Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation.

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 control animals. 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 [interquartile range (IQR), 0.78-0.891 vs. 1.10 [IQR, 1.02-1.24]; P = 0.001). Compared with control animals (24.6 mu m(2)/kg; IQR, 21.6-26.0), median myofiber cross-sectional areas normalized to weight and sarcomere length were significantly smaller in the ventilated-not paced (17.9 mu,m(2)/kg; IQR, 15.3-23.7; P = 0.005) but not in the ventilated-paced group (24.9 mu m(2)/kg; IQR, 16.6-27.3; P = 0.351). After 60 hours of mechanical ventilation all six ventilated-paced subjects tolerated 8 minutes of intense phrenic stimulation, whereas three of six ventilated-not paced subjects did not (P = 0.055). There was a nonsignificant decrease in diaphragm tetanic force production over 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.