Martin Dres1,2, Marcelo Gama de Abreu3,4,5, Hamid Merdji6, Holger Müller-Redetzky7, Dominic Dellweg8, Winfried J Randerath9, Satar Mortaza10, Boris Jung11, Christian Bruells12, Onnen Moerer13, Martin Scharffenberg3, Samir Jaber14, Sébastien Besset15, Thomas Bitter16, Arnim Geise17, Alexander Heine18, Maximilian V Malfertheiner19, Andreas Kortgen20, Jonathan Benzaquen21, Teresa Nelson22, Alexander Uhrig7, Olaf Moenig8, Ferhat Meziani6, Alexandre Demoule1,2, Thomas Similowski1,23. 1. Experimental and Clinical Respiratory Neurophysiology, Sorbonne University, INSERM, UMRS1158, Paris, France. 2. AP-HP, Pitié-Salpêtrière Hospital, Médecine Intensive Réanimation, R3S Department, Sorbonne University, Paris, France. 3. Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 4. Department of Intensive Care and Resuscitation, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. 5. Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. 6. Université de Strasbourg, Service de Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, France. 7. Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. 8. Department of Pulmonary and Critical Care Medicine, Fachkrankenhaus Kloster Grafschaft GmbH, Schmallenberg, Germany. 9. Institute for Pneumology at the University of Cologne Bethanien Hospital, Clinic for Pneumology and Allergology, Centre of Sleep Medicine and Respiratory Care, Solingen, Germany. 10. Département de Médecine Intensive, Réanimation et Médecine Hyperbare, CHU d'Angers, Faculté de Santé, Université d'Angers, Angers, France. 11. Medical Intensive Care Unit, Lapeyronie Teaching Hospital and PhyMedExp, University of Montpellier, Montpellier, France. 12. Department of Anesthesiology, Aachen University Hospital of the RWTH Aachen, Aachen, Germany. 13. Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany. 14. Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, PhyMedExp, INSERM U1046, CNRS UMR, 9214, Montpellier, France. 15. AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France. 16. Clinic for General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr-Universität Bochum, Bad Oeynhausen, Germany. 17. Department of Respiratory Medicine, Allergology and Sleep Medicine/Nuremberg Lung Cancer Center, Paracelsus Medical University, General Hospital Nuremberg, Nuremburg, Germany. 18. Department of Internal Medicine B, Cardiology, Pneumology, Weaning, Infectious Diseases, Intensive Care Medicine, University Hospital Greifswald, Greifswald, Germany. 19. Department of Internal Medicine II, Cardiology and Pneumology, University Hospital Regensburg, Regensburg, Germany. 20. Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany. 21. Department of Pulmonary Medicine and Oncology, Université Côte d'Azur, CHU de Nice, University Hospital Federation OncoAge, Nice, France. 22. Technomics Research, LLC, Minneapolis, Minnesota; and. 23. AP-HP, Pitie-Salpêtrière Hospital, R3S Department, Sorbonne Université, Paris, France.
Abstract
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 (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).
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 (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).