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), 0.78‐0.89] vs. 1.10 [IQR, 1.02‐1.24]; P = 0.001). Compared with control animals (24.6 &mgr;m2/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 &mgr;m2/kg; IQR, 15.3‐23.7; P = 0.005) but not in the ventilated‐paced group (24.9 &mgr;m2/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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