Rationale: Diaphragm dysfunction impedes weaning from mechanical ventilation. Transvenous diaphragm neurostimulation can increase diaphragm strength, but its impact on patient outcomes is uncertain.
Objectives: To test the safety and effectiveness of transvenous diaphragm neurostimulation to increase successful weaning in patients with difficulty weaning from mechanical ventilation in comparison with standard of care.
Methods: This international, multicenter, open-label, randomized clinical trial (RESCUE-3) included adult patients requiring mechanical ventilation for ⩾96 hours who met readiness-to-wean criteria and failed two or more weaning attempts. Patients were randomized to twice-daily transvenous diaphragm neurostimulation (treatment) or standard of care (control). The primary outcome was successful weaning at Day 30. Secondary outcomes included duration of ventilation to Day 30 and mortality at Day 30. The prespecified primary analysis utilized a Bayesian approach with borrowing of prior information from a previous Phase-II randomized trial, downweighted to account for possible differences in trials.
Measurements and main results: Because of slow enrollment and financial considerations, the trial was halted at the first interim analysis after 200 patients were randomized. Overall, 216 patients were randomized in the modified intent-to-treat population (treatment group, n = 102; control group n = 114). At Day 30, 71 (70%) patients in the treatment group and 69 (61%) patients in the control group were successfully weaned (adjusted hazard ratio, 1.34; 95% credible interval = 1.01-1.78; posterior probability of superiority, 97.9%). Treatment reduced the duration of ventilation (adjusted difference, -2.5 d; 95% credible interval = -5.0 to 0.1; posterior probability of superiority, 97.1%). Serious adverse events were reported in 36% of patients in the treatment group and 24% of patients in the control group; 9.8% of patients in the treatment group and 10.5% of patients in the control group died (adjusted hazard ratio, 0.74; 95% credible interval = 0.37-1.46; posterior probability of superiority, 80.6%).
Conclusions: Although the trial was stopped early because of slow enrollment, transvenous diaphragm neurostimulation showed a high probability of potential benefit for weaning success but with a possible increase in serious adverse events.
Keywords: acute respiratory distress syndrome; intensive care; maximal inspiratory pressure; phrenic nerve; tracheostomy.
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