Reduction In Cerebral Metabolism Research Articles

Sex Differences in the Effect of Diabetes on Cerebral Glucose Metabolism.

The neuroimaging literature indicates that brain structure and function both deteriorate with diabetes, but information on sexual dimorphism in diabetes-related brain alterations is limited. This study aimed to ascertain whether brain metabolism is influenced by sex in an animal model of diabetes. Eleven rats (male, n = 5; female, n = 6) received a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to develop diabetes. Another 11 rats (male, n = 5; female, n = 6) received the same amount of solvent through a single intraperitoneal injection. Longitudinal positron emission tomography scans were used to assess cerebral glucose metabolism before and 4 weeks after STZ or solvent administration. Before STZ or solvent injections, there was no evidence of sexual dimorphism in cerebral metabolism (p > 0.05). Compared with healthy control animals, rats with diabetes had significantly decreased brain metabolism in all brain regions (all p < 0.05). In addition, female diabetic rats exhibited further reduction in cerebral metabolism, relative to male diabetic rats (p < 0.05). The results of this study may provide some biological evidence, supporting the existence of a sexual dimorphism in diabetes-related complications.

Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease.

IntroductionLanabecestat, a beta‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) inhibitor, was investigated as a potential Alzheimer's disease (AD)‐modifying treatment. As previously reported, amyloid beta (Aβ) neuritic plaque burden reduction did not result in clinical benefit. Lanabecestat's effects on neuroimaging biomarkers and correlations between neuroimaging biomarkers and efficacy measures are reported.MethodsAMARANTH and DAYBREAK‐ALZ were 104‐ and 78‐week, multicenter, randomized, double‐blind, placebo‐controlled studies of lanabecestat in early symptomatic AD (AMARANTH) and mild AD dementia (DAYBREAK‐ALZ). Patients randomly (1:1:1) received placebo, lanabecestat 20 mg, or lanabecestat 50 mg daily (AMARANTH, n = 2218; DAYBREAK‐ALZ, n = 1722). Florbetapir positron emission tomography (PET), fluorodeoxyglucose (FDG) PET, flortaucipir PET, and volumetric magnetic resonance imaging (MRI) were used to measure Aβ neuritic plaque burden, cerebral metabolism, aggregated tau neurofibrillary tangles, and brain volume, respectively. Additionally, florbetapir perfusion scans were performed in DAYBREAK‐ALZ. Efficacy measures included 13‐item Alzheimer's Disease Assessment Scale–Cognitive Subscale, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, Clinical Dementia Rating–Sum of Boxes, Functional Activities Questionnaire, and Mini‐Mental State Examination. These studies stopped early due to futility.ResultsDespite previously observed annualized reduction in Aβ neuritic plaque burden, there were no treatment differences in annualized change of aggregated tau neurofibrillary tangle burden (AMARANTH, n = 284; DAYBREAK‐ALZ, n = 70), cerebral metabolism (AMARANTH, n = 260; DAYBREAK‐ALZ, n = 38) and perfusion (DAYBREAK‐ALZ, n = 213). Greater brain volume reduction (AMARANTH, n = 1697 [whole brain]; DAYBREAK‐ALZ, n = 650 [whole brain]) occurred on lanabecestat compared to placebo. Higher baseline aggregated tau neurofibrillary tangle burden, lower cerebral metabolism, and lower brain volumes correlated with poorer baseline efficacy scores and greater clinical worsening. Lower baseline cerebral perfusion correlated with poorer baseline efficacy scores. Reduction in cerebral metabolism or whole brain volume correlated with clinical worsening, regardless of treatment assignment.DiscussionTau pathology and cerebral metabolism assessments showed no evidence of lanabecestat slowing pathophysiologic progression of AD. Lanabecestat exposure was associated with brain volume reductions. Correlations between imaging measures and cognitive assessments may aid future study design.

P01-9 - Gas exchange and brain metabolism in patients during cardiac surgery: hypo-vs.normothermiс CPB

Neurologicalimpairments remain an important complication of cardiac surgery, despite significant advances in operative techniques. To improve this situation there are several techniques of artificial perfusion. One of them is decreasing core temperature to gain reduction of cerebral metabolism.

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia.

The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3min36s to 7min26s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery-jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non-oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia-induced oxygen-conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2 ) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea-divers performed a maximal apnoea (range 3min 36s to 7min 26s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2 was reduced by ∼29% (P<0.01, Cohen's d=1.18) near the termination of apnoea compared to baseline, although non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7mmHg), but not mild-hypercapnia (arterial CO2 tension: ∼46.3mmHg), depressed the CMRO2 (∼17%, P=0.04, Cohen's d=0.87). Similarly to the apnoea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.

Cerebral arterial gas embolism following cardiopulmonary bypass surgery

A 13-year-old boy with a history of tetrology of Fallot underwent a pulmonary value replacement procedure. Gas bubbles were observed in the bypass circuit during the procedure. Trendelenburg position, one of the older standard recommendations when AGE is suspected, was established during the remainder of the procedure [2]. The patient could not support respirations adequately and remained minimally responsive following the procedure. Hyperbaric oxygen therapy was implemented to reduce gas bubble volume and facilitate diffusion of gas back into solution [3]. During the hyperbaric oxygen therapy, the patient experienced three cardiac arrests requiring chest compressions and pressor support. Following the hyperbaric procedure, the patient remained without brainstem reflexes and did not breathe spontaneously. Crepitus was present throughout the abdominal and pelvic areas. The accompanying scan (Fig. 1) was performed six hours after the hyperbaric procedure ended to confirm the diagnosis. Fig. 1 Computerized tomography scan of the brain after hyperbaric treatment for iatrogenic arterial gas embolism. The white and gray matter differentiation is lost and the sulcal pattern is obliterated. Numerous cortical vessels, especially in the anterior and ... Arterial gas embolism (AGE) is a known complication of underwater diving using compressed air and a rare complication of medical procedures. Iatrogenic causes are more common in procedures that access the arterial circulation, such as cardiopulmonary bypass surgery and angiography, but can also be caused by procedures that access the venous system when accompanied by a cardiovascular defect that results in shunting of blood from the venous to the arterial system [1,2]. Although AGE and the central nervous system complications of AGE have been discussed in the literature, examples of neuroimages associated with central nervous system complications are not well documented. A case is presented to familiarize the neurologist with the conspicuous neuroimaging findings associated with AGE. Iatrogenic AGE is uncommon, but can occur as a result of pulmonary barotrauma during mechanical ventilation and through direct injection of air into the vascular system [1,2]. Procedures that access the arterial system, such as cardiopulmonary bypass or angiography, can results in injection of air directly into the arterial system. Gas in the venous system can rarely result in AGE when a right-to-left shunt exists. Such shunts are common when an atrial septal defect or patent foramen ovale exists and in congenital cardiac anomalies. Since children are more likely to have untreated congenital cardiac abnormalities and vascular shunts and are at high risk for barotraumas, AGE is an entity with which pediatric specialists should be familiar. Initial supportive procedures are implemented when AGE occurs. These include administration of 100% oxygen, discontinuation of nitrous oxide and support of vital functions. Although Trendelenburg and lateral decubitus positions have been recommended in the past, since the buoyancy of gas bubbles is not sufficient to counteract the force of the blood flow towards the head, supine positioning in now recommended [1, 2]. In addition, Trendelenburg position can exacerbate cerebral edema [3]. Hyperbaric oxygen treatment or retrograde perfusion can be considered if supportive procedures are not effective [4,5]. A reduction in cerebral metabolism through barbiturate coma, especially when seizures are present, may be effective [1].

Sleep Slow-Wave Activity Regulates Cerebral Glycolytic Metabolism

Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of <10 Hz. The induction of 1-Hz oscillations, but not 10-Hz oscillations, in the electroencephalogram by optogenetic stimulation of cortical pyramidal cells during wakefulness triggers a decline in lactate concentration. We conclude that cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.

Chapter 11. Barbiturates

Chapter 11. Barbiturates

Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer’s disease.

Dementia, especially Alzheimer's disease, has a high prevalence in the elderly population. Therefore, identifying individuals who are at a high risk for early diagnosis is crucial to allow both pharmacological and behavioral therapeutic interventions, which in some cases can delay the progression of dementia. This paper describes neuropsychological and neurobiological markers for the early diagnosis of Alzheimer's disease and presents the main risk factors, including neuropathological, neuroanatomical, neurofunctional, genetic, and neuropsychological. The literature shows that the combination of these markers is the best method for predicting Alzheimer's disease, years before its clinical manifestation. The most prevalent neurobiological and neuropsychological risk factors include (1) senile plaques and neurofibrillary tangles in the medial temporal lobe and cortical regions, (2) low concentrations of Aβ1-42 peptide and high concentrations of total tau protein and phosphorylated tau protein in cerebrospinal fluid, (3) reduced global cerebral volume, increased ventricular volume, and atrophy in the hippocampal formation and entorhinal cortex, (4) global reductions in cerebral metabolism and perfusion in the temporoparietal junction, temporal, parietal, and frontal lobes, hippocampal formation, and posterior cingulate cortex, (5) the presence of the apolipoprotein E e4 allele, and (6) verbal anterograde episodic long-term memory impairment and executive dysfunction. The present review discusses the evidence for markers that identify individuals who are at a high risk of developing Alzheimer's disease and the importance of longitudinal studies in this context.

Anesthetic drugs and sustained neuroprotection in acute cerebral ischemia: can we alter clinical outcomes?

Anesthetic drugs have been tested for their neuroprotective characteristics for decades because of their potential either to interrupt or to slow the sequence of injurious biochemical and molecular events that ultimately result in irreversible neuronal death. Unfortunately, clinical trials examining the neuroprotective effects of anesthetic agents have failed to translate the experimental evidence. The purpose of this editorial is to consider the current stage of knowledge regarding anesthetic neuroprotection in the context of identifying future directions for this important field of research. A fundamental issue in establishing the need for perioperative neuroprotection is to identify target populations that will benefit neurologically from specific anesthetic agents. Perioperative cerebral ischemia remains a significant source of morbidity and mortality in cardiac and noncardiac patients alike. For example, the incidence of acute ischemic stroke varies from 0.8 to 8.8% in patients undergoing peripheral vascular, aortic reconstructive, and cardiac surgery. In patients undergoing colorectal surgery, total hip arthroplasty, and head and neck surgery, the incidence of perioperative stroke varies from 0.3 to 4.8%. Acute neurodegeneration may also present as postoperative neurocognitive decline. It is rather surprising, then, that this important pathogenicity has been disregarded as a target of neuroprotective strategies, yet it clearly deserves a neuroprotective approach. A second important issue is the need to establish the differential neuroprotective potential of the various general anesthetic agents. The proposed mechanisms of anesthetic neuroprotection include reduction of cerebral metabolism and intracranial pressure, suppression of seizure activity, and lessening of sympathetic discharge. Additionally, anesthetics inhibit synaptic release of excitatory neurotransmitters; they activate inhibitory c-aminobutyric acid (GABA) and glycine receptors and slow the intracellular Caand Naaccumulation. Additionally, anesthetics reduce the generation of reactive free radical species; they increase ischemic tolerance by preand post-conditioning, and they also inhibit apoptotic pathways. Thus, there is considerable evidence that multiple pathways exist by which anesthetic agents have the potential to exert clinically important benefits. But what is the experimental evidence for (sustained) anesthetic neuroprotection? In numerous studies, anesthetic neuroprotection has been confirmed in rodents subjected to focal or incomplete hemispheric ischemia where isoflurane, sevoflurane, desflurane, and xenon, as well as barbiturates and propofol, decreased infarct size and improved motor and cognitive function when given prior to the ischemic challenge. The reduction in ischemic neuronal injury has been shown to be most prominent in study designs comparing ‘‘anesthesia’’ with awake or sedated states and less pronounced when different anesthetics were compared with each other. Neurologic outcome is reproducible only with brief episodes of cerebral ischemia, while longer durations of low-flow states or permanent focal ischemia are resistant to anesthetic neuroprotection. In line with this evidence, anesthetics have no neuroprotective properties in the setting of global cerebral ischemia and when given after the ischemic insult. It is questionable whether the effects of anesthetics seen in these different ischemia models are permanent. Studies in rats subjected to focal cerebral or incomplete global ischemia have shown that cell death was substantially reduced in the immediate post-ischemic period; however, C. Werner, MD, PhD (&) Department of Anesthesiology, Johannes Gutenberg-Universitat Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany e-mail: wernerc@uni-mainz.de

Intraoperative use of somatosensory-evoked potentials: is general anaesthesia comparable to awake condition?

Editor, We have read with great interest the article by Fielmuth and Uhlig [1] on the role of somatosensory-evoked potentials (SSEPs) in detecting cerebral ischaemia during carotid endarterectomy. The authors made an assessment of the validity of SSEP monitoring during carotid endarterectomy in awake patients under locoregional anaesthesia. They correctly reported the current substantial variety of SSEP parameters and thresholds related to these SSEP parameters used to detect critical deterioration in cerebral blood flow (CBF). Their study was designed to compare SSEP tracings with the objective clinical–neurological examination in order to evaluate the reliability of the different SSEP-generated criteria. They referred to Shapiro and Aidinis [2], who developed a model, which can be seen as the methodological basis for current neuromonitoring during carotid surgery. This model correlates neuronal integrity and electrical activity with CBF. Using this approach to interpret changes in SSEP tracing as a perfusion-dependent neuronal metabolic situation, different parameters and values have been established to detect a relevant reduction in CBF.

Gender differences in brain reserve

Neuropathological studies suggest that the association between neurodegenerative brain damage and clinical symptoms may be stronger in women than in men. To test the hypothesis that cerebral metabolic deficits due to neurodegeneration are more pronounced in men than in women at the same level of clinical disease severity. 93 patients with mild Alzheimer's disease (AD; 50 men, 43 women) underwent an extensive clinical and neuropsychological examination and (18)F-FDG PET imaging at a university-based outpatient unit for cognitive disorders. An analysis of covariance (with age, total score of the CERAD neuropsychological battery, and years of school education as covariates) was conducted in each study group to identify gender differences in glucose metabolism. Controlling for age, education, and clinical severity, cortical regions were identified,where glucose metabolism was significantly reduced in men as compared with women. These regions were located in areas typically affected by AD pathology (right inferior frontal, superior temporal and insular cortex, and hippocampus). These data suggest that the same clinical severity of dementia is associated with greater reductions in cerebral metabolism in men than in women suggesting a greater degree of brain reserve in men.

Acute hypertension in intracerebral hemorrhage: Pathophysiology and treatment

Non-traumatic or spontaneous intracerebral hemorrhage (ICH) is defined as intra-parenchymal bleeding with or without extension into the ventricles and rarely into the subarachoid space. Primary ICH in most cases is associated with chronic hypertension. Acute hypertension is associated with hematoma expansion, and poor neurological outcome. The treatment of hypertension in acute ICH is a topic of controversy. Experiments have shown an area of ischemia around the hematoma, with the reduction of regional cerebral blood flow (CBF) secondary to compression of microvasculature. Not all scientific results agree with the above findings. Recent studies have shown that CBF decreases in the perihematoma region but with concomitant reduction of cerebral metabolism, which would argue against an area of ischemia in the perihematoma region. Based on the above result, there have been several clinical trials looking at clinical outcome and decrease in hematoma expansion rates with reduction of blood pressure acutely after ICH. The parameters for the blood pressure control are still under investigation. The American Heart Association has put forward guidelines for blood pressure control which have been adopted in the centers around the country. We have described the protocol we use at our center for the blood pressure control in patients with acute ICH.

Statistical Image Analysis of Cerebral Glucose Metabolism in Patients with Cognitive Impairment following Diffuse Traumatic Brain Injury

The aim of this study was to explore the regional cerebral glucose metabolism (rCM) in patients with chronic stage traumatic brain injury (TBI) compared with normal controls. We also investigated the relationship between regional cerebral glucose metabolism and cognitive function. We performed 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) study using statistical parametric mapping (SPM) analysis in 36 diffuse axonal injury (DAI) patients (mean age +/- SD, 36.3 +/- 9.8 years). At 6 months or more after head injury, all patients underwent FDG-PET study and neuropsychological batteries to assess cognitive function. Thirty healthy, gender-matched control subjects who were comparable in age were also studied. Between the TBI patients and normal controls, group comparisons showed regional metabolic decreases in the bilateral frontal lobes, temporal lobes, thalamus, as well as the right cerebellum in the TBI group. Only full-scale Intelligence Quotient (IQ) (mean +/- SD, 78.5 +/- 11.9) correlated positively with rCM in the right cingulate gyrus and the bilateral medial frontal gyrus. In other examinations, the correlation was not provided. DAI may induce functional disconnection and decreased neuronal activity, and finally lead to diffuse glucose hypometabolism. Low full-scale IQ scores may be related to significantly different underlying cognitive impairment. In supporting cognitive function following TBI, which showed diffuse cerebral metabolic reduction compared with normal controls, medial prefrontal cortex and anterior cingulate cortex may be an important component.

CEREBRAL METABOLIC REDUCTION IN SEVERE MALARIA: FLUORODEOXYGLUCOSE-POSITRON EMISSION TOMOGRAPHY IMAGING IN A PRIMATE MODEL OF SEVERE HUMAN MALARIA WITH CEREBRAL INVOLVEMENT

Cerebral metabolic changes in Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi, a primate model of severe human malaria with cerebral involvement, were directly evaluated by fluorodeoxyglucose-positron emission tomography (FDG-PET). We observed diffuse and heterogeneous reduction of metabolism in the cerebral cortex in the acute phase of malaria infection. Neuropathologic examination showed preferential sequestration of parasitized red blood cells in the cerebral microvasculature. However, hemorrhagic change or necrosis was not observed in hematoxylin and eosin-stained and Nissl-stained brain tissues. This suggests that reduction of cerebral metabolism occurs before parenchymal changes appear in the brain. This may be one reason why more than half of the patients with cerebral malaria have no neurologic sequelae after recovery.

Pharmacological and pathological modulation of cerebral physiology

Cerebrovascular physiology is modulated by anaesthetic agents and other drugs commonly used in the perioperative period, and may be substantially modified by common disease processes. The effect of any given intervention depends on baseline physiology, other interventions that are applied at the same time, and the duration for which interventions are used. In general, the intravenous anaesthetic agents tend to cause dose-related reductions in cerebral metabolism, and through flow metabolism coupling, proportionate reductions in cerebral blood flow and cerebral blood volume (and hence intracranial pressure). While intravenous anaesthetics can reduce cerebral activity to an isoelectric electroencephalogram, the opioids and benzodiazepines cannot achieve this. The inhalational anaesthetic agents produce similar effects to the intravenous agents at low dose levels, but at higher MAC values their intrinsic vasodilatory effects become prominent with resultant increases in cerebral blood flow and intracranial pressure. Nitrous oxide is an extremely potent vasodilator, the effects of which are not reversed by hyperventilation. There is much recent interest in xenon, which may have specific neuroprotective properties. Cerebral ischaemia, subarachnoid haemorrhage and head injury all impair cerebral autoregulatory responses and may alter responses to anaesthetic agents. The article outlines a rational approach to management of cerebrovascular physiology in the perioperative period.

Invited commentary

Three management strategies have been described for cerebral protection during aortic arch reconstruction. Hypothermic circulatory arrest (HCA) lowers the brain temperature with a concomitant reduction in cerebral metabolism. The protection imparted by the reduced cerebral metabolic rate is, however, time-dependent. It is oftentimes difficult to perform a complex arch reconstruction in the 45 to 60 minutes recommended as the safe limit for HCA. Retrograde cerebral perfusion (RCP) is, arguably, the most widely employed but least well studied of the three techniques. Selective superior vena caval perfusion cannot meet the brain’s metabolic demand due to perfusate runoff into the systemic venous circulation. The advantage of RCP lies in the continuous washout of particulate emboli from the head vessels. Atheromatous debris from arch aneurysms are thought to be the primary etiologic factor for neurologic sequelae following arch aneurysm repair. The third management strategy, antegrade cerebral perfusion (ACP), is employed by Takahara and colleagues in the current series with superb results. ACP provides better nutritive flow to the brain than either HCA or RCP. Although cannulation of the potentially diseased arch vessels can lead to atheroma embolization or exacerbation of dissection flaps, the enhanced cerebral protection allows the surgeon to operate on the aortic arch with little time constraint. In the current series, the authors cannulate diseased arch vessels under direct vision (using HCA) and employ pH-stat management to abolish cerebral autoregulation. ACP is infrequently employed, as the cardiopulmonary bypass circuit is more complex (multiple roller heads) and the cannulation scheme is more cumbersome. The reported postoperative temporary neurologic dysfunction and stroke rates of 3% and 2%, respectively, should make the reader reconsider utilizing this management strategy in the patient who requires a complex aortic arch reconstruction.

No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury.

Department of Anesthesiology; Duke University,; Durham, North Carolina Department of Anesthesiology; Wake Forest University School of Medicine; Winston-Salem, North Carolina

No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury.

Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs). Nine patients were studied a mean of 11.2+/-1.6 hours (range 8-14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6+/-1.8 and their mean age 27+/-9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30+/-2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls. Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59+/-0.44 ml/100 g/minute [p < 0.01] and 0.31+/-0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5+/-8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8+/-0.56 ml/100 g (p < 0.001), OEF rose to 0.45+/-0.13 (p < 0.02), and CvO2 fell to 8.3+/-3 vol% (p < 0.02); CMRO2 remained unchanged. The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.

Effects of 1 MAC Desflurane on Cerebral Metabolism, Blood Flow and Carbon Dioxide Reactivity in Humans

We investigated the cerebral haemodynamic effects of 1 MAC desflurane anaesthesia in nine male patients scheduled for elective coronary bypass grafting. For the measurement of cerebral blood flow (CBF) a modified Kety-Schmidt saturation technique with argon as inert tracer gas was used. Measurements of CBF were made before induction of anaesthesia and 30 min after induction under normocapnic, hypocapnic and hypercapnic conditions in sequence. Changes in mean arterial pressure after induction of anaesthesia and during the course of the study were minimized using norepinephrine infusion. In comparison with the awake state under normocapnic conditions, desflurane reduced mean cerebral metabolic rate of oxygen (CMRO2) by 51% and mean cerebral metabolic rate of glucose (CMRglc) by 35%. Concomitantly, CBF was significantly reduced by 22%; jugular venous oxygen saturation (SjvO2) increased from 58 to 74%. Hypo- and hypercapnia caused a 22% decrease and a 178% increase in CBF, respectively. These findings may be interpreted as the result of two opposing mechanisms: cerebral vasoconstriction induced by a reduction of cerebral metabolism and a direct vasodilator effect of desflurane. CBF alterations under variation of PaCO2 indicate that cerebrovascular carbon dioxide reactivity is not impaired by application of 1 MAC desflurane.

Neuroprotective effects of anesthetics

During cerebral ischaemia, energetic failure of injured cells together with excessive release of glutamate the most common excitatory amino acid in the brain, lead to excitotoxicity and immediate or delayed neuronal death. There is strong experimental evidence to support the neuroprotective role played by anaesthetic agents. Hence, barbiturates, volatile anesthetics or ketamine exhibit significant protective effects against ischaemic injury in numerous experimental models of ischaemia in vitro or in vivo. The neurobiological substrate of this action is probably a reduction of the activity of glutamate receptors (N-methyl-D-aspartate and kainate), and/or downstream biochemical events. Reduction of cerebral metabolism by these agents seems not to be their primary neuroprotective mechanism. However, no data are available at the present time to support any clinical benefit of these actions in neurosurgical patients, head trauma in contrast to mild hypothermia or cerebrovascular disease. Future research should develop models as close as possible to the clinical situation to examine further pathophysiological hypotheses and clinical implications.