Effects of Subanesthetic Ketamine on Regional Cerebral Glucose Metabolism in Humans

Background: The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ket-amine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism.

Methods: 18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping.

Results: The mean +/- SD measured ketamine serum concentration was 326.4 +/- 86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6 +/- 15.9%; P = 0.029) and in the frontal (13.6 +/- 13.1%; P = 0.011) and parietal cortices (13.1 +/- 11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices.     

Effects of Sevoflurane, Propofol, and Adjunct Nitrous Oxide on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans

Background: Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography.

Methods: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level.

Results: The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 [mu]g/ml during propofol alone and 3.5 +/- 0.7 [mu]g/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone.     

Nitroprusside-Hypotension: Cerebral Blood Flow and Cerebral Oxygen Consumption in Neurosurgical Patients

The effects of nitroprusside-induced hypotension on cerebral blood flow and cerebral oxygen consumption were investigated in nine patients scheduled for cerebral arterial aneurysm surgery. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl; muscle relaxation was achieved with pancuronium; Paco₂ was maintained at 4.79-5.32 kPa. Mean arterial pressure was reduced to 50 mm Hg by nitroprusside infusion after opening of the dura. Measurements were recorded and blood samples were taken 15 min before induction of hypotension, during stable hypotension and 15 min after termination of nitroprusside infusion. Measurements included: cerebral blood flow, using the argon-washin technique, cardiac output (thermodilution), mean arterial pressure and heart rate. Cerebral blood flow averaged 56 ± 6 ml/min. 100 g before hypotension. Nitroprusside produced hypotension but did not significantly alter cerebral blood flow (61 ± 7 ml/min · 100 g). Cerebral blood flow remained virtually at preinfusion values upon cessation of infusion (53 ± 6 ml/min · 100 g). Cerebral oxygen uptake averaged 3 ± 0.2 ml/min · 100 g before hypotension and did not change significantly during hypotension (3.3 ± 0.3 ml/min · 100 g) and after termination of hypotension (2.7 ± 0.3 ml/min · 100 g). In two patients nitroprusside produced a 17 and 20% increase, respectively, in cerebral blood flow with no change in cerebral oxygen consumption, together with a marked increase in cardiac output and heart rate.     

不同剂量异丙酚对脑血流动力学的影响

目的：采用经颅多普勒（ＴＣＤ）监测大脑中动脉血流速率（Ｖ－ＭＣＡ），观察不同剂量异丙酚对脑血流动力学的影响。方法：２４例神经外科病人随机分成三组（每组８例），异丙酚剂量分别为０．２５ｍｇ／ｋｇ、１．０ｍｇ／ｋｇ和２．０ｍｇ／ｋｇ采用经颅多普勒监测双侧大脑中动脉血流速率（Ｖ－ＭＣＡ），同时监测ＢＰ、ＨＲ、ＰＥＴＣＯ２和ＳｐＯ２。分别于给药前、给药后５，１０和１５分钟测定。结果：异丙酚三组剂量均不同程     

The Effect of Nitrous Oxide on Oxygen Consumption and Blood Flow in the Cerebral Cortex of the Rat

The effect of 70% nitrous oxide upon cerebral oxygen consumption (CMRo2) and cerebral blood flow (CBF) was studied in artificially ventilated rats. The control groups consisted of unanaesthetized animals in which a stress-induced increase in CMRo2 and CBF was prevented by previous adrenalectomy, or by administration of a beta blocker (propranolol). There were no significant differences in CMRo2 between animals ventilated with either N2O or N2. It is concluded that if nitrous oxide depresses cerebral metabolism the depression cannot exceed 10%.     

Effects of Xenon Anesthesia on Cerebral Blood Flow in Humans: A Positron Emission Tomography Study

Background: Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF).

Methods: 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was based solely on xenon. Absolute changes in rCBF were quantified using region-of-interest analysis and voxel-based analysis.

Results: Mean arterial blood pressure and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/- SD) xenon concentration during anesthesia was 65.2 +/- 2.3%. Xenon anesthesia decreased absolute rCBF by 34.7 +/- 9.8% in the cerebellum (P < 0.001), by 22.8 +/- 10.4% in the thalamus (P = 0.001), and by 16.2 +/- 6.2% in the parietal cortex (P < 0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2 +/- 8.6% in the gray matter (P = 0.008). A 22.1 +/- 13.6% increase in rCBF was detected in the white matter (P = 0.001). Whole-brain voxel-based analysis revealed widespread cortical reductions and increases in rCBF in the precentral and postcentral gyri.     

Effect of Dexmedetomidine on Cerebral Blood Flow Velocity, Cerebral Metabolic Rate, and Carbon Dioxide Response in Normal Humans

Background: Dexmedetomidine reduces cerebral blood flow (CBF) in humans and animals. In animal investigations, cerebral metabolic rate (CMR) was unchanged. Therefore, the authors hypothesized that dexmedetomidine would cause a decrease in the CBF/CMR ratio with even further reduction by superimposed hyperventilation. This reduction might be deleterious in patients with neurologic injuries.

Methods: Middle cerebral artery velocity (CBFV) was recorded continuously in six volunteers. CBFV, jugular bulb venous saturation (Sjvo2), CMR equivalent (CMRe), and CBFV/CMRe ratio were determined at six intervals before, during, and after administration of dexmedetomidine: (1) presedation; (2) presedation with hyperventilation; at steady state plasma levels of (3) 0.6 ng/ml and (4) 1.2 ng/ml; (5) 1.2 ng/ml with hyperventilation; and (6) 30 min after discontinuing dexmedetomidine. The slope of the arterial carbon dioxide tension (Paco2)-CBFV relation was determined presedation and at 1.2 ng/ml.

Results: CBFV and CMRe decreased in a dose-related manner. The CBFV/CMRe ratio was unchanged. The CBFV response to carbon dioxide decreased from 1.20 +/- 0.2 cm[middle dot]s-1[middle dot]mm Hg-1 presedation to 0.40 +/- 0.15 cm[middle dot]s-1[middle dot]mm Hg-1 at 1.2 ng/ml. Sjvo2 was statistically unchanged during hyperventilation at 1.2 ng/ml versus presedation (50 +/- 11 vs. 43 +/- 5%). Arousal for hyperventilation at 1.2 ng/ml resulted in increased CBFV (30 +/- 5 to 38 +/- 4) and Bispectral Index (43 +/- 10 to 94 +/- 3).     

Early Effects of Acid-Base Management during Hypothermia on Cerebral Infarct Volume, Edema, and Cerebral Blood Flow in Acute Focal Cerebral Ischemia in Rats

Background: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and [alpha]-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats.

Methods: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33[degrees]C). Animals were artificially ventilated with either [alpha]- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[14C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS).

Results: Compared with the [alpha]-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm3vs. 53.6 +/- 21.6 mm3;P >= 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0%vs. 3.1 +/- 2.4%;P >= 0.05). Global CBF during pH-stat management exceeded that of [alpha]-stat animals (69.5 +/- 12.3 ml [middle dot] 100 g-1 [middle dot] min-1vs. 54.7 +/- 13.3 ml [middle dot] 100 g-1 [middle dot] min-1;P >= 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml [middle dot] 100 g-1 [middle dot] min-1 in the pH-stat group versus 48.2 +/- 7.2 ml [middle dot] 100 g-1 [middle dot] min-1 in the [alpha]-stat group (P >= 0.05).     

Dose-dependent Regional Cerebral Blood Flow Changes during Remifentanil Infusion in Humans: A Positron Emission Tomography Study

Background: The current study investigated dose-dependent effects of the [mu]-selective agonist remifentanil on regional cerebral blood flow (rCBF) in volunteers using positron emission tomography (PET).

Methods: Ten right-handed male volunteers were included in a 15O-water PET study. Seven underwent three conditions: control (saline), low remifentanil (0.05 [mu]g [middle dot] kg-1 [middle dot] min-1), and moderate remifentanil (0.15 [mu]g [middle dot] kg-1 [middle dot] min-1). The remaining three participated in the low and moderate conditions. A semi-randomized study protocol was used with control and remifentanil conditions 3 or more months apart. The order of low and moderate conditions was randomized. Cardiovascular and respiratory parameters were monitored. Categoric comparisons between the control, low, and moderate conditions and a pixelwise correlation analysis across the three conditions were performed (P < 0.05, corrected for multiple comparisons) using statistical parametric mapping.

Results: Cardiorespiratory parameters were maintained constant over time. At the low remifentanil dose, significant increases in relative rCBF were noted in the lateral prefrontal cortices, inferior parietal cortices, and supplementary motor area. Relative rCBF decreases were observed in the basal mediofrontal cortex, cerebellum, superior temporal lobe, and midbrain gray matter. Moderate doses further increased rCBF in mediofrontal and anterior cingulate cortices, occipital lobe transition, and caudal periventricular grey. Significant decreases were detected in the inferior parietal lobes. These dose-dependent effects of remifentanil on rCBF were confirmed by a correlation analysis.     

Influence of Althesinr on Coronary Blood Flow and Myocardial Oxygen Consumption in Dogs

Glaxo CT 1341 (Althesin) is a new steroid anaesthetic agent dissolved in Cremophor EL. Its influence on hemodynamics was studied in dogs, especially regarding the myocardial contractility, coronary perfusion and myocardial oxygen consumption.
The unpremedicated experimental animals were induced with 3 mg/kg piritramide intravenously and normoventilated with a mixture of 70% N₂O and 30% O₂. All animals were pretreated with a powerful antihistaminic agent (Tavegil) in order to block reactions to histamine released by Cremophor EL. Five hours later the animals received single intravenous doses of Althesin (1.0 and 2.0 mg/kg).
Significant hemodynamic changes ( P < 0.025-0.0005) were caused by 2.0 mg/kg. Heart rate, cardiac output and mean pulmonary pressure increased, total peripheral resistance decreased; while central venous pressure, mean aortic pressure and renal blood flow remained unchanged. The resulting increased cardiac work caused a rise in coronary blood flow of 88%, an increased myocardial oxygen consumption of 66% and a decreased coronary resistance of 48%. As coronary arteriovenous difference in oxygen decreased slightly, Althesin has coronary dilatory properties. Myocardial depression was seen in a marked fall of dp/dt_max (the rate of change of the left ventricular pressure) (30%), in a decreased stroke volume and in an increased left ventricular end-diastolic pressure. Maximal hemodynamic responses occurred within the first minute after injection and returned to their preinjection levels after approximately 20 min.
A recommended dose in man is 2 mg/kg Althesin Myocardial depression and increased oxygen consumption suggest a cautious use of Althesin in cases of heart and coronary insufficiency.     

Preservation of the Ratio of Cerebral Blood Flow/Metabolic Rate for Oxygen during Prolonged Anesthesia with Isoflurane, Sevoflurane, and Halothane in Humans

Background: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2)) was determined every 20 min during anesthesia lasting more than 4 h in patients.

Methods: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference.

Results: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21+/-4, 20+/-3, and 21+/-5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P < 0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). At 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45+/-8) was significantly (P < 0.01) greater than those in the halothane (32+/-8) and sevoflurane (31+/-8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC.     

Effects of Xenon on Cerebral Blood Flow and Cerebral Glucose Utilization in Rats

Background: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography.

Methods: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only.

Results: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon.     

Reduction of Cerebral Blood Flow and Oxygen Consumption with a Combination of Barbiturate Anaesthesia and Induced Hypothermia in the Rat

The influence of phenobarbitone anaesthesia on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo₂) during hypothermia (23°C & 27°C) was studied in the rat, using a modification of the K ety & S chmidt (1948) technique and arterio-venous differences for oxygen. Phenobarbitone (150 mg/kg) was found to decrease CMRo₂ by 40–60% during hypothermia, when compared to N₂O anaesthesia. At a body temperature of 23°C, and during phenobarbitone anaesthesia, CMRo₂ was reduced to about 15% of normal control value (about 10.3 ml.100g^-l. min^-l). CBF was reduced to about 50% of the phenobarbitone control value but was similar to the value obtained with N₂O anaesthesia at 22°C. It is concluded that the combination of phenobarbitone anaesthesia and hypothermia results in a more pronounced reduction in cerebral metabolic rate for oxygen than can be achieved by administration of barbiturates to normothermic animals, or by reducing body temperature by 15°C during superficial anaesthesia.     

Distribution of Cerebral Blood Flow during Anesthesia with Isoflurane or Halothane in Humans

Background: Halothane and isoflurane have been shown to induce disparate effects on different brain structures in animals. In humans, various methods for measuring cerebral blood flow (CBF) have produced results compatible with a redistribution of CBF toward deep brain structures during isoflurane anesthesia in humans. This study was undertaken to examine the effects of halothane and isoflurane on the distribution of CBF.

Methods: Twenty ASA physical status patients (four groups, five in each) anesthetized with either isoflurane or halothane (1 MAC) during normo- or hypocapnia (PaCO2 5.6 or 4.2 kPa (42 or 32 mmHg)) were investigated with a two-dimensional CBF measurement (CBFxenon, intravenous133 xenon washout technique) and a three-dimensional method for measurement of the regional CBF (rCBF) distribution with single photon emission computer-aided tomography (SPECT;99m Tc-HMPAO). In the presentation of SPECT data, the mean CBF of the brain was defined as 100%, and all relative flow values are related to this value.

Results: The mean CBFxenon level was significantly influenced by the PaCO2 as well as by the anesthetic used. At normocapnia, patients anesthetized with halothane had a mean CBFxenon of 40 plus/minus 3 (SE) ISI units. With isoflurane, the flow was significantly (P < 0.01, 33 plus/minus 3 ISI units) less than with halothane. Hypocapnia decreased mean CBFxenon (P < 0.0001) during both anesthetics (halothane 24 plus/minus 3, isoflurane 13 plus/minus 2 ISI units). The effects on CBFxenon, between the anesthetics, differed significantly (P < 0.01) also during hypocapnia. There were significant differences in rCBF distribution measured between the two anesthetics (P < 0.05). During isoflurane anesthesia, there was a relative increase in flow values in subcortical regions (thalamus and basal ganglia) to 10-15%, and in pons to 7-10% above average. Halothane, in contrast, induced the highest relative flow levels in the occipital lobes, which increased by approximately 10% above average. The rCBF level was increased approximately 10% in cerebellum with both anesthetics. Changes in PaCO2 did not alter the rCBF distribution significantly.     

Blood Flow Velocity of Middle Cerebral Artery during Prolonged Anesthesia with Halothane, Isoflurane, and Sevoflurane in Humans

Background: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca).

Methods: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously.

Results: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst.     

The Effect of Phenobarbitone Anaesthesia on Blood Flow and Oxygen Consumption in the Rat Brain

The influence of phenobarbitone anaesthesia on blood flow (CBF) and oxygen consumption (CMR_o2) was evaluated in the rat brain, using a method that quantitatively measures CBF in mainly cortical areas. The data were compared to those obtained in animals under fentanyl citrate analgesia. Body temperature and arterial CO₂ tension were maintained close to normal values in all groups. With 50 mg/kg of phenobarbitone, CBF and CMR_O2 were reduced by about 20 %. With 150 or 250 mg/kg, further reductions in CBF and CMR_O2 were observed. At 250 mg/kg, CBF was reduced to one third, and CMR_O2 to about 50 % of normal. The results suggest that little further reduction in CBF or CMR_O2 can be expected if the dose of phenobarbitone is increased above 250 mg/kg.     

氯胺酮对兔脑微循环的影响

应用微循环闭路电视显微系统对１２只兔行颅骨开窗法对软脑膜微循环进行录像。通过直接动态观察发现氯胺酮可显著扩张脑微血管。同时使血流加快，网状毛细血管明显充盈，增多，微血管数目增加，由此引起脑脊液动力学和颅压增高。因此提出，对脑损伤，颅内出血，颅内高压或脑脊液压力异常者应慎用氯胺酮。