Susceptibility to ventilator induced lung injury is increased in senescent rats

Setzer, Florian; Oschatz, Karsten; Hueter, Lars; Schmidt, Barbara; Schwarzkopf, Konrad; Schreiber, Torsten

doi:10.1186/cc12744

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…These results support the general finding that age increases the incidence and severity of edema (5)(33). They also demonstrate our experimental model’s ability to induce ventilator-associated pulmonary edema with HVT mechanical ventilation and subsequently attenuate it through conservative fluid administration alone.…”

Section: Discussionsupporting

confidence: 90%

“…The first aim of this study was to establish that older mouse subjects when subjected to HVT MV exhibit an increased severity of ventilator-induced lung injury as was recently reported in an aging rat model (33). Wilson et al established that significant stretch induced lung injury in young healthy mice requires mechanical ventilation with tidal volumes approaching 40mg/ml (38).…”

Section: Discussionmentioning

confidence: 93%

“…These settings however are generally considered significantly higher than those used in the clinical management of patients (38)(39). Setzer et al demonstrated that the increased sensitivity of the aging rat lung to mechanical ventilation allowed their group to achieve significant VILI with tidal volumes of 16–24mg/kg (33). So while a tidal volume of 40mg/kg may be more conventionally referred to as “High Tidal Volume”, our HVT protocol is both sufficient to cause ventilator induced injury and mortality in our older subjects and is closer to clinical relevance than other higher HVT standards.…”

Section: Discussionmentioning

confidence: 99%

“…Setzer et al recently demonstrated that HVT (24 ml/kg) MV caused more lung injury in old rat subjects than in their younger counterparts. Lung wet to dry rations, lavage protein and cytokine concentrations, and systemic markers of inflammation were all elevated in the older HVT MV subjects (33). Additionally it has been shown that short-term mechanical ventilation with low tidal volume and hyperoxia increases pulmonary edema, lung inflammation, and decreases diaphragm function in old rats subjects compared to young adults (1).…”

Section: Introductionmentioning

confidence: 99%

“…The changing mechanical properties of the aging lung lead to increases in lung compliance which can predispose the lung to over-distention and increase susceptibility to atelectasis during mechanical ventilation (2)(4)(14)(32). Further, the aging lung exhibits increasingly dysregulated immune/inflammatory responses to injury leading to pathological increases in pro-inflammatory behavior (33)(28). …”

Section: Introductionmentioning

confidence: 99%

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Conservative fluid management prevents age-associated ventilator induced mortality

Herbert

Valentine

Saravanan

et al. 2016

Experimental Gerontology

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Background 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-hosptial 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. Methods 2 month old and 20 month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4 hours 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. Results At 4hrs, 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 1hr in advanced age HVT subjects. In 4hr ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. Conclusion Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 93%