11 research outputs found
Assessment for early discharge of cardiothoracic surgical patients: Results of a pilot study conducted in one private intensive care unit
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Photocatalytic dehydrogenation of liquid alcohols by platinized anatase and other catalysts
No full textThe work described in this thesis was undertaken at the University of Nottingham between October 1981 and November 1984, under the supervision of Dr. R. Rudham. Except where indicated by reference, it is the original work of the author and has not been submitted for any other degree.
The photocatalytic dehydrogenation of liquid alcohols (methanol, ethanol, propan-1-ol and propan-2-ol) by suspensions of platinum and other metals supported on anatase have been investigated by following carbonyl compound formation under a nitrogen atmosphere. Measurements were made over the temperature range 278-303 K using filtered 366 nm U.V. radiation. Reaction on photodeposited catalysts was consistently associated with an activation energy of 20 + 1 kJ mol-1 , although the activity fell in the sequence: PT/TiO2 > Pd/TiO2 > Rh/TiO2 > Au/TiO2 – O for catalysts with a metal content of 0.5 wt%. The activation energy is identical to that for photoreaction on the anatase support in the presence of oxygen and is believed to be associated with the transport of photoelectrons through the anatase to either metal particles or adsorbed oxygen.
Activities and activation energies for carbonyl compound formation from the photocatalytic dehydrogenation of the individual alcohols were effectively identical on the same catalyst, indicating that the photocatalytic dehydrogenation reaction is not governed by the physical or chemical properties of the reactant alcohol.
With platinized anatase prepared by hydrogen reduction there was an appreciable dark reaction, which was absent with catalysts prepared by photodeposition. It is believed that reduction in hydrogen at elevated temperature renders the anatase support non-stoichiometric, a process favoured by spillover of hydrogen atoms from the platinum particles. The low activation energy for photocatalysis on hydrogen reduced catalyst is considered to be associated with the non-stoichiometric nature of the anatase, which presumably provides an energetically favourable mechanism for photoelectron transport to the metal particles and negates the photoelectron traps responsible for an activation energy of 20 ± 1 kJ mol-1 on the non-reduced catalysts.
A radical mechanism for photocatalytic dehydrogenation is proposed. This mechanism predicts a l1m1 ting quantum yield of one half, which is in good agreement with the value obtained from experiments at different light intensities
Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation.
No full textRATIONALE
Data are suggesting that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO).
OBJECTIVES
The primary aim of this analysis was to describe the pharmacokinetics of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve both effective and safe exposure.
METHODS
This study was a prospective, open-labelled, pharmacokinetic study in six intensive care units from Australia, New Zealand, South Korea and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for eleven antimicrobials. Pharmacokinetic parameters were estimated using non-compartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using pre-defined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks.
MEASUREMENTS AND MAIN RESULTS
We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years and 61.2% were males. Thirty-eight patients (44.7%) were receiving renal replacement therapy (RRT) during first pharmacokinetic sampling. Large variations (coefficient of variation of ≥30%) in antimicrobial concentrations were seen leading to more than five-fold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the pre-defined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and RRT. Poor target attainment was observed across the most frequently used antimicrobials for ECMO patients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%).
CONCLUSION
Antimicrobial pharmacokinetics were highly-variable in critically ill patients receiving ECMO leading to poor target attainment rates
Photocatalytic dehydrogenation of liquid alcohols by platinized anatase and other catalysts
No full textThe work described in this thesis was undertaken at the University of Nottingham between October 1981 and November 1984, under the supervision of Dr. R. Rudham. Except where indicated by reference, it is the original work of the author and has not been submitted for any other degree.
The photocatalytic dehydrogenation of liquid alcohols (methanol, ethanol, propan-1-ol and propan-2-ol) by suspensions of platinum and other metals supported on anatase have been investigated by following carbonyl compound formation under a nitrogen atmosphere. Measurements were made over the temperature range 278-303 K using filtered 366 nm U.V. radiation. Reaction on photodeposited catalysts was consistently associated with an activation energy of 20 + 1 kJ mol-1 , although the activity fell in the sequence: PT/TiO2 > Pd/TiO2 > Rh/TiO2 > Au/TiO2 – O for catalysts with a metal content of 0.5 wt%. The activation energy is identical to that for photoreaction on the anatase support in the presence of oxygen and is believed to be associated with the transport of photoelectrons through the anatase to either metal particles or adsorbed oxygen.
Activities and activation energies for carbonyl compound formation from the photocatalytic dehydrogenation of the individual alcohols were effectively identical on the same catalyst, indicating that the photocatalytic dehydrogenation reaction is not governed by the physical or chemical properties of the reactant alcohol.
With platinized anatase prepared by hydrogen reduction there was an appreciable dark reaction, which was absent with catalysts prepared by photodeposition. It is believed that reduction in hydrogen at elevated temperature renders the anatase support non-stoichiometric, a process favoured by spillover of hydrogen atoms from the platinum particles. The low activation energy for photocatalysis on hydrogen reduced catalyst is considered to be associated with the non-stoichiometric nature of the anatase, which presumably provides an energetically favourable mechanism for photoelectron transport to the metal particles and negates the photoelectron traps responsible for an activation energy of 20 ± 1 kJ mol-1 on the non-reduced catalysts.
A radical mechanism for photocatalytic dehydrogenation is proposed. This mechanism predicts a l1m1 ting quantum yield of one half, which is in good agreement with the value obtained from experiments at different light intensities
ASAP ECMO: antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation: a multi-centre study to optimise drug therapy during ECMO
No full textBackground: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO
Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study
No full textInternational audienceABSTRACT This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC 0-24 /MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose
Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation
No full textSignificant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model.In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (Vd), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and Vd, 0.99 L/kg.We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO
Population Pharmacokinetics and Dosing Simulations of Ceftriaxone in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (An ASAP ECMO Study)
No full textBACKGROUND: Despite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the appropriate dosing of antimicrobials in this setting. Ceftriaxone is an antimicrobial with a high affinity to plasma protein, a property identified in the literature as susceptible to sequestration into extracorporeal circuits and hypothesised to require dosage adjustments in this setting. OBJECTIVE: The aim of this study was to describe the pharmacokinetics of ceftriaxone and identify the best dosing regimen for critically ill adult patients receiving ECMO. METHODS: Serial blood samples were taken from patients receiving both ECMO and ceftriaxone. Total and unbound drug concentrations were measured in plasma by chromatographic assay and analysed using a population pharmacokinetic approach with Pmetrics(®). Dosing simulations were performed to identify the optimal dosing strategy: 60 and 100% of time with free (unbound) drug concentration exceeding the minimum inhibitory concentration (fT(>MIC)). RESULTS: In total, 14 patients were enrolled, of which three were receiving renal replacement therapy (RRT). Total and unbound ceftriaxone was best described in a two-compartment model with total body weight, serum albumin concentrations, creatinine clearance (CrCL), and the presence of RRT included as significant predictors of pharmacokinetics. Patients not on RRT generated a mean renal clearance of 0.90 L/h, non-renal clearance of 0.33 L/h, and central volume of distribution of 7.94 L. Patients on RRT exhibited a mean total clearance of 1.18 L/h. ECMO variables were not significant predictors of ceftriaxone pharmacokinetics. Steady-state dosing simulations found that dosages of 1 g every 12 h and 2 g every 24 h achieved >90% probabilities of target attainment in patients with CrCL of 0 mL/min with RRT and 30 and 100 mL/min and various serum albumin concentrations (17 and 26 g/L). CONCLUSIONS: Dosing recommendations for critically ill adult patients not on ECMO appear to be sufficient for patients on ECMO. Patients exhibiting augmented renal clearance (> 130 mL/min) or treatment of less susceptible pathogens may require higher doses, which requires further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-021-01106-x
Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study)
No full textOur study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analyzed using a population PK approach on Pmetrics. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC(0-24)) of 400–700 mg · h/liter at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 ml/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT, and total body weight found as significant predictors of clearance and central volume of distribution (V(c)). The mean vancomycin renal clearance and V(c) were 3.20 liters/h and 29.7 liters respectively, while the clearance for patients on RRT was 0.15 liters/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5–20 mg/kg every 12 h are associated with a 97–98% probability of efficacy and 11–12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT. (This study is registered with the Australian New Zealand Clinical Trials Registry [ANZCTR] under number ACTRN12612000559819.
