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Intensive Care Medicine
Erschienen in: Intensive Care Medicine 5/2010

01.05.2010 | Experimental

Hypercapnic acidosis in ventilator-induced lung injury

Erschienen in: Intensive Care Medicine | Ausgabe 5/2010

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Abstract

Rationale

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.

Objectives

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.

Methods

A mouse model of VILI was established in vivo. Injurious ventilation was established, hypercapnia applied and markers of inflammation measured.

Measurements

Lung injury was quantified by gas exchange, elastance, microvascular leak, histology and levels of cytokines and eicosanoids, cyclooxygenase and tissue nitrotyrosine.

Main results

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 PaCO2 levels that were protective.

Conclusions

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.
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Metadaten
Titel
Hypercapnic acidosis in ventilator-induced lung injury
Publikationsdatum
01.05.2010
Erschienen in
Intensive Care Medicine / Ausgabe 5/2010
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-010-1787-7

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