(NCT03201094).

Results

Clinical characteristics:

A flow diagram of study enrollment is shown in Figure 1. There were no significant differences in baseline characteristics between intervention groups(Table 1). No differences noted laboratory values were noted other than higher blood urea nitrogen (BUN,mg/dL) values in NMES+HPRO patients at PBDs 7 and 14(Supplementary Table 1). No difference in the amount of physical therapy sessions or amount of mobilization to sitting, standing, and ambulation was noted between the two intervention groups.

Figure 1. Study Flow diagram.

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

Table 1.

Baseline Characteristics of Study Patients

		Intervention Group
Characteristic	Overall (N=25)	Standard of Care (N=13)	NMES + HPRO (N=12)	P value
Age, years	59 (11)	58 (14)	60 (8)	0.51
Age> 55 years	15 (60)	8 (58)	7 (62)	0.51
Women	15 (60)	8 (62)	7 (58)	0.88
Hunt Hess Grade				0.59
Grade 2	7(28)	5 (38)	2 (17)
Grade 3	6(24)	2 (15)	4 (33)
Grade 4	10(40)	5 (38)	5 (42)
Grade 5	2(8)	1 (8)	1 (8)
Grade >3	12 (48)	6 (46)	6 (50)	0.85
modified Fisher 3	21 (84)	11 (85)	10 (83)	1
APACHE II Score	19 (8)	18 (10)	20 (5)	0.99
Aneurysm Coiling	13(52)	7 (54)	6 (50)	0.82
BMI, kg/m2	27 (5)	27 (6)	27(3)	0.86
Prealbumin, mg/dL	17.4 (7.2)	18.5(8.2)	18(4.5)	0.86
CRP, mg/dL	3.5 (2.9)	3.4(2.9)	3.9(2.1)	0.7
Mini-Nutritional Assessment	26 (6)	27(3)	26(8)	0.59

Continuous data shown as mean (SD). Categorical data shown as n (%)

Safety and Feasibility Related to NMES+HPRO

All patients completed the study interventions, and none were lost to follow up. The median(range) number of days for intervention was 12(range:9–14), with 98% of NMES sessions completed and 86% of HPRO goal achieved. The most common reason for inability of achieving higher HPRO goals was inability to provide oral or enteral nutrition due to periprocedural withholding of enteral nutrition and poor appetite. No episodes of emesis or aspiration related to HPRO were documented. One patient refused the last day of NMES and two patients had missed sessions due to inability to be available during treatment period. No major adverse events from NMES were noted, though two subjects had transient muscle soreness that did not impair their ability to continue NMES treatments. There was no difference between the intervention groups in any in hospital complications(Table 2).

Table 2.

Comparison of In-Hospital Complications between Intervention Groups

		INTERVENTION GROUP
In Hospital Complication	Overall	Standard of Care	NMES + HPRO	P value
Hospital Acquired Infection	9 (36)	6(43)	3(25)	0.41
Urinary Tract Infection	8 (32)	5 (39)	3(25)	0.67
Ventriculitis	1 (4)	1(8)	0(0)	1
Pneumonia	2 (8)	2(15)	0(0)	0.48
Neurological Complications
Delayed Cerebral Ischemia	7 (28)	4 (31)	3 (25)	1
Symptomatic Vasospasm	4 (16)	3(23)	1(8)	0.59
Infarct on CT scan	4 (16)	2(15)	2(17)	1
Seizure	4 (16)	4(31)	0(0)	0.1
Delirium	15 (60)	7(54)	8(67)	0.69
Medical Complications
Deep Venous Thrombosis	3 (12)	2(15)	1(8)	1
Gl Bleed	1 (4)	1(8)	0(0)	1
Blood Transfusion	1 (4)	1(8)	0(0)	1
Hyperglycemia	9 (36)	4(31)	5(42)	0.69
Hypernatremia	1 (4)	1(8)	0(0)	1
Hyponatremia	8 (32)	4(31)	4(33)	1
Temperature ≥38.3 C	14 (56)	9(69)	5(42)	0.17
Temperature ≥38.9 C	7(28)	4(31)	3(25)	1

All categorical data shown as N(%) and continuous data as mean (SD). Hyperglycemia defined as any glucose value > 200 mg/dL. Hyponatremia defined as occurrence of any sodium value < 130 mEq/L. Hypernatremia defined as any occurrence of sodium value >150 m Eq/L. No occurrence of rebleeding, blood stream infection, wound infection, pulmonary embolus, acute kidney injury, hepatic insufficiency, or diabetes insipidus

Nutrition data

All patients were prescribed an average daily 24.1+/−7.1 calories/kg/day and received an average CI of 19.9+/−8.5 calories/kg/day and 1.18+/−0.52 grams/kg/day of protein resulting in an average nitrogen balance of −1.8+/− 5.3 grams/day throughout the entire intervention period. The CI was no different between treatment groups(SOC: 19.8+/−9.9 cal/kg/day vs NMES+HPRO:20.0+/−7.1 calories/kg/day,P=0.97) but NMES+HPRO patients received significantly more protein than SOC patients(1.51+/−0.47 g/kg/day vs 0.88+/−0.36 g/kg/day,P=0.001) during the intervention period. Nitrogen balance was higher in the NMES+HPRO group on PBD 2–4 (0.7[−4.2,7.1]g/day v −6.9[−10.1,−2.5]g/day, P=0.002), PBD 7–9(−0.6[−4.4,3.4] g/day v. −6.7[−11.6,−3.1] g/day,P=0.01) and PBD 12–14(2.5[−2.9,6.5]g/day v.−2.9[−4.9,2.3]g/day,P=0.11). A between group comparison of nitrogen balance, CI and PI by PBD is shown in Figure 2. A further analysis by Hunt Hess grade showed no difference in the mean CI(ANOVA F−0.97,P=0.42), PI (ANOVA F−0.15,P=0.92) or nitrogen balance (ANOVA F− 0.13, P=0.94).

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.

Muscle Atrophy

Overall atrophy was 9.5+/−8.7%. There was less atrophy in the NMES+HPRO group vs the SOC group(6.5+/−4.1%vs12.5+/−6.4%,P 0.01). Additional factors correlated with atrophy were the average daily PI(Spearmans ρ=−0.45,P=0.03) and net nitrogen balance throughout the study period (Spearman’s ρ=− 0.47,P=0.02). Age, Hunt Hess Grade, BMI, and sex were not associated with percentage of muscle atrophy.

Outcome data

The mean+/−SD ICU length of stay was 19+/−7 days for entire study population, with no difference between intervention groups (SOC:20+/−8 days vs NMES+HPRO:18+/−7 days, P=0.4). All patients were alive and followed up at PBD 90. Results for all outcome measures by intervention group can be found in Supplemental Table 2. There was a modest correlation between the percent muscle atrophy on PBD 14 and 90-day mRS score(Spearman’s ρ=0.4,P=0.04) and SPPB score (Spearman’s ρ=− 0.3,P=0.1), and MoCA(Spearman’s ρ=−0.4,P=0.06).

Discussion

This single center randomized trial provide preliminary evidence that a combined intervention of HPRO+NMES is safe and feasible to perform in critically ill SAH patients. Furthermore, this combined intervention resulted in a reduction in quadriceps muscle atrophy by PBD 14 as compared to SOC. The resultant reduction in atrophy may also have a beneficial impact on physical and functional recovery by PBD 90.

The ability to execute both NMES+HPRO in a critical care setting, where many logistical obstacles may exist, is meaningful. Our ability to achieve a higher PI goal was mostly hindered by an institutional practice of withholding enteral nutrition for prolonged periods due to invasive surgical or radiology procedures. This was seen in both study groups as the percent of CI delivered to that prescribed was similar in each group(83%). It is common for SAH patients to undergo procedures that require withholding enteral nutrition, though it is not clear that this is necessary in patients with a secured artificial airway^{30, 31}. Poor appetite among study patients was also a hindrance, and may be related to impairment in hypothalamic mediated processes that control satiety³² in SAH patients. For all these reasons administration of intravenous administration of amino acids may be a suitable alternative to achieve goal PI in critically ill SAH patients.

NMES, which has never been formally tested in critically ill SAH patients, was well tolerated with close to 100 % compliance (98%). The primary challenge was coordination of care that was required to allow for two 30-minute sessions every day. Given the success of the NMES+HPRO intervention in our sample, a goal is to implement this across several NCCU in a larger sample. The ability of multiple institutions to replicate this level of coordination deserves study and will be important to evaluate and test if our therapy is a viable option for the SAH patient population.

The percentage of muscle atrophy in the SOC group is similar to reports in other critical care populations^{6, 33, 34} and is likely due to a combination of malnutrition and immobility. We noted no difference in the amount of physical therapy sessions or mobilization with sitting, standing or ambulating between the two study groups. However, this was a based on qualitative data entered in the electronic medical record and therefore our analysis was limited. There are no current standards that define the appropriate level of activity in the acute setting after SAH. While efforts are made to encourage mobilization^35–37, SAH patients often remain bed bound or limited to mobilization to a bedside chair for up to two weeks after injury. Passive mobilization of critically ill patients can reduce days of mechanical ventilation, ICU and hospital length of stay, and the incidence of delirium^{38, 39}. However, there is little data to support its ability to preserve muscle mass.

Both groups received similar amounts of total CI throughout the study period, however, the amount of daily PI(g/kg/day) was significantly higher in the NMES+HPRO group. Protein or essential amino acid ingestion acutely stimulate muscle protein synthesis rates in a dose-dependent manner^{40, 41}. However, disuse similar to the limited mobility or bed rest in the critically ill patient is accompanied by anabolic resistance to PI, requiring higher quantities of PI to stimulate muscle protein synthesis rates^42–45. Therefore HPRO may be one of the keys to preventing acute muscle atrophy. In fact, we noted modest inverse correlation between average daily PI(g/kg/day) with percentage of muscle atrophy at 14 days.

Appropriately timed exercise may be the critical element necessary to realize the benefits of HPRO supplementation⁹. NMES has been demonstrated to increase muscle protein synthesis, translating to a preservation of muscle mass measured by cross sectional area on both CT imaging and histological sections of muscle fibers^{11, 46}. The benefits of NMES are at least partly attributed to an increase in postabsorptive muscle protein synthesis rates⁴⁷, supported by a reported increase in basal mTOR phosphorylation following multiple days of NMES in ICU patients, as well as a reversal of skeletal muscle mRNA expression of key ligases of the ubiquitin proteasome pathway^{11, 48, 49}. The parallel occurrence of an increase in muscle protein synthesis and a reduction of muscle protein breakdown is indicative of a more positive muscle protein balance when NMES is applied on a regular basis.

While this study was not powered to assess the long-term impact of muscle atrophy or the dual interventions on outcome, there were modest associations noted between the percentage of quadriceps muscle atrophy at 14 days and measures of physical and functional recovery at 90 days. Acute muscle atrophy may be an important, and potentially modifiable contributor to impaired long-term physical recovery observed after SAH⁵⁰.

There are limitations to this study worth consideration. Despite randomization and rigorous trial design, this was a small, single center study, and the results are not definitive. The between group difference in the percentage of quadriceps atrophy provides evidence to adequately power more conclusive studies on the impact of these interventions on atrophy and relationship of atrophy to clinical and functional outcomes. The intensity of each NMES session in relation to quadriceps muscle atrophy was not analyzed and therefore we cannot comment on whether a dose–response relationship between quadriceps atrophy and NMES exists. Protein supplementation by itself is likely not adequate, but it is unclear what level of protein supplementation is necessary for NMES to be effective in reducing muscle atrophy. Future studies will address this by testing the impact of NMES+/−HPRO on acute muscle atrophy.

Regardless of these limitations, these results indicate that an approach of NMES+HPRO may be safe and feasible acutely after SAH, and may mitigate the impact of limited mobility and immune-mediated malnutrition in the ICU setting. A multicenter trial to validate the safety and feasibility of this approach and further delineate the impact on NMES+HPRO on acutely reducing muscle atrophy and improving long term recovery after SAH is being planned.

Supplementary Material

12028_2020_1138_MOESM1_ESM

Figure S1. Protocol for Intervention Period. Schematic diagram of study interventions for all patients and by intervention group during post bleed days 0 – 14.

Table S1. Comparison of Laboratory Values between Intervention Groups

Table S2. Outcome Measurements for Intervention Groups

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.