The Experts below are selected from a list of 150 Experts worldwide ranked by ideXlab platform
Stefanie Swoboda - One of the best experts on this subject based on the ideXlab platform.
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continuous infusion of Physostigmine in patients with perioperative septic shock a pharmacokinetic pharmacodynamic study with population pharmacokinetic modeling
Biomedicine & Pharmacotherapy, 2019Co-Authors: Nadine Pinder, Johannes B Zimmermann, Silke Gastine, Gudrun Wurthwein, Georg Hempel, Thomas Bruckner, Torsten Hoppetichy, Markus A Weigand, Stefanie SwobodaAbstract:Abstract Background In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive Physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on Physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for Physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting. Methods In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for up to 120 h, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM. Results Steady state Physostigmine plasma concentrations reached 7.60 ± 2.81 ng/mL (mean ± standard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%–50.6% of baseline activity during Physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by Physostigmine, with an estimated half maximal effective concentration (EC50) of 5.99 ng/mL. Conclusions PK of Physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect.
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effect of Physostigmine on recovery from septic shock following intra abdominal infection results from a randomized double blind placebo controlled monocentric pilot trial anticholium per se
Journal of Critical Care, 2019Co-Authors: Nadine Pinder, Thomas Bruckner, Torsten Hoppetichy, Stefanie Swoboda, Monika Lehmann, J Motsch, Thorsten Brenner, Jan Larmann, Phillip Knebel, Markus A WeigandAbstract:Abstract Purpose The cholinergic anti-inflammatory pathway has been shown to be accessible by Physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated. Materials and methods In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The Physostigmine group received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days. Results Administration of Physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for Physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: −5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the Physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability. Conclusions Treatment with Physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock. Trial registration EudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322 .
Markus A Weigand - One of the best experts on this subject based on the ideXlab platform.
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continuous infusion of Physostigmine in patients with perioperative septic shock a pharmacokinetic pharmacodynamic study with population pharmacokinetic modeling
Biomedicine & Pharmacotherapy, 2019Co-Authors: Nadine Pinder, Johannes B Zimmermann, Silke Gastine, Gudrun Wurthwein, Georg Hempel, Thomas Bruckner, Torsten Hoppetichy, Markus A Weigand, Stefanie SwobodaAbstract:Abstract Background In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive Physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on Physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for Physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting. Methods In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for up to 120 h, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM. Results Steady state Physostigmine plasma concentrations reached 7.60 ± 2.81 ng/mL (mean ± standard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%–50.6% of baseline activity during Physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by Physostigmine, with an estimated half maximal effective concentration (EC50) of 5.99 ng/mL. Conclusions PK of Physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect.
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effect of Physostigmine on recovery from septic shock following intra abdominal infection results from a randomized double blind placebo controlled monocentric pilot trial anticholium per se
Journal of Critical Care, 2019Co-Authors: Nadine Pinder, Thomas Bruckner, Torsten Hoppetichy, Stefanie Swoboda, Monika Lehmann, J Motsch, Thorsten Brenner, Jan Larmann, Phillip Knebel, Markus A WeigandAbstract:Abstract Purpose The cholinergic anti-inflammatory pathway has been shown to be accessible by Physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated. Materials and methods In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The Physostigmine group received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days. Results Administration of Physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for Physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: −5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the Physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability. Conclusions Treatment with Physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock. Trial registration EudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322 .
Nadine Pinder - One of the best experts on this subject based on the ideXlab platform.
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continuous infusion of Physostigmine in patients with perioperative septic shock a pharmacokinetic pharmacodynamic study with population pharmacokinetic modeling
Biomedicine & Pharmacotherapy, 2019Co-Authors: Nadine Pinder, Johannes B Zimmermann, Silke Gastine, Gudrun Wurthwein, Georg Hempel, Thomas Bruckner, Torsten Hoppetichy, Markus A Weigand, Stefanie SwobodaAbstract:Abstract Background In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive Physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on Physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for Physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting. Methods In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for up to 120 h, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM. Results Steady state Physostigmine plasma concentrations reached 7.60 ± 2.81 ng/mL (mean ± standard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%–50.6% of baseline activity during Physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by Physostigmine, with an estimated half maximal effective concentration (EC50) of 5.99 ng/mL. Conclusions PK of Physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect.
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effect of Physostigmine on recovery from septic shock following intra abdominal infection results from a randomized double blind placebo controlled monocentric pilot trial anticholium per se
Journal of Critical Care, 2019Co-Authors: Nadine Pinder, Thomas Bruckner, Torsten Hoppetichy, Stefanie Swoboda, Monika Lehmann, J Motsch, Thorsten Brenner, Jan Larmann, Phillip Knebel, Markus A WeigandAbstract:Abstract Purpose The cholinergic anti-inflammatory pathway has been shown to be accessible by Physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated. Materials and methods In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The Physostigmine group received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days. Results Administration of Physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for Physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: −5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the Physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability. Conclusions Treatment with Physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock. Trial registration EudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322 .
Steven B Backman - One of the best experts on this subject based on the ideXlab platform.
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antagonism of sevoflurane anaesthesia by Physostigmine effects on the auditory steady state response and bispectral index
BJA: British Journal of Anaesthesia, 2003Co-Authors: Gilles Plourde, D Chartrand, Pierre Fiset, S Font, Steven B BackmanAbstract:Background Physostigmine, a centrally acting anticholinesterase, antagonizes the hypnotic effect of propofol, as shown by the return of consciousness (response to commands) or wakefulness (spontaneous eye-opening without response to commands) and by recovery of auditory evoked potentials (40 Hz auditory steady-state response (ASSR)) and the bispectral index (BIS). We measured the effects of Physostigmine on the hypnotic effect of inhaled volatile anaesthetics, using sevoflurane as the representative agent. Methods Eight healthy volunteers received sevoflurane adjusted to produce loss of consciousness. Physostigmine (plus glycopyrrolate) was given while the end-tidal concentration of sevoflurane was kept constant. Results Loss of consciousness was accompanied by a significant (P sd 0.04) to 0.17 (0.06) μV (P Conclusions Physostigmine can antagonize, at least partially, the hypnotic effect of sevoflurane and changes in arousal after Physostigmine are shown by ASSR measurements. However, the antagonism is not as clear or reliable as with propofol.
Torsten Hoppetichy - One of the best experts on this subject based on the ideXlab platform.
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continuous infusion of Physostigmine in patients with perioperative septic shock a pharmacokinetic pharmacodynamic study with population pharmacokinetic modeling
Biomedicine & Pharmacotherapy, 2019Co-Authors: Nadine Pinder, Johannes B Zimmermann, Silke Gastine, Gudrun Wurthwein, Georg Hempel, Thomas Bruckner, Torsten Hoppetichy, Markus A Weigand, Stefanie SwobodaAbstract:Abstract Background In the context of the cholinergic anti-inflammatory pathway, the clinical trial Anticholium® per Se (EudraCT Number: 2012-001650-26, ClinicalTrials.gov NCT03013322) addressed the possibility of taking adjunctive Physostigmine salicylate treatment in septic shock from bench to bedside. Pharmacokinetics (PK) are likely altered in critically ill patients; data on Physostigmine PK and target concentrations are sparse, particularly for continuous infusion. Our objective was to build a population PK (popPK) model for Physostigmine, and further evaluate pharmacodynamics (PD) and concentration-response relationship in this setting. Methods In the randomized, double-blind, placebo-controlled trial, 20 patients with perioperative septic shock either received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for up to 120 h, or equivalent volumes of 0.9% sodium chloride (placebo group). Physostigmine plasma concentrations and acetylcholinesterase (AChE) activity were measured; concentration-response associations were evaluated, and popPK and PD modeling was performed with NONMEM. Results Steady state Physostigmine plasma concentrations reached 7.60 ± 2.81 ng/mL (mean ± standard deviation [SD]). PK was best described by a two-compartment model with linear clearance. Significant covariate effects were detected for body weight and age on clearance, as well as a high inter-individual variability of the central volume of distribution. AChE activity was significantly reduced to 30.5%–50.6% of baseline activity during Physostigmine salicylate infusion. A sigmoidal direct effect PD model best described enzyme inhibition by Physostigmine, with an estimated half maximal effective concentration (EC50) of 5.99 ng/mL. Conclusions PK of Physostigmine in patients with septic shock displayed substantial inter-individual variability with body weight and age influencing the clearance. Physostigmine inhibited AChE activity with a sigmoidal concentration-response effect.
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effect of Physostigmine on recovery from septic shock following intra abdominal infection results from a randomized double blind placebo controlled monocentric pilot trial anticholium per se
Journal of Critical Care, 2019Co-Authors: Nadine Pinder, Thomas Bruckner, Torsten Hoppetichy, Stefanie Swoboda, Monika Lehmann, J Motsch, Thorsten Brenner, Jan Larmann, Phillip Knebel, Markus A WeigandAbstract:Abstract Purpose The cholinergic anti-inflammatory pathway has been shown to be accessible by Physostigmine salicylate in animal models. However, the cholinesterase inhibitor is not approved for adjunctive therapy in sepsis, and tolerability and safety of high initial doses followed by continuous infusion have not been investigated. Materials and methods In this trial, 20 patients with perioperative septic shock due to intra-abdominal infection were eligible. The Physostigmine group received an initial dose of 0.04 mg/kg Physostigmine salicylate, followed by continuous infusion of 1 mg/h for 120 h; the placebo group was treated with 0.9% sodium chloride. Primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score during treatment and up to 14 days. Results Administration of Physostigmine salicylate was well tolerated. Mean SOFA scores were 8.9 ± 2.5 and 11.3 ± 3.6 (mean ± SD) for Physostigmine and placebo group, respectively. Adjusted for age, difference between means was not statistically significant (−2.37, 95% CI: −5.43 to 0.70, p = 0.121). Norepinephrine doses required only appeared lower in the Physostigmine group (p = 0.064), along with a more rapid reduction from an elevated heart rate possibly indicating less hemodynamic instability. Conclusions Treatment with Physostigmine salicylate was feasible and safe. Further studies are justified to assess the effect on recovery from septic shock. Trial registration EudraCT Number 2012-001650-26, ClinicalTrials.gov identifier NCT03013322 .
