Salmaan Kanji1, Jason A Roberts2,3, Jiao Xie4, Sheryl Zelenitsky5, Swapnil Hiremath6, Guijun Zhang7, Irene Watpool6, Rebecca Porteous6, Rakesh Patel6. 1. The Ottawa Hospital, The Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, ON, Canada. skanji@toh.ca. 2. Faculty of Medicine and School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. 3. Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. 4. Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. 5. College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. 6. The Ottawa Hospital, The Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, ON, Canada. 7. Clinical Investigations Unit, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Abstract
BACKGROUND: 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) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC24]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC24 ≥ 700), a loading dose of 2400 mg followed by daily doses of 1600 mg 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.
BACKGROUND:Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically illpatients 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 illpatients receiving SLED, and use simulation studies to propose dosing strategies. METHODS: Serial serum samples were obtained from 31 critically illpatients 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) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC24]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC24 ≥ 700), a loading dose of 2400 mg followed by daily doses of 1600 mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels. CONCLUSIONS: In critically illpatients 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.
Authors: Michael N Neely; Michael G van Guilder; Walter M Yamada; Alan Schumitzky; Roger W Jelliffe Journal: Ther Drug Monit Date: 2012-08 Impact factor: 3.681
Authors: Jan T Kielstein; David Czock; Timo Schöpke; Carsten Hafer; Stefanie M Bode-Böger; Ernst Kuse; Frieder Keller; Danilo Fliser Journal: Crit Care Med Date: 2006-01 Impact factor: 7.598
Authors: Kimberly N Bogard; Nicole T Peterson; Troy J Plumb; Michael W Erwin; Patrick D Fuller; Keith M Olsen Journal: Crit Care Med Date: 2011-03 Impact factor: 7.598
Authors: Tatiana Tatarinova; Michael Neely; Jay Bartroff; Michael van Guilder; Walter Yamada; David Bayard; Roger Jelliffe; Robert Leary; Alyona Chubatiuk; Alan Schumitzky Journal: J Pharmacokinet Pharmacodyn Date: 2013-02-13 Impact factor: 2.745
Authors: Sean M Bagshaw; Stephen Lapinsky; Sandra Dial; Yaseen Arabi; Peter Dodek; Gordon Wood; Paul Ellis; Jorge Guzman; John Marshall; Joseph E Parrillo; Yoanna Skrobik; Anand Kumar Journal: Intensive Care Med Date: 2008-12-09 Impact factor: 17.440