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

Abstract

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.

The role of omega-3 polyunsaturated fatty acids in the intensive care unit

“…Muscle strength and size of quadriceps and the diaphragm were evaluated at baseline and after 11 days. Ten days of EPA at 2 g/day did not affect muscle size and strength compared to placebo [67]. It may be that the dose of omega-3 PUFAs was too low to see an effect or that DHA, rather than EPA, is important in affecting muscle protein synthesis.…”

Protein supplementation in critical illness: why, when and how?

“…There was no difference in the primary outcome at day 10 of ICU admission, but any effect of HMB is difficult to elucidate in this trial because HMB was administered in conjunction with arginine and glutamine. Supinski et al [45] randomised 83 mechanically ventilated patients in a blinded fashion to one of four groups for 10 days: HMB (3 g/day), HMB (3 g/day) and the omega-3 fatty acid eicosapentaenoic acid, eicosapentaenoic acid alone, or control. There was no difference between groups in diaphragm strength, quadriceps strength or ultrasound-derived diaphragm thickness.…”

Protein metabolism in critical illness

“…Physical activity, while challenging in critical illness, could be achieved using strategies such as neuromuscular stimulation or in-bed cycling [42,43]; a number of trials on this topic are currently underway (ClinicalTrials.gov: NCT04099108 and NCT05197231). Treatment with specific metabolites known for their ability to stimulate MPS such as beta-hydroxy-beta-methylbutyrate (HMB) or impair muscle protein breakdown such as ketone bodies are under investigation, but robust evidence supporting their clinical use is currently lacking [44,45].…”