Prolonged mechanical ventilation (MV) increases the risk of death, disability, and healthcare costs. Over one-third of patients entering the weaning phase experience difficulty, often due to diaphragm dysfunction. Traditional inspiratory muscle training has shown limited success.
Transvenous diaphragm neurostimulation, a novel method involving phrenic nerve stimulation via a central venous catheter, has demonstrated safety and potential to improve inspiratory strength. The RESCUE-3 randomised clinical trial aimed to evaluate the safety and efficacy of this approach in improving weaning outcomes in patients with difficult weaning compared to standard care.
The clinical study involved adults on mechanical ventilation for ≥96 hours who met weaning readiness criteria but had failed at least two prior weaning attempts. Participants were randomised to receive either twice-daily transvenous diaphragm neurostimulation (Treatment) or standard care (Control). The primary outcome was successful weaning by Day 30. Secondary outcomes included ventilation duration and mortality by Day 30.
The RESCUE-3 trial was stopped early after enrolling 216 patients due to slow enrollment and financial constraints. Among the modified intent-to-treat population (102 Treatment, 114 Control), 70% of Treatment patients and 61% of Control patients were successfully weaned by Day 30. Treatment reduced ventilation duration by an adjusted average of 2.5 days. Serious adverse events occurred more frequently in the Treatment group (36% vs. 24%), while mortality rates were similar (9.8% Treatment vs. 10.5% Control), with no statistically significant difference in death risk.
Twice-daily transvenous diaphragm neurostimulation was associated with a high probability of improving weaning success by Day 30, reducing ventilation duration, increasing ventilator-free days, enhancing respiratory muscle strength, and lowering rates of reintubation. Although the Treatment group experienced more adverse events, the overall benefit profile suggests the therapy is well-tolerated and may accelerate recovery.
Unlike traditional inspiratory muscle training, this method enables passive diaphragm activation without patient effort. The study’s early termination, due to financial and logistical constraints, limits the strength of conclusions. Nonetheless, the trial supports diaphragm neurostimulation as a promising strategy to aid liberation from prolonged mechanical ventilation, with further research needed to optimise dosing and timing.
Source: AJRCCM
Image Credit: iStock
References:
Dres M, Ewert R, Conrad SA et al. (2025) Temporary Transvenous Diaphragm Neurostimulation for Weaning from Mechanical Ventilation (RESCUE-3). American Journal of Respiratory and Critical Care Medicine.
