214 L . Andersen et al .: J Extra Corpor Technol 2023 , 55 , 209 – 217
Figure 6 . Illustration of COx index recordings in patient plotted in bins of MAP . Lower MAP limit for preserved CA identified at 55 mmHg . Limit for disturbed autoregulation : COx > 0.4 ( green dotted line ). Error bars show the standard deviation .
Setting the COx index threshold On the critical evaluation of the threshold for the COx index , whichistypicallysetto > 0.4 [ 18 , 33 ], it should be noted that a correlation coefficient ( r ) at this level indicates a weak association , where the degree of explanation ( r 2 ) equals just 16 %. From a statistical viewpoint , there is room for a significant degree of uncertainty . Increasing the COx threshold above the 0.4 level would probably increase the sensitivity , but at the same time significantly decrease the success rate , when loss of CA is detected . Where the balance between the magnitude of COx and the success rate is optimal is yet to be defined . The influence of a constantly high rSO 2 is of interest . It may explain , why only a few patients demonstrated abnormal CA .
The COx threshold > 0.4 to define impaired CA has become more of a gold standard [ 24 ]. However , this threshold was obtained from animal experiments performed in the naive piglet brain [ 16 , 18 ]. In these experiments , MAP was gradually decreased by inflating a balloon catheter placed in the inferior vena cava as a method to identify the lower blood pressure limit of CA . The balloon placed in the inferior cava obstructed the venous return and lowered the filling pressure of both the right and left ventricles . The observed decrease in MAP was , therefore , most likely caused by a simultaneous decrease in cardiac output [ 34 , 35 ]. Cardiac output was unfortunately not reported during these experiments so this cannot be confirmed . It is difficult to isolate the circulatory effects of MAP manipulations even in the setting of an animal experiment , without interfering with other complex regulatory mechanisms and in this case specifically related to the influence on the CBF .
Autoregulation
of cerebral blood flow and cardiopulmonary bypass
The systemic blood flow is established by the pressure wave generated by cardiac muscle contractions . The pressure build-up within the left and right ventricle during systole is continuous until it overtakes the backpressure on the other side of the opening aortic and pulmonary valve . The ejected stroke volume will elevate the systemic and pulmonary blood pressure at two completely different levels directly related to the vascular resistance in the respective circulatory beds . Of note is that the cardiac output will still be the same within both vascular beds , despite these key differences [ 36 ]. The relative difference in blood pressure between the systemic and pulmonary circulation is five-fold [ 37 ]. What this tells us is that the blood pressure per se does not say anything about its relation to the actual blood flow unless vascular resistance is known .
This reasoning can be applied in the process of CPB . The main objective in this context is to establish and maintain adequate systemic blood flow traditionally based on a fixed index related to the patient ’ s body surface area [ 38 ] or more recently to balance the patient ’ s global oxygen demand [ 39 , 40 ]. Blood pressure is still important but is adjusted secondary to the systemic blood flow demand . The approach is in total contrast to overall general clinical practice where blood pressure is the focus and represents the gold standard for the evaluation of patient health and circulatory status [ 41 ]. Blood pressure measurements are easily accomplished , combined with a strong historical impact , which also explains its central role in clinical medicine .
The systemic blood flow delivered from the heart-lung machine will be distributed in a hierarchical manner to all organs and vascular beds [ 42 ]. With respect to cerebral circulation , what would be most important : “ flow or pressure ”? Anyone with clinical experience from CPB will know that a momentous change in the systemic blood flow will respond with a reciprocal momentous change in systemic blood pressure . Therefore , it is difficult to isolate one component from the other ; it merely confirms that these components are closely linked . Is this observation of scientific relevance ? Probably yes , at least with reference to dynamic pressure variations measured in the time domain . Ševerdija et al . showed how variations of the systemic blood flow at 0.1 Hz during CPB covariated with both the CBF and the systemic blood pressure verified by the graphical representation in Figure 7 [ 43 ].
Much of our understanding regarding how CBF control is from the seminal publication by Lassen in 1959 [ 5 ]. Extrapolation of cross-sectional comparisons from 11 groups including ( a total of 376 subjects ) across 7 publications was presented in a graph showing the relation between systemic blood pressure and CBF . Only two data points formed the threshold for a lower blood pressure limit and none for the upper limit . The remaining were aggregated forming a straight line . Despite these formal limitations regarding the research methodology , blood pressure is still regarded as one of the essential components for autoregulation of the CBF . An updated interpretation of Lassen ’ s autoregulation curve suggests it only applies to more gradual amendments of the blood pressure , which will have little or no effect on the CBF . Examples are the treatment of hypertension or the downregulation of the blood pressure occurring during nocturnal sleep [ 11 ].
Even if systemic blood flow and blood pressure are essential in relation to CBF control , other equally essential regulatory mechanisms are also involved , such as neurovascular coupling [ 44 ], cerebrovascular carbon dioxide tension , and oxygen reactivity [ 45 ]. This emphasizes the fact that CA should not be evaluated from the perspective of one of these regulatory