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At least 19 recordsLinked to original sources

PubMed1976

Gas chromatographic assay for free and total plasma levels of thiopental.

A rapid gas chromatographic assay for the determination of free and total plasma thiopental is described. Free thiopental was obtained by ultrafiltration through Amicon Centroflo membrane cones. Gas chromatographic assay utilized secobarbital as an internal standard and employed on-column methylation of the barbiturates to improve peak resolution. In 73 blood samples from 22 patients total thiopental concentrations ranged from 4.2 to 134 mug/ml plasma, with a mean of 28 mug/ml. Free thiopental values ranged from 8.6 to 22.7 per cent of total, with a mean of 13.7 per cent free thiopental and a standard deviation of 3.2 per cent. At a total thiopental level of 10 mug/ml, unbound thiopental averaged 10.7 per cent with ultrafiltration, compared with 11.5 per cent with equilibrium dialysis. Assays of thiopental by gas chromatography and 14C scintillation counting gave similar results. There were progressive increases in the percentages of thiopental that were unbound when thiopental was added to plasma, purified crystalline albumin (4.5 g/l), and normal serum albumin (5 g/l), and a solution of purified protein fractions (5 g/l). Differences in protein binding determined by this method and previously reported methods are discussed.

Chromatography, Gas↗

PubMedDate not supplied

Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys.

We measured total and regional cerebral blood flow (CBF, rCBF) and cerebral metabolic rate (CMR) of oxygen (O2), glucose (G), and lactate (L) levels for 4 h after 16 min global brain ischemia in rhesus monkeys with and without post-insult thiopental therapy. Eleven monkeys weighing 4-5 kg anesthetized with 1 percent halothane, 66 percent nitrous oxide and 33 percent oxygen, were subjected to 16 min global brain ischemia by a combination of trimethaphan hypotension (to a mean arterial pressure of 50 torr) and a high pressure (1500 torr) neck tourniquet. Post-ischemia, 7 monkeys were untreated (controls) and 4 received thiopental 90 mg/kg infused intravenously over 60 min, beginning at 5 min post-ischemia. Total CBF and rCBF were measured by continuous monitoring of cerebral venous (torcula) and parietal-occipital (external scintillation) 133Xe activity, respectively, after intra-innominate artery injection of 500 micronCi 133Xe in saline. In control monkeys, hyperemia in rCBF, but not in total CBF was observed at 6-7 min post-ischemia, whereas both total CBF and rCBF increased in thiopental treated monkeys. The hyperemia in thiopental treated monkeys coincided with an increase in CMRG without a proportional increase in CMRO2 or lactate levels. Indeed, CMRO2 was depressed in the first 30 min post-ischemia. At 30 min post-ischemia, CMRO2 rose to twofold greater than pre-ischemia in control monkeys, but only to pre-ischemic levels in thiopental treated monkeys. The data suggest that thiopental therapy improves distribution of brain blood flow and brain glucose uptake early post-ischemia and depresses CMRO2 later post-ischemia.

Animals↗

PubMed1976

Inhibition of glucose phosphorylation in rat brain by thiopental.

The purpose of the present investigation was to shed some light on the suppression of the glycolytic pathway by anesthetics. The antimetabolite 6-aminonicotinamide (6-AN) was used to discriminate between the key enzymes hexokinase and phosphofructokinase which are suggested to be involved in the effect of anesthetics on glycolysis. The cerebral energy metabolism was studied in the isolated perfused rat brain after the addition of thiopental (0.15 mM) to the perfusion medium, after the administration of 6-AN (35mg/kg i.p.) to the intact animals 15 h before perfusion was started, as well as in brain preparations treated in the same manner with both 6-AN and thiopental. After a perfusion period of 30 min brain levels of the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glycogen, glucose, glucose 6-phosphate, fructose 6-phosphate, pyruvate, lactate, alpha-ketoglutarate, blutamate, ammonia, and 6-phosphogluconate. The metabolic alterations in the isolated rat brain caused by 6-AN or thiopental were such as reported in the literature. When the isolated brains of the 6-AN pretreated rats were perfused with thiopental we found as the most interesting result that the concentration of glucose 6-phosphate was reduced in comparison to that in brains only treated with 6-AN but still significantly higher than that in controls. The glucose concentration was significantly elevated and the lactate concentration decreased considerably. The effect of thiopental on cerebral glycolysis was interpreted as an inhibition of hexokinase activity.

6-Aminonicotinamide↗

PubMed1975

Recovery and simulated driving after intravenous anesthesia with thiopental, methohexital, propanidid, or alphadione.

Recovery from anesthesia was assessed in a double-bind manner in 40 healthy volunteer students after intravenous anesthesia with thiopental (6.0 mg/kg), methohexital (2.0 mg/kg), propanidid (6.6 mg/kg), or alphadione (Althesin), 85 mul/kg using a driving simulator 2,4, 6, and 8 hours after injection of the drugs. Clinical recovery was faster after propanidid and methohexital than after thiopental or alphadione. Driving performances remained significantly (P less than 0.05) worse than in a control group for 6 hours after thiopental and for 8 hours after methohexital, and reaction times 8 hours after thiopental remained worse than in the control subjects. After alphadione driving skills were impaired at 6 hours only. Propanidid produced no impairment in driving skills at any time during the experiment. It is concluded that after the doses used in this study patients should not drive or operate machinery for at least 2 hours after propanidid and for at least 8 hours after alphadione. After methohexital and thiopental patients should probably not drive for 24 hours because of the severity of the disturbances at 8 hours.

Adult↗

PubMed1976

Binding of thiopental to plasma proteins: effects on distribution in the brain and heart.

Thiopental-14C (30 mg and 10 muCi/kg) was injected intravenously into rats 36-48 hours following bilateral nephrectomy and one minute after pretreatment with sulfadimethoxine (30 mg/kg, iv). Control groups of normal and sham-operated animals were used. The distributions of radioactivity in plasma, brain, and heart 1, 5, and 30 minutes after injection were examined. Uremic and sulfonamide-pretreated rats showed significantly higher levels of 14C in brain and heart and more free thiopental in plasma at each time than did control animals. There was a significant correlation between the free thiopental in plasma and total drug concentrations in the brain and heart. Uremic rats bound less thiopental in plasma compared with controls in spite of normal total plasma protein and albumin concentrations. It is concluded that reduced protein binding of thiopental leads to accelerated distribution and increased drug concentrations in the brain and and heart.

Animals↗

PubMed1977

Thiopental inhibition of tumor immunity.

The ability of leukocytes to kill tumor cells appears central to the defense against neoplastic growth. The authors determined the effect of thiopental on this phenomenon in vitro by incubating 51Cr-labelled YAAC-1 tumor cells obtained from the peritoneal cavities of syngeneic A/JAX white mice with immune leukocytes from the peritoneal cavities of allogeneic C57/black mice. Tumor-cell death was quantitated by the amount of 51Cr released into the medium following tumor-cell lysis. Thiopental, in concentrations used during routine anesthesia, inhibited tumor-cell killing in a dose-related manner. Inhibition of cytotoxicity ranged from 8.6 per cent at 2.8 x 10(-5) M thiopental to 38.1 per cent at 8.5 x 10(-5) M thiopental. Moreover, this inhibitory effect was additive to that previously demonstrated with halothane, and was related to the duration of exposure to the anesthetic. It is postulated that thiopental and other anesthetics contribute to the inhibition of leukocyte responsiveness observed in patients with malignancies who have undergone surgical procedures.

Animals↗

PubMed1978

Cardiovascular effects of plasma levels of thiopental necessary for anesthesia.

The cardiovascular effects of plasma levels of thiopental necessary for anesthesia were studied using systolic time intervals (STI). In ten healthy patients anesthesia was induced with thiopental, 2-2.5 mg/kg, intravenously, and maintained with an infusion of 1-1.5 mg/kg/min. STI and thiopental plasma levels were measured before induction and when corneal reflex and trapezius muscle response, indicators of anesthetic depth equivalent to response to surgical stimulation, were lost. Significant changes included: an increase in heart rate with induction of anesthesia; a decrease in 1/pre-ejection period2--indexed for heart rate (1/PEP2-I) at loss of corneal reflex; a decrease in systolic blood pressure and 1/PEP2-I at loss of trapezius muscle response. No other variable was significantly different from control. Control values for STI were in the high-normal range, indicating some sympathetic stimulation. With induction of anesthesia these values decreased to a normal range. Free and total plasma levels were 5.4 and 37.6 microgram/ml at loss of corneal reflex; 6.1 and 41.6 microgram/ml at loss of trapezius muscle response. In comparison with other studies, thiopental causes less cardiac depression than inhalational agents at approximately the same anesthetic depth. It is concluded from this study in healthy patients that plasma levels of thiopental producing surgical anesthesia result in minimal cardiac depression as determined by systolic time intervals.

Adult↗

PubMedDate not supplied

Thiopental and succinylcholine: Action on intraocular pressure.

Intraocular pressure (IOP) measurements were made in a series of 92 male surgical patients, to assess the effects of timing and dosage of succinylcholine given after a standardized sleep dose of thiopental (3 mg./kg.). The major findings of this study were as follows: (1) thiopental alone lowered IOP; (2) a small (0.5 mg./kg.) dose of succinylcholine, given immediately after thiopental, returned IOP to normal; (3) a large (1 mg./kg.) dose of succinylcholine immediately after thiopental maintained the IOP at a low value; (4) if 2 minutes elapsed between thiopental and 1 mg./kg. of succinylcholine, the relaxant raised the IOP to slightly above preanesthetic control values; (5) tracheal intubation caused a significant rise in IOP, more than any effect from succinylcholine itself; (6) succinylcholine drip (0.1 percent), begun after establishment of satisfactory endotracheal halothane-nitrous oxide anesthesia, caused significant IOP elevation in 4 of 11 patients.

Adult↗

PubMedDate not supplied

Naloxone fails to antagonize thiopental anesthesia.

A study was undertaken to determine the effect in man of naloxone on the central nervous system depression produced by IV thiopental. Eight normal volunteers were given 5 mg/kg thiopental IV. On a separate occasion the same 8 volunteers were given 50 microgram/kg naloxone IV 5 minutes prior to 5 mg/kg thiopental. Naloxone had no significant effect on the rate of return of consciousness following administration of thiopental. Naloxone also had no significant effect on the responses of blood pressure, heart rate, or respiratory rate to thiopental.

Adult↗

PubMedDate not supplied

Depression of lung mucociliary dlearance by thiopental and halothane.

It has previously been demonstrated that an induction dose of thiopental, 25 mg/kg, without continuing anesthesia did not depress peripheral lung mucociliary clearance in the dog, whereas 2 hours of anesthesia with halothane, 1.2 MAC, did depress clearance. To determine whether this was because thiopental depresses the mucociliary apparatus less than halothane, this study compared mucociliary clearance after 2 hours of anesthesia with halothane with clearance after 2 hours of anesthesia with thiopental, 40 mg/kg. With thiopental, 40 mg/kg, 50% mucociliary clearance of tantalum from peripheral airways required 280 +/- 65 (SEM) minutes, which was comparable to clearance obtained with halothane, 1.2 MAC, 382 +/- 27 (SEM) minutes. Hence thiopental depresses mucociliary clearance as much as halothane does when both are administered in equivalent anesthetic doses for equal periods of time.

Anesthesia, Inhalation↗

PubMed1977

Solubilization of brain mitochondrial hexokinase by thiopental.

The control of hexokinase activity probably is accomplished by regulating the partitioning of the enzyme between soluble and particulate forms, the latter being more active. In the present investigation we have examined the thiopental effect on the cerebral hexokinase distribution. In anesthesia, after administration of thiopental to male Sprague Dawley rats, the increase of the soluble fraction of hexokinase was dose dependent. The change in the intracellular hexokinase distribution was reversible and lasted as long as general anesthesia existed. Also in experiments in vitro a solubilization of the mitochondrial hexokinase by thiopental (0.1--1 mM) occurred; it was depending on drug concentration. An inhibition of hexokinase was found neither in the total brain extract, nor in the soluble or the particulate fraction. The results suggest that phosphorylation of glucose in brain may be suppressed in anesthesia by shifting hexokinase activity from a more active mitochondrial form to its less active soluble form. This effect seems to be caused by a direct action of thiopental and is obviously correlated with anesthesia.

Animals↗

PubMed1975

Limbic neuronal firing rates in man during administration of nitrous oxide--oxygen or sodium thiopental.

Electroencephalographic activity and extracellular discharges from neurons in deep temporal lobe structures were recorded from fine wire microelectrodes chronically implanted in seven psychomotor epileptic patients for diagnostic localization of seizure foci. In four patients, inhalation of 80 per cent nitrous oxide resulted in loss of consciousness without change in firing rates of temporal lobe neurons (n = 22). In all seven patients, thiopental (400 or 200 mg, iv) decreased limbic neuronal firing rates (n = 38) until the return of wakefulness. In only three of these patients, however, did the firing rates of the neurons (n = 19) decrease significantly (P less than .05). Thiopental suppression of unit activity was not related to systemic hypoxia. This study demonstrates that anesthetic induction with nitrous oxide-oxygen does not significantly affect the firing of neurons in various regions of the human limbic system, which may explain the incidence of patient awareness reported when nitrous oxide-oxygen is administered alone. Thiopental depresses the firing of limbic neurons, and this may account in part for the temporary confusion and amnesia often manifested by patients recovering from the effects of thiopental.

Adolescent↗

PubMed1977

Effects of halothane, thiopental, and lidocaine on fluidity of synaptic plasma membranes and artificial phospholipid membranes.

The effects of halothane, thiopental, and lidocaine were studied with spin-labeling methods in synaptic plasma membranes (order parameter) and artificial phospholipid membranes (lateral diffusion). Halothane had a biphasic action, low concentrations (0.64 mM) ordering and high concentrations (2.9 mM) fluidizing both types of membranes. A biphasic effect in phospholipid membranes was also seen with thiopental, 0.1 mM ordering and 10 mM fluidizing, whereas in synaptic plasma membranes both low and high concentrations caused an increased order in the lipid bilayer region. At high thiopental concentrations, a considerable number of molecules may have reacted with membrane proteins or accumulated in the highly fluidic hydrophobic interior region of the membrane without affecting the rotational movement of the labeled fatty acid. Lidocaine alone, or together with calcium chloride, at various concentrations to 10 mM had no significant effect, and a fluidizing effect of 1 mM calcium chloride was possibly a result of interaction of calcium chloride with the label. The results indicate that the three lipid-soluble anesthetics interact differently with the lipid part of membranes. Lidocaine did not seem to affect bilyer lipids, while thiopental and halothane in phospholipid vesicles and halothane alone in synaptic membranes caused a dose-dependent biphasic effect.

Anesthesia, Inhalation↗

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↗

PubMedDate not supplied

Induction of general anesthesia with diazepam or thiopental: a comparison of the cardiorespiratory effects.

Detailed cardiorespiratory studies were performed in 10 volunteers in whom general anesthesia was induced with thiopental 3 mg/kg and diazepam 0.4 mg/kg.Minimal changes in blood pressure were noted with both agents. Depression of total peripheral resistance lasted in excess of 20 minutes with diazepam but had returned to control levels with thiopental, elevations in cardiac rate and output were most evident and lasted longer with diazepam. In the healthy volunteer induction of anesthesia with diazepam causes alterations in cardiovascular parameters which are more profound than with thiopental. The data presented is in contrast to that obtained when patients with cariovascular disease are studied.With diazepam, considerable individual variation and long recovery times were confirmed.Following extensive clinical use, a detailed study demonstrated minimal cardiovascular depression following intravenous induction of sedation with diazepam, in patients who had prior cardiovascular disease. Subsequent studies suggested that diazepam would be a more suitable alternative for induction of general anesthesia in patients with cardiovascular disease. This was confirmed by Ikram and Rubin. It has been used extensively for sedative techniques in dentistry, and therefore it was logical to extend this concept to the induction of general anesthesia by intravenous diazepam. It was decided to evaluate the use of intravenous diazepam for induction of general anesthesia and to compare the detailed cardiovascular and respiratory effects of this drug with thiopental.

Adult↗

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↗

PubMedDate not supplied

Abnormal embryogenesis induced by thiopental.

The effects of thiopental on chick embryos were analyzed in the present study. Thiopental was dissolved in saline and injected into embryonating chicken eggs at doses ranging from 0.2 to 4.0 mg per egg. The injections were made into the air sacs of eggs after two to four days of incubation. Control eggs were injected with an equivalent volume of saline (0.1 ml per egg). In all 1080 chicken eggs were used for this study. All embryos were examined on day 7. The LD50 for eggs injected on days 2, 3 and 4 was 2.1, 1.9, and 4.1 mg per egg, respectively. The principal malformations observed were exencephaly, anencephaly, twisted limbs, twisted neck, microphthalmia, everted viscera, and hemorrhage above the left eye and in both cerebral hemispheres. The results of the present study indicate that thiopental has a tendency to cause malformations in the chick embryos tested.

Abnormalities, Drug-Induced↗

PubMed1975

The effects of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain.

The effects of glucose concentrations in the perfusion medium ranging from 5 to 15 mM and thiopental, on cerebral energy metabolism were studied using the isolated perfused rat brain. After a perfusion time of 30 min brain levels of the following substrates and metabolites were determined: P-creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6P, fructose-6-P, pyruvate, lactate, alpha-ketoglutarate, glutamate, ammonia. In control experiments increasing the glucose concentration in the perfusion medium produced an increase of intracellular brain glucose concentration only, revealing a linear relationship between glucose content in brain and blood. Neither high-energy phosphates nor glycolytic intermediates were markedly affected by the changes in blood glucose. With an anesthetic dose of thiopental (0.15 mM) in the perfusion medium identical metabolic alterations occured in all experiments: P-creatine and glucose were significantly increased whereas ADP, AMP, lactate and pyruvate were diminished. Also with thiopental brain glucose was linearly related with the glucose concentration in the perfusion medium. The calculated regression line was apparently parallel with that from control experiments; that means thipental always caused an elevation of brain glucose by the same amount of 0.9 mumoles/g--irrespective of the initial cerebral glucose content. The results yield further evidence that glucose transport is not the rate-limiting step in glycolysis. The action of thiopetal on glycolytic pathway is discussed.

Adenine Nucleotides↗