Cardiology meets neurology: clinical presentation and management of patients with primary neurogenic disorders and orthostatic intolerance.

Patients with primary neurogenic disorders such as pure autonomic failure or multiple system atrophy may initially present with cardiocirculatory symptoms such as orthostatic intolerance or fluctuations in heart rate with symptomatic tachycardia. It is therefore clinically important to identify such patients since circulatory manifestations are only one of a series of symptoms resulting from autonomic dysfunction in various organ systems. These patients require a multimodal diagnostic and therapeutic approach and should undergo extensive evaluation in a specialized autonomic nervous system (ANS) outpatient unit. Based on a clinical case presentation, the current review summarizes the diagnostic and therapeutic approach to key cardiovascular symptoms of primary autonomic disorders and their neurological work-up in a specialized autonomic function laboratory.

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. METHODS: The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving ß-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. RESULTS: Forty-eight patients were included. Median age was 58 years old (36-76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS (P=0.007), sedation (P=0.001), World Federation of Neurosurgery score (P=0.001), Glasgow score (P=0.002), Fisher score (P=0.022), and heart rate (P=0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048-1.818; P=0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171-0.706; P=0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. CONCLUSIONS: In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study.

Pre-hospital Predictors of Impaired ICP Trends in Continuous Monitoring of Paediatric Traumatic Brain Injury Patients.

OBJECTIVE: Although secondary insults such as raised intracranial pressure (ICP) or cardiovascular compromise strongly contribute to morbidity, a growing interest can be noticed in how the pre-hospital management can affect outcomes after traumatic brain injury (TBI). The objective of this study was to determine whether pre-hospital co-morbidity has influence on patterns of continuously measured waveforms of intracranial physiology after paediatric TBI. MATERIALS AND METHODS: Thirty-nine patients (mean age, 10 years; range, 0.5-15) admitted between 2002 and 2015 were used for the current analysis. Pre-hospital motor score, pupil reactivity, pre-hospital hypoxia (SpO2 < 90%) and hypotension (mean arterial pressure < 70 mmHg) were documented. ICP and arterial blood pressure (ABP) were monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30 10-s averages of ABP and ICP (PRx). The mean ICP and PRx were calculated for the whole monitoring period for each patient. RESULTS: Those with pre-hospital hypotension were susceptible to higher ICP [20 (IQR 8) vs 13 (IQR 6) mmHg; p = 0.01] and more frequent ICP plateau waves [median = 0 (IQR 1), median = 4 (IQR 9); p = 0.001], despite having similar MAP, CPP and PRx during monitoring. Those with unreactive pupils tended to have higher ICP than those with reactive pupils (18 vs 14 mmHg, p = 0.08). Pre-hospital hypoxia, motor score and pupillary reactivity were not related to subsequent monitored intracranial or systemic physiology. CONCLUSION: In paediatric TBI, pre-hospital hypotension is associated with increased ICP in the intensive care unit.

Computed Tomography Indicators of Deranged Intracranial Physiology in Paediatric Traumatic Brain Injury.

OBJECTIVE: Computed tomography (CT) of the brain can allow rapid assessment of intracranial pathology after traumatic brain injury (TBI). Frequently in paediatric TBI, CT imaging can fail to display the classical features of severe brain injury with raised intracranial pressure. The objective of this study was to determine early CT brain features that influence intracranial or systemic physiological trends following paediatric TBI. MATERIALS AND METHODS: Thirty-three patients (mean age, 10 years; range, 0.5-16) admitted between 2002 and 2015 were used for the current analysis. Presence of petechial haemorrhages, basal cistern compression, subarachnoid blood, midline shift and extra-axial masses on the initial trauma CT head were assessed. ICP and arterial blood pressure (ABP) were then monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30, 10-s averages of ABP and ICP (PRx). The mean ICP, ABP, cerebral perfusion pressure (CPP; ABP minus ICP) and PRx were calculated for the whole monitoring period for each patient. RESULTS: The presence of subarachnoid blood was related to higher ICP, higher ABP and a trend toward higher PRx. Smaller basal cisterns were related to increased ICP (R = -0.42, p = 0.02), impaired PRx (R = -0.5, p = 0.003). The presence of an extra-axial mass was associated with deranged PRx (-0.02 vs. 0.41, p = 0.003) and a trend toward higher ICP (14 vs. 40, p = 0.07). Interestingly the degree of midline shift was not related to ICP or PRx. CONCLUSIONS: The size of the basal cisterns, the presence of subarachnoid blood or an extra-axial mass are all related to disturbed ICP and pressure reactivity in this paediatric TBI cohort. Patients with these features are ideal candidates for invasive multimodal monitoring.

Simultaneous Transients of Intracranial Pressure and Heart Rate in Traumatic Brain Injury: Methods of Analysis.

OBJECTIVES: The detection of increasing intracranial pressure (ICP) is important in preventing secondary brain injuries. Before mean ICP increases critically, transient ICP elevations may be observed. We have observed ICP transients of less than 10 min duration ,which occurred simultaneously with transient increases in heart rate (HR). These simultaneous events in HR and ICP suggest a direct interaction or communication between the heart and the brain. METHODS: This chapter describes four mathematical methods and their applicability in detecting the above heart-brain cross-talk events during long-term monitoring of ICP. RESULTS: Recurrence plots, cross-correlation function and wavelet analysis confirmed the relationship between ICP and HR time series. Using the peaks detection algorithm with a sliding window approach we found an average of 37 cross-talk events (± SD 39). The number of events detected varied among patients, from 1 to more than 150 events. CONCLUSION: Our analysis suggested that the peaks detection algorithm based on a sliding window approach is feasible for detecting simultaneous peaks, e.g. cross-talk events in the ICP and HR signals.

Survey in expert clinicians on the validity of automated calculation of optimal cerebral perfusion pressure.

BACKGROUND: Optimal cerebral perfusion pressure (CPPopt) targeting in traumatic brain injury (TBI) patients constitutes an active and controversial area of research. It has been suggested that an autoregulation guided CPP therapy may improve TBI outcome. Prerequisites of a CPPopt intervention study would be objective criteria for the CPPopt detection. This study compared the agreement between automated and visual CPPopt detection. METHODS: Twenty-five clinicians from 18 centers worldwide, familiar with brain monitoring and using dedicated software, reviewed ten 4-hour CPPopt screenshots at 48 hours after ictus in selected TBI patients. Each screenshot displayed the trends of cerebral perfusion pressure (CPP), intracranial pressure (ICP), cerebrovascular pressure reactivity (PRx) as well as the "CPP-optimal" curve and its associated value (automated CPPopt). The main objective was to evaluate the agreement between expert clinicians as well as the agreement between the clinicians and automated CPPopt. RESULTS: Twenty-two clinicians responded to our call (88%). Three screenshots were judged as "CPPopt not determinable" by >45% of the clinicians. For the whole group, the consensus between automated CPPopt and clinicians' visual CPPopt was high. Three clinicians were identified as outliers. All clinicians recommended to modify CPP when patients differed >±5 mmHg from their CPPopt. The inter-observer consensus was highest in cases with current CPP below the optimal value. CONCLUSIONS: The overall agreement between automated CPPopt and visual CPPopt identified by autoregulation experts was high, except for those cases when the curve was deemed by the clinicians not reliable enough to yield a trustworthy CPPopt.

Cerebrovascular pressure reactivity monitoring using wavelet analysis in traumatic brain injury patients: A retrospective study.

BACKGROUND: After traumatic brain injury (TBI), the ability of cerebral vessels to appropriately react to changes in arterial blood pressure (pressure reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or hyperperfusion. Although, the traditional pressure reactivity index (PRx) has demonstrated that impaired pressure reactivity is associated with poor patient outcome, PRx is sometimes erratic and may not be reliable in various clinical circumstances. Here, we introduce a more robust transform-based wavelet pressure reactivity index (wPRx) and compare its performance with the widely used traditional PRx across 3 areas: its stability and reliability in time, its ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation, and its relationship with patient outcome. METHODS AND FINDINGS: Five hundred and fifteen patients with TBI admitted in Addenbrooke's Hospital, United Kingdom (March 23rd, 2003 through December 9th, 2014), with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP), were retrospectively analyzed to calculate the traditional PRx and a novel wavelet transform-based wPRx. wPRx was calculated by taking the cosine of the wavelet transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated using an automated curve-fitting method that determined the cerebral perfusion pressure (CPP) at which the pressure reactivity (PRx or wPRx) was most efficient (CPPopt_PRx and CPPopt_wPRx, respectively). There was a significantly positive relationship between PRx and wPRx (r = 0.73), and wavelet wPRx was more reliable in time (ratio of between-hour variance to total variance, wPRx 0.957 ± 0.0032 versus PRx and 0.949 ± 0.047 for PRx, p = 0.002). The 2-hour interval standard deviation of wPRx (0.19 ± 0.07) was smaller than that of PRx (0.30 ± 0.13, p < 0.001). wPRx performed better in distinguishing between mortality and survival (the area under the receiver operating characteristic [ROC] curve [AUROC] for wPRx was 0.73 versus 0.66 for PRx, p = 0.003). The mean difference between the patients' CPP and their CPPopt was related to outcome for both calculation methods. There was a good relationship between the 2 CPPopts (r = 0.814, p < 0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard deviation 7.05 ± 3.78 versus 8.45 ± 2.90; p < 0.001). Key limitations include that this study is a retrospective analysis and only compared wPRx with PRx in the cohort of patients with TBI. Prior prospective validation is required to better assess clinical utility of this approach. CONCLUSIONS: wPRx offers several advantages to the traditional PRx: it is more stable in time, it yields a more consistent CPPopt recommendation, and, importantly, it has a stronger relationship with patient outcome. The clinical utility of wPRx should be explored in prospective studies of critically injured neurological patients.

A multiplex network approach for the analysis of intracranial pressure and heart rate data in traumatic brain injured patients.

BACKGROUND: We present a multiplex network model for the analysis of Intracranial Pressure (ICP) and Heart Rate (HR) behaviour after severe brain traumatic injuries in pediatric patients. The ICP monitoring is of vital importance for checking life threathening conditions, and understanding the behaviour of these parameters is crucial for a successful intervention of the clinician. Our own observations, exhibit cross-talks interaction events happening between HR and ICP, i.e. transients in which both the ICP and the HR showed an increase of 20% with respect to their baseline value in the window considered. We used a complex event processing methodology, to investigate the relationship between HR and ICP, after traumatic brain injuries (TBI). In particular our goal has been to analyse events of simultaneous increase by HR and ICP (i.e. cross-talks), modelling the two time series as a unique multiplex network system (Lacasa et al., Sci Rep 5:15508-15508, 2014). METHODS AND DATA: We used a complex network approach based on visibility graphs (Lacasa et al., Sci Rep 5:15508-15508, 2014) to model and study the behaviour of our system and to investigate how and if network topological measures can give information on the possible detection of crosstalks events taking place in the system. Each time series was converted as a layer in a multiplex network. We therefore studied the network structure, focusing on the behaviour of the two time series in the cross-talks events windows detected. We used a dataset of 27 TBI pediatric patients, admitted to Addenbrooke's Hospital, Cambridge, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014. RESULTS: Following a preliminary statistical exploration of the two time series of ICP and HR, we analysed the multiplex network proposed, focusing on two standard topological network metrics: the mutual interaction, and the average edge overlap (Lacasa et al., Sci Rep 5:15508-15508, 2014). We compared results obtained for these two indicators, considering windows in which a cross talks event between HR and ICP was detected with windows in which cross talks events were not present. The analysis of such metrics gave us interesting insights on the time series behaviour. More specifically we observed an increase in the value of the mutual interaction in the case of cross talk as compared to non cross talk. This seems to suggest that mutual interaction could be a potentially interesting "marker" for cross talks events.

An Association Between ICP-Derived Data and Outcome in TBI Patients: The Role of Sample Size.

BACKGROUND: Many demographic and physiological variables have been associated with TBI outcomes. However, with small sample sizes, making spurious inferences is possible. This paper explores the effect of sample sizes on statistical relationships between patient variables (both physiological and demographic) and outcome. METHODS: Data from head-injured patients with monitored arterial blood pressure, intracranial pressure (ICP) and outcome assessed at 6 months were included in this retrospective analysis. A univariate logistic regression analysis was performed to obtain the odds ratio for unfavorable outcome. Three different dichotomizations between favorable and unfavorable outcomes were considered. A bootstrap method was implemented to estimate the minimum sample sizes needed to obtain reliable association between physiological and demographic variables with outcome. RESULTS: In a univariate analysis with dichotomized outcome, samples sizes should be generally larger than 100 for reproducible results. Pressure reactivity index, ICP, and ICP slow waves offered the strongest relationship with outcome. Relatively small sample sizes may overestimate effect sizes or even produce conflicting results. CONCLUSION: Low power tests, generally achieved with small sample sizes, may produce misleading conclusions, especially when they are based only on p values and the dichotomized criteria of rejecting/not-rejecting the null hypothesis. We recommend reporting confidence intervals and effect sizes in a more complete and contextualized data analysis.

Ventricular Volume Load Reveals the Mechanoelastic Impact of Communicating Hydrocephalus on Dynamic Cerebral Autoregulation.

Several studies have shown that the progression of communicating hydrocephalus is associated with diminished cerebral perfusion and microangiopathy. If communicating hydrocephalus similarly alters the cerebrospinal fluid circulation and cerebral blood flow, both may be related to intracranial mechanoelastic properties as, for instance, the volume pressure compliance. Twenty-three shunted patients with communicating hydrocephalus underwent intraventricular constant-flow infusion with Hartmann's solution. The monitoring included transcranial Doppler (TCD) flow velocities (FV) in the middle (MCA) and posterior cerebral arteries (PCA), intracranial pressure (ICP), and systemic arterial blood pressure (ABP). The analysis covered cerebral perfusion pressure (CPP), the index of pressure-volume compensatory reserve (RAP), and phase shift angles between Mayer waves (3 to 9 cpm) in ABP and MCA-FV or PCA-FV. Due to intraventricular infusion, the pressure-volume reserve was exhausted (RAP) 0.84+/-0.1 and ICP was increased from baseline 11.5+/-5.6 to plateau levels of 20.7+/-6.4 mmHg. The ratio dRAP/dICP distinguished patients with large 0.1+/-0.01, medium 0.05+/-0.02, and small 0.02+/-0.01 intracranial volume compliances. Both M wave phase shift angles (r = 0.64; p<0.01) and CPP (r = 0.36; p<0.05) displayed a gradual decline with decreasing dRAP/dICP gradients. This study showed that in communicating hydrocephalus, CPP and dynamic cerebral autoregulation in particular, depend on the volume-pressure compliance. The results suggested that the alteration of mechanoelastic characteristics contributes to a reduced cerebral perfusion and a loss of autonomy of cerebral blood flow regulation. Results warrant a prospective TCD follow-up to verify whether the alteration of dynamic cerebral autoregulation may indicate a progression of communicating hydrocephalus.

The Interaction Between Heart Systole and Cerebral Circulation During Lower Body Negative Pressure Test.

The time constant (τ[s]) estimates how fast the arterial part of the cerebrovascular bed fills with blood volume during the cardiac cycle, whereas a product of τ and heart rate (HR) (τ*HR[%]) assesses how this period of arterial filling is related to an entire heart cycle. In this study we aimed to investigate cerebral hemodynamics using τ and τ*HR during a progressive lower body negative pressure (LBNP) test.Transcranial Doppler cerebral blood flow velocity (CBFV), Finapres arterial blood pressure (ABP), and HR, along with end-tidal CO2, were simultaneously recorded in 38 healthy volunteers during an LBNP test. The τ was estimated using mathematical transformation of ABP and CBFV pulse waveforms. After a gradual shortening of τ from baseline (0.20 ± 0.06 s) to maximal LBNP before the onset of presyncope (0.15 ± 0.05 s), we observed a significant increase in τ at presyncope (0.24 ± 0.15 s; p = 0.0001). In the course of LBNP, the τ*HR did not significantly change from baseline (25.6 ± 5.7 % vs 26.6 ± 8.9 %, p = n.s.) except for presyncope, when it increased to 40.4 ± 21.1 % (p < 0.000001). Because the time needed to fill the arterial part of the cerebrovascular bed with blood is prolonged during presyncope, an increased part of the heart cycle seems to be spent on the cerebral blood supply.

Increasing Intracranial Pressure After Head Injury: Impact on Respiratory Oscillations in Cerebral Blood Flow Velocity.

Experiments have shown that closed-box conditions alter the transmission of respiratory oscillations (R waves) to organ blood flow already at a marginal pressure increase. How does the increasing intracranial pressure (ICP) interact with R waves in cerebral blood flow after head injury (HI)?Twenty-two head-injured patients requiring sedation and mechanical ventilation were monitored for ICP, Doppler flow velocity (FV) in the middle cerebral arteries, and arterial blood pressure (ABP). The analysis included transfer function gains of R waves (9-20 cpm) from ABP to FV, and indices of pressure-volume reserve (RAP) and autoregulation (Mx). Increasing ICP has dampened R-wave gains from day 1 to day 4 after HI in all patients. A large impact (ΔGain /ΔICP right: 0.14 ± 0.06; left: 0.18 ± 0.08) was associated with exhausted reserves (RAP ≥0.85). When RAP was <0.85, rising ICP had a lower impact on R-wave gains (ΔGain /ΔICP right: 0.05 ± 0.02; left: 0.06 ± 0.04; p < 0.05), but increased the pulsatility indices (right: 1.35 ± 0.55; left: 1.25 ± 0.52) and Mx indices (right: 0.30 ± 0.12; left: 0.28 ± 0.08, p < 0.05). Monitoring of R waves in blood pressure and cerebral blood flow velocity has suggested that rising ICP after HI might have an impact on cerebral blood flow directly, even before autoregulation is impaired.

GAD Antibodies as Key Link Between Chronic Intestinal Pseudoobstruction, Autonomic Neuropathy, and Limb Stiffness in a Nondiabetic Patient: A CARE-Compliant Case Report and Review of the Literature.

Chronic intestinal pseudoobstruction (CIP) can be a severe burden and even a life-threatening disorder. Typically, several years of uncertainty are passing before diagnosis. We are reporting the case of a young woman with a decade of severe, progressive gastrointestinal dysmotility. Unusually, she had also developed an autonomic neuropathy, and a stiff limb syndrome.In addition to achalasia and CIP the young woman also developed neuropathic symptoms: orthostatic intolerance, urinary retention, a Horner syndrome, and lower limb stiffness. Careful interdisciplinary diagnostics excluded underlying infectious, rheumatoid, metabolic or tumorous diseases.The detection of GAD (glutamic acid decarboxylase) antibodies, however, seemed to link CIP, autonomic neuropathy, and limb stiffness and pointed at an autoimmune origin of our patient's complaints. This was supported by the positive effects of intravenous immunoglobulin. In response to this therapy the body weight had stabilized, orthostatic tolerance had improved, and limb stiffness was reversed.The case suggested that GAD antibodies should be considered in CIP also in nondiabetic patients. This may support earlier diagnosis and immunotherapy.

Traumatic brain injury: increasing ICP attenuates respiratory modulations of cerebral blood flow velocity.

In vitro experiments have suggested that respiratory oscillations (R waves) in cerebral blood flow velocity are reduced as soon as the intracranial pressure-volume reserve is exhausted. Could R waves hence, provide indication for increasing ICP after traumatic brain injury (TBI)? On days 1 to 4 after TBI, 22 sedated and ventilated patients were monitored for intracranial pressure (ICP) in brain parenchyma, Doppler flow velocity (FV) in the middle cerebral arteries (MCA), and arterial blood pressure (ABP). The analysis included the transfer function gains of R waves (respiratory rate of 9-20 cpm) between ABP and FV (GainFv) as well as between ABP and ICP (GainICP). Also, the index of the intracranial pressure-volume reserve (RAP) was calculated. The rise of ICP (day 1: 14.10 ± 6.22 mmHg; to day 4: 29.69 ± 12.35 mmHg) and increase of RAP (day 1: 0.72 ± 0.22; to day 4: 0.85 ± 0.18) were accompanied by a decrease of GainFv (right MCA; day 1: 1.78 ± 1.0; day 4: 0.84 ± 0.47; left MCA day 1: 1.74 ± 1.10; day 4: 0.86 ± 0.46; p < 0.01) but no significant change in GainICP day 1: 1.50 ± 0.77; day 4: 1.15 ± 0.47; p = 0.07). The transfer of ventilatory oscillations to the intracerebral arteries after TBI appears to be dampened by increasing ICP and exhausted intracranial pressure-volume reserves. Results warrant prospective studies of whether respiratory waves in cerebral blood flow velocity may anticipate intracranial hypertension non-invasively.

Doppler flow velocity and intra-cranial pressure: responses to short-term mild hypocapnia help to assess the pressure-volume relationship after head injury.

To anticipate an increase in intra-cranial pressure (ICP), information about pressure-volume (p/v) compliance is required. ICP monitoring often fails at this task after head injury. Could a test that transiently shifts intra-cranial blood volume produce consistent information about the p/v relationship? Doppler flow velocities in the middle cerebral arteries (left: 80.8 ± 34.7 cm/s; right: 65.9 ± 28.0 cm/s) and ICP (16.4 ± 6.7 mm Hg) were measured in 29 patients with head injury, before and during moderate hypocapnia (4.4 ± 3.0 kPa). The ratio of vasomotor response to change in ICP differed between those with high (left: 14.8 ± 6.9, right: 14.4 ± 6.6 cm/s/kPa/mm Hg) and low (left: 1.8 ± 0.6, right: 2.2 ± 0.9 cm/s/kPa/mm g) intra-cranial compliance. Additionally, the ratio identified 12 patients deviating from the classic non-linear p/v curve (left: 5.7 ± 1.3, right: 5.8 ± 1.0 cm/s/kPa/mm Hg). They exhibited an almost proportional relationship between vasomotor and ICP responses (R = 0.69, p < 0.01). Results suggest that a test that combines the responses of two intra-cranial compartments may provide consistent information about intra-cranial p/v compliance, even if the parameters derived from ICP monitoring are inconclusive.

Time constant of the cerebral arterial bed in normal subjects.

The time constant of cerebral arterial bed (in brief time constant) is a product of brain arterial compliance (C(a)) and resistance (CVR). We tested the hypothesis that in normal subjects, changes in end-tidal CO(2) (EtCO(2)) affect the value of the time constant. C(a) and CVR were estimated using mathematical transformations of arterial pressure (ABP) and transcranial Doppler (TCD) cerebral blood flow velocity waveforms. Responses of the time constant to controlled changes in EtCO(2) were compared in 34 young volunteers. Hypercapnia shortened the time constant (0.22 s [0.17, 0.26] vs. 0.16 s [0.13, 0.20]; p = 0.000001), while hypocapnia lengthened the time constant (0.22 s [0.17, 0.26] vs. 0.23 s [0.19, 0.32]; p < 0.0032). The time constant was negatively correlated with changes in EtCO(2) (R(partial) = -0.68, p < 0.000001). This was associated with a decrease in CVR when EtCO(2) increased (R(partial) = -0.80, p < 0.000001) and C(a) remained independent of changes in EtCO(2). C(a) was negatively correlated with mean ABP (R(partial) = -0.68, p < 0.000001). In summary, the time constant shortens with increasing EtCO(2). Its potential role in cerebrovascular investigations needs further studies.

Time constant of the cerebral arterial bed.

We have defined a novel cerebral hemodynamic index, a time constant of the cerebral arterial bed (τ), the product of arterial compliance (C(a)) and cerebrovascular resistance (CVR). C(a) and CVR were calculated based on the relationship between pulsatile arterial blood pressure (ABP) and transcranial Doppler cerebral blood flow velocity. This new parameter theoretically estimates how fast the cerebral arterial bed is filled by blood volume after a sudden change in ABP during one cardiac cycle. We have explored this concept in 11 volunteers and in 25 patients with severe stenosis of the internal carotid artery (ICA). An additional group of 15 subjects with non-vascular dementia was studied to assess potential age dependency of τ. The τ was shorter (p = 0.011) in ICA stenosis, both unilateral (τ = 0.18 ± 0.04 s) and bilateral (τ = 0.16 ± 0.03 s), than in controls (τ = 0.22 ± 0.0 s). The τ correlated with the degree of stenosis (R = -0.62, p = 0.001). In controls, τ was independent of age. Further study during cerebrovascular reactivity tests is needed to establish the usefulness of τ for quantitative estimation of haemodynamics in cerebrovascular disease.

How does moderate hypocapnia affect cerebral autoregulation in response to changes in perfusion pressure in TBI patients?

In traumatic brain injury, the hypocapnic effects on blood pressure autoregulation may vary from beneficial to detrimental. The consequences of moderate hypocapnia (HC) on the autoregulation of cerebral perfusion pressure (CPP) have not been monitored so far.Thirty head injured patients requiring sedation and mechanical ventilation were studied during normocapnia (5.1 ± 0.4 kPa) and moderate HC (4.4 ± 3.0 kPa). Transcranial Doppler flow velocity (Fv) of the middle cerebral arteries (MCA), invasive arterial blood pressure, and intracranial pressure were monitored. CPP was calculated. The responsiveness of Fv to slow oscillations in CPP was assessed by means of the moving correlation coefficient, the Mx autoregulatory index. Hypocapnic effects on Mx were increasing with its deviation from normal baseline (left MCA: R (2) = 0.67; right MCA: R (2) = 0.51; p < 0.05). Mx indicating normal autoregulation (left: -0.23 ± 0.23; right: -0.21 ± 0.24) was not significantly changed by moderate HC. Impaired Mx autoregulation, however, (left: 0.37 ± 0.13; right: 0.33 ± 0.26) was improved (left: 0.12 ± 0.25; right: -0.0003 ± 0.19; p < 0.01) during moderate HC. Mx was adjusted to normal despite no significant change in CPP levels. Our study showed that short-term moderate HC may optimize the autoregulatory response to spontaneous CPP fluctuations with only a small CPP increase. Patients with impaired autoregulation seemed to benefit the most.