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

Gerald S. Supinski, Paul F. Netzel, Philip M. Westgate, Elizabeth A. Schroder, Lin Wang, Leigh Ann Callahan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article number308
JournalCritical Care
Volume25
Issue number1
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
We wish to thank the medical ICU attending physicians and pulmonary critical care fellows at the University of Kentucky for their assistance in recruiting subjects for this study. We also wish to thank the Research Pharmacy Service of the University of Kentucky for their substantial work in formulating and delivering the study treatments.

Funding Information:
This work was supported by grants from the National Heart, Lung and Blood Institute R01HL113494 and R01HL141356 and the Department of Veterans Affairs 5I01BX002132. All funding bodies supported the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • Beta-hydroxy-beta-methylbutyrate
  • Diaphragm weakness
  • Eicosapentaenoic acid
  • Limb muscle weakness
  • Mechanical ventilation
  • Respiratory failure

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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