Cerebral Autoregulation: From Models to Clinical Applications

Abstract

Short-term regulation of cerebral blood flow (CBF) is controlled by myogenic, metabolic and neurogenic mechanisms, which maintain flow within narrow limits, despite large changes in arterial blood pressure (ABP). Static cerebral autoregulation (CA) represents the steady-state relationship between CBF and ABP, characterized by a plateau of nearly constant CBF for ABP changes in the interval 60-150 mmHg. The transient response of the CBF-ABP relationship is usually referred to as dynamic CA and can be observed during spontaneous fluctuations in ABP or from sudden changes in ABP induced by thigh cuff deflation, changes in posture and other manoeuvres. Modelling the dynamic ABP-CBFV relationship is an essential step to gain better insight into the physiology of CA and to obtain clinically relevant information from model parameters. This paper reviews the literature on the application of CA models to different clinical conditions. Although mathematical models have been proposed and should be pursued, most studies have adopted linear input-output ('black-box') models, despite the inherently non-linear nature of CA. The most common of these have been transfer function analysis (TFA) and a second-order differential equation model, which have been the main focus of the review. An index of CA (ARI), and frequency-domain parameters derived from TFA, have been shown to be sensitive to pathophysiological changes in patients with carotid artery disease, stroke, severe head injury, subarachnoid haemorrhage and other conditions. Non-linear dynamic models have also been proposed, but more work is required to establish their superiority and applicability in the clinical environment. Of particular importance is the development of multivariate models that can cope with time-varying parameters, and protocols to validate the reproducibility and ranges of normality of dynamic CA parameters extracted from these models.

The Leicester cerebral haemodynamics database: normative values and the influence of age and sex

“…Due to the highly effective control exerted by the mechanism of pressure-autoregulation, CBF is normally maintained within narrow limits for mean blood pressures (MBP) in the range 60-150 mm Hg (Paulson, Strandgaard & Edvinsson 1990). Not surprisingly, it is the CBF autoregulation mechanism itself that has been shown to be impaired in a number of conditions such as ischaemic stroke, severe head injury, carotid artery disease, intracranial hypertension, diabetes and liver failure (Aries et al 2010, Czosnyka et al 1996, Dawson et al 2000, Hauerberg, Juhler 1994, Kim et al 2008, Lagi et al 2002, Panerai 2008, White, Markus 1997, van Beek et al 2008.…”

“…The autoregulation index (ARI) proposed by Tiecks et al (Tiecks et al 1995), usually obtained from thigh cuff manoeuvres (Tiecks et al 1995, Aaslid et al 1989, can also be derived by TFA (Panerai et al 1998b) and together with phase has been shown to be the most sensitive parameter to detect abnormalities in CBF regulation (Panerai 2008). Both the ARI and phase have been shown to have satisfactory, but not outstanding, reproducibility (Birch, Neil-Dwyer & Murrills 2002, Brodie et al 2009, Gommer et al 2010.…”

“…To address these two main limitations, the Department of Cardiovascular Sciences, University of Leicester, UK, has constructed a large database incorporating recordings from a series of separate studies that were all performed in the same laboratory, using similar protocols and equipment. Using this new resource, we have extracted normative values of ARI and phase, which are the main parameters of clinical interest (Panerai 2008), and have also, tested the hypotheses that these parameters are not influenced by age and sex. These hypotheses were tested following previous observations showing effect of age and sex on CA and CBFV (Vriens et al 1989, Marinoni et al 1998).…”

Cerebral Autoregulation after Subarachnoid Hemorrhage: Comparison of Three Methods

“…2,6 However, other ways of measuring autoregulation that do not require physical or pharmacological blood pressure stimulation have been described. [19][20][21][22] By using the correlation coefficient method, the dynamic relationship between cerebral blood flow and ABP, encompassing both vasoconstriction and vasodilatation, can be studied. Both TCD and near-infrared spectroscopy (NIRS) are modalities where the correlation coefficient method has been experimentally and clinically verified.…”

Optimising the assessment of cerebral autoregulation from black box models

“…However, given the complexity of the mechanisms controlling cerebral blood flow [21], one cannot be certain whether these parameters directly reflect autoregulation or some (related) physiological phenomenon. Furthermore it is possible that different clinical conditions (or CO 2 levels) have distinct effects [1] and that a single measure of CA may not be optimal for all applications [37]. Throughout this paper we have assumed (as does most of the cited literature) that the parameters used measure cerebral autoregulation, However, given the complexity of the physiology and the often poor correlation found between parameters that have all been considered to measure CA ( [38]), they may not all reflect identical phenomena of cerebrovascular control.…”