Scientists at Toronto General Hospital Research Institute (TGHRI) have tested a method to protect critically ill patients who need help breathing with a ventilator against complications such as damage to the diaphragm and lungs.
When patients rely fully on machines to breathe, their diaphragm—the main muscle used in breathing—can become weak or even injured from lack of use. Maintaining diaphragm activity during ventilation may help prevent these complications, enhance circulation, and preserve muscle mass and function.
Stimulation of the nerve that provides motor control of the diaphragm—called diaphragm neurostimulation—is a way to make the diaphragm muscle contract without the patient having to breathe on their own. However, the feasibility, tolerability, and safety of preventing diaphragm inactivity with temporary, continuous neurostimulation during ventilator use have not been investigated.
A Phase 1 clinical trial was conducted to assess the feasibility of this technique for up to seven days. The trial involved 19 participants recovering from lung surgery or experiencing severe lung failure. Neurostimulation was applied during periods when the patients were not breathing on their own.
Results showed that 95% of participants maintained adequate diaphragm activity during the first 24 hours. Throughout the trial, all participants sustained sufficient diaphragm activity when stimulation was needed, demonstrating the feasibility of this procedure.
Importantly, the treatment was well-tolerated with no serious complications. Patients also showed an increase in diaphragm thickness, and the likelihood of diaphragm atrophy appeared lower than in those who did not receive stimulation in past cases.
“These findings indicate that diaphragm neurostimulation is highly feasible in patients receiving mechanical ventilation,” says Dr. Ewan Goligher, Senior Scientist at TGHRI and senior author of the study. “This method could help prevent long-term damage, increase the chances of survival, and improve recovery for ventilated patients.”
Future clinical trials are required to confirm the long-term safety and effectiveness of this intervention in critically ill patients, with phase II and III trials of this treatment strategy underway at UHN and other centres in Canada and the United States.
Results from a phase III trial have been recently published and indicate that neurostimulation helps patients on prolonged ventilation wean off faster, strengthen breathing muscles, and gain more days alive and free of mechanical ventilation, highlighting the potential benefits of this technique for patients in critical care who have difficulty weaning from mechanical ventilation.
For more information on this approach to diaphragm stimulation, check out this video from UHN Foundation.
The first author of this study is Dr. Idunn Morris, Postdoctoral Researcher at the University Health Network and faculty at the University of Sydney.
The senior author of this study is Dr. Ewan Goligher, Senior Scientist at the Toronto General Hospital Research Institute and Associate Professor of Medicine and Physiology at the University of Toronto.
This work was supported by the National Sanitarium Association, Interdepartmental Division of Critical Care Medicine, and UHN Foundation.
Dr. Ewan Goligher has received personal fees for consulting from multiple companies involved in phrenic nerve stimulation, including Lungpacer Medical, Stimit, and Heecap, as well as consulting for Getinge, Vyaire, Drager, Baxter, Zoll, and BioAge outside the submitted work. The STIMULUS trial received in-kind support in the form of devices and supplies provided by Lungpacer Medical.
For a full list of competing interests, please see the manuscript.
Morris IS, Bassi T, Bellissimo CA, Bootjeamjai P, Roman-Sarita G, de Perrot M, Donahoe L, McRae K, Dianti J, Del Sorbo L, Keshavjee S, Cypel M, Reynolds SC, Dres M, Thakkar V, Mehta N, Brochard L, Ferguson ND, Goligher EC. Continuous On-Demand Diaphragm Neurostimulation to Prevent Diaphragm Inactivity During Mechanical Ventilation: A Phase 1 Clinical Trial (STIMULUS). Am J Respir Crit Care Med. 2025 Mar 5. doi: 10.1164/rccm.202407-1483OC. Epub ahead of print. PMID: 40043207.