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[Pharmacological interactions between diltiazem and thiopental. A study on an electrophysiological model of guinea pig isolated papillary muscle. Value of positive inotropic agent].

This study was designed to assess in vitro the effects of Thiopental alone and Thiopental--Dobutamine association on control and on Diltiazem pretreated papillary muscle. The Diltiazem treatment do not increase the negative inotropic effect of Thiopental but the effect of Dobutamine is less important in pretreated group. The Diltiazem treatment protect to arrhythmogenic action of Thiopental and Thiopental-Dobutamine association.

Animals↗

A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: III. Placental transfer and elimination in neonates.

Forty neonates delivered by cesarean section were studied, half being delivered of mothers in whom anesthesia was induced with midazolam (0.3 mg/kg intravenously) and half of mothers given thiopental (4 mg/kg). At delivery, blood samples from mother and the umbilical vein were drawn for determination of plasma concentrations of thiopental, midazolam, and alpha-hydroxymidazolam. Over the next 60 hours, three blood samples were drawn using a randomized procedure of two blood samples at 30 different times. Placental transfer, expressed as the umbilical/maternal concentration ratio, was 0.96, 0.66, and 0.28, respectively, for thiopental, midazolam, and alpha-hydroxymidazolam. The transfer of thiopental was significantly more rapid than the transfer of midazolam and alpha-hydroxymidazolam. The population average of elimination half-life in neonates was 6.3 hours for midazolam and 14.7 hours for thiopental. Both values are substantially larger than those found in previous studies in adults.

Anesthesia, Obstetrical↗

Pharmacologic EEG suppression during cardiopulmonary bypass: cerebral hemodynamic and metabolic effects of thiopental or isoflurane during hypothermia and normothermia.

We have determined the effects of thiopental or isoflurane upon cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) when these agents are used in sufficient dose to attain a deep burst suppression pattern on the electroencephalogram (EEG) during hypothermic and normothermic cardiopulmonary bypass (CPB). Thirty-one patients undergoing coronary artery bypass graft surgery were anesthetized with fentanyl 0.1 mg X kg-1, and were randomly allocated to one of three groups: control (no further anesthetics during bypass and continuous EEG activity), thiopental treatment (EEG suppression), or isoflurane treatment (EEG suppression). Hypothermia (25-29 degrees C) was routinely induced at onset of nonpulsatile cardiopulmonary bypass. In the treatment groups, thiopental or isoflurane were used during bypass to achieve a deep burst suppression pattern. Cerebral blood flow and cerebral metabolic rate for oxygen were determined during hypothermia and upon rewarming to normothermia (37 degrees C). Pharmacologic EEG suppression with either isoflurane or thiopental was associated with lower cerebral metabolic rate than control values during both hypothermic and normothermic bypass. However, only thiopental-induced EEG suppression was associated with lower cerebral blood flow than control. Cerebral blood flow during isoflurane-induced EEG suppression was similar to control values in spite of the reduced cerebral metabolic rate.

Blood Gas Analysis↗

Lymphatic and portal venous absorption of phenobarbital and thiopental in the dog.

Lymphatic and portal venous absorption of gastrically administered thiopental and phenobarbital were compared in the dog. Thiopental concentrations in lymph were significantly higher than phenobarbital concentrations for 30 min after drug administration. Disparity between portal plasma and lymph concentrations for thiopental during the first 15 min was about 1/3 as great as the same difference for phenobarbital. Thiopental displayed an average of twice the affinity for lipid (chylomicron) lymph as did phenobarbital. Because of its greater lipid solubility, thiopental is absorbed more by lymph than is phenobarbital. Both barbiturates are absorbed more quantitatively by the portal rather than lymphatic circulation, probably due to variation in the rate of flow of these 2 systems.

Anesthesia↗

Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental.

Choroid plexus contains an active transport (influx) and a facilitated diffusion (efflux) system for nucleosides. The ability of diazepam and thiopental to inhibit active transport or facilitated diffusion of thymidine in choroid plexus was measured in vitro under various conditions. When isolated rabbit choroid plexuses were incubated in artificial cerebrospinal fluid containing 1 microM [3H] thymidine for 10 min at 37 degrees C under 95% O2-5% CO2, diazepam (10 microM) and thiopental (500 microM) doubled the tissue-to-medium ratios of [3H] thymidine from 8 to 15 to 16. These results were not due to metabolism or intracellular binding but rather to inhibition of [3H] thymidine efflux from choroid plexus. Diazepam, unlike thiopental, inhibited [3H] thymidine efflux in a concentration-dependent manner. When isolated choroid plexuses were incubated in artificial cerebrospinal fluid containing low concentrations of [3H] thymidine (6 nM) to allow intracellular conversion of [3H] thymidine into [3H] thymidine phosphates and [3H] DNA, both diazepam (10 microM) and thiopental (500 microM) altered [3H] thymidine accumulation and metabolism consistent with inhibition of facilitated diffusion but not active transport of thymidine. These studies provide evidence that, at toxic but not therapeutic concentrations, diazepam and thiopental alter facilitated nucleoside transport in the choroid plexus.

Animals↗

Anaphylaxis due to thiopental sodium anesthesia.

Anaphylaxis due to an anesthetic is one type of cardiovascular emergency that can occur during general anesthesia. Anaphylactic reactions to muscle relaxants have been documented. Barbiturates, used as sedatives, are well known to produce cutaneous reactions, but anaphylaxis after their ingestion seems to be rare. Generalized allergic reactions to thiopental sodium during anesthesia are mentioned in the product monograph for Penthothal sodium, and rare case reports of anaphylactic reactions to infused thiopental have appeared, generally in the anesthesiology literature. Documentation of the immunologic responses to thiopental sodium has been limited to the demonstration of an allergic reaction to thiopental by skin testing in some cases. This report describes a woman who, after having tolerated thiopental sodium and other general anesthetics, became sensitive to this agent and had a severe acute reaction at the time of induction of general anesthesia.

Adult↗

Differences in the myocardial depressant action of thiopental and halothane.

The negative inotropic effects of thiopental (10-30 mg/L) and halothane (0.5-1.5%) were compared in rabbit papillary muscles under various stimulation conditions to gain insight into the action of these anesthetics on the availability of Ca2+ for the activation of myocardial contractile activity. The negative inotropic effect of thiopental was more pronounced at short (0.5 sec) than at long (1 sec) beat-to-beat intervals under steady-state conditions, and thiopental's effect on potentiated state contractions was less than that on steady-state contractions. For all variables studied, the effect of halothane was opposite that of thiopental. These results suggest that thiopental reduces the influx of extracellular Ca2+ and the amount of Ca2+ in sarcolemmal sites and slows the transport of intracellular Ca2+ within the sarcoplasmic reticulum from sites of uptake to sites of release without markedly diminishing the amount of intracellular Ca2+. Halothane does not appreciably affect the transport but does diminish the amount of Ca2+ within the sarcoplasmic reticulum that is available for the activation of myocardial contractile activity.

Animals↗

Comparison of thiopental and midazolam on the neuromuscular responses to succinylcholine or pancuronium in humans.

Midazolam (0.3 mg/kg) was compared to thiopental (4.0 mg/kg) for possible interactions with succinylcholine or pancuronium when used for induction of anesthesia. Neuromuscular function was monitored by recording the force of thumb adduction in response to ulnar nerve stimulation. Following induction of anesthesia with either midazolam (N = 10) or thiopental (N = 10), stable muscle-twitch tension was obtained and succinylcholine (1 mg/kg) was given intravenously. The duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam or thiopental. An additional group of patients anesthetized and monitored in the same manner received pancuronium (0.025 mg/kg) in incremental doses until a 99% depression of muscle-twitch tension was obtained. Dose-response curves for pancuronium, duration of blockade, and adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam (N = 10) or thiopental (N = 10). We conclude that the neuromuscular blockade produced by succinylcholine or pancuronium was no different in patients receiving either midazolam or thiopental for induction of anesthesia.

Anesthesia, Intravenous↗

Reversed-phase liquid-chromatographic simultaneous analysis for thiopental and pentobarbital in serum.

We describe a reversed-phase liquid-chromatographic assay suitable for therapeutic monitoring of thiopental and pentobarbital simultaneously in human serum. The drugs are extracted from serum at pH 6.6 into n-butyl chloride containing thiamylal and barbital as the respective internal standards. The compounds are back-extracted into dilute sodium hydroxide, an aliquot of which is submitted to chromatography. The lowest measurable concentrations are 1.0 mg/L for thiopental and 2.0 mg/L for pentobarbital. The standard curve is linear from 0 to 100 mg/L for both. Between-run CVs are: at 25 mg/L, 4.1% (thiopental) and 3.2% (pentobarbital); at 50 mg/L, 2.8% (thiopental) and 3.4% (pentobarbital). Data on patients receiving thiopental and pentobarbital illustrate use of the method.

Chromatography, High Pressure Liquid↗

Comparison of cardiovascular effects of thiopental and pentobarbital at equivalent levels of CNS depression.

Thiopental and pentobarbital have been used in high doses to protect the brain from injury following hypoxia or to reduce intracranial pressure. This study was performed to determine whether these barbiturates differ in cardiovascular effects when present in plasma concentrations that produce equivalent CNS effects. The effects of thiopental and pentobarbital on heart rate, stroke volume/kg, cardiac output/kg, systemic vascular resistance, mean arterial pressure, and central venous pressure were statistically indistinguishable at plasma concentrations of each barbiturate ranging from 50% to 100% of their concentration producing EEG silence. Three of the seven dogs given thiopental developed ventricular bigeminy at plasma concentrations ranging from 45% to 65% of their concentration producing EEG silence. Lidocaine (1.4-2.0 mg/kg intravenously) reversed the bigeminy to sinus rhythm. When given more than the amount needed to produce a flat EEG, five of the seven dogs given thiopental died, but all dogs given pentobarbital survived. Pentobarbital may be a better choice than thiopental when large doses are indicated.

Animals↗

Lidocaine or thiopental for rapid control of intracranial hypertension?

The effectiveness of intravenously administered lidocaine for rapid control of acute intracranial hypertension was compared to the effectiveness of thiopental in 20 patients with brain tumors undergoing craniotomy. Despite normal radial arterial and intracranial pressures (ICP) after induction of N2O-O2-morphine anesthesia, mean ICP increased from 13.8 torr +/- 1.5 SE to 31 torr +/- 2.3 SE (p less than 0.001) in response to application of a pin-holder or scalp incision. To treat the elevated ICP a bolus injection of lidocaine, 1.5 mg/kg IV, was given to 10 patients, whereas the other 10 received thiopental, 3 mg/kg IV. Lidocaine reduced ICP 15.7 torr +/- 5.6 SE (p less than 0.025) did not significantly affect mean arterial pressure. In contrast, thiopental lowered ICP 18.4 torr +/- 9.6 SE (p less than 0.02) and also lowered mean arterial pressure by 26.1 torr +/- 9.6 SE (p less than 0.025). Mean time for injection of medication to ICP nadir was 66 seconds +/- 10 SE after lidocaine versus 48 seconds +/- 9 SE after thiopental (p greater than 0.20). It is concluded that lidocaine is as effective as thiopental for rapid reduction of intraoperative intracranial hypertension but that it causes less cardiovascular depression. Lidocaine may be of particular benefit to patients with both intracranial hypertension and marginal circulatory function.

Brain Neoplasms↗

Cholinergic action of thiopental on the hypothalamohypophyseal axis.

Ten postmenopausal women were divided into two groups. In five patients (group 1) four venous blood samples were collected at 5-minute intervals before and after thiopental sodium, 6 mg/kg IV, for determination of serum levels of prolactin and thyroid-stimulating hormone. In the other five patients (group 2) the procedure followed was as in group 1, but thiopental administration was preceded by atropine, 0.1 mg/10 kg. Prolactin levels increased significantly after thiopental injection in group 1, but not in group 2. Thyroid-stimulating hormone levels in both groups remained virtually unaltered. The fact that atropine prevented the increase of prolactin due to thiopental suggests that thiopental may have an indirect effect on the hypothalamohypophyseal axis through a cholinergic mechanism.

Atropine↗

A bioassay for a water-soluble benzodiazepine against sodium thiopental.

The authors performed a bioassay of midazolam maleate, an investigational, water-soluble benzodiazepine; to determine the duration of sleep after a single intravenous dose. Sodium thiopental was the standard against which the midazolam maleate was assayed. Prior to operation 60 surgical patients were randomly given one of five doses of drugs, either thiopental, 180 or 270 mg, or midazolam maleate, 6.6, 10, or 15 mg. The designated drug was infused intravenously over 20 sec in a double-blind fashion. Sleep was defined as commencing when the patients stopped counting, and ending when they could respond appropriately to verbal commands. Midazolam maleate, 10 mg (9--12 mg represents 95 per cent confidence limits), was found to be equivalent to thiopental, 200 mg, in the duration of sleep induced. Apnea following the infusion was less frequent and of shorter duration after midazolam maleate than after thiopental. It is concluded that midazolam maleate is a satisfactory agent for the induction of anesthesia, and that it is about 20 times as potent as thiopental.

Adolescent↗

Preembolization functional evaluation in supratentorial cerebral arteriovenous malformations with superselective intraarterial injection of thiopental sodium solution.

Superselective intraarterial injections of thiopental sodium solution for evaluation of local brain function were performed before embolization in 38 consecutive patients with supratentorial arteriovenous malformations to evaluate the role of the test using thiopental sodium solution. Thiopental sodium (30-50 mg) was injected in 68 arteries (44 middle cerebral arteries, 13 anterior cerebral arteries, 7 posterior cerebral arteries, 3 external carotid arteries, and 1 thalamo-perforating artery) through superselective microcatheters just before the injection of cyanoacrylate mixture for the embolization. The test was negative in 57 arteries and there were neurologic dysfunctions in 3 of them after embolization. The neurologic deficits in these cases were caused by reflux of embolic material, spasm of the main arterial trunk, or neglected mild sensory change, respectively, and there was no real false-negative test. The embolization could not be performed due to positive test in 9 arteries. Two arteries with positive tests but acceptable symptoms were embolized and the same neurologic deficits developed immediately after embolization. There was no local arterial complication by an injection of the thiopental sodium solution. All neurologic deficits caused by positive tests developed immediately and were completely relieved within 5 min without specific management. Superselective intraarterial injection of thiopental sodium solution is a safe and reliable test for the evaluation of local brain function before embolization of supratentorial arteriovenous malformations.

Adolescent↗

[Cardiorespiratory evaluation of midazolam and thiopental during their use in patients undergoing translumbar aortography in decubitus prone position and ASA IV].

AIMS: To verify the cardiorespiratory effects of midazolam and thiopental in ASA IV patients undergoing translumbar aortography in the decubitus prone position. METHODS: A prospective double blind study was carried out on 26 patients (mean age, 65.9 yr) allocated randomly to receive either midazolam (0.13 mg/kg) or thiopental (4 mg/kg) i.v. Without being premedicated all the patients had fentanyl 1.5 micrograms/kg i.v. and were preoxygenated with 50% oxygen before induction of anaesthesia. Blood pressure was measured by oscilometry and blood oxygenation by pulseoxymetry. RESULTS: No significant differences were found in the hemodynamic values (blood pressure, heart rate, double product) upon comparison of the two groups. Apnea was more frequent in the thiopental group 61.5% (8 out of 13 patients) than in the midazolam group 15.3% (2 out of 13 patients). Hypoxemia appeared only in the former group (61.5% of the cases). CONCLUSIONS: In patients undergoing translumbar aortography midazolam and thiopental behaved similarly with regard to hemodynamics. Midazolam produced less apnea than thiopental.

Aged↗

Influence of ondansetron on thiopental hypnotic requirements.

Ondansetron, a selective 5-HT3 antagonist has been proved to be an effective antiemetic agent for prophylaxis of nausea and vomiting after surgery. This study was conducted to determine whether ondansetron changes thiopental requirements for induction of anesthesia in patients unpremedicated and premedicated with diazepam. One hundred sixty eight adult female patients classified as American Society of Anesthesiologists (ASA) physical status I (normal healthy patient) or II (patient with mild systemic disease) participated in this prospective, double blinded, randomized study. Patients were assigned to receive either 0.07 mg/Kg diazepam orally or no premedication. They then received saline and ondansetron 0.1 mg/Kg or 0.2 mg/Kg intravenously 5 minutes before thiopental induction. Thiopental was administered at a rate of 25 mg/min until the patient lost the ability to open eyes on command. Thiopental requirements were not significantly different among groups. The results indicate that ondansetron in clinically used doses does not influence the hypnotic requirements of thiopental.

Adolescent↗

Cardiovascular Response and Anesthetic Recovery in Electroconvulsive Therapy with Propofol or Thiopental.

Propofol provokes a slight hypotensive effect that could mitigate the cardiovascular response to electroconvulsive therapy (ECT). In this study we compared the effects of propofol and thiopental for ECT anesthesia in seven women (22-67 years of age). Anesthesia was induced with either thiopental or propofol, and with atropine and suxamethonium for each treatment. The first anesthesia was assigned to thiopental or propofol at random; the next anesthesia was induced with the other drug, and alternated thereafter. Systolic blood pressure, diastolic blood pressure (DBP), and heart rate (HR) were recorded before anesthesia, after anesthetic induction, and 1 and 5 min after ECT. ECT-induced increases in DBP and HR were less marked with propofol than with thiopental. Seizure durations were decreased with propofol compared with thiopental.

Journal Article↗

Suppressive effects of thiopental and halothane on specific arms of the immune response.

The effect of thiopental, halothane and surgery on specific arms of the immune response of normal mice was studied. These experiments represent the first step in localizing a potentially correctable anesthesia/surgery-induced defect in immune reactivity which may be involved with postoperative increases in tumor growth. The delayed-type hypersensitivity (DTH) response of mice to 2,4-dinitrochlorobenzene (DNCB) was studied. Combinations of induction and inhalation anesthesia and surgery were administered at various phases of the immune response to DNCB. Thiopental impaired the afferent response while halothane impaired the efferent response. When the agents were combined, both arms of the immune response were suppressed. A surgical procedure, in most experiments, did not produce a greater immunosuppression than thiopental and halothane. The administration of an immunorestorative agent, thiabendazole, returned reactivity to normal levels. Thiopental and halothane either affect different immune cell populations or they affect different functions of a cell population active in both arms of the DTH response. In relation to tumor growth, the degree of suppression may not be as significant as the cell population impaired.

Anesthesia↗