Hood's own, or, laughter from year to year : being former runnings of his comic vein, with an infusion of new blood for general circulation /

Mode of access: Internet.

Propofol infusion syndrome in a super morbidly obese patient (BMI = 75)

Propofol infusion syndrome (PRIS) is a rare but often fatal complication as a result of large doses of propofol infusion (4–5 mg/kg/hr) for a prolonged period (>48 h). It has been reported in both children and adults. Besides large doses of propofol infusion, the risk factors include young age, acute neurological injury, low carbohydrate and high fat intake, exogenous administration of corticosteroid and catecholamine, critical illness, and inborn errors of mitochondrial fatty acid oxidation. PRIS manifestation include presence of metabolic acidosis with a base deficit of more than 10 mmol/l at least on one occasion, rhabdomyolysis or myoglobinuria, acute renal failure, sudden onset of bradycardia resistant to treatment, myocardial failure, and lipemic plasma. The pathophysiology of PRIS may be either direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. We report a case of supermorbidly obese patient who received propofol infusion by total body weight instead of actual body weight and developed PRIS.

Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita)

Objective To determine the pharmacokinetics of carboplatin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. Design A pharmacokinetic study of carboplatin, following a single intravenous (IV) or intraosseus (10) infusion over 3 min, was performed in six healthy sulphur-crested cockatoos (Cacatua galerita). Procedure Birds were anaesthetised and a jugular vein cannulated for blood collection. Carboplatin (5 mg/kg) was infused over 3 min by the IV route in four birds via the contralateral jugular vein, and by the 10 route in two birds via the ulna. Serial blood samples were collected for 96 h after initiation of the infusion. Tissue samples from 11 organs were obtained at necropsy, 96 h after carboplatin administration. Total Pt and filterable Pt in plasma and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma data. Results The mean +/- SD for the C-max of filterable Pt was 27.3 +/- 4.06 mg/L and in all six birds occurred at the end of the 3 min infusion, thenceforth declining exponentially over the next 6 h to an average concentration of 0.128 +/- 0.065 mg/L. The terminal half-life (T-1/2) was 1.0 +/- 0.17 h, the systemic clearance (CI) was 5.50 +/- 1.06 mL/min/kg and the volume of distribution (Vss) was 0.378 +/- 0.073 L/kg. The extrapolated area under the curve (AUC(0-x)) was 0.903 +/- 0.127 mg/mL.min; the area extrapolated past the last (6 h) data point to infinite time averaged only 1.25% of the total AUC(0-x). The kidneys had the greatest accumulation of Pt (7.04 +/- 3.006 mug/g), followed by the liver (3.08 +/- 1.785 mug/g DM). Conclusions and clinical relevance Carboplatin infusion in sulphur-crested cockatoos produced mild, transient alimentary tract signs and the Pt plasma concentration was similar whether carboplatin was given intravenously or intraosseously. Filterable plasma Pt concentrations for carboplatin persisted longer than for cisplatin, due mostly to the difference in systemic clearance between these drugs in sulphur-crested cockatoos. The distribution of tissue Pt after carboplatin administration was similar to that reported for cisplatin in sulphur-crested cockatoos. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo shares some features with the kinetics reported previously in other animals and human beings.

Doxorubicin pharmacokinetics following a single-dose infusion to sulphur-crested cockatoos (Cacatua galerita)

Objective To determine the pharmacokinetics of doxorubicin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. Design A pharmacokinetic study of doxorubicin, following a single intravenous (IV) infusion over 20 min, was performed in four healthy sulphur-crested cockatoos (Cacatua galerita). Procedure Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused IV over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse-phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL. Established non-parametric methods were used for the analysis of plasma doxorubicin data. Results During the infusion the mean +/- SD for the C-max of doxorubicin was 4037 +/- 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (beta-phase) half-life was 41.4 +/- 18.5 min, the systemic clearance (Cl) was 45.7 +/- 18.0 mL/min/kg, the mean residence time (MRT) was 4.8 +/- 1.4 min, and the volume of distribution at steady state (V-SS) was 238 131 mL/kg. The extrapolated area under the curve (AUC(0-infinity)) was 950 +/- 677 ng/mL.h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate-limited pharmacokinetics of doxorubicinol. Conclusions and clinical relevance Doxorubicin infusion in sulphur-crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half-life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home Cl of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Development of a dosage strategy in patients receiving enoxaparin by continuous intravenous infusion using modelling and simulation

Aim To develop an appropriate dosing strategy for continuous intravenous infusions (CII) of enoxaparin by minimizing the percentage of steady-state anti-Xa concentration (C-ss) outside the therapeutic range of 0.5-1.2 IU ml(-1). Methods A nonlinear mixed effects model was developed with NONMEM (R) for 48 adult patients who received CII of enoxaparin with infusion durations that ranged from 8 to 894 h at rates between 100 and 1600 IU h(-1). Three hundred and sixty-three anti-Xa concentration measurements were available from patients who received CII. These were combined with 309 anti-Xa concentrations from 35 patients who received subcutaneous enoxaparin. The effects of age, body size, height, sex, creatinine clearance (CrCL) and patient location [intensive care unit (ICU) or general medical unit] on pharmacokinetic (PK) parameters were evaluated. Monte Carlo simulations were used to (i) evaluate covariate effects on C-ss and (ii) compare the impact of different infusion rates on predicted C-ss. The best dose was selected based on the highest probability that the C-ss achieved would lie within the therapeutic range. Results A two-compartment linear model with additive and proportional residual error for general medical unit patients and only a proportional error for patients in ICU provided the best description of the data. Both CrCL and weight were found to affect significantly clearance and volume of distribution of the central compartment, respectively. Simulations suggested that the best doses for patients in the ICU setting were 50 IU kg(-1) per 12 h (4.2 IU kg(-1) h(-1)) if CrCL < 30 ml min(-1); 60 IU kg(-1) per 12 h (5.0 IU kg(-1) h(-1)) if CrCL was 30-50 ml min(-1); and 70 IU kg(-1) per 12 h (5.8 IU kg(-1) h(-1)) if CrCL > 50 ml min(-1). The best doses for patients in the general medical unit were 60 IU kg(-1) per 12 h (5.0 IU kg(-1) h(-1)) if CrCL < 30 ml min(-1); 70 IU kg(-1) per 12 h (5.8 IU kg(-1) h(-1)) if CrCL was 30-50 ml min(-1); and 100 IU kg(-1) per 12 h (8.3 IU kg(-1) h(-1)) if CrCL > 50 ml min(-1). These best doses were selected based on providing the lowest equal probability of either being above or below the therapeutic range and the highest probability that the C-ss achieved would lie within the therapeutic range. Conclusion The dose of enoxaparin should be individualized to the patients' renal function and weight. There is some evidence to support slightly lower doses of CII enoxaparin in patients in the ICU setting.

Application of Monte Carlo simulations to identify an appropriate dosage strategy for patients receiving a continuous intravenous infusion of enoxaparin

Aim: To identify an appropriate dosage strategy for patients receiving enoxaparin by continuous intravenous infusion (CII). Methods: Monte Carlo simulations were performed in NONMEM, (200 replicates of 1000 patients) to predict steady state anti-Xa concentrations (Css) for patients receiving a CII of enoxaparin. The covariate distribution model was simulated based on covariate demographics in the CII study population. The impact of patient weight, renal function (creatinine clearance (CrCL)) and patient location (intensive care unit (ICU)) were evaluated. A population pharmacokinetic model was used as the input-output model (1-compartment first order output model with mixed residual error structure). Success of a dosing regimen was based on the percent of Css that is between the therapeutic range of 0.5 IU/ml to 1.2 IU/ml. Results: The best dose for patients in the ICU was 4.2IU/kg/h (success mean 64.8% and 90% prediction interval (PI): 60.1–69.8%) if CrCL60ml/min, the best dose was 8.3IU/kg/h (success mean 65.4%, 90% PI: 58.5–73.2%). Simulations suggest that there was a 50% improvement in the success of the CII if the dose rate for ICU patients with CrCL

The impact of e-business infusion on channel coordination, conflict and reseller performance

Manufacturer–reseller interactions are becoming more technology-enabled as channels of distribution increasingly utilize e-business tools on the Internet. This research examines the performance consequences for resellers as these technological advances are applied to distribution activities between channel members. Using a sample of 216 resellers of computer products, the research explores the impact of e-business tools in 2 areas of manufacturer–reseller interactions: supply tasks and demand tasks. The results suggest that e-business in supply tasks increases relationship coordination between manufacturer and reseller, whereas e-business in demand tasks increases coordination as well as conflict within the channel dyad. The increase of conflict constitutes a potential “dark side” of e-business in channel relationships that may provide an explanation for e-business implementation failures and negative returns on investment in technology.

Towards an operations strategy for the infusion of product-centric services into manufacturing:service systems implementation

The work in this chapter is concerned with product-centric servitization. This is where a portfolio of services are formed and integrated to support product availability and use. Such servitization can be a valuable source of revenue for a manufacturer, yet little attention has been given to the configuration of the wider operations strategy that needs to be in place to deliver integrated products and services successfully. Therefore, the purpose of this chapter is to put forward a generic set of characteristics for such operations. Our intention is that these characteristics will be valuable to practitioners contemplating sophisticated forms of servitization, as they suggest the likely and significant changes that will be needed to the operations strategy of a conventional manufacturing organisation.

Stability of anthracycline cytotoxic agents in solution and infusion fluids

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Rôle du niveau d'expression d'ABCC2 dans la sensibilité à la cholestase intrahépatique induite par une infusion de taurocholate

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.