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 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.

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 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.

Continuous Renal Replacement Therapy for Critically Ill Patients: An Update

1994 ◽  
Vol 9 (6) ◽  
pp. 265-280 ◽  
Author(s):  
Eric F. H. van Bommel ◽  
Karel M. L. Leunissen ◽  
Willem Weimar
Keyword(s):  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Fluid Balance ◽  
Critically Ill Patients ◽  
Clinical Aspects ◽  
Intermittent Hemodialysis ◽  
Organ Systems

van Bommel EFH, Leunissen KML, Weimar W. Continuous renal replacement therapy for critically ill patients: an update. J Intensive Care Med 1994; 9: 265–280. Despite continuous progress in intensive care during the last decades, the outcome of critically ill patients in whom acute renal failure (ARF) develops is still poor. This outcome may be explained partially by the frequent occurrence of ARF as part of multiple organ systems failure (MOSF). In this complex and unstable patient population, the provision of adequate renal support with either intermittent hemodialysis or peritoneal dialysis may pose major problems. Continuous renal replacement therapy (CRRT) is now increasingly accepted as the preferred treatment modality in the management of ARF in these patients. The technique offers adequate control of biochemistry and fluid balance in hemodynamically unstable patients, thereby enabling aggressive nutritional and inotropic support without the risk of exacerbating azotemia or fluid overload. In addition, experimental and clinical data suggest that CRRT may have a beneficial influence on hemodynamics and gas exchange in patients with septic shock and (nonrenal) MOSF, independent of an impact on fluid balance. We review both technical and clinical aspects of various continuous therapies, including their impact on serum drug levels and nutrient balance. In addition, an attempt is made to clarify the possible beneficial role of CRRT in reducing patient morbidity and mortality in the ICU.

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