Disturbed Autoregulation Research Articles

Intracranial pressure pulse amplitude during changes in head elevation: a new parameter for determining optimum cerebral perfusion pressure?

During short-term postural changes, the factors determining the amplitude of intracranial pulse pressure (ICPPA) remain constant, except for cerebrovascular resistance (CVR). Therefore, it may be possible to draw conclusions from the ICPPA onto the cerebrovascular resistance (CVR) and thus the relative change in cerebral perfusion pressure (CPP). Age, sex, disease, Glasgow Coma Scale score, placement of ventricular drain, blood gas analysis, and parameters of airway management were prospectively recorded in 40 patients. The changes in intracranial pressure (ICP), CPP, mean arterial pressure (MAP), and ICPPA at head elevations of 0 degrees, 30 degrees, and 60 degrees were measured and analyzed online. Status of cerebrovascular autoregulation was checked using the pressure-reactivity index (PRx). Altogether 36 subjects fulfilled the study conditions. Three patients had positive PRx indicating disturbed autoregulation and were excluded. Thus, 33 were left for analysis (18 females and 15 males). All of them were sedated and mechanically ventilated with Glasgow Coma scores ranging from 3-8. During change in head elevation from 0 degrees to 60 degrees, we found a significant (p < 0.05) improvement of the ICP, an increase of the ICCPA, a reduction of the MAP, and a decrease in the CPP. Increasing ICPPA was linked to decreasing CPP (0 degrees to 60 degrees, r = -0.42, p < 0.05). Head elevation is an important part of the ICP and CPP therapy in neurointensive care. When searching for the patient-specific optimum upper body position, ICPPA may provide additional information. Providing that the cerebral autoregulation is intact, the lowest ICPPA of a patient corresponds to the individual upper body position with the highest CPP.

Monitoring of Cerebrovascular Autoregulation: Facts, Myths, and Missing Links

The methods for continuous assessment of cerebral autoregulation using correlation, phase shift, or transmission (either in time- or frequency-domain) were introduced a decade ago. They express dynamic relationships between slow waves of transcranial Doppler (TCD), blood flow velocity (FV) and cerebral perfusion pressure (CPP), or arterial pressure (ABP). We review a methodology and clinical application of indices useful for monitoring cerebral autoregulation and pressure-reactivity in various scenarios of neuro-critical care. Poor autoregulation and loss of pressure-reactivity are independent predictors of fatal outcome following head injury. Autoregulation is impaired by too low or too high CPP when compared to autoregulation with normal CPP (usually between 60 and 85 mmHg; and these limits are highly individual). Hemispheric asymmetry of the bi-laterally assessed autoregulation has been associated with asymmetry of CT scan findings: autoregulation was found to be worse ipsilateral to contusion or lateralized edema causing midline shift. The pressure-reactivity (PRx index) correlated with a state of low CBF and CMRO2 revealed using PET studies. The PRx is easier to monitor over prolonged periods of time than the TCD-based indices as it does not require fixation of external probes. Continuous monitoring with the PRx can be used to direct CPP-oriented therapy by determining the optimal CPP for pressure-reactivity. Autoregulation indices are able to reflect transient changes of autoregulation, as seen during plateau waves of ICP. However, minute-to-minute assessment of autoregulation has a poor signal-to-noise ratio. Averaging across time (30 min) or by combining with other relevant parameters improves the accuracy. MYTHS: It is debatable whether the TCD-based indices in head injured patients can be calculated using ABP instead of CPP. Thresholds for functional and disturbed autoregulation dramatically depends on arterial tension of CO2--therefore, comparison between patients cannot be performed without comparing their PaCO2. The TCD pulsatility index cannot accurately detect the lower limit of autoregulation. MISSING LINKS: We still do not know whether autoregulation-oriented therapy can be understood as a consensus between CPP-directed protocols and the Lund-concept. What are the links between endothelial function and autoregulation indices? Can autoregulation after head injury be improved with statins or EPO, as in subarachnoid hemorrhage? In conclusion, monitoring cerebral autoregulation can be used in a variety of clinical scenarios and may be helpful in delineating optimal therapeutic strategies.

The Mechanism of Glaucomatous Damage to the Optic Nerve

The pathogenesis of glaucomatous damage involves activation of astrocytes and involvement of oxidative stress in the mitochondria, which are located numerously in the axons of the optic nerve head (ONH). Astrocytes are activated by both mechanical and ischaemic stress. The major cause of oxidative stress is unstable blood flow, which is unstable if either intraocular pressure (IOP) fluctuates on a high level, exceeding the capacity for autoregulation from time to time, or if autoregulation by itself is disturbed. The main cause of disturbed autoregulation is primary vascular dysregulation syndrome. The simultaneous production of superoxide anions and nitric oxide leads to the damaging peroxinitrite, which induces apoptosis. Simultaneously, the entire microenvironment is changed, including an upregulation of matrix metalloproteinases (MMPs), contributing to tissue remodelling and thereby to excavation.

The relationship between the intracranial pressure–volume index and cerebral autoregulation

The pressure-volume index (PVI) can be used to assess the cerebrospinal fluid dynamics and intracranial elastance in critically ill brain injured patients. The dependency of PVI on the state of cerebral autoregulation within the physiologic range of cerebral perfusion pressure (CPP) can be described by mathematical models that account for changes in cerebral blood volume during PVI testing. This relationship has never been verified clinically using direct PVI measurement and independent cerebral autoregulation assessment. PVI and cerebral autoregulation were prospectively assessed in a cohort of 19 comatose patients admitted to an academic intensive care unit in Brescia, Italy. None. PVI was measured injecting a fixed volume of 2 ml of 0.9% sodium chloride solution into the cerebral ventricles through an intraventricular catheter. Cerebral autoregulation was assessed using transcranial Doppler transient hyperaemic response (THR) test. Fifty-nine PVI assessments and 59 THR tests were performed. Mean PVI was 20.0 (SD 10.2) millilitres in sessions when autoregulation was intact (THR test >or=1.1) and 31.6 (8.8) millilitres in sessions with defective autoregulation (THR test <1.1) (DeltaPVI = 11.7 ml, 95% CI = 4.7-19.3 ml; P = 0.002). Intracranial pressure, CPP and brain CT findings were not significantly different between the measurements with intact and disturbed autoregulation. Cerebral autoregulation status can affect PVI estimation despite a normal CPP. PVI measurement may overestimate the tolerance of the intracranial system to volume loads in patients with disturbed cerebral autoregulation.

Transkranielle Dopplersonographie und Hämodynamik

13 patients without cerebral or cerebrovascular diseases were investigated by transcranial Doppler sonography during Swan-Ganz catheterisation for cardiologic purposes. Massive increases of mean arterial pressure, heart rate and cardiac index were observed during exercise; flow velocities in the middle cerebral artery increased only to the same extent as the endexpiratory carbon dioxide rose. However, the pulsatility index increased significantly (p less than 0.01) although a decrease should have been expected due to carbon dioxide accumulation. These results are indicative of a functioning autoregulation independent of carbon dioxide; they are relevant for interpretation of TCD results in patients with disturbed autoregulation.

Cerebral perfusion in sepsis-associated delirium

IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100β (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

What Is the Present Pathogenetic Concept of Glaucomatous Optic Neuropathy?

Glaucomatous optic neuropathy implies loss of neural tissue, activation of glial cells, tissue remodeling, and change of blood flow. The blood flow reduction is not only secondary but has a primary component. Activation of astrocytes leads to an altered microenvironment. An unstable ocular perfusion, either due to IOP fluctuation or a disturbed autoregulation (due to primary vascular dysregulation syndrome) leads to a mild reperfusion injury. The superoxide (O 2 −) anion produced in the mitochondria of the axons, fuses with the nitric oxide (NO) diffusing from the astrocytes, leading to the damaging peroxynitrite (ONOO −). It is possible that the diffusion of endothelin and metalloproteinases to the surrounding of the optic nerve head leads to a local vasoconstriction and thereby increases the risk for venous occlusion and weakens the blood–brain barrier, which in extreme situations results in splinter hemorrhages. Activated retinal astrocytes can be visualized clinically. The involvement of primary vascular dysregulation in the pathogenesis of glaucomatous optic neuropathy may explain why women, as well as Japanese, suffer more often from normal-tension glaucoma.

Influence of Galantamine on Vasomotor Reactivity in Alzheimer’s Disease and Vascular Dementia Due to Cerebral Microangiopathy

Recent reports suggest that vascular factors play a crucial role in the development and progression of Alzheimer's disease. We aimed to assess vasomotor reactivity in patients with Alzheimer's disease and vascular dementia due to microangiopathy using transcranial Doppler sonography and near-infrared spectroscopy during a CO(2) exposition task. The normalized CO(2) reactivity assessed at the middle cerebral artery and the oxygenated and deoxygenated hemoglobin of the frontal cortex were obtained. To investigate the impact of cholinergic deficiency known for Alzheimer's disease on vasomotor reactivity, both groups were reinvestigated during treatment with the acetylcholine esterase inhibitor galantamine. Transcranial Doppler analysis revealed significantly reduced normalized CO(2) reactivity for Alzheimer's disease and vascular dementia. Vasomotor reactivity assessed by near-infrared spectroscopy was decreased in patients with vascular dementia, but not in Alzheimer's disease. Galantamine treatment showed a beneficial effect, normalizing these parameters close to age-matched control levels. Our results suggest that Alzheimer's disease is associated with a lack of vasomotor reactivity, which might be associated with disturbed autoregulation indicating a potential risk for a decreased protection of brain tissue against blood pressure changes. Additionally, a diminished increase of cortical oxygenated hemoglobin during the CO(2) test was apparent in patients with vascular dementia. Galantamine treatment influenced vascular reactivity in the CO(2) test, thus providing evidence for the cholinergic deficiency, thereby adding to vascular dysregulation in Alzheimer's disease, but also indicating an important role of cholinergic system dysfunction for vascular dementia.

Spatial alterations in endothelin receptor expression are temporally associated with the altered microcirculation after brain trauma

Objectives: To study the cellular distribution of endothelin receptors A and B (ETrA and ETrB) in the post-traumatic sensorimotor cortex and hippocampus.Materials and methods: We inflicted closed head trauma to male Sprague–Dawley rats and visualized ETrA and ETrB immunoreactivity with 3,3′-diaminobenzidine.Results: ETrA immunolabeling was the most prominent in pyramidal neurons 24 and 48 hours post-trauma, while it reached its peak in the microvasculature at hour 4. ETrB immunolabeling was observed in endothelial cells, perivascular neurons, smooth muscle cells (SM) and pericytes, the expression being the most pronounced 24 hours post-trauma.Discussion: The results suggest that the vasoconstrictor effect of endothelin-1 (ET-1) is mediated primarily by ETrA. The dual effects of ETrB are reflected in its vasoconstrictor role at the vascular bed and conversely, in the attenuation of ET-1 availability and synthesis. We conclude that both receptors play a role in the disturbed microvascular autoregulation and in the sustained reduction of blood flow following trauma to the brain.

Continuous Monitoring of Cerebrovascular Autoregulation After Subarachnoid Hemorrhage by Brain Tissue Oxygen Pressure Reactivity and Its Relation to Delayed Cerebral Infarction

Disturbances of cerebrovascular autoregulation are thought to be involved in delayed cerebral ischemia and infarction after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the continuous monitoring of brain tissue oxygen (PtiO(2)) pressure reactivity enables the detection of impaired autoregulation after SAH and that impaired autoregulation is associated with delayed infarction. In 67 patients after severe SAH, continuous monitoring of cerebral perfusion pressure (CPP) and PtiO(2) was performed for an average of 7.4 days. For assessment of autoregulation, the index of PtiO(2) pressure reactivity (ORx) was calculated as a moving correlation coefficient between values of CPP and PtiO(2). Higher ORx values indicate disturbed autoregulation, whereas lower ORx values signify intact autoregulation. Twenty patients developed delayed cerebral infarction, and 47 did not. Mean ORx was significantly higher in the infarction group compared with the noninfarction group (0.43+/-0.09 vs 0.23+/-0.14, respectively; P<0.0001). In a day-by-day analysis, ORx did not differ between groups from days 1 to 4 after SAH but was significantly higher from day 5 onward in the infarction group, indicating a deficit of autoregulatory capacity. In a logistic-regression model, ORx values from days 5 and 6 after SAH carried predictive value for the occurrence of delayed infarction but before this event ultimately occurred (P=0.003). ORx indicates impaired autoregulation in patients who develop delayed infarction after SAH. Furthermore, this index may distinguish between patients who finally develop delayed infarction and those who do not.

Aminophylline influences cerebral hyperperfusion after severe birth hypoxia

Doppler sonographic investigations have presented cerebral hyperperfusion in neonates after severe asphyxia. Neonates with disturbed cerebral blood flow velocity (CBFV) tend to have poor outcomes. The purpose of this clinical study was to examine the influence of aminophylline on cerebral hyperperfusion. An intravenous bolus of 4 mg/kg aminophylline was given to nine neonates with Doppler sonographic signs of cerebral hyperperfusion. CBFV was determined before, 5 min, 60min and 120 min after aminophylline administration and on the following day. After aminophylline the mean systolic (56.5 vs. 41.6 cm/s) and end diastolic (21.0 vs. 12.3 cm/s) blood flow velocity decreased and the mean pulsatility index (0.83 vs. 1.1) increased significantly. Repeated measurements showed a decrease in blood flow velocities and an increase in pulsatility index on the following days. Heart rate, mean arterial blood pressure and pCO2 were not significantly changed. We conclude that aminophylline influences cerebral hyperperfusion in neonates with disturbed autoregulation.

Oscillatory cerebral hemodynamics—the macro- vs. microvascular level

The phase shift between oscillations of blood pressure (BP) and Doppler middle cerebral artery flow velocity (MCAFV) reflects continuous cerebral autoregulatory action. It is not known whether a similar phase shift exists for cortical hemodynamics (‘microvascular level’) assessed by near infrared spectroscopy (NIRS) and what the effects are of pathological conditions. This study investigates the phase relations between oscillations of BP, MCAFV and NIRS parameters in 38 healthy older adults and 28 patients with unilateral severe obstructive carotid disease. BP was recorded noninvasively by finger plethysmography. Stable 0.1 Hz oscillations of all hemodynamic parameters were induced by regular breathing at a rate of 6/min. Basic results were that: (1) BP-induced cortical microvascular oscillations (NIRS) follow those of macrovascular oscillations (MCAFV) with a phase of 80–90° (corresponding to 2–2.5 s at 0.1 Hz), most likely reflecting a transit time phenomenon; (2) oxy- and deoxyhemoglobin thereby oscillate in counterphase; (3) hemodynamic compromise in carotid obstruction leads to (a) delayed NIRS oscillations in comparison to BP which are highly correlated to a shorter phase lead of MCAFV against BP and (b) a decoupling of the oxy-/deoxyhemoglobin counterphase to 240°. Cortical hemodynamic responses to BP oscillations follow specific phase relationships due to cerebral autoregulatory action and circulatory transit times. With hemodynamic impairment, as in unilateral carotid obstruction, these phases are significantly changed reflecting disturbed autoregulation.

Time Course of Microvascular Resistance of the Infarct and Noninfarct Coronary Artery Following an Anterior Wall Acute Myocardial Infarction

Previous studies have suggested that coronary flow velocity reserve (CFVR) in the early phase of acute myocardial infarction (AMI) is abnormal in infarcted and remote regions. This study determined the coronary microvascular resistance of infarct-related arteries (IRAs) and non-IRAs during AMI and at follow-up in patients who were treated with primary percutaneous intervention. In 73 patients with a first anterior wall AMI, baseline and minimal microvascular resistance in IRAs and non-IRAs immediately after reperfusion and at 1-week and 6-month follow-up were calculated as the ratio of mean transvascular pressure gradient to mean baseline and to adenosine-induced hyperemic blood flow velocity, respectively. CFVR in IRAs increased from 1.6 +/- 0.4 after reperfusion to 1.9 +/- 0.5 at 1 week and to 3.0 +/- 0.8 at 6 months (p <0.0001) and in non-IRAs from 2.4 +/- 0.5 to 2.7 +/- 0.6 at 1 week to 3.3 +/- 0.6 at 6 months (p <0.0001). Minimal microvascular resistance in IRAs and non-IRAs (3.2 +/- 1.7 and 2.2 +/- 0.6 mm Hg/second/cm, respectively) decreased significantly at follow-up (2.0 +/- 0.6 and 1.7 +/- 0.6 mm Hg/second/cm at 1 week and 1.8 +/- 0.6 and 1.8 +/- 0.7 mm Hg/second/cm at 6 months, respectively). After correction for rate-pressure product, baseline microvascular resistance after reperfusion and at 6 months did not significantly differ between IRAs and non-IRAs. In conclusion, minimal microvascular resistance is higher in infarcted and noninfarcted regions during AMI than at follow-up. The low CFVR in remote regions during AMI is probably due more to disturbed autoregulation than to increased myocardial workload.

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

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. Animal research and clinical intervention study. Surgical intensive care unit of a university hospital. Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. 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. 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. 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.

Blood flow in glaucoma

Glaucoma, one of the leading causes of blindness in the world, is characterized by progressive visual field loss and distinctive excavation of the optic nerve head. Although elevated intraocular pressure is the major risk factor, there is increasing evidence that the pathogenesis of glaucoma is also linked to altered ocular blood flow. This review summarizes the recent publications relevant to blood flow in glaucoma. Several studies indicate that a perfusion instability, rather than a steady reduction of ocular blood flow, might contribute to glaucomatous optic neuropathy. The main cause of the instability is a disturbed autoregulation in the context of a general vascular dysregulation. The underlying mechanism of such a vascular dysregulation is not known. A dysfunction of both the autonomic nervous system and vascular endothelial cells is discussed. The mechanical and vascular theories are not mutually exclusive; on the contrary, a vascular dysregulation increases the susceptibility to intraocular pressure. Therapeutically, therefore, both an intraocular pressure reduction and an improvement of the ocular blood flow might be considered.

Continuous assessment of cerebral autoregulation: clinical and laboratory experience.

The method for the continuous assessment of cerebral autoregulation using slow waves of MCA blood flow velocity (FV) and cerebral perfusion pressure (CPP) or arterial pressure (ABP) has been introduced seven years ago. We intend to review its clinical applications in various scenarios. Moving correlation coefficient (3-6 min window), named Mx, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or ABP (when ICP is not measured directly). Data from ventilated 243 head injuries and 15 patients after poor grade subarachnoid haemorrhage, 38 patients with Carotid Artery stenosis, 35 patients with hydrocephalus and fourteen healthy volunteers is presented. Good agreement between the leg-cuff test and Mx has been confirmed in healthy volunteers (r = 0.81). Mx also correlated significantly with the static rate of autoregulation and transient hyperaemic response test. Autoregulation was disturbed (p < 0.021) by vasospasm after SAH and worse in patients with hydrocephalus in whom CSF circulation was normal (p < 0.02). In head injury, Mx indicated disturbed autoregulation with low CPP (< 55 mmHg) and too high CPP (> 95 mmHg). Mx strongly discriminated between patients with favourable and unfavourable outcome (p < 0.00002). This method can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising treatment strategies.

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.

Anesthetic management of deep hypothermic circulatory arrest for cerebral aneurysm clipping.

This article will briefly review the rationale for DHCA in the setting of cerebral aneurysm treatment. We will then use the main aspects of the protocol practiced by the senior author (WLY), as a point of departure to review the issues regarding anesthetic and perioperative management. Rationale The ability to temporarily eliminate or reduce blood flow into an aneurysm gives the surgeon an important advantage—without flow, an aneurysm is converted from a hard, pulsating mass into a soft, collapsed sac, allowing more aggressive manipulation of the aneurysm to complete its dissection. With most aneurysms, temporary occlusion of the proximal parent artery or arteries will effectively control blood flow into the lesion. With large or complex aneurysms, the aneurysm mass may prevent optimal visualization and clip application to the neck. Collapse of the aneurysm mass creates more working space for dissection and precise clip application. Deep hypothermic circulatory arrest is used for aneurysms that cannot be adequately controlled by conventional surgical or endovascular techniques. Aneurysms in the anterior circulation are, in general, accessible enough to be managed with temporary clipping. Aneurysms that defy conventional treatment are typically in the posterior circulation and large (10 –25 mm in diameter) or giant (25 mm in diameter) in size. 11 Often these aneurysms cannot be collapsed easily because of the breadth of the neck, the complexity of the arterial branches at the base, the presence of thrombus or endovascular coils in the lumen, artheroma or calcium in the walls, and fusiform configuration. These anatomic features make direct clipping more difficult and lower the efficacy of conventional techniques. The surgeon’s ability to manage these anatomic factors is directly related to operative exposure. When proximal and distal arteries are inaccessible with these complex aneurysms, DHCA may provide the only safe and effective means of vascular control. Deep hypothermic circulatory arrest should be considered an option of last resort for these unusual aneurysms, when all conventional techniques have failed or have been carefully considered. Rarely, DHCA has also been proposed or described for other central nervous system lesions, such as tumors 8 or arteriovenous malformations, 12 but this discussion is not

Clinical significance of cerebral autoregulation.

Disturbed cerebral autoregulation is believed to be associated with an unfavourable outcome following head injury. Previously, using ICP monitoring and transcranial Doppler ultrasonography, we investigated whether cerebral response to spontaneous variations in arterial pressure (ABP) or cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve. In the present study we have correlated these methods with clinical findings. 188 head injured sedated and ventilated patients were studied daily. Waveforms of intracranial pressure (ICP), arterial pressure and transcranial Doppler flow velocity (FV) were captured over a half to two hour periods. Time averaged mean flow velocity (FV) and CPP were resolved. The correlation coefficient indices between FV and CPP (Mx) and between ICP and ABP (PRx) were calculated over 3 minutes epochs, and averaged for each investigation. The relationship between indices of autoregulation and outcome (favourable-unfavourable) was significant and stronger than the association between admission GCS and outcome. With rigorously maintained CPP-oriented therapy relationship between CPP and outcome became non-significant. Mortality in patients with consistently disturbed autoregulation ranged 47%, while in patients with good autoregulation mortality was 11% (difference: p < 0.0001). Positive values of indices of autoregulation, expressing positive association between slow waves of CPP and blood flow velocity or ABP and ICP, indicate disturbed autoregulation. These indices correlate with unfavourable outcome following head injury and should be used to guide intensive therapy.

Dysfunction of vasomotor reactivity in severe sepsis and septic shock.

Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock, leading to organ dysfunction. We investigated whether carbon dioxide (CO2)-induced vasomotor reactivity (VMR) is impaired in septic patients, compared with values obtained outside sepsis. Prospective, clinical study. Six-bed neurologic critical care unit of a university hospital. Eight consecutive patients with severe sepsis and septic shock. CO2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy (NIRS). VMR was calculated as the percentage change of cerebral blood flow velocity (normalized CO2-reactivity, NCR) and absolute changes in concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO2, Hb, HbT) and Hbdiff (difference between HbO2 and Hb) in micromol/l per 1% increase in end-tidal CO2 (CR-HbO2, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p < 0.02; CR-HbO2 0.70 (0.61) versus 2.33 (1.11), p < 0.02; CR-Hb -0.17 (0.74) versus -1.42 (1.28), p < 0.04; CR-HbT 0.53 (0.48) versus 1.05 (0.40), p < 0.03; CR-Hbdiff 0.91 (1.33) versus 3.75 (2.33), p < 0.02. This indicates a severely disturbed VMR. In the advent of a disturbed cerebral autoregulation, critical drops in blood pressure during sepsis are transferred directly into the vascular bed, leading to cerebral hypoperfusion. This mechanism might contribute to the pathogenesis of septic encephalopathy.