Christian Bauhuf

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/m2) 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.

Slow Rhythmic Oscillations of Blood Pressure, Intracranial Pressure, Microcirculation, and Cerebral Oxygenation Dynamic Interrelation and Time Course in Humans

BACKGROUND AND PURPOSEnVarious biological signals show nonpulsatile, slow rhythmic oscillations. These include arterial blood pressure (aBP), blood flow velocity in cerebral arteries, intracranial pressure (ICP), cerebral microflow, and cerebral tissue PO2. Generation and interrelations between these rhythmic fluctuations remained unclear. The aim of this study was to analyze whether stable dynamic interrelations in the low-frequency range exist between these different variables, and if they do, to analyze their exact time delay.nnnMETHODSnIn a clinical study, 16 comatose patients with either higher-grade subarachnoid hemorrhage or severe traumatic brain injury were examined. A multimodal digital data acquisition system was used to simultaneously monitor aBP, flow velocity in the middle cerebral artery (FVMCA), ICP, cerebral microflow, and oxygen saturation in the jugular bulb (SjO2). Cross-correlation as a means to analyze time delay and correlation between two periodic signals was applied to a time series of 30 minutes duration divided into four segments of 2048 data points (approximately 436 seconds) each. This resulted in four cross-correlations for each 30-minute time series. If the four cross-correlations were consistent and reproducible, averaging of the original cross-correlations was performed, resulting in a representative time delay and correlation for the complete 30-minute interval.nnnRESULTSnReproducible cross-correlations and stable dynamic interrelations were found between aBP, FVMCA, ICP, and SjO2. The mean time delay between aBP and ICP was 6.89 +/- 1.90 seconds, with a negative correlation in 81%. A mean time delay of 1.50 +/- 1.29 seconds (median, 0.85 seconds) was found between FVMCA and ICP, with a positive correlation in 94%. The mean delay between ICP and SjO2 was 9.47 +/- 2.21 seconds, with a positive correlation in 77%. Mean values of aBP and ICP did not influence the time delay and dynamic interrelation between the different parameters.nnnCONCLUSIONSnThese results strongly support Rosners theory that ICP B-waves are the autoregulatory response of spontaneous fluctuations of cerebral perfusion pressure. There is casuistic evidence that failure of autoregulation significantly modifies time delay and the correlation between aBP and ICP.

Effect of Intra-Arterial Papaverine on Regional Cerebral Blood Flow in Hemodynamically Relevant Cerebral Vasospasm

Background and Purpose — It remains controversial whether the intra-arterial administration of papaverine (IAP) is effective in reversing vasospasm-associated cerebral hypoperfusion after aneurysmal subarachnoid hemorrhage. The aim of the present study was to continuously assess regional cerebral blood flow (rCBF) during and after IAP with the use of quantitative, bedside thermal diffusion flowmetry. Methods — Eight patients with cerebral vasospasm after subarachnoid hemorrhage (mean flow velocity >120 cm/s; angiographic vessel constriction >33%; hemispheric cerebral blood flow [CBF] <32 mL/100 g per minute) were prospectively entered into the study. Before IAP, thermal diffusion microprobes were implanted into the white matter of each affected vascular territory (n=10) for rCBF monitoring. During and after IAP (300 mg papaverine/50 mL saline over 1 hour), mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, thermal diffusion rCBF (TD-rCBF), and cerebrovascular resistance (CVR) were recorded continuously. Results — IAP significantly increased TD-rCBF from 7.3±1.6 to 37.9±6.6 mL/100 g per minute (mean±SEM), indicating reversal of cerebral hypoperfusion. This TD-rCBF response was dependent on the degree of cerebral vasospasm and reduced perfusion within the vascular territory. Long-term analysis of TD-rCBF, however, demonstrated that this beneficial effect of IAP on cerebral hypoperfusion was only transient: within 3 hours after treatment, TD-rCBF and CVR returned to baseline values. Furthermore, a lack of correlation between transcranial Doppler sonography and thermal diffusion flowmetry suggested that transcranial Doppler sonography is not suited for CBF-based neuromonitoring after IAP. Conclusions — IAP is not effective in permanently reversing cerebral hypoperfusion in patients with cerebral vasospasm. The need to validate alternative therapeutic strategies that seek to improve cerebral perfusion in vasospasm warrants continued development of CBF-based neuromonitoring strategies.

Therapy of malignant intracranial hypertension by controlled lumbar cerebrospinal fluid drainage.

ObjectivesTo evaluate the effect of controlled lumbar cerebrospinal fluid drainage in adult patients with refractory intracranial hypertension. DesignProspective, pre- vs. postintervention study. SettingSurgical intensive care unit of a university hospital. PatientsTwenty-three patients with severe traumatic brain injury or delayed ischemia after subarachnoid hemorrhage with intracranial hypertension refractory to aggressive treatment, including repeated applications of tromethamine, hypertonic saline solution, barbiturate coma, and decompressive craniectomy. Patients were considered for controlled lumbar cerebrospinal fluid drainage if basal cisterns on computerized tomography scan were discernible. InterventionsAfter institution of a lumbar drain, cerebrospinal fluid was gradually aspirated, and then, continuous cerebrospinal fluid drainage was maintained under control of intracranial pressure (ICP) and pupillary status. Measurements and Main Results ICP and cerebral perfusion pressure before and after initiation of lumbar cerebrospinal fluid drainage and related complications were documented. The neurologic outcome of the patients was assessed according to the Glasgow Outcome Scale 6 months after injury. As a result of lumbar cerebrospinal fluid drainage, all patients demonstrated an immediate and lasting decrease of ICP and a concomitant increase of cerebral perfusion pressure. Two patients temporarily showed a unilateral fixed and dilated pupil 6 and 8 hrs after onset of lumbar cerebrospinal fluid drainage, respectively. Ten patients showed a favorable outcome, four patients survived with a severe permanent neurologic deficit, one patient remained in a persistent vegetative state, and eight patients died. ConclusionsControlled lumbar cerebrospinal fluid drainage significantly reduces refractory intracranial hypertension. The danger of transtentorial or tonsillar herniation is minimized by considering lumbar drainage in the presence of discernible basilar cisterns only.

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 methods 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 → FVMCA left] of 6.45 ± 2.1 secs, and for CC [BP → FVMCA right] 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.

Controlled drainage of lumbar cerebrospinal fluid for the management of increased intracranial pressure in patients with subarachnoid hemorrhage

Abstract Intercranial hypertension represents a significant complication in patients with severe subarachnoid hemorrhage (SAH) from aneurysm rupture. In the acute state of SAH, increased intracranial pressure (ICP) is usually due to the direct effect of the initial hemorrhage. Over the following days, ICP may rise as a result of cerebral ischemia from developing vasospasm. Management protocols for intercranial hypertension include hyperventilation, use of mannitol ventricular cerebrospinal fluid (CSF) drainage, sedation, hypertonic saline, barbiturate coma, and decompressive surgery. In addition to these measures, we have introduced lumbar CSF drainage for the control of malignant hypertension over the last 3 years. A total of 21 patients included. All had SAH from ruptured aneurysm and underwent early surgery. Postoperative increase of ICP was treated according to a standard protocol. When all other measures had failed, lumbar CSF drainage was initiated under continuous ICP monitoring. In all patients, this resulted in an immediate decrease of ICP and an increase of cerebral perfusion pressure (CPP). Lumbar drainage was continued for a mean of 4.8 days, and without exception, resulted in lasting control of elevated ICP. In two patients with absent basal cisterns before treatment, transient herniation of the brain resulted from lumbar drainage. We conclude that controlled lumbar CSF drainage represents an effective method to control refractory intercranial hypertension in carefully selected patients.