thiopental and Brain-Damage--Chronic

We studied the effect of thiopental loading during resuscitation of 53 patients following cardiopulmonary arrest and compared the outcome with that found in 54 patients treated conventionally in the 30 previous months. Thiopental therapy (10 mg/kg i.v.) was begun within 30 min of the arrest once hemodynamic stability had been established. Thiopental infusion (20 mg/kg over 6 h) was followed by phenobarbital sodium (125 mg every 12 h), tolerance to the initial dose having been assessed. The in-hospital mortality rate for both groups was similar. In patients with ischemic heart disease, the mortality rate within the first 6 h was significantly higher in the thiopental group (p less than 0.05), although for the remaining patients there were more survivors among the thiopental treated patients (p less than 0.05). Excluding the patients who died within the first 6 h, 61% of the patients in the thiopental group survived cardiac arrest with normal cerebral performance, whereas only 37% in the standard treatment group showed normal functional outcome (p less than 0.03). These results suggest a favorable neurologic effect of thiopental loading during resuscitation of patients without ischemic heart disease. In patients with ischemic heart disease, an initial hemodynamic deterioration may contribute to minimising the beneficial effect of barbiturate therapy.

Topics: Adult; Aged; Brain Damage, Chronic; Clinical Trials as Topic; Critical Care; Female; Heart Arrest; Humans; Male; Middle Aged; Phenobarbital; Prognosis; Resuscitation; Thiopental

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

ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 microM, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Barbiturates; Brain Damage, Chronic; Cell Membrane; Dose-Response Relationship, Drug; Hypnotics and Sedatives; Intracellular Fluid; Membrane Potentials; Neural Inhibition; Neurons; Neuroprotective Agents; Organ Culture Techniques; Patch-Clamp Techniques; Pentobarbital; Potassium; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Substantia Nigra; Thiopental

We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading, and even more so with the further addition of phenytoin and methylprednisolone. Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1 = normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs. 2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/- 15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81 +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs. group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone.

Topics: Animals; Anticonvulsants; Brain; Brain Damage, Chronic; Dogs; Drug Therapy, Combination; Heart Arrest; Male; Methylprednisolone; Neuroprotective Agents; Phenytoin; Resuscitation; Thiopental; Time Factors; Treatment Outcome

Clinical strategy to maximize effectiveness and to minimize adverse influences remains to be determined for mild hypothermia therapy for traumatic brain injury. This study was conducted to evaluate the clinical feasibility of the titration method of mild hypothermia in severely head-injured patients in whom a reduction in intracranial pressure was regarded as the target effect.. Nine consecutive patients with severe head injury were studied. Patient age ranged between 18 and 66 years, Glasgow Coma Scale scores were equal to or less than 8, and intracranial pressures were equal to or greater than 20 mm Hg despite removal of intracranial hematoma and drugs, including glycerol and thiopental. During a maximum of 6 days of hypothermia therapy, jugular venous blood or cerebrospinal fluid temperature was titrated to reduce intracranial pressure to less than 20 mm Hg by means of repeated intragastric cooling with our nasoduodenal tube and surface cooling. The feasibility and the effects on systemic complications of this titration method of mild hypothermia were evaluated.. Intracranial pressure variably decreased from before to 3 hours after the beginning of all procedures of cooling. The mean intracranial pressure significantly decreased from 24 to 15 mm Hg with cooling, while temperature reduced an average of 2.0 degrees C. Four patients had systemic infection complications. Increased C-reactive protein and decreased platelet count were observed in all patients during hypothermia. The incidence of good recovery and moderate disability according to the Glasgow Outcome Scale was seven of nine patients.. The titration method of mild hypothermia to control intracranial hypertension in severely head-injured patients is clinically feasible. However, the method failed to reduce the incidence of infectious and hematological complications.

Topics: Adolescent; Adult; Aged; Brain Damage, Chronic; Brain Injuries; Combined Modality Therapy; Cross Infection; Cryotherapy; Dobutamine; Dopamine; Feasibility Studies; Female; Glasgow Coma Scale; Glycerol; Humans; Hypothermia, Induced; Intracranial Hypertension; Intubation, Gastrointestinal; Male; Middle Aged; Thiopental; Thrombocytopenia; Treatment Outcome

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

This study reports on clinical outcome in 38 patients with severe head injuries (posttraumatic coma for 6 hours or more) treated with barbiturate coma because of intracranial hypertension. Eighteen patients died, 4 patients remained in a severely disabled or a chronic vegetative state, and 16 patients reached the levels good recovery/moderate disability. Six of these patients returned to work or school full time, 4 for half time and 3 were in a rehabilitation program. Fourteen patients were subjected to a comprehensive neuropsychological assessment. All patients except one exhibited varying degrees of cognitive dysfunction and 6 patients had signs of personality change. The quality of life for the majority of surviving patients was relatively good but the positive effects of barbiturate coma therapy in the age groups over 40 years appeared to be limited.

Topics: Adult; Brain Damage, Chronic; Brain Injuries; Child; Cognition Disorders; Critical Care; Disability Evaluation; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Male; Neurologic Examination; Neuropsychological Tests; Quality of Life; Survival Rate; Thiopental

Topics: Animals; Brain Damage, Chronic; Brain Injuries; Cerebrovascular Disorders; Coma; Heart Arrest; Humans; Resuscitation; Thiopental

Brain damage following open-heart surgery is receiving increasing attention. Efforts are being made to improve the setting for cardiac surgery so as to avoid such complications. When they occur, their recognition is retrospective, when the cerebral lesion is inevitable. Because heavy sedation is necessary, clinical supervision with respect to brain function is both difficult and unreliable in the early postoperative period. We therefore submitted 34 selected patients to neurosurgical intensive care supervision. The measures included postoperative monitoring of intracranial epidural pressure (EDP), of arterial blood pressure (BP) and of central venous pressure (CVP). In 25 patients there was rise in EDP during the first postoperative hours. Six of these patients received mannitol treatment and in three of them barbiturate was additionally given, in order to reduce EDP and improve the cerebral perfusion pressure (CPP = BP-EDP). Nevertheless EDP progressed to brain tamponade six days postoperatively in one case. In patients with raised EDP, weaning from the ventilator should be postponed until EDP has almost normalized. The EDP recording is a valuable guide in the postoperative management of the individual patient.

Topics: Blood Pressure; Brain Damage, Chronic; Carbon Dioxide; Extracorporeal Circulation; Heart Diseases; Humans; Intracranial Pressure; Mannitol; Postoperative Complications; 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

Three cases of severe carbon monoxide poisoning are described presenting with deep coma, generalised extensor spasms and myoclonia as symptoms of acute midbrain syndrome. Despite this poor prognosis all patients survived without essential neurological impairment. This favourable outcome is thought to be due to the administration of thiopentone for the amelioration of hypoxic brain damage in dosages commonly employed in anaesthesia.

Topics: Adult; Brain Damage, Chronic; Carbon Monoxide Poisoning; Humans; Hypoxia, Brain; Male; Respiration, Artificial; Thiopental

It has been shown experimentally that irreversible brain injury and death may follow after 5-7 min of cerebral ischemia and that even brief periods, 2 min or less, can produce focal damage to the nervous system. All published studies demonstrating a protective effect of barbiturates have been performed in animals. A patient is presented who recovered full neurological function after 13 min of hypovolemic hypotension. This remarkable outcome may have been due to the rapid institution of high-dose barbiturate therapy. The extent to which such therapy affected his outcome is unclear, but does add to the growing body of evidence suggesting a favorable effect from this type of barbiturate therapy.

Topics: Brain Damage, Chronic; Coronary Artery Bypass; Heart-Lung Machine; Humans; Intraoperative Complications; Ischemic Attack, Transient; Male; Middle Aged; Shock; Thiopental

Irreversible brain damage after a short period of cerebral ischemia is a clinical drama. Not neuronal dead in se, but a hemodynamic event, described as no reflow phenomenon (NRF) seems to be the primary pathogenetic factor towards fatal outcome. A combination of four flow promoting therapeutic measures (heparinisation, hemodilution, systemic arterial hypertension and brainflushing with dextran 40) greatly improves recovery of the brain function after 12 min. of cardiac arrest in dogs. Short acting barbiturates provide remarkable amelioration of postischemic encephalopathy in the monkey.

Topics: Animals; Brain; Brain Damage, Chronic; Cats; Dogs; Haplorhini; Hemodynamics; Intracranial Pressure; Ischemia; Thiopental; Time Factors

All physicians performing surgery while the patient is under general anesthesia must be aware of the existence of idiopathic malignant hyperthermia. A young adult had a malignant hyperthermic reaction despite four prior uneventful administrations of general anesthetics. To my knowledge, this is the first report of a patient who survived following a hyperthermic reaction, having sustained considerable residual brain damage. There is a great need for continuous body-temperature monitoring during general anesthesia.

Topics: Adolescent; Anesthesia, Inhalation; Brain Damage, Chronic; Chlorides; Heart Arrest; Humans; Male; Malignant Hyperthermia; Methoxyflurane; Sodium; Strabismus; Succinylcholine; Tachycardia; Thiopental

Topics: Adolescent; Adult; Anesthesia, Dental; Brain Damage, Chronic; Carbon Dioxide; Child; Child, Preschool; Electroencephalography; Epilepsy; Female; Halothane; Humans; Injections, Intramuscular; Injections, Intravenous; Ketamine; Male; Methohexital; Movement Disorders; Oxygen; Partial Pressure; Seizures; Thiopental

Topics: Brain Damage, Chronic; Desipramine; Humans; Hydrocortisone; Infant; Procaine; Thiopental; Urea