In this review the role of PaCO2 in regulating cerebral blood flow and flow/metabolism coupling, as well as its impact on intracellular metabolic processes are discussed. Starting with a discussion of alpha-stat versus pH-stat ventilatory management, the apparently contradictory finding of exacerbation of ischemic injury by extracellular acidosis in some experimental models versus others in which neuroprotection is evidenced is discussed and contrasted with the conclusion that the relatively small degree of change in pH associated with clinical changes in PaCO2 is unlikely to directly impact ischemia/reperfusion processes. However, examples of susceptible patients in whom relatively small changes in PaCO2 can produce adverse effects on cerebral perfusion are also illustrated re-emphasizing the necessity for individualization rather than generalization of care.
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