Conservative fluid management prevents age-associated ventilator induced mortality

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 l...

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Veröffentlicht in:Experimental gerontology 2016-08, Vol.81, p.101-109
Hauptverfasser: Herbert, Joseph A., Valentine, Michael S., Saravanan, Nivi, Schneck, Matthew B., Pidaparti, Ramana, Fowler, Alpha A., Reynolds, Angela M., Heise, Rebecca L.
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container_end_page 109
container_issue
container_start_page 101
container_title Experimental gerontology
container_volume 81
creator Herbert, Joseph A.
Valentine, Michael S.
Saravanan, Nivi
Schneck, Matthew B.
Pidaparti, Ramana
Fowler, Alpha A.
Reynolds, Angela M.
Heise, Rebecca L.
description 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. •4h mechanical ventilation causes lung injury and death in elderly mice.•The effect is strongly blunted in young subjects or by using a low tidal volume.•Pulmonary edema was hypothesized as an upstream mechanism of this mortality.•A novel conservative fluid protocol was proposed to attenuate these effects.•Conservative fluid support significantly decre
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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. 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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. 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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. •4h mechanical ventilation causes lung injury and death in elderly mice.•The effect is strongly blunted in young subjects or by using a low tidal volume.•Pulmonary edema was hypothesized as an upstream mechanism of this mortality.•A novel conservative fluid protocol was proposed to attenuate these effects.•Conservative fluid support significantly decreased edema and mortality in old mice.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>27188767</pmid><doi>10.1016/j.exger.2016.05.005</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6602-6700</orcidid><oa>free_for_read</oa></addata></record>
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subjects Aging
Animals
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Fluid management
Fluid Therapy - methods
Inflammation - pathology
Kaplan-Meier Estimate
Lung - pathology
Male
Mechanical ventilation
Mice
Mice, Inbred C57BL
Pulmonary edema
Respiratory mechanics
Tidal Volume
Ventilator associated mortality
Ventilator-induced lung injury
Ventilator-Induced Lung Injury - mortality
Ventilator-Induced Lung Injury - pathology
Ventilator-Induced Lung Injury - therapy
title Conservative fluid management prevents age-associated ventilator induced mortality
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