Moving Correlation Coefficient Research Articles

Effects of Xenon and Hypothermia on Cerebrovascular Pressure Reactivity in Newborn Global Hypoxic—ischemic Pig Model

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.

Cerebrovascular Pressure Reactivity and Cerebral Oxygen Regulation After Severe Head Injury

To investigate the relationship between cerebrovascular pressure reactivity and cerebral oxygen regulation after head injury. Continuous monitoring of the partial pressure of brain tissue oxygen (PbrO2), mean arterial blood pressure (MAP), and intracranial pressure (ICP) in 11 patients. The cerebrovascular pressure reactivity index (PRx) was calculated as the moving correlation coefficient between MAP and ICP. For assessment of the cerebral oxygen regulation system a brain tissue oxygen response (TOR) was calculated, where the response of PbrO2 to an increase of the arterial oxygen through ventilation with 100 % oxygen for 15 min is tested. Arterial blood gas analysis was performed before and after changing ventilator settings. Arterial oxygen increased from 108 ± 6 mmHg to 494 ± 68 mmHg during ventilation with 100 % oxygen. PbrO2 increased from 28 ± 7 mmHg to 78 ± 29 mmHg, resulting in a mean TOR of 0.48 ± 0.24. Mean PRx was 0.05 ± 0.22. The correlation between PRx and TOR was r = 0.69, P = 0.019. The correlation of PRx and TOR with the Glasgow outcome scale at 6 months was r = 0.47, P = 0.142; and r = -0.33, P = 0.32, respectively. The results suggest a strong link between cerebrovascular pressure reactivity and the brain's ability to control for its extracellular oxygen content. Their simultaneous impairment indicates that their common actuating element for cerebral blood flow control, the cerebral resistance vessels, are equally impaired in their ability to regulate for MAP fluctuations and changes in brain oxygen.

Low-frequency autoregulation index for calculation of optimal cerebral perfusion pressure in severe traumatic brain injury

Traumatic brain injury (TBI) is a major cause of permanent disability and death in young patients. Controversy exists regarding the optimal cerebral perfusion pressure (CPP) required in TBI management. A tool for monitoring autoregulation and determining an optimal CPP is the pressure reactivity index (PRx), defined as a moving correlation coefficient between the mean arterial blood pressure (MAP) and intracranial pressure (ICP) at a frequency of at least 60 Hz. This requirement of high frequency has constrained its use to a few academic centers. An association was shown between outcome and continuous optimal CPP based on 4 hours of PRx [1]. We present a novel low-frequency autoregulation index (LAx), based on correlations between ICP and MAP at a standard minute-by-minute time resolution.

Abstract 55: Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Variations of Dynamic Cerebral Autoregulation

The risk of delayed cerebral ischemia (DCI) after cerebral aneurysm rupture is increased in patients with large cerebral artery vasospasm (VS). The predictive value of VS is, however, far to be optimal. Assessment of cerebral microcirculation impairment using dynamic cerebral autoregulation (DCA) measurement might improve our ability to predict DCI in these patients. Methods. We included consecutive patients with low-grade aneurysmal subarachnoid hemorrhage (SAH) (WFNS 1 to 3) within 4 days of aneurysm rupture. DCA was evaluated using the moving correlation coefficient Mx calculated from spontaneous fluctuations of cerebral blood flow velocities and arterial blood pressure. Impairment of DCA was defined as Mx ≥ 0.3. Transcranial colour-coded sonography was performed every 48 hours to look for VS. Diagnosis of VS was based on a Lindegaard ratio >3 (MCA), or mean flow velocities > 130 cm/s (ACA). DCI was defined as neurologic deterioration caused by brain ischemia confirmed by brain imaging. Results. Thirty patients (19 women; mean age ± SD: 44.7 ± 12.1 years) were included. Twenty (66.7%) patients had VS. DCI occurred in six (20%) patients after a median delay of 10 days (range 8 to 13 days). Mx (mean ± SD) was heightened at baseline (0.43 ± 0.2) and at day 7 (0.46 ± 0.2), then decreased at day 14 (0.37 ± 0.18 (p = 0.034). Isolated measures of VS and Mx were not associated with DCI. However, the elevation of Mx between baseline and day 7 in patients with VS was predictive of subsequent DCI (positive likelihood ratio=5.01; negative likelihood ratio=0.19; P=0.005). Conclusion. Findings suggest that DCA assessment may help to predict better the risk of DCI after cerebral aneurysm rupture than the simple recordings of mean flow velocities.

Positive end-expiratory pressure oscillation facilitates brain vascular reactivity monitoring

The pressure reactivity index (PRx) identifies optimal cerebral perfusion pressure after traumatic brain injury. We describe a method to improve PRx precision by induced variations in arterial blood pressure (ABP) using positive end-expiratory pressure (PEEP) modulation (iPRx). Neonatal swine (n = 10) were ventilated with static PEEP and then with PEEP oscillated between 5 and 10 cmH(2)O at a frequency of 1/min. PRx was recorded as a moving correlation coefficient between ABP and intracranial pressure (ICP) from spontaneous ABP activity (0.05-0.003 Hz) during static PEEP. iPRx was similarly recorded with PEEP oscillation-induced ABP waves. The lower limit of autoregulation (LLA) was delineated with continuous cortical laser Doppler flux monitoring. PEEP oscillation increased autoregulation-monitoring precision. The ratios of median absolute deviations to range of possible values for the PRx and iPRx were 9.5% (8.3-13.7%) and 6.2% (4.2-8.7%), respectively (P = 0.006; median, interquartile range). The phase-angle difference between ABP and ICP above LLA was 161° (150°-166°) and below LLA, -31° (-42° to 12°, P < 0.0001). iPRx above LLA was -0.42 (-0.67 to -0.29) and below LLA, 0.32 (0.22-0.43, P = 0.0004). A positive iPRx was 97% specific and 91% sensitive for perfusion pressure below LLA. PEEP oscillation caused stable, low-frequency ABP oscillations that reduced noise in the PRx. Safe translation of these findings to clinical settings is expected to yield more accurate and rapid delineation of individualized optimal perfusion-pressure goals for patients.

Clinical Significance of Impaired Cerebrovascular Autoregulation After Severe Aneurysmal Subarachnoid Hemorrhage

The purpose of this study was to investigate the relationship between cerebrovascular autoregulation and outcome after aneurysmal subarachnoid hemorrhage. In a prospective observational study, 80 patients after severe subarachnoid hemorrhage were continuously monitored for cerebral perfusion pressure and partial pressure of brain tissue oxygen for an average of 7.9 days (range, 1.9-14.9 days). Autoregulation was assessed using the index of brain tissue oxygen pressure reactivity (ORx), a moving correlation coefficient between cerebral perfusion pressure and partial pressure of brain tissue oxygen. High ORx indicates impaired autoregulation; low ORx signifies intact autoregulation. Outcome was determined at 6 months and dichotomized into favorable (Glasgow Outcome Scale 4-5) and unfavorable outcome (Glasgow Outcome Scale 1-3). Twenty-four patients had a favorable and 56 an unfavorable outcome. In a univariate analysis, there were significant differences in autoregulation (ORx 0.19±0.10 versus 0.37±0.11, P<0.001, for favorable versus unfavorable outcome, respectively), age (44.1±11.0 years versus 54.2±12.1 years, P=0.001), occurrence of delayed cerebral infarction (8% versus 46%, P<0.001), use of coiling (25% versus 54%, P=0.02), partial pressure of brain tissue oxygen (24.9±6.6 mm Hg versus 21.8±6.3 mm Hg, P=0.048), and Fisher grade (P=0.03). In a multivariate analysis, ORx (P<0.001) and age (P=0.003) retained an independent predictive value for outcome. ORx correlated with Glasgow Outcome Scale (r=-0.70, P<0.001). The status of cerebrovascular autoregulation might be an important pathophysiological factor in the disease process after subarachnoid hemorrhage, because impaired autoregulation was independently associated with an unfavorable outcome.

Continuous Monitoring of Cerebrovascular Reactivity Using Pulse Waveform of Intracranial Pressure

Guidelines for the management of traumatic brain injury (TBI) call for the development of accurate methods for assessment of the relationship between cerebral perfusion pressure (CPP) and cerebral autoregulation and to determine the influence of quantitative indices of pressure autoregulation on outcome. We investigated the relationship between slow fluctuations of arterial blood pressure (ABP) and intracranial pressure (ICP) pulse amplitude (an index called PAx) using a moving correlation technique to reflect the state of cerebral vasoreactivity and compared it to the index of pressure reactivity (PRx) as a moving correlation coefficient between averaged values of ABP and ICP. A retrospective analysis of prospective 327 TBI patients (admitted on neurocritical care unit of a university hospital in the period 2003-2009) with continuous ABP and ICP monitoring. PAx was worse in patients who died compared to those who survived (-0.04 ± 0.15 vs. -0.16 ± 0.15, χ2 = 28, p < 0.001). In contrast to PRx, PAx was able to differentiate between fatal and non-fatal outcome in a group of 120 patients with ICP levels below 15 mmHg (-0.04 ± 0.16 vs. -0.14 ± 0.16, χ2 = 6, p = 0.01). PAx is a new modified index of cerebrovascular reactivity which performs equally well as established PRx in long-term monitoring in severe TBI patients, but importantly is potentially more robust at lower values of ICP. In view of establishing an autoregulation-oriented CPP therapy, continuous determination of PAx is feasible but its value has to be evaluated in a prospective controlled trail.

Continuous Monitoring of the Monro-Kellie Doctrine: Is It Possible?

The Monro-Kellie doctrine describes the principle of homeostatic intracerebral volume regulation, which stipulates that the total volume of the parenchyma, cerebrospinal fluid, and blood remains constant. Hypothetically, a slow shift (e.g., brain edema development) in the irregular vasomotion-driven exchanges of these compartmental volumes may lead to increased intracranial hypertension. To evaluate this paradigm in a clinical setting and measure the processes involved in the regulation of systemic intracranial volume, we quantified cerebral blood flow velocity (CBFv) in the middle cerebral artery, arterial blood pressure (ABP), and intracranial pressure (ICP), in 238 brain-injured subjects. Relative changes in compartmental compliances C(a) (arterial) and C(i) (combined venous and CSF compartments) were mathematically estimated using these raw signals through time series analysis; C(a) and C(i) were used to compute an index of cerebral compliance (ICC) as a moving correlation coefficient between C(a) and C(i). Conceptually, a negative ICC would represent a functional Monro-Kellie doctrine by illustrating volumetric compensations between C(a) and C(i). Clinical observations show that Lundberg A-waves and arterial hypertension were associated with negative ICC, whereas in refractory intracranial hypertension, a positive ICC was observed. In subjects who died, ICC was significantly greater than in survivors (0.46 ± 0.027 versus 0.22 ± 0.017; p<0.01) over the first 5 days of intensive care. The mortality rate is 5% when ICC is less than 0, and 43% when above 0.7. ICC above 0.7 was associated with terminally elevated ICP (chi-square p=0.026). We propose that the Monro-Kellie doctrine can be monitored in real time to illustrate the state of intracranial volume regulation.

Low-frequency sampling for PRx calculation does not reduce prognostication and produces similar CPPopt in intracerebral haemorrhage patients

The cerebral pressure reactivity index (PRx) correlates with the outcome in intracerebral haemorrhage (ICH) patients and has been used to define an autoregulation-oriented "optimal cerebral perfusion pressure" (CPPopt). PRx has been calculated as a moving correlation coefficient between mean arterial pressure (MAP) and intracranial pressure (ICP) averaged over 5-10 s, using a 2.5- to 5-min moving time window, in order to reflect changes in MAP and ICP within a time frame of 20 s to 2 min. We compared PRx with a different calculation method [low-frequency PRx (L-PRx)], where rapid fluctuations of MAP and ICP are cancelled (waves with frequencies greater than 0.01 Hz). A total of 548.5 h of artefact-free data (sampling frequency 1 Hz) from 18 patients suffering from non-traumatic ICH were included in the analysis. L-PRx was calculated using minute averages, between both MAP and ICP, in 20-min moving correlation windows. CPPopt was calculated based on PRx and on L-PRx. The averaged PRx values for each patient correlated with L-PRx (P = 0.846, p < 0.001). CPPopt based on standard PRx was identified in eight patients. In contrast, a CPPopt value based on L-PRx could be found in 12 patients. CPPopt values by both methods correlated strongly with each other (P = 0.980, p < 0.001). L-PRx had a similar correlation with the National Institutes of Health Stroke Scale Score (NIHSS) (0.667, p = 0.002) as did PRx (0.563, p = 0.015). L-PRx correlated with the outcome as good as PRx did. CPPopt could be identified in more patients using L-PRx. Slower MAP and ICP changes (in the range of 1-20 min) can be used for autoregulation assessment and contain important prognostic information.

Evaluation of the cerebrovascular pressure reactivity index using non-invasive finapres arterial blood pressure

A pressure reactivity index (PRx) can be assessed in patients with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP) as a moving correlation coefficient between slow fluctuations of these two signals within a low frequency bandwidth. The study aimed to investigate whether the invasive ABP monitoring can be replaced with non-invasive measurement of ABP using a Finapres plethysmograph (fABP) to calculate the fPRx. There is a well-defined group of patients, suffering from hydrocephalus and undergoing CSF pressure monitoring, which may benefit from such a measurement. 41 simultaneous day-by-day monitoring of ICP, ABP and fABP were performed for about 30 min in 10 head injury patients. A Bland–Altman assessment for agreement was used to compare PRx and fPRx calculations. Performance metrics and the McNemary test were used to determine whether fPRx is sensitive enough to distinguish between functioning and disturbed cerebrovascular pressure reactivity. The fPRx correlated with PRx (RSpearman = 0.92, p < 0.001; bias = −0.04; lower and upper limits of agreement: −0.26 and 0.17, respectively). The fPRx distinguished between active and passive reactivity in more than 89% cases. The fPRx can be used with care for assessment of cerebrovascular reactivity in patients for whom invasive ABP measurement is not feasible. The fPRx is sensitive enough to distinguish between functional and deranged reactivity.

Continuous Assessment of Cerebral Autoregulation With Near-Infrared Spectroscopy in Adults After Subarachnoid Hemorrhage

In patients with subarachnoid hemorrhage, the assessment of cerebral autoregulation aids in prognosis as well as detection of vasospasm. Mx is a validated index of cerebral autoregulation based on measures of cerebral perfusion pressure and mean flow velocity on transcranial Doppler but is impractical for longer-term monitoring. Near-infrared spectroscopy is noninvasive and suitable for continuous monitoring of cerebral tissue oxygenation using the Tissue Oxygenation Index. In this study, we compared near-infrared spectroscopy-based indices of cerebral autoregulation (TOx) with Mx in patients with subarachnoid hemorrhage. Arterial blood pressure, intracranial pressure, mean flow velocity, and Tissue Oxygenation Index were recorded. Mx and TOx were calculated as moving correlation coefficients between 10-second averaged values of cerebral perfusion pressure and mean flow velocity and between cerebral perfusion pressure and Tissue Oxygenation Index. We also calculated TOxA, the moving correlation coefficient between arterial blood pressure and Tissue Oxygenation Index. Fifty-one recording sessions were performed in 27 patients with subarachnoid hemorrhage with a total duration of 62.5 hours. Correlations of Mx and TOx over time varied markedly among individual recordings. However, time-averaging over the entire recording interval in each of the 51 recordings, we found correlations between Mx and TOx and between Mx and TOxA were highly significant. This correlation was even stronger after correction for multiple sampling for each patient, reaching r=0.81 for Mx and TOx and r=0.72 for Mx and TOxA. Near-infrared spectroscopy can be used to continuously assess cerebral autoregulation in adults after subarachnoid hemorrhage.

Integration of Brain Signals in Multimodal Bedside Monitoring After Traumatic Brain Injury

Background: During the last decade, with the development of on-line monitoring and waveform analysis, inte- gration of brain signals has increasingly been used in patients with traumatic brain injury (TBI) to guide clinical manage- ment and predict outcome. Objective: The goal of this review is to describe current methodology for brain signal integration in TBI patients focusing on 'reactivity indices'. Methods: We reviewed selected techniques to monitor patients in the acute phase of TBI using the comparison and inte- gration of different physiological signals. The autoregulation indices, Mx and Mxa were defined as the moving correla- tion between cerebral blood flow velocities (CBFV) and cerebral perfusion pressure (CPP) or arterial blood pressure (ABP), respectively. The cerebrovascular pressure reactivity index PRx was defined as the moving correlation coefficient between ABP and intracranial pressure (ICP). The oxygen reactivity index, Orx, was defined as the moving correlation co- efficient between brain tissue oxygenation and CPP. Finally, Tox was defined as the moving correlation coefficient be- tween brain tissue oxygenation measured by Near Infrared Spectroscopy (NIRS) and ABP. Results: Both Mx > 0.3 and Mxa > 0.45 as well as an asymmetry of Mx between both hemispheres of the brain in the acute phase were associated with poor outcome. PRx may be used to determine the individual optimal CPP and is also a powerful and independent predictor of outcome. Orx showed conflicting results and more studies are need to determine its role in the acute setting of TBI. Studies concerning the role of NIRS in the acute phase of TBI are ongoing. Conclusion: Multimodal neuromonitoring (MNM) is useful in the neuroICU as it provides valuable insights into the pathophysiological mechanisms occurring in the acute phase of TBI. Furthermore, indices obtained with MNM have been shown to be strong predictors of outcome. Further studies combining current and emergent techniques such as NIRS em- phasize on the ability for MNM to continuously evolve.

A comparison study of cerebral autoregulation assessed with transcranial Doppler and cortical laser Doppler flowmetry

Objectives: We compared autoregulation monitored with cortical laser Doppler flowmetry (LDF) and autoregulation monitored with transcranial Doppler (TCD) in the middle cerebral artery (MCA) to verify the hypothesis that, following brain trauma, cortical vessel autoregulation to intracranial hypertension is different than assessed in the MCA.Methods: Data collected from 29 head injured patients were analysed retrospectively. Arterial blood pressure (ABP), intracranial pressure (ICP), flow velocity (FV) of the MCA and cortical flux (LDF) were monitored. Indices of cortical autoregulation (Lx) and autoregulation of cerebral blood flow in the MCA (Mx) were calculated as a moving correlation coefficient between slow waves of LDF and cerebral perfusion pressure (CPP) (Lx) or FV and CPP (Mx), respectively. Intact autoregulation was indicated by negative values for Lx and Mx; disturbed autoregulation was reflected by positive values.Results: FV and LDF showed a high coherence in the slow wave spectrum of 1–4 cycles/min (mean: 0·79 ± 0·12), indicating that similar information regarding autoregulation is carried by both signals. Mx and Lx correlated in all patients (R=0·43, p=0·02). On average, Lx was significantly higher than Mx; the mean difference was 0·13 ± 0·38 (p=0·032), potentially due to severe intracranial hypertension above 40 mmHg, driving CPP values below 60 mmHg.Conclusion: After traumatic brain injury, cortical autoregulation appears to be worse than autoregulation assessed in the MCA during rising ICP and falling CPP. When CPP is above 60 mmHg, cortical assessed autoregulation is similar to autoregulation assessed in the MCA.

Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury*

To evaluate the concept of a cerebrovascular pressure reactivity-guided optimal cerebral perfusion pressure after traumatic brain injury by analyzing the relationship between optimal cerebral perfusion pressure and brain tissue oxygen. Prospective observational cohort study. Neurosurgical intensive care unit of a university hospital. Thirty-eight patients after head injury. Continuous computerized monitoring of mean arterial pressure, intracranial pressure, and brain tissue oxygen for 5.3 +/- 2.6 days. The index of cerebrovascular pressure reactivity was calculated as a moving correlation coefficient between spontaneous low-frequency fluctuations of mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure was defined as the cerebral perfusion pressure level with the lowest average index of cerebrovascular pressure reactivity. Optimal cerebral perfusion pressure could be identified in 32 of 38 patients. Median optimal cerebral perfusion pressure was between 70 and 75 mm Hg (range, 60-100 mm Hg). Below the level of optimal cerebral perfusion pressure, brain tissue oxygen decreased in parallel to cerebral perfusion pressure, whereas brain tissue oxygen reached a plateau above optimal cerebral perfusion pressure. Optimal cerebral perfusion pressure correlated significantly with the cerebral perfusion pressure level, where brain tissue oxygen reached its plateau (r = .79; p < .01). Average brain tissue oxygen at optimal cerebral perfusion pressure was 24.5 +/- 6.0 mm Hg. This study supports the concept of cerebrovascular pressure reactivity-based individual optimal cerebral perfusion pressure. Driving cerebral perfusion pressure in excess of optimal cerebral perfusion pressure does not yield improvements in brain tissue oxygen after head injury and should be avoided, whereas cerebral perfusion pressure below optimal cerebral perfusion pressure may result in secondary cerebral ischemia.

Cerebral autoregulation in patients with obstructive sleep apnea syndrome during wakefulness

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for stroke. Impairment of cerebral autoregulation may play a potential role in the pre-disposition to stroke of OSAS patients. In this study, we aimed to assess dynamic cerebral autoregulation (DCA) during wakefulness in OSAS patients and a group of matched controls. Patients and controls were examined in the morning after an overnight complete polysomnography. Mean cerebral blood flow velocity (CBFV) in the middle cerebral artery and mean arterial blood pressure (ABP) were continuously recorded using transcranial Doppler and Finapres. DCA was assessed using the Mx autoregulatory index. Mx is a moving correlation coefficient between mean CBFV and mean ABP. More positive value of Mx indicates worse autoregulation. Eleven OSAS patients (mean age +/- SD; 52.6 +/- 7.9) and 9 controls (mean age +/- SD; 49.1 +/- 5.3) were enrolled. The mean apnea-hypopnea index (AHI) in the OSAS group was of 22.7 +/- 11.6. No significant difference was found between the two groups as for age, body mass index, mean ABP and endtidal CO(2) pressure. Cerebral autoregulation was impaired in OSAS patients compared with controls (Mx index: 0.414 +/- 0.138 vs. 0.233 +/- 0.100; P = 0.009). The severity of autoregulation impairment correlated to the severity of the sleep respiratory disturbance measured by the AHI (P = 0.003). Cerebral autoregulation is impaired in patients with OSAS during wakefulness. Impairment of cerebral autoregulation is correlated with the severity of OSAS.

Impaired Cerebral Vasomotor Activity in Spontaneous Intracerebral Hemorrhage

Impairment of cerebrovascular autoregulation may promote secondary brain injury in acute brain insults. Until now, only limited data are available on autoregulation in patients with spontaneous intracerebral hemorrhage. In the current study, we aimed to investigate cerebrovascular reactivity and its significance for outcome in spontaneous intracerebral hemorrhage. We continuously recorded mean arterial pressure, intracranial pressure, and cerebral perfusion pressure for mean 95 hours in 20 patients with spontaneous intracerebral hemorrhage. The moving correlation coefficient between mean arterial pressure and intracranial pressure (pressure reactivity index), an index of cerebral vasoreactivity, was calculated from the available artifact-free monitoring time (mean, 50.4 hours). In the univariate analysis pressure reactivity index (r=0.66; P=0.002), hemorrhage volume (r=0.62; P=0.007), cerebral perfusion pressure (r=-0.71; P=0.001), mean arterial pressure (r=-0.61; P=0.005), and hematoma growth (r=0.53; P=0.02) significantly correlated with National Institutes of Health Stroke Scale Score at discharge. In a multivariate stepwise linear regression model, pressure reactivity index remained the only independent predictor of outcome (beta=0.659; P=0.004). In the subgroup of patients with pressure reactivity index greater than a functional threshold of >0.2, the correlation between mean cerebral perfusion pressure and outcome remained significant (r=-0.73; P=0.0102), whereas National Institutes of Health Stroke Scale Score at discharge did not correlate with cerebral perfusion pressure in patients with pressure reactivity index <0.2 (r=-0.05; P=0.9078). We found evidence for impaired cerebral vasomotor activity as measured by pressure reactivity index in patients with spontaneous intracerebral hemorrhage. We suggest that impaired cerebrovascular reactivity contributes to poor outcome in intracerebral hemorrhage patients. This effect may be mediated by fluctuations in cerebral perfusion.

Continuous monitoring of carbon dioxide reactivity in traumatic brain injury

The objective is to study the relationship between end-tidal carbon dioxide (EtCO2) and cerebrovascular pressure reactivity in traumatic brain injury (TBI). Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between the mean intracranial pressure (ICP) and mean arterial blood pressure. A negative or zero value reflects a normally reactive vascular bed whereas positive values reflect passive, non-reactive vessels. This index correlates significantly with outcome after TBI [1]. Carbon dioxide affects the cerebral vascular response. Our aim is to identify the optimal EtCO2, at which PRx reaches its lowest value.

Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury

Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between mean intracranial pressure (ICP) and mean arterial blood pressure. The authors analyzed a database consisting of 398 patients with head injuries who underwent continuous monitoring of cerebrovascular pressure reactivity. In 298 patients, the PRx was compared with a transcranial Doppler ultrasonography assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17 patients with the PET-assessed static rate of autoregulation, and in 22 patients with the cerebral metabolic rate for O(2). Patient outcome was assessed 6 months after injury. There was a positive and significant association between the PRx and Mx (R(2) = 0.36, p < 0.001) and with the static rate of autoregulation (R(2) = 0.31, p = 0.02). A PRx > 0.35 was associated with a high mortality rate (> 50%). The PRx showed significant deterioration in refractory intracranial hypertension, was correlated with outcome, and was able to differentiate patients with good outcome, moderate disability, severe disability, and death. The graph of PRx compared with cerebral perfusion pressure (CPP) indicated a U-shaped curve, suggesting that too low and too high CPP was associated with a disturbance in pressure reactivity. Such an optimal CPP was confirmed in individual cases and a greater difference between current and optimal CPP was associated with worse outcome (for patients who, on average, were treated below optimal CPP [R(2) = 0.53, p < 0.001] and for patients whose mean CPP was above optimal CPP [R(2) = -0.40, p < 0.05]). Following decompressive craniectomy, pressure reactivity initially worsened (median -0.03 [interquartile range -0.13 to 0.06] to 0.14 [interquartile range 0.12-0.22]; p < 0.01) and improved in the later postoperative course. After therapeutic hypothermia, in 17 (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold of 37 degrees C, ICP remained stable, but the average PRx increased to 0.32 (p < 0.0001), indicating significant derangement in cerebrovascular reactivity. The PRx is a secondary index derived from changes in ICP and arterial blood pressure and can be used as a surrogate marker of cerebrovascular impairment. In view of an autoregulation-guided CPP therapy, a continuous determination of a PRx is feasible, but its value has to be evaluated in a prospective controlled trial.

Near-Infrared Spectroscopy can Monitor Dynamic Cerebral Autoregulation in Adults

To study the correlation between a dynamic index of cerebral autoregulation assessed with blood flow velocity (FV) using transcranial Doppler, and a tissue oxygenation index (TOI) recorded with near-infrared spectroscopy (NIRS). Twenty-three patients with sepsis, severe sepsis, or septic shock were monitored daily on up to four consecutive days. FV, TOI, and mean arterial blood pressure (ABP) were recorded for 60 min every day. An index of autoregulation (Mx) was calculated as the moving correlation coefficient between 10-s averaged values of FV and ABP over moving 5 min time-windows. The index Tox was evaluated as the correlation coefficient between TOI and ABP in the same way. The indices Mx and Tox, ABP and arterial partial pressure of CO(2) were averaged for each patient. Synchronized slow waves, presenting with periods from 20 s to 2 min, were seen in the TOI and FV of most patients, with a reasonable coherence between the signals in this bandwidth (coherence >0.5). The indices, Mx and Tox, demonstrated good correlation with each other (R = 0.81; P < 0.0001) in the whole group of patients. Both indices showed a significant (P < 0.05) tendency to indicate weaker autoregulation in the state of vasodilatation associated with greater values of arterial partial pressure of CO(2) or lower values of ABP. NIRS shows promise for the continuous assessment of cerebral autoregulation in adults.

How does CSF dynamics change after shunting?

Hydrocephalus is much more complex than a simple disorder of cerebrospinal fluid (CSF) circulation. Shunting primarily corrects disturbed fluid flow which may have an impact on cerebral blood flow and metabolism. We studied hydrocephalic patients before and after shunting to characterize changes in their CSF compensatory parameters. We selected 25 patients and studied them retrospectively. All patients had ventriculomegaly and clinical symptoms of normal pressure hydrocephalus. After shunting, they were still presenting with some adverse symptoms, mainly headaches, slow improvement or no improvement of ventriculomegaly. Therefore, they underwent further infusion studies to assess shunt function. In all cases, the shunts were confirmed to be draining CSF adequately. Parameters of CSF dynamics: baseline intracranial pressure (ICP), resistance to CSF outflow, cerebrospinal elasticity, content of vasogenic pressure waves (pulse, respiratory and B waves) and compensatory reserve assessed as moving correlation coefficient between mean CSF pressure and pulse amplitude (RAP), were compared before and after shunting. Mean ICP and resistance to CSF outflow decreased (P < 0.003) after shunting. All vasogenic pressure waves decreased (P < 0.005). Compensatory reserve (RAP) significantly improved (P < 0.005). A functioning shunt has an important impact on CSF circulation and pressure-volume compensation. Infusion studies can demonstrate the return of disturbed CSF dynamics to normal values even if clinical or radiological changes are not dramatic.