Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients
Authors: Martin Dres, Marcelo Gama de Abreu, Hamid Merdji, Holger Müller-Redetzky, Dominic Dellweg, Winfried J. Randerath, Satar Mortaza, Boris Jung, Christian Bruells, Onnen Moerer, Martin Scharffenberg, Samir Jaber, Sébastien Besset, Thomas Bitter, Arnim Geise, Alexander Heine, Maximilian V. Malfertheiner, Andreas Kortgen, Jonathan Benzaquen, Teresa Nelson, Alexander Uhrig, Olaf Moenig, Ferhat Meziani, Alexandre Demoule, Thomas Similowski, François Beloncle, Pierre-Yves Olivier, Marie Lemerle, Pierre Asfar, Alain Mercat, Katharina Böllinger, Marc Giesa, Carmen Garcia, Till Jacobi, Nikolas Lambiris, Felix Machleid, Panagiotis Pergantis, Bastian Grube, Damien Roux, Santiago Freita Ramos, Noemie Zucman, Louis Marie Dumont, Laura Federici, Marc Amouretti, Jean-Damien Ricard, Didier Dreyfuss, Jakob Wittenstein, Andreas Güldner, Max Ragaller, Peter Spieth, Christopher Uhlig, Lars-Olav Harnisch, Frank Bloos, Daniel O. Thomas-Rüddel, Gérald Chanques, Mathieu Capdevila, Yassir Aarab, Fanny Garnier, Vincent Brunot, Kada Klouche, Valérie Moulaire, Philippe Corne, Fernand Macone, François Durand, Charles Hugo Marquette, Julie Delemazure, Julien Mayaux, Elise Morawiec, Alexandra Monnier, Hassene Rahmani, Louise-Marie Jandeaux, Antoine Studer, Julie Helms, Raphaël Clere-Jehl
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [−10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and −14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT 03096639) and the European Database on Medical Devices (CIV-17-06-020004).