The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Igor Kissin - One of the best experts on this subject based on the ideXlab platform.
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Isobolographic Analysis of Propofol-Thiopental Hypnotic Interaction in Surgical Patients
Anesthesia and analgesia, 1999Co-Authors: Edwin L. Bradley, Igor KissinAbstract:Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-Thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and Thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and Thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of Thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-Thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-Thiopental synergy, as demonstrated with midazolam-Thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and Thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. The propofol-Thiopental hypnotic interaction is additive.
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Metoclopramide decreases Thiopental hypnotic requirements.
Anesthesia and analgesia, 1993Co-Authors: Dhirendra Mehta, Edwin L. Bradley, Igor KissinAbstract:We compared the effect of metoclopramide (MCA) with droperidol (DPD) on Thiopental hypnotic requirements in 96 unpremedicated female patients. The study was randomized, double-blind, and placebo-controlled. The response to the verbal command was used as an end-point of anesthesia. Two methods of determination of Thiopental hypnotic requirements were used: titration (infusion of Thiopental at a rate of 0.5 mg.kg-1 x min-1) until the end-point was reached and construction of the dose-response curve based on bolus injections of predetermined doses of Thiopental (with the use of probit analysis). The ED50 value of Thiopental determined by probit analysis was reduced after the 0.2 mg/kg MCA administration by 44% (P < 0.0001). The Thiopental hypnotic requirements obtained with the titration method were as follows: 5.3 +/- 0.3 mg/kg in control, 4.5 +/- 0.2 mg/kg (delta 14%, P < 0.03) with 0.1 mg/kg MCA, 3.2 +/- 0.2 mg/kg (delta 39%, P < 0.0001) with 0.2 mg/kg MCA, and 2.9 +/- 0.2 mg/kg (delta 45%, P < 0.0001) with 0.4 mg/kg MCA. DPD decreased Thiopental hypnotic requirements almost to the same degree as MCA, with the ceiling effect observed at doses of 0.01 and 0.02 mg/kg (delta 44%, P < 0.0001). The results indicate that MCA causes a profound decrease in Thiopental hypnotic requirements. The similarity between the Thiopental sparing effects of MCA and DPD suggests that the blockade of D2 receptors is the main mechanism underlying this effect.
Pierre O. Maitre - One of the best experts on this subject based on the ideXlab platform.
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Dexmedetomidine Decreases Thiopental Dose Requirement and Alters Distribution Pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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dexmedetomidine decreases Thiopental dose requirement and alters distribution pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:BACKGROUND: alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. METHODS: Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. RESULTS: Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. CONCLUSIONS: The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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Thiopental pharmacodynamics i defining the pseudo steady state serum concentration eeg effect relationship
Anesthesiology, 1992Co-Authors: Michael Bührer, Pierre O. Maitre, William F. Ebling, Orlando Hung, Steven L Shafer, Donald R. StanskiAbstract:To assess depth of anesthesia for intravenous anesthetics using clinical stimuli and observed responses, it is necessary to achieve constant serum concentrations of drug that result in constant biophase or central nervous system concentrations. The goal of this investigation was to use a computer-controlled infusion pump (CCIP) to obtain constant serum Thiopental concentrations and use the electroencephalogram (EEG) as a measure of Thiopental's central nervous system drug effect. The number of waves per second obtained from aperiodic waveform analysis was used as the EEG measure. A CCIP was used in six male volunteers to attain rapidly and then maintain for 6-min time periods the following pseudo-steady-state constant serum Thiopental target concentrations: 10, 20, 30, and 40 micrograms/ml. The median performance error (bias) of the CCIP using 149 measurements of Thiopental serum concentrations in six subjects was +5%, and the median absolute performance error (accuracy) was 16%. Following the step change in serum Thiopental concentration, the EEG number of waves per second stabilized within 2-3 min and the remained constant until the target serum Thiopental concentration was changed. When the constant serum Thiopental concentration was plotted against the number of waves per second for each subject, a biphasic serum concentration versus EEG effect relationship was seen. This biphasic concentration:response relationship was characterized with a nonparametric pharmacodynamic model. The awake, baseline EEG was 10.6 waves/s; at peak activation the EEG was 19.1 waves/s and occurred at a serum Thiopental concentration of 13.3 micrograms/ml. At a serum Thiopental concentration of 31.2 micrograms/ml the EEG had slowed to 10.6 waves/s (back to baseline) and at 41.2 micrograms/ml was 50% below the baseline, awake value. Zero waves per second occurred at serum Thiopental concentrations greater than 50 micrograms/ml. Using a CCIP it is possible to establish constant serum Thiopental concentration rapidly and characterize the concentration versus EEG drug effect relationship.
Donald R. Stanski - One of the best experts on this subject based on the ideXlab platform.
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Thiopental uncouples hippocampal and cortical synchronized electroencephalograpbic activity
Anesthesiology, 1996Co-Authors: Bruce M Maciver, Donald R. Stanski, Jaap W Mandema, Brian H BlandAbstract:BACKGROUND Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of Thiopental. The current study investigated Thiopental actions on cortical EEG and hippocampal electrical activity, to determine whether similar effects occur on both structures and to compare synchronized activity between these structures. METHODS Thiopental was administered intravenously via an implanted catheter in freely moving rats. Arterial blood oxygen/carbon dioxide concentration, Thiopental concentrations, and temperature were monitored and controlled. Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal neuron electrical activity was recorded from stereotaxically placed microelectrodes. Pharmacokinetic models were used to determine effect site concentrations. RESULTS Thiopental produced an increase in EEG frequency and amplitude at low concentrations (15-20 micrograms/ml total plasma, approximately 10 microM unbound), which produced a loss of righting reflex. This was followed by a frequency decrease and burst suppression activity at higher concentrations (50-80 micrograms/ml, approximately 60 microM), which produced a loss of tail pinch and corneal reflexes. Higher concentrations of Thiopental ( > 60 micrograms/ml) uncoupled synchronized burst discharges recorded in hippocampus and cortex. Isoelectric EEG activity was associated with concentrations of 70-90 micrograms/ml (approximately 80 microM) and a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar concentration-EEG effect relationships were observed for cortical and hippocampal signals, only differing in the magnitude of response. A reversed progression of effects was observed on recovery. CONCLUSIONS The results confirm earlier findings in humans and animals and demonstrate that both the hippocampus and neocortex exhibit burst suppression and isoelectric activity during Thiopental anesthesia. Thiopental-induced synchronized burst activity was depressed by progressively higher concentrations. The lost synchronization suggests a depression of synaptic coupling between cortical structures contributes to anesthesia.
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Dexmedetomidine Decreases Thiopental Dose Requirement and Alters Distribution Pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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dexmedetomidine decreases Thiopental dose requirement and alters distribution pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:BACKGROUND: alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. METHODS: Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. RESULTS: Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. CONCLUSIONS: The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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Thiopental pharmacodynamics i defining the pseudo steady state serum concentration eeg effect relationship
Anesthesiology, 1992Co-Authors: Michael Bührer, Pierre O. Maitre, William F. Ebling, Orlando Hung, Steven L Shafer, Donald R. StanskiAbstract:To assess depth of anesthesia for intravenous anesthetics using clinical stimuli and observed responses, it is necessary to achieve constant serum concentrations of drug that result in constant biophase or central nervous system concentrations. The goal of this investigation was to use a computer-controlled infusion pump (CCIP) to obtain constant serum Thiopental concentrations and use the electroencephalogram (EEG) as a measure of Thiopental's central nervous system drug effect. The number of waves per second obtained from aperiodic waveform analysis was used as the EEG measure. A CCIP was used in six male volunteers to attain rapidly and then maintain for 6-min time periods the following pseudo-steady-state constant serum Thiopental target concentrations: 10, 20, 30, and 40 micrograms/ml. The median performance error (bias) of the CCIP using 149 measurements of Thiopental serum concentrations in six subjects was +5%, and the median absolute performance error (accuracy) was 16%. Following the step change in serum Thiopental concentration, the EEG number of waves per second stabilized within 2-3 min and the remained constant until the target serum Thiopental concentration was changed. When the constant serum Thiopental concentration was plotted against the number of waves per second for each subject, a biphasic serum concentration versus EEG effect relationship was seen. This biphasic concentration:response relationship was characterized with a nonparametric pharmacodynamic model. The awake, baseline EEG was 10.6 waves/s; at peak activation the EEG was 19.1 waves/s and occurred at a serum Thiopental concentration of 13.3 micrograms/ml. At a serum Thiopental concentration of 31.2 micrograms/ml the EEG had slowed to 10.6 waves/s (back to baseline) and at 41.2 micrograms/ml was 50% below the baseline, awake value. Zero waves per second occurred at serum Thiopental concentrations greater than 50 micrograms/ml. Using a CCIP it is possible to establish constant serum Thiopental concentration rapidly and characterize the concentration versus EEG drug effect relationship.
Michael Bührer - One of the best experts on this subject based on the ideXlab platform.
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Dexmedetomidine Decreases Thiopental Dose Requirement and Alters Distribution Pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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dexmedetomidine decreases Thiopental dose requirement and alters distribution pharmacokinetics
Anesthesiology, 1994Co-Authors: Michael Bührer, Donald R. Stanski, Andreas Mappes, Rolf Lauber, Pierre O. MaitreAbstract:BACKGROUND: alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known. METHODS: Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, Thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of Thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for Thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for Thiopental. RESULTS: Dexmedetomidine reduced the Thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated Thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of Thiopental. CONCLUSIONS: The Thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in Thiopental distribution volume and distribution clearances. Dexmedetomidine reduces Thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
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Thiopental pharmacodynamics i defining the pseudo steady state serum concentration eeg effect relationship
Anesthesiology, 1992Co-Authors: Michael Bührer, Pierre O. Maitre, William F. Ebling, Orlando Hung, Steven L Shafer, Donald R. StanskiAbstract:To assess depth of anesthesia for intravenous anesthetics using clinical stimuli and observed responses, it is necessary to achieve constant serum concentrations of drug that result in constant biophase or central nervous system concentrations. The goal of this investigation was to use a computer-controlled infusion pump (CCIP) to obtain constant serum Thiopental concentrations and use the electroencephalogram (EEG) as a measure of Thiopental's central nervous system drug effect. The number of waves per second obtained from aperiodic waveform analysis was used as the EEG measure. A CCIP was used in six male volunteers to attain rapidly and then maintain for 6-min time periods the following pseudo-steady-state constant serum Thiopental target concentrations: 10, 20, 30, and 40 micrograms/ml. The median performance error (bias) of the CCIP using 149 measurements of Thiopental serum concentrations in six subjects was +5%, and the median absolute performance error (accuracy) was 16%. Following the step change in serum Thiopental concentration, the EEG number of waves per second stabilized within 2-3 min and the remained constant until the target serum Thiopental concentration was changed. When the constant serum Thiopental concentration was plotted against the number of waves per second for each subject, a biphasic serum concentration versus EEG effect relationship was seen. This biphasic concentration:response relationship was characterized with a nonparametric pharmacodynamic model. The awake, baseline EEG was 10.6 waves/s; at peak activation the EEG was 19.1 waves/s and occurred at a serum Thiopental concentration of 13.3 micrograms/ml. At a serum Thiopental concentration of 31.2 micrograms/ml the EEG had slowed to 10.6 waves/s (back to baseline) and at 41.2 micrograms/ml was 50% below the baseline, awake value. Zero waves per second occurred at serum Thiopental concentrations greater than 50 micrograms/ml. Using a CCIP it is possible to establish constant serum Thiopental concentration rapidly and characterize the concentration versus EEG drug effect relationship.
Edwin L. Bradley - One of the best experts on this subject based on the ideXlab platform.
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Isobolographic Analysis of Propofol-Thiopental Hypnotic Interaction in Surgical Patients
Anesthesia and analgesia, 1999Co-Authors: Edwin L. Bradley, Igor KissinAbstract:Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-Thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and Thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and Thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of Thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-Thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-Thiopental synergy, as demonstrated with midazolam-Thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and Thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. The propofol-Thiopental hypnotic interaction is additive.
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Metoclopramide decreases Thiopental hypnotic requirements.
Anesthesia and analgesia, 1993Co-Authors: Dhirendra Mehta, Edwin L. Bradley, Igor KissinAbstract:We compared the effect of metoclopramide (MCA) with droperidol (DPD) on Thiopental hypnotic requirements in 96 unpremedicated female patients. The study was randomized, double-blind, and placebo-controlled. The response to the verbal command was used as an end-point of anesthesia. Two methods of determination of Thiopental hypnotic requirements were used: titration (infusion of Thiopental at a rate of 0.5 mg.kg-1 x min-1) until the end-point was reached and construction of the dose-response curve based on bolus injections of predetermined doses of Thiopental (with the use of probit analysis). The ED50 value of Thiopental determined by probit analysis was reduced after the 0.2 mg/kg MCA administration by 44% (P < 0.0001). The Thiopental hypnotic requirements obtained with the titration method were as follows: 5.3 +/- 0.3 mg/kg in control, 4.5 +/- 0.2 mg/kg (delta 14%, P < 0.03) with 0.1 mg/kg MCA, 3.2 +/- 0.2 mg/kg (delta 39%, P < 0.0001) with 0.2 mg/kg MCA, and 2.9 +/- 0.2 mg/kg (delta 45%, P < 0.0001) with 0.4 mg/kg MCA. DPD decreased Thiopental hypnotic requirements almost to the same degree as MCA, with the ceiling effect observed at doses of 0.01 and 0.02 mg/kg (delta 44%, P < 0.0001). The results indicate that MCA causes a profound decrease in Thiopental hypnotic requirements. The similarity between the Thiopental sparing effects of MCA and DPD suggests that the blockade of D2 receptors is the main mechanism underlying this effect.
