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  Am. J. Resp. Crit. Care Med. Feb 1, 2017, vol. 135, no. 3: 339-348

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), 0.78–0.89] vs. 1.10 [IQR, 1.02–1.24]; P = 0.001). Compared with control animals (24.6 μm2/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 μm2/kg; IQR, 15.3–23.7; P = 0.005) but not in the ventilated-paced group (24.9 μm2/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.

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