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J G Bovill – One of the best experts on this subject based on the ideXlab platform.

  • INFLUENCE OF CROHN'S DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF Alfentanil
    , 2016
    Co-Authors: B. Gesink-van Der J. Veer, A A Vletter, A G L Burm, J G Bovill
    Abstract:

    We have compared the dose requirements, pharma-cokinetics and pharmacodynamics of Alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing abdominal surgery. Plasma concentrations of ar acid glycoprotein (AAG) and Alfentanil protein binding were also measured. Anaesthesia was induced with Alfentanil 100 ng kg~1 and thiopentone, and maintained with nitrous oxide in oxygen and Alfentanil 25-200 fig kg'1 h'1. Arterial blood samples were obtained before and after each change in the Alfentanil infusion rate and for 6 h after stopping the infusion. Pharmacokinetic data were derived using non-compartmental methods. Alfentanil concen-tration-effect data were evaluated by non-linear regression, where effect was either response or no response to surgical stimulation. Mean intra-operative Alfentanil requirement was greater in patients with Crohn's disease (2.48 fig kg- ' min~1) than in control patients (1.35 fig kg-1 min~1) (P < 0.01). Mean elimination half-life, total plasma clearance and steady state distribution volume in patients with Crohn's disease were comparable to those in control patients (80 vs 81 min, 5.7 vs 6.4 ml kg-1 min-1 and 0.70 vs 0.68 litre kg-1, respectively). Mean plasma concentration at which the probability of no response was 50 % for the intra-abdominalperiod of surgery was greater in the Crohn group (359ngml~1) than in the control group (199 ng ml~1) (P < 0.02). Plasma AAG con-centrations were greater in the Crohn group, but the free fraction of Alfentanil was similar in both groups. This study indicates that the increased Alfentanil requirement in patients with Crohn's disease may be attributed to a change in pharmacodynamics

  • Alfentanil infusion in the elderly: prolonged computer-assisted infusion of Alfentanil in the elderly surgical patient
    Anaesthesia, 2007
    Co-Authors: Harry J. M. Lemmens, J G Bovill, A G L Burm, P. J. Hennis
    Abstract:

    Summary The use of a computer-assisted infusion of Alfentanil, combined with 66% nitrous oxide in oxygen, for induction and maintenance of anaesthesia was evaluated in IS elderly patients. The target Alfentanil concentration for induction was varied between 300 and 475 ng/ml, to be achieved in 2 minutes. During maintenance, the Alfentanil concentration was increased or decreased according to each patient’s responses. Arterial blood samples were taken for measurement of Alfentanil concentration. There were high incidences of muscle rigidity, bradycardia and hypotension during induction. Hypotension was dose- and concentration-dependent. Signs of light anaesthesia during maintenance were controlled rapidly by increasing the target plasma concentration. Nine patients required naloxone at the end of surgery. Ventilatory depression recurred in three of these. The use of published Alfentanil pharmacokinetic data from elderly patients to predict plasma concentrations during prolonged infusion resulted in significant prediction errors, notably in the higher concentration range.

  • Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers
    Anesthesiology, 2001
    Co-Authors: Martijn J. Mertens, Jaap Vuyk, J G Bovill, Erik Olofsen, A G L Burm
    Abstract:

    Background: The influence of propofol on the pharmacokinetics of Alfentanil is poorly understood. The authors therefore studied the effect of a pseudo‐steady state concentration of propofol on the pharmacokinetics of Alfentanil. Methods: The pharmacokinetics of Alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 mg/kg intravenous Alfentanil was given in 2 min, followed by 25 m g·k g 21 ·h 21 for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 mg/ml) was given from 10 min before the start until 6 h after termination of the Alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma Alfentanil concentration were collected until 6 h after termination of the Alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed. Results: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration‐time curves of Alfentanil. Propofol decreased the elimination clearance of Alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model. Conclusions: Propofol alters the pharmacokinetics of Alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of Alfentanil.

A G L Burm – One of the best experts on this subject based on the ideXlab platform.

  • INFLUENCE OF CROHN'S DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF Alfentanil
    , 2016
    Co-Authors: B. Gesink-van Der J. Veer, A A Vletter, A G L Burm, J G Bovill
    Abstract:

    We have compared the dose requirements, pharma-cokinetics and pharmacodynamics of Alfentanil in 12 patients with Crohn's disease and 10 control patients undergoing abdominal surgery. Plasma concentrations of ar acid glycoprotein (AAG) and Alfentanil protein binding were also measured. Anaesthesia was induced with Alfentanil 100 ng kg~1 and thiopentone, and maintained with nitrous oxide in oxygen and Alfentanil 25-200 fig kg'1 h'1. Arterial blood samples were obtained before and after each change in the Alfentanil infusion rate and for 6 h after stopping the infusion. Pharmacokinetic data were derived using non-compartmental methods. Alfentanil concen-tration-effect data were evaluated by non-linear regression, where effect was either response or no response to surgical stimulation. Mean intra-operative Alfentanil requirement was greater in patients with Crohn's disease (2.48 fig kg- ' min~1) than in control patients (1.35 fig kg-1 min~1) (P < 0.01). Mean elimination half-life, total plasma clearance and steady state distribution volume in patients with Crohn's disease were comparable to those in control patients (80 vs 81 min, 5.7 vs 6.4 ml kg-1 min-1 and 0.70 vs 0.68 litre kg-1, respectively). Mean plasma concentration at which the probability of no response was 50 % for the intra-abdominalperiod of surgery was greater in the Crohn group (359ngml~1) than in the control group (199 ng ml~1) (P < 0.02). Plasma AAG con-centrations were greater in the Crohn group, but the free fraction of Alfentanil was similar in both groups. This study indicates that the increased Alfentanil requirement in patients with Crohn's disease may be attributed to a change in pharmacodynamics

  • Alfentanil infusion in the elderly: prolonged computer-assisted infusion of Alfentanil in the elderly surgical patient
    Anaesthesia, 2007
    Co-Authors: Harry J. M. Lemmens, J G Bovill, A G L Burm, P. J. Hennis
    Abstract:

    Summary The use of a computer-assisted infusion of Alfentanil, combined with 66% nitrous oxide in oxygen, for induction and maintenance of anaesthesia was evaluated in IS elderly patients. The target Alfentanil concentration for induction was varied between 300 and 475 ng/ml, to be achieved in 2 minutes. During maintenance, the Alfentanil concentration was increased or decreased according to each patient’s responses. Arterial blood samples were taken for measurement of Alfentanil concentration. There were high incidences of muscle rigidity, bradycardia and hypotension during induction. Hypotension was dose- and concentration-dependent. Signs of light anaesthesia during maintenance were controlled rapidly by increasing the target plasma concentration. Nine patients required naloxone at the end of surgery. Ventilatory depression recurred in three of these. The use of published Alfentanil pharmacokinetic data from elderly patients to predict plasma concentrations during prolonged infusion resulted in significant prediction errors, notably in the higher concentration range.

  • Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers
    Anesthesiology, 2001
    Co-Authors: Martijn J. Mertens, Jaap Vuyk, J G Bovill, Erik Olofsen, A G L Burm
    Abstract:

    Background: The influence of propofol on the pharmacokinetics of Alfentanil is poorly understood. The authors therefore studied the effect of a pseudo‐steady state concentration of propofol on the pharmacokinetics of Alfentanil. Methods: The pharmacokinetics of Alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 mg/kg intravenous Alfentanil was given in 2 min, followed by 25 m g·k g 21 ·h 21 for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 mg/ml) was given from 10 min before the start until 6 h after termination of the Alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma Alfentanil concentration were collected until 6 h after termination of the Alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed. Results: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration‐time curves of Alfentanil. Propofol decreased the elimination clearance of Alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model. Conclusions: Propofol alters the pharmacokinetics of Alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of Alfentanil.

Tom Heier – One of the best experts on this subject based on the ideXlab platform.

  • Alfentanil during rapid sequence induction with thiopental 4 mg kg and rocuronium 0 6 mg kg tracheal intubation conditions
    Acta Anaesthesiologica Scandinavica, 2015
    Co-Authors: M H Abouarab, John Feiner, Olav Spigset, Tom Heier
    Abstract:

    Background Opioids have become an integral part of anaesthesia induction. We aimed to determine the dose of Alfentanil needed to obtain perfect tracheal intubation conditions during rapid sequence induction with standard doses of thiopental and rocuronium, where laryngoscopy was initiated 55 s after commencement of drug administration. The influence of covariates (sex, body weight, age, Alfentanil plasma concentration at laryngoscopy) was tested. Methods Eighty-four healthy individuals were randomly assigned to receive one of the seven assessor-blinded Alfentanil doses (0, 10, 20, 30, 40, 50 and 60 μg/kg) in conjunction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. For drug administration, 15 s was allowed. Laryngoscopy was initiated 40 s after rocuronium and tracheal intubation concluded within 70 s after commencement of drug administration. Alfentanil doses associated with 50%, 90% and 95% probability of perfect intubation conditions were determined with logistic regression. Multiple logistic regressions were used to test the influence of covariates. The relationship between Alfentanil dose and concentration at laryngoscopy was analysed with linear regression. The effects of covariates on plasma concentrations of Alfentanil were tested with multiple linear regressions. Results Perfect intubation conditions of 95% probability was obtained with 56 μg/kg (confidence intervals 44–68). None of the covariates were significant predictors of perfect intubation conditions. Alfentanil plasma concentration correlated with dose and increased with increasing body weight (1.7 ng/ml/kg). Conclusion Perfect intubation conditions during rapid sequence induction can be obtained with clinically relevant doses of Alfentanil in most healthy patients anaesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

  • dose of Alfentanil needed to obtain optimal intubation conditions during rapid sequence induction of anaesthesia with thiopentone and rocuronium
    BJA: British Journal of Anaesthesia, 2007
    Co-Authors: M H Abouarab, Tom Heier, James E Caldwell
    Abstract:

    Background The primary aim of the present study was to determine the dose of Alfentanil that must be added to a rapid-sequence induction (RSI) regimen using thiopentone and rocuronium to obtain optimal intubation conditions in >95% of the individuals. Methods A total of 60 ASA I patients were randomly allocated to five different Alfentanil dose groups (0, 15, 30, 45, or 60 µg kg−1). A blinded dose of Alfentanil followed by thiopentone 4 mg kg−1 and rocuronium 1 mg kg −1 was administered in rapid succession, and tracheal intubation was attempted 40 s thereafter. The relationship between the Alfentanil dose and the probability of optimal intubation conditions was determined by non-linear logistic regression analysis. Blood pressure (BP) changes were recorded continuously using an intra-arterial catheter. Results The success rate of optimal intubation conditions increased with increasing doses of Alfentanil. The Alfentanil dose needed to obtain optimal intubation conditions in >95% of the patients was 36.4 (CI 33.4–39.4) μg kg−1. In 12 patients, the systolic BP declined to Conclusion Adding 36–40 µg kg−1 Alfentanil to a regimen of thiopentone and rocuronium during RSI of anaesthesia may significantly increase the success rate of optimal intubation conditions. Significant hypotension requiring vasopressor treatment may occur.

M H Abouarab – One of the best experts on this subject based on the ideXlab platform.

  • Alfentanil during rapid sequence induction with thiopental 4 mg kg and rocuronium 0 6 mg kg tracheal intubation conditions
    Acta Anaesthesiologica Scandinavica, 2015
    Co-Authors: M H Abouarab, John Feiner, Olav Spigset, Tom Heier
    Abstract:

    Background Opioids have become an integral part of anaesthesia induction. We aimed to determine the dose of Alfentanil needed to obtain perfect tracheal intubation conditions during rapid sequence induction with standard doses of thiopental and rocuronium, where laryngoscopy was initiated 55 s after commencement of drug administration. The influence of covariates (sex, body weight, age, Alfentanil plasma concentration at laryngoscopy) was tested. Methods Eighty-four healthy individuals were randomly assigned to receive one of the seven assessor-blinded Alfentanil doses (0, 10, 20, 30, 40, 50 and 60 μg/kg) in conjunction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. For drug administration, 15 s was allowed. Laryngoscopy was initiated 40 s after rocuronium and tracheal intubation concluded within 70 s after commencement of drug administration. Alfentanil doses associated with 50%, 90% and 95% probability of perfect intubation conditions were determined with logistic regression. Multiple logistic regressions were used to test the influence of covariates. The relationship between Alfentanil dose and concentration at laryngoscopy was analysed with linear regression. The effects of covariates on plasma concentrations of Alfentanil were tested with multiple linear regressions. Results Perfect intubation conditions of 95% probability was obtained with 56 μg/kg (confidence intervals 44–68). None of the covariates were significant predictors of perfect intubation conditions. Alfentanil plasma concentration correlated with dose and increased with increasing body weight (1.7 ng/ml/kg). Conclusion Perfect intubation conditions during rapid sequence induction can be obtained with clinically relevant doses of Alfentanil in most healthy patients anaesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

  • dose of Alfentanil needed to obtain optimal intubation conditions during rapid sequence induction of anaesthesia with thiopentone and rocuronium
    BJA: British Journal of Anaesthesia, 2007
    Co-Authors: M H Abouarab, Tom Heier, James E Caldwell
    Abstract:

    Background The primary aim of the present study was to determine the dose of Alfentanil that must be added to a rapid-sequence induction (RSI) regimen using thiopentone and rocuronium to obtain optimal intubation conditions in >95% of the individuals. Methods A total of 60 ASA I patients were randomly allocated to five different Alfentanil dose groups (0, 15, 30, 45, or 60 µg kg−1). A blinded dose of Alfentanil followed by thiopentone 4 mg kg−1 and rocuronium 1 mg kg −1 was administered in rapid succession, and tracheal intubation was attempted 40 s thereafter. The relationship between the Alfentanil dose and the probability of optimal intubation conditions was determined by non-linear logistic regression analysis. Blood pressure (BP) changes were recorded continuously using an intra-arterial catheter. Results The success rate of optimal intubation conditions increased with increasing doses of Alfentanil. The Alfentanil dose needed to obtain optimal intubation conditions in >95% of the patients was 36.4 (CI 33.4–39.4) μg kg−1. In 12 patients, the systolic BP declined to Conclusion Adding 36–40 µg kg−1 Alfentanil to a regimen of thiopentone and rocuronium during RSI of anaesthesia may significantly increase the success rate of optimal intubation conditions. Significant hypotension requiring vasopressor treatment may occur.

Harry J. M. Lemmens – One of the best experts on this subject based on the ideXlab platform.

  • Alfentanil infusion in the elderly: prolonged computer-assisted infusion of Alfentanil in the elderly surgical patient
    Anaesthesia, 2007
    Co-Authors: Harry J. M. Lemmens, J G Bovill, A G L Burm, P. J. Hennis
    Abstract:

    Summary The use of a computer-assisted infusion of Alfentanil, combined with 66% nitrous oxide in oxygen, for induction and maintenance of anaesthesia was evaluated in IS elderly patients. The target Alfentanil concentration for induction was varied between 300 and 475 ng/ml, to be achieved in 2 minutes. During maintenance, the Alfentanil concentration was increased or decreased according to each patient’s responses. Arterial blood samples were taken for measurement of Alfentanil concentration. There were high incidences of muscle rigidity, bradycardia and hypotension during induction. Hypotension was dose- and concentration-dependent. Signs of light anaesthesia during maintenance were controlled rapidly by increasing the target plasma concentration. Nine patients required naloxone at the end of surgery. Ventilatory depression recurred in three of these. The use of published Alfentanil pharmacokinetic data from elderly patients to predict plasma concentrations during prolonged infusion resulted in significant prediction errors, notably in the higher concentration range.

  • Pharmacodynamics of Alfentanil. The role of plasma protein binding.
    Anesthesiology, 1992
    Co-Authors: Harry J. M. Lemmens, J G Bovill, A G L Burm, Pim J. Hennis, M. P. R. R. Gladines
    Abstract:

    The role of protein binding in relation to the pharmacodynamics of Alfentanil was investigated in 15 female and 13 male patients, aged 21-85 yr, ASA physical status 1 or 2, undergoing upper abdominal surgery. All patients had normal cardiac, hepatic, renal, and pulmonary function. None was receiving medication or had a history of alcohol or other drug abuse. Anesthesia was induced and maintained with 66% nitrous oxide in oxygen and Alfentanil. Alfentanil was administered by a computer-controlled infusion pump. If, during surgery, the patient exhibited signs of inadequate anesthesia (i.e., response), the target Alfentanil plasma concentration was increased by 50-100 ng/ml. If there was no response during a 15-min period, the target concentration was decreased by 50-100 ng/ml. Arterial blood samples were taken before any change of the target concentration and 4 min after the computer had indicated that the new target concentration had been reached. In addition, blood samples were taken before intubation, skin incision, and in the patients in whom ventilation recovered spontaneously before extubation. In the remaining patients a blood sample was taken before the administration of naloxone. Plasma Alfentanil concentrations were determined by capillary gas chromatography. Alfentanil protein binding was determined by equilibrium dialysis in an arterial blood sample taken before induction of anesthesia. Alfentanil concentration-effect data were evaluated by logistic regression, where effect was either response or no response to perioperative stimuli. The average free fraction of Alfentanil was 9.3 +/- 3.9% (range 3.7-19.1%). For intubation, skin incision, and postanesthesia ventilation, it was not possible to characterize the concentration-effect curves based on total plasma concentrations with logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS)