The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia.

Although acute respiratory acidosis may be a sign of impending respiratory failure in spontaneously breathing patients, it is commonly encountered in intubated patients with acute lung injury (ALI). This is especially the case now that limiting tidal volumes and airway pressures have been proven to reduce mortality in ALI, presumably by reducing additional lung injury caused by mechanical ventilation itself [1]. A respiratory acidosis arising from lung-protective ventilation strategies has been termed permissive hypercapnia [2–5]. As the name indicates, permissive hypercapnia has been regarded as an inconvenient side-effect that must be tolerated in order to realise the mortality benefits of a low lung-stretch strategy. There is growing evidence that hypercapnic acidosis may itself minimise or reduce lung injury as a result of suppressing inflammatory events. The mechanism(s) for this effect is (are) not entirely known. Nonetheless, there was sufficient suggestive data from cell culture and isolated organ studies over the past two decades for LAFFEY and KAVANAGH [6] not only to support the use of permissive hypercapnia but also to advocate the use of "therapeutic hypercapnia" through the addition of carbon dioxide (CO 2) to the inspired gas. In addition to the possibility of improved outcomes due to anti-inflammatory effects, hypercapnic acidosis has effects on ventilation-perfusion matching that improve gas exchange. Therapeutic hypercapnia has previously been shown to increase arterial oxygena-tion by this mechanism in normal animals [7, 8] and in a sheep model of Klebsiella pneumonia [9]. The only study of changes in gas exchange with permissive hypercapnia in humans with ALI showed an increase in shunt [10]. This was most likely due to a reduction in tidal volume used to produce a hypercapnic acidosis than to permissive hypercapnia itself. Thus, the effects of hypercapnic acidosis on ventilation, perfusion, and their regional matching in injured lungs remain largely unknown. While the acute respiratory distress syndrome (ARDS) Network data have stated that physiological end-points such as gas exchange do not necessarily correlate with outcome, there are unanswered questions about the tolerable limits of hypoxaemia and acidosis which may influence clinical outcomes. With the growing acceptance of permissive hypercapnia in support of patients with lung injury on mechanical ventilation, studies such as that by NAOKI et al. [11] in this issue of the European Respiratory Journal, will be essential for a full understanding of the mechanisms by which hypercapnic acidosis affects gas exchange and inflammation. The authors have revealed an obviously …