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Effect of high pressure on EEG burst suppression dose of thiopental in rats.

The anesthetic induction dose of thiopental in rats was studied at 1 ATA air, 1 ATA helium-oxygen (He-O2), 4 ATA air, and at 4 ATA air plus 67 ATA helium (71 ATA). The compression rate was 0.3 ATA/min, and 1 h was spent at pressure before the experiment started. Thiopental was infused at a rate of 7.5 mg X kg-1 X min-1. The depth of anesthesia was assessed by electroencephalographic (EEG) recording using burst suppression of 1 s as the biological end point. The mean induction dose at 1 ATA air was 53.1 mg/kg and at 71 ATA was 74.7 mg/kg, an increase of 41%. The induction doses at 1 ATA He-O2 and 4 ATA air were 46.4 mg/kg and 45.3 mg/kg, respectively.

Animals↗

Influence of thiopental on intracellular distribution of hexokinase activity in various tumor cells.

In earlier work it has been shown that mitochondrially bound brain hexokinase is solubilized by anesthetics. This effect was reevaluated using cultured cells. For the present experiments Ehrlich ascites, Harding-Passey melanoma, C-1300-neuroblastoma and C-6-glioma cells were used. The great portion of hexokinase activity bound to the mitochondria of these cells was similar to that in rat brain. After incubation with thiopental the soluble hexokinase activity was increased in all cells studied. Using neuroblastoma and glioma cells the thiopental effect was demonstrated to be dose-dependent. Thus, cultured tumor cells seem to be useful for studying the relationship of the intracellular distribution of hexokinase activity, energy metabolism and the effect of anesthetics.

Cell Division↗

[Single dose of thiopental or fentanyl. Hemodynamic effects after treatment by an anti-hypertensive drug: guanoxabenz (author's transl)].

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

Aged↗

The "ultra-free" ultrafiltration technique compared with equilibrium dialysis for determination of unbound thiopental concentrations in serum.

We compare a new ultrafiltration technique, involving a unique Millipore membrane, with the classical method of equilibrium dialysis for determining the fraction of thiopental not bound to serum proteins. This fraction, as determined by equilibrium dialysis at 37 degrees C, ranged between 12 and 16% for total concentrations at 50 microgram/L to 10 mg/L of serum. In contrast, ultrafiltration at 37 degrees C yielded a 49% higher value for unbound thiopental: 26.3 (SD 2.6)%. Determined at room temperature (24 degrees C), there was no statistically significant difference for results by the two methods: 14.2 and 15.9%, respectively. The discrepancy between results at 37 degrees C may partly be explained by serum proteins penetrating the Ultra-Free filter. For the routine clinical measurement of unbound drug concentrations, the ultrafiltration membrane at room temperature appears to be sufficiently accurate and less time-consuming than equilibrium dialysis.

Blood Chemical Analysis↗

Effect of thiopental, saffan, and propofol anesthesia on cardiovascular parameters and bronchial smooth muscle in the rhesus monkey.

The application of human pediatric equipment for measuring respiratory function in nonhuman primates is rapidly gaining popularity in the evaluation of anti-asthma drugs. An important difference between primate procedures and the human clinical situation is the requirement for anesthesia for some techniques because of poor animal compliance. We studied the actions of three potential maintenance anesthetic agents-thiopental, saffan, and propofol-and their effects on a range of cardiovascular parameters under conditions of a broncho-provocation test in rhesus monkeys. The spasmolytic effect of saffan on bronchial smooth muscle was investigated in smooth muscle preparations in vitro and in the rhesus monkey in vivo. Thiopental proved to be a useful sedating agent for this application. Saffan proved to be a bronchodilator in vitro, but the sedative dose was lower than that required to induce appreciable bronchodilator activity in vivo. In comparison, propofol was not appropriate for this application because of the poor sedative effect at nonbronchodilator doses.

Alfaxalone Alfadolone Mixture↗

[Changes in cerebrospinal fluid pressure in neurosurgical patients during hexenal and thiopental-sodium preanesthesia].

Before undergoing operation on the brain, 30 neurosurgical patients were examined to determine the effect of hexenal (in 15) and thiopental sodium (in 15) central venous pressure were taken. Arterial pressure was measured by Korotkov's method. The cerebral perfusion pressure was calculated. Both anesthetics caused reduction of CSFP: hexenal by 91 +/- 12.1 mm water, thiopental sodium by 108 +/- 21 mm water. A smallrise of cerebral perfusion pressure was noted at the same time.

Adolescent↗

Prevention of thiopental and thiopental/halothane cardiac sensitization to epinephrine in the sheep.

The effects of epinephrine (5 microgram/kg of body weight) on ten unanesthetized sheep were experimentally tested: all sheep displayed serious arrhythmias. Sheep anesthetized with thiopental and thiopental/halothane combination displayed cardiac arrhythmias of the order of 10% and 20% respectively. Challenge injections of epinephrine (5 microgram/kg of body weight) to ten sheep anesthetized with thiopental, and to the same number of animals after 45 minutes of anesthesia with thiopental/halothane, produced serious arrhythmias. However, following preanesthetic treatment with acepromazine maleate (0.5 mg/kg) to 15 sheep, serious arrhythmias were prevented in all of them when they were given arrhythmic doses of epinephrine.

Acepromazine↗

EMLA cream and lidocaine local injection in the treatment of extravenous thiopental injection--a case report.

Thiopental extravasation which would cause tissue edema and necrosis in rapid progression by chemical reaction and vascular spasm is a potentially serious complication in anesthesia. Early diagnosis and treatment may bear a favorable outcome. A patient who sustained thiopental extravasation and received local injection of lidocaine and local application of EMLA (Eutectic Mixture of Local Anesthetics) for treatment with excellent results is presented hereunder.

Anesthetics, Intravenous↗

Evidence of polydrug use using hair analysis: a fatal case involving heroin, cocaine, cannabis, chloroform, thiopental and ketamine.

A case is presented involving a young woman on several illicit drugs (heroin, cocaine and cannabis) as well as two medications and a solvent used for their anesthetic and narcotic properties: thiopental, ketamine and chloroform. This complex drug use was supported by hair analysis over a 10.5 cm segment of the hair taken at autopsy. The average measured concentrations in hair were: thiopental = 5.3 ng/mg, pentobarbital = 10.0 ng/mg, ketamine = 11.3 ng/mg norketamine = 1.0 ng/mg, diazepam = 1.2 ng/mg, nordiazepam = 0.1 ng/mg, 6-acetylmorphine = 4.4 ng/mg, morphine = 3.4 ng/mg, codeine = 1.2 ng/mg, cocaine = 5.5 ng/mg, benzoylecgonine = 1.5 ng/mg and methylecgonine ester = 1.0 ng/mg. While the ketamine/norketamine ratio is consistent with that already reported on drug detection in hair, the thiopental/pentobarbital ratio seems to be inverted.

Adult↗

A comparative study of intravenous anaesthesia with thiopental versus althesin in outpatient dental practice.

Clinical effects of two intravenous anaesthetics--thiopental and althesin--were compared in a group of 160 outpatients. Each anaesthetic was used in 80 cases. The administration of these anaesthetics was preceded by an intravenous injection of fentanyl and atropine sulphate. Anaesthesia was carried out with the patient sitting in dental chair. The observations confirmed that this method of anaesthesia provides good conditions for carrying out minor dental operations and is safe for the patient, as evidenced by a negligible number of minor complications. A comparison of the results of clinical observations and gasometric determinations indicates that althesin is superior in outpatient practice to thiopental. This simple and easy technique of anaesthesia without the necessity of using expensive apparatus should be widely introduced in outpatient practice.

Adolescent↗

[The comparison of ketamine with methohexital and thiopental in the intraoperative EEG in drug-resistant epilepsy].

UNLABELLED: The acute (ECoG) was examined in 291 patients with intractable epilepsy, without structural brain lesion--from 1971 to 1997. Temporal lobectomy was performed in 198 cases and extratemporal (frontal, parietal or occipital) in remaining 93 cases to achieve seizure control. Epileptic foci was activated during acute ECoG by i.v. administration of ketamine (154 cases) or short-acting barbiturates--methohexital (110 cases) and thiopental (27 cases). RESULTS: Ketamine significantly more often caused ECoG identified electrographic seizures than methohexital: p = 0, 00001 or thiopental, which in no cases resulted in seizures. Also electrographic seizures occurred more frequently after administration of ketamine in patients with the extratemporal seizure focus localisation in comparison with temporal focus (p < 0.05). Electrographic seizures provoked after administration of ketamine improved the localisation of the area to be resected, more often in extratemporal epileptic foci. CONCLUSIONS: The results of our investigations indicate that ketamine more effectively activated epileptic focus than short-acting barbiturates.

Adolescent↗

[Total intravenous anesthesia with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase].

A randomized, prospective and multi-institutional study was performed to investigate whether different anesthetic methods affected differently the quality of recovery from anesthesia. Two hundred and eleven patients were allocated to one of two groups; total intravenous anesthesia (TIVA) with propofol and fentanyl (group P, n = 107) and general anesthesia with thiopental, sevoflurane and nitrous oxide (group TS, n = 104). The rapidity of emergence from anesthesia and postoperative incidence of nausea, vomiting, and headache were compared between the two groups. The group P showed significantly shorter emergence times for verbal command responses (7.4 +/- 5.6 min), extubation (10.0 +/- 6.0 min) and orientation (13.1 +/- 7.8 min) than the group TS (9.1 +/- 5.0 min, 11.7 +/- 6.2 min, 16.4 +/- 7.9 min, respectively). The postoperative incidence of vomiting was not significantly different between the two groups (3.7% in the group P and 9.6% in the group TS), but the postoperative incidences of nausea and headache were significantly lower in the group P compared with the group TS (10.3%, 17.8%, respectively in the group P and 34.6%, 29.8%, respectively in the group TS). We conclude that TIVA with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase.

Adult↗

Effect of thiopental, pentobarbital and diethyl ether on early steps of insulin action in liver and muscle of the intact rat.

A large number of experimental studies have investigated insulin signaling in rats. In these studies different anaesthetics have been used to anaesthetize rats. However, the direct effects of anaesthetics on the regulation of the early steps of insulin action are not known. In the present study, we investigated the effect of thiopental, pentobarbital and diethyl ether on the plasma glucose disappearance rate, IR, IRS-1 and IRS-2 tyrosine phosphorylation, IRSs association with PI 3-kinase, Akt and Erk phosphorylation, in liver and muscle of rats. Fasting plasma glucose levels were higher in animals anaesthetized with ether. No differences in plasma glucose disappearance rates were observed, however. Insulin-induced IR, IRS-1 and IRS-2 tyrosine phosphorylation, association of these substrates with PI 3-kinase and Akt and ERK phosphorylation were similar in the three groups of animals in both tissues. These data suggest that both thiopental and pentobarbital may be used in studies where changes in insulin signaling are being measured and where adequate general anaesthesia is required.

Animals↗

Effect of massive intraoperative thiopental loading on cardiovascular hemodynamics and myocardial performance.

Anesthetics that protect the brain may also depress the heart. We recently anesthetized a patient with a giant cerebral aneurysm of the basilar artery who had it clipped during circulatory arrest. Thiopental loading was carried out prior to and during cardiopulmonary bypass, and we monitored transesophageal echocardiographic function and the hemodynamic profile throughout. The patient demonstrated little change in cardiovascular parameters or myocardial performance, and we conclude that the massive dose of thiopental was well tolerated.

Journal Article↗

Comparison of five preanesthetic medicaments in thiopental-anesthetized cats: antagonism by selected compounds.

Effects of IM injections of saline solution (groups 1, 2, 3, and 4), xylazine (2.2 mg/kg of body weight, groups 5 and 6), acepromazine (0.11 mg/kg, groups 7 and 8), ketamine (11 mg/kg, groups 9 and 10), meperidine (4.4 mg/kg, groups 11 and 12), and diazepam (1 mg/kg, groups 13 and 14) were compared in atropinized cats. Treated cats were anesthetized to loss of palpebral reflex with thiopental, IV. Within 2 minutes, the cats were given IV injections of 0.15 mg of 4-aminopyridine (4-AP) with 0.125 mg of yohimbine/kg (groups 2, 6, 8, and 10), 0.04 mg of naloxone/kg (groups 3 and 12), or 5 mg of the benzodiazepine antagonist Ro 15-1788/kg (groups 4 and 14). Groups 1, 5, 7, 9, 11, and 13 were given saline solution instead of the test antagonists. Required doses of thiopental, arousal time, walk time (measured from injection of antagonists), respiratory rate, and heart rate were recorded. Induction phenomena were also recorded. Emergence was graded as smooth, fairly smooth, fairly smooth in some cats to fairly rough in other cats, rough, or very rough. In group 1 cats, mean arousal time (MAT) was 20.1 minutes, mean walk time (MWT) was 50 minutes, and emergence was rough. In groups given saline solution as the antagonist, the MAT, MWT (both expressed in minutes), and emergence, respectively, were: group 5 = 52.5, 65.5, smooth; group 7 = 15.6, 36.2, fairly smooth; group 9 = 22.5, 58.1, rough; group 11 = 31.3, 52.7, fairly smooth to fairly rough; and group 13 = 91.8, 427, very rough.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

Potentiation of differential hyperthermic sensitivity of AKR leukemia and normal bone marrow cells by lidocaine or thiopental.

Previous work has utilized spleen colony formation to evaluate the fractional survival of AKR leukemia and normal bone marrow cells after in vitro heat exposure. An inherently greater sensitivity of neoplastic cells to thermal killing, as compared to normal syngeneic stem cells, has been established both at 41.8 degrees C and 42.5 degrees C. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 cGy) mice. Leukemic colony-forming units were assayed in nonirradiated mice. Using this methodology, the authors demonstrated that the differential effect of hyperthermia on AKR murine leukemia and AKR bone marrow cells can be further enhanced by the addition of lidocaine or thiopental to incubation mixtures. These findings may have application to autologous bone marrow transplantation in humans.

Animals↗

From piecewise to full physiologic pharmacokinetic modeling: applied to thiopental disposition in the rat.

Physiologically based pharmacokinetic modeling procedures employ anatomical tissue weight, blood flow, and steady tissue/blood partition data, often obtained from different sources, to construct a system of differential equations that predict blood and tissue concentrations. Because the system of equations and the number of variables optimized is considerable, physiologic modeling frequently remains a simulation activity where fits to the data are adjusted by eye rather than with a computer-driven optimization algorithm. We propose a new approach to physiological modeling in which we characterize drug disposition in each tissue separately using constrained numerical deconvolution. This technique takes advantage of the fact that the drug concentration time course, CT(t), in a given tissue can be described as the convolution of an input function with the unit disposition function (UDFT) of the drug in the tissue, (i.e., CT(t) = (Ca(t)QT)*UDFT(t) where Ca(t) is the arterial concentration, Q tau is the tissue blood flow and * is the convolution operator). The obtained tissue until disposition function (UDF) for each tissue describes the theoretical disposition of a unit amount of drug infected into the tissue in the absence of recirculation. From the UDF, a parametric model for the intratissue disposition of each tissue can be postulated. Using as input the product of arterial concentration and blood flow, this submodel is fit separately utilizing standard nonlinear regression programs. In a separate step, the entire body is characterized by reassembly of the individuals submodels. Unlike classical physiologic modeling the fit for a given tissue is not dependent on the estimates obtained for other tissues in the model. Additionally, because this method permits examination of individual UDFs, appropriate submodel selection is driven by relevant information. This paper reports our experience with a piecewise modeling approach for thiopental disposition in the rat.

Algorithms↗