To the Editor:—
In the December 1998 issue of ANESTHESIOLOGY, Lenz et al. 1reported that close coupling between local cerebral blood flow (LCBF) and glucose utilization (LCGU) is preserved in animals anesthetized with 1 minimum alveolar concentration (MAC) of isoflurane or sevoflurane, (fig. 2). 1This conclusion seems to have been based on linear regression of the mean values of LCBF against LCGU for each of the regions examined and evaluation of the derived correlation coefficients (fig. 2). 1
Regression analysis of LCBF and LCGU values derived from autoradiographic experiments has been criticized on methodologic and statistical grounds. 2“Blood flow–metabolism coupling” conventionally refers to changes in blood flow within a brain region in response to changes in metabolism in that region. 3,4Evaluation of LCBF in relation to LCGU in many different brain regions under one particular set of conditions does not fit this concept. 2Regression analysis of LCBF on LCGU examines the homogeneity of the ratio of LCBF to LCGU among the various brain regions examined. 2
The results of the study by Lenz et al. 1suggest that isoflurane and sevoflurane alter the LCBF:LCGU ratio. We compared the LCBF:LCGU ratios for the 40 structures studied in the five conditions from their data (tables 1 2 and 3). Isoflurane and sevoflurane both increased the mean ratio of LCBF:LCGU in a dose-dependent fashion, with isoflurane producing the most marked effect (table 1).
This analysis remains open to the statistical criticism 2that the variability between animals was eliminated by using mean values of LCBF and LCGU, thereby underestimating the real uncertainty in the LCBF–LCGU relation.
The experimental design used by Lenz et al. 1does permit exploration of blood flow–metabolism coupling through analysis of the relation between LCBF and LCGU within specific brain regions as the LCGU is depressed by increasing concentrations of anesthetic. Figure 1
(based on data 1from their tables 2 and 3) shows the LCBF response to increasing anesthetic concentrations in two brain regions, with similar mean values for LCGU and LCBF in the conscious animals. The data suggest that LCBF in these two brain regions responds differently to increasing concentrations of isoflurane and sevoflurane, because, despite similar decreases in LCGU with increasing MAC multiples, LCBF appears to decrease in auditory cortex but to increase in the inferior colliculus. The analysis of these data 2could not be attempted with the information provided in the original report. 1
In summary, further analysis of the data reported by Lenz et al. 1supports previous observations that inhalational anesthetics increase the ratio of mean cerebral blood flow/cerebral metabolic rate for oxygen (CBF/CMRO2) in a dose-dependent fashion. 5Inspection of the data for individual brain regions suggests that a detailed analysis 2of flow–metabolism coupling may reveal significant regional differences.