Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients: a randomized controlled feasibility study and pooled analysis

Annemijn H. Jonkman, Tim Frenzel, Euan J. McCaughey, Angus J. McLachlan, Claire L. Boswell-Ruys, David W. Collins, Simon C. Gandevia, Armand R.J. Girbes, Oscar Hoiting, Matthijs Kox, Marco Peters, Eline Oppersma, Peter Pickkers, Lisanne H. Roesthuis, Jeroen Schouten, Zhong Hua Shi, Peter H. Veltink, Heder J. de Vries, Cyndi Shannon Weickert, Carsten WiedenbachYingrui Zhang, Pieter R. Tuinman, Angélique M.E. de Man, Jane E. Butler, Leo M.A. Heunks*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Expiratory muscle weakness leads to difficult ventilator weaning. Maintaining their activity with functional electrical stimulation (FES) may improve outcome. We studied feasibility of breath-synchronized expiratory population muscle FES in a mixed ICU population (“Holland study”) and pooled data with our previous work (“Australian study”) to estimate potential clinical effects in a larger group. Methods: Holland: Patients with a contractile response to FES received active or sham expiratory muscle FES (30 min, twice daily, 5 days/week until weaned). Main endpoints were feasibility (e.g., patient recruitment, treatment compliance, stimulation intensity) and safety. Pooled: Data on respiratory muscle thickness and ventilation duration from the Holland and Australian studies were combined (N = 40) in order to estimate potential effect size. Plasma cytokines (day 0, 3) were analyzed to study the effects of FES on systemic inflammation. Results: Holland: A total of 272 sessions were performed (active/sham: 169/103) in 20 patients (N = active/sham: 10/10) with a total treatment compliance rate of 91.1%. No FES-related serious adverse events were reported. Pooled: On day 3, there was a between-group difference (N = active/sham: 7/12) in total abdominal expiratory muscle thickness favoring the active group [treatment difference (95% confidence interval); 2.25 (0.34, 4.16) mm, P = 0.02] but not on day 5. Plasma cytokine levels indicated that early FES did not induce systemic inflammation. Using a survival analysis approach for the total study population, median ventilation duration and ICU length of stay were 10 versus 52 (P = 0.07), and 12 versus 54 (P = 0.03) days for the active versus sham group. Median ventilation duration of patients that were successfully extubated was 8.5 [5.6–12.2] versus 10.5 [5.3–25.6] days (P = 0.60) for the active (N = 16) versus sham (N = 10) group, and median ICU length of stay was 10.5 [8.0–14.5] versus 14.0 [9.0–19.5] days (P = 0.36) for those active (N = 16) versus sham (N = 8) patients that were extubated and discharged alive from the ICU. During ICU stay, 3/20 patients died in the active group versus 8/20 in the sham group (P = 0.16). Conclusion: Expiratory muscle FES is feasible in selected ICU patients and might be a promising technique within a respiratory muscle-protective ventilation strategy. The next step is to study the effects on weaning and ventilator liberation outcome. Trial registration:, ID NCT03453944. Registered 05 March 2018—Retrospectively registered,

Original languageEnglish
Article number628
JournalCritical care
Issue number1
Publication statusPublished - 30 Oct 2020


  • Expiratory muscles
  • Functional electrical stimulation
  • Mechanical ventilation


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