Mechanical Ventilation Weaning Issues May Improve With Transvenous Diaphragm Neurostimulation

Transvenous diaphragm neurostimulation was associated with successful weaning from mechanical ventilation (MV) in patients who have had difficulty with such weaning, according to study findings published in the American Journal of Respiratory and Critical Care Medicine.

The findings are from the open-label, randomized, clinical RESCUE-3 trial (ClinicalTrials.gov Identifier: NCT03783884), which evaluated the safety and effectiveness of transvenous diaphragm neurostimulation to increase successful weaning in patients with difficulty weaning from MV vs standard of care. The study was conducted at 48 centers in the United States and Europe.

Eligible participants were adults who were mechanically ventilated for at least 96 hours, met protocolized readiness-to-wean criteria, and had failed at least 2 weaning attempts at least 48 hours after MV initiation on different days.

The patients were randomly assigned 1:1 to the treatment or control group, with the treatment group receiving transvenous diaphragm neurostimulation in addition to standard of care. The diaphragm neurostimulation sessions were conducted twice daily and at least 3 hours apart.

The primary outcome was successful weaning at day 30, which meant passing a standardized weaning trial and being removed from MV without returning to MV within 48 hours.

The participants were enrolled from June 2019 through January 2023. The trial was halted at the first planned interim analysis (N=200), although the prespecified criterion for statistical superiority were not met. A total of 223 patients were randomly assigned to the treatment group (n=109) and control groups (n=114). Participants’ mean (SD) age was 64 years (11.8), and 66% were male.

A modified intent-to-treat (mITT) population included 216 patients, with 102 in the treatment group and 114 in the control group. Among this group, 71 (70%) participants in the treatment group and 69 (61%) in the control group were weaned successfully at 30 days. The posterior probability of superiority for weaning success was 97.9% (median adjusted hazard ratio [HR], 1.34; 95% CrI, 1.01-1.78) in the primary analysis. In a sensitivity analysis with successful weaning regarded as disconnection from the ventilator for at least 7 days, a similar effect was observed (median adjusted HR, 1.38; 95% CrI, 1.03-1.86; posterior probability of superiority 98.4%).

MV duration to successful weaning or day 30 was decreased in the treatment group compared with the control group (median adjusted difference, −2.5 days; 95% CrI, −5.0 to 0.1; posterior probability of superiority, 97.1%). At day 30, the mortality was 9.8% for the treatment group and 10.5% in the control group (median adjusted HR, 0.74; 95% CrI, 0.37-1.46; posterior probability of superiority, 80.6%).

Serious adverse events (SAEs) occurred in 39 of 109 participants (35.8%) in the treatment group vs 27 of 114 (23.7%) in the control group. SAEs considered as device- or procedure-related were found in 9.6% of patients in the treatment group at a rate of 8 SAEs per 1000 catheter days.

A study limitation was the decision to discontinue the trial before a prespecified trigger for superiority was achieved. Also, the study was not blinded, and adverse events could have been affected by reporting bias.

“Although the trial was stopped early dtransvenous diaphragm neurostimulation showed a high probability of potential benefit for weaning success but with a possible increase in SAEs.ue to slow enrollment, transvenous diaphragm neurostimulation showed a high probability of potential benefit for weaning success but with a possible increase in SAEs,” the investigators stated.

Disclosure: The research was supported by Lungpacer Medical, Inc. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Pulmonology Advisor