Pediatric Continuous Renal Replacement Therapy

Pediatric Continuous Renal Replacement Therapy

Farahnak Assadi Fatemeh Ghane Sharbaf Pediatric Continuous Renal Replacement Therapy Principles and Practice

Farahnak Assadi, M.D. Professor Emeritus Department of Pediatrics Section of Nephrology Rush University Medical Center Chicago, IL, USA Fatemeh Ghane Sharbaf, M.D. Associate Professor Department of Pediatrics Section of Nephrology Mashhad University of Medical Sciences Mashhad, Iran ISBN 978-3-319-26201-7 DOI 10.1007/978-3-319-26202-4 ISBN 978-3-319-26202-4 (ebook) Library of Congress Control Number: 2015959353 Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com)

This book is dedicated to all patients for whom we care and always teach us so much.

Preface Acute kidney injury (AKI) is a common cause of morbidity and mortality rates in critically ill patients requiring intensive care therapies (40 50 %). The incidence of AKI varies from 5 % of all hospitalized patients to 30 40 % of patients admitted to the pediatric intensive care unit. The critically ill children with AKI often have multiple organ dysfunctions and are frequently treated with several drugs including antibiotics, anticonvulsants, vasopressors, and antihypertensive and cardiovascular agents or which require appropriate dosing and interval. Despite significant improvements in the care of critically ill patients, the mortality and morbidity associated with AKI remains high (>50 %) and can lead to end-stage renal disease. Approach to the treatment of AKI patients requiring dialysis has gone under evolution with the advent of continuous renal replacement therapy (CRRT) techniques over the last two decades. Critically ill and hemodynamic instable children better tolerate CRRT than the intermittent hemodialysis. CRRT technology attempts to replace the excretory function of the kidney. CRRT provides a slow and gentle fluid removal from body much like the native kidneys and removes inflammatory mediators of sepsis such as interleukin, TNF-alpha, and complement. CRRT also provides adequate nutritional support for the catabolic AKI patients, a controlled desired fluid balance. Many AKI patients receiving CRRT suffer from multiple organ dysfunctions and have various types of medications including antibiotics, anticonvulsants, anticoagulants, and cardiovascular agents. Drugs predominantly eliminated by the normal kidneys often undergo substantial changes by CRRT. Therefore, a dose adjustment is required to prevent under dosing of the medication or drug toxicity. Unfortunately, few clinical studies have been published, and few drugs have been studied pharmacoclinically in intensive care patients. Many guidelines for drug dosing during CRRT are extrapolated from experiences with adult chronic hemodialysis, and there has been a relative paucity of published data about drug dosing during CRRT in critically ill children. Doses used in adults CRRT cannot be directly applied to these children, as the CRRT dialysate prescription and pharmacokinetics are different in adults compared with children. Failure to correctly dose may result in either drug toxicity or treatment failure. In order to understand the optimal drug vii

viii Preface dosing for children receiving CRRT, one must understand the pattern of water and solutes transport through a semipermeable membrane by all forms of CRRT. In this book, we review the current understanding of CRRT techniques, with a focus on drug dosing in critically ill children receiving CRRT. The effect of CRRT on drug pharmacokinetics, which provides guidelines whether or not dose adjustment is required, is provided in an accompanying reference table. Variations in the drug properties regarding their molecular weights, dialysis and blood flow rates, and dialysis membranes are discussed. The book also provides a simple and easy method for estimating drug clearance as a function of total creatinine clearance when the information on the pharmacokinetics of a particular drug is not available. In this book, we provide a series of challenging, clinically oriented case studies. The selected case reports focus on the essential aspects of the patient s presentation and laboratory data and management to accelerate recovery. A series of logical questioning from the presentation is followed by a detailed explanation that reviews recent publications and translates emerging areas of science into data that is useful at the bedside. We hope that the book will expand the clinical knowledge of nephrology and critical care trainees and other practicing physicians from different specialties who are frequently involved in the care of critically ill children suffering from severe AKI to improve and sustain their quality of life. We are grateful to the staff at Springer Publishers, Inc., for their outstanding editorial contributions to this endeavor and all those who have dedicated their skills to make this effort entirely possible. Chicago, IL, USA Mashhad, Iran Farahnak Assadi Fatemeh Ghane Sharbaf

Contents 1 Introduction: Acute Kidney Injury and Continuous Renal Replacement Therapy... 1 Introduction... 1 Acute Kidney Injury... 4 Definition... 4 The RIFLE Criteria... 5 Determination of Glomerular Filtration Rate... 7 Urinary AKI Biomarkers... 9 AKI Pathogenesis... 10 Patient-Related Risk Factors... 11 AKI Etiology... 11 Drug-Induced AKI... 19 Prevention Strategies... 23 Practical Considerations to Drug Dosing in AKI... 28 2 Water and Solute Movements: Basic Physiology... 35 Basic Concept of Solute Transport Mechanism... 35 Convection Transport Mechanism... 35 Diffusion Transport Mechanism... 37 Hemofiltration (Convection) Versus Hemodialysis (Diffusion)... 38 Adsorption Transport Mechanism... 39 References... 40 3 Continuous Renal Replacement Therapy (CRRT)... 41 Principle of Continuous Renal Replacement Therapy... 41 Advantages of Continuous Renal Replacement Therapy... 44 Indications for CRRT... 46 Practical Considerations for Pediatric CRRT... 47 Timing of CRRT... 47 Kinetic Modeling of Solute Clearance... 48 CRRT Dosing Recommendation... 48 CRRT Modality Choice... 49 ix

x Contents Slow Continuous Ultrafiltration... 49 Continuous Veno-venous Hemofiltration (CVVH)... 51 Replacement Fluid During CVVH: Pre-filter Versus Post-filter... 53 Continuous Veno-venous Hemodialysis (CVVHD)... 54 Continuous Veno-venous Hemodiafiltration... 55 Choosing Between the CVVH and CVVHD... 57 Combined CRRT and Extracorporeal Membrane Oxygenation... 58 CRRT Solutions... 59 Vascular Access and Catheter Size... 61 Monitoring... 62 CRRT Machinery... 63 Extracorporeal Blood Volume... 63 Intravascular Blood Volume Determination... 64 Hemofilter Membrane... 65 References... 65 4 CRRT Prescription... 71 CRRT Technical Considerations... 71 Ultrafiltration Rates (Removal Rates)... 71 Calculating the Desired Patient Fluid Removal Rate... 72 Blood Flow Rates... 72 Dialysate/Replacement Solution Flow Rates... 72 Net Fluid Balance... 73 Circuit Priming... 74 Anticoagulation... 74 Heparin-Free CRRT... 75 Heparin Protocol... 75 Citrate Dextrose (ACD)... 77 Citrate Protocol for CVVH (PRISMA)... 77 Prostacyclin... 81 Nutrition... 82 CRRT Complications and Troubleshootings... 85 CRRT Outcome... 90 Management of Electrolyte Imbalances During CRRT... 90 Azotemia... 91 Hyponatremia... 91 Hypernatremia... 91 Metabolic Acidosis... 91 Metabolic Alkalosis... 91 Hypercalcemia... 91 Hypocalcemia... 91 Hypomagnesemia... 92 Hypermagnesemia... 92 Hypophosphatemia... 93 Hypo- and Hyperkalemia... 93 References... 94

Contents xi 5 Pharmacokinetics of CRRT... 99 Drug Removal During CRRT: Basic Principles... 99 Absorption... 103 Distribution... 104 Drug Dosing During CRRT... 107 Factors Influencing the Clearance of Drugs During CRRT... 108 Sieving Coefficient (SC)... 108 Protein Binding... 109 Volume of Distribution... 109 Half-Life... 110 Water Solubility... 111 Plasma Clearance... 111 CRRT Membrane... 111 Blood and Dialysate Flow Rates... 112 CRRT Impact on Pharmacokinetic Parameters... 112 Drug Dosage Adjustments in CRRT... 113 Loading Dose (LD)... 115 Maintenance Dose... 115 Antimicrobial Agents... 115 Analgesics, Sedatives, and Psychotropic Drugs... 117 Antihypertensive Agents... 117 Anticoagulants... 118 Endocrine Drugs... 118 Rheumatologic... 118 Anticonvulsants... 118 Vasopressors... 118 References... 118 6 Case Management... 121 Case Study... 121 Case Study... 123 Case Study... 124 Case Study... 126 Case Study... 127 Case Study... 128 Case Study... 129 Case Study... 130 Case Study... 131 Case Study... 132 References... 138 Appendix... 145 Index... 155

Abbreviations ACD ACE ACT ARF AKI ARDS APPT BP BUN CL CKD Cr CRRT CVVH CVVHD CVVHDF ECV ESRD GFR HD HF HIT ICU IHD IJV INR LMW MODS NSAID PD PICU Acid citrate dextrose Angiotensin-converting enzyme Activated clotting time Acute renal failure Acute kidney injury Acute respiratory distress syndrome Activated partial thromboplastin time Blood pressure Blood urea nitrogen Clearance Chronic kidney disease Creatinine Continuous renal replacement therapy Continuous veno-venous replacement therapy Continuous veno-venous hemodialysis Continuous veno-venous hemodiafiltration Extracorporeal volume End-stage renal failure Glomerular filtration rate Hemodialysis Hemofiltration Heparin-induced thrombocytopenia Intensive care unit Intermittent hemodialysis Internal jugular vein International normalization ratio Low molecular weight Multiple-organ dysfunction syndrome Nonsteroidal anti-inflammatory drug Peritoneal dialysis Pediatric intensive care unit xiii

xiv Abbreviations PK PT RCA RIFLE RRT RVU SC SCUF SIRS T 1/2 TMP TPN UF V d Pharmacokinetics Prothrombin time Regional citrate anticoagulation Risk, injury, failure, loss, end-stage kidney disease Renal replacement therapy Relative unit value Sieving coefficient Slow continuous ultrafiltration Systemic inflammatory response syndrome Half-life Transmembrane pressure Total parenteral nutrition Ultrafiltration Volume distribution