Cerebral metabolic rate in hypercapnia: controversy continues.

Thirty years ago, a publication by Seisjo, entitled ‘Cerebral metabolic rate in hypercarbia—a controversy’ summarized the current state of knowledge related to the influence of hypercapnia (increased pCO2) on cerebral metabolic rate of oxygen consumption (CMRO2) (Siesjo, 1980). Seisjo quoted a number of papers that provided controversial results ranging from reduced, to unchanged, to increased CMRO2 and concluded his paper with the following comment: ‘Since hypercarbia is a common pathophysiologic condition, its effects on cerebral metabolism and blood flow are of obvious concern to many scientists and clinicians, anesthesiologists included. It is disconcerting that 30 years after the first quantitative report (Kety and Schmidt, 1948), we still do not know how hypercarbia affects cerebral metabolic rate.’ Today, 30 years later, scientists still debate this matter. In the current issue of this journal, Jain et al (2011) report on the measurement of global CMRO2 in human brain during rest and hypercapnia. The authors developed a magnetic resonance imaging (MRI)-based technique that allows simultaneous measurements of cerebral blood flow (CBF) and venous blood oxygenation level (SvO2) with a temporal resolution of 30 seconds. Using the widely accepted principle that CMRO2 is proportional to the product of CBF and arterial–venous difference in blood oxygenation level, Jain et al found decreases in CMRO2 during mild hypercapnia (5% inspired CO2) that were small and not significant. At the same time, they found significant increases in CBF and SvO2—a result that is in agreement with practically all previous studies. A similar result was recently reported by Chen and Pike (2010), whose findings also suggested no significant change in global CMRO2 with mild hypercapnia. However, in another recently published study, Xu et al (2011) reported that mild hypercapnia resulted in a 13% suppression of CMRO2. This result is similar to (for example) previously published data in rhesus monkey (Kliefoth et al, 1979), but is opposite to reported increases in CMRO2 in rats (Horvath et al, 1994). Some of this inconsistency in results between human and animal studies can be attributed to the different physiological conditions under which the experiments were performed. However, the data in Jain et al (2011), Chen and Pike (2010) and Xu et al (2011) were obtained in normal awake humans, and one can only speculate that differences should be attributed to differences in experimental techniques. Substantial progress has been made in developing in vivo methods to study brain metabolism and hemodynamics since the initial publication (Kety and Schmidt, 1948), and the paper by Jain et al contributes significantly to this development. Yet, the accuracy of this and other methods must be further scrutinized before we can put narrowenough error bars on the results to provide an accurate answer to the old question: How does hypercapnia influence brain metabolism? One more compelling reason to seek a definitive answer to this question lies in current attempts to use hypercapnia to tease out the effects of changes in blood flow and brain metabolism during functional brain activation (so-called calibrated functional MRI (Davis et al, 1998; Kim et al, 1999)). We hope that the paper by Jain et al will help in resolving this controversy as well.