Leslie Newberg Milde

Correlation of regional cerebral blood flow (rCBF) with EEG changes during isoflurane anesthesia for carotid endarterectomy: critical rCBF

A prospective evaluation of regional cerebral blood flow (rCBF) (ipsilateral middle cerebral artery distribution) was determined using a 133Xe clearance technique in 31 ASA P.S. II–III patients anesthetized with isoflurane-50% N2O in O2 for carotid endarterectomy. Each patient was monitored with 16-channel EEG throughout anesthesia and surgery. Critical rCBF was defined as that flow below which EEG signs of ischemia occurred. Critical rCBF (T1/2 method of analysis) was <10 ml.100 g-1.min−1 (mean ± SE 5.9 ± 1.2) in the six patients in whom transient EEG changes occurred at the time of temporary surgical carotid artery occlusion. No EEG changes occurred with occlusion in the other 25 patients; mean (±SE) occlusion rCBF in this group was 18.9 ± 1.3 ml.100 g−1.min−1 (P <0.001). Preocclusion flows were not significantly different in the two groups. Critical rCBF during isoflurane anesthesia was less than that previously determined during halothane anesthesia (18–20 ml.100 g−1.min−1), and is compatible with the effects of isoflurane on CMRo2 and CBF.

Cerebral Functional, Metabolic, and Hemodynamic Effects of Etomidate in Dogs

The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg · kg−1 · min−1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg · kg−1 · min−1 etomidate when the animals had received a total of 10.7 mg · kg−1 over 91 min. At this time the CMRO2 was 2.6 ml · min−1 · 100 g−1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg · kg−1 CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2 CBF decreased precipitously from 145 ± 23 to 72 ± 6 ml · min−1 · 100 g−1 during the lowest infusion rate of 0.02 mg · kg−1 · min−1 etomidate and stabilized at 34–36 ml · min−1 · 100 g−1 during an infusion rate of 0.1 mg · kg−1 · min−1 · CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2 · Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 μmol · g−1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.

The cerebral functional, metabolic, and hemodynamic effects of desflurane in dogs

The effects of 0.5-2.0 MAC (3.6-15%) desflurane on cerebral function, metabolism, and hemodynamics and on systemic metabolism and hemodynamics were examined in dogs. Desflurane produced a significant dose-related decrease in cerebral vascular resistance from 1.53 +/- 0.21 mmHg.ml-1.min.100 g at 0.5 MAC to 0.50 +/- 0.03 mmHg.ml-1.min.100 g at 2.0 MAC desflurane. This was accompanied by an increase in cerebral blood flow (CBF) from 61 +/- 7 ml.min-1.100 g-1 at 0.5 MAC to 78 +/- 3 ml.min-1.100 g-1 at 1.5 MAC desflurane. At 2.0 MAC desflurane CBF was 52 +/- 2 ml.min-1.100 g-1 but was associated with a decrease in mean arterial pressure (MAP) to 43 +/- 2 mmHg. When MAP was increased to 73 +/- 3 mmHg with phenylephrine, CBF increased to 87 +/- 3 ml.min-1.100 g-1 at this concentration. At 0.5 MAC desflurane, intracranial pressure (ICP) was 15 +/- 5 mmHg, higher than normal, but did not change significantly with increasing concentrations of desflurane. Increasing concentrations of desflurane initially produced on the EEG the common pattern sequence of increasing depth of anesthesia with decreasing frequency and increasing amplitude progressing to burst suppression and then at 2.0 MAC desflurane to regular attenuation with interruption by periodic polyspiking, a pattern similar to that seen with isoflurane. At both 1.5 and 2.0 MAC the EEG pattern initially observed at that concentration changed to one with faster background activity with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sufentanil on cerebral circulation and metabolism in dogs

The cerebral and peripheral vascular effects of sufentanil (10–200 μg/kg) were examined in dogs. The cerebral blood flow (CBF) was measured continuously by an electromagnetic flow probe on the outflow of the posterior sagital sinus. Sufentanil at all doses significantly increased CBF that lasted for ∼20 min. The CBF then gradually decreased so that it was significantly below baseline levels by the end of the 60-min study period. The transient increase in CBF was accompanied by an equally transient statistically significant decrease in cerebrovascular resistance. Intracranial pressure did not change. Sufentanil produced an electroencephalographic pattern of deep anesthesia accompanied by a decrease in cerebral oxygen consumption significantly below baseline levels. At the end of the study tissue concentrations of metabolites taken from the cerebral hemispheres were within normal limits, indicative of a normal cerebral energy state. Sufentanil had little effect on systemic hemodynamics. The observation that sufentanil significantly increases CBF in the absence of seizure activity makes it unique among the narcotics. It is hypothesized that in the presence of decreased intracranial compliance, this sudden increase in CBF, although transient, may be detrimental if it is accompanied by an acute increase in intracranial pressure which could produce cerebral ischemia.

Delayed Treatment with Nimodipine Improves Cerebral Blood Flow after Complete Cerebral Ischemia in the Dog

Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 μg kg−1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 μg kg−1 min−1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min−1 100 g−1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min−1 100 g−1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min−1 100 g−1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.

The effect of desflurane and isoflurane on cerebrospinal fluid pressure in humans with supratentorial mass lesions

Desflurane, a new volatile anesthetic, produces cerebral vasodilation. The purpose of this study was to compare the effects of 1 MAC desflurane with those of isoflurane on cerebrospinal fluid pressure (CSFP) in patients with supratentorial mass lesions and a mass effect on computerized tomography (CT scan). Twenty adult patients undergoing craniotomy for removal of supratentorial mass lesions were studied. Ten patients received desflurane and 10 patients received isoflurane. Prior to induction of anesthesia, a radial artery catheter was inserted and a 19-G needle was inserted into the lumbar subarachnoid space to measure CSFP. Baseline arterial blood gases and CSFP were measured with the patient awake and unmedicated. Anesthesia was induced with thiopental (6-9 mg/kg) and muscle relaxation achieved with vecuronium (0.2 mg/kg). The lungs of all patients were hyperventilated to achieve an arterial CO2 tension of 24-28 mmHg. Anesthesia was maintained with 1 MAC volatile anesthetic, either 7.0% desflurane or 1.2% isoflurane in an air:O2 mixture to maintain an inspired O2 fraction (FIO2) of 0.50. Patients were not administered any other anesthetic until the dura was incised. Mean arterial pressure was kept within 20% of the patients mean ward values with the use of esmolol or phenylephrine. CSFP, mean arterial pressure, end-tidal CO2 concentration (PETCO2), hemoglobin O2 saturation, and cerebral perfusion pressure were recorded with the patient awake, immediately postinduction with thiopental, postintubation, after institution of the volatile anesthetic, and every 5 min until the dura was incised. There was no difference in the mean (+/- SD) awake CSFP between the desflurane (11 +/- 4 mmHg) and the isoflurane (10 +/- 2 mmHg) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs.

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of isoflurane and thiopental on neurologic outcome and neuropathology after temporary focal cerebral ischemia in primates

In an attempt to determine whether one anesthetic might be clearly advantageous over another in clinical situations of temporary focal ischemia, isoflurane or thiopental (in concentrations producing equal suppression of cerebral function as measured by the electroencephalogram) were studied for their effects on neurologic outcome and cerebral infarct size in pigtailed monkeys exposed to temporary focal ischemia produced by 5 h of middle cerebral artery occlusion (MCAo). Burst suppression was produced for 15 min before MCAo and maintained throughout the ischemic period by 2.18 +/- 0.11% (mean +/- SE) end-expired isoflurane or 135 +/- 18 mg.kg-1 thiopental. Mean arterial pressure was supported with phenylephrine and maintained at approximately 90 mmHg in both groups throughout the ischemic period. At the end of the ischemic period, the isoflurane or thiopental was discontinued, allowing the animals to awaken. Intensive care was provided as needed. Neurologic function was scored for 8 days at the end of which surviving animals were killed and the brains were fixed in formalin and then examined for infarct size. There was no significant difference in final neurologic outcome between the animals receiving isoflurane and those receiving thiopental as determined by the Mann-Whitney rank sum test. Neurologic deficit scores ranged from normal (one of eight in the group receiving isoflurane and three of nine in the group receiving thiopental) to death resulting from brain injury (three in the isoflurane group and five in the thiopental-treated group). There also was no significant difference in infarct size between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The Cerebral and Systemic Hemodynamic and Metabolic Effects of Desflurane-induced Hypotension in Dogs

The cerebral and systemic hemodynamic and metabolic effects of hypotension induced with desflurane were examined in 11 dogs. During a steady-state baseline period under 1 MAC desflurane (7.2%), the following were measured or derived: arterial, pulmonary artery, and pulmonary artery occlusion pressures; arterial, mixed venous, and sagittal sinus blood gases; cardiac index and cerebral blood flow (CBF); whole-body and cerebral O2 consumption; systemic and cerebral vascular resistance; intracranial pressure; and blood glucose and lactate concentrations. After the baseline period, hypotension to a mean arterial pressure (MAP) of 50 mmHg was produced by 15.5% (2.2 MAC), and hypotension to an MAP of 40 mmHg was produced by 17.1% (2.4 MAC) for 1 h. During this hypotensive period all measurements were taken at 5- or 15-min intervals. At the end of the hypotensive period, brain biopsy specimens were taken for measurement of cerebral concentrations of ATP, phosphocreatine, and lactate to determine whether there was any metabolic evidence of cerebral ischemia. Desflurane-induced hypotension produced a significant, 40-50% decrease in cardiac index with a significant change in systemic vascular resistance at the lower blood pressure, but produced little change in heart rate. Even though whole-body O2 consumption did not decrease, adequate peripheral perfusion was maintained with the lower cardiac output, as evidenced by lack of accumulation of blood lactate. Induced hypotension caused a significant, 50 (at MAP = 50 mmHg) to 64% (at MAP = 40 mmHg) decrease in cerebral perfusion pressure, accompanied by a significant, 36 (at MAP = 50 mmHg) to 60% (at MAP = 40 mmHg) decrease in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

The Response of the Canine Cerebral Circulation to Hyperventilation during Anesthesia with Desflurane

Arterial CO2 tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) and cerebral vascular resistance (CVR) in animals and humans. The normal responsiveness of the cerebral vasculature to PaCO2 is approximately 2 ml.min-1.100 g-1.mmHg-1. This study examined the effect of desflurane, a new volatile anesthetic, on the responsiveness of the cerebral vasculature to changes in PaCO2. Mean arterial pressure (MAP), CBF, CVR, intracranial pressure (ICP), and cerebral metabolic rate for O2 (CMRO2) were measured in five dogs anesthetized with desflurane (0.5-1.5 MAC) at normocapnia (PaCO2 = 40 mmHg) and at two levels of hypocapnia (PaCO2 = approximately 30 and approximately 20 mmHg). Under desflurane anesthesia, similar changes in CBF and CVR occurred with hyperventilation at all MAC levels of desflurane. At 0.5 MAC, CBF decreased significantly, from 81 +/- 6 to 40 +/- 3 ml.min-1.100 g-1 (P less than 0.05, mean +/- SE) when PaCO2 was decreased from 40 to 24 mmHg; i.e., the CBF decreased approximately 2.6 ml.min-1.100 g-1.mmHg-1. At 1.0 MAC desflurane, CBF decreased significantly, from 79 +/- 10 to 43 +/- 5 ml.min-1.100 g-1 with hyperventilation (2.0 ml.min-1.100 g-1.mmHg-1); at 1.5 MAC desflurane, CBF decreased from 65 +/- 6 to 38 +/- 2 ml.min-1.100 g-1 with hyperventilation (1.6 ml.min-1.100 g-1.mmHg-1). Despite the significant decreases in CBF with hyperventilation, there was no significant change in ICP. Dose-dependent decreases in MAP were observed with increasing concentrations of desflurane but were not significantly affected by ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)