Muscle Weakness and 5-Year Survival in Acute Respiratory Distress Syndrome Survivors.

OBJECTIVES: To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. DESIGN: Longitudinal prospective cohort study over 5 years of follow-up. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: One hundred fifty-six acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the association was attenuated (1.54 [0.82-2.89]) when evaluated longitudinally over follow-up. Persisting and resolving trajectories of muscle weakness, occurring in 50% of patients during follow-up, were associated with worse survival (3.01 [1.12-8.04]; and 3.14 [1.40-7.03], respectively) compared to a trajectory of maintaining no muscle weakness. CONCLUSIONS: At hospital discharge, greater than one third of acute respiratory distress syndrome survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post-ICU weakness, both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up.

Physical declines occurring after hospital discharge in ARDS survivors: a 5-year longitudinal study.

PURPOSE: Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physical declines after hospital discharge. The objective of our study was to evaluate the epidemiology of physical declines over 5-year follow-up and identify patients at risk for decline. METHODS: This multi-site prospective cohort study evaluated ARDS survivors who completed a physical status assessment at 3 or 6 months post-discharge. Three measures were evaluated: muscle strength (Medical Resource Council sumscore); exercise capacity [6-min walk test (6MWT)]; physical functioning [36-Item Short Form Health Survey (SF-36 survey)]. Patients were defined as "declined" if a comparison of their current and prior score showed a decrease that was greater than the Reliable Change Index-or if the patient died. Risk factors [pre-ARDS baseline status, intensive care unit (ICU) illness severity, and other intensive care variables] were evaluated using longitudinal, generalized linear regression models for each measure. RESULTS: During the follow-up of 193 ARDS survivors (55 % male; median age 49 years), 166 (86 %) experienced decline in ≥1 physical measure (including death) and 133 (69 %) experienced a physical decline (excluding death). For all measures, age was a significant risk factor [odds ratios (OR) 1.34-1.69 per decade; p < 0.001]. Pre-ARDS comorbidity (Charlson Index) was independently associated with declines in strength and exercise capacity (OR 1.10 and 1.18, respectively; p < 0.02), and organ failure [maximum daily Sequential Organ Failure Assessment (SOFA) score in ICU] was associated with declines in strength (OR 1.06 per 1 point of SOFA score; p = 0.02). CONCLUSIONS: Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.

Neuromuscular electrical stimulation in mechanically ventilated patients: a randomized, sham-controlled pilot trial with blinded outcome assessment.

PURPOSE: The purpose of the study is to compare neuromuscular electrical stimulation (NMES) vs sham on leg strength at hospital discharge in mechanically ventilated patients. MATERIALS AND METHODS: We conducted a randomized pilot study of NMES vs sham applied to 3 bilateral lower extremity muscle groups for 60 minutes daily in the intensive care unit (ICU). Between June 2008 and March 2013, we enrolled adults who were receiving mechanical ventilation within the first week of ICU stay and who could transfer independently from bed to chair before hospital admission. The primary outcome was lower extremity muscle strength at hospital discharge using Medical Research Council score (maximum, 30). Secondary outcomes at hospital discharge included walking distance and change in lower extremity strength from ICU awakening. Clinicaltrials.gov: NCT00709124. RESULTS: We stopped enrollment early after 36 patients due to slow patient accrual and the end of research funding. For NMES vs sham, mean (SD) lower extremity strength was 28 (2) vs 27 (3), P = .072. Among secondary outcomes, NMES vs sham patients had a greater mean (SD) walking distance (514 [389] vs 251 [210] ft, P = .050) and increase in muscle strength (5.7 [5.1] vs 1.8 [2.7], P = .019). CONCLUSIONS: In this pilot randomized trial, NMES did not significantly improve leg strength at hospital discharge. Significant improvements in secondary outcomes require investigation in future research.

Neuromuscular electrical stimulation for intensive care unit-acquired weakness: protocol and methodological implications for a randomized, sham-controlled, phase II trial.

BACKGROUND: As the population ages and critical care advances, a growing number of survivors of critical illness will be at risk for intensive care unit (ICU)-acquired weakness. Bed rest, which is common in the ICU, causes adverse effects, including muscle weakness. Consequently, patients need ICU-based interventions focused on the muscular system. Although emerging evidence supports the benefits of early rehabilitation during mechanical ventilation, additional therapies may be beneficial. Neuromuscular electrical stimulation (NMES), which can provide some muscular activity even very early during critical illness, is a promising modality for patients in the ICU. OBJECTIVE: The objectives of this article are to discuss the implications of bed rest for patients with critical illness, summarize recent studies of early rehabilitation and NMES in the ICU, and describe a protocol for a randomized, phase II pilot study of NMES in patients receiving mechanical ventilation. DESIGN: The study was a randomized, sham-controlled, concealed, phase II pilot study with caregivers and outcome assessors blinded to the treatment allocation. SETTING: The study setting will be a medical ICU. PARTICIPANTS: The study participants will be patients who are receiving mechanical ventilation for 1 day or more, who are expected to stay in the ICU for an additional 2 days or more, and who meet no exclusion criteria. INTERVENTION: The intervention will be NMES (versus a sham [control] intervention) applied to the quadriceps, tibialis anterior, and gastrocnemius muscles for 60 minutes per day. MEASUREMENTS: Lower-extremity muscle strength at hospital discharge will be the primary outcome measure. LIMITATIONS: Muscle strength is a surrogate measure, not a patient-centered outcome. The assessments will not include laboratory, genetic, or histological measures aimed at a mechanistic understanding of NMES. The optimal duration or dose of NMES is unclear. CONCLUSIONS: If NMES is beneficial, the results of the study will help advance research aimed at reducing the burden of muscular weakness and physical disability in survivors of critical illness.

Inter-rater reliability of manual muscle strength testing in ICU survivors and simulated patients.

OBJECTIVE: The goal of the paper is to determine inter-rater reliability of trained examiners performing standardized strength assessments using manual muscle testing (MMT). DESIGN, SUBJECTS, AND SETTING: The authors report on 19 trainees undergoing quality assurance within a multi-site prospective cohort study. INTERVENTION: Inter-rater reliability for specially trained evaluators ("trainees") and a reference rater, performing MMT using both simulated and actual patients recovering from critical illness was evaluated. MEASUREMENTS AND RESULTS: Across 26 muscle groups tested by 19 trainee-reference rater pairs, the median (interquartile range) percent agreement and intraclass correlation coefficient (ICC; 95% CI) were: 96% (91, 98%) and 0.98 (0.95, 1.00), respectively. Across all 19 pairs, the ICC (95% CI) for the overall composite MMT score was 0.99 (0.98-1.00). When limited to actual patients, the ICC was 1.00 (95% CI 0.99-1.00). The agreement (kappa; 95% CI) in detecting clinically significant weakness was 0.88 (0.44-1.00). CONCLUSIONS: MMT has excellent inter-rater reliability in trained examiners and is a reliable method of comprehensively assessing muscle strength.