MP264A PREDICTIVE MODEL FOR SUCCESSFUL CONVERSION OF CONTINUOUS RENAL REPLACEMENT THERAPY TO INTERMITTENT HEMODIALYSIS IN CRITICALLY ILL PATIENTS

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

Pharmacy ◽

10.3390/pharmacy8010018 ◽

2020 ◽

Vol 8 (1) ◽

pp. 18 ◽

Cited By ~ 1

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.

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Continuous Renal Replacement Therapy for Critically Ill Patients: An Update

Journal of Intensive Care Medicine ◽

10.1177/088506669400900602 ◽

1994 ◽

Vol 9 (6) ◽

pp. 265-280 ◽

Cited By ~ 28

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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CONTINUOUS RENAL REPLACEMENT THERAPY VS INTERMITTENT HEMODIALYSIS AND RECOVERY OF RENAL FUNCTION IN CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY

CHEST Journal ◽

10.1016/j.chest.2020.08.658 ◽

2020 ◽

Vol 158 (4) ◽

pp. A701

Author(s):

Manuel Huerfano ◽

Roberto Buitrago ◽

Maria Jose Vargas ◽

Gabriel Ortiz Jaimes ◽

Maurcio Sanabria ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Intermittent Hemodialysis

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1481 ◽

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)

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