ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity

Background

To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately.

Methods

Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)—correlation between ICP and mean arterial pressure (MAP), PAx—correlation between pulse amplitude of ICP (AMP) and MAP, RAC—correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx—correlation between mean flow velocity (FVm) and CPP, Mx_a—correlation between FVm and MAP, Sx—correlation between systolic flow velocity (FVs) and CPP, Sx_a—correlation between FVs and MAP, Dx—correlation between diastolic flow index (FVd) and CPP, Dx_a—correlation between FVd and MAP], and LDF derived (Lx—correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a—correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA).

Results

LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin.

Conclusions

Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

     

Monitoring cerebral autoregulation after head injury. Which component of transcranial Doppler flow velocity is optimal?

Background

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI.

Methods

300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10?s averaged values. The relationship with age, severity of injury, and dichotomized 6?months outcome was examined.

Results

Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F?=?20.11; P?=?0.00001 and F?=?13.10; P?=?0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F?=?12.49; P?=?0.0005 and F?=?5.32; P?=?0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome.

Conclusions

Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.     

Continuous Monitoring of Cerebrovascular Reactivity Using Pulse Waveform of Intracranial Pressure

Background

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.

Methods

A retrospective analysis of prospective 327 TBI patients (admitted on neurocritical care unit of a university hospital in the period 2003?C2009) with continuous ABP and ICP monitoring.

Results

PAx was worse in patients who died compared to those who survived (?0.04?±?0.15 vs. ?0.16?±?0.15, ??²?=?28, p?2?=?6, p?=?0.01).

Conclusions

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.     

Association between intracranial,arterial pulse pressure amplitudes and cerebral autoregulation in head injury patients

Abstract

Objective: To explore whether intracranial pulse pressure amplitudes relate to arterial pulse pressure amplitudes and whether correlations between time-related changes in intracranial and arterial pulse pressure amplitudes associate with indices of cerebral autoregulation.

Methods: A total of 257 continuous and simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and middle cerebral artery (MCA) blood velocity recordings were obtained 1–14 days after ictus in 76 traumatic head injury patients and analysed retrospectively. Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse pressure amplitudes of corresponding single ICP and ABP waves were correlated in consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and mean and systolic MCA blood flow velocities, were computed in consecutive 6 second time windows. The indices of cerebral autoregulation PRx (moving correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation between mean and systolic MCA blood velocity and cerebral perfusion pressure) were calculated over 4 minute periods and averaged over each recording.

Results: Intracranial pulse pressure amplitudes were not related to arterial pulse pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome was related to mean ICP, PRx and Sx (p ≤ 0.04, multiple regression analysis). Correlations between intracranial and arterial pulse pressure amplitudes were weakly related to PRx (Pearson's correlation coefficient: 0.16; p=0.01), but were not related to the indices of cerebral autoregulation Mx (Pearson's correlation coefficient: 0.07) and Sx (Pearson's correlation coefficient: 0.04).

Conclusions: In this cohort of pressure recordings, we found no evidence of a correlation between intracranial and arterial blood pressure amplitudes. The correlation appeared not to be related to the state of cerebral autoregulation, although a weak correlation was found with pressure reactivity index PRx.     

Reactivity of Brain Tissue Oxygen to Change in Cerebral Perfusion Pressure in Head Injured Patients

Objective  It has been reported recently that correlation between brain tissue oxygen (PbtO₂) and cerebral perfusion pressure (CPP) may serve as an indicator of cerebral autoregulation after subarachnoid hemorrhage. We aimed to compare similar indices describing interaction between changes in intracranial pressure (ICP), arterial blood pressure (ABP), and brain tissue oxygen to verify their clinical utility in patients after traumatic brain injury. Materials and Methods  Retrospective analysis of multimodal monitoring of 32 patients suffering from head injury, admitted in the Neurosciences Critical Care Unit, Addenbrooke’s Hospital, Cambridge, UK. Initial 24 h intervals of continuous ABP, ICP, and PbtO₂ recordings were analyzed. Index of tissue oxygen reactivity ORx was evaluated as the correlation coefficient between PbtO₂ and CPP over a period of 60 min and compared to the index of pressure reactivity PRx. “Optimal CPP” and a hypothetical “optimal PbtO₂” were defined as the ranges of CPP and PbtO₂ at which PRx or ORx were indicating best cerebrovascular milieu. Results  PRx and ORx mean values did not show any correlation with each other (R = 0.012; P = 0.95) between patients. There was also no correlation between ORx and PbtO₂ (R = 0.098; P = 0.61) and between PRx and PbtO₂ (R = 0.019; P = 0.923). No clear and consistent value of “optimal CPP” minimizing ORx or of hypothetical “optimal PbtO₂” were found analyzing PbtO₂ or ORx trend over the 24 h of monitoring. However, in most of patients ‘optimal CPP’ has been found for PRx index. The same has been confirmed when the data from whole monitoring period were analyzed. There was no correlation between values of ‘optimal CPP’ assessed using ORx and ‘optimal CPP’ assessed with PRx. Conclusion  The relationships between PbtO₂, ORx, and CPP in head injury appear less useful than reported before for patients after subarachnoid hemorrhage.     

Temporal changes in cerebral tissue oxygenation with cerebrovascular pressure reactivity in severe traumatic brain injury

Objective

To investigate the temporal relationship between cerebrovascular pressure reactivity and brain tissue oxygenation in patients with severe head injury.

Methods

In 40 patients, brain tissue oxygenation and intracranial pressure were monitored. Time‐averaged values for intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain tissue oxygenation (PtiO₂) were computed. The pressure reactivity index (PRx) was calculated. The mean values of the variables were obtained at the 6‐h and 72‐h post‐injury time points, and the difference between the two time points for each of the variables was denoted as delta (δ).

Results

Of the 40 patients, 32 were survivors and 8 were non‐survivors. Statistically significant differences were present between these two groups with regard to δMAP (p = 0.013), ICP at 6 h (p = 0.027), CPP at 72 h (p = 0.018), δCPP (p = 0.033), PRx at 6 h (p = 0.029), PRx at 72 h (p = 0.002), PtiO₂ at 72 h (p<0.0005) and δPtiO₂ (p = 0.023) values, reflecting an improvement with time in survivors and a deterioration with time in non‐survivors. In non‐survivors, the magnitude of change in PtiO₂ and CPP with time correlated in a negative linear fashion (p = 0.042 and 0.029, respectively) with the change in PRx with time, whereas no such relationship was seen in survivors.

Conclusion

The severity of brain tissue oxygenation derangement correlates with increasing cerebrovascular dysautoregulation in patients succumbing to severe head injury, supporting the utility of PRx as a monitoring variable and the rationale for a target‐driven approach to head injury management.Cerebral ischaemia is a critical contributory factor to secondary brain injury after trauma. In the presence of an unstable cerebral perfusion pressure (CPP), the autoregulatory cerebrovascular reactivity attempts to maintain an adequate cerebral blood flow. Increasing CPP may result in raised or lowered intracranial pressure (ICP), depending on whether cerebral autoregulation is preserved. Rosner et al¹ have described how increases in CPP within the autoregulatory range lead to compensatory vasoconstriction to maintain a stable cerebral blood flow. In so doing, cerebral blood volume and thus ICP levels fall. However, outside of these autoregulatory limits, a pressure‐passive scenario exists where increases in CPP lead to vasodilatation and a rise in ICP. Investigators have defined an index comparing arterial blood pressure (ABP) and ICP to quantify this relationship between CPP and ICP, known as the pressure reactivity index (PRx).^2,3 If a rise in ABP (and hence CPP) leads to a parallel increase in ICP, a good correlation exists, and the PRx is positive. However, in the face of intact cerebral autoregulatory capacity, vasoconstriction in the face of rising CPP leads to a drop in ICP, and hence PRx approaches zero or takes a negative value. Measurement of PRx could thus form the basis for target‐driven management, as ABP can be manipulated.Clinical studies on patients with head injury have shown the feasibility of continuous monitoring of local brain tissue oxygenation (PtiO₂) as a variable for cerebral oxygenation.^4,5,6 Despite the limitations of such a local method of measurement, PtiO₂ indicates global cerebral oxygenation when the monitoring is carried out in a relatively uninjured part of the brain.⁶ The presence of autoregulation disturbance could conceivably lead to disturbance in oxygen tension in the tissue of interest by virtue of blood flow metabolism uncoupling as PtiO₂ reflects the net balance between oxygen supply and demand at the tissue level.⁷We hypothesised that a worsening PRx indicative of increasing dysautoregulation during the temporal course of monitoring is related to mortality, and this may arise from specific patterns of change in various physiological variables including PtiO₂.     

Association between intracranial, arterial pulse pressure amplitudes and cerebral autoregulation in head injury patients

OBJECTIVE: To explore whether intracranial pulse pressure amplitudes relate to arterial pulse pressure amplitudes and whether correlations between time-related changes in intracranial and arterial pulse pressure amplitudes associate with indices of cerebral autoregulation. METHODS: A total of 257 continuous and simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and middle cerebral artery (MCA) blood velocity recordings were obtained 1-14 days after ictus in 76 traumatic head injury patients and analysed retrospectively. Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse pressure amplitudes of corresponding single ICP and ABP waves were correlated in consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and mean and systolic MCA blood flow velocities, were computed in consecutive 6 second time windows. The indices of cerebral autoregulation PRx (moving correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation between mean and systolic MCA blood velocity and cerebral perfusion pressure) were calculated over 4 minute periods and averaged over each recording. RESULTS: Intracranial pulse pressure amplitudes were not related to arterial pulse pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome was related to mean ICP, PRx and Sx (p 相似文献   

Relationship of Vascular Wall Tension and Autoregulation Following Traumatic Brain Injury

Background

The vascular wall tension (WT) of small cerebral vessels can be quantitatively estimated through the concept of critical closing pressure (CrCP), which denotes the lower limit of arterial blood pressure (ABP), below which small cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as the difference between CrCP and intracranial pressure (ICP) and represent active vasomotor tone. In this study, we investigated the association of WT and CrCP with autoregulation and outcome of a large group of patients after traumatic brain injury (TBI).

Methods

We retrospectively analysed recordings of ABP, ICP and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median age: 29 years; interquartile range: 20–43). CrCP and WT were calculated using the cerebrovascular impedance methodology. Autoregulation was assessed based on TCD-based indices, Mx and ARI.

Results

Low values of WT were found to be associated with an impaired autoregulatory capacity, signified by its correlation to FV-based indices Mx (R = ?0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No relationship could be established between CrCP and any of the autoregulatory indices. Neither CrCP nor WT was found to correlate with outcome.

Conclusions

Impaired autoregulation was found to be associated with a lower WT supporting the role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no links between CrCP and autoregulation could be identified.     

Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

Background

Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility.

Methods

Retrospective analysis was performed in 85 patients with traumatic brain injury (TBI). ORx was calculated using three time windows of 5, 20, and 60 min. Correlation coefficients and individual “optimal CPP” (CPP_opt) were calculated using both PRx and ORx, and relation to patient outcome investigated.

Results

Correlation coefficients for all comparisons between PRx and ORx indicated poor association between these indices (range from ?0.04 to 0.07). PRx was significantly lower in patients with good outcome (p = 0.01), while none of the ORx indices proved to be significantly different in the two outcome groups. Higher mortality related to average CPP < CPP_opt was found regardless of which index was used to calculate CPP_opt.

Conclusion

In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear.

     

Comparison of frequency and time domain methods of assessment of cerebral autoregulation in traumatic brain injury

The impulse response (IR)-based autoregulation index (ARI) allows for continuous monitoring of cerebral autoregulation using spontaneous fluctuations of arterial blood pressure (ABP) and cerebral flow velocity (FV). We compared three methods of autoregulation assessment in 288 traumatic brain injury (TBI) patients managed in the Neurocritical Care Unit: (1) IR-based ARI; (2) transfer function (TF) phase, gain, and coherence; and (3) mean flow index (Mx). Autoregulation index was calculated using the TF estimation (Welch method) and classified according to the original Tiecks'' model. Mx was calculated as a correlation coefficient between 10-second averages of ABP and FV using a moving 300-second data window. Transfer function phase, gain, and coherence were extracted in the very low frequency (VLF, 0 to 0.05 Hz) and low frequency (LF, 0.05 to 0.15 Hz) bandwidths. We studied the relationship between these parameters and also compared them with patients'' Glasgow outcome score. The calculations were performed using both cerebral perfusion pressure (CPP; suffix ‘c'') as input and ABP (suffix ‘a''). The result showed a significant relationship between ARI and Mx when using either ABP (r=−0.38, P<0.001) or CPP (r=−0.404, P<0.001) as input. Transfer function phase and coherence_a were significantly correlated with ARI_a and ARI_c (P<0.05). Only ARI_a, ARI_c, Mx_a, Mx_c, and phase_c were significantly correlated with patients'' outcome, with Mx_c showing the strongest association.     

Should the Neurointensive Care Management of Traumatic Brain Injury Patients be Individualized According to Autoregulation Status and Injury Subtype?

Introduction

The status of autoregulation is an important prognostic factor in traumatic brain injury (TBI), and is important to consider in the management of TBI patients. Pressure reactivity index (PRx) is a measure of autoregulation that has been thoroughly studied, but little is known about its variation in different subtypes of TBI. In this study, we examined the impact of PRx and cerebral perfusion pressure (CPP) on outcome in different TBI subtypes.

Methods

107 patients were retrospectively studied. Data on PRx, CPP, and outcome were collected from our database. The first CT scan was classified according to the Marshall classification system. Patients were assigned to “diffuse” (Marshall class: diffuse-1, diffuse-2, and diffuse-3) or “focal” (Marshall class: diffuse-4, evacuated mass lesion, and non-evacuated mass lesion) groups. 2 × 2 tables were constructed calculating the proportions of favorable/unfavorable outcome at different combinations of PRx and CPP.

Results

Low PRx was significantly associated with favorable outcome in the combined group (p = 0.002) and the diffuse group (p = 0.04), but not in the focal group (p = 0.06). In the focal group higher CPP values were associated with worse outcome (p = 0.02). In diffuse injury patients with disturbed autoregulation (PRx >0.1), CPP >70 mmHg was associated with better outcome (p = 0.03).

Conclusion

TBI patients with diffuse injury may differ from those with mass lesions. In the latter higher levels of CPP may be harmful, possibly due to BBB disruption. In TBI patients with diffuse injury and disturbed autoregulation higher levels of CPP may be beneficial.     

Cerebral vasomotor reactivity testing in head injury: the link between pressure and flow

BACKGROUND: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity in patients with head injury. OBJECTIVES: To validate this index and study its relation with cerebral blood flow velocity and cerebral autoregulation; and to identify variables associated with impairment or preservation of cerebral vasomotor reactivity. METHODS: The PRx was validated in a prospective study of 40 head injured patients. A PRx value of less than 0.3 indicates intact cerebral vasomotor reactivity, and a value of more than 0.3, impaired reactivity. Arterial blood pressure, intracranial pressure, mean cerebral perfusion pressure, and cerebral blood flow velocity, measured bilaterally with transcranial Doppler ultrasound, were recorded. Dynamic cerebrovascular autoregulation was measured using a moving correlation coefficient between arterial blood pressure and cerebral blood flow velocity, the Mx, for each cerebral hemisphere. All variables were compared in patients with intact and impaired cerebral vasomotor reactivity. RESULTS: No correlation between arterial blood pressure or cerebral perfusion pressure and cerebral blood flow velocity was seen in 19 patients with intact cerebral vasomotor reactivity. In contrast, the correlation between these variables was significant in 21 patients with impaired cerebral vasomotor reactivity, whose cerebral autoregulation was reduced. There was no correlation with intracranial pressure, arterial blood pressure, cerebral perfusion pressure, or interhemispheric cerebral autoregulation differences, but the values for these indices were largely within normal limits. CONCLUSIONS: The PRx is valid for monitoring and quantifying cerebral vasomotor reactivity in patients with head injury. This intracranial pressure based index reflects changes in cerebral blood flow and cerebral autoregulatory capacity, suggesting a close link between blood flow and intracranial pressure in head injured patients. This explains why increases in arterial blood pressure and cerebral perfusion pressure may be useful for reducing intracranial pressure in selected head injured patients (those with intact cerebral vasomotor reactivity).     

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.     

Critical closing pressure in cerebrovascular circulation

OBJECTIVE: Cerebral critical closing pressure (CCP) has been defined as an arterial pressure threshold below which arterial vessels collapse. Hypothetically this is equal to intracranial pressure (ICP) plus the contribution from the active tone of cerebral arterial smooth muscle. The correlation of CCP with ICP, cerebral autoregulation, and other clinical and haemodynamic modalities in patients with head injury was evaluated. METHOD: intracranial pressure, arterial blood pressure (ABP) and middle cerebral artery blood flow velocity were recorded daily in ventilated patients. Waveforms were processed to calculate CCP, the transcranial Doppler-derived cerebral autoregulation index (Mx), mean arterial pressure (ABP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). RESULTS: Critical closing pressure reflected the time related changes in ICP during plateau and B waves. Overall correlation between CCP and ICP was mild but significant (R=0.41; p<0.0002). The mean difference between ABP and CCP correlated with CPP (R=0.57, 95% confidence interval (95% CI) for prediction 25 mm Hg). The difference between CCP and ICP, described previously as proportional to arterial wall tension, correlated with the index of cerebral autoregulation Mx (p<0.0002) and CPP (p<0.0001). However, by contrast with the Mx index, CCP-ICP was not significantly correlated with outcome after head injury. CONCLUSION: Critical closing pressure, although sensitive to variations in ICP and CPP, cannot be used as an accurate estimator of these modalities with acceptable confidence intervals. The difference CCP-ICP significantly correlates with cerebral autoregulation, but it lacks the power to predict outcome after head injury.     

Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation in a porcine model

Objectives: In the present study, our objective was to determine if hypercarbia would alter cerebral blood flow (CBF) autoregulation and reduce the ability of cerebrovascular reactivity monitoring to identify the lower limit of cerebrovascular autoregulation (LLA).

Methods: Anaesthetised juvenile pigs were assigned between two groups: normocarbia (control group, n?=?10) or hypercarbia [high carbon dioxide (CO₂) group, n?=?8]. Normocarbia subjects were maintained with an arterial CO₂ of 40?Torr, while the hypercarbia subjects had an increase of inspired CO₂ to achieve an arterial pCO₂ of >80?Torr. Gradual hypotension was induced by continuous haemorrhage from a catheter in the femoral vein, and the LLA was determined by monitoring cortical laser Doppler flux (LDF). Vascular reactivity monitoring was performed using the pressure reactivity index (PRx) and haemoglobin volume index (HVx).

Results: There were no sustained differences in ICP between groups. Autoregulation was present in both groups, despite elevation in pCO₂.The control group had an average LLA of 45?mmHg (95% CI: 43–47?mmHg) and the high CO₂ group had a LLA of 75?mmHg (95% CI: 73–77?mmHg). The detected LLA for each subject correlated with the level of pCO₂ (spearman R?=?0.8243, P?<?0.0001). Both the PRx and HVx accurately detected the LLA despite the presence of hypercarbia.

Discussion: Hypercarbia without acidosis increases the observed LLA independent of alterations in ICP. Elevations in CO₂ can impair cerebrovascular autoregulation, but if there is a sufficient increase in blood pressure above the CO₂ altered LLA, then autoregulation persists.     

Critical closing pressure determined with a model of cerebrovascular impedance

Critical closing pressure (CCP) is the arterial blood pressure (ABP) at which brain vessels collapse and cerebral blood flow (CBF) ceases. Using the concept of impedance to CBF, CCP can be expressed with brain-monitoring parameters: cerebral perfusion pressure (CPP), ABP, blood flow velocity (FV), and heart rate. The novel multiparameter method (CCPm) was compared with traditional transcranial Doppler (TCD) calculations of CCP (CCP1). Digital recordings of ABP, intracranial pressure (ICP), and TCD-based FV from previously published studies of 29 New Zealand White rabbits were reanalyzed. Overall, CCP1 and CCPm showed correlation across wide ranges of ABP, ICP, and PaCO2 (R=0.93, P<0.001). Three physiological perturbations were studied: increase in ICP (n=29) causing both CCP1 and CCPm to increase (P<0.001 for both); reduction of ABP (n=10) resulting in decrease of CCP1 (P=0.006) and CCPm (P=0.002); and controlled increase of PaCO2 (n=8) to hypercapnic levels, which decreased CCP1 and CCPm, albeit insignificantly (P=0.123 and P=0.306 respectively), caused by a spontaneous significant increase in ABP (P=0.025). Multiparameter mathematical model of critical closing pressure explains the relationship of CCP on brain-monitoring variables, allowing the estimation of CCP during cases such as hypercapnia-induced hyperemia, where traditional calculations, like CCP1, often reach negative non-physiological values.     

Barbiturate therapy for patients with refractory intracranial hypertension following severe traumatic brain injury: its effects on tissue oxygenation, brain temperature and autoregulation.

The aim of this study was to explore the effects of barbiturate coma on cerebral tissue oxygen tension and cerebrovascular pressure reactivity (PRx), as an index of cerebral autoregulation in severe head injury patients. This was a prospective observational clinical study of 12 patients with severe traumatic brain injury, carried out at a tertiary-level neurosurgical intensive care unit between April 2002 and May 2005. All patients received standard neurosurgical intensive care and monitoring. Probes for intracranial pressure (ICP), brain temperature (BT) and brain tissue oxygenation (PTiO2) were inserted into (noncontused) normal-looking white matter. Cerebrovascular PRx was measured as a moving correlation between ICP and arterial blood pressure. Barbiturate coma was instituted when ICP became refractory (ICP>20 mmHg). All data from the multimodal monitoring were digitally extracted and statistically analysed. The mean ICP decreased with barbiturate coma in eight of the 12 patients (75% of the patients), but only four achieved a value below 20 mmHg. Of eight patients with prebarbiturate PTiO2 levels above 10 mmHg, six had a further improvement in oxygenation. Thus, concordant favourable changes in ICP, PRx and PTiO2 with barbiturate coma were seen in those who survived. Effective response to barbiturates can be detected by improved PTiO2 and autoregulation (PRx) in severe head injury patients.     

Modified flow- and oxygen-related autoregulation indices for continuous monitoring of cerebral autoregulation

Continuous monitoring of brain tissue partial pressure of oxygen (ptiO₂), thermal-diffusion regional cerebral blood flow (TD-rCBF) and cerebral perfusion pressure (CPP) allows the calculation of flow- and oxygen-related autoregulation indices ORx and FRx. The influence of temporal phase shifts on ORx and FRx due to a delay in the response time of ptiO₂ and TD-rCBF has received little attention. We investigated the impact of phase shifts between changes in CPP and the corresponding ptiO₂ and TD-rCBF responses on the degree of correlation of ORx and FRx. In five patients with aneurysmal subarachnoid hemorrhage continuous multimodal neuromonitoring was performed for 7-10 days. In each patient the phase shift of the ptiO₂- and TD-rCBF-response after spontaneous positive or negative CPP fluctuations during two 1-h time periods of disturbed cerebral autoregulation was determined. For these periods, ORx and FRx were calculated as Pearson correlation coefficients before (ORx and FRx) and after (ORx_sync and FRx_sync) temporal synchronization of ptiO₂, TD-rCBF and CPP. The mean temporal phase shift after CPP fluctuations was 65 ± 11 s for ptiO₂ and 12 ± 4 s for TD-rCBF. Before synchronization, ORx and FRx were determined at 0.52 ± 0.3 and 0.59 ± 0.3, respectively. After synchronization, ORx_sync and FRx_sync correlated significantly stronger than unsynchronized indices (ORx_sync: 0.66 ± 0.3; FRx_sync: 0.62 ± 0.3; p < 0.01 vs. ORx and FRx, respectively). These findings suggest that ORx and FRx are subject to temporal latency shifts of ptiO₂ and TD-rCBF in regard to spontaneous CPP fluctuations. Temporal synchronization for the calculation of both ORx and FRx may permit continuous monitoring of these indices with higher sensitivity.     

Near-Infrared Spectroscopy can Monitor Dynamic Cerebral Autoregulation in Adults

Objective  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). Methods  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 CO₂ were averaged for each patient. Results  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 CO₂ or lower values of ABP. Conclusion  NIRS shows promise for the continuous assessment of cerebral autoregulation in adults.