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ATSJournals Publication – Mitigation of Ventilator-Induced Diaphragm Atrophy by Transvenous Phrenic Nerve

Mitigation of Ventilator-Induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation
Steven C Reynolds, Ramasamy Meyyappan, Viral Thakkar, Bao D Tran, Marc-André Nolette, Gautam Sadarangani, Rodrigo A Sandoval, Laura Bruulsema, Brett Hannigan, Jason W Li, Elizabeth Rohrs, Jason Zurba, and Joaquín Andrés Hoffer

Am J Respir Crit Care Med. First published online August 08, 2016 as doi:10.1164/rccm.201502-0363OC


Rationale: Ventilator-induced Diaphragm Dysfunction is a significant contributor to weaning difficulty in ventilated critically ill patients. It has been hypothesized that electrically pacing the diaphragm during mechanical ventilation could reduce diaphragm dysfunction.

Objectives: We tested a novel, central line catheter-based, transvenous phrenic nerve pacing therapy for protecting the diaphragm in sedated and ventilated pigs.

Methods: Eighteen Yorkshire pigs were studied. Six pigs were sedated and mechanically ventilated for 2.5 days with pacing on alternate breaths at intensities that reduced the ventilator pressure-time-product by 20%-30%. Six matched subjects were similarly sedated and ventilated, but were not paced. Six pigs served as never-ventilated, never-paced controls.

Measurements and Main Results: Cumulative duration of pacing therapy ranged from 19.7 to 35.7 hours. Diaphragm thickness assessed by ultrasound and normalized to initial value showed a significant decline in ventilated-not paced but not in ventilated-paced subjects (0.84, IQR=0.78-0.89 vs. 1.10, IQR=1.02-1.24; P=0.001). Compared to Controls (24.6 µm2/kg, IQR=21.6-26.1), median myofiber cross-sectional areas normalized to weight and sarcomere length were significantly smaller in ventilated-not paced (17.8 µm2/kg, Interquartile Range=15.3-23.7; P=0.001) but not in the ventilated-paced group (24.9 µm2/kg, Interquartile Range =16.6-27.3; P=0.189). After 60 hours of mechanical ventilation all 6 ventilated-paced subjects tolerated 8 minutes of intense phrenic stimulation whereas 3 of 6 ventilated-not paced subjects did not (P=0.055). There was a non-significant decrease in diaphragm tetanic force production over the course of the experiment in the ventilated-paced and ventilated-not paced groups.

Conclusions: These results suggest that early transvenous phrenic nerve pacing may mitigate Ventilator-induced Diaphragm Dysfunction.