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Hypercapnic acidosis in ventilator-induced lung injury.

Research paper by Vanya V Peltekova, Doreen D Engelberts, Gail G Otulakowski, Satoko S Uematsu, Martin M Post, Brian P BP Kavanagh

Indexed on: 10 Mar '10Published on: 10 Mar '10Published in: Intensive Care Medicine



Abstract

Permissive hypercapnia is established in lung injury management. Therapeutic hypercapnia causes benefit or harm, depending on the context. Ventilator-associated lung injury has a wide spectrum of candidate mechanisms, affording multiple opportunities for intervention such as hypercapnia to exert benefit or harm.To confirm (1) that hypercapnia attenuates in vivo ventilator-induced lung injury (VILI); (2) biological plausibility of such protection (e.g., dose-response, time series, inflammatory profile); and (3) that the associated biochemical events are consistently beneficial.A mouse model of VILI was established in vivo. Injurious ventilation was established, hypercapnia applied and markers of inflammation measured.Lung injury was quantified by gas exchange, elastance, microvascular leak, histology and levels of cytokines and eicosanoids, cyclooxygenase and tissue nitrotyrosine.Injurious ventilation caused significant lung injury (mechanics, microvascular leak, histology) and release of inflammatory cytokines, chemokines and eicosanoids. Hypercapnia attenuated these responses, with dose-response and time-dependent effects. No adverse effects of hypercapnia were observed in controls. Hypercapnia suppressed the transcription (mRNA) and translation (protein) of the major inducible prostanoid-generating enzyme (COX-2), but the effects on the downstream eicosanoids were modest. However, hypercapnia significantly increased lung tissue nitrotyrosine-at PaCO(2) levels that were protective.Hypercapnia provided consistent and biologically plausible in vivo protection against VILI, but elevated lung tissue levels of nitro-tyrosine as previously described in sepsis. Clinicians and those designing clinical trials need to be aware of the potential for detrimental effects when using hypercapnia in order to balance benefits versus harm with this approach.