thiamylal and Cerebrovascular-Disorders

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP.

Topics: Adult; Aged; Aged, 80 and over; Brain Injuries, Traumatic; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Female; Glasgow Coma Scale; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Injury Severity Score; Intracranial Hypertension; Intracranial Pressure; Male; Middle Aged; Thiamylal; Treatment Outcome

Mild barbiturate-moderate hypothermia therapy was established for severe head injury and cerebrovascular disease. This study was conducted on 152 patients from April 1984 through July 1995. In this study were included patients with Glagow Coma Scale score of less than 8 points but those with serious systemic complications and elderly and infantile patients were excluded. Our protocol consisted of administration of thiamylal Na 1.25-2.5 mg/kg/h and droperidol 20-40 micrograms/kg/h (mild barbiturate) while maintaining a core temperature of 32-34 degrees C (moderate hypothermia). The clinical outcome was good (GR, MD) in 58 cases, poor (SD) in 24 cases and bad (PVS, D) in 70 cases. This therapy was found to be particularly effective for preventing ischemic neurological damage in the vasospasm stage following SAH and severe head injury in young patients. However, this therapy did not prevent pneumonia, cardiac failure, arrhythmia and hypopotassemia from occurring frequently. We conclude that this therapy is contraindicated in the elderly, i.e., those older than 65 years.

Topics: Adolescent; Adult; Aged; Brain Injuries; Cerebrovascular Disorders; Child; Droperidol; Female; Glasgow Coma Scale; Humans; Hypnotics and Sedatives; Hypothermia, Induced; Intracranial Aneurysm; Male; Middle Aged; Thiamylal; Treatment Outcome

In an attempt to clarify the neurochemical background of central post-stroke pain and to undertake a pharmacological analysis, the basic pharmacological characteristics of this intractable pain syndrome were investigated by the morphine, thiamylal and ketamine tests. In addition, the correlation between the pharmacological characteristics and the effects of chronic motor cortex stimulation therapy was examined. The study employed 39 central post-stroke pain patients who had intractable hemibody pain associated with dysesthesias, and radiologically demonstrated lesions in the thalamic area (thalamic pain, n = 25) or suprathalamic area (suprathalamic pain, n = 14). The pharmacological evaluations showed that definite pain reduction occurred in eight of the 39 cases (20.5%) by the morphine test, in 22 of the 39 cases (56.4%) by the thiamylal test, and in 11 of 23 cases (47.8%) by the ketamine test. Based on these pharmacological assessments, there was no obvious difference between thalamic and suprathalamic pain. A comparison of the long-term follow-up results of chronic motor cortex stimulation therapy revealed that thiamylal and ketamine-sensitive and morphine-resistant cases displayed long-lasting pain reduction with chronic motor cortex stimulation therapy, whereas the remaining cases did not show good results. We conclude that pharmacological classification of central post-stroke pain by the morphine, thiamylal and ketamine tests could be useful for predicting the effects of chronic motor cortex stimulation therapy. It has recently been suggested that excitatory amino acids may be involved in the development of central post-stroke pain. However, the fact that only 23 of the present 39 cases (59.0%) of thalamic and suprathalamic pain were sensitive to the thiamylal or ketamine test reflects the complex pharmacological background and the difficulties associated with treating central post-stroke pain.

Topics: Adult; Aged; Analgesics, Opioid; Anesthetics; Cerebrovascular Disorders; Female; Humans; Ketamine; Linear Models; Male; Middle Aged; Morphine; Motor Cortex; Pain; Stimulation, Chemical; Syndrome; Thalamus; Thiamylal

We report two cases of traumatic cerebral vascular disease which were treated successfully with barbiturate. The first case sustained blunt trauma to the bilateral vertebral arteries, resulting in complete occlusion of both arteries. After ligation of the injured vertebral arteries, multiple cerebral infarction appeared. Cerebral angiography revealed dissection and stenosis of the bilateral internal carotid arteries. We treated this case with barbiturate (Thiamylal) in combination with administration of heparin. The second case sustained cerebral contusion and traumatic subarachnoidal hemorrhage as a result of a motor cycle accident. This patient deteriorated and cerebral angiography showed diffuse cerebral arterial vasospasms. When this was treated with induced hypertension, he developed recurrent subarachnoid hemorrhage. In order to protect the brain from ischemia without elevating blood pressure, we employed barbiturate therapy and the patient recovered without major neurological deficit. The condition of severe head injury with cerebral ischemia is complicated. Therefore it has been hard for neurosurgeons to cure the patient with this condition. But we treated it with barbiturate successfully. Barbiturate therapy in severe head injury with cerebral ischemia may decrease the mortality in that group of patients considered difficult to treat with the usual therapeutic modalities.

Topics: Adolescent; Brain Concussion; Brain Injuries; Cerebral Angiography; Cerebral Infarction; Cerebrovascular Disorders; Humans; Ischemic Attack, Transient; Male; Subarachnoid Hemorrhage; Thiamylal; Tomography, X-Ray Computed; Wounds, Nonpenetrating