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Dres M, de Abreu MG, Merdji H, Muller-Redetzky H, Dellweg D, Randerath WJ, Mortaza S, Jung B, Bruells C, Moerer O, Scharffenberg M, Jaber S, Besset S, Bitter T, Geise A, Heine A, Malfertheiner MV, Kortgen A, Benzaquen J, Nelson T, Uhrig A, Moenig O, Meziani F, Demoule A, Similowski T, Investigators R-SG: Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients. Am J Respir Crit Care Med 2022; 205: 1169-1178

November 19, 2022

Rationale:
Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation.

Objectives:
To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure.

Methods:
Multicenter, open-label, randomized, controlled study. Patients aged >18 years on invasive mechanical ventilation for >4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain.

Measurements and Main Results:
The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [210 to 25]), P = 0.59. Mechanical ventilation duration (mean 6 SD) was 12.7 6 9.9 days and 14.1 6 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was 117% and 214%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain)

Conclusions:
Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction.
Clinical trial registered with www.clinicaltrials.gov (NCT 03096639) and the European Database on Medical Devices (CIV-17-06-020004)

Keywords: diaphragm weakness; weaning; mechanical ventilation; ventilator-induced diaphragmatic dysfunction

At a Glance Commentary

Scientific Knowledge on the Subject:
Ventilator-induced diaphragm dysfunction (VIDD) is frequently observed in patients with difficult weaning and prolonged mechanical ventilation. There is currently no established strategy to directly treat or reverse VIDD.
What This Study Adds to the Field:
Although bilateral phrenic nerve stimulation did not increase the proportion of successful weaning from mechanical ventilation compared with the standard of care, it resulted in substantial improvements in inspiratory pressure generation capacity without major safety issues. In the absence of previous clinical data, these findings suggest that diaphragm pacing could be effective in mitigating diaphragm dysfunction in patients who are difficult to wean from mechanical ventilation.