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PubMed1975

Effects of thiopental (Trapanal) on coronary blood flow and myocardial metabolism in man.

The influence of thiopental (Trapanal) on coronary blood flow (MPF), myocardial oxygen consumption (MVO2), and general haemodynamics was investigated in seven patients without heart disease. Besides measurement of MBF, the amount of substrates (glucose, lactate, pyruvate and free fatty acids (FFA) was also determined in arterial and coronary sinus blood samples. Thiopental was given intravenously in a mean dose of 4 mg/kg b,w, MBF was measured by means of the argon method. After injection of thiopental, all seven patients showed a significant increase of MBF and MVO2, a fact which can essentially be explained by the increase of heart rate. The effects of thiopental on arterial concentrations, arterior-coronary substrate differences, myocardial uptake, and O2-extraction ratio of the different substrates are discussed.

Adult↗
PubMed1981

Pharmacokinetics of thiopental in caesarian section.

Anaesthesia for planned caesarian section in nine women was induced with an i.v. thiopental injection. The injection was stopped when the ciliary reflex disappeared. 250-300 mg was given over 60-85 seconds. The concentration of thiopental in peripheral venous blood 20 s after the disappearance of the ciliary reflex varied from 4.3 to 33.7 micrograms/ml. The simultaneously obtained concentrations at delivery (11-25 min after the start of the induction) were 1.7-6.0 micrograms/ml in venous blood from the mothers and 1.3-5.5 micrograms/ml in cord vein blood. In two of the newborns, the Apgar scores were 8 and 9, in the other seven it was 10. The baby with Apgar score 8 was delivered after 25 min and had a concentration in cord vein blood of 3.5 micrograms/ml. The decline in the concentration of thiopental in the venous blood of the mothers was described by a three-compartment open model. The terminal half-life was relatively short, between 91 and 595 min. The blood levels of thiopental in the newborns were followed for 22-33 h. The terminal half-lives in the babies ranged from 616 to 2560 min.

Adult↗
PubMed1983

Influence of moderate alcohol intake on wakening plasma thiopental concentration.

In an earlier study, an inverse correlation between thiopental-induced sleeping time and alcohol intake in the preceding week was demonstrated in women undergoing termination of pregnancy. In order to investigate the mechanism behind the apparent cross-tolerance, the relationship between alcohol consumption in the week preceding thiopental/nitrous oxide/oxygen anesthesia and wakening plasma thiopental concentration on one hand and sleeping time on the other was examined in 68 women scheduled for termination of pregnancy and in 37 women scheduled for diagnostic uterine dilatation and curettage. In terms of pure alcohol, the weekly intake (mean +/- s.d.) was 1.17 +/- 2.07 ml . kg-1 in the former and 1.49 +/- 1.70 ml . kg-1 in the latter group. A positive correlation between alcohol consumption and wakening plasma thiopental concentration was found in both groups, reaching statistical significance (P less than 0.05) in the group undergoing termination of pregnancy, but not in the other. The inverse correlation found earlier between alcohol intake and sleeping time was not reproduced significantly in any of the groups. The results indicate that moderate alcohol intake may induce cerebral tolerance to thiopental.

Abortion, Induced↗
PubMed1987

The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently.

In man, a change of thiopental pharmacokinetics was observed under halothane anesthesia, but not when patients were anesthetized with enflurane and isoflurane. After an initial subanesthetic dose of 50 mg thiopental, the concentrations in serum (T) were determined over 15 min (4 samples). From these T-values the pharmacokinetic parameters Vc (central volume of distribution), t1/2 alpha and Cl were established (control). 16 min after the first thiopental dose, one of the inhalation anesthetics was administered (randomized). After 45 min exposure to the respective inhalation anesthetic (2-3 MAC in combination with N2O, steady-state a second dose of 50 mg thiopental was injected and the T-values were determined again over 15 min. The T-values of the control course varied considerably; the logarithmic frequency distribution revealed two distinct subgroups of patients, A and B, with characteristic Vc and t1/2 alpha. Both subgroups were influenced by the volatile anesthetics in a similar way with regard to pharmacokinetic parameters. With halothane, Vc was decreased and t1/2 alpha was shortened. In contrast, enflurane and isoflurane did not affect the pharmacokinetic parameters.

Adult↗
PubMed1989

Induction and recovery characteristics of propofol, thiopental and etomidate.

Propofol, thiopental and etomidate, with 20 patients in each group, were compared for anesthesia of short duration in women undergoing termination of pregnancy, with respect to: 1: pain on injection (equally often after propofol and etomidate, but more rarely after thiopental); 2: apnea following induction (no difference); 3: involuntary muscular movements more frequent after etomidate); 4: blood pressure (larger drop after propofol); 5: heart rate (greater increase after thiopental); 6: time to eye opening on command (longer after propofol); 7: Steward score on eye opening (no difference); 8: coin counting after 15, 30 and 60 min (performance better after propofol at 15 and 30 min, producing even shorter times than preoperatively at 60 min); 9: reaction time after 15, 30 and 60 min (performance better after propofol, producing even shorter times than preoperatively at 60 min. It is concluded that the faster recovery gives propofol an advantage over thiopental and etomidate in outpatient anesthesia.

Abortion, Induced↗
PubMed1991

Basophil histamine release in atopic patients after in vitro provocation with thiopental, Diprivan and chlormethiazole.

The degree of histamine release induced by three different anesthetic drugs was studied in vitro using basophil leukocytes from atopic patients (n = 11) and controls (n = 14). In all, eight dilutions (1/2 to 10(-5)) of Diprivan and its solvent Intralipid, thiopental and chlormethiazole in aqueous solution, were used. Histamine was released in four controls with weak dilutions (1/2 to 10(-5)) of Diprivan (n = 2) and thiopental (n = 2). The reaction with thiopental was greater than that with Diprivan. Five of the atopic subjects released histamine with one or more drug: thiopental and Diprivan four times each, Intralipid twice, and chlormethiazole once. Histamine release was greater in these patients than in controls, and occurred with dilutions ranging from 1/2 to 10(-2), except for one case. It is concluded that atopic patients release histamine with hypnotic anesthetic drugs more easily than normal subjects. In the clinical setting, where blood concentration of the drugs studied is equivalent to a dilution of less than 10(-3), they do not release much histamine. They may be used in atopic patients if the drugs are injected slowly.

Basophils↗
PubMed1995

Comparison of eltanolone and thiopental in anaesthesia for termination of pregnancy.

Eltanolone, a new steroid hypnotic, was compared to thiopental in short anaesthesia. Sixty unpremedicated, Asa 1-2 women were randomized to receive eltanolone 0.6 (group E1) or 0.8 mg.kg-1 (group E2) or thiopental 4 mg.kg-1 (group T) for induction of anaesthesia. One minute before induction glycopyrrolate 0.2 mg and alfentanil 15 micrograms.kg-1 i.v. were administered. If induction failed, additional boluses of the test drug were given. Anaesthesia was maintained with 67% nitrous oxide in oxygen, and additional bolus doses of the test drug were given in a standardized fashion, if needed. Recovery was assessed by a research nurse blinded to the agent used. Mean +/- s.d. induction doss were 0.7 +/- 0.1 mg.kg-1 (group E1), 0.8 +/- 0.1 mg.kg-1 (group E2) and 4.0 +/- 0.0 mg.kg-1 (group T). Induction time was prolonged in the group E1 compared to the other two groups (P < 0.05). Side effects were few in all groups, but involuntary muscle movements or hypertonus occurred in 23% of the patients in the eltanolone and in 3% in the thiopental groups (n.s). Early recovery (eye opening, orientation and sitting) was slower in both eltanolone groups compared to the thiopental group (P < 0.01). No differences between the groups were found in toleration of oral fluids, walking, voiding, postoperative analgesic requirements or postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗
PubMed1989

Studies on lorazepam as a premedicant for thiopental anaesthesia in the dog.

Four mg of lorazepam was given intravenously 5 min prior to thiopental anaesthesia in 5 clinically healthy dogs weighing 14 +/- 2 kg and aged about 10-12 months. Animals required only 7.0 +/- 1.5 ml of 5% thiopental sodium to achieve surgical anaesthesia which lasted about 30.4 +/- 3.3 minutes. There was adequate muscle relaxation and loss of pedal and palpebral reflexes. Five min after administration of lorazepam, there was no appreciable change in various cardiopulmonary dynamics. However, there was moderate arterial hypertension, tachycardia and arterial hypoxemia 15 min after the onset of the thiopental anaesthesia. There was no respiratory depression. The lorazepam-thiopental combination was also attempted in 16 clinical cases varying from repair of fractures of long bones (9), mammary tumour (2), ear haematoma (1), ear cropping (1), tail gangrene (2) and rectal prolapse (1). This combination of anaesthesia proved extremely useful for orthopaedic surgery as the muscle relaxation was adequate and reduction of the fractured ends was comparatively easier.

Anesthesia↗
PubMed2005

A comparison of propofol, thiopental or ketamine as induction agents in goats.

OBJECTIVE: To compare propofol, thiopental and ketamine as induction agents before halothane anaesthesia in goats. STUDY DESIGN: Prospective, randomized cross-over study. Animals Seven healthy adult female goats with mean (+/-SD; range) body mass of 38.9 +/- 3.29 kg; 35-45 kg. METHODS: The seven animals were used on 21 occasions. Each received all three anaesthetics in a randomized cross-over design, with an interval of at least 2 weeks before re-use. Anaesthesia was induced with intravenous (IV) propofol (3 mg kg(-1)), thiopental (8 mg kg(-1), IV) or ketamine (10 mg kg(-1), IV). Following tracheal intubation, anaesthesia was maintained with halothane for 30 minutes. Indirect blood pressure, heart rate, respiratory rate and arterial blood gases were monitored. The quality of induction and recovery, recovery times and incidence of side-effects were recorded. RESULTS: Induction of anaesthesia was smooth and uneventful, and tracheal intubation was easily performed in all but two goats receiving ketamine. Changes in cardiopulmonary variables and acid-base status were similar with all three induction agents and were within clinically acceptable limits. Mean recovery times (time to recovery of swallowing reflex and to standing) were significantly shorter, and side-effects, e.g. apnoea, regurgitation, hypersalivation and tympany, were less common in goats receiving propofol, compared with the other treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol 3 mg kg(-1) IV is superior to thiopental and ketamine as an induction agent before halothane anaesthesia in goats. It provides uneventful recovery which is more rapid than thiopental or ketamine, so reduces anaesthetic risk.

Anesthesia↗
PubMed1980

The binding of thiopental to serum proteins determined by ultrafiltration and equilibrium dialysis.

An ultrafiltration method is described by which it is possible to estimate the protein bound fraction of a drug at its original concentration in a serum sample. The determination is carried out at 37 degrees and pH 7.4. For thiopental no difference was found between the values of protein binding whether they were determined by the ultrafiltration method or by a less time consuming equilibrium dialysis against an equal volume of phosphate buffered isotonic sodium chloride solution. The equilibrium dialysis was used to measure the concentration of bound and unbound thiopental molecules and the binding parameters in a two class binding model were determined. No evidence was found for binding to other proteins than albumin. About one binding site belonging to the first class was found per 1000 albumin molecules whereas an average of about 5 secondary sites were found for each albumin molecule. The association constants for the primary class of binding sites were 3.4 X 10(6)M-1 for albumin and 13.3 X 10(6)M-1 for serum while the values for the secondary class were 2.2 and 1.2 X 10(3)M-1 for albumin and serum respectively. The estimates of association constants and number of binding sites were based on experiments with total thiopental concentrations ranging from 0.4 to 80 microgram/ml. In a phosphate buffered albumin solution with 2 g albumin per 100 ml, a pH increase from 5 to 8 caused an increase in protein binding from 36 to 76%. A Scatchard plot using data from experiments with increasing albumin concentrations resulted in a "plot" with positive slope. The use of a curve like this is discussed and it is concluded that the binding parameters for thiopental are influenced by the albumin concentration.

Dialysis↗
PubMed2000

Randomised controlled trial of thiopental for intubation in neonates.

AIMS: To determine the effects of premedication with thiopental on heart rate, blood pressure, and oxygen saturation during semi-elective nasotracheal intubation in neonates. METHODS: A randomised, placebo controlled, non-blinded study design was used to study 30 neonates (mean birthweight 3.27 kg) requiring semi-elective nasotracheal intubation. The babies were randomly allocated to receive either 6 mg/kg of thiopental (study group) or an equivalent volume of physiological saline (control group) one minute before the start of the procedure. Six infants were intubated primarily and 24 were changed from orotracheal to a nasotracheal tube. The electrocardiogram, arterial pressure wave, and transcutaneous oxygen saturation were recorded continuously 10 minutes before, during, and 20 minutes after intubation. Minute by minute measurements of heart rate, heart rate variability, mean blood pressure (MBP) and transcutaneous oxygen saturation (SpO(2)) were computed. The differences for all of these between the baseline measurements and those made during and after intubation were determined. Differences in the measurements made in the study and the control groups were compared using Student's t test. RESULTS: During intubation, heart rate increased to a greater degree (12.0 vs -0.5 beats per minute, p < 0.03) and MBP increased to a lesser degree (-2.9 vs 4.4 mm Hg; p < 0.002) in the infants who were premedicated with thiopental. After intubation only the changes in MBP differed significantly between the two groups (-3.8 vs 4.6 mm Hg; p < 0.001). There were no significant changes in the oxygen saturation between the two groups during or after intubation. The time taken for intubation was significantly shorter in the study group (p < 0.04). CONCLUSIONS: The heart rate and blood pressure of infants who are premedicated with thiopental are maintained nearer to baseline values than those of similar infants who receive no premedication. Whether this lessening of the acute drop in the heart rate and increase in blood pressure typically seen during intubation of unmedicated infants is associated with long term advantages to the infants remains to be determined.

Birth Weight↗
PubMed1975

The influence of chronic ethanol consumption on the distribution of thiopental in rats.

Ethanol was administered chronically for 14 days to male Sprague-Dawley rats. Day 15 was ethanol-free. On day 16 the rats received 25 mg of thiopental per kilogram (intravenously). One minute after the injection, the ethanol-treated rats showed lower blood levels of thiopental and higher liver levels of the drug than control rats given sucrose in place of ethanol. Samples of blood drawn 5 and 10 min after injection showed no significant difference in thiopental levels between the ethanol and control groups. The ethanol-treated group slept for a significantly shorter period of time. It is concluded that chronic ethanol consumption for 14 days decreases the pharmacological effects of thiopental and alters its initial distribution in the body.

Animals↗
PubMed1988

Pharmacokinetics of thiopental in the asphyxiated neonate.

The pharmacokinetic properties of thiopental were studied in 10 asphyxiated neonates (mean +/- SE; birth weight, 3,244 +/- 212 g; gestational age, 40 +/- 1 weeks) as part of a randomized, controlled trial which tested the ability of barbiturate therapy to decrease central nervous system damage secondary to perinatal asphyxia. Therapy was begun at a mean age of 2.3 h in all and was initially given as a loading dose of 15 mg/kg over 30 min followed by a constant infusion. The mean steady-state thiopental concentration was 13.4 +/- 3.7 micrograms/ml (mean +/- SD) and the average time to reach steady state was 7 +/- 5 h. Mean elimination half-life, plasma clearance and volume of distribution for thiopental were 39 h (range 26-70), 66 ml/(h x kg) (range 31-172), and 3.6 liters/kg (range 1.1-6.7), respectively. Arterial blood pressure support was required in 8 of 10 patients. While it appears feasible to give thiopental to the asphyxiated neonate at the reported infusion rates, the risk-benefit ratio is increased by the frequent associated hypotension and need for pharmacologic blood pressure support.

Asphyxia Neonatorum↗
PubMed2005

Propofol and thiopental for refractory status epilepticus in children.

To assess safety and efficacy of propofol and thiopental for refractory status epilepticus (RSE) in children, the authors reviewed 34 episodes of RSE. Thiopental was effective in most patients, but there were serious side effects. Propofol was used according to a strict protocol. It was effective in most patients, so that thiopental was not needed. Side effects were infrequent, of minor severity, and fully reversible. The authors suggest the use of propofol before thiopental.

Anticonvulsants↗
PubMed1993

Effects of isoflurane, fentanyl, or thiopental anesthesia on regional cerebral blood flow and brain surface PO2 in the presence of a focal lesion in rabbits.

These studies were conducted to determine the effect of anesthetic drugs on tissue perfusion and O2 supply in the brain with focal cerebral edema. Using an open cranium preparation, we studied the effects of isoflurane (I; 1 minimum alveolar anesthetic concentration), of fentanyl (F; 0.5-1 microgram.kg-1 x min-1), or of thiopental (T; 32.5 mg.kg-1 x h-1) on regional cerebral blood flow (rCBF) and regional brain tissue PO2 in albino rabbits (n = 6 per group) with a focal brain lesion (cold injury). The doses of anesthetics were sufficient to suppress nociception. rCBF (H2 clearance) and tissue PO2 (multiwire surface electrode) were studied adjacent to and distant from the lesion. Cerebral hyperemia developed immediately after trauma in all groups, although the flow increase did not attain statistical significance. rCBF was subsequently reduced by about 25% in the vicinity of the lesion. Distant from the trauma, a continuing hyperemia (+30%) was later observed in animals with isoflurane, whereas rCBF was decreased then by 10%-20% in animals with fentanyl, or was unchanged with thiopental. Brain tissue PO2 was increased with isoflurane in areas distant from the lesion, but decreased with fentanyl. However, with thiopental, the PO2 level had already been lowered before trauma with a subsequent tendency toward normalization. The heterogeneity of the tissue PO2 in fentanyl anesthesia, as well as the increased frequency of hypoxic PO2 values with thiopental, might have resulted from microcirculatory disturbances. Thus, although isoflurane seemed to facilitate hyperemia with an increased O2 supply to the brain, fentanyl tended to induce the opposite response. Although these properties suggest the potential to manipulate perfusion and O2 supply in cerebral ischemia or hyperemia after head injury, the effects of such measures on intracranial pressure, neurologic status, and outcome have yet to be proven.

Anesthetics↗
PubMed1994

Quantifying the interaction of rocuronium (Org 9426) with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of rocuronium infusion.

The present study was designed to evaluate the interactions of rocuronium with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of infusion of rocuronium. Sixty patients were randomly assigned to one of six sequences where anesthesia was maintained with etomidate, fentanyl, midazolam, propofol, or thiopental and nitrous oxide, or with isoflurane and nitrous oxide. The possible interaction of rocuronium with the anesthetics was quantified by determining the asymptotic steady-state rate of infusion (Iss) of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set-point, did not differ significantly between the groups. Iss values calculated per lean body mass were 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15, and 0.39 +/- 0.17 mg.kg-1.h-1 in the etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane groups, respectively. The isoflurane group had a lower steady-state rate of infusion of rocuronium than the other five groups (P < 0.05). Compared to intravenous anesthetics, etomidate, fentanyl, midazolam, propofol, or thiopental, isoflurane reduced the infusion requirement of rocuronium by 35%-40%.

Adult↗
PubMed1985

Contraction and relaxation of rabbit basilar artery by thiopental.

Tension measurements were made on rabbit basilar artery segments to test the direct effect of thiopental on serotonin (5HT)- and norepinephrine (NE)-induced contraction. At concentrations of 3 X 10(-5) M or greater, thiopental caused relaxation of NE-induced tension. Thiopental doses greater than 3 X 10(-4) M had a similar relaxing effect on 5HT-induced contraction. However, thiopental doses below 3 X 10(-4) M demonstrated an unexpected dose-dependent potentiation of the 5HT-induced contraction.

Animals↗
PubMed1995

Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury.

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.

Anesthesia, General↗