Intracranial pressure and cerebral haemodynamics

Intracranial pressure (ICP) refers to the pressure within the skull, which is determined by the volumes of the intracranial contents; blood, brain and cerebrospinal fluid. Monro–Kellie homeostasis stipulates that a change in the total intracranial volume is accompanied by a change in the ICP, which is more precisely described by the intracranial pressure–volume relationship. Maintenance of a relatively constant ICP is essential for maintenance of the cerebral perfusion pressure, which in turn determines global cerebral blood flow. Although the physiological process of autoregulation ensures that cerebral blood flow is tightly maintained over a range of cerebral perfusion pressures, large increases in the ICP can result in severely impaired autoregulation, meaning that cerebral blood flow may be compromised. In this review article we provide an overview of the physiological determinants of the ICP and cerebral blood flow. We go on to illustrate how pathological states can compromise physiological compensatory mechanisms in order to potentially dangerous disturbances of the ICP and cerebral blood flow.     

Intracranial pressure and cerebral haemodynamics

Intracranial pressure (ICP) refers to the pressure within the skull, which is determined by the volumes of the intracranial contents; blood, brain and cerebrospinal fluid. Monro–Kellie homeostasis stipulates that a change in the total intracranial volume is accompanied by a change in the ICP, which is more precisely described by the intracranial pressure–volume relationship. Maintenance of a relatively constant ICP is essential for maintenance of the cerebral perfusion pressure, which in turn determines global cerebral blood flow. Although the physiological process of autoregulation ensures that cerebral blood flow is tightly maintained over a range of cerebral perfusion pressures, large increases in the ICP can result in severely impaired autoregulation, meaning that cerebral blood flow may be compromised. In this review article we provide an overview of the physiological determinants of the ICP and cerebral blood flow. We go on to illustrate how pathological states can compromise physiological compensatory mechanisms in order to potentially dangerous disturbances of the ICP and cerebral blood flow.     

Cerebral blood flow and intracranial pressure

The Monro–Kellie hypothesis states that ‘if the skull is intact, then the sum of the volumes of the brain, cerebrospinal fluid (CSF) and intracranial blood volume is constant’. An increase in volume in one of the three components within the skull must be compensated for by a decrease in the volume of the other remaining components, otherwise the intracranial pressure (ICP) will increase. Brain tissue is not easily displaced; therefore changes in venous blood or CSF volumes initially act as the major buffers against a rise in ICP. In the normal adult, the ICP is 5–13 mm Hg, with minor cyclical variations owing to the effects of the arterial pressure waveform and respiration. Cerebral blood flow (CBF) is determined by a number of factors. It is closely linked to the metabolic activity of the brain to ensure adequate delivery of oxygen and substrates. The relationship between partial pressure of carbon dioxide in arterial blood (PaCO₂) and CBF is almost linear. CBF increases by 25% for each kPa increase in PaCO₂. Hypoxia (PaO₂ < 6.7 kPa) is also a potent stimulus for increasing CBF. The brain is intolerant of hypo- or hyperperfusion and therefore requires a constant flow of blood over a range of pressures, which is achieved by autoregulation. Below the lower limit of autoregulation, CBF mirrors mean arterial pressure (MAP), and eventually a reduced flow causes cerebral ischaemia. Monitoring of the central nervous system, including measurements of neuronal function, ICP, CBF and cerebral oxygenation, can guide pharmacological and surgical treatment according to the individual status of the patient.     

Pediatric neck injuries. A clinical study

In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the changes in intracranial pressure (ICP) and cerebral blood flow (CBF) after mannitol administration in a group of severely head-injured patients with intact or defective autoregulation. The xenon-133 inhalation method was used to measure CBF. Autoregulation was tested by slowly increasing or decreasing the blood pressure by 30% and measuring CBF again. Mannitol was administered intravenously in a dose of 0.66 gm/kg; 25 minutes later, CBF and ICP were measured once again. In the group with intact autoregulation, mannitol had decreased ICP by 27.2%, but CBF remained unchanged. In the group with defective autoregulation, ICP had decreased by only 4.7%, but CBF increased 17.9%. One of the possible explanations for these findings is based on strong indications that autoregulation is mediated through alterations in the level of adenosine in response to oxygen availability changes in cerebral tissue. The decrease in blood viscosity after mannitol administration leads to an improved oxygen transport to the brain. When autoregulation is intact, more oxygen leads to decreased adenosine levels, resulting in vasoconstriction. The decrease in resistance to flow from the decreased blood viscosity is balanced by increased resistance from vasoconstriction, so that CBF remains the same. This might be called blood viscosity autoregulation of CBF, analogous to pressure autoregulation. Vasoconstriction also reduces cerebral blood volume, which enhances the effect of mannitol on ICP through dehydration of the brain. When autoregulation is not intact there is no vasoconstriction in response to increased oxygen availability; thus, CBF increases with decreased viscosity. With the lack of vasoconstriction, the effect on ICP through dehydration is not enhanced, so that the resulting decrease in ICP is much smaller. Such a mechanism explains why osmotic agents do not change CBF but decrease ICP in normal animals or patients with intact vasoconstriction, but do (temporarily) increase CBF in the absence of major ICP changes after stroke.     

Angiotensin converting enzyme inhibition,CBF autoregulation,and ICP in patients with normal-pressure hydrocephalus

Summary Fourteen patients with normal pressure hydrocephalus had the autoregulation of cerebral blood flow (CBF) and intracranial pressure (ICP) investigated. In 8 of the patients the effect of Captopril on ICP and CBF was also investigated. The mean arterial blood pressure (MABP) was 109 mmHg (intra-arterially), and ICP was 11 mmHg (intraventricularly). Changes in global CBF were estimated by the arterio-venous oxygen difference method. The autoregulation of CBF was present in 13 of the patients (p < 0.01). The lower limit of CBF autoregulation was 86% of the baseline perfusion pressure. One hour after 50 mg of captopril perorally, MABP was reduced 16 mmHg, and ICP and CBF were unchanged. The autoregulation was maintained and the lower limit was decreased 19 mmHg. Thus patients would be expected to benefit from captopril treatment in hypotensive anaesthesia.     

Cerebral blood flow at constant cerebral perfusion pressure but changing arterial and intracranial pressure: relationship to autoregulation

Therapeutic agents for reducing raised intracranial pressure (ICP) may do so at the expense of reduced mean arterial pressure (MAP). As a consequence, cerebral perfusion pressure (CPP) = (MAP - ICP) may not improve. It is unknown whether the level of MAP alters cerebral blood flow (CBF) when MAP and ICP change in parallel so that CPP remains constant. This study investigates CBF at a constant CPP but varying levels of MAP and ICP in 12 anaesthetized cats. CBF was studied at three levels of CPP: 60 (n = 4), 50 (n = 4), and 40 mm Hg (n = 4) under conditions of both intact and impaired autoregulation. At CPP levels of 50 and 60 mm Hg, when autoregulation was intact, CBF remained unchanged. With loss of autoregulation, there was a trend for CBF to increase as MAP and ICP were increased in parallel at a CPP of 50 and 60 mm Hg, although the relationship did not achieve statistical significance. Absolute CBF levels were, however, significantly different between the autoregulating and nonautoregulating groups (p <0.001). At a CPP of 40 mm Hg, CBF showed a linear correlation with blood pressure (BP) (r = 0.57, p <0.05). These results demonstrate that when autoregulation is impaired, there is a functional difference between autoregulating and nonautoregulating cerebral vessels despite similar MAP and CPP. These results also show that at a CPP of 40 mm Hg when autoregulation is impaired, CBF depends more on arterial driving pressure than on CPP.     

Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow.

Increased brain tissue stiffness following severe traumatic brain injury is an important factor in the development of raised intracranial pressure (ICP). However, the mechanisms involved in brain tissue stiffness are not well understood, particularly the effect of changes in systemic blood pressure. Thus, controversy exists as to the optimum management of blood pressure in severe head injury, and diverging treatment strategies have been proposed. In the present study, the effect of induced alterations in blood pressure on ICP and brain stiffness as indicated by the pressure-volume index (PVI) was studied during 58 tests of autoregulation of cerebral blood flow in 47 comatose head-injured patients. In patients with intact autoregulation mechanisms, lowering the blood pressure caused a steep increase in ICP (from 20 +/- 3 to 30 +/- 2 mm Hg, mean +/- standard error of the mean), while raising blood pressure did not change the ICP. When autoregulation was defective, ICP varied directly with blood pressure. Accordingly, with intact autoregulation, a weak positive correlation between PVI and cerebral perfusion pressure was found; however, with defective autoregulation, the PVI was inversely related to cerebral perfusion pressure. The various blood pressure manipulations did not significantly alter the cerebral metabolic rate of oxygen, irrespective of the status of autoregulation. It is concluded that the changes in ICP can be explained by changes in cerebral blood volume due to cerebral vasoconstriction or dilatation, while the changes in PVI can be largely attributed to alterations in transmural pressure, which may or may not be attenuated by cerebral arteriolar vasoconstriction, depending on the autoregulatory status. The data indicate that a decline in blood pressure should be avoided in head-injured patients, even when baseline blood pressure is high. On the other hand, induced hypertension did not consistently reduce ICP in patients with intact autoregulation and should only be attempted after thorough assessment of the cerebrovascular status and under careful monitoring of its effects.     

The control mechanism involved in post-subarachnoid hemorrhage vasospasm

In the present work the main relationships among cerebral blood volume (CBV), cerebrospinal fluid (CSF) dynamics, cerebral blood flow (CBF) and cerebrovascular reactivity following subarachnoid hemorrhage are critically examined and discussed. It is hypothesized that, following the rupture of an aneurysm, antagonistic mechanism which regulate CBF (through a vasodilatation of the arteriolar vessels) and CBV (through a constriction of basal intracranial arteries) are activated, due to the initial increase in intracranial pressure (ICP) the time pattern of ICP and cerebral hemodynamics in the following days can be largely different depending on the state of CSF dynamics. When the CSF outflow is not altered by blood in the subarachnoid space ICP suddenly returns to the basal value, and a normal cerebral hemodynamics is rapidly restored. By contrast, in conditions in which the normal CSF dynamics is impaired, the opposite action of mechanisms regulating CBF and CBV may lead to instability of the cerebrovascular bed, with the result of a maximal dilatation of pial vessels and a strong constriction of basal arteries (spasm). In our opinion the phenomenon of vasospasm can be better understood if the reactivity of basal intracranial arteries is analyzed as a part of the complex physiological system of cerebrovascular regulation.     

Volume-targeted therapy of increased intracranial pressure: the Lund concept unifies surgical and non-surgical treatments

Opinions differ widely on the various treatment protocols for sustained increase in intracranial pressure (ICP). This review focuses on the physiological volume regulation of the intracranial compartments. Based on these mechanisms we describe a protocol called 'volume-targeted' ('Lund concept') for treatment of increased ICP. The driving force for transcapillary fluid exchange is determined by the balance between effective transcapillary hydrostatic and osmotic pressures. Fluid exchange across the intact blood-brain barrier (BBB) is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB. This contrasts to most other capillary regions where the osmotic pressure is mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the level of the cerebral perfusion pressure (CPP) is of less importance under physiological conditions. In addition cerebral intracapillary hydrostatic pressure (and cerebral blood flow) is physiologically tightly autoregulated, and variations in systemic blood pressure are generally not transmitted to these capillaries. If the BBB is disrupted, transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under these pathological conditions, pressure autoregulation of cerebral blood flow is likely to be impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The volume-targeted 'Lund concept' can be summarized under four headings: (1) Reduction of stress response and cerebral energy metabolism; (2) reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic pressure and control of fluid balance; and (4) reduction of cerebral blood volume. The efficacy of the protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.     

Mannitol causes compensatory cerebral vasoconstriction and vasodilation in response to blood viscosity changes

There is no proof that osmotic agents such as mannitol lower intracranial pressure (ICP) by decreasing brain water content. An alternative mechanism might be a reduction in cerebral blood volume through vasoconstriction. Mannitol, by decreasing blood viscosity, would tend to enhance cerebral blood flow (CBF), but the cerebral vessels would constrict to keep CBF relatively constant, analogous to pressure autoregulation. The cranial window technique was used in this study to measure the pial arteriolar diameter in cats, together with blood viscosity and ICP changes after an intravenous bolus of 1 gm/kg of mannitol. Blood viscosity decreased immediately; the greatest decrease (23%) occurred at 10 minutes, and at 75 minutes there was a "rebound" increase of 10%. Vessel diameters decreased concomitantly, the largest decrease being 12% at 10 minutes, which is exactly the same as the 12% decrease in diameter associated with pronounced hyperventilation (PaCO2 30 to 19 mm Hg) in the same vessels; at 75 minutes vessel diameter increased by 12%. With hyperventilation, ICP was decreased by 26%; 10 minutes after mannitol was given, ICP decreased by 28%, and at 75 minutes it showed a rebound increase of 40%. The correlation between blood viscosity and vessel diameter and between vessel diameter and ICP was very high. An alternative explanation is offered for the effect of mannitol on ICP, the time course of ICP changes, "rebound effect," and the absence of influence on CBF, all with one mechanism.     

An experimental study of the acute stage of subarachnoid hemorrhage

A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.     

Opioide,Hirndurchblutung und intrakranieller Druck

The effects of the opioids alfentanil (A), fentanyl (F), and sufentanil (S) on cerebral blood flow (CBF) and intracranial pressure (ICP) have been discussed in several recent publications. The purpose of this review is to describe the results of studies in animals, healthy volunteers, and patients with and without intracranial diseases. Clinical relevance and mechanisms of the reported ICP and CBF increases are analysed. Methods. Approximately 70 original articles and abstracts were retrieved by a systematic literature search using the key word list at the end of this abstract. The cited studies came from computerised database systems like Silver Platter and DIMDI, the SNACC reference list, and the bibliographies of pertinent articles and books. These studies were classified into three groups: significant increase of ICP and/or CBF; no significant or clinically relevant alterations; and significant decreases of ICP and/or CBF. Results. The numerical relationship was 6 : 7 : 3 for A, 7 : 16 : 9 for F, and 5 : 11 : 8 for S. Increases of previously normal or only slightly elevated ICP were registered in some studies in connection with a decrease in mean arterial pressure (MAP). On the other hand, in patients with brain injury and elevated ICP opioids did not further increase ICP despite MAP decreases. In studies monitoring ICP and/or CBF continuously, transient and moderate increases of questionable clinical relevance became apparent a few minutes after bolus injection of opioids. Alterations of systemic and cerebral haemodynamics observed after bolus application were not registered during continuous infusion of A and S. Discussion and conclusions. The cerebral effects of opioids are dependent on several factors, e.g., age, species, ventilation, anaesthesia before and during measurements, systemic haemodynamics, and underlying diseases. The probable mechanism of ICP increase during decreasing MAP is cerebral vasodilatation due to maintained autoregulation. With increasing severity of the cerebral lesion autoregulation is often disturbed. Therefore, ICP often remains unaltered despite MAP decreases. However, the resulting decrease in cerebral perfusion pressure makes such patients more susceptible to develop ischaemic neurological deficits. Induction of somatic rigidity or (with high doses) convulsions, exceeding the upper limit of autoregulation, histamine release, cerebral vasodilatation, increased cerebral oxygen consumption, or carbon dioxide accumulation during spontaneous breathing were discussed as mechanisms for transient ICP/CBF increases. It is concluded that opioids are often beneficial and not generally contraindicated for patients with cerebral diseases and compromised intracranial compliance. However, since negative side effects cannot be excluded, opioid effects and side effects should be monitored (MAP, ICP, cerebrovenous oxygen saturation, transcranial Doppler sonography) in patients at risk. It has to be stressed that opioids should be administered only to patients with stable haemodynamic situations and preferably in well-titrated, continuous infusions. Eingegangen am 3. Januar 1994 / Angenommen am 22. M?rz 1994     

Effect of Xenon on elevated intracranial pressure as compared with nitrous oxide and total intravenous anesthesia in pigs

BACKGROUND: Xenon in low concentrations has been investigated in neuroradiology to measure cerebral blood flow (CBF). Several reports have suggested that inhalation of Xenon might increase intracranial pressure (ICP) by increasing the cerebral blood flow and blood volume, raising concerns about using Xenon as an anesthetic in higher concentrations for head-injured patients. A porcine study is presented in which the effects of inhaled 75% Xenon on elevated ICP, cerebral perfusion pressure and the efficacy of hyperventilation for ICP treatment were compared with nitrous oxide anesthesia and total intravenous anesthesia (TIVA). METHODS: Twenty-one pentobarbital-anesthetized pigs (age: 12-16 weeks) were randomly assigned to three groups to receive either 4 h of Xenon-oxygen ventilation, nitrous oxide-oxygen ventilation or air-oxygen (75%/25%) ventilation, respectively. After instrumentation for parenchymal ICP measurement and ICP manipulation, an epidurally placed 6-F balloon catheter was inflated until a target ICP of 20 mmHg was achieved. After 4 h of anesthesia hyper- and hypoventilation maneuvers were performed and consecutive ICP and CBF changes were investigated. RESULTS: Intracranial pressure and CBF increased significantly in the nitrous oxide group as compared with the controls. There was no increase of ICP or CBF in the Xenon or control group. Intracranial pressure changed in all three groups corresponding to hyper- and hypoventilation. CONCLUSIONS: During Xenon anesthesia, elevated ICP is not increased further and is partially reversible by hyperventilation. Our study suggests that inhalation of 75% Xenon seems not to be contraindicated in patients with elevated ICP.     

Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients.

The traditional practice of elevating the head in order to lower intracranial pressure (ICP) in head-injured patients has been challenged in recent years. Some investigators argue that patients with intracranial hypertension should be placed in a horizontal position, the rationale being that this will increase the cerebral perfusion pressure (CPP) and thereby improve cerebral blood flow (CBF). However, ICP is generally significantly higher when the patient is in the horizontal position. This study was undertaken to clarify the issue of optimal head position in the care of head-injured patients. The effect of 0 degree and 30 degrees head elevation on ICP, CPP, CBF, mean carotid pressure, and other cerebral and systemic physiological parameters was studied in 22 head-injured patients. The mean carotid pressure was significantly lower when the patient's head was elevated at 30 degrees than at 0 degrees (84.3 +/- 14.5 mm Hg vs. 89.5 +/- 14.6 mm Hg), as was the mean ICP (14.1 +/- 6.7 mm Hg vs. 19.7 +/- 8.3 mm Hg). There was no statistically significant change in CPP, CBF, cerebral metabolic rate of oxygen, arteriovenous difference of lactate, or cerebrovascular resistance associated with the change in head position. The data indicate that head elevation to 30 degrees significantly reduced ICP in the majority of the 22 patients without reducing CPP or CBF.     

Relationship between cardiac output and cerebral blood flow in patients with intact and with impaired autoregulation

Intravascular volume expansion has been successfully employed to promote blood flow in ischemic brain regions. This effect has been attributed to both decreased blood viscosity and increased cardiac output resulting from volume expansion. The physiological mechanism by which changes in cardiac output would affect cerebral blood flow (CBF), independent of blood pressure variations, is unclear, but impaired cerebral autoregulation is believed to play a role. In order to evaluate the relationship between cardiac output and CBF when autoregulation is either intact or defective, 135 simultaneous measurements of cardiac output (thermodilution method) and CBF (by the 133Xe inhalation or intravenous injection method) were performed in 35 severely head-injured patients. In 81 instances, these measurements were performed after manipulation of blood pressure with phenylephrine or Arfonad (trimethaphan camsylate), or manipulation of blood viscosity with mannitol. Autoregulation was found to be intact in 55 of these cases and defective in 26. A wide range of changes in cardiac output occurred after administration of each drug. No correlation existed between the changes in cardiac output and the changes in CBF, regardless of the status of blood pressure autoregulation. A significant (40%) increase in CBF was found after administration of mannitol when autoregulation was defective. These data support the hypothesis that, within broad limits, CBF is not related to cardiac output, even when autoregulation is impaired. Thus, the effect of intravascular volume expansion appears to be mediated by decreased blood viscosity rather than cardiac output augmentation.     

Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs

Pressure-passive perfusion beyond the upper limit of cerebral blood flow (CBF) autoregulation may be deleterious in patients with intracranial pathology. Therefore, monitoring of changes in CBF would be of clinical relevance in situations where clinical evaluation of adequate cerebral perfusion is impossible. Noninvasive monitoring of cerebral blood flow velocity using transcranial Doppler sonography (TCD) may reflect relative changes in CBF. This study correlates the effects of angiotensininduced arterial hypertension on CBF and cerebral blood flow velocity in dogs. Heart rate (HR) was recorded using standard ECG. Catheters were placed in both femoral arteries and veins for measurements of mean arterial blood pressure (MAP), blood sampling and drug administration. A left ventricular catheter was placed for injection of microspheres. Cerebral blood flow velocity was measured in the basilar artery through a cranial window using a pulsed 8 MHz transcranial Doppler ultrasound system. CBF was measured using colour-labelled microspheres. Intracranial pressure (ICP) was measured using an epidural probe. Arterial blood gases, arterial pH and body temperature were maintained constant over time. Two baseline measures of HR, MAP, CBF, cerebral blood flow velocity and ICP were made in all dogs (n = 10) using etomidate infusion (1.5 mg · kg^?1 · hr^?1) and 70% N₂O in O₂ as background anaesthesia. Following baseline measurements, a bolus of 1.25 mg angiotensin was injected iv and all variables were recorded five minutes after the injection. Mean arterial blood pressure was increased by 76%. Heart rate and ICP did not change. Changes in MAP were associated with increases in cortical CBF (78%), brainstem CBF (87%) and cerebellum CBF(64%). Systolic flow velocity increased by 27% and Vmean increased by 31% during hypertension (P < 0.05). Relative changes in CBF and blood flow velocity were correlated (CBF cortex — Vsyst: r = 0.94, CBF cortex — Vmean: r = 0.77; P < 0.001; CBF brainstem — Vsyst: r = 0.82, CBF brainstem — Vmean: r = 0.69; P < 0.05). Our results show that increases in arterial blood pressure beyond the upper limit of cerebral autoregulation increase CBF in dogs during etomidate and N₂O anaesthesia. The changes in CBF are correlated with increases in basilar artery blood flow velocity. These data suggest that TCD indicates the upper limit of the cerebral autoregulatory response during arterial hypertension. However, the amount of CBF change may be underestimated with the TCD technique.     

Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome in patients with poor-grade spontaneous subarachnoid hemorrhage

OBJECT: Systemic administration of 23.5% hypertonic saline enhances cerebral blood flow (CBF) in patients with poor-grade spontaneous subarachnoid hemorrhage (SAH). Whether the increment of change in CBF correlates with changes in autoregulation of CBF or outcome at discharge remains unknown. METHODS: Thirty-five patients with poor-grade spontaneous SAH received 2 ml/kg 23.5% hypertonic saline intravenously, and they underwent bedside transcranial Doppler (TCD) ultrasonography and intracranial pressure (ICP) monitoring. Seventeen of them underwent Xe-enhanced computed tomography (CT) scanning for measuring CBF. Outcome was assessed using the modified Rankin Scale (mRS) at discharge from the hospital. The data were analyzed using repeated-measurement analysis of variance and Dunnett correction. A comparison was made between patients with favorable and unfavorable outcomes using multivariate logistic regression. RESULTS: The authors observed a maximum increase in blood pressure by 10.3% (p < 0.05) and cerebral perfusion pressure (CPP) by 21.2% (p < 0.01) at 30 minutes, followed by a maximum decrease in ICP by 93.1% (p < 0.01) at 60 minutes. Changes in ICP and CPP persisted for longer than 180 and 90 minutes, respectively. The results of TCD ultrasonography showed that the baseline autoregulation was impaired on the ipsilateral side of ruptured aneurysm, and increments in flow velocities were higher and lasted longer on the contralateral side (48.75% compared with 31.96% [p = 0.045] and 180 minutes compared with 90 minutes [p < 0.05], respectively). The autoregulation was briefly impaired on the contralateral side during the infusion. A dose-dependent effect of CBF increments on favorable outcome was seen on Xe-CT scans (mRS Score 1-3, odds ratio 1.27 per 1 ml/100 g tissue x min, p = 0.045). CONCLUSIONS: Bolus systemic hypertonic saline therapy may be used for reversal of cerebral ischemia to normal perfusion in patients with poor-grade SAH.     

Implementation of cerebral autoregulation into computational fluid dynamics studies of cardiopulmonary bypass

Peri‐ or postoperative neurological complications are among the main risks for patients undergoing extracorporeal circulatory support (ECC). Two of the main reasons are an increased risk for strokes and altered flow conditions leading to cerebral hypoperfusion. This is strongly affected by cerebral autoregulation, which is the body's intrinsic ability to provide sufficient cerebral blood flow (CBF) despite changes in cerebral perfusion pressure (CPP). This complex mechanism has been mainly neglected in numerical studies, which have often been applied for analysis of ECC. In this study, a mathematical model is presented to implement cerebral autoregulation into computational fluid dynamics (CFD) studies. CFD simulations of cardiopulmonary bypass (CPB) were performed in a 3D model of the cardiovascular system, with flow variations between 4.5–6 L/min. Cerebral outlets were modeled using an equation to calculate CBF based on CPP. Assuming full regulation, CBF was kept constant for CPP between 80 and 120 mm Hg. A deviation in CBF of 20% occurred for CPP between 55–80 mm Hg and 120–145 mm Hg, respectively. The level of regulation was varied to take possible impairment of cerebral autoregulation into account. Furthermore, chronic hypertension was modeled by increasing the baseline CPP. Results indicate that even for full autoregulation, CBF is decreased during CPB. It is even lower for impaired autoregulation and hypertensive patients, demonstrating the strong impact of autoregulation on CBF. It is therefore imperative to include this mechanism into CFD studies. The presented model can help to improve CPB support conditions based on patient‐specific autoregulation parameters.     

Cerebral blood flow and metabolism in severely head-injured children. Part 2: Autoregulation

Autoregulation of cerebral blood flow ("CBF15") was tested in a series of 26 pediatric patients (mean age 13.2 years) with severe head injury (average Glasgow Coma Scale (GCS) score 5.5) in the acute stage. A baseline 133Xe CBF measurement was performed and then repeated, after blood pressure was increased by 29% with intravenous phenylephrine or decreased by 26% with intravenous trimethaphan camsylate. Correlations were made between CBF and clinical condition, outcome, time after injury, intracranial pressure (ICP), and pressure-volume index (PVI) changes, and the site of injury (hemispheres, diencephalon, or brain stem). The site of injury was determined with multimodality evoked potential measurements. Autoregulation was intact in 22 (59%) of 37 measurements. There was no correlation with GCS score, outcome, time after injury, site of injury, or way of testing (decreasing or increasing blood pressure). Autoregulation was statistically significantly more often impaired when CBF was either below normal -2 standard deviations (SD) (reduced flow) or above normal +2 SD (absolute hyperemia). In cases with intact autoregulation, mean ICP decreased from 17.5 to 15.0 mm Hg with higher blood pressure and increased from 19.0 to 21.3 mm Hg with lower blood pressure. When PVI was measured during the blood pressure manipulations, it was found to change in a direction opposite to the ICP change. The consequences of these findings in the management of ICP problems with blood pressure control are discussed.     

Computer simulation of intracranial pressure changes during induction of anesthesia: comparison of thiopental, propofol, and etomidate

We have developed a computer model of cerebrovascular hemodynamics that interacts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood flow (CBF) and intracranial pressure (ICP). The model is a seven-compartment constant-volume system. A series of resistances and compliances relate blood and cerebrovascular fluid fluxes to pressure gradients between compartments. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capillary resistance (Rar-c) simulate autoregulation and drug effects, respectively. Rar-c is also used to account for the effect of CO2 on the cerebral circulation. A three-compartment pharmacokinetic model predicts concentration-time profiles of intravenous induction agents. The effect-site compartment is included to account for disequilibrium between drug plasma and biophase concentrations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible personal computer. Using the model, we have predicted ICP responses during induction of anesthesia for a simulated patient with normal as well as elevated ICP. Simulation shows that the induction dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiopental > etomidate). The duration of this effect is limited to less than 5 minutes by rapid drug redistribution and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial ICP. ICP elevation is more pronounced in a nonautoregulated cerebral circulation. Simulation results are in good agreement with the available experimental data. The presented model allows comparison of various drug administration schedules to control ICP.