Effects of hypervolemia and hypertension on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation after subarachnoid hemorrhage.

OBJECTIVE: Hypertensive, hypervolemic, hemodilution therapy (triple-H therapy) is a generally accepted treatment for cerebral vasospasm after subarachnoid hemorrhage. However, the particular role of the three components of triple-H therapy remains controversial. The aim of the study was to investigate the influence of the three arms of triple-H therapy on regional cerebral blood flow and brain tissue oxygenation. DESIGN: Animal research and clinical intervention study. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients with subarachnoid hemorrhage. INTERVENTIONS: First, we investigated the effect of the three components of triple-H therapy under physiologic conditions in an experimental pig model. In the next step we applied the same study protocol to patients following aneurysmal subarachnoid hemorrhage. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, cardiac output, regional cerebral blood flow, and brain tissue oxygenation were continuously recorded. Intrathoracic blood volume and central venous pressure were measured intermittently. Vasopressors and/or colloids and crystalloids were administered to stepwise establish the three components of triple-H therapy. MEASUREMENTS AND MAIN RESULTS: In the animals, neither induced hypertension nor hypervolemia had an effect on intracranial pressure, brain tissue oxygenation, or regional cerebral blood flow. In the patient population, induction of hypertension (mean arterial pressure 143 +/- 10 mm Hg) resulted in a significant (p < .05) increase of regional cerebral blood flow and brain tissue oxygenation at all observation time points. In contrast, hypervolemia/hemodilution (intrathoracic blood volume index 1123 +/- 152 mL/m) induced only a slight increase of regional cerebral blood flow while brain tissue oxygenation did not improve. Finally, triple-H therapy failed to improve regional cerebral blood flow more than hypertension alone and was characterized by the drawback that the hypervolemia/hemodilution component reversed the effect of induced hypertension on brain tissue oxygenation. CONCLUSIONS: Vasopressor-induced elevation of mean arterial pressure caused a significant increase of regional cerebral blood flow and brain tissue oxygenation in all patients with subarachnoid hemorrhage. Volume expansion resulted in a slight effect on regional cerebral blood flow only but reversed the effect on brain tissue oxygenation. In view of the questionable benefit of hypervolemia on regional cerebral blood flow and the negative consequences on brain tissue oxygenation together with the increased risk of complications, hypervolemic therapy as a part of triple-H therapy should be applied with utmost caution.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation.

OBJECTIVE: Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. DESIGN: Animal research and clinical intervention study. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. INTERVENTIONS: Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. MEASUREMENTS AND MAIN RESULTS: In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. CONCLUSIONS: Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.

Continuous cerebral autoregulation monitoring by cross-correlation analysis.

In order to validate cross-correlation analysis between spontaneous slow oscillations of arterial blood pressure (aBP) and intracranial pressure (ICP) or flow velocity as a means to assess the status of cerebral autoregulation continuously, we compared its results with different autoregulation bedside tests. The second aim was to check the method's stability over longer time periods. aBP, ICP, and flow velocity in the middle cerebral artery (FV(MCA)) was measured continuously in 13 critically ill comatose patients. Cross-correlation analysis was performed online and offline between aBP and ICP (CC [aBP --> ICP]) and aBP/FV(MCA) (CC [aBP --> FV(MCA)]). Three different autoregulation bedside tests (cuff deflation, transient hyperemic response, orthostatic hypotension) were performed immediately before a 29-min cross-correlation test period. In addition, continuous cross-correlation autoregulation monitoring was performed over multiple hours (in order to analyze for stability and to assess the influence of other factors). Cluster analysis revealed two main clusters. Cluster 1 (indicative for disturbed autoregulation) showed a centroid at t = -0.21 +/- 3.32 sec, r = 0.43 +/- 0.18 for CC [aBP --> ICP], and t = 0 +/- 3.14 sec, r = 0.44 +/- 0.18 for CC [aBP --> FV(MCA)]. Cluster 2 (indicative for normal autoregulation) revealed a centroid at t = 4.94 +/- 3.74 sec, r =- 0.4 +/- 0.16 for CC [aBP --> ICP], and t = 3.38 +/- 4.44 sec, r = -0.38 +/- 0.18 for CC [aBP --> FV(MCA)]. Comparison between the cross-correlation test results and the bedside tests showed a sensitivity of 44-73% for CC [aBP --> FV(MCA)], whereas CC [aBP --> ICP] was more specific (60-80%). Long-term monitoring revealed stable cross-correlation tests in about 45% of the measurement time. It is concluded that cross-correlation between aBP, ICP, and FV(MCA) is a valid means to monitor the autoregulation status continuously, although further improvement of sensitivity and specificity is needed to make it reliable for clinical decision making.

Continuous cerebral autoregulation monitoring by cross-correlation analysis: evaluation in healthy volunteers.

OBJECTIVE: In a former study, we applied cross-correlation (CC) analysis to recordings of arterial blood pressure (BP), intracranial pressure (ICP), and intracranial blood flow velocity (FV). A lack of significant time delay and a positive correlation coefficient of slow oscillations between these parameters was interpreted as indicative of impaired cerebral autoregulation, whereas a significant time delay and a negative correlation was regarded as preserved autoregulation. To test this hypothesis, cross-correlation was applied on recordings of BP and FV (CC [BP --> FV]) in healthy volunteers with a presumably preserved cerebral autoregulation. DESIGN: Study of a diagnostic test. SUBJECTS: A total of 17 healthy volunteers. MEASUREMENTS AND MAIN RESULTS: BP was recorded by using a tonometric device, and bilateral FV in the middle cerebral arteries (MCA) was measured by transcranial Doppler sonography. Signals were sampled at a resting horizontal position for 29 mins. Cluster analysis showed a mean +/- sd time delay for CC [BP --> FV(MCA right)] of 6.45 +/- 2.1 secs, and for CC [BP --> FV(MCA left) ] of 6.09 +/- 1.8 secs. The mean correlation coefficient was -.33 +/-.17 for the left and -.36 +/-.09 for the right side. In about 30%, differing results with a correlation coefficient between -.2 and.2 and a time delay near zero were found. Cross-correlation between left and right FV showed a mean time delay of 0.09 +/- 0.18 secs, with a mean correlation coefficient of.82 +/-.16. CONCLUSION Spontaneous slow oscillations of BP and FV were detected, and cross-correlation analysis showed a negative correlation and a positive time delay in about 70% of the examinations. These findings corroborate the hypothesis that CC [BP --> FV] might be able to assess the status of cerebral autoregulation continuously. The observed time delay between BP and FV oscillations is in good agreement with former studies on the dynamic properties of cerebral autoregulation.

Laser Doppler flowmetry mapping of cerebrocortical microflow: characteristics and limitations.

The aim of this study was to quantitatively analyze the amount of methodological noise and the spatial and temporal variability of laser Doppler flowmetry (LDF) signals mapping cerebrocortical microflow. In an experimental setup with latex beads, the methodological LDF-signal variability was determined (coefficient of variation or CV(method)). The biological variability of the LDF signals was measured in animal experiments using 10 anesthetized rabbits. One stationary reference probe was used to assess temporal heterogeneity (CV(temp)) and a micromanipulator-driven scanning probe was used to assess spatial heterogeneity (CV(spat)) in a cortical area of 3.5 x 4.5 mm with 252 measurement points. CO(2) tests were used to modulate cerebrovascular resistance. CV(method) was found to be 4.94 +/- 1.7. The CV(temp) for the LDF-velocity signal was assessed to be 13.93 +/- 5.9 during normocapnia. Scanning of the brain surface with the scanning probe revealed a CV(spat) for LDF velocity of 65.0 +/- 16.2 during normocapnia. CO(2) modulation (hypocapnia --> normocapnia --> hypercapnia) of the cerebral resistance did not show a significant change in temporal heterogeneity (10.84 +/- 3.1 --> 13.93 +/- 5.9 --> 14.82 +/- 3.9), whereas spatial heterogeneity decreased significantly (81.31 +/- 12.0 --> 65.0 +/- 16.2 --> 54.04 +/- 21.8). Although the spatial and temporal variability of LDF signals evoked by cerebrocortical microflow is in the same range as with other methods and in other organs, LDF cerebrocortical mapping is restricted by the large temporal and spatial heterogeneity of the cerebrocortical vasculature. The definitions of sample volume, scanning step width, probe to brain surface distance, and average time per scanning point are critical concerning reliable LDF cerebrocortical mapping techniques.