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PubMed1986

[Thiopental distribution in the blood of surgical patients].

The influence of hematocrit, of the concentration of plasma proteins, and of CO2 pressure on the distribution of thiopental in the blood was studied in vitro in 30 venous blood samples. Thiopental was bound to plasma proteins to 80.3-89.2%, mean 85.0%, at a plasma protein concentration of 60 g/l and a pH of 7.37. Considerable changes in the plasma protein concentration had a considerable influence on the binding rate. By halving the protein concentration the free fraction was almost doubled. Increasing the protein concentration to 90 g/l led to binding rates of around 88-89%. When the pCO2 was increased from 40 to 60 torr protein binding decreased slightly, indicating that this barbiturate is mainly bound in its anionic form. At a hematocrit of just under 40 vol.%, 14-34% of the thiopental was absorbed by the erythrocytes. Changes in the plasma protein binding rate influenced the thiopental proportion of erythrocytes, as changes in the hematocrit influenced the plasma thiopental proportion. The concentration of liposoluble thiopental acid physically dissolved in the plasma fluid, just under 8% of the thiopental in the blood, changed relatively little on variation of the hematocrit and the CO2 pressure, thanks to the compensatory function of the plasma proteins and erythrocytes. Since most of the thiopental in the blood is bound to plasma proteins, changes in the protein concentration had the greatest effect on the proportion of thiopental acid of the barbiturate content of the blood.

Anesthesia, General↗
PubMed1993

Uptake and effects of thiopental in isolated heart preparations of the rat in the presence of halothane.

The uptake of thiopental (CAS 76-75-5) (0.13-0.27 mmol.l-1) into tissue of rat hearts (Langendorff's preparation) was studied in the presence of halothane (CAS 151-67-7). Up to a thiopental concentration of 0.19 mmol.l-1 in the perfusion medium its concentration in heart tissue was significantly increased vs. control when halothane (0.8 vol%) simultaneously was present; using 0.13 mmol.l-1 thiopental and 0.8, 1.5 or 2.0 vol% halothane this increase amounted +12%, +29% and +43%, respectively. Frequency of spontaneously beating rat hearts decreased in the presence of increasing thiopental concentrations. 0.8 vol% halothane (without thiopental) did not influence heart rate; in the presence of thiopental it attenuated heart rate reduction. This attenuation was absent in hearts of rats pretreated with reserpine. 1.5 vol% halothane (itself also without influence on heart rate) increased the negative chronotropic action of thiopental. In isolated right and left atria of rat hearts frequency and contractility decreased concentration-dependently in the presence of thiopental; simultaneously present halothane additionally increased this negative chronotropic and negative inotropic effect of thiopental.

Animals↗
PubMed1996

Myocardial uptake of thiopental enantiomers by the isolated perfused rat heart.

Myocardial uptake of thiopental enantiomers by an isolated perfused rat heart preparation was examined after perfusion with protein-free perfusate. Outflow perfusate samples were collected at frequent intervals for 20 min during single-pass perfusion with 10 micrograms/ml racemic thiopental (washin phase) and for another 45 min during perfusion with drug-free perfusate (washout phase). (+)- and (-)-thiopental concentrations were assayed by chiral high-performance liquid chromatography. Heart rate, perfusion pressure, and electro-cardiogram were also monitored. During the washin phase, there was no significant difference between the mean values of the equilibration rate constants of (+)- and (-)-thiopental enantiomers (0.44 +/- 0.07 min-1 and 0.43 +/- 0.09 min-1, respectively, P > 0.05). Mean volumes of distribution of (+)- and (-)-thiopental enantiomers were similar (6.34 +/- 1.20 and 6.45 +/- 1.29 ml/g for the washin phase and 7.22 +/- 0.71 and 7.47 +/- 0.81 ml/g for the washout phase, respectively, P > 0.05). This indicates that tissue accumulation of thiopental enantiomers in the isolated perfused rat heart was not stereoselective. Uptake of thiopental by the heart was perfusion flow rate-limited and independent of capillary permeability. These findings suggest that myocardial tissue concentration of racemic thiopental should be an accurate predictor of myocardial drug effect.

Anesthetics, Intravenous↗
PubMedDate not supplied

Prediction of thiopental induction dose based on caffeine volume of distribution.

Similarities in the physicochemical properties of caffeine and thiopental would suggest that the apparent volume of distribution of caffeine (aVd) may be comparable to the initial volume of distribution of thiopental. It is the initial volume of distribution of thiopental that is critical in the early minutes of anesthetic induction. A comparison of the aVd of caffeine and thiopental induction dose was made in 21 male New Zealand white rabbits. The aVd of caffeine was determined from serial saliva determinations following intravenous injection of caffeine (7.5 mg/kg). The loss of the pupillary light reflex was used as the end point for induction with thiopental. A statistically significant correlation (r = .722, P less than .0001) was found between the aVd of caffeine and thiopental induction dose. Also, both thiopental induction dose and caffeine aVd decreased significantly with age in these animals. These findings provide a basis for development of an uninvasive test for predicting thiopental dose in humans.

Animals↗
PubMed1993

A pharmacokinetic-pharmacodynamic model for quantal responses with thiopental.

The pharmacokinetic-pharmacodynamic model developed here characterizes the relationship between simulated plasma concentrations of thiopental and two dichotomous endpoints determined at induction of anesthesia: loss of voluntary motor power (clinical endpoint), and burst suppression of the electroencephalogram (EEG endpoint). The model incorporated data from two separate thiopental patient studies: a pharmacokinetic study with 21 males, and a pharmacodynamic study with 30 males. In the pharmacodynamic study, cumulative quantal dose-response curves for the clinical and EEG endpoints were developed from observations made during a constant-rate infusion of thiopental. Population mean parameters, derived from the bolus pharmacokinetic thiopental study, were used to simulate concentration-time data for the 150 mg.min-1 thiopental infusion rate used in the dose-response study. A single biophase model incorporating the two endpoints was generated, combining the pharmacokinetic and pharmacodynamic data from the two groups. Estimates of the mean effective thiopental concentrations affecting 50% of the population (EC50S) for the clinical and EEG endpoints were 11.3 and 33.9 micrograms.ml-1, respectively. The half-time for equilibration between arterial thiopental and the effect compartment was 2.6 min. These results are in reasonable agreement with previously described quantal concentration-response data, and with pharmacodynamic models developed for graded EEG responses. Simulation of bolus doses of thiopental with the new model provided ED50s for the clinical and EEG endpoints of 265 mg and 796 mg, respectively; the dose predicted to produce loss of voluntary motor power in 90% of an adult male population was 403 mg. A model combining population pharmacokinetics with cumulative dose-response relationships could prove useful in predicting dosage regimens for those drugs with responses that are categorical.

Adolescent↗
PubMed1983

Thiopental bolus during carotid endarterectomy-rational drug therapy?

Ten studies were performed to examine the time course of arterial and venous thiopental concentrations following the administration of thiopental (4 mg X kg-1 over 3 min) for cerebral protection during carotid occlusion in nine patients undergoing elective carotid endarterectomy; in five patients the time course of EEG change was also studied. The arterial and venous thiopental concentrations were similar with no evidence of a sustained arterial-venous gradient. The average arterial concentration was 20.1 microgram X ml-1 +/- 10 (SD) at 2 min after thiopental, and fell rapidly to 13.0 micrograms X ml-1 +/- 3.2 at 5 min, 10.7 micrograms X ml-1 +/- 4.4 at 10 min and 6.2 micrograms X ml-1 at 30 min. After thiopental the EEG record showed an increase in delta activity and in four patients a burst suppression pattern was seen. The duration of burst suppression activity was variable (130 to 367 seconds) but in all instances cortical activity had returned to the pre-thiopental level by five to ten minutes. Thus concentrations of thiopental of 10-30 micrograms X ml-1 were associated with EEG burst suppression and both were seen only within the first five minutes after drug administration. In contrast the carotid artery was occluded for considerably longer (26 +/- 4) minutes. We conclude that, since there was no sustained arterial-venous gradient, either arterial or venous concentrations are adequate for the study of thiopental pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Thiopental inhibits K+ permeability of rat and mouse pancreatic beta-cells.

The effects of thiopental on the insulin release and 86Rb efflux from isolated rat islets and on parameters of the electrical activity of single beta-cells of mice were studied. Thiopental 0.2 and 1.0 mM increased by 16.6 and 33.3%, respectively, the insulin release induced by 6.0 mM glucose. Thiopental reduced the 86Rb efflux rate in both 0 and 6.0 mM glucose, but had only a slight effect in 16.7 mM glucose. Menadione (20 microM) did not block the inhibitory effect of thiopental on 86Rb efflux. Thiopental induced a reversible membrane depolarization in a dose-dependent manner (0.2-1.0 mM). It also induced electrical activity at a subthreshold glucose concentration and continuous spiking in presence of 11.1 mM glucose. In the presence of 2,4-dinitrophenol (20 microM) this continuous spiking was changed to an oscillatory activity similar to that induced by 11.1 mM glucose. Thiopental (0.5 mM) induced an increase in input resistance of 12.7, 17.9 and 16.0% in 0, 5.6 and 11.1 mM glucose, respectively. The thiopental-induced changes in insulin secretion, 86Rb efflux and electrical parameters indicate that K+ permeability was affected in both rat and mouse beta-cells. Our results suggest that thiopental is a direct inhibitor of the glucose-sensitive K+ permeability in the beta-cell.

Animals↗
PubMed1992

The barbiturate thiopental reduces ATP levels during anoxia but improves electrophysiological recovery and ionic homeostasis in the rat hippocampal slice.

The barbiturate anesthetic thiopental enhances recovery of the evoked population spike recorded from rat hippocampal slices after short periods of anoxia. Thiopental reduces changes in sodium, potassium and calcium but enhances the fall in ATP levels during anoxia. The postsynaptic population spike recorded from the CA1 pyramidal cell region of the slices treated with thiopental (600 microM) recovered to 67% of the preanoxic amplitude after 3.5 min of anoxia. There was less recovery (24%) when a lower concentration of thiopental (250 microM) was used. Untreated slices recovered to only 10% of their preanoxic amplitude after 3.5 min of anoxia. Other studies have demonstrated that maintaining ATP levels during anoxia may be an important mechanism of protection. In contrast to those studies, thiopental was protective although it enhanced the fall of ATP levels after 3.5 min of anoxia in the CA1 region and after 3.5 and 5 min in the dentate region. Thus enhanced recovery of the population spike with thiopental is not due to its preservation of ATP levels. This result allows a clear separation of improved ATP levels during anoxia from other mechanisms of protection. We therefore looked for other mechanisms of protection. Sodium and potassium levels were measured after 10 min of anoxia. In untreated tissue, sodium levels in the slice rose and potassium levels fell significantly. In thiopental-treated tissue, changes in sodium and potassium caused by anoxia and by veratridine under normoxic conditions were significantly reduced. During anoxia calcium-45 uptake increases; thiopental significantly reduces this uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Thiopental sodium by single bolus dose compared to infusion for cerebral protection during cardiopulmonary bypass.

The authors previously demonstrated that thiopental sodium infused throughout cardiopulmonary bypass (CPB) considerably reduced persistent but not transient neuropsychiatric complications after open-chamber cardiac operations. Based on the probability that emboli released at the time of aortic declamping cause most postoperative central nervous system (CNS) dysfunction, this study was designed to test whether administration of a single bolus dose of thiopental before aortic declamping provided cerebral protection equal to that of infusion throughout bypass as well as a decrease in unwanted side effects. One hundred adult patients undergoing open-chamber cardiac operations with CPB received either thiopental sodium by infusion throughout CPB (n = 52) or thiopental sodium 15 mg/kg by bolus before aortic declamping (n = 48). In 90% of the patients, thiopental sodium 15 mg/kg produced electroencephalographic (EEG) burst suppression, with more than 60 seconds between bursts. Postoperative CNS dysfunction occurred in 3 (6%) of the infusion group patients (thiopental sodium 36 +/- 10 mg/kg) and 2 (4%) of the bolus group patients (thiopental sodium 16 +/- 2 mg/kg). CNS dysfunction persisting to the tenth postoperative day occurred in only one patient, who was in the infusion group. Requirements for inotropic support on separation from CPB did not differ between groups, but average time to extubation was 2.7 hours shorter in the bolus group. The authors conclude that thiopental sodium 15 mg/kg given as a single bolus immediately before aortic declamping without the need for EEG monitoring provided the same brain protection as larger doses given by infusion titrated to burst suppression, but it did not reduce the need for inotropic support during separation from CPB.

Adult↗
PubMedDate not supplied

Infusion of large particles of thiopental sodium during anesthesia induction.

STUDY OBJECTIVE: To determine the potential clinical significance of admixtures of thiopental sodium and acidic drugs, which are used during induction of general anesthesia and can cause the formation of particles of thiopental. DESIGN: Using an infusion setup similar to that used for a rapid-sequence induction of general anesthesia, injection of either pancuronium bromide or vecuronium bromide caused formation of particles of thiopental that were measured using a particle analyzer. The effects of delaying the injection of the muscle relaxant on particle formation and the effects of plasma on particle dissolution were studied. MEASUREMENTS AND MAIN RESULTS: The thiopental particles had a diameter of 17 to 39 microns, with a concentration of 15,000 to 20,000 particles/ml. Particle formation was prevented when a 30-second delay preceded administration of pancuronium or vecuronium following injection of thiopental. No particle formation was detected when succinylcholine was injected. Human plasma was far more effective than a crystalloid solution in dissolving thiopental particles. CONCLUSIONS: It is unlikely that clinically significant particles of thiopental will remain intact upon entering the bloodstream. However, mixing thiopental with pancuronium or vecuronium has the potential of disrupting intravenous access due to occlusion with particles.

Anesthesia, General↗
PubMed1995

A re-evaluation of the ability of thiopental to identify cerebrospinal fluid in epidural catheter aspirate.

STUDY OBJECTIVE: Sodium thiopental has been used to determine whether fluid aspirated from an epidural catheter is previously injected local anesthetic or cerebrospinal fluid (CSF). The purpose of this study was to test the efficacy of this test in distinguishing opioids from CSF. DESIGN: in vitro study. SETTING: Laboratory of a university hospital. MEASUREMENTS AND MAIN RESULTS: Three in vitro studies were performed. The first study tested for precipitation when thiopental was mixed with several commonly used epidural medications. Then, thiopental was mixed in combinations of opioids with local anesthetics to see if the opioid might prevent the precipitation of the local anesthetics. Finally, lidocaine was serially diluted and precipitation with thiopental was assessed. It was found that certain concentrations of opioids as well as normal saline do not precipitate with thiopental. In addition, the ratio of opioids to local anesthetic of 10:1 prevented precipitation when thiopental was added. Local anesthetics combined with cerebrospinal fluid in a 1:10 ratio produced a precipitate on mixing with thiopental. CONCLUSIONS: Use of thiopental to differentiate opioids from cerebrospinal fluid is unreliable. In addition, in some simulated situations, opioids may mask the presence of local anesthetic.

Anesthesia, Epidural↗
PubMedDate not supplied

Effects of thiopental on transport and metabolism of glutamate in cultured cerebellar granule neurons.

This study was performed to analyze the effects of the barbiturate thiopental on neuronal glutamate uptake, release and metabolism. Since barbiturates are known to bind to the GABA(A) receptor, some experiments were carried out in the presence of GABA. Cerebellar granule neurons were incubated for 2 h in medium containing 0.25 mM [U-(13)C]glutamate, 3 mM glucose, 50 microM GABA and 0.1 or 1 mM thiopental when indicated. When analyzing cell extracts, it was surprisingly found that in addition to glutamate, aspartate and glutathione, GABA was also labeled. In the medium, label was observed in glutamate, aspartate and lactate. Glutamate exhibited different labeling patterns, indicating metabolism in the tricarboxylic acid cycle, and subsequent release. A net uptake of [U-(13)C]glutamate and unlabeled glucose was seen under all conditions. The amounts of most metabolites synthesized from [U-(13)C]glutamate were unchanged in the presence of GABA with or without 0.1 mM thiopental. In the presence of 1 mM thiopental, regardless of the presence of GABA, decreased amounts of [1,2, 3-(13)C]glutamate and [U-(13)C]aspartate were found in the medium. In the cell extracts increased [U-(13)C]glutamate, [1,2, 3-(13)C]glutamate, labeled glutathione and [U-(13)C]aspartate were observed in the 1 mM thiopental groups. Glutamate efflux and uptake were studied using [(3)H]D-aspartate. While efflux was substantially reduced in the presence of 1 mM thiopental, this barbiturate only marginally inhibited uptake even at 3 mM. These results may suggest that the previously demonstrated neuroprotective action of thiopental could be related to its ability to reduce excessive glutamate outflow. Additionally, thiopental decreased the oxidative metabolism of [U-(13)C]glutamate but at the same time increased the detectable metabolites derived from the TCA cycle. These latter effects were also exerted by GABA.

Animals↗
PubMed2002

Efficacy and safety of rectal thiopental, intramuscular cocktail and rectal midazolam for sedation in children undergoing neuroimaging.

BACKGROUND: This study was designed to investigate the overall usefulness of rectal thiopental, rectal midazolam and i.m. modified cocktail (meperidine-chlorpromazine hydrochloride-feniramin maleat) in 70 children undergoing computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: The dosage of thiopental was 50 mg per kg for infants under 6 months of age, 35 mg per kg between six and 12 months, and 25 mg per kg for older children. The maximal dose did not exceed 700 mg in this study. The dosage of midazolam was 1 mg per kg for all children. A modified cocktail was described as a formulation including 11 mg/mL of meperidine, 2.8 mg/mL of chlorpromazine and 2.8 mg/mL of pheniramine maleat. The dosage of modified cocktail was 0.1 mL per kg for all children. RESULTS: The mean induction time for the i.m. cocktail was significantly longer than that for rectal thiopental (P < 0.001). The mean duration of deep sedation was 60.79 +/- 27.00 min with rectal thiopental and 58.74 +/- 39.70 min with i.m. cocktail (P > 0.05). Although the mean duration of sleep for rectal thiopental and i.m. cocktail was similar, the mean discharge duration for i.m. cocktail was significantly longer than that for rectal thiopental (P < 0.05). Children sedated with the cocktail therapy also required a longer period of observation in the department. Significant decreases in heart rate, systolic blood pressure and oxygen saturation occurred in three groups (P < 0.001). Significant decreases in body temperature occurred after rectal thiopental and i.m. cocktail therapy (P < 0.01). The effect of rectal midazolam was minimal. CONCLUSIONS: Rectal thiopental may be the drug of choice for pediatric sedation because it has a more rapid onset and offset of action. It is also safe and effective at the dosage studied in children undergoing MRI. Rectal midazolam also may be used in children undergoing CT imaging because of minimal side-effects.

Administration, Rectal↗
PubMed1999

Protective effect of thiopental against cerebral ischemia during circulatory arrest.

BACKGROUND: One of the most important disadvantages of the hypothermic circulatory arrest technique is the limited time allowable for circulatory arrest. Thiopental is usually used to protect the brain against ischemic injuries. However, it remains uncertain how well thiopental reduces cerebral metabolism. We investigated its effectiveness by comparing outcomes after different doses. METHODS: Fifty patients who underwent aortic arch repair with hypothermic circulatory arrest had their records reviewed. Electroencephalograms (EEG) and partial pressures of oxygen in the internal jugular vein (PjO2) were monitored. Following confirmation of total disappearance of EEG activity, 15 or 30 mg/kg thiopental was administered before circulatory arrest Th duration of circulatory arrest ranged from 16 to 77 min. RESULTS: Hospital mortality rate was 10% and 4 (8%) patients developed neu-rologic complications, but 3 of them were transient. After thiopental infusion, PjO2 increased significantly from 430 to 499mmHg (p <0.01), indicating that thiopental reduces cerebral oxygen consumption. The rate of the decrease in PjO2 during circulatory arrest was slower with the higher thiopental dose, suggesting that thiopental lowered the cerebral metabolic rate of oxygen during circulatory arrest. CONCLUSION: It appears that thiopental has protective effects against cerebral ischemia under profound hypothermia.

Adult↗
PubMed2003

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs.

BACKGROUND: Thiopental sometimes causes bronchospasm during induction of anaesthesia. In addition, we have reported previously that thiopental produced transient bronchospasm, which was blocked by atropine pretreatment, and worsened histamine-induced bronchoconstriction in dogs. Previous in vitro reports suggest that synthesis of contractile cyclooxygenase products, such as thromboxane A(2), may be involved in the mechanism of bronchospasm. However, the in vivo spastic effects have not been defined comprehensively. METHODS: Twenty-seven mongrel dogs were anaesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1)+5.0 microg kg(-1) min(-1); Mch group, n=7) or serotonin (10 microg kg(-1)+1 mg kg(-1) h(-1); 5HT group, n=20), and assessed as percentage changes in bronchial cross-sectional area (BCA, basal=100%) using a bronchoscope. In the 5HT group, dogs were subdivided into four groups of five each: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HT groups, 30 min before serotonin infusion dogs were given saline and indomethacin respectively at 5 mg kg(-1) i.v. In all groups, 30 min after bronchoconstrictor infusion started, dogs were given thiopental at doses between 0 (saline) and 20 mg kg(-1). In the 5HT-S and 5HT-A groups, dogs were given saline or atropine 0.2 mg kg(-1) i.v. 5 min after thiopental 20 mg kg(-1). RESULTS: Methacholine and serotonin reduced BCA by about 50 and 40% respectively. Thiopental 20 mg kg(-1) increased and decreased BCA by about 20 and 10% in the Mch and 5HT groups respectively. Indomethacin and atropine did not attenuate the potentiation of serotonin bronchoconstriction produced by thiopental. CONCLUSION: The present study indicates that thiopental may attenuate or worsen bronchoconstriction induced by muscarinic or serotonin receptor stimulation, respectively. The synthesis of contractile cyclooxygenase products and cholinergic stimulation may not be involved in the contractile effect of thiopental on serotonin bronchoconstriction.

Anesthetics, Intravenous↗
PubMed1997

Postoperative analgesic requirement after cesarean section: a comparison of anesthetic induction with ketamine or thiopental.

UNLABELLED: In a randomized, double-blind study, we compared postoperative pain and analgesic requirement in patients who underwent elective cesarean section under general anesthesia induced with thiopental 4 mg/kg (n = 20) or ketamine 1 mg/kg (n = 20). Anesthesia was maintained with nitrous oxide and isoflurane. Postoperative analgesia was provided by patient-controlled analgesia (PCA) using morphine. Median (range) time to first PCA demand was greater in the ketamine group (28 [3-134] min) compared with the thiopental group (20.5 [3-60] min; P = 0.04). Median (range) morphine consumption over 24 h was less in the ketamine group (24.3 [3-41] mg) compared with the thiopental group (35 [4-67] mg; P = 0.017). Visual analog scale pain scores were similar between groups. No patients had recall of intraoperative events or unpleasant dreams. Two patients in the thiopental group and one patient in the ketamine group had pleasant intraoperative dreams. Apgar scores were similar between groups. Median umbilical venous pH was higher (7.33 vs 7.31; P = 0.04) and attributable to lower median umbilical venous Pco2 (5.72 vs 6.14 kPa; P = 0.02) in the ketamine group compared with the thiopental group. Induction of anesthesia for cesarean section using ketamine is associated with a lower postoperative analgesic requirement compared with thiopental. IMPLICATIONS: Patients who had anesthesia for cesarean section induced with ketamine required less analgesic drugs in the first 24 h compared with patients who received thiopental. Ketamine, unlike thiopental, has analgesic properties that may reduce sensitization of pain pathways and extend into the postoperative period.

Adult↗
PubMed1998

The chemical stability and sterility of sodium thiopental after preparation.

UNLABELLED: Manufacturer's instructions recommend discarding unused portions of sodium thiopental 24 h after reconstitution. Heeding this recommendation may result in the disposal of a large proportion of prepared thiopental. Although thiopental is relatively inexpensive, the volume prepared by many anesthesia departments could make this waste significant. To address this possibility, we investigated the chemical stability and sterility of thiopental in pharmacy-prepared, prefilled syringes. Stock solutions of thiopental were mixed and drawn into syringes under sterile conditions by pharmacists or pharmacy assistants. Fifty-six samples were stored under refrigeration (3 degrees C); the remaining 56 samples were stored at room temperature (22 degrees C). Each day for 7 days, eight samples from each group were analyzed by using high-performance liquid chromatography for chemical stability and cultured for microbiological colonization. Differences in thiopental concentration between the room temperature and the refrigerated samples were measured over time by using repeated-measures analysis of variance (P < or = 0.05). Three positive culture samples (S. epidermidis and S. hemolyticus) most likely represent laboratory contamination and not colonization. At 22 degrees C, thiopental remains stable and sterile for 6 days and well beyond 7 days at 3 degrees C. IMPLICATIONS: This study examines the shelf life of the anesthetic drug thiopental in pharmacy-filled syringes stored at either room temperature or under refrigeration. The results justify the use of prepared solutions beyond the package insert recommendation of 24 h.

Anesthetics, Intravenous↗
PubMed1985

Different effects of thiopental in severe hypoxia, total ischemia, and low-flow ischemia in rat heart muscle.

The effect of thiopental (100 mg X 1(-1] during total ischemia, low-flow ischemia, and severe hypoxia with maintained flow was investigated in the isolated perfused rat heart. During total ischemia the rate of decline of tissue creatine phosphate and adenosine triphosphate was no different in thiopental-treated and untreated hearts. The development of ultrastructural damage during total ischemia, the release of creatine kinase on reperfusion, and the exacerbation of ultrastructural damage after reperfusion were unaffected by thiopental. When thiopental was added to the perfusate during hypoxia and during low-flow ischemia at a normal pH(7.4), creatine kinase release during reoxygenation and during reperfusion was significantly less (P less than 0.005 and P less than 0.05, respectively) than in the untreated groups. After low-flow ischemia at a low pH (6.5), creatine kinase release was no different in thiopental-treated and untreated hearts. Thus, thiopental afforded protection of the myocardium in hypoxia and low-flow ischemia at pH 7.4 but not in total ischemia and low-flow ischemia at pH 6.5. The data are consistent with the hypothesis that during total ischemia and low-flow ischemia at pH 6.5, acidosis favors the entry of thiopental into the cell, causing inhibition of mitochondrial function and reduction of ATP production. During hypoxic perfusion and low-flow ischemia at pH 7.4, when the decrease in pH is less, the cardiodepressant effect of thiopental may offset any deleterious effect of the drug on intracellular organelles such as mitochondria.

Adenosine Triphosphate↗