Cerebral metabolism and EEG during combination of hypocapnia and isoflurane-induced hypotension in dogs

Isoflurane (ISF)-induced hypotension causes equal reductions of cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) so that no disturbance of cerebral energy stores or metabolites occurs. While hypocapnia during ISF-induced hypotension causes a further reduction of CBF, the effects on cerebral energy stores and metabolites produced by combining hypocapnia with ISF-induced hypotension are not known. This study examined the effect of hypocapnia (PaCO2 = 20 mmHg) on CMRO2, the electroencephalogram (EEG), and levels of adenine nucleotides, phosphocreatine, lactate, pyruvate, and glucose in brain tissue in 12 dogs during ISF-induced hypotension. All dogs were examined at: normocapnia with normotension; hypocapnia with normotension; hypocapnia combined with ISF-induced hypotension to cerebral perfusion pressures of 60, 50, and 40 mmHg; and restoration of normocapnia with normotension. In six dogs CMRO2 was determined, and the EEG was evaluated using compressed spectral analysis. In the other six dogs brain tissue metabolites were determined. Hypocapnia combined with ISF-induced hypotension (all levels) caused a decrease of the power of the beta-2 spectra, an increase of the power of the alpha and beta-1 spectra, but no change in total power of the EEG. There was no change in cerebral energy stores or brain tissue metabolites. CMRO2 was reduced by approximately 27%. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites remained unchanged and CMRO2, and the power of the alpha, beta-1, and beta-2 spectra of the EEG returned to control values. These results suggest no adverse effect on cerebral metabolism or function during hypocapnia combined with ISF-induced hypotension.     

Partial preservation of cerebral vascular responsiveness to hypocapnia during isoflurane-induced hypotension in dogs

This study was undertaken to determine whether the cerebral vascular response to hypocapnia is preserved during isoflurane-induced hypotension. In six dogs (group 1) cerebral vascular resistance and cerebral blood flow were determined at normocapnia (PaCO2 40 mm Hg) and at hypocapnia (PaCO2 20 mm Hg) while mean arterial pressure was normal, and then again during isoflurane-induced hypotension to a mean arterial pressure of 50 mm Hg. Hypocapnia increased cerebral vascular resistance and decreased cerebral blood flow during both normotension and isoflurane-induced hypotension. However, the magnitude of these responses was greater when mean arterial pressure was normal. In another six dogs (group 2), CO2 responsiveness was examined during isoflurane-induced hypotension without prior determination of CO2 responsiveness at normal mean arterial pressure and during sodium nitroprusside-induced hypotension to a mean arterial pressure of 50 mm Hg. As in group 1, partial preservation of CO2 responsiveness was observed during isoflurane-induced hypotension; the magnitude of the response in group 2 during isoflurane-induced hypotension was similar to that in group 1. In contrast, in group 2 during sodium nitroprusside-induced hypotension, hypocapnia caused no significant change of cerebral vascular resistance or cerebral blood flow. It is concluded that cerebral vessels respond to changes in PaCO2 differently during isoflurane-induced hypotension than during hypotension with other commonly used hypotensive treatments. Hypocapnia decreases cerebral blood flow during isoflurane-induced hypotension and, therefore, may also decrease cerebral blood volume, brain bulk, and intracranial pressure.     

Effect of isoflurane-induced hypotension on cerebral autoregulation in the anesthetized pig

The influence of isoflurane-induced hypotension on regional cerebral blood flow (rCBF) and cerebrovascular autoregulation was evaluated in 11 normocapnic pigs during anesthesia comprising fentanyl and nitrous oxide in oxygen. rCBF was determined as sagittal sinus outflow and recorded continuously by an electromagnetic technique. Regional cerebral metabolic rate for oxygen (rCMRO2) was calculated as rCBF multiplied by the arteriosagittal sinus oxygen content difference. Cerebral autoregulation was evaluated by two formal tests; blood pressure increase by infusion of angiotensin and blood pressure decrease by caval block. Light hypotension [mean arterial blood pressure (MABP) 94 +/- 3 mm Hg] and moderate hypotension (MABP 56 +/- 1 mm Hg) were achieved with the inspired concentrations of 1.7 +/- 0.2 and 2.7 +/- 0.2% isoflurane, respectively. rCBF was measured and the tests were performed before, during, and after isoflurane administration. Isoflurane produced no significant change in rCBF at either level of hypotension. At moderate hypotension the rCMRO2 was decreased by 40 +/- 6%. At both levels of hypotension, isoflurane produced a dose-dependent impairment of the auto-regulatory response to the angiotensin test as well as to the caval block. After hypotension, the autoregulatory response to increased blood pressure was restored within 15-25 min and to decreased blood pressures within 25-50 min.     

Cardiovascular effects of isoflurane-induced hypotension for cerebral aneurysm surgery

Deliberate hypotension was induced with isoflurane in 13 patients, undergoing craniotomy for clipping of aneurysms. Cardiovascular function and gas exchange were monitored before, during, and after hypotension. In all cases, the desired level of hypotension [40 +/- 1 (SEM) mm Hg] was achieved readily with prompt onset (5.7 +/- 1.0 min) and recovery (6.3 +/- 0.7 min). Cardiac output during hypotension (4.6 +/- 0.3 L/min) was not significantly different from the control normotensive value (4.80 +/- 0.3 L/min). Gas tensions during hypotension and during normotension were; PaO2 116 +/- 6 and 111 +/- 8 mm Hg; PaCO2 33 +/- 1 and 34 +/- 1 mm Hg; respectively. No complication could be attributed to the use of isoflurane. We conclude that isoflurane can be employed safely and effectively as a hypotensive agent in neurosurgery.     

Cerebral effects of nitrous oxide during isoflurane-induced hypotension in the pig

We have studied the effects of nitrous oxide on cerebral bloodflow (CBF), cerebral blood flow velocity (CBFV) and intracranialpressure (ICP) during isoflurane-induced hypotension in 10 pigs.CBF was measured using laser Doppler flowmetry, CBFV in theright middle cerebral artery was calculated using Doppler ultrasoundand ICP was measured using an extradural ICP monitor. Each animalwas studied under four conditions, examined sequentially: (i)mean intra-arterial pressure (MAP) 85 mm Hg, maintained withisoflurane, (ii) MAP 50–55 mm Hg, induced by isofluraneonly, (iii) MAP 85 mm Hg, maintained with isoflurane and 50%nitrous oxide, and (iv) MAP 50–55 mm Hg, induced by isofluraneand 50% nitrous oxide. No significant differences were notedbetween conditions with respect to ICP. There was a significantdifference in CBF during condition (ii) compared with (i) (mean75(SD 21) vs 100(0) %) and during condition (iv) compared with(iii) (90(26) vs 109(13)%). Animals under condition (iv) exhibiteda 20% reduction in CBFV compared with those under condition(iii) (57 vs 69 cm s^–1). For animals under normotensiveconditions, addition of nitrous oxide to isoflurane resultedin a 16% increase in CBFV (69 vs 60 cm s^–1). Comparingisoflurane-induced hypotension ((ii) vs (iv)), there was nostatistical difference in either CBF or CBFV on addition of50% nitrous oxide. The correlation between changes in CBF andCBFV was not significant. We conclude that the use of nitrousoxide during isoflurane-induced hypotension has no significanteffect on CBF, CBFV or ICP compared with the use of isofluranealone.     

Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans

The effect of isoflurane-induced hypotension on glomerular function and renal blood flow was investigated in 20 human subjects. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate (PAH) clearance, respectively. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and isoflurane. Hypotension was induced for 236.9 +/- 15.1 min by increasing the isoflurane inspired concentration to maintain a mean arterial pressure of 59.8 +/- 0.4 mmHg. GFR and ERPF decreased with the induction of anesthesia but not significantly more during hypotension. Postoperatively, ERPF returned to preoperative values, whereas GFR was higher than preoperative values. Renal vascular resistance increased during anesthesia but decreased when hypotension was induced, allowing the maintenance of renal blood flow. We conclude that renal compensatory mechanisms are preserved during isoflurane-induced hypotension and that renal function and hemodynamics quickly return to normal when normotension is resumed.     

Effect of hypothermia during hypoxic hypotension on cerebral metabolism

The beneficial vs deleterious effects of hypothermia superimposed on hypoxia and hypotension have been argued and are clinically important. In this study, cerebral cytochrome a,a₃ redox state and the quantity of intracerebral oxygenated hemoglobin (HbO₂) were measured continuously and noninvasively in rats subjected to hemorrhagic hypotension (MAP = 30 mm Hg) and hypoxia (F₁O₂ = 7.5%) utilizing near infrared spectrophotometry. Prior to the experiment the rats were briefly respired on 100% oxygen to establish 100% oxidation of cytochrome a,a₃ and hemoglobin, and at the conclusion of the experiment they were respired on 100% nitrogen to establish 100% reduction. Data are reported as percent oxidation within this range at baseline and after 15 and 30 min of hypoxic hypotension. Arterial blood gases were measured. Body temperature as monitored by a rectal probe was altered by placing anesthetized-paralyzed rats inside a circulating water jacket. Three groups of rats were studied: 38, 33, and 22°C.Group III rats had a significantly (P < 0.01) greater quantity of intracranial HbO₂ than group I or II. Since MAP was held constant at 30 mm Hg, we assume this is largely due to the higher (P < 0.01) arterial PO₂ in group III (101.5) compared to group I and II (48.5, 51.3). Both groups II and III had a significantly (P < 0.01) greater oxidation of cytochrome a,a₃ indicating greater oxygen availability for a given metabolic rate. This was associated with improved survival inasmuch as all rats in groups II and III lived, and only one group I rat survived. It can be concluded that, as used in this study, hypothermia is beneficial and deserves further investigation.     

Electrocardiographic changes during and after isoflurane-induced hypotension for neurovascular surgery

We evaluated the effects of isoflurane anaesthesia and induced hypotension in 33 neurosurgical patients by electrocardiographic monitoring and serial cardiac enzyme measurements. An electrocardiogram (ECG) and serum enzymes were obtained preoperatively, intraoperatively and postoperatively in the recovery room and for three consecutive days. ECG leads II, V1 and V5 were monitored continuously during anaesthesia. Patients who had had a subarachnoid haemorrhage and a high incidence of abnormal preoperative ECG (42 per cent). Ten patients developed ECG changes intraoperatively, but these changes were unrelated to isoflurane-induced hypotension. Fifty-three per cent of patients developed an abnormal postoperative ECG. These abnormalities consisted mostly of nonspecific ST segment or T wave changes. At no time was there an elevation in cardiac enzyme activity. We found that nonspecific ECG changes are relatively common in patients undergoing vascular neurosurgical procedures. There was no enzymatic evidence of myocardial infarction and we can only speculate that these ECG changes are related to intracranial surgical manipulation.     

Influence of converting enzyme inhibition on isoflurane-induced hypotension for cerebral aneurysm surgery

Twenty-five patients (aged 18 to 72 years), who recovered after the first bleed from a cerebral aneurysm, were operated on under neuroleptanaesthesia. Isoflurane was added to induce hypotension. It was found that the required hypotension (51 (SEM 1) mmHg) could be obtained and maintained at much lower isoflurane concentrations (less than 1%) after blockade of the angiotensin converting enzyme activity by enalaprilat (2.5 mg i.v.) than without such inhibition. During the hypotension which lasted 78 (SEM 10) min, only minor adjustments of the isoflurane concentration (0.70 (0.04%) were needed. The desired level of hypotension was obtained with preservation of the cardiac output and without tachycardia. No resistance to the blood pressure lowering effect of isoflurane was observed. On recovery from anaesthesia, a small increase of blood pressure above control values was seen in 16 patients and was easily reversed by small doses of clonidine (mean total dose: 220 (61) micrograms). The operative conditions were excellent and the postoperative recovery was uneventful and complete in 23 patients.     

异氟醚控制性降压对颅内动脉瘤夹闭术病人血液动力学及组织氧合的影响

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Cerebrovascular response to carbon dioxide during sodium nitroprusside- and isoflurane-induced hypotension

We have examined the cerebrovascular response to carbon dioxideduring normotension, sodium nitroprusside (SNP)-induced hypotensionand high dose isoflurane-induced hypotension in 10 patientswho received a standardized general anaesthetic. Carbon dioxidereactivity was determined by varying Pa_co2 between 3.0 and 8.0kPa and recording simultaneously blood flow velocity from themiddle cerebral artery (vmca). The paired vmca-Pa_co2 data wereanalysed using linear regression to determine carbon dioxidereactivity. During hypotension, both high-dose isoflurane andSNP reduced significantly mean absolute (from 17.4 (SEM 2.3)to 13.0 (1.7) and 8.8 (1.3) cm s^–1 kPa^–1 respectively;P < 0.05) and relative (from 32.5 (3.8) to 23.6 (2.0) and15.5 (1.3) % kPa^– respectively; P < 0.05) cerebrovascularreactivity to carbon dioxide. This reduction was greater duringSNP-induced hypotension (P < 0.05). We conclude that cerebrovascularreactivity to carbon dioxide was attenuated during isofluraneand SNP-induced hypotension, and that it was better preservedduring isoflurane-induced hypotension. (Br. J. Anaesth. 1995;74: 296–300) Present addresses: Department of Anaesthesia, The Ipswich Hospital,Ipswich IP4 5PD, UK. Present addresses: Phoenix Anesthesia Group, 2950 North 7thSt, Phoenix, AZ 85014, USA. Present addresses: University of Basel/Kantonsspital, Departmentof Anesthesia, CH-4031, Basel, Switzerland.     

The effect of isoflurane-induced hypotension on cerebral blood flow and cerebral metabolic rate for oxygen in humans

Deliberate hypotension was induced with isoflurane (mean inspired concentration 2.3 +/- 1.0%) in 12 patients undergoing craniotomy for clipping of cerebral aneurysms. Global cerebral blood flow (CBF) was measured before, during, and after hypotension. Arterio-venous O2 content difference was measured concomitantly, and the cerebral metabolic rate for oxygen (CMRO2) was calculated from these data. Mean arterial pressure (MAP) was reduced from 78 +/- 5 mmHg to 51 +/- 7 mmHg and then returned to 82 +/- 8 mmHg. Mean CBF before hypotension was 49 +/- 14 ml X 100 g-1 X min-1 and was unchanged during (45 +/- 12 ml X 100 g-1 X min-1) and after (49 +/- 15 ml X 100 g-1 X min-1) hypotension. The CMRO2 before hypotension was 2.0 +/- 0.6 ml X 100 g-1 X min-1. This was statistically significantly (P less than 0.025) reduced to 1.5 +/- 0.5 ml X 100 g-1 X min-1 during hypotension and then returned to 2.2 +/- 0.6 ml X 100 g-1 X min-1 on return to normotension. This indicates that the global cerebral O2 supply-demand balance was favorably influenced by isoflurane. No complications could be attributed to the hypotensive technique. We conclude that, with regard to global cerebral oxygenation, isoflurane is a safe agent with which to induce hypotension during neurosurgery.     

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.     

Cardiovascular and cerebrovascular effects of isoflurane-induced hypotension in the baboon

Mean arterial pressure (MAP) decreased by 10, 20, 40, and 50% of its baseline value in six anesthetized baboons with the administration of increasing concentrations of isoflurane. Mean arterial pressure, right atrial pressure, pulmonary artery pressures, and cardiac output were measured at each decrement in arterial pressure, and after the withdrawal of the isoflurane. At the same times, cerebral blood flow, the cerebral metabolic rate for oxygen, and the cerebral metabolic rate for glucose were determined. Cerebrovascular reactivity was assessed before, during, and after the administration of isoflurane, and morphologic evidence of ischemic cell change was sought at the end of the investigation. Isoflurane produced dose-related decreases in systemic vascular resistance and MAP; heart rate, cardiac output, and stroke volume did not change significantly. Although cerebral metabolism was depressed in a dose-related manner, the response of the cerebral blood flow (CBF) was biphasic. At low isoflurane concentrations, CBF decreased significantly and then increased to reach baseline values at the highest concentration. Cerebrovascular reactivity was intact at baseline and at the 20% decrement in MAP; it was impaired at the 50% decrease in MAP and when studied 100 min after the withdrawal of isoflurane. There was no morphologic evidence of ischemic cell damage in any animal.     

七氟醚控制性降压对脑代谢的影响

目的 观察七氟醚控制性降压的效果及对脑氧供需平衡、脑能量代谢的影响,并与硝普钠（ＳＮＰ）降压进行对比。方法 择期手术病人４０例随机分为三组：Ｉ组七氟醚降压组,Ⅱ组七氟醚常压组和Ⅲ组ＳＮＰ降压组。Ｉ组增加七氟醚吸入浓度,Ⅲ组静滴ＳＮＰ溶液,降至基础值的５０％～６０％持续４０ｍｉｎ,连续监测ＭＡＰ、ＨＲ、及ＥＣＧ,并同步采集桡动脉和颈内静脉血行血气分析,计算动－颈内静脉氧含量差（Ｄａ－ｊｖＯ２）;测定     

Effects of adenosine-induced hypotension on myocardial hemodynamics and metabolism during cerebral aneurysm surgery

The effects of adenosine-induced hypotension on central as well as myocardial hemodynamics and metabolism were studied in five neurolept-anesthetized patients without known heart or lung diseases, who were undergoing cerebral aneurysm surgery. Adenosine (217 +/- 32 micrograms.kg-1.min-1) decreased mean arterial pressure 30% from 77 +/- 5 to 54 +/- 3 mm Hg. Cardiac filling pressures and heart rate remained unchanged during hypotension. Adenosine decreased systemic vascular resistance 50 +/- 5% while cardiac index increased 39 +/- 10%. Coronary sinus blood flow increased by 73 +/- 13% from 128 +/- 18 to 224 +/- 36 ml/min with a concomitant decrease in calculated coronary vascular resistance (66 +/- 4%). Both systemic and myocardial arteriovenous oxygen content differences decreased, and myocardial oxygen consumption decreased 42 +/- 9%. There were no alterations in myocardial fractional lactate extraction. Arterial plasma renin activity and arterial catecholamine levels were unaffected by hypotension. It is concluded that adenosine hypotension in this group of patients produced a hyperkinetic circulation in the systemic as well as in the myocardial vascular bed. Cardiac output and coronary sinus blood flow increased at the same time as myocardial oxygen consumption decreased.