• 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.
• 1 Department of Critical Care, Royal Columbian Hospital, New Westminster, British Columbia, Canada.
• Am. J. Respir. Crit. Care Med. 2017 Feb 1; 195 (3): 339-348.

RationaleVentilator-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.ObjectivesWe tested a novel, central line catheter-based, transvenous phrenic nerve pacing therapy for protecting the diaphragm in sedated and ventilated pigs.MethodsEighteen 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 ResultsCumulative 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.ConclusionsThese results suggest that early transvenous phrenic nerve pacing may mitigate ventilator-induced diaphragm dysfunction.

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