INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke.

RATIONALE: Disturbances in dynamic cerebral autoregulation after ischemic stroke may have important implications for prognosis. Recent meta-analyses have been hampered by heterogeneity and small samples. AIM AND/OR HYPOTHESIS: The aim of study is to undertake an individual patient data meta-analysis (IPD-MA) of dynamic cerebral autoregulation changes post-ischemic stroke and to determine a predictive model for outcome in ischemic stroke using information combined from dynamic cerebral autoregulation, clinical history, and neuroimaging. SAMPLE SIZE ESTIMATES: To detect a change of 2% between categories in modified Rankin scale requires a sample size of ∼1500 patients with moderate to severe stroke, and a change of 1 in autoregulation index requires a sample size of 45 healthy individuals (powered at 80%, α = 0.05). Pooled estimates of mean and standard deviation derived from this study will be used to inform sample size calculations for adequately powered future dynamic cerebral autoregulation studies in ischemic stroke. METHODS AND DESIGN: This is an IPD-MA as part of an international, multi-center collaboration (INFOMATAS) with three phases. Firstly, univariate analyses will be constructed for primary (modified Rankin scale) and secondary outcomes, with key co-variates and dynamic cerebral autoregulation parameters. Participants clustering from within studies will be accounted for with random effects. Secondly, dynamic cerebral autoregulation variables will be validated for diagnostic and prognostic accuracy in ischemic stroke using summary receiver operating characteristic curve analysis. Finally, the prognostic accuracy will be determined for four different models combining clinical history, neuroimaging, and dynamic cerebral autoregulation parameters. STUDY OUTCOME(S): The outcomes for this study are to determine the relationship between clinical outcome, dynamic cerebral autoregulation changes, and baseline patient demographics, to determine the diagnostic and prognostic accuracy of dynamic cerebral autoregulation parameters, and to develop a prognostic model using dynamic cerebral autoregulation in ischemic stroke. DISCUSSION: This is the first international collaboration to use IPD-MA to determine prognostic models of dynamic cerebral autoregulation for patients with ischemic stroke.

Inter-subject analysis of transfer function coherence in studies of dynamic cerebral autoregulation.

OBJECTIVE: The gain and phase of the arterial blood pressure (BP)-cerebral blood flow velocity (CBFV) relationship, assessed by transfer function analysis (TFA), are widely used dynamic cerebral autoregulation (CA) metrics, but their reliability depend on the statistical significance of the magnitude squared coherence (MSC) function. We tested a new approach, based on inter-subject data, to estimate the confidence limits of MSC. APPROACH: Five minute beat-to-beat time series of mean arterial BP (MAP, Finometer) and CBFV (transcranial Doppler) were used for intra-subject (MAP and CBFV from same subject) and inter-subject (BP and CBFV swapped between subjects) estimates of MSC. The 95% confidence limit of MSC was obtained by non-parametric methods for the cases of single frequency harmonics in the range (0.02-0.50 Hz), and also from the mean value of all possible frequency intervals in this range. MAIN RESULTS: Intra-subject estimates of MSC were obtained from 100 healthy subjects (48 female, age range: 21-82 years old) allowing calculation of 9900 inter-subject estimates, with 95% confidence limits in excellent agreement with classical values derived from surrogate random data. Confidence limits of MSC, derived from mean values, decreased asymptotically to around 0.16 with the increasing number of harmonics averaged. SIGNIFICANCE: Replacing estimates of MSC at a single frequency harmonic by the mean calculated over the range (0.02-0.30 Hz) could lead to more robust studies of dynamic CA with greater acceptance of recordings, an important consideration in clinical studies where measurements tend to be more susceptible to noise and artefacts.

Sex differences in cerebral haemodynamics across the physiological range of PaCO2.

OBJECTIVE: Cerebral blood flow (CBF) is influenced by changes in arterial CO2 (PaCO2). Recently, cerebral haemodynamic parameters were demonstrated to follow a four parameter logistic curve offering simultaneous assessment of dCA and CO2 vasoreactivity. However, the effects of sex on cerebral haemodynamics have yet to be described over a wide range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in healthy volunteers at baseline, and in response to hypo- (-5 mmHg and -10 mmHg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: Forty-five subjects (19 male, 26 female, mean age 37.5 years) showed significant differences between males and females in CBFV (50.9 ± 10.4 versus 61.5 ± 12.3 cm · s-1, p = 0.004), EtCO2 (39.2 ± 2.8 versus 36.9 ± 3.0 mmHg, p = 0.005), RAP (1.16 ± 0.23 versus 0.94 ± 0.40 mmHg cm · s-1, p = 0.005) and systolic BP (125.2 ± 8.0 versus 114.6 ± 12.4 mmHg, p = 0.0372), respectively. Significant differences between sexes were observed in the four logistic parameters: y min, y max, k (exponential coefficient) and x (EtCO2 level) across the haemodynamic variables. Significant differences included the CBFV-EtCO2 and ARI-EtCO2 relationship; ARImin (p = 0.036) and CBFVmax (p = 0.001), respectively. Furthermore, significant differences were observed for both CrCPmin (p = 0.045) and CrCPmax (p = 0.005) and RAPmin (p < 0.001) and RAPmax (p < 0.001). SIGNIFICANCE: This is the first study to examine sex individually within the context of a multi-level CO2 protocol. The demonstration that the logistic curve parameters are influenced by sex, highlights the need to take into account sex differences between participants in both physiological and clinical studies.

How many squat-stand manoeuvres to assess dynamic cerebral autoregulation?

PURPOSE: Squat-stand manoeuvres (SSMs) have been used to induce blood pressure (BP) changes for the reliable assessment of dynamic cerebral autoregulation. However, they are physically demanding and thus multiple manoeuvres can be challenging for older subjects. This study aimed to determine the minimum number of SSMs required to obtain satisfactory coherence, thus minimising the subjects' workload. METHOD: 20 subjects performed SSMs at a frequency of 0.05 Hz. End-tidal CO2, cerebral blood flow velocity, heart rate, continuous BP and the depth of the squat were measured. 11 subjects returned for a repeat visit. The time points at which subjects had performed 3, 6, 9, 12 and 15 SSMs were determined. Transfer function analysis was performed on files altered to the required length to obtain estimates of coherence and the autoregulation index (ARI). RESULTS: After three SSMs, coherence (0.05 Hz) was 0.93 ± 0.05, and peaked at 0.95 ± 0.02 after 12 manoeuvres. ARI decreased consecutively with more manoeuvres. ARI was comparable across the two visits (p = 0.92), but coherence was significantly enhanced during the second visit (p < 0.01). The intra-subject coefficients of variation (CoV) for ARI remained comparable as the number of manoeuvres varied. CONCLUSIONS: This analysis can aid those designing SSM protocols, especially where participants are unable to tolerate a standard 5-min protocol or when a shorter protocol is needed to accommodate additional tests. We emphasise that fewer manoeuvres should only be used in exceptional circumstances, and where possible a full set of manoeuvres should be performed. Furthermore, these results need replicating at 0.10 Hz to ensure their applicability to different protocols.

Modelling the cerebral haemodynamic response in the physiological range of PaCO2.

OBJECTIVE: Arterial CO2 (PaCO2) has a strong effect on cerebral blood flow (CBF), but its influence on CBF regulatory mechanisms and circulatory systemic variables has not been fully described over the entire physiological range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in 45 healthy volunteers (19 male, mean age 37.5 years, range 21-71) at baseline, and in response to hypo- (-5 mm Hg and -10 mm Hg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: CBFV, cerebral dynamic autoregulation index (ARI), heart rate (HR), arterial blood pressure (ABP), critical closing pressure (CrCP) and resistance-area product (RAP) changed significantly (all p < 0.0001) for hypo- and hyper-capnia. These parameters were shown to follow a logistic curve relationship representing a 'dose-response' curve for the effects of PaCO2 on the cerebral and systemic circulations. The four logistic model parameters describing each 'dose-response' curve were specific to each of the modelled variables (ANOVA p < 0.0001). SIGNIFICANCE: The ability to model the CBFV, ARI, HR, ABP, CrCP and RAP dependency of PaCO2 over its entire physiological range is a powerful tool for physiological and clinical studies, including the need to perform adjustments in disease populations with differing values of baseline PaCO2.

Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip in patients with heart failure.

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

Reproducibility of task activation using the Addenbrooke's cognitive examination in healthy controls: A functional Transcranial Doppler ultrasonography study.

INTRODUCTION: Cerebral blood flow velocity (CBFv) changes occurring with cognitive stimulation can be measured by Transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the reproducibility of CBFv changes to the Addenbrooke's cognitive examination (ACE-III). NEW METHOD: 13 volunteers underwent bilateral TCD (middle cerebral artery), continuous heart rate (HR, 3-lead ECG, Finometer), beat-to-beat mean arterial pressure (MAP, Finometer), and end-tidal CO2 (ETCO2, capnography). After 5min baseline, all ACE-III tasks were performed in 3 domains (A/B/C). Data presented are population CBFv peak normalised changes and area under the curve (AUC). Statistical analysis was by 2-way repeated measures (ANOVA), intra-class correlation coefficient (ICC), standard error of measurement (SEM) and coefficient of variation (CV). RESULTS: 12 bilateral data sets were obtained (10 right hand dominant, 6 female). Baseline parameters (MAP, HR, ETCO2) did not differ between visits. All tasks increased CBFv. Only domain A on AUC analysis differed significantly on ANOVA, and one task on post hoc testing (p <0.05). ICC values were poor (<0.4) for most tasks, but 3 tasks produced more consistent results on AUC and peak CBFv analysis (range ICC: 0.15-0.73, peak CV: 16.2-56.1(%), AUC CV: 23.2-60.2(%), peak SEM: 2.5-6.0 (%), AUC SEM: 21.8-135.8 (%*s). COMPARISON WITH EXISTING METHODS: This is the first study to examine reproducibility of CBFv changes to a complete cognitive assessment tool. CONCLUSIONS: Reproducibility of CBFv measurements to the ACE-III was variable. AUC may provide more reliable estimates than peak CBFv responses. These data need validating in patient populations.

Transcranial Doppler ultrasonography in the assessment of neurovascular coupling responses to cognitive examination in healthy controls: A feasibility study.

BACKGROUND: We tested the hypothesis that paradigms from the Addenbrooke's Cognitive Examination (ACE-III), including those that had not been studied using TCD previously (novel) versus those which had been (established), would elicit changes in CBF velocity (CBFv). NEW METHOD: Healthy subjects were studied with bilateral transcranial Doppler (TCD), beat-to-beat blood pressure (Finapres), continuous electrocardiogram (ECG), and end-tidal CO2 (nasal capnography). After a 5-min baseline recording, cognitive tests of the ACE-III were presented to subjects, covering attention (SUB7, subtracting 7 from 100 sequentially), language (REP, repeating words and phrases), fluency (N-P, naming words), visuospatial (DRAW, clock-drawing), and memory (MEM, recalling name and address). An event marker noted question timing. RESULTS: Forty bilateral data sets were obtained (13 males, 37 right-hand dominant) with a median age of 31 years (IQR 22-52). Population normalized mean peak CBFv% in the dominant and non-dominant hemispheres, respectively, were: SUB7 (11.3±9.6%, 11.2±10.5%), N-P (12.7±11.7%, 11.5±12.0%), REP (12.9±11.7%, 11.6±11.6%), DRAW (13.3±11.7%, 13.2±15.4%) and MEM (13.2±10.3%, 12.0±10.1%). There was a significant difference between the dominant and non-dominant CBFv responses (p<0.008), but no difference between the amplitude of responses. COMPARISON WITH EXISTING METHODS: For established paradigms, our results are in excellent agreement to what has been found previously in the middle cerebral artery. CONCLUSIONS: Cognitive paradigms derived from the ACE-III led to significant lateralised changes in CBFv that were not distinct for novel paradigms. Further work is needed to assess the potential of paradigms to improve the interpretation of cognitive assessments in patients at risk of mild cognitive impairment.

PaCO2 measurement in cerebral haemodynamics: face mask or nasal cannulae?

OBJECTIVE: PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the effects of CO2 measurement technique on cerebrovascular parameters are unknown. In order to determine if the two most commonly used approaches, face mask (FM) or nasal cannulae (NC), are interchangeable or not, we tested the hypothesis that the use of FM versus NC does not lead to significant differences in CO2-related systemic and cerebrovascular parameters. APPROACH: Recordings of CBF velocity (CBFV), blood pressure (BP), heart rate, and end-tidal CO2 (EtCO2) were performed in 42 subjects during normocapnia (FM or NC) and 5% CO2 inhalation (FM) or hyperventilation (NC). Dynamic cerebral autoregulation was assessed with the autoregulation index (ARI), derived by transfer function analysis from the CBFV response to a hypothetical step change in BP. MAIN RESULTS: Significant differences in physiological parameters were seen between FM and NC: EtCO2 (37.40 versus 35.26 mmHg, p = 0.001) and heart rate (69.6 versus 66.7 bpm, p = 0.001) respectively. No differences were observed for mean BP, CBFV or the ARI index. SIGNIFICANCE: Use of FM or NC for measurement of EtCO2 leads to physiological changes and differences in parameter values that need to be taken into consideration when interpreting and/or comparing results in studies of cerebral haemodynamics.

Cerebral Hemodynamic Effects of Cheyne-Stokes Respiration in a Patient with Stroke.

INTRODUCTION: Cheyne-Stokes respiration (CSR) and central sleep apnea (CSA) are common in patients with heart failure and/or stroke. We aim to describe the cerebrovascular effects of CSR during the acute phase of stroke in a heart failure patient. CASE REPORT: A 74-year-old male with previous dilated cardiomyopathy had sudden onset of right hemiparesis and aphasia. A transcranial Doppler was performed with continuous measurement of blood pressure (BP) (Finometer) and end-tidal CO2 (nasal capnography). Offline analysis of hemodynamic data disclosed relatively large periodic oscillations of both cerebral blood flow velocity and BP related to the CSR breathing pattern. Derivate variables from the cerebrovascular resistance were calculated (critical closing pressure and resistance-area product), demonstrating that there may be a myogenic impairment of cerebral blood flow (CBF) control in the affected hemisphere of this subgroup of patient. CONCLUSION: There is an impairment of CBF regulation in the affected hemisphere of the patient with ischemic stroke and CSR, highlighting the role of cerebral hemodynamic monitoring in this scenario.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Cerebral hemodynamics with intra-aortic balloon pump: business as usual?

OBJECTIVE: Intra-aortic balloon pump (IABP) is commonly used as mechanical support after cardiac surgery or cardiac shock. Although its benefits for cardiac function have been well documented, its effects on cerebral circulation are still controversial. We hypothesized that transfer function analysis (TFA) and continuous estimates of dynamic cerebral autoregulation (CA) provide consistent results in the assessment of cerebral autoregulation in patients with IABP. APPROACH: Continuous recordings of blood pressure (BP, intra-arterial line), end-tidal CO2, heart rate and cerebral blood flow velocity (CBFV, transcranial Doppler) were obtained (i) 5 min with IABP ratio 1:3, (ii) 5 min, starting 1 min with the IABP-ON, and continuing for another 4 min without pump assistance (IABP-OFF). Autoregulation index (ARI) was estimated from the CBFV response to a step change in BP derived by TFA and as a function of time using an autoregressive moving-average model during removal of the device (ARI t ). Critical closing pressure and resistance area-product were also obtained. MAIN RESULTS: ARI with IABP-ON (4.3 ± 1.2) were not different from corresponding values at IABP-OFF (4.7 ± 1.4, p = 0.42). Removal of the balloon had no effect on ARI t , CBFV, BP, cerebral critical closing pressure or resistance area-product. SIGNIFICANCE: IABP does not disturb cerebral hemodynamics. TFA and continuous estimates of dynamic CA can be used to assess cerebral hemodynamics in patients with IABP. These findings have important implications for the design of studies of critically ill patients requiring the use of different invasive support devices.

Cerebral blood flow autoregulation in ischemic heart failure.

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

The carotid artery as an alternative site for dynamic autoregulation measurement: an inter-observer reproducibility study.

The internal carotid artery (ICA) has been proposed as an alternative site to the middle cerebral artery (MCA) to measure dynamic cerebral autoregulation (dCA) using transcranial Doppler ultrasound (TCD). Our aim was to test the inter-operator reproducibility of dCA assessment in the ICA and the effect of interaction amongst different variables (artery source × operator × intra-subject variability). Two operators measured blood flow velocity using TCD at the ICA and MCA simultaneously on each side in 12 healthy volunteers. The autoregulation index (ARI) was estimated by transfer function analysis. A two-way repeated measurements ANOVA with post-hoc Tukey tested the difference between ARI by different operators and interaction effects were analysed based on the generalized linear model. In this healthy population, no significant differences between operator and no interaction effects were identified amongst the different variables. This study reinforced the validity of using the ICA as an alternative site for the assessment of dCA. Further work is needed to confirm and extend our findings, particularly to disease populations.

Statistical criteria for estimation of the cerebral autoregulation index (ARI) at rest.

The autoregulation index (ARI) can reflect the effectiveness of cerebral blood flow (CBF) control in response to dynamic changes in arterial blood pressure (BP), but objective criteria for its validation have not been proposed. Monte Carlo simulations were performed by generating 5 min long random input/output signals that mimic the properties of mean beat-to-beat BP and CBF velocity (CBFV) as usually obtained by non-invasive measurements in the finger (Finometer) and middle cerebral artery (transcranial Doppler ultrasound), respectively. Transfer function analysis (TFA) was used to estimate values of ARI by optimal fitting of template curves to the output (or CBFV) response to a step change in input (or BP). Two-step criteria were adopted to accept estimates of ARI as valid. The 95% confidence limit of the mean coherence function (0.15-0.25 Hz) ([Formula: see text]) was estimated from 15 000 runs, resulting in [Formula: see text] = 0.190 when using five segments of data, each with 102.4 s (512 samples) duration (Welch's method). This threshold for acceptance was dependent on the TFA settings and increased when using segments with shorter duration (51.2 s). For signals with mean coherence above the critical value, the 5% confidence limit of the normalised mean square error (NMSEcrit) for fitting the step response to Tieck's model, was found to be approximately 0.30 and independent of the TFA settings. Application of these criteria to physiological and clinical sets of data showed their ability to identify conditions where ARI estimates should be rejected, for example due to CBFV step responses lacking physiological plausibility. A larger number of recordings were rejected from acute ischaemic stroke patients than for healthy volunteers. More work is needed to validate this procedure with different physiological conditions and/or patient groups. The influence of non-stationarity in BP and CBFV signals should also be investigated.

Cerebrovascular effects of the thigh cuff maneuver.

Arterial hypotension can be induced by sudden release of inflated thigh cuffs (THC), but its effects on the cerebral circulation have not been fully described. In nine healthy subjects [aged 59 (9) yr], bilateral cerebral blood flow velocity (CBFV) was recorded in the middle cerebral artery (MCA), noninvasive arterial blood pressure (BP) in the finger, and end-tidal CO2 (ETCO2) with nasal capnography. Three THC maneuvers were performed in each subject with cuff inflation 20 mmHg above systolic BP for 3 min before release. Beat-to-beat values were extracted for mean CBFV, BP, ETCO2 , critical closing pressure (CrCP), resistance-area product (RAP), and heart rate (HR). Time-varying estimates of the autoregulation index [ARI(t)] were also obtained using an autoregressive-moving average model. Coherent averages synchronized by the instant of cuff release showed significant drops in mean BP, CBFV, and RAP with rapid return of CBFV to baseline. HR, ETCO2 , and ARI(t) were transiently increased, but CrCP remained relatively constant. Mean values of ARI(t) for the 30 s following cuff release were not significantly different from the classical ARI [right MCA 5.9 (1.1) vs. 5.1 (1.6); left MCA 5.5 (1.4) vs. 4.9 (1.7)]. HR was strongly correlated with the ARI(t) peak after THC release (in 17/22 and 21/24 recordings), and ETCO2 was correlated with the subsequent drop in ARI(t) (19/22 and 20/24 recordings). These results suggest a complex cerebral autoregulatory response to the THC maneuver, dominated by myogenic mechanisms and influenced by concurrent changes in ETCO2 and possible involvement of the autonomic nervous system and baroreflex.

Relating external compressing pressure to mean arterial pressure in non-invasive blood pressure measurements.

Arterial volume clamping uses external compression of an artery to provide continuous non-invasive measurement of arterial blood pressure. It has been assumed that mean arterial pressure (MAP) corresponds to the point where unloading leads to the maximum oscillation of the arterial wall as reflected by photoplethysmogram (PPG), an assumption that has been challenged. Five subjects were recruited for the study (three males, mean age (SD) = 32 (15) years). The PPG waveform was analysed to identify the relationship between the external compressing pressure, PPG pulse amplitude and MAP. Two separate tests were carried out at compression step intervals of 10 mmHg and 2 mmHg, respectively. No significant differences were found between the two tests. The bias between the compressing pressure and the MAP was -4.7 ± 5.63 mmHg (p < 0.001) showing a normal distribution. Further research is needed to identify optimal algorithms for estimation of MAP using PPG associated with arterial compression.

Optimising the assessment of cerebral autoregulation from black box models.

Cerebral autoregulation (CA) mechanisms maintain blood flow approximately stable despite changes in arterial blood pressure. Mathematical models that characterise this system have been used extensively in the quantitative assessment of function/impairment of CA. Using spontaneous fluctuations in arterial blood pressure (ABP) as input and cerebral blood flow velocity (CBFV) as output, the autoregulatory mechanism can be modelled using linear and non-linear approaches, from which indexes can be extracted to provide an overall assessment of CA. Previous studies have considered a single--or at most a couple of measures, making it difficult to compare the performance of different CA parameters. We compare the performance of established autoregulatory parameters and propose novel measures. The key objective is to identify which model and index can best distinguish between normal and impaired CA. To this end 26 recordings of ABP and CBFV from normocapnia and hypercapnia (which temporarily impairs CA) in 13 healthy adults were analysed. In the absence of a 'gold' standard for the study of dynamic CA, lower inter- and intra-subject variability of the parameters in relation to the difference between normo- and hypercapnia were considered as criteria for identifying improved measures of CA. Significantly improved performance compared to some conventional approaches was achieved, with the simplest method emerging as probably the most promising for future studies.