scholarly journals Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Megan E. Kunka ◽  
Elizabeth A. Cady ◽  
Heejung C. Woo ◽  
Melissa L. Thompson Bastin
Keyword(s):  
Case Report ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Patient Specific ◽  
Critically Ill Patient ◽  
Pharmacokinetic Parameters ◽  
Intermittent Hemodialysis ◽  
Pharmacokinetic Studies

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 disseminatedCryptococcus neoformansinfection. 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. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued.Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient’s actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Lacosamide Pharmacokinetics in a Critically Ill Patient During Continuous Renal Replacement Therapy

2018 ◽  
Vol 33 (3) ◽  
pp. 395-398 ◽  
Author(s):  
Patrick M. Wieruszewski ◽  
Arnaldo Lopez-Ruiz ◽  
Robert C. Albright ◽  
Jennifer E. Fugate ◽  
Erin Frazee Barreto
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Drug Exposure ◽  
Critically Ill Patient ◽  
Therapeutic Drug ◽  
Intermittent Hemodialysis ◽  
Pharmacokinetic Studies ◽  
Extracorporeal Removal

The objective of this study is to describe the pharmacokinetics of lacosamide in a critically ill adult during continuous venovenous hemofiltration (CVVH). A 78-year-old male developed sepsis and acute kidney injury following cardiac surgery. He was initially treated with intermittent hemodialysis but developed nonconvulsive status epilepticus at the end of the first session and was subsequently initiated on CVVH. In addition to lorazepam boluses, levetiracetam, and midazolam infusion, he was loaded with lacosamide 400 mg intravenously and started on 200 mg intravenously twice daily as maintenance therapy. Noncompartmental modeling of lacosamide pharmacokinetics revealed significant extracorporeal removal, a volume of distribution of 0.69 L/kg, elimination half-life of 13.6 hours, and peak and trough concentrations of 7.4 and 3.7 mg/L, respectively (goal trough, 5-10 mg/L). We found significant extracorporeal removal of serum lacosamide during CVVH, which was higher than previously reported. This led to subtherapeutic concentrations and decreased overall antiepileptic drug exposure. The relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations.

scholarly journals Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 18 ◽  
Author(s):  
Soo Min Jang ◽  
Sergio Infante ◽  
Amir Abdi Pour
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Intermittent Hemodialysis ◽  
Drug Dosing ◽  
Low Efficiency

Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

scholarly journals 1298. Population Pharmacokinetics of Ceftazidime-avibactam among Critically-ill Patients with and without Receipt of Continuous Renal Replacement Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S663-S664
Author(s):  
Ellen G Kline ◽  
Minh Hong T Nguyen ◽  
Erin K McCreary ◽  
Brett Wildfeuer ◽  
Josh Kohl ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Panel Member ◽  
Pharmacokinetic Parameters ◽  
Intermittent Hemodialysis ◽  
Review Panel ◽  
Research Grant

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is used to treat multidrug-resistant infections. There are limited pharmacokinetic (PK) data among critically-ill patients (pts) and no dosing recommendations for those receiving continuous renal replacement therapy (CRRT). Methods We conducted a PK study of CAZ-AVI among pts with and without CRRT. Serial blood samples were collected at 0 (pre-dose), 2, 4, 6, and 8 hours after CAZ-AVI administration. All doses were infused over 2h. Samples were centrifuged and plasma stored at -80°C until analysis by a Shimadzu Nexera XD UHPLC with a Shimadzu 8045 MS. Transitions were monitored in positive mode for CAZ (m/z 274.05 < 80.05) and negative mode for AVI (264.00 < 95.90). The assay was reproducible and linear over a range of 0.1 – 20 µg/mL for AVI and 1 – 200 µg/mL for CAZ. non-compartmental analyses were used. Results 96 plasma samples from 20 pts were included in the study. Median age was 56 years (range: 31 – 74), 55% were male, and 90% were in the ICU at the time of collection. CZA dosing regimens included 2.5g IV q 8h (n=15), 1.25g IV q 8h (n=2), 0.94g IV q 24h (n=1), and 0.94g IV q 48h (n=2). 7 pts received CRRT (median blood and dialysate flow rates were 250 mL/min and 2.5 L/h, respectively; 86% received 2.5g IV q 8h) and 2 pts received intermittent hemodialysis (iHD). Among remaining pts, median creatinine clearance (CrCl) by Cockcroft-Gault was 91ml/min (range: 37 – 168 ml/min). PK values for CAZ and AVI are shown in the Table. Individual concentration-time profiles for patients receiving 2.5g IV q 8h are shown in the Figure. For patients receiving 2.5g IV q8h, CAZ and AVI median (IQR) AUCs were 525.6 hr*µg/ml (403.2, 762.0) and 83.7 (57.3, 129.5), respectively. For those on CRRT receiving the same dose, CAZ and AVI median (IQR) AUCs were 450.2 (450.0, 558.4) and 102.4 (100.7, 142.3), respectively. CAZ pharmacodynamics (PD) targets of 100% fT > 1x and 4x MIC were achieved in 90% and 55% of pts, respectively. AVI PD targets of 100% fT > 1 and 2.5µg/mL were achieved in 100% and 80% of pts, respectively. Treatment-emergent adverse events were not reported in any case. Ceftazidime and avibactam pharmacokinetic parameters among critically-ill patients Conclusion Among this cohort of critically-ill pts, CAZ and AVI exposures varied; however, most pts achieved PD targeted exposures, including those patients receiving CRRT and a standard dosing regimen of 2.5g IV q 8h. Disclosures Erin K. McCreary, PharmD, Entasis (Advisor or Review Panel member)Summit (Advisor or Review Panel member) Ryan K. Shields, PharmD, MS, Allergan (Advisor or Review Panel member, Research Grant or Support)Entasis (Advisor or Review Panel member)Melinta (Research Grant or Support)Menarini (Consultant)Merck (Advisor or Review Panel member, Research Grant or Support)Shionogi (Advisor or Review Panel member, Research Grant or Support)Summit (Advisor or Review Panel member)Tetraphase (Research Grant or Support)Venatorx (Advisor or Review Panel member, Research Grant or Support)

scholarly journals Imipenem dosing recommendations for patients undergoing continuous renal replacement therapy: systematic review and Monte Carlo simulations

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dhakrit Rungkitwattanakul ◽  
Taniya Charoensareerat ◽  
Pathakorn Kerdnimith ◽  
Nutsinee Kosumwisaisakul ◽  
Piyakamol Teeranaew ◽  
...  
Keyword(s):  
Systematic Review ◽  
Monte Carlo ◽  
Renal Replacement Therapy ◽  
Monte Carlo Simulations ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Optimal Dose ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Dosing Regimens

Abstract Background The appropriate dosing of imipenem for critically ill AKI patients undergoing CRRT remains scarce. Purpose This study aimed to (1) gather the available published pharmacokinetic studies conducted in septic patients receiving continuous renal replacement therapy (CRRT) and (2) to define the optimal imipenem dosing regimens in these populations via Monte Carlo simulations. Methods The databases of PubMed, Embase, and ScienceDirect were searched from inception to May 2020. We used the Medical Subject Headings of “Imipenem,” “CRRT,” and “pharmacokinetics” or related terms or synonym to identify the studies for systematic reviews. A one-compartment pharmacokinetic model was conducted to predict imipenem levels for the initial 48 h of therapy. The pharmacodynamic target was 40% of free drug level above 4 times of the MIC (40% fT > 4 MIC). The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Results Eleven articles were identified and included for our systematic review. The necessary pharmacokinetic parameters such as the volume of distribution and the CRRT clearance were mentioned in 100 and 90.9%, respectively. None of the current studies reported the complete necessary parameters. A regimen of 750 mg q 6 h was the optimal dose for the predilution-CVVH and CVVHD modality with two effluent rates (25 and 35 mL/kg/h) for the pharmacodynamic target of 40% fT > 4MIC. Conclusions None of the current studies showed the complete necessary pharmacokinetic parameters for drug dosing. Pharmacodynamic target significantly contributed to imipenem dosing regimens in these patients. Different effluent rates and types of CRRT had minimal impact on dosing regimens. Clinical validation of the recommendation is necessary.

scholarly journals Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update

2019 ◽  
Vol 54 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Brian M. Hoff ◽  
Jenana H. Maker ◽  
William E. Dager ◽  
Brett H. Heintz
Keyword(s):  
Renal Function ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Response To Therapy ◽  
Intermittent Hemodialysis ◽  
Intermittent Renal Replacement Therapy ◽  
Antibiotic Dosing

Objective: To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. Data Sources: A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. Study Selection and Data Extraction: All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Data Synthesis: Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. Relevance to Patient Care and Clinical Practice: This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Conclusions: Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient’s needs.

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