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PubMed1991

Cardiovascular and respiratory effects of thiopental administration in hypovolemic dogs.

The cardiopulmonary effects of thiopental sodium were studied in hypovolemic dogs from completion of until 1 hour after administration of the drug. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 8 mg of thiopental/kg of body weight was administered IV to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to thiopental administration, heart rate and oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after thiopental administration, heart rate, mean arterial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and mixed venous oxygen tension increased, whereas oxygen utilization ratio and arterial and mixed venous pH decreased from values measured prior to thiopental administration. Fifteen minutes after thiopental administration, heart rate was still increased; however by 60 minutes after thiopental administration, all measurements had returned to values similar to those obtained prior to thiopental administration.

Anesthesia↗
PubMedDate not supplied

Binding of thiopental to human serum albumin in the presence of halogenated hydrocarbons and ethers.

Thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) studied by equilibrium dialysis in 1/15 M phosphate buffer solution (pH 7.4) was increased significantly from 40.2% (= control) to 55% in the presence of 4.71.10(-3) M halothane (= 11.36 vol%); 1.18.10(-3) M = 2.84 vol% halothane caused a lesser but still significant increase (vs. control) of thiopental binding. This halothane effect on the binding of thiopental to HSA was studied under several experimental conditions (variation of thiopental concentration, HSA concentration, pH of the buffer solution, temperature). Other halogenated hydrocarbons such as chloroform (6.2.10(-3) M) and carbon tetrachloride (5.2.10(-3) M) also markedly increased the binding of thiopental to HSA as compared to the control (percentage of fraction bound, 53 and 61%, respectively); the same effect, but to a lesser extent, was obtained under the influence of three halogenated ethers, i.e., enflurane (4.1.10(-3) M--greater than 45% thiopental bound), isoflurane (4.1.10(-3) M--greater than 50% bound) and methoxyflurane (4.3.10(-3) M--greater than 47% bound). Under the same experimental conditions, ethanol (up to 8.9.10(-2) M) and diethylether (up to 4.9.10(-2) M) did not increase the percentage of thiopental bound to HSA.

Carbon Tetrachloride↗
PubMed1988

Thiopental does not alter Ca2+ uptake by cardiac sarcoplasmic reticulum.

The effect of thiopental on Ca2+ uptake by cardiac sarcoplasmic reticulum (SR) isolated from the rabbit was examined to clarify the role of the sarcoplasmic reticulum in the negative inotropic action of thiopental. Thiopental, from 0 to 378 microM, did not alter the rate of Ca2+ uptake by the SR. We also compared the ATP dependence of Ca2+ uptake in the presence and absence of 284 microM thiopental. The Km for ATP and the Vmax of Ca+ uptake were unaffected by thiopental. It is concluded that thiopental does not alter Ca2+ uptake by the SR and that the negative inotropic effects of thiopental occur at other sites in the myocardial cell.

Animals↗
PubMed1983

Inotropic and anesthetic potencies of etomidate and thiopental in dogs.

The effects of etomidate and thiopental on myocardial contractility were compared in 10 experiments on isolated papillary muscle preparation perfused by a conscious donor dog. Equianesthetic doses of etomidate (1.4 mg/kg) and thiopental (15.5 mg/kg) were determined separately in conscious dogs. Tension developed by the papillary muscle decreased significantly less after etomidate (17 +/- 2%) than after thiopental (33 +/- 3%) (P less than 0.002) when injected intravenously in equianesthetic doses in donor dogs. When added to arterial blood perfusing the papillary muscle, etomidate had 4-5 times more negative inotropic effect than thiopental. At the same time, the anesthetic potency of etomidate was approximately 11 times greater than that of thiopental. We conclude that both etomidate and thiopental produce a dose-dependent direct negative inotropic effect but that in equianesthetic doses, etomidate causes less pronounced depression of myocardial contractility than thiopental.

Anesthetics↗
PubMed1986

Correlation between thiopental induction dose and the volume of distribution of caffeine in human subjects.

The correlation between the apparent volume of distribution (aVd) of caffeine and the induction dose of thiopental was studied in 23 patients. Caffeine, which has an effective partition coefficient that approaches that of thiopental, was used as an indicator substance to estimate the immediate volume of distribution of thiopental. The immediate volume of distribution is critical in determining thiopental induction dose. The aVd of caffeine was determined noninvasively from serial saliva samples after consumption of caffeine, which was given to the patients as coffee. A strong correlation (r = .69; P less than .01) was found between the aVd of caffeine and the anesthetic induction dose of thiopental when the loss of eyelid reflex was used as the end point. The correlation between thiopental induction dose and body weight for the same individuals (r = .188) was not statistically significant.

Adult↗
PubMed1988

Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol.

The effect of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, on the potentiation of thiopental-induced sleep by delta 9-tetrahydrocannabinol (THC), which inhibits the histamine turnover in the brain, was examined in mice and rats. The sleeping time after injection of thiopental sodium (40 mg/kg, IV) was prolonged by THC (10 mg/kg, IP, 1 h before) to approximately twice the control value. alpha-FMH (50 mg/kg, IP) administered alone had no significant influence on the thiopental sleeping time. However, alpha-FMH given 1 or 3 h before THC treatment markedly enhanced the THC potentiation of thiopental-induced sleep. Such an enhancement by alpha-FMH was not observed when alpha-FMH was administered 15 h before THC treatment. The brain histamine level decreased by 60% during the first 4 h after alpha-FMH injection and remained low until 15 h after the treatment. The thiopental sleep-potentiating action of morphine, chlorpromazine and diazepam was not affected by pretreatment with alpha-FMH. The transient enhancing effect of alpha-FMH on the THC potentiation of thiopental-induced sleep suggests that the histaminergic system is one of the activating transmitter systems in the brain.

Animals↗
PubMedDate not supplied

Propofol ensures a more stable A-line ARX index than thiopental during intubation.

BACKGROUND: The A-line autoregressive modelling with exogenous input index (AAI) is a new method of assessing depth of anesthesia. We examined the effects of tracheal intubation on the AAI and hemodynamics during induction of anesthesia with propofol compared with thiopental in patients aged over 50 yr. METHODS: 40 patients scheduled for a laminectomy, posterior spinal fusion, vertebroplasty, or total hip replacement, ASA physical status I or II and aged over 50 yr, were randomly divided into two groups. Thiopental 5 mg.kg(-1) iv, fentanyl 2.5 microg.kg(-1) iv, and rocuronium 0.7 mg.kg(-1) iv were used in the thiopental group (n = 20) for anesthetic induction; the same protocol was used in the propofol group (n = 20) except that 2 mg.kg(-1) propofol iv was given instead of thiopental. The AAI, non-invasive blood pressure, and heart rate were measured every minute before induction for three minutes, at 1.5 min post-induction, and then each minute post-intubation for eight minutes. RESULTS: The AAI increased significantly at one and two minutes after intubation in the thiopental group (to 56.5 +/- 18.6 at 1 min and 44.7 +/- 18.7 at 2 min after intubation vs 19.9 +/- 7.5 at 1.5 min after induction; P < 0.05). Thereafter, AAI values gradually decreased three minutes after intubation. The AAI was inhibited continuously after intubation in the propofol group, and no significant elevation was seen. CONCLUSION: Our results, using the AAI to monitor anesthetic depth during induction and tracheal intubation, suggest that at equipotent doses propofol provided a more stable level of anesthesia than did thiopental.

Anesthetics, Intravenous↗
PubMed2005

Thiopental sodium reduces glutamate extracellular levels in rat intact prefrontal cortex.

To investigate the effect of thiopental sodium on glutamate extracellular levels in the prefrontal cortex (PFC) of rats, a microdialysis probe was inserted into the PFC, the perfusate was collected every 10 min throughout the experiment with thiopental sodium ip or perfused into the PFC locally. The concentrations of glutamate in the perfusate were determined by reversed-phase high performance liquid chromatography. Thiopental sodium 30 mg kg(-1) ip significantly decreased glutamate levels in the perfusate after 10, 20, 30, and 40 min; glutamate levels in the perfusate were also decreased from 10 to 90 min after thiopental sodium 50 mg kg(-1) ip. Thiopental sodium with concentrations of 30, 100, or 300 microM perfused into the PFC also decreased glutamate levels in the perfusate significantly. The results suggest that thiopental sodium decreases glutamate extracellular levels in rat intact PFC.

Animals↗
PubMedDate not supplied

The differential cost of anesthesia and recovery with propofol-nitrous oxide anesthesia versus thiopental sodium-isoflurane-nitrous oxide anesthesia.

STUDY OBJECTIVE: To assess the recovery room profile of propofol in outpatient anesthesia and to compare it to the profile of a standard technique. DESIGN: A comparative, randomized, double-blind, third-party open study. SETTING: Ambulatory Surgery Center at The Emory Clinic. PATIENTS: Ninety-nine ASA physical status I, II, or III nonpregnant female patients who had been diagnosed as needing breast biopsies. INTERVENTIONS: All patients were given 1 microgram/kg of fentanyl prior to induction. Those in the propofol group were induced with 2.0 to 2.5 mg/kg of propofol and maintained with a 100 to 200 microgram/kg/min infusion of propofol with nitrous oxide (N2O) in oxygen (O2). In the thiopental sodium-isoflurane group, patients were induced with 4.0 to 5.0 mg/kg of thiopental sodium and maintained with isoflurane and N2O in O2. MEASUREMENTS AND MAIN RESULTS: Recovery from anesthesia was assessed by an evaluator who was unaware of the anesthetic technique used for each patient. Immediate recovery time was measured in terms of awakening, response to verbal command, and orientation to time and place. A brief postoperative follow-up questionnaire was completed to assess the patients' subjective feelings regarding their ability to eat, concentrate, and resume normal activities. In the thiopental sodium-isoflurane group, 15 of 50 patients (30%) had nausea and vomiting, but in the propofol group, only 4 of 49 patients (8.1%) had nausea and vomiting (p less than 0.01). The latter group resumed normal activity (i.e., reading and watching television) 7.93 +/- 0.76 hours postanesthesia, whereas the thiopental sodium-isoflurane group resumed normal activity 17.02 +/- 1.21 hours postanesthesia (p less than 0.001). Patients in the propofol group returned to work in an average of 1.5 +/- 0.09 days, compared with 2.0 +/- 0.09 days for the thiopental sodium-isoflurane group (p less than 0.001). CONCLUSIONS: The propofol group needed less nursing care and returned to more productive activity earlier than did the thiopental sodium-isoflurane group.

Ambulatory Surgical Procedures↗
PubMedDate not supplied

Electroconvulsive therapy-induced cardiac arrhythmias during anesthesia with methohexital, thiamylal, or thiopental sodium.

STUDY OBJECTIVE: To determine the frequency of electroconvulsive therapy (ECT)-induced arrhythmias under methohexital, thiamylal, or thiopental sodium anesthesia with and without atropine premedication. DESIGN: A randomized, double-blind study, placebo-controlled for atropine. SETTING: The inpatient psychiatric unit at a university medical center. PATIENTS: Forty-nine patients scheduled for ECT. INTERVENTIONS: Atropine 0.6 mg intravenously (IV) or an equal volume of normal saline IV was given before IV induction of anesthesia with methohexital 0.5 to 1.0 mg/kg, thiamylal 1.5 to 2.5 mg/kg, or thiopental sodium 1.5 to 2.5 mg/kg. MEASUREMENTS AND MAIN RESULTS: Single-lead electrocardiogram (ECG) recordings were made for 1 minute before induction, during induction of anesthesia, and for 5 minutes after the ECT stimulus. Each ECG was evaluated for arrhythmias and evidence of ischemia in a blinded fashion. Blood pressure and ECG evidence of ischemia did not differ among the groups. Seizure duration was significantly (p less than 0.05) prolonged by a mean of 5 seconds during methohexital anesthesia compared with thiopental sodium and thiamylal (47.6 +/- 18.6 seconds, 42.7 +/- 13.2 seconds, and 42.7 +/- 15.2 seconds, respectively). The frequency of sinus bradycardia was decreased (p less than 0.05) with methohexital (8%) compared with thiopental sodium (20%) and thiamylal (20%). The frequency of premature atrial contractions was decreased (p less than 0.05) with methohexital (43%) compared with thiamylal (61%) but not with thiopental sodium (57%). The frequency of premature ventricular contractions was decreased (p less than 0.05) with methohexital (27%) compared with thiopental sodium (44%) but not with thiamylal (40%). Atropine decreased the frequency of bradycardia (9% vs. 24%) and premature atrial contractions (47% vs. 61%) and increased the frequency of sinus tachycardia (88% vs. 75%). CONCLUSIONS: These data suggest that anesthesia for ECT therapy should be induced with methohexital to minimize the possibility of potentially life-threatening cardiac arrhythmias. Atropine premedication may further decrease the frequency of premature atrial contractions and bradycardia, while increasing the frequency of tachycardia.

Adult↗
PubMedDate not supplied

Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements.

STUDY OBJECTIVE: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Teaching hospital. PATIENTS: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery. INTERVENTIONS: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug. MEASUREMENTS AND MAIN RESULTS: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference. CONCLUSION: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.

Adult↗
PubMed1991

Thiopental as an adjunct to hypothermia for EEG suppression in infants prior to circulatory arrest.

Fifteen infants were studied to evaluate the effect of profound hypothermia (16 degrees C to 18 degrees C) and hypothermia plus thiopental on the electroencephalogram (EEG) prior to circulatory arrest. Mean patient age and weight were 5.5 +/- 1.2 months and 4.9 +/- 0.3 kg, respectively. After core cooling on cardiopulmonary bypass (CPB), all patients received thiopental, 8 mg/kg, 5 minutes prior to circulatory arrest. Satisfactory EEG recordings were obtained for 9 patients, and serum thiopental concentration was measured in 12 patients. Hypothermia (mean venous return temperature, 17.8 degrees C +/- 1.6 degrees C) alone was associated with persistent cerebral electrical activity in 8 of 9 patients (89%). The addition of thiopental, 8 mg/kg, produced an isoelectric EEG in 6 of these 8 patients (75%). Mean circulatory arrest duration was 44 +/- 4 minutes. EEG activity resumed after reinstitution of CPB in all patients. Serum thiopental concentration at the end of CPB was negligible. It is concluded that hypothermia alone often may not produce EEG isoelectricity, and that the associated cerebral metabolic activity may be suppressed by adjunctive use of thiopental.

Blood Proteins↗
PubMed2004

Rapid sevoflurane induction compared with thiopental.

STUDY OBJECTIVES: To examine whether the speed of induction of anesthesia with sevoflurane/nitrous oxide (N2O) utilizing a 10-second vital capacity rapid inhalation induction (VCRII) followed by tidal breathing was similar or faster than cautious intravenous (i.v.V) thiopental induction with inhaled N2O. DESIGN: Prospective, randomized, double-blinded study. SETTING: Veterans Affairs Medical Center. PATIENTS: 50 male ASA physical status I, II, and III patients scheduled for general anesthesia. INTERVENTIONS: Patients were randomized to receive either 8% sevoflurane or i.v. thiopental. Patients were allocated to one of two groups of 25 patients each. In both groups, the breathing circuit was initially primed for 5 minutes with (4 L/min) and O2 (2 L/min), while the Y-piece was occluded. In the sevoflurane group, the circuit was additionally primed with 8% sevoflurane. Patients were trained to perform a vital capacity breath. After maximal exhalation, the occluding plug was rapidly removed from the Y-piece and connected to the facemask. The patient then inspired to vital capacity, held his breath for 10 seconds, and then was allowed to breathe normally. At the end of the 10-second breathhold, and as the patient started normal breathing, either thiopental (thiopental group) or normal saline (sevoflurane group) was injected at a rate of 4 mL every 10 seconds. MEASUREMENTS: A study-blinded observer recorded the time to induction, as defined by the time to loss of eyelash reflex, and noted the occurrence of side effects. MAIN RESULTS: The speed of induction was the same for both groups (p > 0.05). An average of eight breaths was required before loss of eyelash reflex. Side effects occurred in 36% of the patients in the thiopental group, and 32% in the sevoflurane group (p > 0.05); these were minor and did not affect induction. CONCLUSION: Sevoflurane/N2O VCRII as used in this investigation is an effective inhalation technique; it resulted in an induction time similar to that of slow i.v. thiopental with inhaled N2O.

Administration, Inhalation↗
PubMed2001

The effect of thiopental on glutamate metabolism in mouse cerebellar astrocytes in vitro.

The effect of thiopental on [U-(13)C]glutamate metabolism was studied in cerebellar astrocytes from mice using (13)C magnetic resonance spectroscopy. The cells were incubated with 0.5 mM [U-(13)C]glutamate for 2 h in the presence of 1 mM thiopental and 1 mM thiopental plus 0.2 mM gammaamino butyric acid (GABA). Labeled glutamate, glutamine, aspartate and glutathione were observed in cell extracts, and glutamine, aspartate and lactate in the media. Not only uniformly labeled glutamate was present in the medium, but also glutamate derived from the tricarboxylic acid (TCA) cycle. In the presence of thiopental, the amount of unlabeled glucose and [U-(13)C]glutamate removed from the medium was unchanged. This is in contrast to previous results obtained in cortical astrocytes, showing cellular heterogeneity. The concentrations of [1,2,3-(13)C]glutamate and [U-(13)C]glutamine were increased in the cell extracts, but unchanged in the medium, indicating an increased synthesis and an unchanged exchange or release. It should be noted that [U-(13)C]lactate is formed from [U-(13)C]glutamate via the TCA cycle and is released to the medium. In the presence of thiopental less [U-(13)C]lactate was observed in the medium. GABA had no influence on the effects of thiopental on cerebellar astrocytes.

Animals↗
PubMed2002

Thiopental impairs neutrophil oxidative response by inhibition of intracellular signalling.

BACKGROUND AND OBJECTIVE: Thiopental in clinically relevant concentrations inhibits the oxidative function of neutrophils, whereas only very high, non-therapeutic concentrations of methohexital induce a similar effect. The study characterized the molecular basis of this differential action of oxy- and thiobarbiturates on neutrophils. METHODS: Neutrophils were incubated in vitro with thiopental or methohexital using concentrations within the therapeutic range. Neutrophil responses were induced using different stimuli: N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), C5a and 1,2-dioctanoyl-sn-glycerol (DiC8-DAG). FMLP and C5a bind to specific G-protein-coupled receptors that share the same second messenger cascade. In contrast, DiC8-DAG, an activator of protein kinase C, bypasses the signal transduction pathway downstream of the receptors. Hydrogen peroxide production by neutrophils was assessed using flow cytometry. To characterize the localization of the interaction site, FMLP receptor expression and cytosolic-free calcium were further analysed. RESULTS: FMLP and C5a-induced hydrogen peroxide production were both significantly impaired by thiopental, but not by methohexital. When postreceptor signalling was bypassed, by stimulation with DiC8-DAG, neither thiopental nor methohexital affected hydrogen peroxide production. Additionally, neither of the barbiturates impaired the cytosolic Ca2+ response. CONCLUSIONS: We conclude that neither protein kinase C nor the hydrogen peroxide-generating enzymes are affected by thiopental or methohexital. The unimpaired Ca2+ response suggests that the function of the receptors and G-proteins were also unimpaired. Taken together, this indicates that the site of action of thiopental is in the cellular signalling upstream of protein kinase C.

Anesthetics, Intravenous↗
PubMed1989

Intravascular mixing and drug distribution: the concurrent disposition of thiopental and indocyanine green.

The dispositions of concomitantly administered indocyanine green (ICG) and thiopental were determined in 12 patients undergoing general anesthesia and surgery. These were best characterized by a two-compartment ICG model and a four-compartment thiopental model, chiefly because of data obtained from frequent early arterial blood samples. The models had a common central volume (V1), and the peripheral ICG compartment was the subset of a peripheral thiopental compartment. The two-compartment ICG model described its mixing within the intravascular space. The traditional VC of three-compartment models of thiopental disposition is described by the present four-compartment model as an initial distribution volume, V1, codetermined by ICG as central blood volume, and a rapidly equilibrating peripheral volume, V4. The combined simultaneous ICG-thiopental model more clearly reflects physiology than do the results of earlier curve-fitting techniques and may be useful in studying the pharmacokinetic basis of altered reactivity to thiopental.

Adult↗
PubMed2006

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats.

BACKGROUND AND PURPOSE: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor alpha production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. EXPERIMENTAL APPROACH: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. KEY RESULTS: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. CONCLUSIONS AND IMPLICATIONS: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans.

Acute Disease↗
PubMed1995

[Clonidine increases the anesthetic effectiveness of thiopental].

OBJECTIVE: Treatment with alpha 2-agonists has been demonstrated to improve intra- and postoperative haemodynamic stability. After administration of alpha 2-agonists anaesthetic requirements have been shown to be reduced up to 90% for volatile anaesthetics as well as for intravenous anaesthetics like barbiturates. This study was designed to determine the effect of the alpha 2-agonist clonidine on the anaesthetic potency of the intravenous anaesthetic thiopental in absence of pharmacokinetic influences. METHODS: With approval by the local animal care committee all experiments were performed using Xenopus laevis tadpoles in the early pre-limb-bud stage. The animals were exposed to thiopental (0.1-250 microM) or a combination of thiopental (0.1-250 microM) + clonidine (100 microM) for up to 120 min. For each concentration at least ten animals were used. Anaesthesia was defined as loss of righting reflex for 10 s. Based on the response of the tadpoles at different concentrations of the anaesthetic a concentration-response curve was generated according to a method for quantal biologic data and halfmaximal concentrations (EC50) as well as slopes of the curves were calculated. All values are reported as mean +/- sem. Statistical significance was determined by Student's t-test (p < 0.05). RESULTS: The fraction of anaesthetised animals increased with increasing concentrations of thiopental. The logistic concentration-response plots showed a sigmoidal curve with a slope of 2.14 +/- 0.3. Calculation of the EC50 resulted in a value of 25.5 +/- 2.0 microM. In presence of clonidine thiopental exhibited a left shift of the concentration-response curve with an EC50 of 12.3 +/- 1.6 microM (Slope: 2.75 +/- 0.3). CONCLUSION: The presented data confirm the clinical impression that clonidine exercises an anaesthetic sparing effect. Clonidine enhances the anaesthetic potency of thiopental under equilibrium conditions, thus allowing to exclude pharmacokinetic influences as well as excluding effects of adjuvants. It is concluded that the reduction of requirement of anaesthetics by clonidine is due to a pharmacodynamic effect.

Adrenergic alpha-Agonists↗