The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Virginia D Schmith - One of the best experts on this subject based on the ideXlab platform.
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the influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of Doxacurium
Anesthesia & Analgesia, 1999Co-Authors: Dennis M Fisher, Robert L Lennon, Virginia D Schmith, Kellie S Reynolds, James Hsu, M D Sokoll, James E CaldwellAbstract:UNLABELLED Doxacurium's clearance (C1) is markedly decreased in patients with renal failure undergoing kidney transplantation. However, no studies have determined the influence of renal function (as assessed by creatinine clearance [CrCl]) on its pharmacokinetics in patients without renal failure. We studied 53 patients aged 19-59 yr. During N2O/isoflurane anesthesia, Doxacurium was infused over 10 min, plasma was sampled for up to 6 h, and twitch tension was measured. A three-compartment model was fit to plasma concentration data and an effect compartment model to twitch data. Mixed-effects modeling was used to determine the influence of covariates, including CrC1, on Doxacurium's pharmacokinetic/pharmacodynamic parameters. Obesity decreased both Doxacurium's Cl (1.1% per percent above ideal body weight [IBW]) and its neuromuscular junction sensitivity (0.4% per percent above IBW). Cl increased 0.6% per mL/min increase in CrCl. In addition, the rate constant for equilibration between plasma concentration and effect decreased 46% per 1% increase in isoflurane, central compartment volume decreased 86% per 1% increase in isoflurane concentration, and slow distributional Cl decreased 69% per mg/ 100 mL increase in serum albumin. Simulations showed that the latter two covariates influence the time course of bolus Doxacurium administration minimally. Both obesity and renal dysfunction prolong Doxacurium's recovery markedly. When dosing is based on IBW, effects of CrCl on neuromuscular recovery are smaller compared with dosing based on actual weight. Therefore, obese patients should be dosed based on IBW. No further dosage adjustment is necessary for patients with renal dysfunction; however, recovery will take longer in patients with moderate-to-severe renal dysfunction. IMPLICATIONS We examined the factors influencing Doxacurium's pharmacokinetic and pharmacodynamic characteristics. Both creatinine clearance and obesity significantly influence its time course. The effect of obesity is minimized if patients are dosed based on ideal body weight.
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population pharmacodynamics of Doxacurium
Clinical Pharmacology & Therapeutics, 1992Co-Authors: Martha M Aboudonia, Virginia D Schmith, Jill Fiedlerkelly, Cameron S Huffman, Thaddeus H GraselaAbstract:The nonlinear mixed-effects modeling (NONMEM) computer program was used to investigate the variability in the duration of Doxacurium-induced neuromuscular block in 408 patients enrolled in phase II and phase III clinical trials of Doxacurium. Spontaneous recovery data in the 10% to 90% block range from all patients were pooled and fitted to a linear model. Two parameters were estimated: (1) the slope, which is related to the pharmacokinetics and to the steepness of the dose-response curve, and (2) the intercept, which is linearly related to dose but has no physiologic meaning. The primary goal was to determine the factors affecting the slope by use of univariate and multivariate analyses techniques. Estimates of the slope ranged from 0.67% to 1.1% block/min (interindividual variability, 39%). Factors with clinically significant effects on the slope included the following: age, obesity, and anesthesia type. Thus these factors influence the time course of Doxacurium-induced block and may require individualization of dose. Clinical Pharmacology and Therapeutics (1992) 52, 528–536; doi:10.1038/clpt.1992.181
Thaddeus H Grasela - One of the best experts on this subject based on the ideXlab platform.
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population pharmacodynamics of Doxacurium
Clinical Pharmacology & Therapeutics, 1992Co-Authors: Martha M Aboudonia, Virginia D Schmith, Jill Fiedlerkelly, Cameron S Huffman, Thaddeus H GraselaAbstract:The nonlinear mixed-effects modeling (NONMEM) computer program was used to investigate the variability in the duration of Doxacurium-induced neuromuscular block in 408 patients enrolled in phase II and phase III clinical trials of Doxacurium. Spontaneous recovery data in the 10% to 90% block range from all patients were pooled and fitted to a linear model. Two parameters were estimated: (1) the slope, which is related to the pharmacokinetics and to the steepness of the dose-response curve, and (2) the intercept, which is linearly related to dose but has no physiologic meaning. The primary goal was to determine the factors affecting the slope by use of univariate and multivariate analyses techniques. Estimates of the slope ranged from 0.67% to 1.1% block/min (interindividual variability, 39%). Factors with clinically significant effects on the slope included the following: age, obesity, and anesthesia type. Thus these factors influence the time course of Doxacurium-induced block and may require individualization of dose. Clinical Pharmacology and Therapeutics (1992) 52, 528–536; doi:10.1038/clpt.1992.181
David R Bevan - One of the best experts on this subject based on the ideXlab platform.
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dose responses for neostigmine and edrophonium as antagonists of mivacurium in adults and children
Anesthesiology, 1996Co-Authors: Joan C Bevan, Claude Tousignant, Catherine Stephenson, Lee Blackman, Eleanor Reimer, Michael F Smith, David R BevanAbstract:BackgroundReversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or Doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and Doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults.
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Reversal of Doxacurium and pancuronium neuromuscular blockade with neostigmine in children
Canadian journal of anaesthesia = Journal canadien d'anesthesie, 1994Co-Authors: Joan C Bevan, Eleanor Reimer, Jonathan P. Purday, David R BevanAbstract:Recovery after Doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2–10 yr (ASA 1–2) were studied. They were randomized to receive Doxacurium 30 μg · kg−1 or pancuronium 70 μg · kg−1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 μg · kg−1) with atropine by random allocation when first twitch height (TI) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following Doxacurium (mean ± SEM values of 45.0 ± 3.9 vs 49.5 ± 10.0 % for TI and 25.2 ± 3.8 vs 14.8 ± 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of TI or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED70 and ED90 doses for TI of 14.3 ± 1.8 and 25.7 ± 2.7 μg·kg−1 for Doxacurium and 12.5 ± 1.7 and 25.3 ± 2.3 μg· kg−1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 ng · kg−1 was 2.3 ± 1.0 and 4.2 ± 1.7 min (P = NS) following pancuronium and Doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine. Thus, in children, the spontaneous recovery and reversal of neuromuscular blockade is similar with Doxacurium and pancuronium. However, compared with previous adult studies, they recover twice as quickly from Doxacurium neuromuscular blockade and neostigmine antagonism is achieved at 25–50% of the adult doses.
Joan C Bevan - One of the best experts on this subject based on the ideXlab platform.
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dose responses for neostigmine and edrophonium as antagonists of mivacurium in adults and children
Anesthesiology, 1996Co-Authors: Joan C Bevan, Claude Tousignant, Catherine Stephenson, Lee Blackman, Eleanor Reimer, Michael F Smith, David R BevanAbstract:BackgroundReversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or Doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and Doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults.
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Reversal of Doxacurium and pancuronium neuromuscular blockade with neostigmine in children
Canadian journal of anaesthesia = Journal canadien d'anesthesie, 1994Co-Authors: Joan C Bevan, Eleanor Reimer, Jonathan P. Purday, David R BevanAbstract:Recovery after Doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2–10 yr (ASA 1–2) were studied. They were randomized to receive Doxacurium 30 μg · kg−1 or pancuronium 70 μg · kg−1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 μg · kg−1) with atropine by random allocation when first twitch height (TI) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following Doxacurium (mean ± SEM values of 45.0 ± 3.9 vs 49.5 ± 10.0 % for TI and 25.2 ± 3.8 vs 14.8 ± 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of TI or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED70 and ED90 doses for TI of 14.3 ± 1.8 and 25.7 ± 2.7 μg·kg−1 for Doxacurium and 12.5 ± 1.7 and 25.3 ± 2.3 μg· kg−1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 ng · kg−1 was 2.3 ± 1.0 and 4.2 ± 1.7 min (P = NS) following pancuronium and Doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine. Thus, in children, the spontaneous recovery and reversal of neuromuscular blockade is similar with Doxacurium and pancuronium. However, compared with previous adult studies, they recover twice as quickly from Doxacurium neuromuscular blockade and neostigmine antagonism is achieved at 25–50% of the adult doses.
Phillip E Scuderi - One of the best experts on this subject based on the ideXlab platform.
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dose response recovery and cost of Doxacurium as a continuous infusion in neurosurgical intensive care unit patients
Critical Care Medicine, 1997Co-Authors: Richard C. Prielipp, James C Robinson, John A Wilson, Drew A Macgregor, Phillip E ScuderiAbstract:Objectives: To determine the optimal dosing of Doxacurium as a continuous infusion in neurosurgical patients with traumatic brain injury; to determine the effects of bolus administration of Doxacurium on heart rate (HR), blood pressure (BP), and intracranial pressure (ICP); to monitor neuromuscular recovery after discontinuation of prolonged Doxacurium infusion; and to compare the cost of Doxacurium with other current neuromuscular blocking drugs. Design: Prospective, open-label study. Setting: Neurosurgical intensive care unit (ICU) of a university-affiliated teaching hospital. Patients: Eight critically ill, mechanically ventilated patients with traumatic head injury and normal renal and hepatic function. Patients had ICP monitoring. Interventions: A bolus injection of Doxacurium (0.05 mg/kg) followed by a continuous infusion (0.015 mg/kg/hr), adjusted to maintain one twitch during Train-of-Four nerve stimulation of the adductor pollicis muscle. Measurements and Main Results: Bolus injections of Doxacurium did not alter the HR, BP, or ICP. Patients were paralyzed 66 ± 12 (SEM) hrs, with recovery of the fourth twitch occurring 118 ± 19 mins after infusion of the Doxacurium was discontined. There were no incidences of prolonged weakness, myopathy, or other adverse events. Conclusions: Continuous infusion of Doxacurium provides stable neuromuscular blockade for neurosurgical patients with traumatic brain injury. Doxacurium is devoid of clinically important interactions with HR, BP, or ICP and is less costly than other neuromuscular blockers used in the ICU.
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double blind randomized multicenter study of Doxacurium vs pancuronium in intensive care unit patients who require neuromuscular blocking agents
Critical Care Medicine, 1995Co-Authors: Michael J Murray, Phillip E Scuderi, Douglas B Coursin, Gerard S Kamath, Donald S Prough, Diane M Howard, Martha AboudoniaAbstract:Objective To compare the neuromuscular-blocking and hemodynamic effects of Doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for >or=to24 hrs. Design A multicenter, prospective, double-blind, randomized study comparing Doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. Setting ICUs of three tertiary care hospitals. Patients Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). Interventions With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either Doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (Doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular-blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t-tests, when appropriate. Spearman's rank-correlation coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. A p Measurements and Main Results There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for Doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 +/- 23 vs. 109 +/- 22 beats/min postinjection vs. preinjection, respectively; p Conclusions In critically ill patients requiring neuromuscular block for >24 hrs, Doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile.