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Crrt, drug dosing

Xiaoying Xu, Dmytro Khadzhynov, Harm Peters, Ricardo L Chaves, Kamal Hamed, Micha Levi, Natascia Corti
AIM: The objective of this population pharmacokinetic (PK) analysis was to provide guidance for the dosing interval of daptomycin in patients undergoing continuous renal replacement therapy (CRRT). METHODS: A previously published population PK model for daptomycin was updated with data from patients undergoing continuous veno-venous haemodialysis (CVVHD; n = 9) and continuous veno-venous haemodiafiltration (CVVHDF; n = 8). Model-based simulations were performed to compare the 24 h AUC, Cmax and Cmin of daptomycin following various dosing regimens (4, 6, 8, 10, and 12 mg/kg every [Q] 24 h and Q48h), with the safety and efficacy exposure references for Staphylococcus aureus bacteraemia/right-sided infective endocarditis...
September 15, 2016: British Journal of Clinical Pharmacology
Sherif Hanafy Mahmoud
Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted...
September 1, 2016: Clinical Drug Investigation
Anna P Kempke, Abbie S Leino, Farzad Daneshvar, John Andrew Lee, Bruce A Mueller
Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers...
2016: Critical Care Research and Practice
Claire Roger, Steven C Wallis, Laurent Muller, Gilbert Saissi, Jeffrey Lipman, Jean-Yves Lefrant, Jason A Roberts
The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed...
August 2016: Antimicrobial Agents and Chemotherapy
Alexander R Shaw, Weerachai Chaijamorn, Bruce A Mueller
Appropriate antibiotic dosing in critically ill, infected, patients receiving continuous renal replacement therapy (CRRT) is crucial to improve patient outcomes. Severe sepsis and septic shock result in changes in pharmacokinetic parameters, including increased volume of distribution, hypoalbuminemia, and changes in renal and nonrenal clearances. The lack of CRRT standardization, nonrecognition of how CRRT variability affects antibiotic removal, fear of antibiotic toxicity, and limited drug dosing resources all contribute to suboptimal antibiotic therapy...
July 2016: Seminars in Dialysis
Derek N Bremmer, David P Nicolau, Pam Burcham, Anil Chunduri, Ganesh Shidham, Karri A Bauer
Limited data are available on ceftolozane/tazobactam dosing in patients receiving continuous renal replacement therapy (CRRT). Thus we performed a pharmacokinetic analysis of intravenous ceftolozane/tazobactam in a critically ill patient receiving CRRT at our medical center. A 47-year-old critically ill man with multidrug-resistant Pseudomonas aeruginosa pneumonia, bacteremia, and osteomyelitis was receiving ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) every 8 hours while receiving continuous venovenous hemodiafiltration (CVVHDF)...
May 2016: Pharmacotherapy
Hyeong Jin Lee, Bongjin Lee, June Dong Park, Hyung Joo Jeong, Yu Hyeon Choi, Hee Young Ju, Che Ry Hong, Ji Won Lee, Hyery Kim, Dong In Suh, Kyung Duk Park, Hyoung Jin Kang, Hee Young Shin, Hyo Seop Ahn
PURPOSE: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug. MATERIALS AND METHODS: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013...
2015: Drug Design, Development and Therapy
Farahnak Assadi, Fatemeh Ghane Shahrbaf
The dosage of drugs in patients requiring continuous renal replacement therapy need to be adjusted based on a number of variables that that affect pharmacokinetics (PK) including patient weight, CRRT modality (convention, vs. diffusion), blood and/or effluent flow, hemofilter characteristics, physiochemical drug properties, volume of distribution, protein binding and half-life as well as residual renal function. There is a paucity of data on PK studies in children with acute kidney injury requiring CRRT. When possible, therapeutic drug monitoring should be utilized for those medications where serum drug concentrations can be obtained in a clinically relevant time frame...
2016: Frontiers in Bioscience (Scholar Edition)
Wai-Tat Wong, Gordon Choi, Charles D Gomersall, Jeffrey Lipman
Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction...
October 2015: Current Opinion in Pharmacology
Ping Zhao, Ruiqiang Zheng, Lu Xue, Min Zhang, Xiaoyan Wu
This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 µg/kg/h)...
2015: BioMed Research International
Megan E Kunka, Elizabeth A Cady, Heejung C Woo, Melissa L Thompson Bastin
Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations...
2015: Case Reports in Critical Care
Marta Ulldemolins, Dolors Soy, Mireia Llaurado-Serra, Sergi Vaquer, Pedro Castro, Alejandro H Rodríguez, Caridad Pontes, Gonzalo Calvo, Antoni Torres, Ignacio Martín-Loeches
Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested)...
September 2015: Antimicrobial Agents and Chemotherapy
Takanori Funaki, Ippei Miyata, Kensuke Shoji, Yuki Enomoto, Seisuke Sakamoto, Mureo Kasahara, Isao Miyairi
Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure...
July 2015: Pediatrics
Bin Yu, Lixia Liu, Dong Xing, Congcong Zhao, Zhenjie Hu
OBJECTIVE: To investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment. METHODS: A prospective observational study was conducted...
May 2015: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Darren M Roberts, Xin Liu, Jason A Roberts, Priya Nair, Louise Cole, Michael S Roberts, Jeffrey Lipman, Rinaldo Bellomo
INTRODUCTION: Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics. METHODS: We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL, and volume of distribution (Vd) by non-linear mixed-effects modelling...
2015: Critical Care: the Official Journal of the Critical Care Forum
Katja M Gist, Tomoyuki Mizuno, Stuart L Goldstein, Alexander Vinks
OBJECTIVES: Milrinone is an inotropic agent with vasodilating properties used in the treatment of ventricular dysfunction. Milrinone is predominantly eliminated by the kidneys and accumulates in the setting of acute kidney injury (AKI). The purpose of this study was to evaluate milrinone pharmacokinetics in children with AKI with or without continuous renal replacement therapy (CRRT). METHODS: Retrospective collection of milrinone therapeutic drug monitoring data in patients with AKI, including those requiring CRRT, through chart review from January 2008 to March 2014...
December 2015: Therapeutic Drug Monitoring
Darren M Roberts, Xin Liu, Jason A Roberts, Priya Nair, Louise Cole, Michael S Roberts, Jeffrey Lipman, Rinaldo Bellomo
INTRODUCTION: Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg/hour) and lower (25 mL/kg/hour) intensity CRRT on antibiotic pharmacokinetics. METHODS: We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL and volume of distribution (Vd) by nonlinear mixed effects modelling...
December 2015: Critical Care: the Official Journal of the Critical Care Forum
Atsuo Nakamura, Osamu Takasu, Yoshiro Sakai, Teruo Sakamoto, Norio Yamashita, Shinjiro Mori, Toshio Morita, Masakazu Nabeta, Nobuhisa Hirayu, Naomasa Yoshiyama, Mariko Moroki, Keita Tashiro, Mikinori Kannae
We performed high-dose loading (12 mg/kg every 12 h for 48 h; 4 doses total) of teicoplanin (TEIC) in patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections, with the goal of achieving target serum concentration (TEICc) ≥ 15 mg/l within 48 h of starting administration. The safety and effectiveness of the fixed, early-stage administration method were evaluated across a range of kidney dysfunction severity levels. TEIC high-dose loading was administered to 106 patients with MRSA infection from February 2010 to February 2013...
June 2015: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Jeffrey J Cies, Wayne S Moore, Kyle Miller, Christine Small, Dominick Carella, Susan Conley, Jason Parker, Paul Shea, Arun Chopra
Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS...
February 2015: Pharmacotherapy
Patrick M Honoré, Rita Jacobs, Elisabeth De Waele, Jouke De Regt, Thomas Rose, Viola Van Gorp, Olivier Joannes-Boyau, Willem Boer, Herbert D Spapen
The knowledge on PK behavior of steroid drugs such as prednisolone or prednisone has indeed been expanding but at a rather slow pace. First, convenient, rapid, and specific determination of plasma levels of these steroids was largely indebted to the breakthrough of high performance liquid chromatography (HPLC). Second, prednisolone is non-linearly protein-bound. Since unbound prednisolone is the biologically active compound, only the measurement of this free fraction in plasma is relevant. Third, the short half-life of prednisolone precludes to reach steady-state levels and requires determination of the area under the concentration-time curve...
2014: Blood Purification
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