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PubMed1977

The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane, and thiopental.

The relationship between cerebral oxygen consumption (CMRO2) and anesthetic concentration has been assumed (based upon isolated measurements) to be approximately linear at concentrations less than 1 MAC. The shapes of the anesthetic dose-response curves for both CMRO2 and cerebral blood flow (CBF) were examined by multiple measurements made at small, progressive concentration increments from 0 to 2 MAC halothane (six dogs), enflurane (six dogs), and isoflurane (six dogs), and during a constant 23 mg/kg/hr infusion of thiopental (six dogs). The EEG was continuously recorded and changes in EEG patterns from "awake" to "anesthetic" were correlated with changes in anesthetic concentration, CBF, and CMRO2. The significance of changes in the slopes of regression lines for CMRO2 before, during and after changes in EEG patterns from "awake" to "anesthetic" were then determined. Contrary to previous inferences, CMRO2 dose-response curves were found to be nonlinear at anesthetic concentrations less than 1 MAC for all anesthetics studied. CMRO2 decreased precipitously until a stable "anesthetic" pattern was observed on the EEG; thereafter, CMRO2 decreased at a markedly reduced rate. The onset of this change occurred at concentrations well below MAC for the inhalational anesthetics. With the thiopental infusion, CMRO2 decreased most rapidly during the first 25 minutes. With halothane and enflurane, CBF was maximal during the period of transition in the EEG from an "awake" to an "anesthetic" pattern. CBF was elevated at all concentrations of isoflurane studied. CBF decreased rapidly during thiopental infusion until the EEG pattern changed from "awake" to "anesthetic" and then more slowly. The results demonstrate that the change in the EEG to an "anesthetic" pattern, which occurs at concentrations well below MAC, is accompanied by an abrupt metabolic depression. It is speculated that these events coincide with the onset of functional depression.

Animals↗
PubMed1982

Thiopental disposition as a function of age in female patients undergoing surgery.

The effect of age on the disposition kinetics of thiopental was studied in 22 lean female patients having a body mass index (weight (kg/height(m)2) less than 30 and whose age ranged between 25 to 83 years. Patients underwent primarily abdominal surgery. A strong positive correlation between age and the apparent volumes of distribution, V beta and Vss, was found (P less than 0.001). No significant relationship was found between total body clearance and age. The elimination half-life (t1/2) of thiopental increased with age, and was primarily a function of volume of distribution. The free or unbound fraction of thiopental in serum (alpha) ranged between 0.168 and 0.276 and was significantly correlated with age (P less than 0.005). Multiple regression analysis indicated that age was the independent variable which contributed most the variability in t1/2, V beta, and Vss. No conclusion can be reached concerning the potential differences in anesthetic induction doses required as a function of age; however, these data suggest that care may be required in the use of a balanced anesthetic technique in the elderly as a result of prolonged elimination.

Abdomen↗
PubMed1983

Comparative renal effects of midazolam and thiopental in humans.

Midazolam is a water-soluble benzodiazepine whose quick onset after intravenous injection, short duration of action, absence of venous irritation, and mild cardiovascular and respiratory effects suggest its use for induction of anesthesia. The renal effects of midazolam-N2O-O2 anesthesia, as determined by renal clearance of injected inulin and para-aminohippuric acid (PAH), in hydrated ASA Class I-II surgical patients (N = 8) were compared in a double-blind fashion with a similar group of patients (N = 9) anesthetized with thiopental-N2O-O2. Except for glomerular filtration rate, there were no significant changes in any of the measured variables (blood pressure, effective renal plasma flow, renal blood flow, and renal vascular resistance). The per cent reduction in glomerular filtration rate in patients given thiopental differed significantly from that in patients given midazolam. This study suggests that midazolam, as opposed to thiopental, offers minimal advantage in maintaining renal performance at least during the period of anesthetic administration.

Anesthesia↗
PubMed1984

Thiopental treatment after global brain ischemia in pigtailed monkeys.

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)

Animals↗
PubMed1986

Effects of thiopental, fentanyl, and etomidate on upper extremity somatosensory evoked potentials in humans.

The effects of three anesthetic induction agents on somatosensory evoked potentials (SEP) were assessed in unpremedicated patients who were without neurologic abnormality of the upper extremities. SEP was assessed by stimulation of the nondominant median nerve and responses were recorded over Erbs point (N10), second cervical vertebra (N14), and the contralateral cortex (P15, N20, P23 latencies, and P15-N20 and N20-P23 amplitudes). Nine patients received thipental (4 mg/kg, iv bolus), nine patients received fentanyl (25 micrograms/kg, iv bolus), and nine patients received etomidate (0.4 mg/kg, iv bolus). SEP was assessed before and after drug administration at motor threshold stimulus intensity. Thiopental increased the latency of N10, N14, and N20. The amplitudes of N10-, N14-, and scalp-recorded waves were not altered by thiopental. Fentanyl increased N20 and P23 latency and decreased the amplitude of P15-N20. Etomidate increased latency of N20 and P23 without alteration of latencies of N10 or N14 and increased the amplitude of P15-N20 and N20-P23, while the amplitude of N10 was unchanged and the amplitude of N14 was decreased. It is concluded that thiopental or fentanyl causes only modest alterations in early waves of upper extremity SEP, whereas etomidate increases the amplitude of scalp-recorded waves. The effect of etomidate on SEP may make diagnosis of neurologic injury more difficult because of the changing waveform.

Adult↗
PubMed1989

Fentanyl-induced muscle rigidity in unanesthetized and ketamine- or thiopental-anesthetized rats.

This study was undertaken to search for an alternative experimental model in the evaluation of fentanyl-induced muscle rigidity. Unanesthetized, spontaneously ventilating Sprague-Dawley rats, and rats anesthetized with either ketamine or thiopental whose ventilation was mechanically controlled, were studied. Intravenous administration of fentanyl (25, 50, or 100 micrograms/kg) caused an increase in electromyographic (EMG) activity in both unanesthetized and ketamine-anesthetized, but not in thiopental-anesthetized, animals. Muscle rigidity was more prominently manifested in the gastrocnemius muscle, when compared with the rectus abdominis muscle. Hypoxemia was exhibited during the course of rigidity by both spontaneously ventilating and ketamine-anesthetized rats, but not by thiopental-anesthetized animals. In addition, unanesthetized, spontaneously ventilating rats developed hypercarbia and respiratory acidosis. The authors suggest that, in addition to using unanesthetized animals, EMG activity in the gastrocnemius muscle of rats anesthetized with ketamine in whom ventilation is controlled may provide an alternative approach in the evaluation of fentanyl-induced muscle rigidity.

Anesthesia↗
PubMed1989

Thiopental requirements for induction of anesthesia in neonates and in infants one to six months of age.

The authors determined the thiopental dose needed for satisfactory induction in ten neonates, 0-14 days of age, and 20 infants, 1-6 months of age. A single iv bolus of thiopental was given. Thirty seconds after injection the anesthesia mask was applied and the response was observed during the following 30 s while the patient breathed oxygen. Induction was considered satisfactory if there were no gross movements or coughing. The dose required for satisfactory induction in 50% of patients, ED50 (+/- SE), was 3.4 +/- 0.2 mg/kg in neonates and 6.3 +/- 0.7 mg/kg in infants (P less than 0.001). It is concluded that the thiopental dose needed for satisfactory induction is less in neonates than in infants.

Anesthesia, Intravenous↗
PubMed1992

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.

Adult↗
PubMed1997

Decreased thiopental requirements in early pregnancy.

BACKGROUND: Anesthetic requirements for inhalational agents are decreased during pregnancy, but there are no data regarding requirements for intravenous agents. The quantal dose-response curves for thiopental were calculated for 70 nonpregnant women having gynecologic surgery and for 70 pregnant women of 7-13 weeks' gestation having elective abortions. METHODS: Groups of 10 patients were given 2, 2.4, 2.8, 3.3, 3.8, 4.5, or 5.3 mg/kg thiopental as a bolus dose during a period of 10 s. Two minutes later, patients were asked to open their eyes as a test for hypnosis. Patients who did not open their eyes were given a 10-s, 50-Hz, 80-mA transcutaneous tetanic electrical stimulus to the ulnar nerve as a test for anesthesia. Purposeful movement indicated that there was no anesthesia. Log dose-response curves for hypnosis and anesthesia were calculated after logit transformation. RESULTS: In the nonpregnant women, the median effective doses (ED50s) (95% confidence interval) for hypnosis and anesthesia were 3.1 (2.8-3.4) mg/kg and 4.9 (4.5-5.4) mg/kg, whereas in the pregnant women the corresponding ED50s were 2.6 (2.3-2.8) mg/kg and 4 (3.7-4.4) mg/kg. In the non-pregnant women, the ED95s (95% CI) for hypnosis and anesthesia were 4.4 (3.9-5.4) mg/kg and 6.4 (5.7-7.9) mg/kg, whereas in the pregnant women the corresponding ED95s were 3.7 (3.3-4.5) mg/kg and 5.2 (4.7-6.3) mg/kg. The pregnant to nonpregnant relative median potency (95% CI) ratio for hypnosis was 0.83 (0.67-0.96) and for anesthesia it was 0.82 (0.62-0.94). CONCLUSIONS: The dose of thiopental for hypnosis was 17% less and that for anesthesia was 18% less in pregnant women of 7-13 weeks' gestation compared with that in nonpregnant women.

Adult↗
PubMed1999

Thiopental attenuates energetic impairment but fails to normalize cerebrospinal fluid glutamate in brain-injured patients.

OBJECTIVES: Brain-injured patients are susceptible to secondary brain damage related to decreased cerebral perfusion pressure associated with edema formation and increased intracranial pressure (ICP). Whenever conventional therapy fails to reduce elevated ICP, barbiturate coma represents an additional intervention that may control ICP. In patients suffering from severe traumatic brain injury, cerebrospinal fluid levels of glutamate, hypoxanthine, and lactate were measured during barbiturate coma and correlated to electroencephalographic recordings and ICP. DESIGN: Prospective, descriptive study. SETTING: Ten-bed surgical intensive care unit in a university hospital. PATIENTS: Twenty-one patients with severe traumatic brain injury (Glasgow Coma Scale score < or = 9); 11 required barbiturate coma because of refractory intracranial hypertension, and 10 were manageable with continuous administration of fentanyl and midazolam. INTERVENTIONS: Thiopental was administered continuously for increased ICP within the first 24 hrs after trauma and adjusted to the burst-suppression pattern (four to six bursts per minute) on continuous electroencephalographic monitoring. MEASUREMENTS AND MAIN RESULTS: Glutamate and hypoxanthine were analyzed using high-performance liquid chromatography, whereas lactate was measured enzymatically. Patients requiring thiopental presented with significantly higher ICP, glutamate, and hypoxanthine levels than patients receiving fentanyl and midazolam (p < .05). Within the first 24 hrs, thiopental significantly reduced cerebrospinal fluid glutamate and hypoxanthine levels in all patients, i.e., the burst-suppression pattern was successfully induced (p < .001). Interestingly, in five patients cerebrospinal fluid glutamate increased to initial values again despite unchanged neuronal activity. In these patients, ICP, hypoxanthine, and lactate remained significantly elevated compared with the six patients with steadily decreasing cerebrospinal fluid glutamate, hypoxanthine, lactate, and ICP values (p < .02). CONCLUSIONS: Barbiturate coma does not unequivocally preserve energetic stability despite successful suppression of neuronal activity. Despite the use of barbiturate coma in patients with refractory intracranial hypertension, persistent release or impaired uptake of glutamate may be associated with continuous anaerobic metabolism, as shown by increases in cerebrospinal fluid hypoxanthine and lactate levels.

Adolescent↗
PubMedDate not supplied

Effects of thiopental on tension development, action potential, and exchange of calcium and potassium in rabbit ventricular myocardium.

Thiopental in concentrations of 28 and 227 mumoles/liter reduced the tension developed by isolated rabbit ventricular myocardium by 50 and 80%, respectively. The effect was rapid, reversible, and independent of heart rate. Thiopental (227 mumoles/liter) inhibited influx and efflux of potassium to the same extent, so that no net gain or loss occurred. Calcium influx and efflux were also reduced, but calcium was not displaced from the myocardium in association with the decline of tension. The maximum rate of depolarization of the action potential and the time to 50% repolarization were decreased, but resting membrane potential, amplitude, and time to 90% depolarization were unchanged. The negative inotropic effect of thiopental appears to be due to reduced availability of calcium to the myofibrils.

Action Potentials↗
PubMed1993

Effects of thiopental and ketamine on cardiac function during moderate hemorrhage in chronically instrumented rats.

This study was designed to assess the effects of thiopental and ketamine on cardiac function after a blood loss of 2 ml/100 g of body weight. In nine Sprague-Dawley rats, a catheter was placed in the abdominal aorta, a pulsed Doppler probe was positioned around the thoracic aorta, and a wall-thickness probe was sutured onto the left ventricle. On three occasions, all rats were studied awake, during thiopental anesthesia, and during ketamine anesthesia. In awake rats, a 30% blood loss resulted in an immediate, transient hypotension (49%) and a prolonged decrease in cardiac output (39%) and stroke volume (28%). No significant changes were observed in the wall-thickening fraction, which is an index of cardiac contractility, and in the heart rate. The effect of thiopental on cardiovascular responses to moderate hemorrhage was minimal. Although ketamine did not affect the hypotensive response to moderate hemorrhage, it did accentuate systemic vasoconstriction and cardiac depression as indicated by a decrease in cardiac output (57%), stroke volume (49%), and wall thickness (47%).

Animals↗
PubMed2006

Seizure length with sevoflurane and thiopental for induction of general anesthesia in electroconvulsive therapy: a randomized double-blind trial.

In general, seizure length does not correlate with clinical outcome with electroconvulsive therapy (ECT), but whether markedly short seizures are still therapeutic is unknown. Furthermore, seizure length effects on clinical outcome in ECT may be different among the various anesthetic agents available. Several studies have investigated the use of inhalational anesthesia in ECT with sevoflurane. In general, seizure length when reported has been in the range of typical values encountered in practice. We recently completed a randomized double blind trial with sevoflurane induction compared with thiopental. Seizure duration with sevoflurane anesthesia was 8 seconds shorter than with thiopental for electroencephalogram and 6.4 seconds shorter for motor, the latter just barely missing statistical significance. Absolute values for seizure duration with both sevoflurane and thiopental are well within typical ranges for those seen with the more commonly used methohexital as anesthetic.

Anesthesia, General↗
PubMed1982

Influence of moderate alcohol intake on thiopental anesthesia.

The relationship between alcohol intake over the week preceding anesthesia and various anesthetic parameters was examined in 119 women scheduled for termination of pregnancy under thiopental-nitrous oxide anesthesia. In terms of pure alcohol, the weekly intake was 1.03 +/- 1.09 ml.kg-1 (mean +/- s.d.), range 0-5.93, i.e. below average consumption in Denmark. Alcohol intake was negatively correlated with anesthetic sleeping time (P less than 0.01). Time and quality of anesthesia induction and frequency of anesthetic complications were not significantly correlated with the use of alcohol. Preanesthetic anxiety was not significantly correlated with any of the above data. Induction time and postoperative awareness were positively and sleeping time negatively correlated with age (P less than 0.05). The results indicate cross-tolerance between alcohol and thiopental, even when the regular intake of the former is low, and increasing thiopental requirements with increasing age.

Abortion, Induced↗
PubMed1983

Pharmacokinetics and pharmacodynamics of thiopental in patients undergoing renal transplantation.

The effects and pharmacokinetics of thiopental were studied in eight patients undergoing renal transplantation. The results were compared with findings in a group of patients with normal renal function. No differences were observed in induction doses or between arterial or venous sleep concentrations. The average V3 in the renal failure group was 1441 or 2.5 times the value of the control group (P less than 0.01). The apparent differences indicating longer elimination half-lives and higher serum clearances in the renal patients were not significant. The average binding of thiopental to serum protein shortly after the induction was 83.9% (78.2-88.1) in the renal patients and 89.0% (85.2-91.6) in the control patients (P less than 0.05). The difference in V3 could be explained by the differences in protein binding and when the serum clearance was calculated by using the unbound fraction, this "intrinsic clearance" was significantly lower in the renal failure group (P less than 0.05). Haemodynamic parameters were determined during the initial 5 min. No significant difference was observed between the thiopental-induced changes in stroke volume. Cardiac output was unchanged in both patient groups.

Adult↗
PubMed1985

Increased thiopental sensitivity in cardiac patients.

The average dose of thiopental necessary for induction was 3.4 mg/kg body weight in seven patients on long-term therapy with digoxin and a diuretic and 4.7 mg/kg body weight in seven matched control patients (P less than 0.05). The initial volumes of distribution (V1) did not differ significantly. The amounts of thiopental redistributed (removed from V1) during the induction were calculated as V1 X k12 X ct and V1 X k13 X ct, where k12 and k13 are the rate constants describing the drug transfer from V1 to V2 and V3 and ct the computer-calculated average thiopental concentration in V1 during the initial 40 s of the induction period. There was no evidence of a lower amount being removed during the induction in the cardiac patients. The intravascular drug concentration at the time of sleep was expressed as the average of the arterial and the venous sleep concentrations. In the cardiac patients the average of that value was 20.1 micrograms/ml and in the control patients 30.2 micrograms/ml (P less than 0.05). It is concluded that the lower dose requirement in the cardiac patients was caused at least in part by a higher cerebral sensitivity to the drug.

Aged↗
PubMed1986

Hypertensive response to thiopental in man during cardiopulmonary bypass.

We report the effect of 250 mg of sodium thiopental on vascular tone at constant blood flow in 26 patients undergoing cardiopulmonary bypass while the ascending aorta was cross-clamped. Light anaesthesia was effected with fentanyl and enflurane, muscle relaxation with pancuronium. After a latent period of 10.5 +/- 0.7 s there was a hypertensive response of 9.8 +/- 0.5 s duration and of 21.4 +/- 1.7 mmHg (2.8 +/- 0.2 kPa) magnitude; this was followed by hypotension of 39.6 +/- 4.2 s duration and of 18.4 +/- 1.9 mmHg (2.4 +/- 0.3 kPa) magnitude. There was a statistically significant inverse correlation between the hypertension and body temperature (P = 0.005); the time to onset of hypertension correlated directly with pump volume (P = 0.001), weight of the patient (P = 0.03), and cross-clamp time before the drug was given (P = 0.002), and correlated inversely with the serum sodium concentration (P = 0.001). The duration of hypertension was inversely related to the plasma bicarbonate (P = 0.01) and body temperature (P = 0.04). The duration of hypotension was significantly longer in women (P = 0.0001) and was directly related to the duration of cross-clamping (P = 0.0007), to pH (P = 0.0016), and to PCO2 (P = 0.04). We speculate that thiopental induced the hypertensive response due to a potentiation of the vasoconstrictive (local) effect of norepinephrine, and induced the hypotensive response by a central nervous system effect. Thiopental had no apparent effect on venous tone.

Anesthesia, General↗
PubMed1989

Effects of thiopental on granulocyte oxidative microbicidal capacity.

Some anaesthetics are known to depress granulocyte chemiluminescence responses in the phagocytosis of zymosan as a measure of their oxidative microbicidal capacity. In this study the effects of thiopental were measured on chemiluminescence responses in the phagocytosis of Staphylococcus aureus and Escherichia coli, which are the commonest bacteria causing postoperative infections. Granulocytes from 14 healthy volunteers (mean age 35 +/- 9 (s.d.) years) were tested in vitro in the presence of clinical thiopental concentrations 0, 5, 10 and 25 micrograms/ml (0, 18, 36 and 91 mumol/l, respectively). During a 60-min exposure period, decreased chemiluminescence responses occurred to Staph. aureus at 5 micrograms/ml (P less than 0.01) and higher thiopental concentrations and to E. coli at 10 micrograms/ml (P less than 0.01) and higher concentrations, as a sign of depressed oxidative microbicidal activity.

Adult↗