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PubMed1986

[Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry].

Thiopental is an anaesthetic drug which is currently used for cerebral resuscitation. In this last indication the drug is administrated at high doses over a period of several days. Under clinical trials thiopental and two metabolites namely 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been determined by high performance liquid chromatography and mass spectrometry. In human plasma high concentrations of thiopental and 5 ethyl-5 (1' methyl-3' hydroxy-butyl) 2 thiobarbituric acid and a lower concentration of 5 ethyl-5 (1' methyl-3' carboxy-propyl) 2 thiobarbituric acid have been found. In urine samples these metabolites are excreted in large and approximately equal quantities, whereas small amounts of thiopental were recovered.

Adult↗
PubMedDate not supplied

[Role of cholinergic and adrenergic mechanisms in the action of ketamine and thiopental sodium on the structures of the hippocampal-reticular complex and the neocortex].

Under conditions of free behaviour of rabbits with electrodes implanted into the brain structures it was found that ketamine and sodium thiopental decrease the excitability in the dorsal hippocamp, reticular formation and periaqueductal gray matter of the midbrain. Excitability of the frontal neocortex increases during general anesthesia with ketamine and decreases during thiopental narcosis. Changes in excitability of the studied cerebral structures during general anesthesia can be determined by common N-cholinoblocking and alpha-adrenomimetic properties of ketamine and thiopental at the level of the dorsal hippocamp, cholinoblocking and adrenoblocking properties at the level of the reticular formation and central gray matter. In the frontal cortex ketamine presented properties of an M-cholinomimetic and adrenomimetic agent, sodium thiopental--those of a M-cholinoblocker and beta-adrenoblocker.

Animals↗
PubMed1986

[Effects of thiopental on sensory evoked potentials in the cat].

Noninvasive electrophysiological evaluation with sensory evoked potentials would be of clear diagnostic and prognostic value in evaluating comatose patients with stroke or severe head injury. In order to protect the brain from such kinds of insults, barbiturate coma therapy has been employed and its effectiveness has been already established. However, in the barbiturate coma therapy, it is occasionally difficult to distinguish the pharmacological effect of barbiturate from the preexisting brain dysfunction caused by the underlying process of the disease. In adult cats, authors studied changes of sensory evoked potentials following cumulative intravenous administration of thiopental which is used clinically for barbiturate coma therapy. P1 and N1 of cortical SEP showed tendency of gradual decrease in amplitude. However, no significant changes occurred in latency by stepwise increment of thiopental dose. Changes in amplitude of P1 and N1 of cortical SEP preceded to the flattening on electroencephalogram. Around at the level of the concentration where EEG changes began, I-II interpeak latency of BAEP and latency of wave I of short latency SEP started to increase. BAEP and early components of SEP (I.II.III.IV) persisted even in by far the higher level of serum concentration of thiopental than that of clinical use. Furthermore, most of these parameters showed no statistically significant change neither in amplitude nor in latency. These experimental results suggest that sensory evoked potentials will provide us with useful information in the assessment of the brainstem function in patients under thiopental induced deep coma.

Animals↗
PubMed1986

Morphine and fentanyl interactions with thiopental in relation to movement response to noxious stimulation.

The effects of morphine-thiopental and fentanyl-thiopental combinations on the movement response caused by tail clamping were studied in rats. Doses that prevented movement response when the agents were given singly and when the agents were given in combination were determined by a probit procedure and compared with isobolographic analysis. With doses of the above agents sufficient to block the movement response to tail clamping (ED50 values: 4.7 (3.3-6.6) mg/kg intravenously for morphine; 8.3 (5.8-11.3) micrograms/kg intravenously for fentanyl; and 18.8 (17.9-19.7) mg/kg intravenously for thiopental) both fentanyl and, to a lesser extent, morphine have a less than additive or an antagonistic interaction with thiopental. This antagonism is a relative one that does not increase the requirement for one agent upon the addition of another agent.

Animals↗
PubMed1986

Priming with atracurium: improving intubating conditions with additional doses of thiopental.

The effects of different intubating doses of atracurium on the time of onset, and the effect of an additional dose of thiopental on intubating conditions, were studied in 72 patients divided into six groups (n = 12 in each). Stratified sampling was used to obtain an even sex distribution. Groups I, III, and V (controls) received atracurium as a single bolus dose of 0.4, 0.5 or 0.6 mg/kg respectively. Groups II, IV, and VI received an initial (priming) dose of 0.05 mg/kg followed 3 min later by 0.35, 0.45, or 0.55 mg/kg respectively. The time of onset, that is the time from the intubating dose to complete suppression of the train-of-four (TOF) response, was significantly accelerated after administration of atracurium in divided doses. Increasing the intubating dose of atracurium after an initial 0.05 mg/kg from 0.35 to 0.55 mg/kg did not result in further significant acceleration of the onset time, but resulted in prolongation of the duration of neuromuscular blockade. When divided doses of atracurium were given, administration of 2 mg/kg thiopental (in addition to the 5 mg/kg used for induction) before the injection of the intubating dose resulted in improvement of intubating conditions as reflected by statistically significant changes in intubating scores. This result was probably due to the increase by thiopental in the depth of anesthesia. Therefore, when thiopental is given as supplement, the priming technique can be made to provide better conditions for tracheal intubation in less than 90 sec.

Atracurium↗
PubMed1985

Etomidate versus thiopental for induction of anesthesia.

Hemodynamic changes and side effects of anesthesia induction with etomidate or thiopental were evaluated in 83 ASA class I or II patients. Patients were randomly assigned to one of 12 groups according to pretreatment drug (fentanyl, 100 micrograms, or normal saline intravenously), induction agent (etomidate, 0.4 mg/kg, or thiopental, 4 mg/kg), and maintenance anesthetic technique (isoflurane-oxygen, isoflurane-nitrous oxide-oxygen, or fentanyl-nitrous oxide-oxygen). The purpose of this experiment, of factorial design, was to evaluate the combined effects of two or more experimental variables used simultaneously and to observe interaction effects. There were significant increases in heart rate in all groups, especially after tracheal intubation. These increases were attenuated but not eliminated by fentanyl pretreatment. Systolic arterial blood pressure increased significantly after intubation and was not affected either by fentanyl pretreatment or by the induction agent. Patients in whom anesthesia was induced with etomidate had a greater incidence of pain on injection and myoclonus and a lesser incidence of apnea than patients in whom anesthesia was induced with thiopental. Fentanyl pretreatment significantly decreased the incidence of pain on injection and myoclonus, but it increased the incidence of apnea when anesthesia was induced with etomidate. The incidence of postoperative nausea and vomiting was similar after thiopental and etomidate and was unaffected by fentanyl pretreatment. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1980

Key enzymes of glycolysis in brain as influenced by thiopental.

It has been demonstrated in previous work that hexokinase is solubilized from the mitochondrial membrane in anesthesia. In the present investigation this effect was strongly correlated with the surgical stage of anesthesia by the application of thiopental to rats (80 mg/kg), mice (100 mg/kg) and guinea pigs (32 mg/kg). The solubilization of hexokinase was demonstrable, too, in different areas of rat brains under thiopental treatment (80 mg/kg). In order to elevate the cerebral concentration of glucose 6-phosphate, which is the most potent substrate for the solubilization of bound hexokinase, male Sprague-Dawley rats were pretreated with the antimetabolite 6-aminonicotinamide (6-AN). After i.p. injection of 6-AN (35 mg/kg) we measured an increased activity of soluble brain hexokinase in the same order of magnitude as it was determined in anesthesia. Thiopental application did not show a further significant increase. A solubilization of hexokinase activity by 6-AN was not measurable in vitro. Furthermore, we examined the other key enzymes in the glycolytic pathway. We found a competitive inhibition of phosphofrucktokinase activity by thiopental, but no inhibition of hexokinase and pyruvate-kinase activity.

Anesthesia↗
PubMed1983

MAC values of thiopental and fentanyl in rats.

A comparison of the effects of thiopental or fentanyl with those of inhaled anesthetics requires the establishment of a comparable level of anesthetic potency. Accordingly, using the response of male Sprague-Dawley rats to tail-clamping, we determined the ED50S for thiopental and fentanyl. Half of the rats were pretreated with phenobarbital. After subcutaneous injection of various doses of thiopental or fentanyl, each rat was tested for movement in response to tail-clamping at 15-min intervals for 2 h. In untreated rats, the maximal effect of thiopental (i.e., the lowest ED50 value was 107 +/- 10 mg/kg, mean +/- SEM) occurred 75 min after injection. Although higher values were found at other times, differences from the nadir were relatively small. In rats pretreated with phenobarbital, the lowest value (130 +/- 8 mg/kg) occurred at 60 min. The lowest ED50S for fentanyl (52 +/- 7 micrograms/kg for control rats, and 73 +/- 14 micrograms/kg for pretreated rats) were found at 15 min.

Anesthesia, Intravenous↗
PubMed1982

Alteration of renal hemodynamics by thiopental, diazepam, and ketamine in conscious dogs.

Renal hemodynamic changes associated with thiopental, diazepam, and ketamine were studied in conscious dogs after previous surgical placement of an aortic catheter and a Doppler ultrasonic flow probe on the left renal artery. Thiopental, 10 mg/kg, changed blood pressure minimally whereas 20 mg/kg significantly decreased blood pressure by 5% to 10%. Renal blood flow initially increased significantly, then returned to control levels after both doses. Renal resistance was not significantly altered by 10 mg/kg of thiopental whereas 20 mg/kg significantly reduced resistance by 10%. Diazepam, 1 and 2 mg/kg, caused transient increases in arterial pressure of approximately 10%. Renal blood flow significantly decreased 5% to 10% from control levels with both doses. Renal resistance did not change with the 1-mg/kg dose of diazepam, but 2 mg/kg of diazepam increased it by 8% to 12%. Ketamine, 2.5 and 5 mg/kg, elevated arterial pressure 20% to 40%. Renal blood flow increased significantly by 10% to 15% with both doses of ketamine. This effect lasted longer with the large dose. Renal resistance was significantly elevated by the 2.5-mg/kg dose of ketamine, whereas 5 mg/kg did not alter this variable. In conclusion, each of these drugs maintains renal blood flow reasonably well in an unanesthetized animal. However, ketamine appears to be more beneficial than thiopental, which in turn, is superior to diazepam in this regard. Little dose-response effect was evident for any of the drugs. Furthermore, it should be noted that changes in arterial pressure can be misleading when perfusion of this vascular bed is considered.

Animals↗
PubMed1982

Thiopental suppression of neurons of the nucleus reticularis gigantocellularis of the cat.

The effects of sodium thiopental on the single-unit activity of cells in the nucleus reticularis gigantocellularis (NRGG) were examined in decerebrated cats. Only cells in the NRGC that responded exclusively to electrical stimulation of A-delta fibers (noxious stimulation) in the superficial radial nerve were studied. Sodium thiopental caused a significant, dose-dependent suppression of spontaneous and evoked neuronal activity of cells in the NRGC. Spontaneous activity was suppressed by 66% and 98% after intravenous administration of sodium thiopental, 2.5 mg/kg and 5.0 mg/kg, respectively. Evoked activity was suppressed by 65% and 79%. These findings, when added to previous reports of the suppressive effects of nitrous oxide, morphine sulfate, ketamine hydrochloride, and halothane, suggest the involvement of the NRGC in nociception and provide evidence that sodium thiopental significantly modifies the neuronal message about a noxious stimulus as recorded at the level of the NRGC.

Action Potentials↗
PubMed1980

Differences between the actions of thiopental and pentobarbital in squid giant axons.

The action of thiopental and pentobarbital on the giant nerve fiber of the squid Doryteuthis plei under membrane potential control conditions was investigated. The effect of pentobarbital was found to be similar to that reported by other investigators, however, the replacement of the oxygen in C2 by a sulfur atom bestows excitatory properties on the molecule. Thiopental depolarizes the nerve fibers and produces spontaneous repetitive discharges. With concentrations (0.2 mM) of thiopental, the amplitude of the action potential, spontaneous or otherwise, does not change much, but its falling phase is drastically prolonged. Under voltage clamp conditions it is possible to show that either at rest or during activity the thiobarbiturate exhibits a high affinity for the potassium channels. The apparent dissociation constant of perntobarbital on sodium and potassium conductances are respectively 1.89 and 0.63 mM, whereas those of thiopental are 0.52 mM and 32.6 mM and 32.6 muM. The results also indicate that both barbiturates act as competitive synergists to suppress the increase in sodium and the potassium conductance which occurs during activity.

Action Potentials↗
PubMedDate not supplied

[Pharmacokinetics and pharmacodynamics of thiopental sodium in pregnant women during cesarean section].

Comparative study of thiopental pharmacokinetics and hemodynamics has been conducted in two groups of pregnant women subjected to planned cesarean section. Group I consisted of 6 women (thiopental dose 8.0 mg/kg was combined with components of neuroleptanalgesia), group II consisted of 7 women (the drug dose 4.68 mg/kg was combined with moradol analgesia). Dose-dependent differences in pharmacokinetic regularities of sodium thiopental in the groups compared have been revealed. Moradol did not cause the drug accumulation in the bodies of mother and fetus. The higher Apgar score was characteristic of the newborns from group II. Adequate anesthesia in pregnant women from group II was due to the potentiating effect of moradol. In both groups a correlation has been established between pharmacokinetic parameters and hemodynamic changes, as well as between sodium thiopental concentration in maternal and umbilical blood and pharmacokinetic parameters.

Adult↗
PubMedDate not supplied

[Evaluation of the hemodynamic and endocrino-metabolic response to tracheal intubation in patients anesthetized with thiopental or propofol].

OBJECTIVES: To compare the effects of thiopental and propofol on hemodynamic and metabolic endocrine response to laryngoscopy and intubation. MATERIAL AND METHODS: We selected two homogeneous groups of 14 healthy patients premedicated with midazolam i.m. (0.07 mg/kg). Induction was with diazepam (0.1 mg/kg), fentanyl (2 micrograms/kg), atropine 0.5 mg and thiopental or propofol (4-6.5 mg/kg and 1.5-2.5 mg/kg, respectively). Parameters recorded were direct arterial pressure, baseline heart rate, and heart rate after induction and at 2 and 5 minutes after intubation. We measured adrenaline (A), noradrenaline (NA), dopamine (Da), glucagon, beta-endorphines, ACTH, cortisol, glucose and amino acids in the baseline and post-intubation blood samples. RESULTS: We observed a significant increase (p < 0.05) in systolic and diastolic arterial pressure after intubation (10% and 22% respectively) in the thiopental group as compared with the propofol group. With both induction agents, heart rate was higher than baseline values at the three times (p < 0.001). In the thiopental group heart rate was higher after intubation than after induction (p < 0.05). Cortisol fell after intubation in the propofol group (p < 0.05); no other hormonal differences were observed. Hyperglycemia (p < 0.0001) was similar for both groups, while in the propofol group there were significant decreases in several amino acids. CONCLUSIONS: Propofol has a greater mitigating effect on the hyperdynamic response to intubation in healthy patients. For the two induction agents we measured no significant differences in stress hormone levels, apart from the drop in cortisol with propofol. We observed a change in energy-producing metabolites.

Adult↗
PubMed1993

The anticonvulsant effects of propofol, diazepam, and thiopental, against picrotoxin-induced seizure in the rat.

The anticonvulsant effects of propofol administered intravenously against picrotoxin-induced seizure were studied and compared with those of diazepam and thiopental in the rat using picrotoxin-seizure threshold. Comparable doses of the three agents ranging between 1.25-20.0 mg/kg, produced dose-dependent increases in picrotoxin-threshold dose. At the lowest administered dose (1.25 mg/kg), there were no significant differences in picrotoxin-threshold dose among the three agents. Using 2.5 mg/kg dose, propofol and diazepam were equally effective and both were significantly more effective than thiopental in increasing picrotoxin-threshold dose. At higher doses of anticonvulsants (10.0 and 20.0 mg/kg), propofol was significantly more effective than both diazepam and thiopental. These results indicate that propofol is an effective anticonvulsant against picrotoxin-induced seizure, and this effect is significantly greater than diazepam and thiopental at doses producing clear sedative and behavioral effects.

Animals↗
PubMed1996

Sedation for children undergoing magnetic resonance imaging: efficacy and safety of rectal thiopental.

UNLABELLED: The need to reappraise sedation policy is dictated by newer noninvasive imaging modalities. In this study we evaluate the safety and efficacy of rectally-administered thiopental in children undergoing MRI. Eighty-three consecutive patients with congenital heart disease (mean age 2.9 years, SD 2.5) undergoing MRI evaluation of the heart were given thiopental (25-50 mg/kg, 700 mg max) per rectum. In order to prevent leakage, a female urinary catheter was used. In 79 patients (95.2%) successful sedation was achieved and adequate MR imaging could be obtained. In 4 patients (4.8%) the sedation was inadequate. Respiratory depression was not encountered in any of the patients. The presence of cyanotic congenital heart disease in 26 patients had no influence on the safety and efficacy of thiopental. All successfully sedated children were asleep within 30 min and adequate sedation was maintained for at least 45 min. All patients could be aroused within 90 min, and sent home thereafter. Minor side-effects occurred in two patients. CONCLUSION: Rectally-administered thiopental is a safe and effective sedative drug with a duration of action tailored to performing MRI.

Administration, Rectal↗
PubMed1976

The influence of albumin degradation products on central effect of thiopental.

The influence of trypsin- and leukocyte-induced degradation products of albumin on the potency of thiopental action was studied. Degradation products of albumin increased the potency of this drug as evaluated by Lat's test, prolonged the duration of thiopental sleep and potentiated the hypothermic effects of thiopental. Thiopental action under the influence of albumin degradation products did not depend on the changes to accumunlation of this drug in the brain tissue.

Animals↗
PubMed1987

Effects of thiopental on cardiac energy metabolisms in postischemic reperfusion in rat.

In experiments on isolated rat heart lung preparation, the effects of thiopental on myocardial metabolisms in postischemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate, pyruvate and glycogen. The release of CPK in the perfusate blood was also measured at the end of reperfusion. After 10 min perfusion, hearts were made globally ischemic for 8 min and reperfused for 12 min. Large dose of thiopental (100 microg/ml) reduced the energy charge and glycogen content. Reperfusion with an anesthetic dose of thiopental (10 microg/ml) resulted in an exacerbation of the CPK release. Protection by thiopental during ischemia was not observed and its high dose may be harmful.

Journal Article↗
PubMed1991

Thiopental effect on cerebral blood flow during carotid endarterectomy.

To investigate the effect of thiopental on cerebral blood flow (CBF) during carotid endarterectomy, five patients receiving isoflurane-N2O anesthesia were studied. During the period of temporary bypass shunting, a baseline CBF was measured using i.v. Xe washout, and global CBF was calculated from the mean of 10 detectors. Thiopental was given in a dose sufficient (mean 4.5, range 2.6-5.8 mg/kg) to result in burst-suppression on the electroencephalogram (EEG) of approximately 1:1 duration and CBF was measured again. Data were compared using repeated measures analysis of variance. Thiopental significantly reduced mean (+/-SE) CBF (ml/100 g/min) from 37 +/- 6 to 18 +/- 2 (p <0.02). Corresponding PaCO2 (mm Hg) values were 42.8 +/- 1.2 and 41.2 +/- 1.6 and mean systemic blood pressure (mm Hg) was 101 +/- 3 and 100 +/- 6, respectively (NS). Mean % change in CBF was 48 +/- 5 (range 32-62%). There was no relationship between the dose administered and the change in CBF. During steady-state anesthesia, a small dose of thiopental capable of suppressing EEG resulted in a profound reduction in CBF.

Journal Article↗