Biomedical subjects
L N Milde
Publications and source records attributed to L N Milde.
Alfentanil-induced epileptiform activity in patients with partial epilepsy.
We performed a retrospective study investigating the effect of alfentanil hydrochloride on electrocorticography (ECoG) in 23 patients with intractable nonlesional partial epilepsy undergoing anterior temporal lobectomies at this institution. Alfentanil is a short-acting, parenteral, opioid analgesic with a rapid onset of action. Opioid drugs have the potential to induce hippocampal electrographic seizures. Pre-excision ECoG was obtained before and after the administration of 50 micrograms/kg of alfentanil. ECoG was performed using subdural strips placed on the lateral temporal surface and in the suprasylvian region and monopolar depth electrodes implanted into the amygdala and hippocampus. The surgically excised temporal lobes revealed cortical gliosis and varying degrees of hippocampal neuronal loss in all patients. A quantitative assessment of the effect of alfentanil on the ECoG was performed by measuring the frequency of interictal spikes. There was a significant increase in the mesial temporal lobe mean spike frequency after the administration of alfentanil (p < 0.001). One patient had an alfentanil-induced mesial temporal lobe electrographic seizure. Alfentanil did not have a significant effect on spike activity in the suprasylvian region (p = 0.500). Further studies will be necessary to determine the specificity of alfentanil activation in patients with partial seizures of temporal lobe origin.
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 patient's 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)
Clinical use of mild hypothermia for brain protection: a dream revisited.
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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)
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)
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)
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 micrograms/kg) were examined in dogs. The cerebral blood flow (CBF) was measured continuously by an electromagnetic flow probe on the outflow of the posterior sagittal sinus. Sufentanil at all doses significantly increased CBF that lasted for approximately 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.
Cerebral effects of fentanyl in dogs.
We have studied the cerebral haemodynamic and metabolic effects of fentanyl 50 micrograms kg-1 and 100 micrograms kg-1 in dogs undergoing ventilation with oxygen and nitrogen at normocapnia. Cerebral blood flow was measured continuously by direct measurement of the outflow of the posterior sagittal sinus. Arterial and sagittal sinus blood-gas tensions were measured intermittently for calculation of cerebral metabolism. Systemic pressures were measured continuously with intermittent measurements of cardiac output. These doses of fentanyl had minimal effect on cerebral blood flow, cerebral oxygen consumption and the energy state of the brain reflected by the normal concentration of cerebral metabolites at the end of the study. There was also little effect on systemic haemodynamics. It is concluded that, in the absence of other anaesthetic agents which might influence cerebral haemodynamics and metabolism, large doses of fentanyl have little effect on the cerebral circulation.
Pathophysiology of ischemic brain injury.
This article reviews normal cellular function including ion homeostasis, cerebral metabolism, the utilization of glucose, and oxidative phosphorylation. A description of the types of cerebral ischemia is followed by the flow thresholds of ischemia, the concept of selective vulnerability, and the secondary biochemical and pathophysiologic consequences of ischemia. Pathophysiologically, cerebral ischemia includes both vascular and neuronal changes, which in turn reflect alterations in the mitochondria, intracellular ion concentrations, glucose, prostaglandins, free radicals, and excitatory amino acid neurotransmitters.
An anaphylactic reaction to fibrin glue.
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Status of the match in anesthesiology: 1988.
The majority of anesthesia program directors agreed 2 years ago to use the National Resident Matching Program (NRMP) as the mechanism for appointing senior medical students to second postgraduate year positions in anesthesiology. Eighty-seven applicants for the Mayo Clinic program were surveyed to measure the level of cooperation with the NRMP by programs and applicants. Low percentages of applicants reported pressures to sign contracts (22.4%) or make verbal commitments before February (32.8%). The frequency of these incidents was extremely low when considered in light of the number of applicant interviews reported by the applicants who responded. Nonparticipation in the match is a more important problem than infractions of NRMP rules.
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 hypoxic mouse model for screening cerebral protective agents: a re-examination.
The hypoxic mouse model, in which mice are subjected to an atmosphere of 5% O2 in nitrogen, has been used to screen anesthetics for possible cerebral protection by measuring their ability to prolong survival in mice exposed to hypoxia. Although prolonged survival time in this model is primarily due to a decreased cerebral metabolic rate produced by a specific anesthetic, results can also be influenced by body temperature, dose of anesthetic, and ventilatory or circulatory depression produced by the anesthetic. Using the hypoxic mouse model, the effects of thiopental in conjunction with changes in ambient temperature, changes in thiopental dose, and the presence or absence of nitrous oxide (N2O) were examined. Survival times were measured in eight groups of animals, either untreated animals or animals pretreated with 100 mg/kg thiopental intraperitoneally; exposed to hypoxia in the presence or absence of N2O; at ambient temperatures of either 25 degrees C or 35.5 degrees C. Survival times of seven additional groups of mice, either untreated or treated with doses of 50, 60, 70, 80, 90 or 120 mg/kg thiopental intraperitoneally, exposed to hypoxia in an ambient temperature of 35.5 degrees C were measured to determine a dose-response curve. At an ambient temperature of 35.5 degrees C in which the rectal temperature of both untreated and thiopental-treated animals was maintained near 36 degrees C, thiopental-treated animals did not survive any longer than the untreated animals. Exposure to N2O shortened survival times of both groups by approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)
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 less than 10 ml X 100 g-1 X 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 X 100 g-1 X min-1 (P less than 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 X 100 g-1 X min-1), and is compatible with the effects of isoflurane on CMRO2 and CBF.
The detrimental effect of lidocaine on cerebral metabolism measured in dogs anesthetized with isoflurane.
Previous studies in dogs have demonstrated that massive doses of intravenous lidocaine (160 mg X kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg X kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 +/- 19 ml X min-1 X 100 g-1 during 3% isoflurane anesthesia, and was 102 +/- 11 ml X min-1 X 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 +/- 0.23 ml X min-1 X 100 g-1 during isoflurane anesthesia, and was 2.18 +/- 0.09 ml X min-1 X 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 +/- 0.04 mumol X g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 +/- 0.01 mumol X g-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Short-term neurological recovery with flunarizine.
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