Brain Injuries, Respiratory Failure
Conditions
Keywords
Epidural spinal cord stimulation, Respiratory failure, Diaphragmatic electrical activity
Brief summary
Patients with severe brain injury may develop impaired respiratory drive, diaphragm dysfunction, prolonged mechanical ventilation, and difficulty recovering spontaneous breathing. Epidural spinal cord stimulation may activate preserved spinal respiratory circuits and improve respiratory muscle activity. This prospective, single-center, non-randomized, single-arm exploratory study will enroll 10 patients with stroke or traumatic brain injury who have impaired consciousness and require invasive mechanical ventilation. Participants will undergo epidural spinal cord stimulation in addition to standard clinical care. Diaphragmatic electrical activity, respiratory function, diaphragm ultrasound findings, diaphragm electromyography, duration of mechanical ventilation, pulmonary infection, length of stay, mortality, safety events, and 6-month neurological outcome will be assessed. The study aims to evaluate the safety and preliminary efficacy of epidural spinal cord stimulation for improving respiratory function after brain injury.
Detailed description
Severe central nervous system injury, including stroke and traumatic brain injury, may impair respiratory drive and disrupt descending pathways between brainstem respiratory centers and spinal respiratory motor networks. This can lead to diaphragm weakness, ineffective cough, secretion retention, prolonged mechanical ventilation, pulmonary infection, and difficulty with ventilator liberation. Epidural spinal cord stimulation is a neuromodulation approach that may increase the excitability of preserved spinal neural circuits and facilitate respiratory motor output. Preclinical and early clinical evidence suggests that spinal stimulation can enhance respiratory muscle activation and improve ventilatory performance. This study is a prospective, single-center, interventional, non-randomized, single-arm exploratory trial. Ten adults with imaging-confirmed stroke or traumatic brain injury, a Glasgow Coma Scale score of 3 to 8, and a requirement for invasive mechanical ventilation for at least 24 hours will be enrolled. All participants will undergo epidural spinal cord stimulation in addition to standard treatment. Respiratory physiological measurements will be obtained before and after stimulation. Participants will be followed until hospital discharge and subsequently assessed for survival and neurological outcome at 6 months after injury. The study will evaluate changes in diaphragmatic electrical activity and other respiratory parameters, as well as pulmonary infection, duration of mechanical ventilation, intensive care unit and hospital length of stay, in-hospital mortality, neurological outcome, and intervention-related adverse events.
Interventions
PROCEDUREEpidural Electrode Implantation
Participants will undergo surgical implantation of an epidural spinal cord stimulation electrode under anesthesia. The electrode will be positioned at the spinal level specified in the final surgical protocol and connected to a stimulation system.
Sponsors
Zhongda Hospital
The 904th Hospital of the People's Liberation Army of China
Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Chinese PLA General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 74 years. Body mass index less than 30 kg/m². Imaging-confirmed stroke or traumatic brain injury. Glasgow Coma Scale score of 3 to 8, with relatively stable vital signs. Requirement for invasive mechanical ventilation through an oral or nasal endotracheal tube or tracheostomy for at least 24 hours. Written informed consent provided by the participant's legally authorized representative; if the participant regains decision-making capacity, continued participation will be reconfirmed with the participant. Willingness and ability of the participant or legally authorized representative to comply with the study intervention and follow-up procedures.
Exclusion criteria
* Suspected or confirmed infection at the planned electrode implantation site, severe uncontrolled systemic infection, known metal allergy relevant to the implanted device, or uncontrolled intracranial hypertension. Respiratory failure primarily attributable to severe pneumonia, pulmonary contusion, pneumothorax, hemothorax, chronic obstructive pulmonary disease with respiratory failure, severe asthma, or a requirement for home oxygen therapy within the previous 6 months. New York Heart Association class III or IV heart failure or presence of an implanted cardiac pacemaker. Severe hepatic dysfunction, including Child-Pugh class C, severe renal dysfunction with estimated glomerular filtration rate ≤30 mL/min/1.73 m², or dialysis dependence. Status epilepticus or active convulsions. Cervical spinal cord injury, other spinal cord injury, major chest wall deformity, myasthenia, or respiratory dysfunction primarily caused by brainstem injury. Severe psychiatric or pre-existing neurological or cognitive disorders that would interfere with study evaluation or completion, including amyotrophic lateral sclerosis, dementia, Parkinson disease, Huntington disease, or another clinically significant central nervous system disorder unrelated to the index brain injury. Expected survival of 72 hours or less, or a decision to withhold endotracheal intubation, cardiopulmonary resuscitation, or other life-sustaining treatment. Pregnancy or breastfeeding. Any other condition that, in the investigator's judgment, may place the participant at unacceptable risk or interfere with completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Electrical Activity of the Diaphragm From Before to After Spinal Cord Stimulation | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | Peak electrical activity of the diaphragm will be measured using an electrical activity of the diaphragm catheter. The change from the pre-stimulation value to the post-stimulation value will be reported in microvolts (μV). |
| Change in Diaphragmatic Electrical Activity Frequency From Before to After Spinal Cord Stimulation | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | The frequency of diaphragmatic electrical activity signals will be measured using an electrical activity of the diaphragm catheter. The change from before to after stimulation will be reported as events per minute. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Frequency of Diaphragmatic Electrical Activity Signals With Peak Amplitude of at Least 3 μV | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | The number of diaphragmatic electrical activity signals with a peak amplitude of at least 3 μV will be determined using an electrical activity of the diaphragm catheter. The change from before to after stimulation will be reported as events per minute. |
| Change in the Frequency of Spontaneous Inspiratory Efforts Detected by Diaphragmatic Electrical Activity | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | Spontaneous inspiratory efforts generated by the participant's neural respiratory drive will be detected using an electrical activity of the diaphragm catheter. Ventilator-delivered breaths without a corresponding diaphragmatic electrical activity signal will not be counted. The change from before to after stimulation will be reported as inspiratory efforts per minute. |
| Spontaneous Respiratory Rate | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | The participant's spontaneous respiratory rate will be determined from respiratory monitoring and reported as breaths per minute. Ventilator-mandated breaths will be excluded. |
| Change in Tidal Volume From Before to After Spinal Cord Stimulation | Immediately before stimulation and within 1 hour after stimulation, upto 30 days | Tidal volume will be measured using the mechanical ventilator under standardized ventilator settings and reported in milliliters (mL). |
| Diaphragmatic Excursion | Immediately before stimulation and within 1 hour after stimulation upto 30 days | Diaphragmatic excursion will be measured by bedside M-mode ultrasonography with the participant in the supine position. Values will be reported in millimeters (mm). |
| Diaphragm Thickening Fraction | Immediately before stimulation and within 1 hour after stimulation upto 30 days | Diaphragm thickening fraction will be calculated from inspiratory and expiratory diaphragm thickness measured by bedside ultrasonography and reported as a percentage. |
| Duration of Mechanical Ventilation | From enrollment through hospital discharge, up to 6 months | Cumulative duration of invasive mechanical ventilation from enrollment until successful liberation from mechanical ventilation, hospital discharge, or death, whichever occurs first. Values will be reported in hours. |
| ICU Length of Stay | From enrollment through intensive care unit discharge, up to 6 months | Time from enrollment or intensive care unit admission to intensive care unit discharge or death, reported in hours. |
| Hospital Length of Stay | From hospital admission through hospital discharge, up to 6 months | Time from hospital admission to hospital discharge or in-hospital death, reported in hours. |
| In-Hospital Mortality | From enrollment through hospital discharge, up to 6 months | Number and percentage of participants who die before hospital discharge. |
| Adverse Events Related to the Procedure or Device | From implantation through the 6-month follow-up | Number and percentage of participants experiencing adverse events considered possibly, probably, or definitely related to epidural electrode implantation or spinal cord stimulation, including infection, bleeding or hematoma, cerebrospinal fluid leakage, neurological injury, device malfunction, stimulation-related discomfort, or other complications. |
Countries
China
Contacts
CONTACTFei Peng, PhD. MD.
CONTACTYi Li, PhD.
Outcome results
None listed