Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.     

Sequential changes in cerebral blood flow and metabolism in patients with subarachnoid haemorrhage

Summary Haemodynamic and metabolic sequences were investigated in nine patients having subarachnoid haemorrhage (SAH) up to 3 months following aneurysmal rupture, using positron emission tomography (PET). In the pre-spasm stage (2–4 days after SAH) cerebral blood flow (CBF, ml/100 ml/min) was 45±11, the cerebral metabolic rate of oxygen (CMRO₂, ml/100 ml/min) was 2.68±0.50, and cerebral blood volume (CBV, ml/100 ml) was 5.5±1.2. CBF within the normal range and a relatively low CMRO₂, indicated relative hyperaemia. This was possibly due to the direct toxic effect of SAH on the brain metabolism. CBV was considerably elevated. The spasm stage (6–15 days after SAH) showed CBF values of 39±7, CMRO₂ values of 2.42±0.50, and CBV values of 5.4±1.7. CBF decreased significantly (p<0.05 vs pre-spasm stage), and CMRO₂ also tended to decrease, while they were coupling. It is likely that this may have been induced by vasospasm. Thereafter, the PET parameters normalized gradually. During all the stages studied, significant laterality of the PET parameters was not observed. This may be because SAH and vasospasm provide diffuse pathophysiological conditions for the entire brain and cerebral arteries.     

Cerebral blood flow and cerebral metabolism in acute increase of intracranial pressure

Summary The effects of a stepwise acute increase of intracranial cerebrospinal fluid pressure on cerebral blood flow, cerebral arteriovenous differences of oxygen and glucose and on the output of lactate were studied in anaesthetized normoventilated normoxic dogs. Intracranial hypertension was produced by infusing mock-CSF into the cisterna magna. Mean arterial blood pressure was kept at a constant level throughout the experimental investigations. At a cerebral perfusion pressure of about 70 mm Hg, CBF and the cerebral metabolic rates of oxygen and glucose were not significantly changed. However, further reduction in the cerebral perfusion pressure to below 40 mm Hg, was accompanied by a statistically significant decrease of CBF and a deterioration of the oxidative metabolism. Glucose uptake was particularly disturbed by raised intracranial pressure. Increased cerebral output of lactate and low CMRO₂ indicated raised glycolysis. But (V-A)lactate was also increased at a relatively moderate reduction of the cerebral perfusion pressure, when autoregulation was still effective and CMRO₂ unchanged. The data are discussed in context with similar experimental results recently published by other investigators.Herrn Prof. Dr. H. Penzholz zum 60. Geburtstag gewidmet.     

Hemodynamic and metabolic effects of cerebral revascularization

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.     

The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism

Using positron emission tomography with 15O-labelled CO2 O2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO2) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol.     

Regional cerebral blood flow and oxygen metabolism in normal pressure hydrocephalus after subarachnoid hemorrhage

To clarify the pathophysiology of normal pressure hydrocephalus (NPH) after subarachnoid hemorrhage, the authors measured cerebral blood flow (CBF), cerebral oxygen metabolic rates (CMRO2), the cerebral oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in eight normal volunteers, six SAH patients with NPH, and seven patients without NPH by 15O-labeled gas and positron emission tomography (PET). In the NPH group, PET revealed a decrease in CBF in the lower regions of the cerebral cortex and a diffuse decrease in CMRO2. The decrease in CBF in the lower frontal, temporal, and occipital cortices was significantly greater in the NPH than in the non-NPH group. Reduction of CMRO2 was also more extensive in the NPH group, and both CBF and CMRO2 were more markedly decreased in the lower frontal region. OEF was increased in all areas in both of the patient groups, but the increase was not significant in most areas. CBF, CMRO2 and OEF did not significantly differ between the non-NPH group and the normal volunteers. There was no significant difference in CBV among the three groups. These results indicate that NPH involves impairment of cerebral oxygen metabolism in the lower regions of the cerebral cortex, particularly in the lower frontal region.     

Measurement of cerebral blood flow and volume with positron emission tomography during isoflurane administration in the hypocapnic baboon

Using positron emission tomography, cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured after the addition of isoflurane (1.3 vols %, end-tidal concentration) to neuroleptanesthesia (fentanyl/droperidol) in hypocapnic baboons. The study was designed to determine whether isoflurane, when administered during hypocapnia, acted as a cerebral vasodilator to increase either CBF or CBV. Mean arterial pressure was maintained within 10% of preisoflurane levels with an angiotensin infusion. In the first protocol (A), CBF and CBV were measured as close together in time as possible in order to detect divergent effects of isoflurane on these variables. When PaCO2 was reduced from 40 mmHg to 25 mmHg, CBF decreased from 44 +/- 4 to 31 +/- 4 ml.100 g-1.min-1 (P less than 0.05) and CBV decreased from 3.1 +/- 0.3 to 2.6 +/- 0.3 ml/100 g (P less than .05). Neither CBF nor CBV was significantly changed by the addition of isoflurane. In the second protocol (B), serial CBV scans were performed frequently during the addition of isoflurane in a fashion designed to detect transient changes in CBV at the time isoflurane was first added to the breathing circuit. Induction of hypocapnia again reduced CBV from 3.1 +/- .3 to 2.7 +/- .2 ml/100 g, (P less than .05) and addition of isoflurane did not change CBV. From these results the authors conclude that in the normal hypocapnic baboon the addition of 1.3% isoflurane does not significantly change cerebral blood flow or volume.     

Combined effects of propofol and mild hypothermia on cerebral metabolism and blood flow in rhesus monkey: a positron emission tomography study

Purpose Propofol reduces the cerebral metabolic rate for oxygen (CMRO₂), regional CMRO₂ (rCMRO₂), cerebral blood flow (CBF), and regional CBF (rCBF), but maintains the coupling of cerebral metabolism and blood flow. Under mild to moderate hypothermia, the coupling is maintained, while rCBF is reduced, but no direct measurement of rCMRO₂ has yet been reported. This study aimed to evaluate the effects of propofol under normothermic and mild hypothermic temperatures upon rCMRO₂, rCBF, and their regional coupling, through direct measurement by positron emission tomography. Methods Rhesus monkeys were anesthetized with 65% nitrous oxide and propofol. Then rCBF and rCMRO₂ were measured under four sets of conditions: infusion of a low-propofol dose (12 mg·kg⁻¹·h⁻¹) at normothermic temperatures (38°C), a high dose (25 mg·kg⁻¹·h⁻¹) at normothermic temperatures, a low dose under mild hypothermia (35°C), and a high dose under mild hypothermia. The ratio of rCBF/rCMRO₂ was calculated from these data. Results Reductions in CMRO₂ and rCMRO₂ in most regions were associated with two factors: the higher propofol dose and the induction of hypothermia, but there was no interaction between these factors. Concerning blood flow, no significant reduction was observed, except for CBF by the induction of hypothermia. The ratio of rCBF/rCMRO₂ was constant in this study setting. Conclusion During propofol anesthesia, it is possible to reduce cerebral metabolism throughout the entire brain as well as in any brain region by increasing the propofol dose or inducing hypothermia. The concurrent use of these two interventions has an additive effect on metabolism, and can be considered as safe, as their combination does not impair the coupling of cerebral metabolism and blood flow.     

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

Summary Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO₂), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO₂ from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO₂, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr⁻¹·min⁻¹ were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO₂, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

Cerebral blood flow and oxidative brain metabolism during and after moderate and profound arterial hypoxaemia

Summary In anaesthetized artificially ventilated dogs, the effect of graded arterial hypoxaemia on cerebral blood flow (CBF) and on the oxidative carbohydrate metabolism of the brain was tested. It is shown that the hypoxic vasodilatory influence on cerebral vessels is present even atmoderate systemic hypoxaemia, provided that PaCO₂ is kept within normal limits. At PaO₂ of about 50 Torr, CBF increased from 56.6 to 89.7 ml/100 g/min. With increasing cerebral hyperaemia (CBF increased to 110.9 ml/100 g/min, at PaO₂ of 30 Torr), CMRO₂ (4.2 ml/100 g/min) was not significantly raised above its normal level (4.7 ml/100 g/min) even with profound arterial hypoxaemia. This shows that CMRO₂ levels are poor indices of hypoxic hypoxia. A disproportionately high increase in cerebral glucose uptake (CMR glucose levels rose from 4.4 to 10.4 mg/100 g/min) and enhanced cerebral glycolysis (CMR lactate changed from 0.2 to 1.6 mg/100 g/min) at moderately reduced PaO₂ (50 Torr) indicated early metabolic changes which became more marked with further falls in arterial oxygen tension. However, 60 minutes after restoration of a normal PaO₂ level, CBF and brain metabolism were found to have completely recovered. It is concluded that a short period of profound systemic hypoxaemia does not produce long lasting metabolic and circulatory disorders of the brain provided the cerebral perfusion pressure does not vary, and is kept at normal levels.     

Haemodynamic and metabolic changes following extra-intracranial bypass surgery

Summary In order to study the haemodynamic and metabolic changes following bypass surgery, the regional cerebral blood flow (rCBF), the oxygen extraction fraction (rOEF), the cerebral metabolic rate of oxygen (rCMRO₂), and the cerebral blood volume (rCBV) were measured using a positron emission tomograph (PET) on 13 patients who had unilateral internal carotid artery and/or middle cerebral artery occlusion. The patients were divided into two subgroups according to pre-operative rOEF values from the arterial occlusion side: the misery perfusion group, which had high rOEF values (0.56), and the coupling perfusion group, which had normal rOEF values (0.38–0.48). A post-operative PET study was performed 1–2 months and/or 1–5 years following the surgery. Six of the misery perfusion cases showed a post-operative CBF increase, where an accompanying OEF decreased to its normal level, indicating an attenuated misery perfusion state. The CMRO₂ values, however, remained low. The other 7 coupling perfusion cases had an ipsilateral CBF increase in the earlier PET study. We conclude that misery perfusion is attenuated following bypass surgery, although the procedure does not consistently improve oxygen metabolism.     

The effect of ketanserin on cerebral blood flow and oxygen metabolism in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on average global cerebral blood flow (CBF) and average global cerebral oxygen metabolism (CMRO₂) was examined in 8 healthy volunteers. CBF and CMRO₂ were measured with the Kety-Schmidt technique before ketanserin administration (baseline) and after administration of 2 different doses of ketanserin intravenously (dose I: 10 mg bolus and an infusion of 6 mg/h; dose II: 20 mg bolus and an ifusion of 20 mg/ h). Baseline CBF and CMRO₂ were 60 and 3.6 ml/100 g/min, respectively, and were not changed by administration of ketanserin dose I. During administration of dose II, however, CBF fell to 52 ml/ 100 g/min (p=0.05) and CMRO₂ was reduced to 3.2 ml/100 g/min (p < 0.05).We conclude that when administered in a high dose, ketanserin has the ability to depress cerebral oxygen metabolism, but when administered in a clinically relevant dose ketanserin does not influence average global CBF or average global CMRO₂. Ketanserin could be a safe antihypertensive drug in neuroanaesthesia or in the neuro-intesive care unit.     

Cerebral blood flow and metabolism following superficial temporal artery to superior cerebellar artery bypass for vertebrobasilar occlusive disease.

In order to clarify the effectiveness of extracranial-intracranial bypass operations in patients with vertebrobasilar occlusive disease, the authors used positron emission tomography to investigate the cerebral blood flow (CBF) and metabolism of eight patients undergoing superficial temporal artery (STA)-superior cerebellar artery (SCA) bypass procedures. In the preoperative studies, CBF in the region of the posterior fossa was low and the oxygen extraction fraction (OEF) was high, the so-called "misery perfusion syndrome." Such changes were evident in both the posterior circulation and the anterior circulation regions. Postoperatively, there was a significant increase in CBF, a significant decrease in the OEF not only in the region of posterior circulation but also over the entire brain, and a disappearance of the uncoupling between CBF and oxygen metabolism. The STA-SCA bypass procedure is effective in improving CBF and metabolism in patients with vertebrobasilar occlusive disease.     

Cerebral circulation and metabolism in adults' Moyamoya disease-PET study

Summary Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral metabolic rate for oxygen (rCMRO₂) and cerebral blood volume (rCBV) in nine cases of moyamoya disease in adults were studied with positron emission CT (PET) scan, using¹⁵O steady-state methods. Three cases showed ischaemic symptoms and the other six cases showed haemorrhagic symptoms. PET scan was performed during the chronic stage. Control data were obtained from eight normal volunteers. Regional cerebral blood flow and other physiological parameters in cerebral gray matter, white matter and basal ganglia were compared with normal controls.All nine cases of Moyamoya disease showed decreased rCBF, though not significant, in cerebral gray matter, white matter and basal ganglia. Reduction of rCBF was significant in the cerebral cortex of six haemorrhagic cases. This significant decrease was considered to be due to diaschisis and also brain atrophy caused by the cerebral haemorrhage. There was a significant increase in rCBV in white matter of the both ischaemic and haemorrhagic cases. The calculated value of CBF/CBV is considered to be an index of perfusion pressure. This value was significantly decreased in all three regions, though rOEF was not significantly increased in moyamoya disease. Hence the cerebral circulation in adults with moyamoya disease appears to be characterized by a mild decrease in perfusion pressure and prolonged circulated time.     

The effect of ketanserin on cerebral blood flow and cerebrovascular CO2 reactivity in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on the cerebral blood flow (CBF) and the cerebrovascular CO₂ reactivity was examined in 10 healthy volunteers. Ketanserin was administered as an intravenous bolus of 10 mg followed by an infusion of 6mg/h. Before administration CBF was measured by single photon emission computerized tomography (SPECT) of inhaled¹³³ Xenon. Then arterial CO₂ tension was subsequently decreased by voluntary hyperventilation and increased by breathing an air/CO₂ mixture. The relative changes in CBF induced by the changes in arterial CO₂ tension were estimated by the cerebral arterio-venous oxygen content difference method. One hour following the start of ketanserin infusion the SPECT measurement and CO₂ manipulations were repeated.The CO₂ reactivity (expressed as the slope of the regression line of the linear relation between CBF and PaCO₂), was unchanged, i.e. 3.2%/0.1 kPa before ketanserin and 4. 1%/0.1 kPa during ketanserin, respectively. Using regression lines from a semi-logarithmic plot the CO₂ reactivity was also unchanged 3.4%/0.1 kPa and 3.5%/0.1 kPa, respectively. Ketanserin did not change CBF. The cerebral oxygen metabolism (CMRO₂) was decreased 19% one hour after the start of infusion of ketanserin.In conclusion administration of ketanserin in a clinically relevant dose to healthy volunteers does not change the regional CBF not the cerebrovascular CO₂ reactivity, but a decrease in CMRO₂ was observed. However further studies are needed to clarify whether ketanserin in fact has a depressing effect on CMRO₂ or whether the different results are caused by methodological errors or stocastic variation.     

Measurement of regional cerebral blood flow with H2 15O positron emission tomography during matas test

Summary The authors carried out a Matas test with a regional cerebral blood flow (rCBF) study using H₂ ¹⁵O positron emission tomography (PET) for three cases of large internal carotid artery aneurysms. There is a likely correlation between the cerebral blood flow (CBF) reduction rate obtained by PET, and the mean stump pressure available from a conventional balloon occlusion test. The advantages of this noninvasive and quantitative method are presented in comparison with other methods.     

Cerebral blood volume and blood flow responses to hyperventilation in brain tumors during isoflurane or propofol anesthesia

Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P < 0.05), but without accompanying changes in intracranial pressure. However, the percent reduction in regional CBF with hypocapnia was two times larger than that observed in the CBV response (P < 0.01). In contrast, there were no significant changes in CBV and CBF in the Propofol group with hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane. IMPLICATIONS: In rabbits with brain tumors, brain blood flow and volume were significantly larger in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol during normocapnia, and remained responsive to a reduction in PaCO(2). Consequently, during hypocapnia, brain blood flow and volume values with isoflurane were similar to values with propofol.     

Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.

Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. Implications: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.     

Propofol in der Neuroanästhesie

The quality, result, and prognosis of neurosurgery relies heavily on the anaesthetic technique. Many different classes of drugs have been used during neurosurgical anaesthesia. This article reviews the use of intravenous (IV) propofol as an alternative to volatile anaesthetic techniques. Anaesthesia requirements for neurosurgical procedures are elaborated upon in the first part of the article. The priority of neuroanaesthesia is to preserve neuronal function by avoiding complications such as hypoxia, hypercarbia, and cardiovascular instability. Thereafter, the chosen anaesthetic technique should minimally interfere with cerebral autoregulation and CO₂ responsiveness, while brain relaxation is encouraged by decreasing the cerebral metabolic rate for oxygen (CMRO₂) and cerebral blood flow (CBF). In addition, the anaesthetic technique should be associated with rapid and predictable recovery in the operating theatre in order to allow early evaluation of the surgery. The second part of the article describes IV techniques for neurosurgery as an alternative to volatile anaesthetics, all of which increase CBF, cerebral blood volume, and intracranial pressure (ICP) in a dose-related manner and diminish cerebral autoregulation and interfere with cerebrovascular CO₂ reactivity. Nitrous oxide has a stimulant effect on cerebral metabolism and is associated with an increase in CBF. On the other hand, all IV agents except ketamine are associated with decreases in CMRO₂ and are cerebral vasoconstrictors. For this reason, it is rational to use them for the induction and maintenance of anaesthesia for neurosurgery as part of a total IV anaesthetic technique. The third part of the article focuses on propofol as the newest representative of IV anaesthetics. It is a sedative-hypnotic agent that has a pharmacokinetic-dynamic profile ideally suited for continuous infusion. Propofol reduces ICP, CBF, and CMRO₂. Animal models have suggested the possibility of cerebral protection. The responsiveness of the cerebral circulation to alterations in arterial blood pressure is maintained. Evaluating propofol for major neurosurgery demonstrated good quality and depth of anaesthesia, excellent brain relaxation, and minimal surgical bleeding. In conclusion, total IV anaesthesia with propofol has proven to be a valid alternative to conventional thiopentone-isoflurane anaesthesia for intracranial surgery.     

Zum Einfluß der präischämischen Blutzuckerkonzentration auf Hämodynamik und regionale Organdurchblutung während und nach kardiopulmonaler Reanimation (CPR) beim Schwein

Blood glucose alterations prior to cerebral ischaemia are associated with poor neurologic outcome, possibly due to extensive lactic acidosis or energy failure. Cerebral effects of hyper- or hypoglycaemia during cardiopulmonary resuscitation (CPR) are less well known. In addition, little information is available concerning cardiac effects of blood glucose alterations. The aim of this study was to evaluate the effects of pre-cardiac-arrest hypo- or hyperglycaemia compared to normoglycaemia upon haemodynamics, cerebral blood flow (CBF) and metabolism (CMRO₂), and regional cardiac blood flow during CPR subsequent to 3?min of cardiac and respiratory arrest and after restoration of spontaneous circulation. Methods. After approval by the State Animal Investigation Committee, 29 mechanically ventilated, anaesthetised pigs were instrumented for haemodynamic monitoring and blood flow determination by the radiolabeled microsphere technique. The animals were randomly assigned to one of three groups: in group I (n=9) blood glucose was not manipulated; in group II (n=10) blood glucose was increased by slow infusion of 40% glucose to 319±13 mg/dl; in group III (n=10) blood glucose was lowered by careful titration with insulin to 34±2 mg/dl. After 3 min of untreated ventricular fibrillation and respiratory arrest, CPR (chest compressor/ventilator (Thumper^®) and epinephrine infusion) was commenced and continued for 8?min. Thereafter, defibrillation was attempted, and if successful, the animals were observed for another 240?min. Cerebral perfusion pressure (CPP), CBF, CMRO₂, coronary perfusion pressure (CorPP), and regional cardiac blood flow were determined at control, after 3?min of CPR, and at 10, 30, and 240?min post-CPR. Results. In group I, 4/9 animals (44%) could be successfully resuscitated; in group II 4/10 (40%); and in group III 0/10 (0%). Prior to cardiac arrest, mean arterial pressure, CPP, and CorPP in group III were significantly lower compared to groups I and II. In group I, CPP during CPR was 26±6?mmHg; CBF 31±9?ml/min/100?g CMRO₂ 3.8±1.2 ml/min/100?g; CorPP 18±5 mmHg; and left ventricular (LV) flow 35±15 ml/min/100 g. In group II: CPP=21±5; CBF 21±7; CMRO₂ 1.8±0.8; CorPP 16±6; and LV flow 22±9; and in group III: CPP 15±3; CBF 11±8; CMRO₂ 1.5±1.1; CorPP 4±2; and LV flow 19±10. During the 240-min post-resuscitation period, there were no differences in CBF, CMRO₂, or LV flow between groups I and II. Conclusion. Hypoglycaemia prior to cardiac arrest appears to be predictive for a poor cardiac outcome, whereas hyperglycaemia does not impair resuscitability compared to normoglycaemia. In addition, hyperglycaemia did not affect LV flow, CBF, or CMRO₂. However, it has to be kept in mind that haemodynamics and organ blood flow do not permit conclusions with respect to functional neurologic recovery or histopathologic damage to the brain, which is very likely to be associated with hyperglycaemia.