Cerebral Blood Flow and Blood Pressure: Dependent or Codependent?

Critical Care Medicine www.ccmjournal. org 1007 In this issue of Critical Care Medicine, Sekhon et al (1) used the pressure reactivity index (PRx) to indirectly monitor cerebral autoregulation in ten patients with hypoxic/ ischemia brain injury after resuscitation from cardiac arrest. During 50% of monitored time, PRx, which consists of a moving Pearson’s correlation coefficient between mean arterial pressure (MAP) and intracranial pressure (ICP), exceeded a threshold of 0.3, that is, ICP, and by inference cerebral blood flow (CBF), tended to increase or decrease in association with increases or decreases in MAP. Based on this assessment of autoregulation, the investigators derived for this specific group of patients a mean optimal MAP, defined as an MAP associated with adequate brain perfusion, of 89 ± 11 (sd) mm Hg (1). Cerebral pressure autoregulation is an integral mechanism of cerebral circulatory control. Impaired cerebral autoregulation is associated with critical neurologic illness. In traumatic brain injury (TBI), use of PRx to determine optimal cerebral perfusion pressure (CPP) demonstrated a strong association between adverse outcome and deviations of actual from individually determined optimal CPP (2). Because of the important clinical implications of cerebral autoregulation, what follows is a brief review of the phenomenon and its assessment in experimental and clinical circumstances. The ability of the cerebral circulation to increase or decrease cerebral vascular resistance (CVR) in response to alterations in local and systemic physiologic variables has been recognized since 1890, when Roy and Sherrington (3) observed that “. the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity. ” Although Roy and Sherrington (3) theorized that the cerebral circulation maintained the brain’s internal environment by reacting to physiologic changes, including blood pressure, they lacked methodologies to test their landmark hypothesis. Fog in 1939 reported dilation and constriction in pial arteries in response to changes in arterial blood pressure (4). Subsequently, Lassen (5) first advanced the specific concept of CBF pressure autoregulation, based on correlations in humans between blood pressure and CBF measured by the Kety-Schmidt nitrous oxide technique. Lassen (5) defined pressure autoregulation as the ability of the cerebral circulation to maintain a constant level of CBF despite primary changes in CPP (CPP = MAP–ICP or central venous pressure, whichever is greater) (5). In response to changes in CPP, cerebral arteries and arterioles increase or decrease CVR (CVR = CPP × CBF). Because vascular resistance is inversely proportional to vessel radius to the fourth power, small variations in cerebral arterial/ arteriolar diameter result in large changes in CVR (6). Cerebral pressure autoregulation is one of several well-characterized cerebral vascular responses to changes of physiologic variables, including Paco 2 (7), Pao 2 (6, 7), extracellular pH (8), brain metabolic activity (9), and hematocrit (10). Rigorous assessment of cerebral pressure autoregulation requires a primary change in CPP, the independent variable, accompanied by measurements of CBF, the dependent variable (Fig. 1A). Direct measurements of CPP and CBF and calculation of CVR permit determination of the autoregulatory index (Δ% CPP × Δ% CVR). In TBI patients, Muizelaar et al (11), using pharmacologic manipulation of MAP and inhaled xenon-133 clearance measurements of CBF, defined intact autoregulation as an autoregulatory index less than or equal to 2, that is, if CPP increased or decreased, CVR decreased at least half as much. This calculation occurs at equilibrium and is considered a static measure of the integrity of cerebral pressure autoregulation. In contrast, Aaslid et al (12) proposed a dynamic measure of autoregulation in which a thigh cuff, inflated above systolic pressure for 2–3 minutes, is suddenly released, resulting in a decrease of MAP of approximately 20 mm Hg. As MAP decreased, middle cerebral flow velocity also decreased, then, as CVR decreased in response to decreased MAP, rapidly increased over a few seconds. Cerebral autoregulation cannot be assessed accurately until the response of CVR reaches equilibrium. In individual patients, tests of dynamic autoregulation provide a more nuanced assessment than do tests of static autoregulation, which require longer time intervals. More importantly, assessment of cerebral pressure autoregulation may be confounded if CPP, rather than being an independent variable, is a variable that, like CBF, is dependent on changes in another independent variable. Figures 1B–D demonstrate this potential problem with interpretation. In Figure 1B, brain activation, for example, by pain, is an independent variable that is associated with dependent changes in MAP/CPP and also (Fig. 1C) with dependent changes in CBF (and inverse changes in CVR). In this circumstance, if MAP/ CPP is plotted, as if it were the independent variable, on the x-axis against CBF on the y-axis, there is apparent disruption of pressure autoregulation. Therefore, interpretation of pressure autoregulation is potentially confounded by changes in 0090-3493