Use of the general health questionnaire in clinical work.

Mechanical ventilation (MV) may lead to ventilator-induced diaphragm dysfunction (VIDD). VIDD is associated with difficult MV weaning and longer MV duration. Mitigating VIDD may thus improve outcomes in patients on prolonged MV. We conducted a preliminary multicenter, open label, randomized controlled trial of temporary transvenous diaphragm neurostimulation (TTDN) using a multi-electrode stimulating central venous catheter (Lungpacer Diaphragm Pacing Therapy System) in difficult-to-wean MV patients. Patients on MV for >96 hours with at least two failed spontaneous breathing trials and satisfying readiness to wean criteria were randomized (1:1) to TTDN (up to 120 stimulations per day; up to 30 days) or standard of care (SoC). Outcomes assessed included the proportion of patients successfully weaned, MV duration, 30-day survival, and maximal inspiratory pressure (MIP). 112 patients were randomized (57 TTDN; 55 SoC). TTDN was successfully delivered in 75% of cases. The frequency of serious adverse events was similar in both groups. For TTDN and SoC, respectively, the incidence of successful weaning was 82% and 74% (p=0.586); MV duration was 12.7±9.9 and 14.1±10.8 days (p=0.498); 30-day survival was 93% and 85% (p=0.216); MIP increased by 17±3 cmH2O vs. 5±2 cmH2O (p=0.001), with a significant stimulation dose-response relationship in TTDN patients. TTDN is feasible and safe in difficult to wean patients. A significant diaphragm-related improvement in MIP was achieved independent of patients9 cooperation.This study will help define the patient population and effect size to appropriately power future studies for clinical efficacy.