Lung, Mechanical Ventilation, Organ Donation
Conditions
Keywords
Lung organ donors, Phrenic nerve pacing, Diaphragm stimulation, Critical Care
Brief summary
The goal of this clinical trial is to test the feasibility of pacing the phrenic nerve to stimulate the diaphragm in order to improve the lung function in brain dead organ donors. The main questions it aims to answer are: * Proof of concept and feasibility * Can lung function be improved in lungs that have been disqualified for donation Participants will have an AeroPace catheter inserted and will be paced on every breath up to the time of organ donation.
Detailed description
Single-center, single-arm, proof-of-concept trial. Up to twenty (20) subjects on mechanical ventilation who are determined to be brain dead and whose lungs are declined for donation based on a PaO2/FiO2 ratio \< 300 mmHg will be enrolled. Subjects may also be enrolled in the study at the request of the donation team if the lungs are accepted for donation but of marginal quality. Consent from the temporary substitute decision maker (TSDM) will be obtained for (i) organ donation and (ii) for study participation. All subjects will receive Lungpacer AeroPace Protect System catheter-based transvenous phrenic nerve stimulation (LAPS-PNS) with lung-protective mechanical ventilation and standard of care for transplant donors. Insertion of the AeroPace Catheter will be conducted as soon as possible after the determination of lung transplant ineligibility. LAPS-PNS will be titrated with the ventilator to provide a contribution to the work of breathing sufficient to retain diaphragm activation. Measurements to determine the effects of LAPS-PNS on donor lung function and physiology will be conducted until the time of organ donation. An esophageal-gastric manometer and electrical impedance tomography (EIT) unit will be utilized, respectively, to assess transdiaphragmatic pressure and lung volume distribution. Data collected for brain dead donors admitted to the same ICU over the 2 years preceding the study start who did not qualify for lung donation will serve as an unmatched comparator group.
Interventions
DEVICELungpacer AeroPace catheter and device
Diaphragm neurostimulation device for phrenic nerve pacing during mechanical ventilation.
Sponsors
Fraser Health
Lotte & John Hecht Memorial Foundation
Lungpacer Medical Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-center, single-arm, proof-of-concept trial designed to establish the feasibility of LAPS-PNS for maintaining diaphragm activation with mechanical ventilation in donors after brain death whose lungs are ineligible for transplantation due to a PaO2/FiO2 ratio \< 300 mmHg. This study will determine the number of subjects in whom LAPS-PNS can recover lung function as shown by a PaO2/FiO2 ratio \> 300 mmHg by the time of organ donation.
Eligibility
Sex/Gender
ALL
Age
19 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Designated as brain dead according to BC provincial guidelines, and * Are 19 years or older, and * Are mechanically ventilated, and * TSDM consented for organ donation, and * TSDM consented to study participation, and * Accepted by BC transplant team to donate at least 1 organ system, and * Declined by BC transplant team for lung donation based on hypoxia with the PaO2/FiO2ratio \< 300 mmHg or other criterion that precludes lung donation as requested by the organ donation team.
Exclusion criteria
* Greater than 8 hours from time declined for lung donation and initiation of LAPS-PNS, * Inability to place a central venous catheter in the left internal jugular or left subclavian vein, * Neuromuscular disease (e.g., Amyotrophic Lateral Sclerosis, Guillain-Barre), * Previous phrenic nerve injury, * Spinal cord injury above the 6th cervical spine level, * Implanted electronic cardiac or neurostimulation device in situ * 2nd or 3rd degree heart block on at least 2 EKGs conducted during routine care, * Treating physician deems enrollment not clinically appropriate for other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PaO2/FiO2 ratios from baseline | ABG measurements will be taken every 6 hours from enrolment until study endpoint for each participant. | PaO2/FiO2 ratio measured from arterial blood gas values. |
| Number of safety events | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | Determine whether any unexpected, or device-related or procedure-related complications occur in brain dead subjects. Standardized checklists will be developed to track safety events including arrhythmia, bradycardia, discomfort, hypertension/hypotension, inappropriate stimulation, pain or discomfort, phrenic nerve damage or injury, and syncope. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine percent of eligible ventilator breaths delivered with LAPS-PNS | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | Eligible breaths are defined as those breaths in which PNS is not precluded by clinical care/procedures or subject transport. |
| Change in distribution of ventilation using Electrical Impedance Tomography (EIT) | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | Measured in impedance units, percentage change from baseline |
| Total vasopressor use (mg/mL) during LAPS-PNS use | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | — |
| Total fluid administration (mL/kg) during LAPS-PNS dose | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | — |
| Change in kidney function during LAPS-PNS dose from baseline | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | Measures of urine output (mL/kg) and creatinine (umol/L) |
| Average vital sign recording during LAPS-PNS dose | Under continuous observation from subject enrolment until study endpoint (organ donation), an average of 40 hours. | Collection variables include temperature (degrees celsius), heart rate (bpm), SBP/DBP, MAP, RR (breaths/min) |
Countries
Canada
Outcome results
None listed