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Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury.

Following permanent occlusion of the left middle cerebral artery (MCA) in rats, electrophysiological and hemodynamic characteristics of the periinfarct border zone were investigated in sham-operated (n = 6), untreated (n = 6), and MK-801-treated (3.0 mg/kg; n = 6) animals. For this purpose, direct current potential (DC), EEG, and blood flow (laser-Doppler flowmetry) were recorded from the cortex in the periphery of the MCA territory. In sham-operated rats, a single negative cortical DC deflection was observed after electrocoagulation of the cortex, whereas in untreated MCA-occluded animals, three to eight transient DC deflections were monitored during the initial 3 h of ischemia. The duration of these cortical DC shifts gradually increased from 1.2 +/- 0.3 to 3.7 +/- 2.7 min (mean +/- SD; p less than 0.05) during this time. In animals treated intraperitoneally with MK-801 (3.0 mg/kg) immediately after MCA occlusion, the number of cortical DC shifts significantly declined to one to three deflections (p less than 0.005). The EEG of the treated animals revealed low-amplitude burst-suppression activity. In the untreated and treated experimental group, the reduction of cortical blood flow amounted to 69 +/- 25 and 49 +/- 13% of control, respectively. Despite the more pronounced cortical oligemia, MK-801 treatment resulted in a significant decrease of the volume of the ischemically injured tissue from 108 +/- 38.5 (untreated group) to 58 +/- 11.5 (p less than 0.05) mm3. Our results suggest that repetitive cortical DC deflections in the periinfarct border zone contribute to the expansion of ischemic brain infarcts.

Action Potentials↗

Open comparative study with treatment-refractory depressed patients: electroconvulsive therapy--anesthetic therapy with isoflurane (preliminary report).

Isoflurane is the only routine volatile anesthetic which leads to a burst-suppression EEG in nontoxic concentrations and for which no memory impairments can be expected subsequent to anesthesia. After electrically induced spike-wave activity in electroconvulsive therapy (ECT), a brief period of a very flat EEG can be observed. This phenomenon may be closely related to the therapeutic effects of ECT. The results which have been achieved up to now in comparing ECT to anesthetic therapy with isoflurane, without seizures being induced, are presented.

Adult↗

EEG monitoring of prolonged thiopentone administration for intractable seizures and status epilepticus in infants and young children.

Thiopentone anaesthesia was used in the treatment of seizures in 19 infants and young children. Nine had a pre-existing seizure disorder without acute cerebral injury and 10 had status epilepticus secondary to an acute cerebral illness. Clinical details, drug levels and findings from serial multichannel electroencephalograms (EEG) and continuous 1 to 2 channel signal processed EEGs using a Cerebral Function Analysing Monitor (CFAM) were reviewed to evaluate the contribution of these techniques to clinical management. Initial EEGs showed discharges that were not generalised in 16/19 patients. This necessitated the use of 7 different montages for continuous monitoring. Three different CFAM patterns representing particular EEG paroxysmal findings were seen. Acute seizure control was achieved in all 19 patients. All patients with a pre-existing seizure disorder survived, although 4/10 with an acute cerebral illness died. During treatment, patterns of burst-suppression to electrocerebral silence (ECS) were eventually seen in 16/19 patients and repeat EEGs demonstrated concordant multi-channel findings in 8/8. Although increasing thiopentone levels (13 patients) correlated with deeper suppression of cortical electrical activity, there was marked inter-patient variability. Inotropic support was not required during the period of treatment even when ECS was induced. In young children a combination of multi-channel EEG and continuous 1 to 2 channel monitoring has advantages over either method used alone. In individual patients on-line monitoring can be easily incorporated in a protocol of controlled cortical suppression and drug titration for seizure control.

Child, Preschool↗

Thiopental pharmacokinetics under conditions of long-term infusion.

Thiopental was used in long-term infusion (3-4.5 mg . kg-1 . h-1 during 4-8 days) to protect the brain from injury following trauma. Thiopental plasma concentrations were measured during infusion (48 patients) and after infusion (14 patients) to determine the kinetics of the drug in continuous infusion. All mean values were mean +/- SD. Steady state concentrations (Css) were 31.8 +/- 10.7 mg/l for an infusion rate of 3.05 +/- 0.37 mg . kg-1 . h-1 and 48.9 +/- 14.6 mg/l for a rate of 4.2 +/- 0.3 mg . kg-1 . h-1. Corresponding steady state clearance decreased when Css increased, indicating possible saturation of the metabolic enzymatic system. Michaelis-Menten kinetics were confirmed by postinfusion data that give, for higher Css, a nonlinear decay of log C versus time. First-order kinetics were only obtained with Css below 30 mg/l. The maximum rate of elimination (Vm) was 1.76 +/- 1.15 mg . l-1 . h-1 (n = 11), and the Michaelis constant (Km) was 26.7 +/- 22.9 mg/l (n = 11). Hepatic enzyme saturation was between 35 and 85%. The volume of distribution at steady state was 4.35 +/- 1.83 l/kg (n = 11). Apparent half-lives of elimination were between 18 and 36 h at the end of infusion, and predicted terminal half-lives were 10.15 +/- 5.43 h (n = 11). Phases of burst-suppression were observed on electroencephalographic traces for concentrations greater than 40 mg/l. The authors' results suggest that a continuous infusion at a dose of 4 mg . kg-1 . h-1 induces EEG changes consistent with a near-maximum reduction in cerebral metabolism. Because of the thiopental Michaelis-Menten kinetics at doses above 4 mg . kg-1 . h-1, the authors suggest that thiopental plasma concentrations be measured and/or the drug effect be measured with the EEG to prevent excessive thiopental overdosage, causing a prolonged recovery time.

Adolescent↗

Local cerebral blood flow and glucose utilization during isoflurane anesthesia in the rat.

Volatile anesthetic agents have profound and heterogeneous effects on global and local cerebral blood flow (l-CBF) and metabolism. The relationship between l-CBF and local cerebral glucose uptake (l-CMRg) during isoflurane anesthesia is unknown. Because these relationships might influence neuronal homeostasis during periods of cerebral ischemia of different causes, it becomes important to understand them. Accordingly, the authors evaluated the l-CBF and l-CMRg effects of isoflurane with quantitative autoradiography in normal rats. As the dose of isoflurane increased in a stepwise fashion to 0.5, 1.0 (1.38%), 1.5, and 2.0 MAC levels, the number of structures with a significant (P less than 0.05) l-CBF increase or l-CMRg decrease became greater. At each respective MAC level l-CBF was increased in 0%, 11%, 34%, and 30%, while l-CMRg decreased in 11%, 70%, 74%, and 81% of the structures in which autoradiographic measurements were performed. Between 1.5 MAC and 2.0 MAC the l-CMRg decrease stabilized at about -50% to -70% of cerebral metabolic values obtained in awake control rats in association with attainment of a burst-suppression of isoelectric electroencephalogram. In contrast to these general changes, l-CMRg in two subcortical limbic system structures (dentate gyrus and interpeduncular nucleus) did not decrease, even at the highest doses of isoflurane. L-CBF was significantly (P less than 0.05) increased only at the highest dose ranges (1.5-2.0 MAC) and increased from 34% to 238% in about one-third of the structures evaluated. Isoflurane anesthesia causes heterogeneous changes in l-CBF and metabolism, which are most apparent at doses at or above 1.0 MAC.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Effect of epoch length on power spectrum analysis of the EEG.

To study the effect of epoch length on the variability of power spectrum analysis of the EEG, 22 64-s segments of EEG were analyzed using epoch lengths of 2, 4, 8, 16, and 32 s. Nine of these segments exemplified EEG changes during transient anesthetic states or surgical conditions. Epoch-to-epoch variability was computed within frequency bins for all segments, and ANOVA with hierarchal classification was used to determine the length of the EEG segment necessary to identify a statistically significant change in those EEG segments recorded during changing conditions. In 16 segments, the epoch-to-epoch variability with power spectra were computed using 2-s epochs was significantly less than the variability when power spectra were computed using longer epoch lengths. In five segments, no significant difference existed between the variance at 2-s epochs and longer (4-s) epochs. In one case, an EEG containing a burst-suppression pattern, the variability was significantly increased when 2-s epochs were used. Analysis using 2-s epochs also identified changes more rapidly than analysis using any longer epoch length in eight of nine segments, and the differences were clinically significant as well (over 30 s faster when 2-s epochs were used instead of 16-s epochs). These findings suggest the preferability of short epoch lengths when power spectrum analysis is used for intraoperative EEG monitoring.

Analysis of Variance↗

I653 and isoflurane produce similar dose-related changes in the electroencephalogram of pigs.

I653 is a new volatile anesthetic structurally similar to enflurane and isoflurane. Since enflurane can induce convulsions, whereas isoflurane progressively depresses cortical electrical activity, the authors believed it important to assess the effect of I653 on the EEG (in both the "time" and "frequency" domain). The EEG was assessed visually and quantitatively, and a new EEG parameter was introduced. The burst-suppression ratio (percentage of time the EEG was isoelectric) quantified the extent of burst suppression phenomena. Eight swine were anesthetized with I653 or isoflurane in oxygen and in random sequence, exposed to approximately 0.8, 1.2, or 1.6 MAC with normocapnea and to 1.2 MAC with hypocapnea (PETCO2 of 25 mmHg). Four animals were also anesthetized with 3.2% (1.2 MAC) enflurane in oxygen. Both I653 and isoflurane produced a dose-related depression of cortical electrical activity. At 0.8 and 1.2 MAC of either agent, occasional sharp waves occurred singly, were apparently not related to external (auditory) stimuli, and probably represented normal variation in the EEG. No electrographic or gross motor seizures occurred with either I653 or isoflurane. In contrast, all pigs given enflurane developed seizures during hypocapnea. At equipotent concentrations, I653 and isoflurane had the same effect on EEG parameters. Increasing doses of either I653 or isoflurane caused decreasing amplitude and frequency and increasing suppression. Hypocapnea during either agent slightly increased high-frequency activity, and slightly decreased burst suppression.

Anesthesia, Inhalation↗

Isoflurane for refractory status epilepticus: a clinical series.

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Adolescent↗

Comparison of methohexital and isoflurane on neurologic outcome and histopathology following incomplete ischemia in rats.

Using a rat model of incomplete cerebral ischemia the effects of isoflurane (iso) and methohexital (metho) were compared with those of 70% nitrous oxide controls (N2O). Two levels of incomplete cerebral ischemia were produced by right carotid occlusion plus hypotension for 30 min: moderate = 30 mmHg, FIO2 = 0.30; severe = 25 mmHg, FIO2 = 0.20. The iso doses (1 and 2 MAC) and metho doses (0.01 and 0.1 mg.kg-1.min-1) were tested at each ischemic level. These iso and metho doses were selected because without ischemia they produced similar decreases in cerebral oxygen consumption (CMRO2) compared with that produced in N2O controls. In the absence of ischemia, the electroencephalogram (EEG) was suppressed by 0.01 mg.kg-1.min-1 metho and 1 MAC iso and showed burst-suppression with 0.1 mg.kg-1.min-1 metho and 2 MAC iso. The EEG was further depressed by ischemia under all anesthetic conditions. Neurologic outcome was evaluated for 3 days following incomplete cerebral ischemia by using a graded deficit score (0 = normal, 5 = death associated with stroke). Following moderate ischemia all four anesthetic treatments improved outcome compared with N2O controls, but after severe ischemia only 2 MAC iso significantly improved outcome. Neurohistopathology was evaluated on a scale of 0 to 40, 24 h after ischemia. The neurohistopathology score was significantly improved by all four anesthetic treatments compared with N2O following moderate ischemia and was better with 2 MAC iso compared with 0.1 mg.kg-1.min-1 metho after both moderate and severe ischemia. These results show that both iso and metho improve outcome from cerebral ischemia compared with that associated with N2O, but only 2 MAC iso resulted in an improved outcome following severe ischemia. This difference in outcome between the two anesthetics may be related to greater neuronal depression with iso, which may occur with little difference in cerebral metabolic depression.

Animals↗

Neonatal electroencephalography and neuropathology.

One-hundred-eight EEGs from 47 newborn infants were compared with the postmortem neuropathological findings. The degree of EEG background abnormality had good correlation with the severity of the brain lesion; the more severe the EEG background abnormality, the more extensive and intensive the morphological change. Widespread encephalomalacia was demonstrated in six infants who manifested isoelectric tracings. In particular, cerebral cortex, corpus striatum, thalamus, midbrain, and pons were affected in all patients with this abnormal EEG pattern. Burst-suppression patterns, which were seen in seven infants, also correlated with multifocal severe brain damage, but there was no common structure that was consistently affected for all patients with this pattern. Positive rolandic sharp-wave transients (PRS) appeared highly specific for white matter lesions. All eight infants with PRS had white matter lesions. However, the sensitivity of PRS for white matter lesions was not high (32%), and the white matter lesions of PRS-positive patients were not necessarily composed of periventricular leukomalacia. The sensitivity of EEG asymmetry was also low (40%) for the focality of morphological change, although the specificity was relatively high (85%). The origin of seizure discharges, on the other hand, had poor correlation with the site of the brain lesion.

Brain↗

Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion.

Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used.

Acute Disease↗

Sympathetic nervous system response to lidocaine induced seizures in cats.

The effect on arterial pressure, EEG, preganglionic sympathetic nervous activity and pulse rate of repeated intravenous administrations of lidocaine (3 mg/kg) was investigated in cats anaesthetized with nitrous oxide. A continuous high voltage, burst-suppression EEG indicating constant seizure activity was found, whereas arterial pressure and sympathetic nervous activity did not change significantly. Although the onset of EEG seizure activity did not change the mean sympathetic activity level, the pattern of firing changed dramatically as every EEG seizure triggered a burst of sympathetic impulses. Barostatic reflexes were active after lidocaine administration unless seizure activity occurred. Thiopental 5 mg/kg given intravenously to cats during continuous lidocaine-induced EEG seizures always abolished the seizure activity without excessive depression of arterial pressure.

Animals↗

Effect of insulin-induced hypoglycemia on the concentrations of glutamate and related amino acids and energy metabolites in the intact and decorticated rat neostriatum.

The glutamate (Glu) terminals in rat neostriatum were removed by a unilateral frontal decortication. One to two weeks later the effects of insulin-induced hypoglycemia on the steady-state levels of amino acids [Glu, glutamine (Gln), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine] and energy metabolites (glucose, glycogen, alpha-ketoglutarate, pyruvate, lactate, ATP, ADP, AMP, phosphocreatine) were examined in the intact and decorticated neostriatum from brains frozen in situ. The changes in the metabolite levels were examined during normoglycemia, hypoglycemia with burst-suppression (BS) EEG, after 5 and 30 min of hypoglycemic coma with isoelectric EEG, and 1 h of recovery following 30 min of isoelectric EEG. In normoglycemia Glu decreased and Gln and glycogen increased significantly on the decorticated side. During the BS period no significant differences in the measured compounds were noted between the two sides. After 5 min of isoelectric EEG Glu, Gln, GABA, and ATP levels were significantly lower and Asp higher on the intact than on the decorticated side. No differences between the two sides were found after 30 min of isoelectric EEG. After 1 h of recovery from 30 min of isoelectric EEG Glu, Gln, and glycogen had not reached their control levels. Glu was significantly lower, and Gln and glycogen higher on the decorticated side. The Asp and GABA levels were not significantly different from control levels. The results indicate that the turnover of Glu is higher in the intact than in decorticated neostriatum during profound hypoglycemia.

Amino Acids↗

Status epilepticus: clinical experience with two special devices for continuous cerebral monitoring.

Continuous cerebral monitoring (CCM) was performed on 34 patients in status epilepticus (SE), using changes in amplitude detected by the cerebral function monitor (CFM) and changes in frequency detected by compressed spectral array (CSA). The EEG was used intermittently to help identify seizure patterns obtained with these methods. Seventeen patients in clinically manifest SE also had non-convulsive seizures. In 17 patients, SE was refractory to conventional anticonvulsants, requiring treatment with pentobarbital or paraldehyde. In these patients, CCM provided dynamic electroencephalographic monitoring of burst-suppression and prompt detection of breakthrough seizures. Patients in SE should undergo CCM to differentiate between non-convulsive seizures and post-ictal state both of which may produce prolonged unresponsiveness following clinical seizures. CCM after data reduction with the two special devices used is a viable and practical alternative to continuous conventional EEG monitoring during SE. However, in order to evaluate the sensitivity and specificity of these methods, it will be necessary to design a study in which both the EEG and the devices using data reduction be used continuously and concurrently.

Adolescent↗

Recovery of neuronal transmission after prolonged cerebral ischemia.

The potentials of postischemic functional recovery were studied in cats submitted to 1 h of complete cerebrocirculatory arrest in normothermia. Neuronal activity was estimated by recording the electroencephalogram (EEG), the pyramidal response following stimulation of the motor cortex and the somatosensorily evoked cortical potentials. During ischemia EEG was suppressed within 12-15 s, evoked potentials within 2 min, and the pyramidal response within 5 min. After recirculation following ischemia, the electrically evoked D wave of the pyramidal response began to reappear between 7 and 9 min and the synaptically evoked I wave between 25 and 60 min. The evoked cortical potentials returned in parallel with the I wave of the pyramidal response but control amplitude was not reached before 3 h. The peak latencies of the evoked potentials were consistently prolonged for at least 24 h but normalized after a few days, provided secondary postischemic circulatory disturbances could be prevented. EEG began to recover after the beginning appearance of the somatosensorily evoked cortical potentials; initially it exhibited a burst-suppression pattern but it gradually progressed to continuous activity. The frequency pattern of the EEG normalized within 24 h and the amplitude after a few days. After recovery, the behavior of the pyramidal response and of evoked potentials to repetitive stimulation was the same as under control conditions.

Animals↗

Thiopentone cerebral protection under EEG control during carotid endarterectomy.

Seventy patients who underwent a total of 77 consecutive carotid endarterectomies were given thiopentone (mean dose 19 mg/kg) under EEG control for cerebral protection during the period of carotid clamping. This technique was used instead of elective insertion of a temporary bypass shunt in response to adverse EEG changes occurring after clamping. The EEG was monitored continuously throughout operation. The EEG burst-suppression pattern with electrically inactive periods of 30-60 seconds was taken as indicating a depth of barbiturate anaesthesia adequate to provide brain protection. Patients exhibited a drop in blood pressure during barbiturate administration: in most the pressure recovered spontaneously but in twenty operations metaraminol was needed to re-establish an adequate pressure before clamping. No adverse cardiological effects were associated with the administration of thiopentone or metaraminol. There was no mortality and no neurological morbidity in this series.

Aged↗

Patterns resembling tracé alternant in quiet sleep of an adult.

An 18-year-old man with lymphoma and Listeria meningitis developed a pattern similar to tracé alternant during quiet sleep. This is a pattern normally seen in the neonate during quiet sleep and probably represents diffuse brain disturbance of both cortical and deep gray matter if occurring in the adult, as with other discontinuous or burst-suppression patterns.

Adolescent↗

Periodic complexes and alternating rotatory nystagmus with cyclic pupillary changes.

A 69-year-old male, with a history of a previous subdural hematoma, multistroke dementia and ventricular shunting for hydrocephalus, exhibited while comatose isolated periodic alternating rotatory nystagmus with cyclic pupillary changes and periodic alternating gaze. His simultaneous EEG showed PLEDs and subsequently burst-suppression pattern. The latter abnormality was associated, in addition, to transient eyelid opening, synchronized with the EEG bursts. Complex neuro-ophthalmologic clinical signs, sometimes subtle, may be the sole manifestation of EEG periodic complexes that have potential prognostic and therapeutic implications.

Aged↗