title: Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: 1 Department of Critical Care, Royal Columbian Hospital, New Westminster, British Columbia, Canada.|2 Department of Respiratory Therapy, Royal Columbian Hospital, New Westminster, British Columbia, Canada.|3 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Steven C
authors: http://orcid.org/0000-0002-2624-640X
authors: SC
authors: Reynolds
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Ramasamy
authors: R
authors: Meyyappan
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Viral
authors: V
authors: Thakkar
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Bao D
authors: BD
authors: Tran
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Marc-André
authors: MA
authors: Nolette
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Gautam
authors: G
authors: Sadarangani
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.
authors: Rodrigo A
authors: RA
authors: Sandoval
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.|5 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Laura
authors: L
authors: Bruulsema
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.|5 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Brett
authors: B
authors: Hannigan
authors: 5 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Jason W
authors: JW
authors: Li
authors: 2 Department of Respiratory Therapy, Royal Columbian Hospital, New Westminster, British Columbia, Canada.
authors: Elizabeth
authors: E
authors: Rohrs
authors: 2 Department of Respiratory Therapy, Royal Columbian Hospital, New Westminster, British Columbia, Canada.
authors: Jason
authors: J
authors: Zurba
authors: 4 Lungpacer Medical Inc., Burnaby, British Columbia, Canada; and.|5 Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Joaquín Andrés
authors: http://orcid.org/0000-0003-2259-1908
authors: JA
authors: Hoffer
mesh_terms: D000818:Animals; D002405:Catheterization, Central Venous / Q000379:methods*; D003964:Diaphragm / Q000503:physiopathology*; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods*; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010791:Phrenic Nerve / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D013552:Swine
keywords: atrophy; electrical stimulation; mechanical ventilation; ventilator weaning