thiopental and Glioma

Disturbed autoregulation and CO2 reactivity have been reported in patients with brain tumors. Therefore, we decided to monitor the cerebrovascular effects of anesthetic drugs and hyperventilation. Transcranial Doppler sonography (TCD) can measure noninvasively alterations of flow velocities (v) and cross-sectional vessel area (VA) in large brain arteries. Twenty-eight patients with large malignant brain tumors in the territory of the middle cerebral artery (MCA) randomly received propofol or thiopental for induction and maintenance of anesthesia. Mean arterial pressure (MAP), heart rate (HR), and TCD parameters (vMCA and VA of the tumor or nontumor side) were determined at six data points (DP). The first measurements (MAP, HR, and TCD of the nontumor side) were performed before (DP I) and 60 s after (DP II) induction of anesthesia with either 2 mg/kg propofol or 4 mg/kg thiopental. After intubation and normoventilation (50% O2 in air), 0.05-0.1 mg/kg midazolam and an alfentanil infusion (100 micrograms/kg x h) were initiated. Then MAP, HR, vMCA, and VA of the tumor side were analyzed before (DP III) and 60 s after (DP IV) either propofol (1 mg/kg) or thiopental (2 mg/kg) were given. Finally, the effects of hyperventilation on HR, MAP, vMCA, and VA (tumor side) were determined (DP V and VI). Mean +/- SD, thiopental or propofol reactivity (non-tumor and tumor side) and CO2 reactivity (tumor side) were calculated; statistical comparison between DP I and II, III and IV, and V and VI was performed by paired t tests (p < 0.05). Unpaired t tests were used to evaluate differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anesthesia, General; Astrocytoma; Brain Neoplasms; Female; Glioma; Hemodynamics; Humans; Hyperventilation; Male; Middle Aged; Monitoring, Intraoperative; Propofol; Thiopental; Ultrasonography

Thiopental is one of the intravenous anesthetics used widely. Several reports have demonstrated that thiopental inhibits the immune responses. We investigated whether or not thiopental inhibits the production of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in human glioma cells (A-172). Moreover, we determined whether or not thiopental modulates activation of the transcription factor NF-kappaB, a factor that regulates expression of the genes that code for proinflammatory cytokines in A-172 cells and in experimental murine brain inflammation. Thiopental inhibited TNF-alpha production induced by LPS in A-172 cells. Electrophoretic mobility shift assays demonstrated that thiopental inhibited NF-kappaB activation induced by LPS in A-172 cells. In experimental murine brain inflammation induced by intracerebroventricular injection of LPS, intraperitoneal injection of thiopental inhibited NF-kappaB activation. Western blot analysis indicated that this inhibition was linked to preservation of IkappaBalpha protein expression in A-172 cells. The chloramphenicol acetyltransferase assay revealed that NF-kappaB-dependent reporter gene expression was suppressed in A-172 cells exposed to thiopental. These findings are consistent with the idea that thiopental exerts antiinflammatory effects in cultured cells and experimental murine brain inflammation, through suppression of TNF-alpha production via inhibition of NF-kappaB activation.

Topics: Anesthetics, Intravenous; Animals; Brain; Brain Neoplasms; DNA-Binding Proteins; Encephalitis; Gene Expression Regulation; Genes, Reporter; Glioma; Humans; I-kappa B Proteins; Immune System; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Thiopental; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Glucose utilization by normal and neoplastic cerebral tissue can be measured in humans using positron emission tomography (PET) with fluorine-18-labeled 2-deoxy-D-glucose (FDG). Malignant gliomas are known to exhibit hypermetabolic glucose consumption compared to normal brain. Barbiturate-sensitive cerebral glucose utilization is coupled to neuronal activity, and lesions lacking neuronal activity should be relatively insensitive to barbiturate suppression of glucose utilization. In a study to examine this phenomenon, three patients with cerebral gliomas underwent FDG-PET while awake and during deep barbiturate coma. Cerebral glucose utilization was measured in normal brain, tumor, and a homologous, non-neoplastic control site in the contralateral hemisphere. A glucose utilization ratio for tumor/control tissue was calculated. The mean reduction of glucose utilization during barbiturate coma was: gray matter 67%, white matter 47%, basal ganglia 66%, thalamus 57%, cerebellar cortex 55%, tumor 32%, and the contralateral control site 64%. The mean tumor glucose utilization ratio was 1.48:1 in the awake state and 2.69:1 during barbiturate coma. The changes in gray matter, basal ganglia, thalamus, cerebellar cortex, and tumor/control tissue ratio were significant (p less than 0.05). In one patient, deep tumor invasion not evident on computerized tomography, magnetic resonance imaging, or baseline FDG-PET was apparent during barbiturate-enhanced FDG-PET scanning. The study findings suggest that gliomas resist suppression of glucose utilization by barbiturates; this supports the hypothesis that barbiturates reduce neuronal metabolism by blocking synaptic activity. This differential effect on normal brain and gliomas enhances the capability to assess the extent of neoplastic tissue in brain and may represent the basis for novel therapeutic strategies.

Topics: Adult; Brain; Brain Neoplasms; Deoxyglucose; Fluorodeoxyglucose F18; Glioma; Glucose; Humans; Thiopental; Tomography, Emission-Computed

The case of a 7-year-old child is presented, who suffered circulatory arrest during induction of anaesthesia for surgery for a posterior fossa tumour. A brain ischaemia lasting 6 minutes duration had to be assumed. After restoration of circulation, 825 mg ethiopenta were administered in order to ameliorate a possible post-ischaemic anoxia of the brain according to a protocol by Safar [18]. 11 hours after circulatory arrest the child awoke. Except for a more pronounced left sided hemiparesis and paresis of the left n. abducens no additional neurological deficit was observed compared to the neurological status before induction of anaesthesia.

Topics: Anesthesia; Cerebellar Neoplasms; Child; Dose-Response Relationship, Drug; Female; Glioma; Heart Arrest; Heart Massage; Hemiplegia; Humans; Hypoxia, Brain; Thiopental

Topics: Astrocytoma; Basal Ganglia; Brain Neoplasms; Electroencephalography; Glioma; Humans; Oligodendroglioma; Radiography; Spinal Neoplasms; Thiopental

Topics: Adult; Astrocytoma; Brain; Brain Neoplasms; Electroencephalography; Female; Glioblastoma; Glioma; Humans; Male; Oligodendroglioma; Thiopental; Ultraviolet Therapy