Effects of Subanesthetic Doses of Ketamine on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans

Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned.

Methods: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine quantitative regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV), respectively, on selected regions of interest of nine healthy male volunteers at baseline and during three escalating concentrations of ketamine (targeted to 30, 100, and 300 ng/ml). In addition, voxel-based analysis for relative changes in rCBF and rCMRO2 was performed using statistical parametric mapping.

Results: The mean +/- SD measured ketamine serum concentrations were 37 +/- 8, 132 +/- 19, and 411 +/- 71 ng/ml. Mean arterial pressure was slightly elevated (maximally by 15.3%, P < 0.001) during ketamine infusion. Ketamine increased rCBF in a concentration-dependent manner. In the region-of-interest analysis, the greatest absolute changes were detected at the highest ketamine concentration level in the anterior cingulate (38.2% increase from baseline, P < 0.001), thalamus (28.5%, P < 0.001), putamen (26.8%, P < 0.001), and frontal cortex (25.4%, P < 0.001). Voxel-based analysis revealed marked relative rCBF increases in the anterior cingulate, frontal cortex, and insula. Although absolute rCMRO2 was not changed in the region-of-interest analysis, subtle relative increases in the frontal, parietal, and occipital cortices and decreases predominantly in the cerebellum were detected in the voxel-based analysis. rCBV increased only in the frontal cortex (4%, P = 0.022).     

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%.     

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.     

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 Sevoflurane with and without Nitrous Oxide on Human Cerebral Circulation: Transcranial Doppler Study

Background: This study was designed to evaluate the effects of sevoflurane with and without nitrous oxide on human middle cerebral artery (MCA) flow velocity, cerebrovascular carbon dioxide reactivity, and autoregulation compared with the awake state using transcranial Doppler ultrasonography.

Methods: In 14 patients, the time-mean middle cerebral artery flow velocity (Vmca) was measured when the end-tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with 1.2 MAC sevoflurane-60% nitrous oxide. In six other patients, the cerebrovascular autoregulation during anesthesia was determined using intravenous phenylephrine to increase blood pressure.

Results: Sevoflurane (1.2 MAC) significantly decreased Vmca compared with the awake value at each level of end-tidal carbon dioxide, whereas 1.2 MAC sevoflurane-60% nitrous oxide did not exert significant influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible effect on cerebrovascular carbon dioxide reactivity. A phenylephrine-induced increase of mean arterial pressure did not influence Vmca during anesthesia.     

Effects of Surgical Levels of Propofol and Sevoflurane Anesthesia on Cerebral Blood Flow in Healthy Subjects Studied with Positron Emission Tomography

Background: The authors report a positron emission tomography (PET) study on humans with parallel exploration of the dose-dependent effects of an intravenous (propofol) and a volatile (sevoflurane) anesthetic agent on regional cerebral blood flow (rCBF) using quantitative and relative (Statistical Parametric Mapping [SPM]) analysis.

Methods: Using H215O, rCBF was assessed in 16 healthy (American Society of Anesthesiologists [ASA] physical status I) volunteers awake and at three escalating drug concentrations: 1, 1.5, and 2 MAC/EC50, or specifically, at either 2, 3, and 4% end-tidal sevoflurane (n = 8), or 6, 9, and 12 [mu]g/ml plasma concentration of propofol (n = 8). Rocuronium was used for muscle relaxation.

Results: Both drugs decreased the bispectral index and blood pressure dose-dependently. Comparison between adjacent levels showed that sevoflurane initially (0 vs. 1 MAC) reduced absolute rCBF by 36-53% in all areas, then (1 vs. 1.5 MAC) increased rCBF in the frontal cortex, thalamus, and cerebellum (7-16%), and finally (1.5 vs. 2 MAC) caused a dual effect with a 23% frontal reduction and a 38% cerebellar increase. In the propofol group, flow was also initially reduced by 62-70%, with minor further effects. In the SPM analysis of the "awake to 1 MAC/EC50" step, both anesthetic agents reduced relative rCBF in the cuneus, precuneus, posterior limbic system, and the thalamus or midbrain; additionally, propofol reduced relative rCBF in the parietal and frontal cortices.     

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.     

单肺通气期间七氟醚或丙泊酚对脑氧代谢的影响

目的观察单肺通气期间七氟醚或丙泊酚联合靶控持续输注瑞芬太尼对脑氧代谢的影响。方法选择行肺叶切除术患者30例,随机分为七氟醚组（S组）或丙泊酚组（P组）,每组各15例。麻醉诱导后,分别持续吸入七氟醚1%-2.5%或静脉持续泵入丙泊酚4-8 mg/（kg.h）。于双肺通气15 min（T1）,单肺通气15 min（T2）,单肺通气30 min（T3）,恢复双肺通气之后15min（T4）时点记录HR、MAP及BIS值,同时采集桡动脉、颈内静脉球血行血气分析,测定颈静脉球氧饱和度（SjvO2）,并计算脑动静氧含量差（AjvDO2）及COER值。结果两组在T2、T3时点的PaO2值较T1时点明显降低（P〈0.05）;S组各时点的SjvO2值、AjvDO2值、COER值与P组相应时点比较,无统计学差异（P〉0.05）。结论单肺通气过程中七氟醚与丙泊酚联合瑞芬太尼均能够达到满意麻醉效果,并保持脑氧供需平衡。     

The Haemodynamic Effects of Nitrous Oxide Anaesthesia on Myocardial Blood Flow in Dogs

The effects of ventilation with nitrous oxide in oxygen on myocardial blood flow and oxygen metabolism were investigated in 31 mongrel dogs. The results of this study showed that, compared with controls, hyperoxic nitrous oxide mixtures did not cause any great changes in myocardial haemodynamics, despite a decrease in cardiac output and an increase in systemic vascular resistance.
Normoxic nitrous oxide mixtures produced an increase of the coronary blood flow due to decreased coronary vascular resistance. To what extent this coronary vasodilatation resulted from an increased myocardial metabolism or from a direct effect of nitrous oxide on the coronary vascular bed cannot be quantified from the present results.     

Propofol and Thiopental Do Not Interfere with Regional Cerebral Blood Flow Response at Sedative Concentrations

Background: Anesthetics may affect the regional cerebral blood flow (rCBF) response associated with increased brain activity in humans. rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration.

Methods: After informed consent, 10 right-handed male volunteer participants (aged 33.5 +/- 10.4 yr, weighing 74.5 +/- 8.4 kg) received thiopental (n = 4) or propofol (n = 6) intravenously at stepwise target concentrations of propofol 1.2 and 2.5-3, or thiopental 4 and 7-9 [mu]g/ml, representing sedative and hypnotic drug concentrations. The latter made volunteers unresponsive to voice or mild stimulation. Quantitative positron emission tomographic brain images were obtained at 0, 20, and 40 auditory words per minute at each drug concentration. Using SPM99 analysis, 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations. Individual mean rCBF responses in these and primary auditory cortex (Heschl's gyri) were obtained.

Results: Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline (significance, T = 4.95). There was no change in this response during sedation (T = 5.60). During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe (T = 3.18). Global CBF, corrected for changes in Pco2 (3% [middle dot]mmHg Pco2-1), was reduced 15% by sedation and 27% during unresponsiveness.     

Subjective, Psychomotor, Cognitive, and Analgesic Effects of Subanesthetic Concentrations of Sevoflurane and Nitrous Oxide

Background: Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations.

Methods: A crossover design was used to test the effects of two end-tidal concentrations of sevoflurane (0.3% and 0.6%), two end-tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold-water test.

Results: Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects.     

Effects of Sevoflurane on Regional Myocardial Blood Flow Distribution: Quantification with Myocardial Contrast Echocardiography

Background: Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs.

Methods: In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level correlated for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration).

Results: In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery.     

异丙酚对体外循环中脑氧代谢的影响

目的：探讨异丙酚对体外循环（ＣＰＢ）各阶段脑氧及乳酸代谢的影响。方法：选择心内直视手术病人３１例，随机分为异现酚组（Ａ组）１６例，对照组（Ｂ组）１５例。分别于ＣＰＢ前、降温及３３℃和３０℃，低温期，复温至３０℃和３３℃以及ＣＰＢ后１５分钟七个时点动脉，颈内静脉血气及乳酸值（ＬＡ）并计算脑摄氧率（Ｏ２Ｅｘｔ）及动脉－颈内静脉乳酸差值。     

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.     

异丙酚或依托咪酯复合硬膜外阻滞对血流动力学和肝氧供的影响

目的：探讨硬膜外阻滞与异丙酚或依托咪酯复合麻醉对血流这和肝血流及氧供的影响。方法：选用２健康杂种犬２２只行胸理解上阻滞后,随机分为两组,分别静脉注射异丙酚２．５ｍｇ／ｋｇ或依托咪酯０．４ｍｇ／ｋｇ,监测１０分钟内体循环、肝动脉、门静 脉血流动力学及肝脏氧供。结果硬膜外阻滞后ＨＲ、ＭＡＰ、ＳＶＲ、门静脉血流和氧供下降,异丙酚诱导后ＨＲ、ＭＡ字符怨于２－５分钟时下降,依托咪酯诱导后各参数无进一步明显变     

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).     

Cerebral Blood Volume (CBV) in Humans during Normo- and Hypocapnia: Influence of Nitrous Oxide (N2O)

Background : It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N2O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N2O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N2O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia.

Methods : Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N2O, and hypocapnia + 40-50% N2O. CBV was measured after 99mTc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning.

Results : Global CBV during normocapnia and inhalation of 50% O2 was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N2O in O2. Decreasing carbon dioxide (CO2) by 1.5 kPa (11 mmHg) without N2O inhalation and by 1.4 kPa (11 mmHg) with N2O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml [middle dot] 100 g-1 [middle dot] kPa-1) without N2O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml [middle dot] 100 g-1 [middle dot] kPa-1) during N2O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in [DELTA]CBV when CO2 is changed. N2O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or [DELTA]CBV/[DELTA]CO2 in these nine subjects.