thiopental and Craniocerebral-Trauma

A number of clinical studies have reported poor clinical outcomes for patients treated with barbiturate therapy in acute neurological and neurosurgical emergencies. Barbiturate therapy, as currently practised with thiopentone and pentobarbitone at least, is also associated with a prolonged post-infusion period of clinical unresponsiveness. Hence, the popularity of barbiturate therapy for sedation of critically ill neurological and neurosurgical patients has declined over the past decade. A retrospective study of traumatic brain injury patients treated at the Royal North Shore Hospital, Sydney, with high-dose thiopentone therapy between 1987 and 1997 has found disappointing results with a 1-month mortality outcome of 50% (14 of 28 patients). Nevertheless, barbiturate therapy remains a consideration for patients with severe cranial trauma in whom preferred treatments have failed to control intracranial or cerebral perfusion pressures. More favourable results ( approximately 10% 1-month mortality rate) were encountered for patients with refractory vasospasm complicating subarachnoid haemorrhage or intracerebral haemorrhage complicating supratentorial arteriovenous malformation resection. A well designed, prospective and randomised controlled trial may be of value in further determining the role of barbiturate therapy in acute neurovascular emergencies refractory to standard therapy.

Topics: Barbiturates; Brain Injuries; Craniocerebral Trauma; Emergencies; Humans; Hypnotics and Sedatives; Intracranial Pressure; Neurosurgery; Randomized Controlled Trials as Topic; Retrospective Studies; Status Epilepticus; Thiopental; Treatment Outcome; Vasospasm, Intracranial

Pharmacological therapy, present and future, will undoubtedly continue to play a large role within the overall management of patients with severe head injury. Nevertheless, limited clinical data are available to evaluate the effect of severe head injury on pharmacokinetics. The disruption of the blood-brain barrier secondary to trauma and/or subsequent hyperosmolar therapy can be expected to result in higher than expected brain drug concentrations. Aggressive dietary protein supplementation may result in increased oxidative drug metabolism. These effects may counterbalance inhibitory influences on drug metabolism secondary to cytokine release during the acute phase response. Alterations in protein binding can also be anticipated with the hypoalbuminaemia and increases in alpha 1-acid glycoprotein typically observed in these patients. Based on studies in other patient populations, moderate hypothermia, a treatment strategy in patients with head injury, can decrease drug metabolism. The pharmacokinetics of the following drugs in patients with severe head injury have been studied: phenytoin, pentobarbital (pentobarbitone), thiopental (thiopentone), tirilazad, and the agents used as marker substrates, antipyrine, lorazepam and indocynanine green (ICG). Several studies have documented increase in metabolism over time with phenytoin, pentobarbital, thiopental, antipyrine and lorazepam. Increases in tirilazad clearance were also observed but attributed to concurrent phenytoin therapy. No changes in the pharmacokinetics of ICG were apparent following head injury. With the frequent use of potent inhibitors of drug metabolism (e.g., cimetidine, ciprofloxacin) the potential for drug interaction is high in patients with severe head injury. Additional pharmacokinetic investigations are recommended to optimise pharmacological outcomes in patients with severe head injury.

Topics: Aminopyrine; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Blood-Brain Barrier; Craniocerebral Trauma; Drug Interactions; Humans; Hypnotics and Sedatives; Lorazepam; Pentobarbital; Phenytoin; 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

The role of barbiturate therapy in the development of pneumonia in head trauma patients in the intensive care unit of a university hospital was studied retrospectively. A total of 151 ventilated head trauma patients were included in the study. Intravenous thiopentone was administered to 75 patients (Group A), and 76 patients were managed without thiopentone therapy (Group B). Pneumonia was diagnosed when a new persistent pulmonary infiltrate appeared, with at least two of the following: (a) fever greater than 38 degrees C, (b) a white blood cell count greater than 15,000/mm3, or (c) the presence of purulent bronchial secretions. On admission, there were no differences in the acute physiology and chronic health evaluation 2 revision (APACHE II) and Glasgow Coma Score between Groups A and B. Fifty-three per cent of the patients treated with thiopentone (Group A) developed pneumonia compared with 35% in Group B (odds ratio 1.85, 95% confidence interval 0.97-3.51). Gram-negative and Staphylococcus aureus organisms were the most frequently isolated in all cases. No differences in age, sex, APACHE II, Glasgow Coma Score, nutritional status or dexamethasone treatment were observed between the groups with and without pulmonary infection. In the multivariate analysis, prolonged mechanical ventilation before pneumonia and thiopentone treatment remained as the only independent risk factors for the appearance of pneumonia in head trauma patients (p = 0.001 for both). Nevertheless, thiopentone did not increase the rate of mortality in patients with pneumonia. In conclusion, head trauma victims treated with thiopentone have a greater risk for the development of nosocomial pneumonia independent of mechanical ventilation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Confidence Intervals; Craniocerebral Trauma; Female; Humans; Hypnotics and Sedatives; Incidence; Intensive Care Units; Male; Middle Aged; Odds Ratio; Pneumonia; Prognosis; Respiration, Artificial; Survival Rate; Thiopental

Topics: Adolescent; Adult; Aged; Anesthesia, General; Brain Diseases; Brain Neoplasms; Carbon Dioxide; Cerebral Angiography; Cerebrovascular Disorders; Child; Child, Preschool; Craniocerebral Trauma; Droperidol; Female; Fentanyl; Humans; Male; Middle Aged; Neuroleptanalgesia; Nitrous Oxide; Partial Pressure; Thiopental

Low-frequency (0.5-2.5 Hz) and individually defined high-frequency (7-11 or 8-12 Hz; 11-15 or 14-18 Hz) oscillatory components of the electroencephalogram (EEG) burst activity derived from thiopental-induced burst-suppression patterns (BSP) were investigated in seven sedated patients (17-26 years old) with severe head injury. The predominant high-frequency burst oscillations (>7 Hz) were detected for each patient by means of time-variant amplitude spectrum analysis. Thereafter, the instantaneous envelope (IE) and the instantaneous frequency (IF) were computed for these low- and high-frequency bands to quantify amplitude-frequency dependencies (envelope-envelope, envelope-frequency, and frequency-frequency correlations). Time-variant phase-locking, phase synchronization, and quadratic phase couplings are associated with the observed amplitude-frequency characteristics. Additionally, these time-variant analyses were carried out for modeled burst patterns. Coupled Duffing oscillators were adapted to each EEG burst and by means of these models data-based burst simulations were generated. Results are: (1) strong envelope-envelope correlations (IE courses) can be demonstrated; (2) it can be shown that a rise of the IE is associated with an increase of the IF (only for the frequency bands 0.5-2.5 and 7-11 or 8-12 Hz); (3) the rise characteristics of all individually averaged envelope-frequency courses (IE-IF) are strongly correlated; (4) for the 7-11 or 8-12 Hz oscillation these associations are weaker and the variation between the time courses of the patients is higher; (5) for both frequency ranges a quantitative amplitude-frequency dependency can be shown because higher IE peak maxima are accompanied by stronger IF changes; (6) the time range of significant phase-locking within the 7-11 or 8-12 Hz frequency bands and of the strongest quadratic phase couplings (between 0.5-2.5 and 7-11 or 8-12 Hz) is between 0 and 1,000 ms; (7) all phase coupling characteristics of the modeled bursts accord well with the corresponding characteristics of the measured EEG burst data. All amplitude-frequency dependencies and phase locking/coupling properties described here are known from and can be discussed using coupled Duffing oscillators which are characterized by autoresonance properties.

Topics: Adolescent; Adult; Algorithms; Craniocerebral Trauma; Electroencephalography; Female; Humans; Hypnotics and Sedatives; Male; Mathematics; Models, Neurological; Pattern Recognition, Automated; Periodicity; Signal Processing, Computer-Assisted; Thiopental; Time Factors

Topics: Adult; Craniocerebral Trauma; Fatal Outcome; GABA Modulators; Humans; Hyperkalemia; Male; Thiopental

Thiopental has been used for decades in the treatment of refractory intracranial hypertension in patients with traumatic and nontraumatic head injuries. Commonly reported adverse effects include hypotension, hypokalemia, respiratory complications, and hepatic dysfunction. Neutropenia has rarely been reported as an adverse effect of thiopental. We witnessed probable thiopental-induced neutropenia in two patients with traumatic brain injuries who developed increased intracranial hypertension that was refractory to standard therapy. Based on a MEDLINE search of published case reports and literature, we propose two mechanisms by which thiopental-related neutropenia might be explained. The first is inhibition of inflammatory mediator nuclear factor-kappa B (NF-kappa B), leading to granulocyte apoptosis. The second mechanism involves inhibition of calcineurin. Although the precise link between these two mechanisms has not been elucidated, calcineurin is known to regulate NF-kappa B activity. Development of neutropenia does not appear to be correlated with time but may correlate with plasma concentrations of thiopental. The optimum management of drug-induced neutropenia is unclear. The decision to discontinue thiopental in patients who develop neutropenia should be made by weighing the risks versus benefits. Broad-spectrum antibiotics may be required in the presence of fever. The role of hematopoietic growth factors such as granulocyte colony-stimulating factor is not yet defined. Given the adverse infectious consequences of neutropenia, it is essential to closely monitor neutrophil counts in patients receiving thiopental.

Topics: Adult; Barbiturates; Calcineurin; Craniocerebral Trauma; Female; Humans; Male; Neutropenia; NF-kappa B; Severity of Illness Index; Thiopental

The safety of hemodynamic reactions were studied at the stages of operative treatment of patients with severe cranio-cerebral traumas (CCT) during anesthesia using alfa-2 adrenoagonist Clofelin and opioid analgetic Fentanyl and basal hypnotics Propofol and sodium Thiopental. It was shown that the using of these techniques of anesthesia in CCT patients is followed by a formation of a sufficient and physiologically justified level of neurovegetative stabilization. It facilitates a coordinated work of the mechanisms of auto-regulation of blood circulation responsible for the maintenance of stable tissue perfusion at all steps of operations.

Topics: Analgesics; Anesthetics, Combined; Anesthetics, Intravenous; Blood Circulation; Clonidine; Craniocerebral Trauma; Fentanyl; Glasgow Coma Scale; Hemodynamics; Homeostasis; Humans; Hypnotics and Sedatives; Propofol; Thiopental

Efficacy and limitation of barbiturate therapy employed as postoperative treatment for acute traumatic intracranial hematomas were studied in 20 patients. The clinical cases in this series included 15 males and 5 females with mean age of 41.8 years who all were operated on for intracranial hematomas within 3 days after injury. Glasgow Coma Scale (GCS) score was less than 7 in all instances and intracranial pressure (ICP) as well as arterial pressure was monitored postoperatively with Gaeltec and Gould transducers. Barbiturate therapy (5 mg/kg of thiopental as an initial dose and loading dose of 2-3 mg/kg/hour) was given when ICP rose above 20 mmHg and maintained for 3 days after operation. The outcome of the patients was assessed by Glasgow Outcome Scale 3 months after injury. The response of barbiturate on ICP and the changes of cerebral perfusion pressure (CPP) during the therapy in relation to the outcome were studied. Final outcome of the patients revealed 5 of good (good recovery and moderate disability), 3 of poor (severe disability and vegetative state) outcomes and 60% of mortality rate. Eleven out of 20 patients responded to barbiturate therapy and 0-20 mmHg of ICP reduction (mean reduction of 10 mmHg) was obtained in these cases. Among these cases, 2 out of 3 dead patients were older than 60 years. There were no responses of barbiturate in 7 patients to whom the therapy was started when ICP rose above 40 mmHg. No response of the therapy on ICP was also observed in the patients with GCS score of 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Cerebral Hemorrhage; Craniocerebral Trauma; Female; Hematoma; Humans; Intracranial Pressure; Male; Middle Aged; Postoperative Complications; Prognosis; Thiopental

Topics: Barbiturates; Coma; Craniocerebral Trauma; Humans; Thiopental

The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.

Topics: Adrenal Cortex Hormones; Cell Count; Craniocerebral Trauma; Critical Care; Dexamethasone; Fever; Humans; Intensive Care Units; Pneumonia; Respiration, Artificial; Sputum; Thiopental

Despite of controversial findings, High-Dose-Barbiturate Therapy is advocated by many authors for treatment of postischemic/anoxic encephalopathy and head trauma with elevated intracranial pressure. The adverse effects to thiopentone are analyzed in a retrospective study including 30 patients treated by high-dose thiopentone for raised intracranial pressure after severe head injury. The pathophysiology and occurrence of clinical complications in many systems of the organism are illustrated. The specific prevention measures and the extended monitoring of barbiturate-treated patients are described. Considering the high incidence of clinical complications the indication for HDBT has to be reevaluated.

Topics: Cardiovascular System; Craniocerebral Trauma; Digestive System; Humans; Intracranial Pressure; Liver; Monitoring, Physiologic; Respiratory Center; Thiopental

Barbiturate therapy is a controversial mode of therapy instituted in patients with acute head injuries after conventional means of treatment to decrease intracranial hypertension have been unsuccessful. Thiopental is a fast-acting central nervous system depressant and is one of the agents used for barbiturate therapy. Baseline laboratory values and access to four IV sites, including a Swan-Ganz catheterization site, should be obtained prior to institution of barbiturate therapy. While a patient is on barbiturate therapy, it is difficult to assess his clinical status. Nursing care for a patient on barbiturate therapy is an exciting challenge. It is the nurse's responsibility to continuously assess the patient's pressure readings, laboratory values, fluid balance, and pulmonary status to accurately interpret his clinical status.

Topics: Blood Chemical Analysis; Cardiovascular System; Craniocerebral Trauma; Humans; Immunosuppression Therapy; Infusions, Parenteral; Intracranial Pressure; Lung; Neurologic Examination; Thiopental

Topics: Acute Disease; Barbiturates; Craniocerebral Trauma; Humans; Intracranial Pressure; Monitoring, Physiologic; Thiopental

The hemodynamic effects of a single dose of fentanyl (4 micrograms/kg) and of thiopental (5 mg/kg) were studied on cranial trauma patients who have hypertension and who are ventilated at constant volume and frequency. At first the results were collected without an hypertensive treatment, in the second time the same results were collected after the injection of an anti-hypertensive drug (guanoxabenz 70 micrograms/kg). The results showed that in two series the modification in the measured parameters was not statistically significant; the used drugs produced little change in the hemodynamic profile: a) Even with insignificant, we noted that the injection of fentanyl after an anti-hypertensive drug caused a smaller change in the blood pressure and cardiac index then was seen in untreated subjects. b) With thiopental treated subjects, the arterial pressure is not decreased because of the increased systemic resistances, at the same time changes in cardiac index are essentially identical whether or not the subject was treated with guanoxabenz. The results therefore tend to show that the anti-hypertensive treatment can be continued without any interruption by a surgical operation.

Topics: Aged; Antihypertensive Agents; Craniocerebral Trauma; Drug Interactions; Fentanyl; Guanabenz; Guanidines; Hemodynamics; Humans; Hypertension; Middle Aged; Thiopental

Chest physiotherapy causes increases in intracranial pressure (ICP) in patients with severe head injuries. In mechanically hyperventilated severe head injuries (PaCO2 3.3 - 4 kPa) 50% nitrous oxide in 50% oxygen exacerbated ICP increases associated with chest physiotherapy, while thiopentone and Althesin reduced these changes in ICP.

Topics: Alfaxalone Alfadolone Mixture; Anesthetics; Carbon Dioxide; Craniocerebral Trauma; Humans; Intracranial Pressure; Nitrous Oxide; Oxygen; Partial Pressure; Respiration, Artificial; Thiopental

Topics: Adolescent; Adult; Alfaxalone Alfadolone Mixture; Anesthesia, General; Brain Edema; Craniocerebral Trauma; Humans; Hypoxia; Intracranial Pressure; Intubation, Intratracheal; Male; Oxygen; Positive-Pressure Respiration; Postoperative Care; Respiration, Artificial; Thiopental

Topics: Adolescent; Blood Pressure; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Coma; Craniocerebral Trauma; Female; Humans; Hypothermia, Induced; Intracranial Pressure; Male; Middle Aged; Pentobarbital; Perfusion; Respiration, Artificial; Skull Fractures; Thiopental