title: Conservative fluid management prevents age-associated ventilator induced mortality.
abstract: Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality.
  
  
  
  2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls.
  
  
  
  At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects.
  
  
  
  Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 W Main St, PO Box 843067, Richmond, VA 23284, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Herbert
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 W Main St, PO Box 843067, Richmond, VA 23284, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Valentine
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 W Main St, PO Box 843067, Richmond, VA 23284, United States.
authors.forename: Nivi
authors.initials: N
authors.lastname: Saravanan
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 W Main St, PO Box 843067, Richmond, VA 23284, United States.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Schneck
authors.affiliation: School of Engineering, University of Georgia, United States.
authors.forename: Ramana
authors.initials: R
authors.lastname: Pidaparti
authors.affiliation: Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, United States.
authors.forename: Alpha A
authors.initials: AA
authors.lastname: Fowler
authors.affiliation: Department of Mathematics and Applies Mathematics 1015 Floyd Avenue P.O. Box 842014 Richmond, VA 23284-2014, United States.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Reynolds
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 W Main St, PO Box 843067, Richmond, VA 23284, United States; Department of Physiology and Biophysics VCU School of Medicine 1101 East Marshall Street P.O. Box 980551 Richmond, VA 23298-0551, United States. Electronic address: rlheise@vcu.edu.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Heise
mesh_terms: D000375:Aging; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005440:Fluid Therapy / Q000379:methods*; D007249:Inflammation / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000401:mortality / Q000473:pathology / Q000628:therapy*
keywords: Aging; Fluid management; Mechanical ventilation; Pulmonary edema; Respiratory mechanics; Ventilator associated mortality; Ventilator-induced lung injury