acute continuous renal replacement therapy

Acute Continuous Renal Replacement Therapy

DEVELOPMENTS IN NEPHROLOGY

Cheigh, J.S., Stenzel, K.H., Rubin, A.L., eds.: Manual of Clinical Nephrology of the Rogosin Kidney Center. 1981. ISBN 90-247-2397-3.

Nolph, K.D., ed.: Peritoneal Dialysis. 1981. ISBN 90-247-2477-5.

Gruskin, A.B. and Norman, M.E., eds.: Pediatric Nephrology. 1981. ISBN 90-247-2514-3.

Schlick, 0., ed.: Examination of the Kidney Function. 1981. ISBN 0-89838-565-2.

Strauss, J., ed.: Hypertension, Fluid.,Electrolytes an9.Tubulopathies in Pediatric Nephrology. 1981. ISBN,'90-247-263j-6.

Strauss, J., ed.: Neonatal Kidney and Fluid-Electrolytes. 1983. ISBN 0-89838-575-X.

Strauss, J., ed.: Acute Renal Disorders and Renal Emergencies. 1984. ISBN 0-89838-663-2.

Didio, L.J.A. and Motta, P.M., eds.: Basic, Clinical and Surgical Nephrology. 1985. ISBN 0-89838-698-5.

Friedman, E.A. and Peterson, C.M., eds.: Diabetic Nephropathy: Strategy for Therapy. 1985. ISBN 0-89838-735-3.

Dzurik, R., Lichardus, B. and Guder, W., eds.: Kidney Metabolism and Function. 1985. ISBN 0-89838-749-3.

Strauss, J., ed.: Homeostasis, Nephrotoxicity, and Renal Anomalies in the Newborn. 1986. ISBN 0-89838-766-3.

Oreopoulos, D.G., ed.: Geriatric Nephrology. 1986. ISBN 0-89838-781-7.

Paganini, E.P., ed.: Acute Continuous Renal Replacement Therapy. 1986. ISBN 0-89838-793-0.

Cheigh, J.S., Stenzel, K.H. and Rubin, A.L., eds.: Hypertension in Kidney Disease. 1986. ISBN 0-89838-797-3.


edited by

Emil P. Paganini, M.D., F.A.C.P. Head, Section of Dialysis and Extracorporeal Therapy Department of Hypertension and Nephrology The Cleveland Clinic Foundation Cleveland, Ohio, USA

~ ., Martinus Nijhoff Publishing a member of the Kluwer Academic Publishers Group Boston I Dordrecht I Lancaster

Distributors for North America: Kluwer Academic Publishers 101 Philip Drive Assinippi Park Norwell, MA 02061, USA

Distributors for the UK and Ireland: Kluwer Academic Publishers MTP Press Limited Falcon House, Queen Square Lancaster LAI IRN, UNITED KINGDOM

Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre Post Office Box 322 3300 AH Dordrecht, THE NETHERLANDS

Library of Congress Cataloging-in-Publication Data Main entry under title:

Acute continuous renal replacement therapy.

(Developments in nephrology) I. Renal insufficiency-Treatment. 2. Continuous

arteriovenous hemofiltration. 3. Artificial kidney. I. Paganini, Emil P. II. Series. RC918.R4A325 1986 617'.461059 85-32037

ISBN-13: 978-0-89838-793-3 001: 10.1007/978-1-4613-2311-2

e-ISBN-13: 978-1-4613-2311-2

Copyright 1986 by Martinus Nijhoff Publishing, Boston Reprint of the original edition 1986

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photography, recording, or otherwise, without written permission of the publisher, Martinus Nijhoff Publishing, 101 Philip Drive, Assinippi Park, Norwell, MA 02061.

Second printing

This book is dedicated to the memory of my physician father who introduced me to medicine, to the memory of Peter Kramer whose efforts began continuous arteriovenous hemo-filtration, and to the continued support of my wife, Loretta and children, Elizabeth, Stefanie, and Julia.

CONTENTS

LIST OF CONTRIBUTORS

PREFACE

1. ULTRAFILTRATION/HEMOFILTRATION OVERVIEW: WHERE DOES CAVH FIT? Lee W. Henderson, M.D.

ix

xiii

1

2. CONTINUOUS REPLACEMENT MODALITIES IN ACUTE RENAL DYSFUNCTION 7 Emil P. Paganini, M.D., F.A.C.P.

3. TRANSPORT IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION AND SLOW CONTINUOUS ULTRAFILTRATION 43 Michael J. Lysaght, Ph.D. and Daniel Boggs

4. THE PRACTICAL TECHNICAL ASPECTS OF SLOW CONTINUOUS ULTRAFILTRATION (SCUF) AND CONTINUOUS ARTERIOVENOUS HEMOFILTRATION (CAVH) 51 Samuel Swann, C.D.T. and Emil P. Paganini, M.D., F.A.C.P.

5. FLUID BALANCE IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION 79 H. J. Schurek, M.D.

6. HEMOFILTRATION AND ULTRAFILTRATION: NURSING CONCERNS 91 Gayle R. Whitman, M.S.N., R.N., C.C.R.N.

7. HYPERALIMENTATION IN ACUTE RENAL FAILURE 113 Eben I. Feinstein, M.D., F.A.C.P.

8. CONTINUOUS ARTERIOVENOUS HEMOFILTRATION - THE CONTROL OF AZOTEMIA IN ACUTE RENAL FAILURE 123 C. J. Olbricht, M.D.

9. THE PREDILUTION MODE FOR CONTINUOUS ARTERIOVENOUS HEMOFILTRATION 143 Andre A. Kaplan, M.D.

10. NUTRITION IN ACUTE RENAL FAILURE: TREATMENT MADE POSSIBLE BY CONTINUOUS ARTERIOVENOUS HEMOFILTRATION (CAVH) Robert H. Bartlett, M.D.

173

11. DRUG KINETICS AND CONTINUOUS ARTERIOVENOUS HEMOFILTRATION 185 Thomas A. Go1per, M.D., F.A.C.P.

vii

viii Contents

12. CONTINUOUS ARTERIOVENOUS HEMOFILTRATION IN INFANTS 201 Claudio Ronco, M.D.

13. CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - LABORATORY EXPERIENCE AND THEORY 247 Harold Bregman, M.D. and Todd S. lng, M.D.

14. CONTINUOUS ARTERIOVENOUS HEMODIALYSIS - CLINICAL EXPERIENCE 255 Robert P. Geronemus, M.D. and Neil S. Schneider, M.D.

15. CONTINUOUS AMBULATORY PERITONEAL DIALYSIS IN ACUTE RENAL FAILURE 269 Martin J. Schreiber, Jr., M.D.

16. CONTINUOUS ARTERIOVENOUS HEMOFILTRATION - APPLICATIONS OTHER THAN FOR RENAL FAILURE 283 Ernest WoIner, M.D.

LIST OF CONTRIBUTORS

Robert H. Bartlett, M.D. Department of Surgery University of Michigan Ann Arbor, Michigan 48109

Daniel Boggs, Engineer Specialist Material and Membrane Technology Center (RLT-OZ) Travenol Laboratories Round Lake, Illinois 60073

Harold Bregman, M.D. Director, Nephrology Department Lutheran General Hospital 1775 Dempster Street Park Ridge, Illinois 60068 Clinical Assistant Professor of Medicine University of Illinois School of Medicine 18513 West Polk Avenue Chicago, Illinois 60612

Eben I. Feinstein, M.D., F.A.C.P. Associate Professor of Clinical Medicine University of Southern California School of Medicine Los Angeles, California 90033

Robert P. Geronemus, M.D. - P.A. 4900 West Oakland Park Boulevard, Suite 302 Lauderdale Lakes, Florida 33313

Thomas A. Golper, M.D., F.A.C.P. Associate Professor of Medicine Division of Nephrology and Hypertension Director of Clinical Nephrology, Adult CAPO and Special Extracorporeal Services Oregon Health Sciences University Portland, Oregon 97201

ix

x

Lee W. Henderson, M.D. Professor of Medicine University of California at San Diego Veterans Administration Medical Center San Diego, California 94121

Todd S. lng, M.D. Chief of Nephrology Veterans Administration Hospital Hines, Illinois 60141 Professor of Medicine Loyola University Stritch School of Medicine Maywood, Illinois 60153

Andre A. Kaplan, M.D. Divisions of Nephrology Departments of Medicine University of Connecticut School of Medicine Farmington, Connecticut 06032 Veterans Administration Medical Center Newington, Connecticut 06111

Michael Lysaght, Ph.D. Material and Membrane Technology Center (RLT-OZ) Travenol Laboratories Round Lake, Illinois 60073

C. J. Olbricht, M.D. Assistant Professor of Medicine Center of Internal Medicine Department of Nephrology Hannover Medical School 0-3000 Hannover 61, PO 180, FRG

Contributors

Contributors

Emil P. Paganini, M.D., F.A.C.P. Head, section of Dialysis and Extracorporeal Therapy Department of Hypertension and Nephrology The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, Ohio 44106

Claudio Ronco, M.D. Associate Professor Department of Nephrology and Dialysis Unit St. Bortolo Hospital Vicenza, Italy

Neil S. Schneider, M.D. - P.A. 4900 West Oakland Park Boulevard, Suite 302 Lauderdale Lakes, Florida 33313

Martin J. Schreiber, Jr., M.D. CO-Director, Continuous Ambulatory Peritoneal Dialysis Program Section of Dialysis and Extracorporeal Therapy Department of Hypertension and Nephrology The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, Ohio 44106

H. J. Schurek, M.D. Center of Internal Medicine Department of Nephrology Hannover Medical School 0-3000 Hannover 61, PO 180, FRG

xi

xii

Samuel Swann, C.D.T. Head Dialysis Technician Hospital Acute Dialysis unit The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, Ohio 44106

Gayle R. Whitman, M.S.N., R.N., C.C.R.N. Department Chairman, Cardiac Nursing Department of Hospital Nursing The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland, Ohio 44106

Professor Ernest Wolner, M.D. Head, Department of Surgery University of Vienna Vienna, Austria 1090

Contributors

PREFACE

The initial observations of dialytic support were brought from the laboratory and confined to patients with reversible acute renal failure. The thought at that time was one of short term maintenance. It was theorized that removal of waste products from the blood, albeit incomplete and inefficient, might allow these patients time to regenerate damaged tubules and regain renal function. After a dis-appointing earlier experience in survival, greater sophisti-cation and broader practice refined the dialysis skills and reduced mortality.

It also became apparent that long periods of support were possible and successful attempts were then made in utilizing this technology in patients with chronic renal failure. These early young patients were a very select group who possessed only renal dysfunction and no other systemic involvement. Nonetheless, they demonstrated a one year survival of only 55-64%. There are presently over 80,000 patients on dialytic support in the United States and over 250,000 patients worldwide dependent on artificial replace-ment. Mortality statistics vary but despite a 20-30% systemic disease involvement and a fifth decade average age in the North American experience, the one year survival has risen to apparently 90%.

Acute renal failure support has also demonstrated a growth in both its cognitive and technological aspects. A more complete understanding of renal physiology has led to prevention of acute dysfunction in many areas, and applica-tion of hybrid intermittent technology has stabilized the majority of ARF patients. There still remained, however, an inability to allow these patients free access to fluid in the form of hyperalimentation or medications. Further, many were unable to tolerate the rapid changes necessary with the intermittent approach. Thus, the evolution of continuous renal replacement has been applied to oliguric acute renal failure.

xiii

xiv Preface

This book has drawn together the world authorities on acute continuous renal therapy and has asked the questions: who, what, when, where, and why. Designed for internists, surgeons, intensivists, nephrologists, allied critical care nursing, and technical professions, the goal is to enhance the knowledge of those already using this therapy, and to inform and instruct those who are about to begin treatment.

This text is a "State of the Art" compendium of continuous therapies presently available or evolving. After an overview of its role in renal replacement (Henderson) and the evolution of continuous therapies over the past eight years (paganini), an insight into the transport of physiology of the membrane (Lysaght and Boggs) is given. The practical side of the therapies are explained by addressing the technical aspects of the system (Swann and Paganini), control of the fluid (Schurek), and nursing parameter (Whitman).

Theory and practice is continued in the evaluation of drug handling by CAVH (Golper), and the use of hyperalimenta-tion in acute renal failure (Feinstein) as well as with patients on CAVH (Bartlett) The control of azotemia (Olbricht) and variation such as predilution CAVH (Kaplan) round out the experience. The introduction of continuous hemodialysis both from the laboratory (Bregman and Ing) and patients' bedside (Geronemus), as well as application of access other than renal failure (Wolner) complete the discus-sion.

In contrast continuous renal

to rising medical costs replacement therapy

and complexity, enhances patient

stability, hospital tions.

simplifies medical management, and costs. Its future is limited only by our

reduces innova-

I would like to sincerely thank the artistic and photo-graphic help of Ann Paladino, Jim Reed, and Jeff Loerch, the editorial assistance of Shannon Henry, Helen Thams, and Louise Paskert, and especially the coordinating and secretarial arrangement of Cindy Owens and Jeannie Bongorno.

1 ULTRAFILTRATION/HEMOFILTRATION OVERVIEW: WHERE DOES CAVH FIT? L. HENDERSON University of California, San Diego, California

Hemofiltration was initiated as a test strategy to evaluate the pathophysiologic significance of "middle molecules" for the uremic patient (1,2). was devised for use in the patient with

As such, the system stable end stage

renal failure. As originally applied it was recognized to be at a disadvantage in the removal of low molecular weight solutes 350 daltons) when compared with hemodialysis. Many changes in how convective mass transport is applied have occurred since then. Postdilution versus predilution (3), hemodiafiltration (4-6) combining the best of both diffusion and convection, and continuous low efficiency hemofiltration for the treatment of acute renal failure (7) are some of the creative applications to which this ultrafiltration methodol-ogy has been put. In placing this spectrum of techniques into the perspective of "where does CAVH fit," I would wish to take a brief backward look in order to extrapolate the future.

The pioneering clinical work of Kolff in applying his artificial kidney logically took him first to the application of this device in a young woman with chronic renal failure (8) ("malignant hypertension and shrunken kidneys"), not acute renal failure as has been erroneously reported (9). Her survival of the artificial kidney treatment for more than four weeks, if not her uremia, was sufficiently encouraging to warrant the treatment of 15 more patients suffering from acute renal failure with but a single survivor (8). In spite of these dismal survival statistics, application of the tech-nique continued. Acute renal failure was the disease entity

1

2 UF/HF Overview

to which this new device was applied until the deliberate application to patients with chronic renal failure by Belding Scribner in the early 1960's plunged us into the era of maintenance dialysis (10).

In like token both hemofiltration and CAVH were tested first in the patient with chronic renal failure (11,12). Peter Kramer must be given full recognition for both identi-fying and popularizing CAVH for the treatment of acute renal

failure in Europe (7). His clinical application of CAVH initiated the exponential growth phase of this technique that we are presently experiencing. In the United States, atten-tion was focused more on the fluid removal aspects of this technique (12,13).

I venture to say that there will be numerous technical modifications and improvements in the hardware for CAVH just as there has been for hemodialysis. I believe that by coupling CAVH with parenteral nutrition it will swiftly be-come the "gold standard" for treatment of acute renal failure. A one out of 15 survival rate for the rotating drum may be considered a success only in the context of a very low baseline survival. The monumental efforts of early clinical investigators such as Bluemle and Teschan (14,15) showed that hemodialysis, and in particular aggressive application of hemodialysis ("prophylactic" rather than "crisis interven-tion" dialysis), offered an improved mortality in the patient with acute renal failure. The dire clinical status of this population renders mortality an insensitive parameter requiring an exceedingly large study number to achieve statistically significant information. The failure to report improved survival statistics with acute renal failure treated with CAVH must not be taken than as a negative finding (16-19)

I am confident that with time, CAVH in particular as it is coupled with parenteral hyperalimentation, will result in better wound healing, improved response to infection, and a lower overall morbidity and mortality.

L. Henderson 3

In the final extrapolation, I would suggest that just as the application of hemodialysis to acute renal failure eventuated in its widespread application to chronic renal failure so CAVH will be gradually translated into the chroni-cally applied wearable artificial kidney that has been the Holy Grail of artificial kidney investigators for low these many years.

It will be necessary to solve the chronic access problem (deja vu) and what to do about the large volumes of replace-

ment solution (1-20 L/day) that will not only be required but required in portable (potable?) form, as well as the problem of chronic anticoagulation. However, investigations are already ongoing in these areas and will be lent stimulus by the very success of CAVH in acute renal failure. I must confess to favoring a closed loop device as depicted in Figure 1 in which electro-oxidation (20) is used (an electrode compartment the size of a cigarette package) to combust all organics in the ultrafiltrate to oxygen, hydro-gen, carbon dioxide, and nitrogen with a small amount of

GOAL

PUMP VARIABLE RESISTANCE ~~ _____ F~ILTER~ _____ ~

1-2 LITERS EXCESS FLU 10 TO DRAIN

DETOXIFICATION - SORBENT - LOOSE R.O. - OTHER

Fig. 1. This goal for artificial kidney depicts a closed loop for the ultrafiltrate clude some means of dialysate reprocessing. design might obviate the need for a pump on side.

development (1) that would in-

Proper filter the blood inflow

4 UF/HF Overview

nonvolatile sulfate and phosphate that could be handled both by dietary protein and lipid selection and orally adminis-tered sorbents. Glucose and bicarbonate would of course have to be replaced, but a suitably structured diet with the periodic ingestion of alkali would not be an onerous regimen at all.

Lastly, the loop might be further closed, so to speak, by metering out the required amount of "urine" and channeling it percutaneously to the bladder for storage and its periodic convective transfer to an appropriate porcelain receptacle. This latter event would serve both physiologic and psycho-social ends.

May the flux be with you (21).

REFERENCES 1. Henderson LW: Development of a convective blood

cleansing technique. Proc lOth Ann Contractors Conf, Bethesda, Maryland, 130, 1977.

2. Henderson LW: The beginning of hemofiltration. In: Contributions to nephrology series. Eds: Beryne GM, Giovannetti S, Thomas S, Vol 32, Symposium on Hemofi1-tration Volume, Eds: Shaefer K, Koch KM, Quellhorst E, von Herrath, Publisher, Karger, 1, 1982.

3. Henderson LW: Pre vs. post dilution hemofiltration. Clin Nephro1 11:120, 1979.

4. Leber HW, Wizemann V, Goubeaud G, Rawer P, Schutter Ie G: Simultaneous hemofiltration/hemodialysis: An effective alternative to hemofiltration and conventional hemo-dialysis in the treatment of uremic patients. Clin Nephrol 9:115, 1978.

5. Cheung AK, Kato Y, Leypoldt JK, Henderson LW: Hemodia-filtration using a hybrid membrane system for self generation of diluting fluid. Trans Am Soc Artif Intern Organs 28:61, 1982.

6. von Albertini B, Miller JH, Gardner PW, Norris KC, Roberts CE, Shinaberger JH: High flux hemodiafiltra-tion. Abstract, Am Soc Nephrol 17 Ann Meeting 76, 1984.

7. Kramer P (editor): Arterio-venous hemofiltration, Vandenhoeck & Ruprecht Gottingen, 1982.

8. Kolff WJ: First clinical experience with the artificial kidney. Ann Intern Med 62:608, 1965.

9. McBride PT: Genesis of the artificial kidney. Chpt 3:9, 1979.

10. Quinton WE, Dillard DH, Cole JJ, Scribner BH: Eight months experience with cilastic-teflon bypass cannulas. Trans Am Soc Artif Intern Organs 8:236, 1962.

L. Henderson 5

11. Henderson LW, Besarab A, Michaels A, Bluemle LW Jr: Blood purification by ultrafiltration and fluid replace-ment (diafiltration). Trans Am Soc Artif Intern Organs 12:216, 1967.

12. Silverstein ME, Ford CA, Lysaght MJ, Henderson LW: Treatment of severe fluid overload by ultrafiltration. N Engl J Med 291:747, 1974.

13. paganini EP, Nakamoto S: Continuous slow flow ultrafil-tration in oliguric acute renal failure. Trans Am Soc Artif Intern Organs 26:203, 1980.

14. Bluemle LW Jr, Webster GD Jr, Elkinton JR: Acute tubular necrosis: Analysis of 100 cases with respect to mortality complications and treatment with and without dialysis. Arch Intern Med 104:180, 1959.

15. Teschan PE, Baxter CR, O'Brien TF, et al: Prophylactic hemodialysis in the treatment of acute renal failure. Ann Intern Med 53:922, 1960.

16. Lauer A, Saccaggi A, Ronco C, Belledonne M, Glabman S, Bosch J: Continuous arteriovenous hernofiltration in the critically ill patient. Ann Intern Med 99:455, 1983.

17. Kramer P, Bohler J, Kehr A, et al: Intensive care potential of continuous arteriovenous hemofiltration. Trans Am Soc Artif Organs 28:28, 1982.

18. Olbricht C, Mueller C, Schurek HJ, Stolte H: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am Soc Artif Intern Organs 28:33, 1982.

19. Kaplan AA, Longnecker RE, Folkert VW: Continuous arteriovenous hemofiltration. Ann Intern Med 100:358, 1984.

20. Wright JC: Electrochemical dialysate regeneration: The electro-oxidation of urea at the ruthenium titanium oxide electrode. Ph.D. Dissertation, Dept of Chern Engineering, Stanford Univ, 1982.

21. Kenobi 0: Personal Communication.

2 CONTINUOUS REPLACEMENT MODALITIES IN ACUTE RENAL DYSFUNCTION E. PAGANINI The Cleveland Clinic Foundation, Cleveland, Ohio

INTRODUCTION The occurrence of acute renal failure varies among

hospital settings, generally being more frequent in surgical/trauma units than medical areas. National figures are lacking and variable incidences can be obtained by merely changing the definition of acute renal failure. For example, defining acute renal failure as an acute rise in the serum creatinine level to < 3 mg/dL, a 5 to 20% incidence can be found in all open heart surgical procedures (1). However, defining the cutoff serum creatinine level > 5 mg/dL, a 2 to 5% incidence can be seen (2). If one considers only those patients who need artificial support then 1.2% incidence has been reported (3) following open heart surgery.

The etiology of acute renal failure encountered in our intensive care areas occurred in predominantly surgical (70%) settings, and the remainder occurred in medical situations. Ischemia (74%) was by far the most frequently identified cause; toxic (13%) and other causes (8%) were less prominent. Patients needing support of renal failure frequently had multiorgan compromise (60%) and thus represented a thera-peutic challenge of major proportions.

Until recently intermittent forms of therapy had been used for support in renal failure, with isolated ultrafiltra-tion (4,5) being used for fluid management and intermittent hemodialysis for electrolyte, acid/base, and azotemic control (6) Variants of those basic procedures have brought about combinations of therapy that enhance patient stability and allow for greater control of the end product. Table 1

7

8 Continuous Replacement Modalities

Table 1. Working definitions of available extracorporeal therapies.

Term Definition

Ultrafiltration (UF) The removal of plasma water and its solutes from blood by convective transport through a semipermeable membrane. May be done alone or before, during, or after hemodialy-sis. The sole purpose is fluid removal.

Hemodialysis (HD) A diffusion-based form of blood cleaning using dialysate interfacing with blood via a semipermeable mem-brane. Allows for fluid, electro-lyte, and acid-base balance as well as azotemic control.

Hemofiltration (HF) A convective mode of blood cleaning where ultrafiltration accounts for all solute removal. Can be viewed as a plasma water exchange with sterile fluid replacement.

Hemodiafiltration (HDF) A hybrid form of therapy combining both diffusive and convective mo-dalities.

reflects the working definitions of these therapeutic variations.

Recently, continuous extracorporeal therapeutic modalities have been applied to these patients (7,8). These methods bring a high level of hemodynamic stability, and have been predominantly applied to the sicker, unstable patient with multiorgan failure (9). The systems have also allowed improved fluid balance, permitting a higher intake to be achieved without the worry of fluid overload. As these therapies become more popular, greater understanding of the physiological responses and of indications for such therapy should occur. This chapter deals with the experience obtained in continuous therapies from 1977 through the

E. Paganini 9

present and will give insight into the evolution of an integrated system.

ISOLATED ULTRAFILTRATION Intermittent ultrafiltration.

Fluid removal has always been a goal of all renal replacement therapy, however, symptomatic hypotension because of fluid removal during hemodialysis is a common clinical problem. Although several studies of the hemodynamic instability of uremia have been done (10,11), there still remains a discordance as to the actual underlying cause. Kersh et al (12) have implicated autonomic insufficiency; Zucchelli et al (13) postulated a rapid removal of catechola-mine; and Kim et al (14) investigated body fluid volume changes. Separating the process of hydrostatic ultrafiltra-tion for fluid removal, i.e., isolated ultrafiltration (UF), from diffusion dialysis, Bergstrom et al (5) demonstrated a great de~ree of blood pressure stability. They attributed the stability to the lack of osmolar changes. Silverstein et al (15) noted stable blood pressure in patients with chronic heart failure while evaluating the stability of isolated ultrafiltration in chronic hemodialysis patients. We had noticed the active participation of the venous system in maintaining blood pressure (16,17), by way of maintained central volume.

MacIntyre et al (18) first reported in 1951 the tech-nique of cardiac output (CO) determination using 131I_ labelled human serum albumin in animals. Razzak et al (19) confirmed the accuracy of radioisotope techniques for CO determination in humans. To our knowledge our study represented the first direct measurement of CO and cardio-pulmonary volume (CPV) using radioisotope dilution techniques in patients subjected to UF (Fig. 1). co and CPV were determined from radionuclide dilution curves using an Ohio Nuclear scintillation camera. Following a bolus injection of 99mTC-labelled human serum albumin (99m Tc-HSA) (4 mCi pre-UF, 8 mCI post-UF), the bolus passages through the right and


CARDIAC OUTPUT

7.0 RV LV

6.5

lIJ 6.0 :i! II:: "-

II:: 5.5 lIJ a.. Ul I-z 5.0 ~ 0 0 C) 0 ..J 4.5

4.0

3.5 10 20 30 40 50

FRAME NO.

Fig. 1. Radioisotope technique cardiac output. Actual scan (top). lar time-activity curves (bottom).

for the determination of Right and left ventricu-

left ventricles were defined on the original computer print-out and displayed diagrammatically as time-activity curves. Cardiac output was determined from the formula: F = If C t:" T where I equals the product of blood volume and blood counts at the final dilution phase. C~T equals the counts per unit change of time. CPV is derived from the formula: MTT x CO/60 where MTT equals mean transit time, defined as the time elapsed between the right and left ventricular output curves. We had also investigated the changes in body fluid volumes and compartmental shifts as well as cardiac performance. As

E. paganini 11

in previous reports (5,15) the mean arterial pressure (MAP) remained quite stable despite the average removal of 1.6 L of fluid. Although extracellular fluid (ECF) and plasma volume (PV) dropped significantly, the PV/interstitial fluid volume (IF) ratio remained constant, denoting no disturbance in ECF partition. This is in sharp contrast to classic studies by Guyton et al (20) on hemorrhage where venous return decreased, resulting in a reduction of CO and MAP.

Stroke volume and the CO/CPV ratio remained unchanged. This implies no significant alteration in cardiac performance or function (21) and negates a major role in afterload reduc-tion in maintenance of stable co. Although no absolute change was noted in CPV, all but one of our patients showed a rise in the CPV, CO, and MAP. Brod (22) has noted that angiotensin infusion leads to constriction of peripheral veins and central redistribution of blood, resulting in a rise of central venous pressure. However, the role of angio-tensin was not evaluated in our studies.

We then began looking at the effectiveness of continual fluid removal with ultrafiltration in an effort to establish the possible selected use of ultrafiltration in congestive heart failure. Magnusson et al (23), using lung water measurements in dogs given oleic acid to induce pulmonary capillary dysfunction, noted that ultrafiltration was capable of inducing a marked decrease in lung water. In fact the dogs in the ultrafiltration group had a significant drop in the lung water content compared with both control dogs and dogs with a diuretic-induced negative fluid balance greater than that achieved via ultrafiltration. Colloidal oncotic pressures in the' diuretic and ultrafiltration group were similar, so greater sodium losses or the removal of some "pulmonary factor" with ultrafiltration were postulated.

Magilligan and Oyama (24) reported their use of inter-mittent ultrafiltration (IUF) during cardiopulmonary bypass in both mongrel dogs and ten patients. In both groups ultra-filtration was found to be both safe and effective in removal of excess fluid. Further, they demonstrated the effective-

12 continuous Replacement Modalities

Fig. 2. Slow continuous ultrafiltration using a Travenol 1500 dialyzer.

ness of ultrafiltration in removing lung water in their overhydrated patients.

Hemodynamic stability was enhanced by lowering the efficiency of ultrafiltration during therapy. However, this required a longer course of therapy to compensate for the lower removal rate. Avoiding the "peak and valley" effect of rapid intermittent removal was originally accomplished using a CF 1500 Capillary Dialyzer (Travenol Labs, Deerfield, Michigan) attached in series to a Scribner shunt (see Fig. 2). This arrangement, however, does not lend itself easily to continuous ultrafiltration. Table 2 lists the encountered difficulties and solutions.

Greater fluid removal was obtained with the use of the high-flux polysulfone membrane (Amicon Diafilter 20, Amicon Corp., Danvers, Mass.); earlier success with chronic renal failure (25-27) led to its use in unstable patients with acute renal failure. The early attempts at use were

E. paganini 13

Table 2. Difficulties encountered in slow continuous ultra-filtration.

Problem

Large pressure drop across dialyzer

Low ultrafiltration coefficient of membrane:

70 mL/hr without suction 150 mL/hr with suction

Large surface area and fiber length

Complicated procedure if suction assistance is used, poor nursing acceptance

Clinical Need

Minimal ~ 85 mmHg M.A.P.

Suction-assisted ultra-filtration

High heparin requirement to avoid clotting

Nursing training with equipment not usually handled

intermittent; later longer sessions approached continuous therapy (8). Slow continuous ultrafiltration.

Slow continuous ultrafiltration (SCUF) is defined as a continuous method of fluid removal at a rate not exceeding 5 mL/min, with or without peripheral fluid replacement; SCUF has fluid balance as its sole objective. Often used as an adjunct therapy to hemodialysis, it affords a high degree of stability during fluid removal in patients with acute renal failure.

The most important consideration in any form of continu-ous therapy is the selection of an appropriate access, since this is the only driving force used in the pumpless system. If blood flow is poor because of arterial inadequacy or venous occlusion, the flow characteristics will be greatly changed, which might dampen or limit the ultrafiltration potential. This is of greater importance when employing continuous arteriovenous hemofiltration (CAVH) , where the emphasis is on high ultrafiltration flows (QF) , but will also have an impact on SCUF even though the QF is usually less.


.lI.20

90-' I

60J I

3 0 J_~ttt--I

SCUF/CAUH THERAPY ACCESS TYPE

OJ~~~~~~~~--~~~~~ 7 9

8 .i.

YEAR .PERCUTAH ~SHUHTS

8 3

8 4

8 5

Fig. 3. Types of access used for slow continuous ultrafil-tration (SCUF) and continuous arteriovenous hemofiltration (CAVH) therapy.

In general vascular access is obtained either through surgically created arteriovenous connections (fistula, AV shunts) or by percutaneous cannulation of the arterial and venous systems. The technical aspects of creating these accesses are discussed elsewhere. However it should be noted that both percutaneous and surgical methods have their individual advantages and disadvantages. For example, while AV shunts are certainly easy to use, they are usually associated with minimal or no bleeding because of the open

,WII:! JL60

SCUF/CAVH THERAPY THERAPY TYPE

"II~~(JI~ Fig. 4. Use of slow continuous ultrafiltration (SCUF) and continuous arteriovenous hemofiltration (CAVH).

E. Paganini 15

procedure in their creation. They are easily checked for patency, and are rarely implicated in systemic complications. They are also the source of local infection, frequently clot, generally carry lower vessel pressures and flow, and destroy a future access site for a fistula if the patient were to need chronic support. Also, the clinical situation may have resulted in multiple venipunctures with resultant venous flow compromise, thus having a negative impact on shunt function.

The AV shunt can offer a powerful and useful access site for continuous as well as intermittent replacement therapy. Surgical expertise is necessary, however. Time is needed to choose appropriate vessels, dilate them when necessary, avoid vessel damage or tension, and stabilize the implants. This is nothing more than merely following established surgical procedures and giving appropriate attention to small details. The delay in awaiting the surgeon or in establishing the access may, at times, be considered a drawback to this method of entry.

Arteriovenous cannulation has become increasingly popular and over the past few years its use has increased in frequency in our institution as well (Fig. 3). The details of percutaneous technique are outlined elsewhere. However, it is of interest that the increased popularity of percutane-ous access is accompanied by an increase in the use of CAVH (Fig. 4). This is not totally by chance. The higher cir-cuitry pressures and blood flows achieved with the percutane-ous access allow a higher QF and therefore make CAVH exchanges more appropriate. Olbricht et al (28) noted an improved QF when using femoral arteriovenous cannulation rather than brachial AV shunts as access in performing CAVH. However if SCUF is employed, then modest filtration flows are generally more than adequate.

Table 3 compares AV cannulation of the femoral artery and vein with brachial AV shunts. We have been carrying out a prospective analysis of access complications and have found an equal incidence of possible access-related septic events to either method. While AV shunts have an increased inci-


Table 3. tion.

Comparison of AV shunt to percutaneous AV cannula-

Procedure Blood flow Hydrostatic

pressure Rapidity of

access Bleed ing

Ambulation Systemic

completion Clotting of

circuit Infection

Local Systemic

Complication on removal

AV shunt Low Low

Delay

Minimal

Yes Rare

Frequent

Frequent Rare Rare

open

local

AV cannulation closed High High

Immediate

Minimal (potential retro-peritoneal hematoma on removal)

No (strict bed rest) Infrequent (emboli,

thrombosis) Infrequent

Infrequent Rare Infrequent (arterial

cutaneous fistula hematoma)

dence of local infections, and a higher frequency of clot-ting, the femoral cannulation carries a much higher risk of bleeding and arteriocutaneous fistula formation.

The usual circuitry for SCUF is depicted in Figure 5. As with all continuous methods, there is no blood pump in the circuit and the system's blood flow and pressures are main-tained by the presSure difference between the arterial and venous systems.

If heparin is to be used, then a continuous drip apparatus is attached to the arterial line and the heparin delivered by way of an IV infusion pump. The ultrafiltration flow is also controlled. The filtration rate is "dialed in" on a second IV infusion pump, which allows for accurate collection without undue time commitment from the nursing staff. The rate of ultrafiltration during SCUF will there-fore depend upon the rate of intake, rather than dictating the intake rate as in CAVH.

Short arterial and venous lines are employed in both SCUF and CAVH at The Cleveland Clinic (Fig. 6) (29). These

E. Paganini 17

\

Fig. 5. Slow continuous ultrafiltration (SCUF) circuitry with IV infusion pump control.

lines were designed to allow for blood sampling, but are of pressures

pressure to this circuitry

such a length as to dissipate the systemic minimally, delivering the bulk of this filter. A full technical description of found in later chapters (Swann, Whitman). made continuous therapy without heparin

only the is

These lines have possible (30)

Figure 7 graphically demonstrates differences in reasons for interruptions of SCUF therapy (when heparin is used or not used) While there was a higher incidence of clotting with heparin than without, this difference was not statistically significant.

HEMODYNAMICS AND FILTRATION The laboratory work on ultrafiltration efficiency and

selectivity plus the enhanced hemodynamic stability obtained with isolated ultrafiltration in our patients undergoing


Fig. 6. Arterial and venous lines used in SCUF/CAVH at The Cleveland Clinic Foundation.

chronic dialysis seemed to indicate that continuous ultrafil-tration would be ideal for the oliguric patient with fluid overload. Many times these patients are so unstable that they are unable to tolerate standard hemodialysis: they have multiple hypotensive episodes during the run and may actually gain weight. Early attempts at using a cuprophane membrane proved to be unsatisfactory; using a synthetic plastic (po1y-sulfone) would perhaps allow delivery of the required ultra-filtration at the pressures present within the system without having to add complicated suction devices to enhance removal.

Early hemodynamic data on patients undergoing SCUF therapy are listed in Table 4. Of note was the absolute stability encountered during continuous ultrafiltration. Twenty-three hemodialysis-resistant patients with acute renal failure were placed on SCUF (9). Hemodynamic stability was again noted, thus allowing patients to receive needed medica-tion and eventually to stabilize.

Perhaps the most significant addition to the treatment of acute renal failure has been the ability to remove fluid in these highly unstable patients. We have reported that

E. Paganini 19

Table 4. Hemodynamic data.

Mean arterial pressure (mmHg)

Cardiac output (L/min)

No. 24 6 Pre-therapy 74.96 + 9.38 6.45 + 1.59 12 hr 76.79 -+ 8.45 -6.03 + 0.99 24 hr 74.57 + 8.88 6.13 +" 0.70 36 hr 72 .43 +" 11.12 6.48 +" 1. 74

by also with

significant removal of fluid with SCUF is accompanied stable hemodynamic parameters (8,31) but we are intrigued by the seeming improvement in cardiac function this form of fluid mobilization therapy. Although not sig-

output (Table

nificant, a definite trend toward increased cardiac and diminished systemic vascular resistance was noted 5). Whether this is due to afterload reduction, volume removal, or the elimination of a "myocardial depressant factor" is currently under investigation.

Evaluating oliguric patients with intraaortic balloon pumping and undergoing SCUF, we found continued hemodynamic stability, as shown graphically in Figure 8. Direct measure-ment of left arterial pressure as well as pulmonary artery

i..l.1!lJ:O 60-

I

45-' I

SCUF THERAPY INTERRUPTIONS

Fig. 7. Interruptions during slow continuous ultrafiltration (SCUF) therapy with and without heparin. (0) None, (l) Clotting, (2) Mechanical, (3) Hemodialysis.


Table 5. Patient hemodynamic data.

Mean arterial pressure (mmHg)

Cardiac output (L/min) Systemic vascular resistance (mL/min) Cardiac index

Pre-treatment

76.04 + 19.6 -

5.22 + 1.31

984.5 + 524.3 -

2.94 + .81 -

During SCUF

76.70 + 18.3 -

5.64 + 1.5

887 + 310.4

3.12 + .78

SCUF slow continuous ul trafil tration

Post-treatment

71.96 + 13.9 -

5.28 + 1.43

869 + 255.9 -

2.87 + .78 -

pressure, mean arterial pressure, and cardiac index showed insignificant absolute changes during fluid removal via continuous ultrafiltration (Table 6).

The ability to remove fluid is important in the patient with excess fluid, but exactly what are we removing? To answer this question we continued to use the polysulfone membrane and measured simultaneous arterial, venous, and ultrafiltrate samples of electrolytes, selected amino acids, and other elements. As listed in Table 7, we found that measured sieving coefficients for negatively charged elements were actually higher than unity, perhaps due to a Gibbs-Donnan-like effect. Removal of amino acids such as histidine and threonine was also enhanced. Using the measured sieving coefficient and the known QF, one can predict clearance values and ultimately mass transfer or removal of substances. This is helpful when dealing with drug removal or looking at amino acid balance or urea kinetics. Figure 9 for shows the balance of essential amino acids in receiving hyperalimentation while undergoing SCUF.

example, patients

There was

E. Paganini 21

A 1050

dynes/em 800 ----..cz 550

1300f

300L-~~~--~~~~ __ ~~~~ __ ~-L-L __

8

c

LAP mmHg

MAP mmHg

TIME Hrs.

Fig. 8. Hemodynamic measurements in patients intraaortic balloon pumping while undergoing slow ultrafiltration (SCUF). SVR = systemic vascular LAP = left arterial pressure; MAP = mean arterial

undergoing continuous

resistance; pressure.

a marked positive balance, ranging from 82.8% for phenylala-nine to 97.5% for isoleucine.

There is, however, a time decay in performance for most hemofilters tested in vitro, as well as the hydraulic

so that the sieving coefficient permeability may decrease.

Mineshima et al (32) thought this was secondary to protein polarization during therapy. Leypoldt et al (33) found a significantly greater sieving of polydisperse neutrodextrans when comparing the effects of various surface areas during constant ultrafiltration rates. However, when the data was adjusted for surface area, the sieving for all dextran molecular sizes were comparable, leading to the conclusion that the ratio of filtration rate to surface area is helpful in evaluating filter performance. Trudell et al (34) studied a nonheparinized system of continuous ultrafiltration with an AV shunt as an access in dogs. Varying capillary tubing configurations seemed to playa major role in the time decay of ultrafiltration rates in these pulsatile models.


Table 6. Hemodynamic changes induced by SCUF.

Parameter Change while on SCUF

Cardiac index Mean arterial pressure

pulmonary artery pressure

Central venous pressure Left arterial pressure

systemic vascular resistance

SCUF slow continuous ultrafiltration

.28 4.0 4.6 2.4 2.4 1.5

107

+ -

+

+ -

+

+

+ -

+ -

.35 L/min/m2 2.6 mmHg 6.0 mmHg

3.0 mmHg 1.5 mmHg 1.2 rnrnHg

121 dynes/ern sec2

Although these data will help in the evolution of continuous therapy hardware, several facts must be remembered. The above approaches either failed to account for the pulsatile nature of flow during SCUF/CAVH, used higher blood flows during the investigations then generally encountered in clinical use of continuous therapy (QB 60-100 mL/min versus QB 100-700 mL/min), or used tubing design not yet available for clinical trials. Despite these drawbacks,

Table 7. Measured siev ing coefficients for various elements and selected amino ac ids. *

Sodium 0.993 Blood urea 1.019 Leucine 1.014 ni trogen

Potassium 0.975 Creatinine 1.037 Tyrosine 1.089 Chloride 1.088 Valine 1.069 Phenyl- 1.078

alanine Bicarbonate 1.137 Cystine 1.047 Lysine 1.080 Calcium 0.677 Methionine 1.000 Histidine 1.109 Albumin 0.002 Iso-leucine 1.010 Threonine 1.256

* Sieving coefficient (SC) = UF Art. + ] Ven.

2

E. Paganini

13 12 II 10 9

(!) 8

c ILl 7 U) ::::> 6 u.. z 5 4

3 2 1

-2 BALANCE +9'll +85.8 +96.4 +97.5 +89.3 +89.1 +84.5 +82.8 +89.6 (%)

23

Fig. 9. Essential amino acid (AA) balance during slow continuous ultrafiltration (SCUF). From Paganini E, et al Trans ASAIO, 1982.

however, the development of higher solute efficiency and stable membrane hydraulic characteristics are important steps toward improving clinical performance.

SCUF can, at present, be considered an important adjunctive form of therapy. It totally eliminates any need for fluid removal during standard hemodialysis. Patients have been able to tolerate the diffusive procedure and uremic control has been accomplished. For those patients who are still unable to be supported with standard hemodialysis, CAVH can be instituted so that both fluid and azotemic control are achieved.

CONTINUOUS ARTERIOVENOUS HEMOFILTRATION Since the control of azotemia (Olbricht), drug kinetics

(Golper) , and predilution variants (Kaplan) are well described in later chapters of this book, as well as the


technical (Swann), nursing (Whitman), and transport (Lysaght) characteristics of CAVH, I will limit this section to intro-ductory and general remarks. The original report of arterio-venous hemofiltration by Kramer et al was in 1977 (7). Largely due to their continued use of this form of therapy, and enlightened writing on the subject (35,36), it grew in popularity in Europe.

Introduced in a variant form in the united States by our group in 1980 (8), later published experience by Lauer et al (37) and Kaplan (38) made CAVH an important addition to the treatment of hemodynamically unstable patients with acute renal failure. The hemodynamic stability noted in all the reports, as well as the reduction (39) or elimination of the need for hemodialytic support to control azotemia, made this treatment modality ideal for the intensive-care patient. Its simplicity in design allowed staff not experienced in dialysis to feel comfortable with its mechanics. The only drawback initially identified was with replacement fluid, both in fluid balance and fluid composition. Although convective and conductive forces playa role in standard hemodialysis techniques, Henderson et al published their work in 1967 on the use of convective forces alone as a mode of therapy for end-stage impressed by the large relatively asymptomatic

renal disease amounts of

results. To

(40) They were fluid removed with

accomplish this, a special membrane with a high sieving coefficient and ultra-filtration coefficient similar to the glomerular basement membrane was developed (XM-50).

In Europe, a membrane with similar characteristics (polyacrylonitrile) was already in use as a dialysis mem-brane. Quellhorst et al (41), Kramer et al (42), and others (43-45) began using this membrane as an ultrafilter, and because of its commercial availability, were able to treat a greater number of patients who were suitable subjects for hemofil tration.

Intermittent hemofiltration simply employs the applica-tion of a high transmembrane pressure to a membrane with a

E. Paganini 25

high ultrafiltration coefficient. In this way, large amounts of fluid are removed as the ultrafiltrate; a similar amount of fluid can then be replaced. This replacement fluid can be given either predilution or postdilution (before or after the ultrafiltration). The amount of fluid exchanged (acting as a plasma water exchange) is usually based on the patient's weight. This is translated to total body water, and that amount is exchanged over three separate therapy sessions per week.

The application of this form of therapy in a continuous manner (CAVH) and in a pumpless system requires access and circuitry designed to use the patient's natural pressure drives. The fluid exchange still takes place but at a lower rate over an indefinite time. The unrestrained filtration rate becomes the guide to therapeutic effectiveness, with an exchange of 8 mL/min regarded as minimally effective and 10 mL/min as the standard.

Postdilution fluid replacement, found to be the simplest method of exchange during intermittent hemofiltration, was perpetuated in continuous hemofiltration. The use of suction assistance to enhance the filtration rate led Kaplan to use predilution replacement, which resulted in increased urea and creatinine clearances (46). Since this is a relatively in-efficient system, any improvement in urea clearance might reflect a large percentile change but actually represent only a minor increase in mass transfer. If one is concerned with low urea clearance, then continuous hemodialysis (47,48) or combined hemodialysis and postdilution hemofiltration (continuous hemodiafiltration) (49) might be better suited and less labor-intensive than predilution hemofiltration. Fluid balance and SCUF/CAVH.

As pointed out earlier, the two major continuous thera-pies differ in their goals of treatment. SCUF is generally employed for fluid removal, while CAVH promotes an exchange and therefore mandates that a fluid infusion be initiated. The types of systems used for these methods are detailed in


other areas and include gravity scales, IV infusion pumps, or hourly manual balancing.

SCUF is usually hyperalimentation or with natural diuresis.

used in patients who are receiving other fluids, while having a problem

Also, patients with fluid excess, either iatrogenically or pathologically induced, may be undergoing a pure type of ultrafiltration without concomitant

fluid infusion at the time of SCUF. Therefore, the prescribed type of fluid and its delivery rate is dependent upon these patients' clinical needs. During hemofiltration, however, it is the system itself that ultimately dictates the fluid exchange rate. A high QF will mandate a high replace-ment fluid rate. After the baseline infusions needed by the patient are satisfied, the excess will then need to be prescribed with a goal of electrolyte and acid-base balance. The composition of this substitution fluid, therefore, should be based on the desired serum levels and the losses incurred during CAVH itself.

The exaggerated removal of chloride and bicarbonate in the ultrafiltrate require replacement, along with the losses of ionized calcium, magnesium, and sodium during the process. Potassium and such elements as urea or creatinine should be considered in formulating the replacement fluid. For example, by measuring the urea level in both the ultrafil-trate and serum, one may calculate the urea appearance rate following the formula:

UA = ([Uj uf x Vuf) + VDu ([Uj si - [Uj so)

where (UA) is urea appearance, (V) is timed collection of ultrafiltrate, [Uj is the concentration of urea in the ultra-fil trate (UF), (so) is serum at time 0, and (si) at time of completion. This may help in adjusting the hyperalimentation and thus indirectly change the rate of hemofiltrate infusion.

Interactions among various elements must also be con-sidered when formulating a replacement fluid. The direct mixing of bicarbonate and calcium will form a precipitate and thus render the solution useless. Using acetate or lactate

E. Paganini 27

as the base equivalent will avoid this problem and allow a mixture similar to that found in hemodialysate. We have used a bicarbonate-based fluid prepared in our pharmacy. This fluid is mixed in a laminar flow room and delivered when ready to be infused so that the potential for bacteriologic contamination can be minimized. Using this fluid, however, has necessitated separate infusion for calcium and magnesium and has added labor to the cost of the procedure.

The development of on-line or in-line systems (50-52) of replacement in intermittent hemofiltration may be the fore-runner to on-site production of fluid for CAVH. Also, as industry begins to supply fluid at a reasonable cost for hemofiltration, this procedure will certainly progress at a much faster pace. Lactated Ringer's solution or normal saline with appropriate additions is a reasonable substitute in the short run. However, peritoneal solutions presently available are best left for intraperitoneal infusions and not used as hemofiltrate replacement solution. Clinical practice of SCUF/CAVH.

The patient population described earlier, resistant to intermittent extracorporeal interventions and yet fluid over-loaded and oliguric, is typical of many intensive care units. These same patients are thought to benefit from the delivery of calories and amino acids and frequently require multiple pressor or antibiotic infusions. The classical teaching has been to limit fluid intake, however, this is frequently not practical nor advisable when to do so would also reduce needed medications.

For those reasons, it is often judicious to begin con-tinuous therapy earlier than usual when following standard dialytic criteria. Figure 10 shows the distribution of initial serum creatinine levels in all patients treated with continuous therapy at our institution. This group includes over 200 patients treated for nearly 1,500 patient-days. While close to 90% of the entire population started therapy prior to reaching a serum creatinine level of 8 mg/100 mL, 44% began at levels less than 4 mg/lOO mL. Figure 11 shows

28

B

continuous Replacement Modalities

IHITUAL S. CREAT.

Per-cent 43.66 45.76

9.66 1..1.6

Fig. 10. Initial serum creatinine (S. Creat.) levels in patients undergoing acute continuous therapies at the author's institution. This group includes more than 200 patients monitored for almost 1,500 patient-days. SCUF slow continuous ultrafiltration; CAVH = continuous arterio-venous filtration.

the distribution of creatinine levels between SCUF and CAVH. As might be expected, SCUF was started at lower creatinine levels, while CAVH was initiated more frequently at the higher levels. Not infrequently, the patients may begin to receive support with a standard hemodialysis run (usually at levels of serum creatinine greater than 8 mg/IOO mL) and then be placed on CAVH for maintenance. SCUF is also frequently

F g ~ y %

lll.'i!!.l S(l-

I

SCUF/CAUH THERAPY IHITUAL S. CREAT.

MG % 111I2nd Rx

Fig. 11. Distribution of starting serum creatinine (S. Creat.) levels between SCUF (1st Rx) and CAVH (2nd Rx). SCUF = slow continuous ultrafiltration; CAVH = continuous arterio-venous filtration.

E. paganini

D

SCUF/CAVH THERAPY

SYSTEMS Percen"1: A:GU B:RESP

~~~rE/SKN E:CNS F":OI

.J G: IV H:BOHE/.JT I I:OTHER j:ENDOCAR

CONCUR INFECT

i.8.63 26.66

~f:~J .56

i..62 2.74 i..62 6.56 2.74

29

Fig. 12. Concurrent infections (concur. infect.) in all patients undergoing acute continuous therapies.

used for fluid control and the interposition of intermittent bicarbonate hemodialysis at a reduced schedule.

Of all our patients who have undergone continuous renal support the majority have also had concurrent infection prior to initiation of therapy. Figure 12 shows the distribution of organ system involvement while Figure 13 gives specific differences between patient groups supported on SCUF or CAVH. Respiratory infection and blood dyscrasias dominated in the SCUF-supported patients, whereas wound and skin infection and

G P

~ so

SCUF/CAUH THERAPY CONCURR. INFECT.

45-1--~~~--~~--------------------------I

SYSTEM 11112nd Rx

Fig. 13. Concurrent infections (concur. infect.) in patients undergoing slow continuous ultrafiltration (SCUF) (1st Rx) and continuous arteriovenous hemofiltration (CAVH) (2nd Rx). 1) Genitourinary, 2) Respiratory, 3) Wound and skin, 4) Blood, 5) Central nervous system, 6) Gastrointestinal, 7) IV site, 8) Bone and joint, 9) Other, 10) Endocarditis.


genitourinary disturbances were more frequently encountered in patients receiving CAVH. An effort was made to identify the infective agents and relate them to either the continuous procedure itself or the access necessary for the procedure. This retrospective analysis included comparing the culture results of indwelling catheter tips obtained upon removal (53) with infective agents isolated prior to initiation of therapy. Whether long-term indwelling catheters will prolong an already existing bacteremia is the subject of a prospective study currently underway. However, there seemed to be no introduction of a new infective agent that was attributable to the continuous therapy or its access.

Therapy interruptions are another source of concern (Figs. 14 and 15). While these interruptions may be part of the overall scheme of therapy, there may also be a signifi-cant compromise in overall clearances because relatively long periods (4-8 hrs) may pass awaiting reinstitution of therapy. By far the most frequent cause of interruption is clotting of the filter. The incidence varies enormously depending upon heparin usage, length of blood lines employed, method of fluid collection, access, and related blood flow. Heparin usage seemed to playa role in the frequency of clotting with SCUF, but no difference was found when comparing heparin and no heparin infusion during CAVH (30). We have always used

i.iI;~ sa-

I

saJ I

HEPARIN THEIo!:APY INlfERRUPTIONS

: MECH

REASONS III1CAUH

l I :DIAL

Fig. 14. Therapy interruptions when heparin was used.

E. Paganini

Li1Jlltl 80-

I

60-' I

HO HEPAR!H THERAPY !HlfERRUPTIOHS

REASOHS III1CAUH

Fig. 15. Therapy interruptions when heparin was not used.

31

short blood lines for our continuous therapy and this has produced fewer clotting episodes overall than encountered with the longer lines (see Swann et al [29]). As pointed out by Kramer et al (36) and Lauer et al (37) filtration frac-tions, underlying serum protein concentration, and access-related blood flows will all influence clotting frequency. We have found an overall filter life of 48-55 hours with 10% of patients able to continue 14 days or longer with the same kidney.

Mechanical interruptions were usually related to device failure, preparation mistakes, nursing errors or oversights, or patient-induced disturbances. Membrane rupture was a more frequent problem when using the IV infusion pump, which employs a plunger-type device mechanism for ultrafiltrate control. The sudden withdrawal of fluid from the UF compart-ment side of the kidney caused a rapid creation of negative pressure. Although this pressure did not exceed the manu-facturers's limits for transmembrane pressures, the repeated rapid suction weakened the membrane at its potting site and rupture ensued. Also, during preparation of the hemofilter for use, care should be given to assure air removal so that the full potential of the filter can be realized and air-blood interfaces avoided, since this ultimately leads to loss of surface area and to clotting.


All lines and infusion fluids must be checked frequent-ly. Unnoticed flow disruption either of the infusate (heparin or hemofiltration replacement fluid) or the blood lines or access cannulae, may lead to clotting or blood flows so that continual therapy would be

decreased impossible.

with femoral catheters in place, extreme care must be taken to avoid catheter kinking, which will translate into slow flow states and subsequent malfunction of the system. Patients can be mobilized or may actually be able to undergo surgery while being treated with continuous therapy as long as close attention is given to the circuitry and system parameters.

Finally, baseline activity is an important considera-tion. If patients are entirely uncooperative and incoherent, the use of continuous therapy should be questioned. The unrestrained patient may damage the filter, bend blood lines or access catheter, remove or disconnect lines, and ultimate-ly cause a great deal of harm. In these situations, it is strongly recommended that soft restraints be applied. The circuit should be well anchored to the patient, not the bed or bedside, tory. Table

and close nursing observation should be manda-their

the diagnosis, and problem.

8 lists the causes for interruptions, outlines steps to be taken to resolve

Morbidity and mortality of SCUF/CAVH. All therapeutic interventions have risks associated with

their use and continuous renal replacement therapy is no exception. Although the procedure itself is simple, electro-lyte balance, fluid control, acid-base considerations, and the appropriate use of therapy are best left to those well trained in these areas. The bicarbonate loss (sieving co-efficient 1.069) through the ultrafiltrate, for example, can be used as a powerful tool in the treatment of acid-base disturbances in oliguric renal failure (54,55), or may induce worsening of acidemia if not replaced appropriately.

Electrolyte, calcium, and magnesium balance is another area where iatrogenic morbidity is possible. One must

Tab

le 8

. D

iagn

osis

an

d tr

eatm

en

t o

f co

nti

nu

ou

s th

erap

y i

nte

rru

pti

on

s.

Inte

rru

pti

on

Clo

ttin

g

Acc

ess

fail

ure

Ul t

rafi

l tra

tio

n

un

restr

icte

d

co

llecti

on

: -

Dec

reas

e rate

Co

ntr

oll

ed

co

llecti

on

: -

Sys

tem

ala

rm

-A

ir

in U

F li

ne

As

per

clo

ttin

g

Dia

gn

osi

s

Blo

od

flow

Los

s o

f tr

an

s-

mit

ted

pu

lsat

ion

to

in

fusi

on

lin

e

sep

ara

tio

n o

f b

loo

d

in li

nes

Red

uced

p

uls

atio

n

tran

smis

sio

n

dec

reas

ed

calc

ula

ted

QB

Kid

ney

Dar

k cap

illa

ry

an

d h

eade

r co

lor

Inab

ilit

y t

o

flu

sh c

lean

carefu

lly

wit

h

sali

ne

Incr

ease

d

clo

ttin

g

inci

den

ce

Goo

d fl

ush

w

i th

po

or refi

llin

g

The

rapy

Ev

alu

ate

access

an

d li

nes

Rep

lace

sys

tem

Bol

us

1000

U

hep

arin

Rai

se h

epar

in

infu

sio

n

in n

ew

sys

tem

Rev

ise

sh

un

t

Rep

lace

cath

ete

rs

Ev

alu

ate

vessels

I:'il

'tI

III

1Q

III

::l ...

.

::l

....

w

w

Tab

le 8

. D

iag

no

sis

an

d tr

eatm

en

t o

f co

nti

nu

ou

s th

erap

y i

nte

rru

pti

on

s (c

onti

nued

).

Inte

rru

pti

on

Mem

bran

e ru

ptu

re

Kid

ney

casin

g

dam

age

Acc

ess

ble

edin

g

Inte

rmit

ten

t d

ialy

sis

Ult

rafi

ltra

tio

n

pink

to

red

co

lor

Dec

reas

e rate

Nor

mal

If S

CUF

main

tain

QF

If C

AVH

redu

ce Q

F

Dia

gn

osi

s

Blo

od

flow

Nor

mal

Nor

mal

Nor

mal

to

lo

w

Pum

p g

ener

ated

Kid

ney

Nor

mal

Soa

ked

wra

ppin

gs

Nor

mal

In-l

ine s

etu

p

The

rapy

Rep

lace

kid

ney

Dis

con

tin

ue

neg

ativ

e p

ress

ure

Rep

lace

kid

ney

D/C

hep

arin

C

heck

clo

ttin

g

par

amet

ers

Giv

e pr

otam

ine

App

ly p

ress

ure

Fol

low

HD

pro

toco

l

D/C

repl

acem

ent

flu

id

un

til

Sip

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o

o

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E. paganini 35

realize that the ultrafiltrate contains a sodium level equal to that of the serum (sieving coefficient 0.996). Therefore, in removing 5 liters during SCUF or exchanging 14 liters during CAVH, a substantial sodium loss occurs that may induce a true hyponatremia if not appropriately balanced. For this reason, the use of normal saline or lactated Ringer's solu-tion is generally recommended as the baseline fluid with SCUF, and sodium balance is a prime consideration in adjust-ing the replacement fluid during CAVH. Calcium (sieving coefficient 0.6) is also lost in proportion to its ionized fraction. This must be replaced either with the hyperalimen-tat ion or hemofiltration replacement fluid, along with magnesium. We have experienced the induction of cardiac arrhythmias based at least partially on low calcium and magnesium levels in some patients on CAVH.

Fluid balance is another critical issue. Since there this are very

therapy, few

the hemodynamic disturbances

classical signs of fluid related

depletion to

may be missed. It is, for example, possible to induce a severe volume depletion while not observing any hypotension or tachycardia. Frequently, these patients are unable to respond to the thirst mechanism and, as noted above, sodium and chloride are removed in proportion to serum, so that the usual laboratory parameters of dehydration are not helpful. Daily physical assessment cannot be over-emphasized. Accurate fluid balance, flow charts, and daily weights are a necessity in evaluating patients on SCUF and CAVH. While easily correctable, inappropriate fluid adjustments, left unmonitored, may have a dramatic effect on patient morbidity.

The most frequent morbid event directly associated with this therapy has been bleeding. The use of continuous heparin infusions has reduced the overall heparin dosage and avoided the peak and valley effect of an intermittent regimen. Nonetheless, 18% of our patient population had bleeding episodes while undergoing therapy. While monitoring clotting parameters (PT, PTT, ACT) in the circuit seemed appropriate, patient monitoring was more effective in de-


creasing the bleeding incidence. Our protocol is to monitor patient PT and PTT at least every 24 hours, but usually on a 12-hour basis and to adjust the heparin infusion appropriate-ly. We have been unable to perform satisfactory regional heparinization, partially due to the labor-intensive aspects of this approach. The inability to adjust heparin/ protamine flows accurately makes this a less than desirable approach.

The use of prostacycline as a heparin substitute was considered but abandoned when the anticoagulant dose was found also to induce hypotension. The use of a low-molecular-weight heparin may prove beneficial but is still under investigation (56). Since it can be removed from the circuit by filtration, very little entered the patient and thus a reduced incidence of hemorrhage was found.

Another approach has been the total elimination of heparin. to avoid

With appropriate patient selection it is heparin usage (30). Patients who have

episodes while undergoing treatment can remain

possible bleeding on that

therapy with the heparin discontinued. the incidence of clotting may ensue, tions of therapy are significant.

A slight increase in but overall interrup-

Historically, patients with acute renal failure have demonstrated a high mortality, especially when dialytic modalities are necessary (57-59). Until a well-matched, prospective comparison of the various renal failure are conducted, the

therapies impact of

of acute continuous

therapies on patient mortality will remain unknown. To our knowledge there are no reports that have addressed mortality among patients who are unable to undergo dialytic techniques. Drawn on anecdotal experience, the mortality in our institu-tion has been 100%. It was for this reason that this specific population was identified for continuous renal replacement treatment. We have managed to lower the mortality to 70% , which we think represents a significant advance in the management of acute renal failure.

Based on these results, we have since expanded the population to include all oliguric intensive care patients

E. Paganini

F

5 ~ " C Y

SCUF/CAUH THERAPY PATIENT MORTALITY

STATUS 111I2nd Rx rl'3" Rx

37

Fig. 16. Patient mortality for all acute continuous (1st Rx) therapies among patients with one, two (2nd Rx) or three or more separate bouts of acute renal failure (3rd Rx)

requiring fluid, electrolyte balance, or azotemic control. We have also identified sub-groups of patients that have repeated bouts of renal failure during their hospitalization and require subsequent intervention. The overall mortality statistics are summarized in Figure 16. While mortality remains high in the hemodynamically unstable population with multiorgan failure (70%), those patients who experienced repeated bouts of renal failure showed a mortality of 50% and 61% respectively, in sharp contrast to the higher mortality reported among similar patient populations (60,61). Perhaps the true impact of this therapy is with the severely compromised group rather than the stable oliguric patient. Further data need to be collected to substantiate this trend.

CONCLUSION This chapter has presented an overview of acute continu-

ous extracorporeal treatment modalities for patients with acute renal failure. The hemodynamic stability offered by these therapies and the elimination of fluid restrictions in these patients will open the door to adequate nutrition and appropriate medication scheduling. The system's simplicity will lend itself to ease of implementation but may also allow significant alteration in patient status if not properly


managed. severely

Finally, mortality seems to have been decreased in compromised patients, but whether this will carry

over into other patient populations remains to be seen.

REFERENCES 1. Abel RM, Buckley MJ, Austen WG, et al: Acute postopera-

tive renal failure in cardiac surgical patients. J Surg Research 20:341, 1975.

2. Anderson RJ, Schrier RW: Clinical spectrum of oliguric and non-oliguric acute renal failure. In: Acute Renal Failure, Brenner BM, Stein J (eds). Churchill Livingston, New York, pp 1-16, 1980.

3. Ghattas MA, Sethna DH, Rezkana H, paganini EP, et al: Patterns of acute renal failure requiring dialysis after open heart surgery (Abstract). American Society of Anesthesiology, 1985.

4. Khanna R, popowniak KL, Magnusson M, Nakamoto S: Control of ascites in patients with chronic hemodialysis by modified ultrafiltration using a Dow Hollow Fiber Capillary Kidney (Abstract). Trans Am Soc Artif Intern Organs 2:31, 1973.

5. Bergstrom J, Asaba H, Furst P, Oules R: Dialysis ultra-filtration and blood pressure. Proc Eur Dial Transplant Assoc 13:293, 1976.

6. Hakim RM, Lazarus RM: Hemodialysis in acute renal failure. In: Acute Renal Failure. Brenner B, Lazarus JM (eds) , WB Saunders, Philadelphia, pp 643-688, 1983.

7. Kramer P, Wigger W, Rieger J, et al: Arteriovenous hemofiltration: A new and simple method for treatment of overhydrated patients resistant to diuretics. Klin Waschr 55:1121, 1977.

8. paganini EP, Nakamoto S: Continuous slow ultrafiltra-tion in oliguric acute renal failure. Trans Am Soc Artif Intern Organs 26:201, 1980.

9. Paganini EP, O'Hara P, Nakamoto S: Slow continuous ultrafiltration in hemodialysis resistant oliguric acute renal failure patients. Trans Am Soc Artif Intern Organs 30:173, 1984.

10. DelGreco F, Shere J, Simon NM: Hemodynamic effects of hemodialysis in chronic renal failure. Trans Am Soc Artif Intern Organs 10:353, 1964.

11. Goss JE, Alfrey AC, Vogel JHK, Holmes JH: Hemodynamic changes during hemodialysis. Trans Am Soc Artif Intern Organs 13:68, 1967.

12. Kersh ES, Kronfield SJ, Unger A, et al: Autonomic insufficiency in uremia as a cause of hemodia1ysis-induced hypotension. N Engl J Med 291:650, 1974.

13. Zucchelli P, Catizone L, Esposti ED, et al: Influence of ultrafiltration on plasma renin activity and adrenergic system. Nephron 21:317, 1978.

14. Kim KE, Neff M, Cohen B, et al: Blood volume changes and hypotension during hemodialysis. Trans Am Soc Artif Intern Organs 16:508, 1970.

E. paganini 39

15. Silverstein ME, Ford EA, Lysaght MJ, Henderson LW: Treatment of severe fluid overload by ultrafiltration. N Engl J Med 291:747, 1974.

16. Chen WT, Chaignon M, Omvik P, et al: Hemodynamic studies in chronic hemodialysis patients with hemofil-tration/ultrafiltration. Trans Am Soc Artif Intern Organs 24:632, 1978.

17. paganini EP, Fouad F, Tarazi RC, et al: Hemodynamics of isolated ultrafiltration in chronic hemodialysis patients. Trans Am Soc Artif Intern Organs 25:422, 1979.

18. MacIntyre WM, Pritchard WH, Eckstein RW, Fridell HL: The determination of cardiac output by a continuous recording system utilizing iodinated 1 131 human serum albumin in animal studies. Nucl Med 7:1, 1960.

19. Razzak MA, Botti RE, MacIntyre WJ: A rapid radioisotope dilution technique for the accurate determination of the cardiac output. Nucl Med 7:1, 1960.

20. Guyton AC, Lindsey AW, Kaufmann BN, Abernathy JB: Effects of blood transfusion and hemorrhage on cardiac output and the venous return curves. Am J Physiol 194:263, 1958.

21. Tarazi RC, Ibrahim MM, Dustan HP, Ferrario CM: Cardiac factors in hypertension. Circ Res (Suppl) 1:34-35, 1974.

22. Brod J: Mechanism 1978.

Hypertension and renal parenchymal and management. Cardiovasc Clin

disease: 9 (1) :137,

23. Magnusson M, Sivak E, Meden G, et al: The effect of Furosemide versus ultrafiltration on extravascular lung water in permeability pulmonary edema in dogs (Abstract). IXth Intern Cong of Nephr, p l75A, 1984.

24. Magilligan DJ, Oyama C: Ultrafiltration during cardio-pulmonary bypass: laboratory evaluation and initial clinical experience. Ann Thorac Surg 37:33, 1984.

25. Lamar J, Briggs WA, McDonald FD: Effective fluid re-moval with the Amicon diafilter. Proc Dial Trans Forum 127, 1978.

26. Neff MD, Sadjadi S, Slifkin R: A wearable artificial glomerulus. Trans Am Soc Artif Intern Organs 25:71, 1979.

27. Shaldon S, Beau MC, Deschodt, et al: Continuous ambula-tory hemofiltration. Trans Am Soc Artif Intern Organs 26:210, 1980.

28. Olbricht C, Schurek HJ, Tytul S, et al: Efficiency of CAVH in acute renal failure. Influence of blood pres-sure, blood flow, vascular access and filter type (Abstract). Blood Purif 2:14, 1984.

29. Swann S, Kennedy 0, Paganini EP: Technical aspects of slow continuous ultrafiltration (SCUF) and continuous arterio-venous hemofiltration (CAVH). In preparation.

30. Smith 0, Paganini EP, Suhoza K, et al: Non-heparin continuous renal replacement therapy is possible. Artif Organs 1986 (In print)


31. Desio FJ, Paganini EP: Evaluation of slow continuous ultrafiltration in oliguric patients on intraaortic balloon pumps (Abstract). Blood Purif 2:5, 1984.

32. Mineshima M, Yamagata K, Era K, et al: Kinetic compari-son of hemofilters for continuous arteriovenous hemofil-tration (CAVH). Trans Am Soc Artif Intern Organs, 1985 (In print).

33. Leypoldt JK, Frigon RP, Henderson LW: Impact of ultra-filtrate velocity on solute clearance in CAVH (Abstract). Blood Purif 2:217, 1984.

34. Trudell LA, Aebischer P, Panol G, et al: An implantable continuous ultrafiltration device. Artif Organs, 1986 (In print).

35. Kramer P, Schrader J, Bohnsack W, et al: Continuous arteriovenous hemofiltration: A new kidney replacement therapy. Proc Eur Dial Transplant Assoc 18:743, 1981.

36. Kramer P, Bohler J, Kehr A: Intensive care potentials of continuous arteriovenous hemofiltration. Trans Am Soc Artif Intern Organs 78:28, 1982.

37. Lauer A, Saccaggi A, Ronco C, et al: Continuous arteriovenous hemofiltration in the critically ill patient. Ann Intern Med 99:455, 1983.

38. Kaplan AP, Longnecker RE, Folkert VW: Suction-assisted continuous arterio-venous hemofiltration. Trans Am Soc Artif Intern Organs 29:408, 1983.

39. Dodd NJ, O'Donovan RM, Bennett-Jones Div: Arteriovenous hemofiltration: A recent advance in the management of renal failure. Brit Med J 287:1008, 1983.

40. Henderson LW, Besarab A, Michaels A, et al: Blood purification by ultrafiltration and fluid replacement (diafiltration) Trans Am Soc Artif Intern Organs 13:216, 1967.

41. Quellhorst E, Rieger J, Doht B, et al: Treatment of chronic uremia by an ultrafiltration artificial kidney--first clinical experience. Proc Eur Dial Transplant Assoc 13:134, 1976.

42. Kramer P, Matthaei C, Fuchs C, et al: Assessment of hormone loss through hemofiltration. Artif Organs 2: 128, 1978.

43. Schaefer K, Herrath D, Gul1berg H, et al: Chronic hemofil tration--a cr i tical evaluation of a new method for the treatment of blood. Artif Organs 2:386, 1978.

44. Henderson LW, Colton CK, Ford CA: Kinetics of hemodia-filtration, II. Clinical characterization of a new blood cleansing modality. J Lab Clin Med 85:372, 1975.

45. Colton C, Henderson LW, Ford CA, et al: Kinetics of herndiafiltration, I. In vitro transport characteristics of a hollow fiber blood ultrafilter. J Lab Clin Med 85:355, 1975.

46. Kaplan A: The effect of predilution during continuous arterio-venous hemofil tration (Abstract). ASN 17th annual meeting p 66A, 1984.

47. Scribner BH, Canez JEZ, Buri R, Quinton W: The tech-nique of continuous hemodialysis. Trans Am Soc Artif Intern Organs 6:38, 1960.

E. Paganini 41

48. Geronemus R, hemodialysis: renal failure. 1984.

Schneider N: Continuous arteriovenous A new modality for treatment of acute Trans Am Soc Artif Intern Organs 30:610,

49. Ronco C, Brendo1an A, Bragantini L, et al: Arterio-venous hemodiafiltration combined with continuous arteriovenous hemofiltration (Abstract) ASAIO abstracts 14:36, 1985.

50. Henderson LW, Beans E: Successful production of sterile pyrogen-free electrolyte solution by ultrafiltration. Kid lnt 14:522, 1978.

51. Shaldon S, Bean MC, Deschodt G, et al: Three years of experience with on-line preparation of sterile pyrogen-free infusate for hemofi1tration. Contr Nephro1 32:161, 1982.

52. Luehmann D, Hirsch D, Ebben J, et al: Central on-site preparation of substitution fluid for hemofi1tration. Trans Am Soc Artif Organs 30:195, 1984.

53. Cooper GL, Hopkins CC: Rapid diagnosis of intravascular catheter-associated infection by direct gram staining of catheter segments. N Eng1 J Med 312:1142, 1985.

54. Bosch: Acid/base. 55. Gudis S, Mangi S, Feinroth M, et al: Rapid correction

of severe lactic acidosis with massive isotonic bicarbonate infusion and simultaneous ultrafiltration (Abstract). ASN - 14th annual meeting, p 41, 1981.

56. Moriniere P, Dieua1 J, Renand H, Bene1monfok, et a1: Comparison of low molecular weight heparin with unfrac-tionated heparin in hemofiltration: same antithrombotic activity with decreased hemorrhagic risk (Abstract). Blood Purif 2:56, 1984.

57. Kje11strand C, Gornick C, David T: Recovery from acute renal failure. Clin Exp Dialysis Apher 5:143, 1981.

58. Hilberman M, Myers BD, Carrie BJ, et a1: Acute renal failure following cardiac surgery. J Thorac Cardiovasc Surg 77:880, 1979.

59. Gailiunas P, Chawla R, Lazarus JM, et al: Acute renal failure following cardiac operations. J Thorac Cardio-vasc Surg 79:241.

60. B1uemle LN Jr, Webster GD Jr, Elkinson JR: Acute tubular necrosis. Arch Intern Med 104:18, 1959.

61. London RE, Burton JR: Post-traumatic renal failure in military personnel in southeast Asia. Am J Med 53:137, 1972.

3 TRANSPORT IN CONTINUOUS ARTERIOVENOUS HEMOFILTRATION AND SLOW CONTINUOUS ULTRAFILTRATION M. LYSAGHT D. BOGGS Travenol Laboratories, Round Lake, Illinois

This chapter will review the technological basis of continuous hemofiltration as employed in treating acute renal failure and then discuss the physical factors governing filtration rate and solute removal.

MEMBRANES Figure 1 is a scanning electron micrograph that shows

the unique structure of the membranes employed in hemofiltra-tion. Two distinct regions are visible: the skin, a consolidated layer surrounding the fiber lumen, and the sub-strate, a broad microporous region comprising the remainder of the fiber wall. The skin is less than one micron thick and contains extremely small pores of a size suitable to retain plasma proteins while passing urea and other low-molecular-weight solutes. This skin region determines the transport properties of the membrane; the substrate simply provides mechanical strength and support. If, instead of being confined to the skin, the fine pores extended through the full membrane, resistance to permeation would be much higher and the filtration rate would be far too low to permit hemofiltration.

Membranes for commercially available CAVH filters are manufactured from hydrophobic thermoplastics such as poly-acrylonitrile, polyamide, and polysulfone. (Chemical formu-lae are included in Table l.) Such materials are generally not responsive to the complement system, and the lack of complement activation is an important feature of CAVH

43

44 Transport Characteristics

Fig. 1. Scanning electron micrograph showing a transection of a hollow-fiber ultrafiltration membrane. Inner diameter is 200}J. (Inset shows skin at higher magnification.)

(continuous arteriovenous hemofiltration) and SCUF (slow continuous ultrafiltration). Hydrophobic membranes do absorb proteins from solution (some are absorbed vigorously); the absorbed protein layers influence the infiltration rate and solute transport characteristics of the membrane. Thus, membrane and device performance should always be evaluated with plasma or blood as the perfusate.

Membranes are prepared with the use of a phase-inversion process (1). The polymer is first dissolved in a water-miscible solvent to form a viscous dope. This solution is then extruded, as an annulus or as a sheet, around an aqueous stream. The polymer directly adjacent to the water precipi-tates rapidly, forming the skin; solvent is leached more slowly from the remainder of the film, leaving the substrate. The properties of the membrane depend to a great extent on the kinetics of the precipitation, which can be controlled, albeit in a semiempirical fashion (2).

M. Lysaght and D. Boggs

TABLE I COMMERCIALLY AVAILABLE OEVICES FOR CAVH AND SCUF

PERFORMANCE'

GEOMETRY FILTRATION POISEUILLE PRIMING AREA .OF LENGTH RADIUS RATE RAllO VOLUME DESIGNATION MANUFACTURER MEMBRANE MATERIAL FIBERS

,m microns emlmln mmHg-mlf1Jcm ,m

OIAFllTER.20 AMICON CORPORATION {{~ " 2500 13 100 11 '83 10 OiAl'llTE~30 LEXINGTON, MAUSA 06 4800 20 100 17 06. " POLYSULfONE

ULTRAFILTtRCS ASAHI MEOICAl CO, LTD +iJJJlLiJt os 4JOO 19 100 15 '77 " TOoo,JAPAN ! L! J..! L 1 !..

POLYACAYLONI"TRILE

AV-10 019 " AE~AFLO 0 5 MINNEAPOLIS, MN USA OS 3000 22 140 >20 OJO 50 POLYSULFONE

610SPAl 12005 employs ~ parallel plale ~onflgurallon Wllh 15 compartments each 6 5 em wide, 26 em long. and 250 microns apart F,ltration rates lrom manlJfacturer's literature POl5elllile lallO I~ calculated as pressure drop per UM blood flow rate at a deVice average blood VIscosity 01 5 cps

P"m'''g vOlume 1$ Irom ma"ula~turer's t'terature

DEVICES

45

DiafilterR Hollow Lexington, MA, U.S.A.) of CAVH and SCUF (3);

Fiber Ultrafilters (Amicon Corp., were utilized in the early development additional devices were introduced in

1982, and Table 1 describes those available at this time (February 1985) (4-7). These devices involve both flat-sheet and hollow-fiber geometrics. Design requirements are straightforward. Membranes should not activate complement. Poiseuille resistance should be low. The product of area and permeability must be balanced to yield a filtration rate of 10-20 cm3jmin under normal operating circumstances. Lower rates would be unacceptable to clinicians; higher rates might lead to excessive removal of water from the flowing blood. Priming volume should be minimal. Flow streamlines should be smooth and linear to avoid stagnation, vortices, separated flow, and other factors that may result in thrombosis.

FILTRATION RATE Boundary layer phenomena (e.g., concentration polariza-

tion) have

acute continuous renal replacement therapy

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