43 research outputs found
Supplementary Material, Supplementary_Appendix_C – Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis
No full textSupplementary Material, Supplementary_Appendix_C for Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis by Salmaan Kanji, Jason A. Roberts, Jiao Xie, Abdulaziz Alobaid, Sheryl Zelenitsky, Swapnil Hiremath, Guijun Zhang, Irene Watpool, Rebecca Porteous and Rakesh Patel in Annals of Pharmacotherapy</p
Supplementary Material, Supplementary_Appendix_D – Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis
No full textSupplementary Material, Supplementary_Appendix_D for Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis by Salmaan Kanji, Jason A. Roberts, Jiao Xie, Abdulaziz Alobaid, Sheryl Zelenitsky, Swapnil Hiremath, Guijun Zhang, Irene Watpool, Rebecca Porteous and Rakesh Patel in Annals of Pharmacotherapy</p
Supplementary Material, Supplementary_Appendix_A – Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis
No full textSupplementary Material, Supplementary_Appendix_A for Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis by Salmaan Kanji, Jason A. Roberts, Jiao Xie, Abdulaziz Alobaid, Sheryl Zelenitsky, Swapnil Hiremath, Guijun Zhang, Irene Watpool, Rebecca Porteous and Rakesh Patel in Annals of Pharmacotherapy</p
Supplementary Material, Supplementary_Appedix_B – Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis
No full textSupplementary Material, Supplementary_Appedix_B for Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis by Salmaan Kanji, Jason A. Roberts, Jiao Xie, Abdulaziz Alobaid, Sheryl Zelenitsky, Swapnil Hiremath, Guijun Zhang, Irene Watpool, Rebecca Porteous and Rakesh Patel in Annals of Pharmacotherapy</p
Vancomycin population pharmacokinetics in critically ill adults during sustained low-efficiency dialysis
No full textBackground: Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking. Objective: The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies. Methods: Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses. Results: From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46)\ua0L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration–time curve from time zero to 24\ua0h [AUC]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC ≥ 700), a loading dose of 2400\ua0mg followed by daily doses of 1600\ua0mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels. Conclusions: In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels
Saline versus albumin fluid for extracorporeal removal with slow low-efficiency dialysis (SAFER-SLED): study protocol for a pilot trial
No full textAbstract
Background
Critically ill patients frequently develop acute kidney injury that necessitates renal replacement therapy (RRT). At some centers, critically ill patients who are hemodynamically unstable and require RRT are treated with slow low-efficiency dialysis (SLED). Unfortunately, hypotension is a frequent complication that occurs during SLED treatments and may limit the recovery of kidney function. Hypotension may also limit the amount of fluid that can be removed by ultrafiltration with SLED. Fluid overload can be exacerbated as a consequence, and fluid overload is associated with increased mortality.
Occasionally, intravenous albumin fluid is given to prevent or treat low blood pressure during SLED. The intent of doing so is to increase the colloid oncotic pressure in the circulation to draw in extravascular fluid, increase the blood pressure, and enable more aggressive fluid removal with ultrafiltration. Nonetheless, there is little evidence to support this practice and theoretical reasons why it may not be especially effective at augmenting fluid removal in critically ill patients. At the same time, albumin fluid is expensive.
As such, we present a protocol for a study to assess the feasibility of a randomized controlled trial evaluating the use of albumin fluid versus saline in critically ill patients receiving SLED.
Methods
This study is a single-center, double-blind, and randomized controlled pilot trial with two parallel arms. It involves randomly assigning patients receiving SLED treatment in the ICU to receive either albumin (25%) boluses or normal saline fluid boluses (placebo) to prevent and treat low blood pressure.
Discussion
The results of this pilot trial will help with planning a larger trial comparing the efficacy of the interventions in achieving fluid removal in critically ill patients with AKI on SLED. They will establish whether enough participants would participate in a larger study and accept the study procedures.
Trial registration
This trial is registered on ClinicalTrials.gov Identifier
NCT03665311
, registered on September 11, 2018
Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study)
No full textAbstract
Background
Hemodynamic instability is a frequent complication of sustained low-efficiency dialysis (SLED) treatments in the ICU. Intravenous hyperoncotic albumin may prevent hypotension and facilitate ultrafiltration. In this feasibility trial, we sought to determine if a future trial, powered to evaluate clinically relevant outcomes, is feasible.
Methods
This single-center, blinded, placebo-controlled, randomized feasibility trial included patients with acute kidney injury who started SLED in the ICU. Patients were randomized to receive 25% albumin versus 0.9% saline (control) as 100 mL boluses at the start and midway through SLED, for up to 10 sessions. The recruitment rate and other feasibility outcomes were determined. Secondary exploratory outcomes included ultrafiltration volumes and metrics of hemodynamic instability.
Results
Sixty patients (271 SLED sessions) were recruited over 10 months. Age and severity of illness were similar between study groups. Most had septic shock and required vasopressor support at baseline. Protocol adherence occurred for 244 sessions (90%); no patients were lost to follow-up; no study-related adverse events were observed; open label albumin use was 9% and 15% in the albumin and saline arms, respectively. Ultrafiltration volumes were not significantly different. Compared to the saline group, the albumin group experienced less hemodynamic instability across all definitions assessed including a smaller absolute decrease in systolic blood pressure (mean difference 10.0 mmHg, 95% confidence interval 5.2–14.8); however, there were significant baseline differences in the groups with respect to vasopressor use prior to SLED sessions (80% vs 61% for albumin and saline groups, respectively).
Conclusions
The efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible.
Trial registration ClinicalTrials.gov (NCT03665311); First Posted: Sept 11th, 2018.
https://clinicaltrials.gov/ct2/show/NCT03665311?term=NCT03665311&draw=2&rank=
Piperacillin population pharmacokinetics in critically ill adults during sustained low-efficiency dialysis
No full textBackground: Sustained low-efficiency dialysis (SLED), is increasingly being used in intensive care units (ICUs) but studies informing drug dosing for such patients is lacking. Objective: To describe the population pharmacokinetics (PKs) of piperacillin/tazobactam in critically ill adults receiving SLED and to provide dosing recommendations. Methods: This prospective population PK study was conducted in adult ICU patients prescribed piperacillin/tazobactam while receiving SLED; 321 blood samples were obtained from 34 participants during and between approximately 50 SLED treatments for quantification of piperacillin and tazobactam concentrations in plasma. A population PK model was developed. Monte Carlo simulation was used to determine the probability of target attainment and pathogen-specific fractional target attainment at different doses. Results: From a 2-compartment linear model with zero-order input, the mean (SD) clearance of piperacillin on SLED and off SLED were 4.81 (8.48) and 1.42 (1.54) L/h, respectively. Tazobactam concentrations were not sufficient for analysis. For the target of 50% fT>MIC (unbound concentrations of drug are above the minimum inhibitory concentration for >50% of the dosing interval), 3-g of piperacillin infused over 0.5 hours every 8 hours was appropriate for susceptible organisms with MIC ≤16 mg/L. For life-threatening infections where the target of 100% fT>MIC is preferred, a 9-g dose administered as a continuous infusion every 24 hours was appropriate for susceptible organisms with MIC ≤32 mg/L. Conclusions and Relevance: In critically ill patients receiving SLED, piperacillin doses need to be guided by the frequency of SLED treatments and susceptibility of the known or suspected pathogen
Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis
No full text
