thiopental and Brain-Ischemia

Transcranial Doppler and, if possible, measurement of intracranial pressure (ICP) allow preoperative diagnosis of acute intracranial hypertension (ICH) after brain trauma. The main goal of the anaesthesiologist is to prevent the occurrence of secondary brain injuries and to avoid cerebral ischaemia. Treatment of high ICP is mainly achieved with osmotherapy. High-dose mannitol administration (1.4 to 2 g/kg given in bolus doses) may be considered a better option than conventional doses, especially before emergency evacuation of a cerebral mass lesion. Hypertonic saline seems as effective as mannitol without rebound effect and without diuresis increase. Haemostasis should be normalized before neurosurgery and invasive blood pressure monitoring is mandatory. For anaesthesia induction, thiopental or etomidate may be used. In case of ICH, halogenated and nitrous oxide should be avoided. Until the dura is open, mean arterial pressure should be maintained around 90 mmHg (or cerebral perfusion pressure around 70 mmHg). If a long-lasting (several hours) extracranial surgery is necessary, ICP should be monitored and treatment of ICH should have been instituted before.

Topics: Acute Disease; Anesthesia, General; Blood Pressure; Brain Injuries; Brain Ischemia; Case Management; Combined Modality Therapy; Comorbidity; Contraindications; Diuretics, Osmotic; Etomidate; Humans; Hyperventilation; Intracranial Hypertension; Jugular Veins; Mannitol; Monitoring, Intraoperative; Monitoring, Physiologic; Nitrous Oxide; Oxygen; Preoperative Care; Saline Solution, Hypertonic; Thiopental; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial; Wounds and Injuries

Induced circulatory arrest is a technique used to provide a period of operative stability in a variety of surgical procedures that might otherwise be technically unfeasible. The use of hypothermia and barbiturates for protection against cerebral ischaemia during circulatory arrest is reviewed against a background of the pathophysiology of cerebral ischaemia and possible future therapies are also suggested.

Topics: Anesthesiology; Brain Ischemia; Calcium Channel Blockers; Dicarboxylic Acids; Heart Arrest, Induced; Humans; Hypothermia, Induced; Thiopental

Topics: Animals; Brain Ischemia; Calcium Channel Blockers; Isoflurane; Thiopental

This review has indicated that barbiturates are useful in controlling ICP during anaesthesia in patients with intracranial hypertension. While laboratory data indicate that intraoperative administration of barbiturates during episodes of transient cerebral ischaemia, associated with surgical revascularization procedures, should be efficacious, current intraoperative results claiming benefit are anecdotal. Continuous high-dose barbiturate therapy (induced barbiturate coma) for occlusive stroke and persistently increased intracranial pressure is currently undergoing clinical trials. While it is clear that this therapy can often reduce increased ICP in head injured patients, its influence on neurological outcome remains to be determined by a multicentre trial at present in progress. Despite evidence that high-dose barbiturate therapy can reduce the area of infarction in occlusive stroke in the laboratory, organized clinical trials have not yet commenced. Until more definitive knowledge is available concerning the influence of high-dose barbiturate therapy in treating different forms of cerebral ischaemia, its application should be viewed sceptically and limited to centres willing to create an organized data base for inter-institutional evaluation of this form of treatment. If barbiturate therapy proves successful and the mechanisms involved are better understood, drugs with fewer side-effects and risks may become available to combat cerebral ischaemia.

Topics: Animals; Barbiturates; Brain Ischemia; Cerebral Revascularization; Craniocerebral Trauma; Critical Care; Electroencephalography; Humans; Intracranial Pressure; Intraoperative Period; Ischemic Attack, Transient; Monitoring, Physiologic; Oxygen; Thiopental

Despite advances in the understanding of the pathophysiology of cerebral ischemia, no single brain resuscitation therapy has yet been shown to be clinically superior to brain-oriented intensive care. Basic concepts in cardiopulmonary-cerebral resuscitation (CPCR) are discussed, as are two specific phases of CPCR, cerebral preservation and cerebral resuscitation. Cerebral preservation is initiated during cardiac arrest (ie, prior to restoration of spontaneous circulation [ROSC]) and includes use of artificial perfusion techniques and drugs to produce cerebral perfusion during this phase. Cerebral resuscitation is brain-oriented therapy initiated after ROSC. Pharmacologic agents currently under study for cerebral resuscitation include the barbiturates, calcium antagonists, and iron chelators. With respect to defining efficacy of the pharmacologic agents, the concept of therapeutic window is important. Although no agent has been proven clinically, several appear to be promising.

Topics: Animals; Brain Ischemia; Calcium Channel Blockers; Cerebrovascular Circulation; Chelating Agents; Heart Arrest; Humans; Resuscitation; Thiopental

Topics: Adenosine Triphosphate; Anesthesia; Anesthetics; Aneurysm; Animals; Barbiturates; Brain; Brain Diseases; Brain Ischemia; Cerebrovascular Circulation; Electroencephalography; Energy Metabolism; Humans; Hypothermia, Induced; Intraoperative Complications; Isoflurane; Naloxone; Phenytoin; Thiopental

Topics: Animals; Barbiturates; Brain; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Dogs; Humans; Hypertension; Hypoxia, Brain; Intracranial Pressure; Ischemic Attack, Transient; Phenobarbital; Thiopental

Experimental and clinical studies of the protective effect of barbiturates in cerebral ischaemia are reviewed. Their action in protecting the brain from the effects of ischaemia is related to their action as anaesthetic agents and probably to the depression of neuronal function and metabolism but is incompletely understood. Their effect is dose related. Early administration is likely to be crucial to the success of barbiturate therapy as secondary events following an episode of cerebral ischaemia can lead to irreversible brain damage within 2--3 h. A potential collateral circulation appears to be essential for the protective effect of barbiturates. There may be a possibility of partly overcoming time delays in administration by giving larger doses of barbiturates.

Topics: Animals; Barbiturates; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypothermia, Induced; Pentobarbital; Thiopental; Time Factors

Thiopental produces cerebral metabolic depression and cerebral vasoconstriction. However, the effect of thiopental on brain tissue oxygen pressure (PO2), carbon dioxide pressure, and pH is not known. In a prospective study, we measured brain tissue gases and pH during thiopental or desflurane treatment that was administered for brain protection during brain artery occlusion.. After institutional review board approval, 20 patients undergoing craniotomies for cerebrovascular surgery were tested; 10 were randomized to receive thiopental and 10 to receive desflurane. After each craniotomy, a Neurotrend probe (Diametrics Medical, Minneapolis, MN) was inserted to measure tissue PO2, carbon dioxide pressure, and pH in a tissue region at risk to develop ischemia during temporary brain artery occlusion. Thiopental or desflurane was administered to produce burst suppression of electroencephalography, and then temporary artery occlusion was performed during aneurysm or extracerebral-to-intracerebral bypass surgery.. Thiopental produced no change in tissue gases or pH, but temporary artery clipping in thiopental-treated patients decreased PO2 30% (P < 0.05). Desflurane increased PO2 70% (P < 0.05), and tissue oxygenation remained elevated during temporary artery occlusion. Tissue pH did not decrease in either group during temporary brain artery occlusion.. Thiopental has a metabolically neutral effect on brain tissue gases and pH, even though it is known to decrease cerebral oxygen consumption. The metabolic depressant and vasodilator effects of desflurane enhance tissue oxygenation and attenuate tissue PO2 reductions produced by artery occlusion. Both thiopental and desflurane inhibit ischemic lactic acidosis and decreases in pH.

Topics: Acid-Base Equilibrium; Anesthetics, Inhalation; Brain; Brain Ischemia; Cerebral Revascularization; Craniotomy; Desflurane; Energy Metabolism; Humans; Intracranial Aneurysm; Isoflurane; Monitoring, Intraoperative; Neuroprotective Agents; Oxygen Consumption; Thiopental; Vasodilation

After restoration of spontaneous circulation and adequate oxygenation, 262 comatose survivors of cardiac arrest were randomly assigned to receive standard brain-oriented intensive care or the same standard therapy plus a single intravenous loading dose of thiopental (30 mg per kilogram of body weight). The study was designed to have an 80 percent probability of detecting a 20 percent reduction in the incidence of permanent postischemic cerebral dysfunction. Base-line characteristics were similar in the two treatment groups. At the end of one year of follow-up, there was no statistically significant difference between treatment groups in the proportion of patients who died (77 percent of the thiopental vs. 80 percent of the standard-therapy group), survived with "good" cerebral recovery (20 percent of the thiopental vs. 15 percent of the standard-therapy group), or survived with permanent severe neurologic damage (2 percent of the thiopental vs. 5 percent of the standard-therapy group). The results of this study do not support the use of thiopental for brain resuscitation after cardiac arrest.

Topics: Adolescent; Adult; Aged; Brain Damage, Chronic; Brain Ischemia; Child; Child, Preschool; Clinical Trials as Topic; Coma; Female; Follow-Up Studies; Heart Arrest; Humans; Infant; Male; Middle Aged; Random Allocation; Resuscitation; Thiopental

The possible cerebral sparing effect of thiopental was evaluated in 32 severely asphyxiated neonates randomly assigned to either a thiopental treatment or control group. All infants had neurologic manifestations of asphyxia and required assisted ventilation. Thiopental was begun at a mean age of 2.3 hours and was given as a constant infusion that delivered 30 mg/kg over 2 hours. Treatment was continued at a lower dose for 24 hours. Seizure activity occurred in 76% of infants given thiopental and 73% of control infants at a mean age of 1.5 and 2.5 hours, respectively. Although initial arterial blood pressure was similar in both groups, hypotension occurred in 88% of treated and 60% of control infants. The amount of blood pressure support required was significantly greater (P less than 0.005) in the thiopental treatment group. Three infants died in the control group, and five in the treatment group. Developmental assessment was performed at a minimum of 12 months of age in 22 infants. There were no significant differences in neurologic, cognitive, or motor outcome between groups. Deteriorating performance over time was a consistent trend in both groups. These findings indicate that treatment of severe perinatal asphyxia with thiopental does not appear to have a cerebral sparing effect and may be associated with significant arterial hypotension.

Topics: Apgar Score; Asphyxia Neonatorum; Brain; Brain Ischemia; Child Development; Clinical Trials as Topic; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infusions, Parenteral; Intracranial Pressure; Neurologic Examination; Outcome and Process Assessment, Health Care; Random Allocation; Seizures; Thiopental

Topics: Adolescent; Adult; Aged; Brain Ischemia; Child; Child, Preschool; Clinical Trials as Topic; Data Collection; Female; Heart Arrest; Humans; Infant; Male; Middle Aged; Random Allocation; Resuscitation; Thiopental

Intracranial pressure (ICP), arterial blood pressure (BP) and the calculated cerebral perfusion pressure (CPP) were investigated under standard conditions in 14 patients with severe brain injury. The influence of etomidate 0.3 mg/kg in comparison with thiopentone 6.0 mg/mg was evaluated both in patients with primarily elevated ICP (group I) and with an increase of ICP produced by nitrous oxide in oxygen (group II). In both groups of patients a marked ICP reduction (42%/26%) was produced by etomidate as well as by thiopentone. Whereas the reduction of CPP caused by thiopentone was enhanced by a moderate fall in BP, no influence on either BP or CPP was observed with etomidate. A regular fall in BP by about 10-15% was observed under nitrous oxide in oxygen alone, subsequently reducing the CPP by about 25%. These results emphasize the importance of the actions and interactions of different combinations of anesthetics in patients with acute brain injury in the prevention of further brain ischaemia. We believe that etomidate like thiopentone has brain protective properties in patients with cerebral hypoxia and must therefore be considered as an important therapeutic agent in such patients.

Topics: Blood Pressure; Brain Injuries; Brain Ischemia; Etomidate; Humans; Imidazoles; Intracranial Pressure; Nitrous Oxide; Thiopental

Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8-15.3) vs. 19.5(18-24), p = 0.007)], bronchoconstriction index [2.28(2.08-2.36) vs. 2.64(2.53-2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1β compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1β compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

Topics: Animals; Brain; Brain Ischemia; Dexmedetomidine; Disease Models, Animal; Endothelial Cells; Hypnotics and Sedatives; Interleukin-1beta; Interleukin-6; Ischemic Stroke; Lung; Macrophages, Alveolar; Male; Propofol; Rats; Rats, Wistar; Thiopental; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Ischemic and traumatic brain injury is associated with increased risk for death and disability. The inhibition of penumbral tissue damage has been recognized as a target for therapeutic intervention, because cellular injury evolves progressively upon ATP-depletion and loss of ion homeostasis. In patients, thiopental is used to treat refractory intracranial hypertension by reducing intracranial pressure and cerebral metabolic demands; however, therapeutic benefits of thiopental-treatment are controversially discussed. In the present study we identified fundamental neuroprotective molecular mechanisms mediated by thiopental. Here we show that thiopental inhibits global protein synthesis, which preserves the intracellular energy metabolite content in oxygen-deprived human neuronal SK-N-SH cells or primary mouse cortical neurons and thus ameliorates hypoxic cell damage. Sensitivity to hypoxic damage was restored by pharmacologic repression of eukaryotic elongation factor 2 kinase. Translational inhibition was mediated by calcium influx, activation of the AMP-activated protein kinase, and inhibitory phosphorylation of eukaryotic elongation factor 2. Our results explain the reduction of cerebral metabolic demands during thiopental treatment. Cycloheximide also protected neurons from hypoxic cell death, indicating that translational inhibitors may generally reduce secondary brain injury. In conclusion our study demonstrates that therapeutic inhibition of global protein synthesis protects neurons from hypoxic damage by preserving energy balance in oxygen-deprived cells. Molecular evidence for thiopental-mediated neuroprotection favours a positive clinical evaluation of barbiturate treatment. The chemical structure of thiopental could represent a pharmacologically relevant scaffold for the development of new organ-protective compounds to ameliorate tissue damage when oxygen availability is limited.

Topics: Animals; Brain Injuries; Brain Ischemia; Cell Death; Cell Hypoxia; Cell Line; Elongation Factor 2 Kinase; Humans; Hypnotics and Sedatives; Mice; Neurons; Oxygen; Peptide Elongation Factor 2; Protein Biosynthesis; Thiopental

Thiopental is an anesthetic used for controlling high intracranial pressure (ICP) caused by brain surgery, brain trauma, and severe stroke. However, it remains controversial whether Thiopental is detrimental or beneficial in ischemic stroke. In this study, we used an animal model of ischemic stroke in spontaneously hypertensive rats to determine whether or not Thiopental is neuroprotective in the setting of brain ischemia. We observed that Thiopental caused a prolonged duration of unconsciousness with a high rate of mortality, that Thiopental created exaggerated neurological deficits that were revealed through limb placement tests at 4 days and 4 weeks after brain ischemia, and that infarct volume was increased in Thiopental-anesthetized rats. These data suggest that Thiopental is detrimental in ischemic stroke. Thus, our findings raise a caution about the use of Thiopental in the setting of ischemic stroke.

Topics: Anesthetics, Intravenous; Animals; Brain; Brain Ischemia; Chloral Hydrate; Disease Models, Animal; Dyskinesia, Drug-Induced; Magnesium Sulfate; Male; Methohexital; Pentobarbital; Random Allocation; Rats; Rats, Inbred SHR; Stroke; Thiopental; Time Factors; Treatment Outcome; Unconsciousness

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Brain; Brain Ischemia; Electroencephalography; Extracellular Space; Gerbillinae; Glutamic Acid; Halothane; Male; Microdialysis; Neurons; Neuroprotective Agents; Propofol; Thiopental; Time Factors

Increased release of glutamate is thought to contribute to ischemia-induced neuronal damage. Since general anesthetics such as thiopental and ketamine are thought to provide some degree of cerebral protection, this study was intended to 1) compare the effectiveness of ketamine and thiopental on ischemia-induced tissue damage; and, if so, 2) determine whether attenuation of the increased amino acid release is the sole mechanism for the protective effects demonstrated. Striatal slices prepared from Wistar Albino rats were incubated in an ischemic medium for 1 hour followed by 5 hours in a reoxygenation (REO) medium. Ketamine and thiopental were added medium during ischemia and/or REO periods, and the medium was collected at the end of each incubation period for measurement of amino acid release and lactate dehydrogenase (LDH) leakage. Ischemia significantly increased amino acid release without altering LDH leakage. Ischemia-induced increments in glutamate and aspartic acid releases returned to control levels during REO, but LDH leakage increased (P > 0.001) during this period. Although ketamine (100 microM) and thiopental (100 microM) failed to decrease ischemia-induced excitatory amino acid release, they protected the slices against REO-induced LDH leakage. Ketamine, but not thiopental, was effective even if added after ischemia (P < 0.05). These results indicate that ketamine and thiopental protect the slices against REO-induced LDH leakage. However, mechanisms other than attenuation of the enhanced glutamate release might be responsible for their protective effects.

Topics: Amino Acids; Anesthetics, Dissociative; Anesthetics, Intravenous; Animals; Brain Ischemia; Female; In Vitro Techniques; Ketamine; L-Lactate Dehydrogenase; Male; Proteins; Rats; Rats, Wistar; Reperfusion; Thiopental

To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices.. Cerebral cortical slices were incubated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine, midazolam, thiopental, and propofol were quantitatively evaluated by ELISA reader of absorbance (A) at 490 nm, which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured.. Progressive prolongation of OGD resulted in decreases of TTC staining. The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD (P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited the decrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 micromol/L) and thiopental (400 micromol/L) partly attenuated this decrease. Propofol at high concentration (100 micromol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01).. Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

Topics: Anesthetics, Intravenous; Animals; Brain Ischemia; Cell Hypoxia; Cerebral Cortex; Glucose; In Vitro Techniques; Ketamine; Male; Midazolam; Neuroprotective Agents; Propofol; Rats; Rats, Sprague-Dawley; Thiopental

To observe the effects of lidocaine and thiopental on the neuronal injury induced by the experimental ischemia in hippocampus slice cultures obtained from postnatal 22 days SD rats.. Model of the experimental ischemia was produced by hypoxia and glucose deprivation. Propidium iodide (PI) assay was used to observe the neuronal injury in CA1 and dentate gyrus (DG).. After experimental ischemia, the peak of PI index was appeared in CA1 and DG on the first day (P < 0.01), PI index in DG was less than in CA1 (P < 0.01). PI indices were still higher during seven days after the experimental ischemia than before the experimental ischemia (P < 0.01). 10 nmol/L and 100 nmol/L concentration of lidocaine could significantly decrease PI indices in CA1 and DG (P < 0.01). 250 nmol/L and 600 nmol/L concentration of thiopental also decreased the PI indices in CA1 and DG (P < 0.01). The neuronal injury peaks were postponed to the third day after the experimental ischemia by lidocaine and thiopental.. It suggested that lidocaine and thiopental could decrease the neuronal injury in CA1 and DG induced by the experimental ischemia, and postpone the neuronal injury peaks to the third day after the experimental ischemia.

Topics: Animals; Brain Ischemia; CA1 Region, Hippocampal; In Vitro Techniques; Lidocaine; Neurons; Rats; Thiopental

To investigate the effects of propofol, midazolam and thiopental sodium on outcomes and amino acid accumulation in focal cerebral ischemia-reperfusion in rats.. Male Sprague Dawley (SD) rats were scheduled to undergo 3-hour middle cerebral artery occlusion by intraluminal suture and 24-hour reperfusion. Neurologic outcomes were scored on a 0-5 grading scale. Infarct volume was shown with triphenyltetrazolium chloride staining and measured by an image analysis system. Concentrations of various amino acids (aspartate, glutamate, glycine, taurine, and gama-aminobutyric acid) were measured after 3 hours of reperfusion using high performance liquid chromatography. Propofol, midazolam and thiopental sodium were given intraperitoneally at the beginning of reperfusion.. Both propofol and midazolam attenuated neurological deficits and reduced infarct and edema volumes. Propofol showed better neurological protection than midazolam while thiopental sodium did not exhibit any protective effect. Both propofol and midazolam decreased excitatory amino acids accumulation, while propofol increased gama-aminobutyric acid accumulation in ischemic areas in reperfusion.. Propofol and midazolam, but not thiopental sodium, may provide protective effects against reperfusion induced injury in rats subjected to focal cerebral ischemia. This neurological protection may be due to the acceleration of excitatory amino acids elimination in reperfusion.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Edema; Brain Ischemia; Excitatory Amino Acids; Male; Midazolam; Myocardial Infarction; Neuroprotective Agents; Propofol; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thiopental

Glutamate transporters may be important targets for anesthetic action in the central nervous system. The authors investigated the effects of the intravenous anesthetics, thiopental and ketamine, and the local anesthetics, lidocaine and bupivacaine, on the activity of glutamate transporter type 2, EAAT2. EAAT2 was expressed in Xenopus oocytes by injection of its mRNA. By using two-electrode voltage clamping, membrane currents were recorded after the application of L-glutamate (30 microM) in the presence or absence of various concentrations of anesthetics. Lidocaine and bupivacaine did not change glutamate-induced inward currents at the tested concentrations (1-1000 microM). Thiopental and ketamine also did not affect the activity of EAAT2 at the tested concentrations (0.3-300 microM). Our results suggest that the two commonly used local anesthetics (lidocaine and bupivacaine) and intravenous anesthetics (thiopental and ketamine) do not affect the activity of EAAT2 expressed in oocytes. EAAT2 may not be a target for these anesthetics.

Topics: Anesthetics, Intravenous; Anesthetics, Local; Animals; Brain Ischemia; Bupivacaine; Cell Membrane; Excitatory Amino Acid Transporter 2; Female; Glutamic Acid; Ketamine; Lidocaine; Neuroprotective Agents; Oocytes; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Synaptic Transmission; Thiopental; Xenopus laevis

Cellular swelling has been implicated as an early process after cerebral ischemia. We compared the effects of two commonly used IV anesthetics, thiopental and propofol, on hippocampal CA1 pyramidal cell swelling induced by oxygen/glucose deprivation (OGD) in vitro. Experiments were performed in rat hippocampal slices. Cell swelling in the CA1 pyramidal cell layer was evaluated by determining light transmittance (LT) change through the slices and by histopathological examination. For LT experiments, OGD was induced for 10 min by superfusing slices with glucose-free artificial cerebrospinal fluid equilibrated with 95% nitrogen and 5% CO(2). Thiopental and propofol were present 10 min before and during the period of OGD. The results showed that thiopental (100 and 400 microM), but not propofol (40 and 160 microM), significantly prolonged latency to the peak of LT increase after the onset of OGD. Consistent with the LT experiments, histopathological examination revealed that thiopental, but not propofol, attenuated CA1 pyramidal cell expansion and the gap diminution between CA1 pyramidal cells induced by OGD. These results suggest that thiopental, but not propofol, reduces the neuronal cell swelling caused by OGD. Whether the reduction of cell swelling is related to reduction in cell injury caused by OGD remains to be investigated.. We demonstrated that thiopental, but not propofol, attenuates ischemic neuronal swelling induced by oxygen/glucose deprivation in an in vitro ischemic model.

Topics: Animals; Brain; Brain Ischemia; Glucose; Hippocampus; Male; Oxygen; Propofol; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Thiopental

We report a case of carotid endarterectomy and clipping of an ipsilateral internal carotid artery aneurysm in a patient with complete contralateral carotid stenosis. The patient developed an ischaemic electroencephalographic (EEG) tracing on temporary carotid clamping and bypass shunt was contraindicated. We used thiopentone titrated to EEG burst suppression for pharmacological cerebral protection during the subsequent prolonged carotid clamp necessary for carotid endarterectomy. We review the use of thiopentone for this purpose, in particular the evidence for efficacy, mechanism of action and optimal dosage and timing of administration.

Topics: Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Constriction; Electroencephalography; Endarterectomy, Carotid; Female; Humans; Hypnotics and Sedatives; Intracranial Aneurysm; Intraoperative Complications; Middle Aged; Neuroprotective Agents; Thiopental

We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4 degrees C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24 degrees C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20-28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received assisted circulation to 2 h, 34 degrees C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24 degrees C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n=14). In group 2 (n=9), thiopental (variable total doses of 15-120 mg/kg) was added to the flush and given with reperfusion. In group 3 (n=7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36 degrees C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 (p=0.5). Median NDS were 36% (IQR 22-62%) in group 1; 51% (IQR 22-56%) in group 2; and 55% (IQR 38-59%) in group 3 (p=0.7). Median total HDS were 67 (IQR 56-127) in group 1; 60 (IQR 52-138) in group 2; and 76 (IQR 48-132) in group 3 (p=1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can cons

Topics: Animals; Anticonvulsants; Aorta, Thoracic; Brain Ischemia; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Dogs; Heart Arrest; Hypnotics and Sedatives; Male; Phenytoin; Reperfusion Injury; Thiopental; Time Factors

Although barbiturates are considered to be cerebral protectants, little is known regarding the relative efficacy of different barbiturates to reduce ischemic brain injury. In a model of middle cerebral artery occlusion (MCAo), we compared the relative effects of 1.0 and 0.4 burst-suppression doses of thiopentone, methohexital, and pentobarbitone on cerebral infarct.. During isoflurane anesthesia, MCAo was achieved via a temporal craniotomy. Thirty minutes before MCAo the rats were randomized to receive one of the following which was maintained throughout the study. Halothane (n=20)-1.2 MAC halothane, thiopentone (n=20), methohexital (n=20), or pentobarbitone (n=20). The first ten animals in each barbiturate group received the respective barbiturate in a dose sufficient to maintain burst-suppression of the electroencephalogram (3-5 bursts x min(-1)). The subsequent ten animals in each barbiturate group received 40% of the burst-suppression dose. After 180 min of MCAo and 120 min of reperfusion, cerebral injury was assessed.. For the burst-suppression animals, injury volume (mm3, mean +/- SD) was less in the thiopentone group (88 +/- 14) than the halothane (133 +/- 17), methohexital (126 +/- 19), or pentobarbitone (130 +/- 17) groups (P <0.05). For 0.4 burst-suppression animals, injury volume was less for the methohexital group (70 +/- 22) than the halothane (124 +/- 24), thiopentone (118 +/- 15), or pentobarbitone (121 +/- 20) groups (P <0.05).. These data are inconsistent with the longstanding assumption that electrophysiologically comparable doses of the various classes of barbiturates have equivalent protective efficacy. They in turn suggest that mechanisms other than, or at least in addition to, metabolic suppression may contribute to the protective effect of barbiturates.

Topics: Animals; Brain; Brain Ischemia; Calcium; Electroencephalography; Free Radicals; Glutamic Acid; Male; Methohexital; Nitric Oxide; Pentobarbital; Rats; Rats, Inbred SHR; Thiopental

General anesthetics reduce neuron loss following focal cerebral ischemia in rodents. The relative efficacy of this action among different anesthetics clinically used for neuroprotection is uncertain. In addition, it remains unclear how anesthetics compare to neuroprotection afforded by mild hypothermia. This study was performed to evaluate the comparative effects of isoflurane, sodium pentothal, and mild hypothermia in a hippocampal slice model of cerebral ischemia and to determine if the mechanism of neuroprotection of isoflurane involves inhibition of glutamate excitotoxicity.. Survival and morphology of CA1, CA3, and dentate gyrus neurons in rat hippocampal slices were examined after 10 or 20 min of combined oxygen-glucose deprivation (in vitro ischemia) followed by a 5-h recovery period.. 10 or 20 min in vitro ischemia at 37 degrees C killed 35-40% of neurons in CA1 (P < 0.001), 6% in CA3 (not significant) and 18% in dentate (P < 0.05). Isoflurane (0.7 and 2.0%, approximately 0.45 and 1.5 minimum alveolar concentration), pentothal (50 microm, approximately 1 minimum alveolar concentration equivalent) and mild hypothermia (34 degrees C) all reduced CA1 cell loss and morphologic damage to similar degrees in 10- and 20-min periods of ischemia (P < 0.001). The noncompetitive N-methyl-D-aspartate antagonist MK-801 prevented cell damage, showing that N-methyl-D-aspartate receptor activation is an important mechanism of injury in this model. Glutamate (1 mm) produced cell loss similar to in vitro ischemia. Isoflurane (2%) prevented cell damage from glutamate exposure.. In hippocampal slices, neuron death from simulated ischemia was predominately due to activation of glutamate receptors. Isoflurane, sodium pentothal, an N-methyl-D-aspartate receptor antagonist, and mild hypothermia prevented cell death to similar degrees. For isoflurane, the mechanism appears to involve attenuation of glutamate excitotoxicity.

Topics: Anesthetics; Animals; Brain Ischemia; Cell Death; Hippocampus; Hypothermia; Hypoxia; Isoflurane; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Thiopental

One of the most important disadvantages of the hypothermic circulatory arrest technique is the limited time allowable for circulatory arrest. Thiopental is usually used to protect the brain against ischemic injuries. However, it remains uncertain how well thiopental reduces cerebral metabolism. We investigated its effectiveness by comparing outcomes after different doses.. Fifty patients who underwent aortic arch repair with hypothermic circulatory arrest had their records reviewed. Electroencephalograms (EEG) and partial pressures of oxygen in the internal jugular vein (PjO2) were monitored. Following confirmation of total disappearance of EEG activity, 15 or 30 mg/kg thiopental was administered before circulatory arrest Th duration of circulatory arrest ranged from 16 to 77 min.. Hospital mortality rate was 10% and 4 (8%) patients developed neu-rologic complications, but 3 of them were transient. After thiopental infusion, PjO2 increased significantly from 430 to 499mmHg (p <0.01), indicating that thiopental reduces cerebral oxygen consumption. The rate of the decrease in PjO2 during circulatory arrest was slower with the higher thiopental dose, suggesting that thiopental lowered the cerebral metabolic rate of oxygen during circulatory arrest.. It appears that thiopental has protective effects against cerebral ischemia under profound hypothermia.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm, Thoracic; Brain; Brain Ischemia; Female; Heart Arrest, Induced; Humans; Hypothermia, Induced; Male; Middle Aged; Oxygen Consumption; Thiopental; Treatment Outcome

Thiopental has been shown to protect against cerebral ischemic damage; however, it has undesirable side effects. We have examined how thiopental alters histological, physiological, and biochemical changes during and after hypoxia. These experiments should enable the discovery of agents that share some of the beneficial effects of thiopental.. We made intracellular recordings and measured ATP, sodium, potassium, and calcium concentrations from CA1 pyramidal cells in rat hippocampal slices subjected to 10 minutes of hypoxia with and without 600 micromol/L thiopental.. Thiopental delayed the time until complete depolarization (21+/-3 versus 11+/-2 minutes for treated versus untreated slices, respectively) and attenuated the level of depolarization at 10 minutes of hypoxia (-33+/-6 versus -12+/-5 mV). There was improved recovery of the resting potential after 10 minutes of hypoxia in slices treated with thiopental (89% versus 31% recovery). Thiopental attenuated the changes in sodium (140% versus 193% of prehypoxic concentration), potassium (62% versus 46%), and calcium (111% versus 197%) during 10 minutes of hypoxia. There was only a small effect on ATP (18% versus 8%). The percentage of cells showing clear histological damage was decreased by thiopental (45% versus 71%), and thiopental improved protein synthesis after hypoxia (75% versus 20%).. Thiopental attenuates neuronal depolarization, an increase in cellular sodium and calcium concentrations, and a decrease in cellular potassium and ATP concentrations during hypoxia. These effects may explain the reduced histological, protein synthetic, and electrophysiological damage to CA1 pyramidal cells after hypoxia with thiopental.

Topics: Action Potentials; Adenosine Triphosphate; Animals; Biochemical Phenomena; Biochemistry; Brain Ischemia; Calcium; Electrophysiology; Hippocampus; Hypnotics and Sedatives; Hypoxia, Brain; Male; Membrane Potentials; Neurons; Neuroprotective Agents; Potassium; Protein Biosynthesis; Proteins; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Sodium; Thiopental

Many studies demonstrate an association between brain damage and the extracellular release of catecholamines and amino acids during cerebral ischemia. While the clinical value of hypothermia during periods of compromised cerebral blood flow and oxygen delivery is well established, the role of anesthetic agents is less clear. Furthermore, the interaction between these agents and hypothermia remains to be elucidated. The purpose of this study was to examine the interactive effects of temperature, sodium thiopental (STP) and etomidate (ETOM) on extracellular neurotransmitter accumulation in the rat corpus striatum during cerebral ischemia.. Animals were randomly assigned to one of six subgroups: normal saline (NS-norm, pericranial t approximately equal to 37 degrees C, and NS-hypo, t=30 degrees C), etomidate (ETOM-norm and ETOM-hypo), and sodium thiopental (STP-norm and STP-hypo). Microdialysis probes were inserted into the corpus striatum. Dopamine (DA), glutamate, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were measured. At zero minutes, animals received a 10-min infusion of STP (3 mg x kg(-1) x min(-1)), ETOM (0.6 mg x kg(-1) x min(-1)), or NS. Prior to ischemia, animals were given either intravenous STP (10 mg x kg(-1)), ETOM (3 mg x kg(-1)), or NS in bolus form. Each animal was then subjected to 10 min of forebrain ischemia (Is1) followed by a reperfusion interval (Rep1). The entire sequence was then repeated.. There were significant interactions between temperature and drug for DA (Is1, P=0.006, Is2, P=0.032) and its metabolites (DOPAC, Is1 P=0.01, HVA, Is1 P=0.03), and for glutamate (Is1, P=0.03, Is2 P=0.06). The nature of this interaction differed for DA and glutamate. The reduction in DA accumulation seen during hypothermia was offset by the addition of either STP or ETOM, whereas the addition of these drugs did not affect the reduced glutamate levels seen with hypothermia. During normothermia, STP and ETOM resulted in diminished DA accumulation compared to controls, yet they increased the accumulation of extracellular glutamate.. Consistent with other studies, hypothermia was associated with diminished extracellular DA concentrations during forebrain ischemia. However, depending on the temperature condition, the addition of STP or ETOM in our forebrain ischemia model led to unexpected findings. The administration of these agents during normothermia diminished ischemia-induced DA accumulation yet resulted in significantly higher concentrations of extracellular glutamate. In contrast, STP and ETOM during hypothermia were noted to significantly offset the DA-reducing effects of hypothermia.

Topics: 3,4-Dihydroxyphenylacetic Acid; Anesthetics, Intravenous; Animals; Blood Pressure; Brain Ischemia; Carbon Dioxide; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; Etomidate; Glutamic Acid; Homovanillic Acid; Hydrogen-Ion Concentration; Hypothermia, Induced; Male; Microdialysis; Prosencephalon; Rats; Rats, Inbred WKY; Reperfusion; Thiopental

Temporary interruption or reduction of cerebral blood flow during cerebrovascular surgery may rapidly result in ischemia or cerebral infarction. Thiopental has been shown to have cerebroprotective effects. However, the cerebroprotective dose of thiopental causes burst suppression of the EEG, thus this parameter cannot be used continuously for the detection of metabolic changes in the brain during thiopental anaesthesia. This study was performed in order to examine whether the multiparametric assembly (MPA), which measures energy metabolism CBF and mitochondrial (NADH) as well as extracellular ion concentrations (K+), can shed light on the mechanism of the cerebroprotective effects of thiopental. The MPA was placed on the brain of Mongolian gerbils and burst suppression of the ECoG was induced by thiopental. Cerebral ischemia was induced by occlusion of carotid arteries after burst suppression. Burst suppression of the ECoG was accompanied by a significant decrease in cerebral blood flow. In animals that received thiopental prior to ischemia, NADH increased to a lesser degree and extracellular potassium ion concentration increased to a lesser degree than in the control animals, indicating that thiopental affords protection of the brain under ischemic conditions due to improved energy metabolism. This study also demonstrates that the MPA can monitor changes occurring in the cerebral cortex even after the ECoG can no longer be used. Those findings have a significant value in the development of a new clinical monitoring device.

Topics: Animals; Arterial Occlusive Diseases; Brain Ischemia; Carotid Arteries; Cerebral Cortex; Cerebrovascular Circulation; Electroencephalography; Extracellular Space; GABA Modulators; Gerbillinae; Mitochondria; Neuroprotective Agents; Oxidation-Reduction; Potassium; Thiopental

This study examined the effects of thiopental on intracellular calcium ([Ca2+]i) changes induced by membrane depolarization, N-methyl-D-aspartate (NMDA) receptor activation, and ischemia.. Experiments were performed in brain slices prepared from Wistar rats. [Ca2+]i measurements were taken on the CA1 pyramidal cell layer of the hippocampus or layers II to III of the somatosensory cortex using the fura-2 fluorescence technique. Membrane depolarization and NMDA receptor activation were induced by exposing slices to 60 mM K+ and 100 microM NMDA, respectively. In vitro ischemia was induced by superfusing slices with glucose-free Krebs solution equilibrated with 95% nitrogen and 5% carbon dioxide. Thiopental was applied 5 min before application of high K+ and NMDA, or before in vitro ischemia.. Ischemia for 15 min produced a characteristic [Ca2+]i increase in both hippocampal and cortical slices. Thiopental prolonged the latency to the appearance of the [Ca2+]i plateau and reduced the magnitudes of increase in [Ca2+]i 8, 10, and 15 min after the onset of ischemia. Thiopental also suppressed the high K+- and NMDA-induced [Ca2+]i increases. The NMDA-induced [Ca2+]i increases were attenuated to a greater extent in cortical slices than were those in hippocampal slices. The inhibition of thiopental on the 200-microM NMDA-mediated [Ca2+]i response was confirmed in cultured cortical neurons.. The results indicate that thiopental attenuates ischemia-induced [Ca2+]i increases in the hippocampus and cortex in vitro, probably because of its inhibition of both voltage-gated calcium channels and NMDA receptors. The regionally different inhibition of thiopental on NMDA receptors may relate to its region-specific action against ischemia.

Topics: Anesthetics, Intravenous; Animals; Brain Ischemia; Calcium; Cerebral Cortex; Fura-2; Glucose; Hippocampus; Hypoxia, Brain; Male; Membrane Potentials; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Thiopental

The purpose of this study was to validate the commonly accepted indicators of risk of ischemic stroke that indicate the necessity for cerebral protection during carotid endarterectomy (CEA), and to examine the efficacy of high-dose thiopentone sodium (thiopental) as a cerebral protection method in patients who are at high risk of intraoperative ischemic stroke.. In a prospective study of 37 CEAs performed for symptomatic stenosis > 70%, functional and clinical indicators of risk of ischemic stroke during carotid cross-clamping were identified. Functional indicators of risk were the development of ischemic electro-encephalogram (EEG) changes and stump pressure < 25 mm Hg. Clinical indicators of risk were previous ischemic hemispheric stroke and severe bilateral disease. These indicators were correlated in all patients, some of whom had two or three coexisting indicators of risk. The EEG and stump pressure were monitored continuously during carotid occlusion in all operations. Carotid occlusion times were recorded. Intraluminal shunting was eliminated in favor of high-dose thiopental cerebral protection in all patients. Neurologic outcome was deemed to measure the efficacy of thiopental protection in patients who are identified to be at risk and, hence, in need of cerebral protection. The validity of the indicators used to identify risk of ischemic stroke during CEA was assessed.. The absolute stroke risk was found to be 29.7% for the whole group (37 patients) and 57.9% in 19 patients who had commonly accepted indications for protective shunting. The correlation of ischemic EEG changes with stump pressure < 25 mm Hg was only 27.3%, whereas the expected correlation based on well-documented reports in the literature was 100%. The lack of correlation may have been related to the prevention of ischemic EEG changes by thiopental. There were no neurologic deficits in the series.. The absence of neurologic deficit in the study indicated that thiopental protection was effective in preventing ischemic stroke in high-risk patients and safely replaced intraluminal shunting.

Topics: Aged; Aged, 80 and over; Blood Pressure; Brain Ischemia; Carotid Arteries; Carotid Stenosis; Cerebrovascular Circulation; Cerebrovascular Disorders; Constriction; Electroencephalography; Endarterectomy, Carotid; Female; Hemodynamics; Humans; Intraoperative Complications; Male; Middle Aged; Monitoring, Intraoperative; Neurologic Examination; Neuroprotective Agents; Prospective Studies; Reproducibility of Results; Risk Assessment; Risk Factors; Thiopental; Time Factors; Treatment Outcome

Intraoperative monitoring of brain function may influence the outcome of carotid endarterectomy (CEA).. We performed transcranial Doppler (TCD) monitoring of middle cerebral artery blood flow velocities (VMCAs) and eight-channel electroencephalographic (EEG) recording simultaneously in 82 patients undergoing CEA. Thiopental narcosis limited EEG interpretation in 11 patients, thus allowing direct comparison of both methods in 71 patients.. There was a significant correlation between VMCA decrease and the frequency of EEG changes after carotid clamping (P < .001). Eight patients (11%) showed a VMCA decrease exceeding 60%, accompanied by EEG changes in 7 patients. Altogether, 16 patients (22%) showed severe or moderate EEG changes. Stenosis or occlusion of the contralateral carotid artery led to an increase of abnormal findings with both monitoring methods, which was, however, significant only for TCD (P < .05). Four patients (4.8%) suffered intraoperative transient ischemic attacks. In 3 of these patients, there were no abnormal findings with either of the methods. The events were thus unpredictable and probably of embolic origin. The fourth patient showed VMCA decrease to 0 and severe EEG changes. Nine patients had severe or moderate EEG changes without significant VMCA decrease and without complications. EEG monitoring alone in these would have led to unnecessary use of a shunt with the increased risk of embolism.. EEG and TCD monitoring are complementary techniques. Their results showed a good overall correlation but with marked differences in the individual patient. TCD monitoring alone was sensitive enough to prevent ischemic intraoperative complications. EEG findings are of limited value when barbiturates are used.

Topics: Aged; Aged, 80 and over; Blood Flow Velocity; Brain Ischemia; Carotid Stenosis; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Electroencephalography; Endarterectomy, Carotid; Female; Humans; Hypnotics and Sedatives; Ischemic Attack, Transient; Male; Middle Aged; Monitoring, Intraoperative; Postoperative Complications; Predictive Value of Tests; Retrospective Studies; Thiopental; Treatment Outcome; Ultrasonography, Doppler, Transcranial

Retrograde cerebral perfusion through the superior vena cava (SVC) has been proposed to protect the brain from ischaemic injury during profound hypothermic circulatory arrest (PHCA). Its contribution to cerebral protection is unclear. Furthermore, the addition of anaesthetic or vasodilating agents to the SVC perfusate to enhance brain protection, has never been described.. In three patients undergoing repair of the ascending aorta utilizing PHCA, the upper body was retrogradely perfused with cold (16 degrees C) blood through the SVC by the cardiopulmonary bypass pump. Electroencephalographic activity was monitored using a computerized electroencephalographic monitor (Cerebro Trac 2500, SRD). Perfusion pressure was measured at a port in the cannula connector. Etomidate or thiopentone was injected into the SVC perfusate to arrest reappearing electroencephalographic activity. Nitroglycerin or nitroprusside was injected into the perfusate to increase retrograde flow and maintain a constant perfusion pressure.. During PHCA periods of up to 61 min, recurrent electroencephalographic activity was abolished by the retrograde administration of small boluses of etomidate (total 50 mg) or thiopentone (total 500 mg). Nitroprusside (100 micrograms) and nitroglycerin (2 micrograms.kg-1.min-1) increased retrograde flow from 220 to 550 and 660 ml.min-1, respectively, while maintaining perfusion pressure (25-26 mmHg). Recovery from anaesthesia and surgery was uneventful, with no adverse neurological sequelae.. Injection of anaesthetic agents into the retrograde SVC perfusate during PHCA, can suppress reoccurring electroencephalographic activity and retrograde injection of vasodilators can facilitate an increase in perfusion. It is suggested that both may augment brain protection.

Topics: Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Brain Ischemia; Electrocardiography; Electroencephalography; Etomidate; Heart Arrest, Induced; Humans; Hypothermia, Induced; Male; Middle Aged; Nitroglycerin; Nitroprusside; Perfusion; Thiopental; Vasodilator Agents; Vena Cava, Superior

In an earlier study on the effect of mild hypothermia (34 degrees C) on the cerebral metabolic rate for oxygen (CMRO2) in rats, we used norepinephrine (NE) to support arterial blood pressure while inducing isoelectricity on the electroencephalogram (EEG) with thiopental (TP). Even with administration of sufficient TP to reduce a fully active EEG to an isoelectric EEG, CMRO2 was often unchanged. Based on this observation, we hypothesized that NE had activated CMRO2 despite thiopental coma. Therefore, we studied the effect of NE compared with donor blood (DB) infusion to maintain arterial blood pressure during TP-induced isoelectric EEG on whole-brain CBF (H2 clearance) and CMRO2 during normothermia (38 degrees C) and mild hypothermia (34 degrees C) in rats during 70% N2O/30% O2 analgesia. Cerebral blood flow (CBF) and CMRO2 were measured in four groups of rats at 38 degrees C followed by measurements at either 38 degrees C (two groups) or 34 degrees C (two groups) and during TP-induced EEG isoelectricity. Within each of the two groups at 38 degrees C and 34 degrees C, arterial pressure was sustained by either DB (n = 10) or NE (n = 9) infusion. At 38 degrees C, CMRO2 in the DB and NE groups was 7.92 +/- 1.05 and 6.4 +/- 0.80 mL x 100 g-1.min-1 and decreased to 50% of normal (3.95 +/- 0.70 and 3.32 +/- 0.40 mL x 100 g-1.min-1, respectively) during TP isoelectricity for a functional:basal CMRO2 distribution of 50% +/- 4% and 50% +/- 4%. At 34 degrees C, CMRO2 values in the DB and NE groups were 6.31 +/- 1.41 and 5.41 +/- 2.02 mL x 100 g-1.min-1, respectively. During TP-induced isoelectricity, CMRO2 values in both groups were reduced to 2.37 +/- 0.43 and 3.55 +/- 1.27 mL x 100g-1.min-1, respectively, resulting in a functional:basal CMRO2 distribution of 61%:38% in the DB group and the reverse, or 27%:73%, in the Ne group. Basal CMRO2 was significantly (P < 0.05) larger in the NE-infused rats. These results suggest that NE infusion, by increasing CMRO2 during mild hypothermia, could nullify its protective effects in the ischemic brain.

Topics: Adrenergic alpha-Agonists; Analgesics; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Blood Pressure; Blood Transfusion; Body Temperature; Brain; Brain Ischemia; Cerebrovascular Circulation; Coma; Electroencephalography; Hypothermia; Hypothermia, Induced; Male; Neuroprotective Agents; Nitrous Oxide; Norepinephrine; Oxygen Consumption; Rats; Rats, Wistar; Thiopental

Thiopental, a barbiturate anesthetic, which at high doses suppresses cortical electroencephalogram activity, was evaluated as a neuroprotective agent in a dog model of reversible, hindbrain ischemia. Fourteen dogs were exposed to 20 minutes of isolated brain stem ischemia after pretreatment with 35 mg per kg of thiopental or placebo. Brain stem auditory evoked potentials (BAEPs) and regional cerebral blood flow were measured before and during the ischemia and for 5 hours after reperfusion. During the ischemic period, both control and thiopental-treated animals experienced dramatic declines in the BAEPs to less than 10% of baseline. On reperfusion for 30 minutes, the BAEPs increased in both groups to near 40% of baseline. In the thiopental-treated animals, the BAEPs continued to recover variably to a mean of 70% of baseline by 5 hours of reperfusion. In contrast, untreated animals showed a decline in BAEPs after 30 minutes of reperfusion. The improved recovery of BAEPs in the thiopental-treated animals suggests that thiopental may be of some value as a cerebroprotective agent, although the mechanism remains unclear. The variability in recovery in this group implies that other factors play a significant role in mediating functional recovery from ischemic brain stem damage.

Topics: Anesthetics, Intravenous; Animals; Brain Ischemia; Brain Stem; Dogs; Evoked Potentials, Auditory, Brain Stem; Female; Male; Reaction Time; Regional Blood Flow; Reperfusion Injury; Thiopental

Etomidate and thiopental reduce ischemic neuronal injury but the mechanism by which they do so is not clear. Ischemia-induced release of the excitatory neurotransmitters glutamate and glycine is thought to play a major role in the pathophysiology of ischemic injury. To determine how etomidate and thiopental modulate excitatory transmitter release, their effect on the release of glycine and glutamate during ischemia was evaluated by microdialysis in the hippocampus and cortex of rats. Three groups of Wistar-Kyoto rats (n = 5/group) were studied. In the etomidate and thiopental groups, electroencephalogram (EEG) burst-suppression was achieved and maintained by a continuous infusion of either etomidate (0.6 mg.kg-1.min-1) or thiopental (3 mg.kg-1.min-1) 40 min prior to ischemia. Halothane anesthetized (1 minimum alveolar anesthetic concentration [MAC]) rats served as controls. Ischemia was induced in all three groups by bilateral carotid artery occlusion with simultaneous hypotension to 35 mm Hg for 10 min. Pericranial temperature was controlled at 38 degrees C. Dialysate was collected before, during, and after ischemia. The levels of glutamate and glycine in the dialysate were measured by high-performance liquid chromatography. Within the hippocampus, both glutamate and glycine levels increased significantly in the thiopental and control groups. By contrast, in the etomidate group, glutamate and glycine levels did not increase during ischemia, and peak levels were significantly less than those in the thiopental group. Peak glutamate levels in the thiopental group were significantly larger than in the control group, whereas the peak glycine levels were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Ischemia; Chromatography, High Pressure Liquid; Etomidate; Glutamic Acid; Glycine; Hippocampus; Parietal Lobe; Prosencephalon; Rats; Rats, Inbred WKY; Thiopental

An investigation was performed to compare the cerebral protective properties of etomidate, isoflurane, and thiopental. In separate groups of spontaneously hypertensive rats, etomidate, isoflurane, or thiopental was administered to achieve and maintain burst-suppression of the electroencephalogram (3-5 bursts/min) for the duration of the experiment. A fourth group received 1.2 minimal alveolar concentration halothane. All groups underwent 3 hours of middle cerebral artery occlusion and then 2 hours of reperfusion. Thereafter, the animals were killed and the volume of injured brain was determined by staining with 2,3,5-triphenyltetrazolium. Physiological parameters did not differ among the four groups during the investigation, with the exception that hemolysis occurred in the etomidate group (free hemoglobin levels, approximately 0.4 g.dl-1). The volume of injured brain in the thiopental group (56 +/- 10 mm3) was significantly smaller than that in the halothane control group (99 +/- 13 mm3). The volumes of injured brain in the etomidate and isoflurane groups (145 +/- 11 mm3 and 139 +/- 14 mm3, respectively) were significantly larger than those in the control and thiopental groups. We speculate that the apparently detrimental effect of etomidate may be the result of the binding of nitric oxide of cerebral endothelial origin by the iron component of free hemoglobin. Intracranial pressure was not recorded, and in the isoflurane group, there may have been adverse effects on cerebral perfusion pressure associated with vasodilation caused by high concentrations of isoflurane. The results are consistent with a protective effect by barbiturates.

Topics: Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Brain; Brain Damage, Chronic; Brain Ischemia; Dose-Response Relationship, Drug; Etomidate; Halothane; Hemolysis; Isoflurane; Male; Rats; Rats, Inbred SHR; Regional Blood Flow; Thiopental

Topics: Animals; Barbiturates; Brain; Brain Ischemia; Coronary Circulation; Cryotherapy; Disease Models, Animal; Evaluation Studies as Topic; Hypothermia; Male; Norepinephrine; Oxygen Consumption; Rats; Rats, Wistar; Thiopental

This study reports our experience with thiopental sodium (Pentothal) cerebral protection, without intraluminal shunting, during carotid endarterectomy. Only those complications that occurred during surgery or within 30 days of operation have been addressed.. A prospective, unselected, consecutive series of 621 carotid endarterectomies was done during a 7-year period, with electroencephalography-monitored, high-dose Pentothal for cerebral protection.. Five ischemic strokes (0.8%), completion of two strokes-in-evolution (0.3%) and four strokes caused by cerebral hemorrhage (0.6%) occurred in 11 patients in the perioperative (30-day) period, for a combined cerebral morbidity-mortality rate of 1.7%. Four reversible ischemic neurologic deficits (0.6%) and two transient ischemic attacks (0.3%) in six patients produced a transient deficit rate of 0.9%. Symptomatic coronary artery disease coexisted in 37% of the patients but resulted in only five acute myocardial infarctions (0.7%), one of which was fatal (0.1%). Other perioperative complications in 10 patients (1.5%) were associated with the operative procedure. There were no complications directly attributable to the high-dose Pentothal. Prospective data collection has allowed definition of the disease and cause of all cerebral complications.. The complications in this series have been related to surgical and clinical management problems rather than failure of cerebral protection. Cerebral protection with high-dose Pentothal under electroencephalographic control has been effective and complication free.

Topics: Aged; Brain Ischemia; Carotid Stenosis; Electroencephalography; Endarterectomy, Carotid; Female; Humans; Intraoperative Care; Intraoperative Complications; Male; Monitoring, Intraoperative; Morbidity; Postoperative Complications; Prospective Studies; Thiopental

We evaluated the effect of etomidate, thiopental, and isoflurane on ischemic neuronal injury in rats. Control group animals received 1.2% isoflurane. The animals in the etomidate and thiopental groups received an infusion of either etomidate or thiopental until electroencephalographic (EEG) burst-suppression was attained. In the fourth group, the isoflurane concentration was increased to 3% (sufficient to produce EEG burst-suppression). Forebrain ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension for 10 min. Three days after ischemia, two blinded observers evaluated neuronal injury in coronal brain sections stained with hematoxylin and eosin. Injury to the ventral CA1 of the hippocampus was less in the etomidate group than in the control group. Injury to the entorhinal cortex was less in the thiopental group than in the control group. Histopathologic outcome in animals anesthetized with 1.2% isoflurane and 3% isoflurane was not different. Although these data indicate that etomidate and thiopental might reduce ischemic injury in some structures, the magnitude of the protective effects observed was small.

Topics: Animals; Brain; Brain Ischemia; Etomidate; Isoflurane; Male; Prosencephalon; Rats; Rats, Inbred WKY; Thiopental

The effect of acute hypocarbia on baseline extracellular K+ concentration [( K+]e) and its effect on the ability of the cerebral microenvironment to recover from transient increases in [K+]e has been assessed in rats. Spreading depression of cortical activity was used to present a reproducible K+ load to the extracellular space. Baseline [K+]e and the half-time for resolution of the [K+]e changes seen with spreading depression waves were measured for the hypocarbic and normocarbic states by means of double-barrelled K+ microelectrodes placed approximately 400 micron below the cortical surface. Three spreading depression waves were initiated in each animal for the two CO2 states. In group 1 (n = 10), the rats were initially normocarbic (PaCO2 41.6 +/- 3.0 mmHg; mean +/- SD), then hypocarbic (PaCO2 19.0 +/- 2.5 mmHg) for the second series of measurements. The baseline [K+]e was significantly higher in the normocarbic state 3.4 +/- 0.4 versus 3.0 +/- 0.4 mM l-1, P less than 0.01 (paired t test). During normocarbia, the K+ load (delta[K+]e) presented to the extracellular space following spreading depression was 49.4 +/- 7.5 mM l-1, n = 10 (peak [K+]e - baseline [K+]e). The half-time for resolution of the presented [K+]e load was 24.3 +/- 6.1 s. Following hypocarbia of 1.4 +/- 0.6 h, there was no change in delta[K+]e (49.0 +/- 6.0 mM l-1) but resolution t1/2 had increased to 35.8 +/- 11.2 s, P less than 0.01 paired t test.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, General; Animals; Brain; Brain Ischemia; Carbon Dioxide; Cortical Spreading Depression; Extracellular Space; Male; Potassium; Rats; Thiopental

Cardiac arrest is followed by complete cerebral ischemia, which is characterized by delayed hypoperfusion and transient hypermetabolism. Brain metabolism depressant drugs, such as barbiturates, were suggested to improve neuronal outcome. The hypothesis of a cerebroprotective effect of barbiturates remained nevertheless controversial. In order to define the utility of large doses of thiopentone, the effect of thiopentone on carbohydrate and energy metabolism of 1-year old Wistar rats was investigated in an experimental model of complete reversible ischemia followed by a recovery period. No beneficial effect of high-dose thiopentone could be demonstrated by means of changes in the carbohydrate metabolism and the energyrich compounds. There were no differences between the treated group and the spontaneous recovery group. These results are mainly confirmed by other investigators. In contrast to focal ischemia and hypoxemia beneficial effects of barbiturates can not be demonstrated after complete cerebral ischemia in experimental studies and in clinical studies as well. In conclusion there is no indication for high-dose barbiturate therapy after cardiac arrest and successfull resuscitation.

Topics: Animals; Barbiturates; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Energy Metabolism; Glycolysis; Heart Arrest; Male; Neurons; Rats; Rats, Inbred Strains; Resuscitation; Thiopental

Thiopentone (thp) infusion was administered to 33 patients with cerebral dysfunction or convulsions out of 2986 patients operated on via extracorporeal circulation because of valvular disease, coronary insufficiency, septum defects and intrathoracic aortic aneurysms. If phenytoin, diazepam and clonazepam proved ineffective, thp 10-15 mg/kg was injected slowly, followed by infusion of 2-4 mg/kg/h for 0.5-5 days. 9 patients died. 18 survivors had a good recovery, 6 were moderately disabled. In the survivors embolisation of particulate matter prevailed as a cause of cerebral dysfunction while in nonsurvivors prolonged pre- and postoperative hypotension was the main cause, with one patient suffering a hemispheric infarction. The amelioration of convulsions and psychosyndromes in the survivors is compatible with the known anticonvulsive effect of thp and its alleged influence on cerebral focal ischaemia. However, in protracted cerebral hypoperfusion as a cause of cerebral dysfunction no protection can be expected from thp. The known effects of barbiturates do not justify the use of these substances for the purpose of cerebral protection.

Topics: Adolescent; Adult; Aged; Aortic Aneurysm; Brain Ischemia; Dose-Response Relationship, Drug; Extracorporeal Circulation; Female; Follow-Up Studies; Heart Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Postoperative Complications; Seizures; Thiopental

Topics: Anesthesia, Inhalation; Anesthetics; Animals; Brain; Brain Ischemia; Cerebrovascular Circulation; Dogs; Electroencephalography; Oxygen Consumption; Thiopental

Topics: Animals; Barbiturates; Brain; Brain Ischemia; Heart Arrest; Humans; Macaca mulatta; Resuscitation; Thiopental; Time Factors

The kinetics of thiopentone when administered in high doses were investigated in two patients with elevated intracranial pressure and three patients with focal cerebral ischemia. Initial saturation of the tissues is best achieved by a series of infusions with decreasing infusion rate. Administration of a bolus followed by maintenance doses proved unsuitable. The course of concentration under maintenance dosage was extremely variable, mainly due to interindividual and intraindividual variations in clearance. The apparent distribution volumes in these patients (1.38-3.10 l/kg, mean 2.43 l/kg) corresponded to the volumes determined after bolus administration. The total body clearance was low (45.8-103.4 ml/min, mean 72.3 ml/min) and was the reason for long elimination half-times (15.6-25.0 h, mean 23.2 h). Four patients biotransformed thiopentone regardless of the concentration. In one female patient the biotransforming enzyme systems may have been saturated. While conversion of thiopentone to pentobarbitone is generally only of secondary importance, an unusually high plasma pentobarbitone concentration was observed in one patient, reaching 50% of the concentration of the original substance. On the average, thiopentone was 75-80% proteinbound. The binding rate changed considerably with time. It could not be shown that this was influenced by albumin concentration between 25 and 50 g/l. The thiopentone concentration in the ventricular fluid corresponded approximately to that in the plasma fluid. Owing to the variability of the total body clearance and plasma protein binding, and the possibility of changes in tolerance, thiopentone administration must be controlled individually according to the EEG and intracranial pressure. Monitoring of the drug concentration in plasma is recommended.

Topics: Adult; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Dose-Response Relationship, Drug; Female; Humans; Intracranial Pressure; Kinetics; Male; Middle Aged; Pentobarbital; Protein Binding; Thiopental

The activity of three forms of ATPase were examined in fractions of the brain of the gerbil treated with ethylene glycol-N-N-tetra-acetic acid (EGTA) under a variety of conditions of primary and secondary (reflow) ischemia. In animals which were unilateral ischemic (ligation of the right common carotid), damage to Na+, K+-ATPase alone was observed only after at least 6 hr of ischemia had elapsed. The phenomenon occurred in only symptomatic gerbils and was absent in animals which were either asymptomatic or only displayed partial neurological symptoms. Under conditions of bilateral cerebral ischemia, in which both carotid arteries were clamped, only irreversible ischemia (60 min) followed by reflow, was associated with highly significant damage to cerebral Na+, K+-ATPase. In regional studies of the forebrain involving ischemia for 60 min plus 30 min reflow, damage to Na+, K+-ATPase was evident in the cerebrum, hippocampus, striatum and thalamus, while the hypothalamus and olfactory bulb were spared. Pretreatment of gerbils with allopurinol, clonazepam or combinations of thiopental plus either indomethacin or methylprednisolone offered protection to cerebral Na+, K+-ATPase subsequent to secondary ischemia. With only minor exceptions (striatum) neither Ca2+, Mg2+- nor Mn2+-ATPase were altered by stroke or treatment with drugs.

Topics: Adenosine Triphosphatases; Allopurinol; Animals; Brain; Brain Ischemia; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Clonazepam; Egtazic Acid; Female; Gerbillinae; Indomethacin; Methylprednisolone; Sodium-Potassium-Exchanging ATPase; Thiopental; Time Factors

The cardiovascular and electroencephalographic (EEG) effects of thiopental were investigated, with and without preceding global brain ischemia (GBI). Four groups of pigtailed monkeys were used: Group I received thiopental 90 mg/kg over 1 h after 16 min GBI. Group II received thiopental 90 mg/kg over 1 h without preceding brain ischemia. Group III received 90 mg/kg over 1, 3, 6, or 8 h with varying infusion rates and no brain ischemia. Group IV, after 16 min GBI, received thiopental 90 mg/kg over 12 h with a gradually reduced infusion rate, keeping thiopental serum levels around 120-140 mumol X l-1 throughout the infusion. Large doses of thiopental (Group II) produced serious cardiovascular side-effects. With co-existing brain ischemia (Group I), these side-effects were much worse; five of six animals not receiving lidocaine prophylaxis suffered circulatory arrest. A prolongation of the Q-T interval on the electrocardiogram may be of pathogenetic importance. In contrast, lower thiopental blood levels, sufficient to depress the EEG to burst suppression or isoelectricity, were well tolerated with and without preceding brain ischemia (Groups IV and III).

Topics: Animals; Arrhythmias, Cardiac; Brain; Brain Ischemia; Electrocardiography; Electroencephalography; Female; Heart Arrest; Heart Block; Hemodynamics; Macaca nemestrina; Male; Thiopental

Topics: Brain Ischemia; Combined Modality Therapy; Heart Arrest; Humans; Middle Aged; Prognosis; Random Allocation; Resuscitation; Thiopental; Time Factors

The effect of three modes of anesthesia was evaluated with regard to regional damage to central cyclic nucleotide systems in the gerbil brain as a consequence of bilateral ischemia (clamping the common carotids) followed by various periods of recirculation. The injection of thiopental as much as 90 min before stroke prevented damage to chemical activation [catecholamines, guanosine triphosphate (GTP), or forskolin] of adenylate cyclase. However, the basal enzyme activity was lower in all brain regions whether thiopental was administered to stroke or sham-operated animals. Injection of ketamine drastically shortened the survival times of gerbils undergoing stroke followed by recirculation. About 90% of the animals could tolerate a maximum of only 15 min stroke with 15 min recirculation. At this time frame the patterns of activation of adenylate cyclase in only the olfactory tubercle and hippocampus were altered. When procaine was used as a local anesthetic agent during surgery, damage to catecholamine-, GTP-, or forskolin-activated adenylate cyclase was evident to varying degrees in the frontal cortex, hippocampus or olfactory tubercle, but not in the nucleus accumbens and olfactory bulb of gerbils subjected to 60-min stroke followed by 15 or 150 min of recirculation. The degree of enzyme damage was neither correlated with the fed vs. fasted state of the animal nor with the whole blood concentration of glucose. A depression in the amplitude of visually evoked potentials correlated to neurological signs and to enzyme damage. During anesthesia, ketamine increased steady-state concentrations of cyclic AMP in the frontal cortex and hippocampus from gerbil brains that had been rapidly inactivated by microwave irradiation. Thiopental increased steady-state cyclic AMP in only the olfactory tubercle. Cyclic GMP concentrations were unchanged by any anesthetic agent. In animals completely recovering from anesthesia and occluded for a brief period followed by 10 min of reflow, steady-state concentrations of only cyclic AMP were augmented.

Topics: Adenylyl Cyclases; Animals; Brain; Brain Ischemia; Cyclic AMP; Evoked Potentials, Visual; Fasting; Female; Gerbillinae; Ketamine; Procaine; Thiopental

Topics: Aged; Anesthesia, General; Anesthesia, Inhalation; Blood Pressure; Brain; Brain Ischemia; Carbon Dioxide; Carotid Artery Diseases; Endarterectomy; Humans; Injections, Intravenous; Isoflurane; Lidocaine; Middle Aged; Monitoring, Physiologic; Nitrous Oxide; Oxygen; Oxygen Consumption; Postoperative Care; Preanesthetic Medication; Thiopental

To assess the uses of high dose barbiturate therapy in neurosurgery and intensive care, the authors have undertaken a concise survey of relevant experimental investigations and a comprehensive review of published clinical experiences.

Topics: Barbiturates; Brain; Brain Diseases; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Critical Care; Dose-Response Relationship, Drug; Electroencephalography; Energy Metabolism; Humans; Intracranial Pressure; Lipid Peroxides; Oxygen Consumption; Pentobarbital; Phenobarbital; Thiopental

Topics: Animals; Body Temperature; Brain; Brain Ischemia; Calcium Channel Blockers; Cinnarizine; Computers; Dogs; Electroencephalography; Etomidate; Female; Flunarizine; Imidazoles; Male; Pentobarbital; Piperazines; Thiopental

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Ischemia; Female; Macaca nemestrina; Male; Resuscitation; Thiopental

The effect of barbiturate coma upon regional cerebral blood flow (RCBF) and ultimate neurologic outcome was examined after total cerebral ischemia (TCI). TCI was induced in dogs using a relatively noninvasive double-occlusion balloon technique; cardiopulmonary protection was provided during the period of ischemia. RCBF was measured using 15-mu radioactively labeled microspheres. A reproducible pattern of impaired reperfusion of the central nervous system (CNS) was observed in control animals after the restoration of cerebral perfusion pressure after TCI. This pattern was accentuated by the administration of pentothal to induce barbiturate coma. The additional depression in RCBF in those animals receiving pentothal was most prominent in cortical gray matter and brainstem structures at 3 and 6 h after TCI. It was also observed in cortical white matter. No untreated animal surviving TCI achieved a neurologic functional level better than persistent vegetative (decerebrate) survival over 1 wk of observation. Animals receiving 90 mg/kg body weight of pentothal post-TCI demonstrated irreversible cardiogenic shock related to the myocardial depressant effect of the drug. Animals receiving 40 to 60 mg/kg of pentothal post-TCI demonstrated a survival rate similar to that of untreated animals. Although this study did not establish the possible effectiveness of barbiturate coma in improving residual neurologic damage after TCI, the data do demonstrate that any possible effectiveness in this model is not associated with any improvement in the markedly decreased cerebral perfusion after TCI.

Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Coma; Dogs; Hemodynamics; Regional Blood Flow; Thiopental

Topics: Brain Ischemia; Child; Electroencephalography; Humans; Hypothermia, Induced; Hypoxia, Brain; Resuscitation; Thiopental

Pharmacologic protection should be used cautiously. The author reviews its rationale, use, and recommendations in three clinical conditions associated with ischemic brain damage: stroke, cardiac arrest, and head trauma.

Topics: Adult; Animals; Arterial Occlusive Diseases; Barbiturates; Brain Injuries; Brain Ischemia; Cats; Cerebral Arteries; Cerebrovascular Disorders; Dogs; Female; Heart Arrest; Humans; Intracranial Pressure; Male; Middle Aged; Models, Biological; Papio; Phenobarbital; Saimiri; Thiopental

Recent interest in pharmacotherapy for various cerebral insults with potentially dangerous drugs, such as barbiturate anesthetics, has created a need to determine the lowest or optimal dose resulting in maximal therapeutic effects. Our earlier studies suggested that whole brain free fatty acid (FFA) accumulation during complete global ischemia reflects the evolution of brain damage. Various drugs effective in ameliorating ischemic brain injury were also effective in attenuating FFA accumulation. The degree of attenuation by a given drug at various doses may indicate the optimal dose. We studied the attenuation of whole brain FFAs (i.e., 20:4, 18:0, 18:1, and 16:0) by 15-120 mg/kg of thiopental or pentobarbital, or 50-300 mg/kg of phenytoin or ketamine intraperitoneal (IP), during 10-min decapitation ischemia in rats. Plasma and brain drug levels were measured except ketamine. Maximal attenuation of FFAs occurred at pentobarbital, thiopental, and phenytoin doses of 15, 30, and 150 mg/kg IP reducing total FFA by 18, 22, and 31%, respectively. These results indicate that maximal therapeutic effects are obtained at subanesthetic doses of barbiturates and at the anticonvulsant dose of phenytoin.

Topics: Animals; Brain Chemistry; Brain Ischemia; Fatty Acids, Nonesterified; Female; Hypoxia, Brain; Ketamine; Pentobarbital; Phenytoin; Rats; Rats, Inbred Strains; Thiopental

Topics: Animals; Brain Ischemia; Carotid Arteries; Ether; Ethyl Ethers; Etomidate; Gerbillinae; Imidazoles; Ligation; Thiopental; Time Factors

Topics: Animals; Brain Ischemia; Cats; Glycerol; Mannitol; Thiopental

Topics: Animals; Brain Ischemia; Cats; Glycerol; Mannitol; Thiopental

Topics: Analgesia; Animals; Blood Pressure; Brain Damage, Chronic; Brain Ischemia; Disease Models, Animal; Dogs; Hemodilution; Immobilization; Macaca mulatta; Macaca nemestrina; Respiration, Artificial; Resuscitation; Thiopental

To define the utility of high-dose barbiturate therapy following an episode of complete global cerebral ischemia, we investigate the effects of 60 mg/kg of thiopental given to cats five minutes after resuscitation from 12, 14, or 16 min of electrically induced ventricular fibrillation (VF). All aspects of the arrest, resuscitation, with post-arrest care were carefully controlled, with the EEG becoming isoelectric 20-25 s after the onset mean resuscitation time of 2.5 +/- 0.2 (SEM) min. For any given duration of VF, there were no differences (control vs thiopental) in any pre- or post-arrest parameters (blood pressure, blood gases, electrolytes, etc.) A total of 68 resuscitated cats were entered into various treatment and control groups, and all but one group received 20-24 h of post-resuscitation paralysis, mechanical ventilation, and ICU support before being extubated. Cats received an additional six days of aggressive nursing care, and daily examinations were performed with the assignment of a neurologic deficit score (NDS) between 0 (normal) and (brain dead). Autopsies were performed to determine the cause of death in animals which died before the end of the seven-day observation period. The early post-arrest period was marked by the occurrence of repetitive, rhythmic bursts of high-frequency electroencephalographic (EEG) activity (? seizures) in 38 per cent of control animals (16/42, all arrest times combined). Ten of these animals died as a result of severe neurologic injuries. By contrast, only 12 per cent of treated cats (3/26) developed similar EEG patterns (P less than 0.05) and there were no neurologic deaths in the thiopental groups. The differences in the incidence of neurologic deaths (control vs. thiopental) was significant (P less than 0.02). The change in overall mortality did not quite reach significance (36 per cent vs. 21 per cent), and treatment had no effect on the incidence of deaths due to cardiovascular causes (e.g., myocardial infarctions). In spite of the effects on mortality, treatment had no effect on the neurologic function of survivors (assessed by NDS). These findings suggest that thiopental improved survival rates by suppressing an unusual post-arrest EEG pattern (? anticonvulsant effect), but had no additional cerebral protective effects.

Topics: Animals; Brain Diseases; Brain Ischemia; Cats; Disease Models, Animal; Electroencephalography; Heart Arrest; Resuscitation; Thiopental; Ventricular Fibrillation

Sodium thiopental was administered to 10 dogs following embolization of the middle cerebral artery. Its effect on the "grace period" for revascularization was investigated by performing embolectomies 6 hours later. We observed a striking reduction in the size of infarction in the animals treated with thiopental at moderate and prolonged dosage levels. The control animals treated with pentobarbital received less protection against ischemia although blood levels were similar to those of the experimental groups during the period of vascular occlusion.

Topics: Animals; Barbiturates; Brain Ischemia; Cerebral Infarction; Cerebral Revascularization; Dogs; Dose-Response Relationship, Drug; Pentobarbital; Thiopental; Time Factors

The effect of temperature (37 degrees C, 28 degrees C, and 18 degrees C), 160 mg/kg lidocaine, and 40 mg/kg thiopental on the efflux of cellular potassium in the cerebral cortex during complete global ischemia was examined. Cerebral ischemia was induced in dogs on cardiopulmonary bypass circulation by stopping the pump. Potassium concentration was measured on the brain surface by a valino-mycine-membrane electrode, which in its response corresponded well to an inserted microelectrode. Hypothermia reduced the ischemic potassium efflux rate to about 50 per cent at 28 degrees C, and about 25 per cent at 18 degrees C. At all temperature levels lidocaine caused an additional reduction in the potassium efflux rate of about 50 per cent, probably by reducing membrane ion permeability in accordance with its local anesthetic action. Thiopental had no effect on the potassium efflux during ischemia. This study opens the possibility that lidocaine, like hypothermia, may provide protection of the ischemic brain.

Topics: Animals; Brain; Brain Ischemia; Cardiopulmonary Bypass; Cell Membrane Permeability; Dogs; Hypothermia; Lidocaine; Potassium; Thiopental

Two patients who underwent surgery for cerebral aneurysms are presented. In the first case 31 g thiopentone were given postoperatively over 20 h after the patient had already been comatose for many hours. Such high doses raise considerable problems in patient management. In the second case a loading dose of 50 mg/kg thiopentone was given prophylactically to a patient undergoing cerebral aneurysm surgery beginning at the induction of anaesthesia and before surface cooling was begun. Cerebral activity was monitored continuously with a cerebral function monitor (CFM). There was no significant cardiovascular depression, little delay in postoperative recovery and no permanent neurological sequelae. In cerebral aneurysm surgery, cerebral oedema following cerebral ischaemia, either associated with vasospasm or resulting from surgical occlusion of vessels, remains a major problem postoperatively and may be an indication for preventive treatment with barbiturates. The author contend that this technique merits further evaluation in cerebro-vascular surgery, especially in high risk cases.

Topics: Adult; Brain Ischemia; Drug Administration Schedule; Female; Humans; Intracranial Aneurysm; Middle Aged; Postoperative Period; Thiopental

Topics: Brain Ischemia; Dose-Response Relationship, Drug; Half-Life; Humans; Kinetics; Resuscitation; Thiopental

Topics: Animals; Barbiturates; Brain Ischemia; Cats; Cerebral Infarction; Dogs; Haplorhini; Humans; Hypoxia, Brain; Intracranial Pressure; Pentobarbital; Postoperative Complications; Pseudotumor Cerebri; Rats; Thiopental

Topics: Animals; Barbiturates; Brain; Brain Ischemia; Fatty Acids; Free Radicals; In Vitro Techniques; Lipid Metabolism; Male; Oxidation-Reduction; Promethazine; Rats; Thiopental

Topics: Animals; Brain Ischemia; Hypoxia, Brain; Phenytoin; Placebos; Rabbits; Thiopental

Twenty patients suffering from post-ischaemic encephalopathy were treated with high doses of barbiturates during the period immediately following resuscitation. The duration of cerebral ischaemia was assessed retrospectively. The degree of ischaemic damage was evaluated on the one hand by the pupillary signs seen 10 minutes after the reestablishment of the circulation and secondly by enzyme levels in the CSF. This barbiturate load was not associated with major complications and the excretion of barbiturate continued for several days. The clinical signs seen 12 hours after ischaemia and continuous observation of the tracing of the cerebral function monitor made it possible to give an early favourable prognosis from a neurological standpoint. In all the patients (apart from one) in whom there was total cerebral ischaemia for less than 10 minutes, neurological recovery was complete.

Topics: Adolescent; Adult; Aged; Aspartate Aminotransferases; Brain Ischemia; Female; Heart Arrest; Humans; L-Lactate Dehydrogenase; Lactates; Male; Middle Aged; Pyruvates; Reflex, Pupillary; Resuscitation; Thiopental; Time Factors

Topics: Blood Gas Analysis; Brain Ischemia; Carbon Dioxide; Cats; Cerebral Angiography; Cerebral Infarction; Ethanol; Ischemic Attack, Transient; Mannitol; Oxygen; Pentobarbital; Pharmacology; Research; Thiopental; Trypan Blue; Urea

Topics: Animals; Brain; Brain Ischemia; Cerebral Infarction; Cyanides; Guinea Pigs; Histological Techniques; Hypoxia, Brain; Ischemic Attack, Transient; Nitrogen; Nitrous Oxide; Pathology; Research; Thiopental; Toxicology