Cerebral Autoregulation: The Concept the Legend the Promise

  
By Christos Lazaridis
First Online: 25 January 2021

Pressure-flow autoregulation refers to the physiologic phenomenon of the maintenance of steady flow within a range of arterial blood pressure (ABP). It is one of the mechanisms that collectively contribute to the regulation of cerebral blood flow (CBF). Brain tissue has high metabolic demand and limited substrate storage capacity; for this, efficient and precise regulation of CBF is required. The other mechanisms involved describe relationships between CBF and the partial pressures of CO2 and O2, as well as perivascular pH (chemical vasoreactivity), flow–metabolism coupling, and autonomic neurogenic control of the vasculature. Truth be told, there is much more that we do not know about these mechanisms and how they overlap, compared with what we would call “facts.” Nevertheless, the observation about vascular pressure reactivity was made over a century ago. Bayliss [1] reported on myogenic vasomotor tone change in response to blood pressure fluctuations. However, it was not until 1959 and the work of Lassen that gave us the textbook static cerebral pressure autoregulation graph. Lassen constructed a plot of average ABP and total CBF from seven studies involving 11 different patient groups exhibiting variable ABP levels due to either pharmacologic or pathologic reasons [2]. The plot is classically depicted as having a plateau section of unvarying CBF between upper and lower inflection points beyond which CBF is linearly and passively related to ABP. It turns out that as neat as the graph appears, it is likely an oversimplification, may be a function of the experimental conditions in which it is assessed, and its definitive efficacy remains uncertain. Other controversies include the role of the speed and direction in ABP change (there is evidence of hysteresis, i.e., the brain defends more effectively against acute hypertension than hypotension); the anatomical site of regulation, as in pial arterioles vs. larger intracranial arteries; myogenic vs. neurogenic vs. local metabolic modulation; treating as separate entities chemical and pressure reactivity [3].

Despite incomplete understanding, the relationship between ABP fluctuations (spontaneous or induced) and intracranial pressure (ICP) is clinically commonly observed and exploited in order to identify an optimal combination between mean arterial pressure (MAP) and ICP (and derivative cerebral perfusion pressure; CPP). The so-called MAP challenge is incorporated in recent targeted protocols for the management of severe traumatic brain injury (TBI) such as the protocol for the BOOST-3 trial and the SIBICC algorithm [4]. An intuitive idea arises, that of a method of continuous bedside monitoring of cerebrovascular pressure reactivity and/or pressure-flow autoregulation that would not be dependent on artificial manipulation of ABP. This idea was given form by Czosnyka et al. by deriving the pressure reactivity index (PRx); a moving correlation coefficient from 30 consecutive 10-s averages of ICP and ABP waveforms [5]. Since then, the Cambridge group (and disciples) has generated a large body of literature including new indices, validation studies, and observational outcome data in various acute brain injury (ABI) pathologies. It is useful to offer an epigrammatic account of these accomplishments: PRx has been shown to independently correlate with clinical outcome after TBI [6]; change of PRx from zero or negative to positive identifies Lassen’s lower inflection point under experimental conditions [7]; PRx plotted against CPP shows a U-shaped curve, whose minimum theoretically corresponds to the plateau section of the curve. This value was termed the “optimal CPP” (CPPOPT). Pressures lower and higher than CPPOPT have been associated with worse outcomes [8]; intracranial hypertension in the presence of pressure passivity is related to worse outcomes independently from the absolute ICP burden, which motivates the idea of individualizing the ICP threshold [9].

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