A randomized controlled trial to determine whether beta-hydroxy-beta-methylbutyrate and/or eicosapentaenoic acid improves diaphragm and quadriceps strength in critically Ill mechanically ventilated patients.

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. RESULTS: Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. CONCLUSIONS: These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .

Does Standard Physical Therapy Increase Quadriceps Strength in Chronically Ventilated Patients? A Pilot Study.

OBJECTIVES: Physical therapy is standard care for mechanically ventilated patients, but there is no evidence, using nonvolitional, objective measurements, that physical therapy increases muscle strength in this population. The present study tested the hypothesis that 2 weeks of standard, conventional physical therapy provided at a ventilator weaning facility would increase quadriceps strength in mechanically ventilated patients. DESIGN: Prospective observational study. SETTING: Ventilator weaning unit. PATIENTS: Patients who were transferred from an acute care hospital because of failure to wean from mechanical ventilation and who were receiving physical therapy as prescribed by facility staff. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We employed a novel, nonvolitional objective technique, quadriceps twitch force generation in response to femoral nerve magnetic stimulation, to assess leg strength before and after 2 weeks of conventional physical therapy. The duration and specific exercises provided to patients were also recorded. In a subset of patients, we measured muscle activation intensity using wireless electromyogram recordings. Indices of respiratory function (maximum inspiratory pressure generation and the rapid shallow breathing index) were also assessed. Patients' responses to 2 weeks of physical therapy were poor; on average, quadriceps twitch fell by -1.02 ± 0.71 Newtons. Neither physical therapy duration nor specific forms of exercise were identified to positively impact quadriceps twitch. Electromyogram recordings indicated that during training, muscle activation was poor. Consequently, therapists spent substantial time performing exercises that elicited little muscle activation. Physical therapy did not improve respiratory function. CONCLUSIONS: Standard physical therapy delivered in a ventilator weaning facility failed to improve quadriceps leg strength in a majority of mechanically ventilated patients. The fact that mechanically ventilated patients fail to achieve high levels of muscle activation during physical therapy provides a potential explanation as to why physical therapy may often be ineffective. We speculate that use of novel methods which increase muscle activation during exercise may improve responses of mechanically ventilated patients to physical therapy.

Magnetic twitch assessment of diaphragm and quadriceps weakness in critically ill mechanically ventilated patients.

Critically ill mechanically ventilated (MV) patients develop significant muscle weakness, which has major clinical consequences. There remains uncertainty, however, regarding the severity of leg weakness, the precise relationship between muscle strength and thickness, and the risk factors for weakness in MV patients. We therefore measured both diaphragm (PdiTw) and quadriceps (QuadTw) strength in MV patients using magnetic stimulation and compared strength to muscle thickness. Both PdiTw and QuadTw were profoundly reduced for MV patients, with PdiTw 19 % of normal and QuadTw 6% of normal values. There was a poor correlation between strength and thickness for both muscles, with thickness often remaining in the normal range when strength was severely reduced. Regression analysis revealed reductions in PdiTw correlated with presence of infection (p = 0.006) and age (p = 0.007). QuadTw best correlated with duration of MV (p = 0.036). Limb muscles are profoundly weak in critically ill patients, with a severity that mirrors the level of weakness observed in the diaphragm.