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, Eline Oppersma, Marco Peters, 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


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 - 1 Dec 2020

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