NCCLSc29a2.pdf

C29-A2 Vol. 20 No. 17

Replaces C29-A Vol. 15 No. 1

Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition

This document contains recommendations on the expression of the results of ion-selective electrode measurement of sodium and potassium ion activities in undiluted serum, plasma, or whole blood in clinical practice.

A standard for global application developed through the NCCLS consensus process.

NCCLS...

Serving the World’s Medical Science Community Through Voluntary Consensus

NCCLS is an international, interdisciplinary, nonprofit, standards-developing, and educational organization that promotes the development and use of voluntary consensus standards and guidelines within the healthcare community. It is recognized worldwide for the application of its unique consensus process in the development of standards and guidelines for patient testing and related healthcare issues. NCCLS is based on the principle that consensus is an effective and cost-effective way to improve patient testing and healthcare services.

In addition to developing and promoting the use of voluntary consensus standards and guidelines, NCCLS provides an open and unbiased forum to address critical issues affecting the quality of patient testing and health care.

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Most NCCLS documents are subject to two levels of consensus—“proposed” and “approved.

the need for field evaluation or data collection, documents may also be made available for review at an intermediate (i.e., “tentative”) consensus level.

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COMMENTS

The comments of users are essential to the consensus process. Anyone may submit a comment, and all comments are addressed, according to the consensus process, by the NCCLS committee that wrote the document. All comments, including those that result in a change to the document when published at the next consensus level and those that do not result in a change, are responded to by the committee in an appendix to the document. Readers are strongly encouraged to comment in any form and at any time on any NCCLS document. Address comments to the NCCLS Executive Offices, 940 West Valley Road, Suite 1400, Wayne, PA

19087, USA.

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Volume 20 C29-A2 i

Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition

Abstract

Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved StandardCSecond Edition (NCCLS document C29-A2) offers a protocol for standardizing instruments that contain direct ion-selective electrodes to give results in concentration terms that are verifiable to the reference method (flame photometry) for specimens with normal plasma water (i.e., lipids and proteins). The document describes the preparation of serum pools to carry out the procedure. Laboratories without the resources, equipment, or personnel to prepare the pools can purchase them from the National Institute of Standards and Technology (Gaithersburg, MD). It is recommended in C29-A2 that the accuracy of each new direct potentiometric instrument be verified with these standard pools, together with the flame photometer, if it is also used to report patient results.

NCCLS. Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition. NCCLS document C29-A2 (ISBN 1-56238-410-4). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA 2000.

THE NCCLS consensus process, which is the mechanism for moving a document through two or more levels of review by the healthcare community, is an ongoing process. Users should expect revised editions of any given document. Because rapid changes in technology may affect the procedures, methods, and protocols in a standard or guideline, users should replace outdated editions with the current editions of NCCLS documents. Current editions are listed in the NCCLS Catalog, which is distributed to member organizations, and to nonmembers on request. If your organization is not a member and would like to become one, and to request a copy of the NCCLS Catalog, contact the NCCLS Executive Offices. Telephone: 610.688.0100; Fax: 610.688.0700; E-Mail: exoffice@nccls.org;

Website: www.nccls.org

Number 17 NCCLS ii

C29-A2

ISBN 1-56238-410-4

ISSN 0273-3099

Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition

Volume 20 Number 17

Paul D’Orazio, Ph.D W. Gregory Miller, Ph.D., Chairholder Gary L. Myers, Ph.D., Vice-Chairholder Basil T. Doumas, Ph.D.

John H. Eckfeldt, M.D., Ph.D.

Susan A. Evans, Ph.D.

Gary A. Graham, Ph.D., DABCC Patrick J. Parsons, Ph.D.

Noel V. Stanton, M.S.

iv

This publication is protected by copyright. No part of it may be reproduced, stored in a retrieval system, transmitted, or made available in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without prior written permission of NCCLS, except as stated below.

NCCLS hereby grants permission to reproduce limited portions of this publication for use in laboratory procedure manuals at a single site, for interlibrary loan, or for use in educational programs provided that multiple copies of such reproduction shall include the following notice, be distributed without charge, and, in no event, contain more than 20% of the document’s text.

Reproduced with permission, from NCCLS publication C29-A2—Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition (ISBN 1-56238-410-4). Copies of the current edition may be obtained from NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.

Permission to reproduce or otherwise use the text of this document to an extent that exceeds the exemptions granted here or under the Copyright Law must be obtained from NCCLS by written request.

To request such permission, address inquiries to the Executive Director, NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898, USA.

Copyright ©2000. The National Committee for Clinical Laboratory Standards.

Suggested Citation

(NCCLS. Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—Second Edition. NCCLS document C29-A2 [ISBN 1-56238-410-4]. NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2000.)

Proposed Standard December 1989

Tentative Standard December 1992

Approved Standard March 1995

Approved Standard—Second Edition October 2000

ISBN 1-56238-410-4

ISSN 0273-3099

v

Committee Membership

Area Committee on Clinical Chemistry and Toxicology

Basil T. Doumas, Ph.D.

Chairholder

Medical College of Wisconsin Milwaukee, Wisconsin

W. Gregory Miller, Ph.D.

Vice-Chairholder

Virginia Commonwealth University Richmond, Virginia

Paul D’Orazio, Ph.D. Instrumentation Laboratory Lexington, Massachusetts

John H. Eckfeldt, M.D., Ph.D. Fairview-University Medical Center Minneapolis, Minnesota

Susan A. Evans, Ph.D. Dade Behring Inc.

Deerfield, Illinois

Gary A. Graham, Ph.D., DABCC Ortho-Clinical Diagnostics Rochester, New York

Gary L. Myers, Ph.D. Centers for Disease Control and Prevention Atlanta, Georgia

Patrick J. Parsons, Ph.D. New York State Department of Health Albany, New York

Noel V. Stanton, M.S. University of Wisconsin Madison, Wisconsin

Advisors

Judith T. Barr, Sc.D. Northeastern University Boston, Massachusetts

Stanley Bauer, M.D. Beth Israel Medical Center New York, New York

George N. Bowers, Jr., M.D. Hartford Hospital Hartford, Connecticut

Robert W. Burnett, Ph.D. Hartford Hospital Hartford, Connecticut

Mary F. Burritt, Ph.D. Mayo Clinic Rochester, Minnesota

Kevin D. Fallon, Ph.D. Instrumentation Laboratory Lexington, Massachusetts vi

Advisors (Continued)

Carl C. Garber, Ph.D. Quest Diagnostics, Incorporated Teterboro, New Jersey

Harvey W. Kaufman, M.D. Quest Diagnostics, Incorporated Teterboro, New Jersey

Jan S. Krouwer, Ph.D. Bayer Diagnostics Medfield, Massachusetts

Victoria M. Leitz, Ph.D. International Biomedical Consultants Hilton Head, South Carolina

Richard R. Miller, Jr. Dade Behring Inc.

Newark, Delaware

Robert F. Moran, Ph.D., FCCM, FAIC mvi Sciences Methuen, Massachusetts

Richard B. Passey, Ph.D. University of Oklahoma Oklahoma City, Oklahoma

Edward A. Sasse, Ph.D. Medical College of Wisconsin Milwaukee, Wisconsin

Richard S. Schifreen, Ph.D. Promega Corporation Madison, Wisconsin

Bette Seamonds, Ph.D. National Academy of Clinical Biochemistry Swarthmore, Pennsylvania

Beth Ann Wise, M.T.(ASCP), M.S.Ed.

Staff Liaison

NCCLS

Wayne, Pennsylvania

Patrice E. Polgar Editor

NCCLS

Wayne, Pennsylvania

Donna M. Wilhelm Assistant Editor

NCCLS

Wayne, Pennsylvania vii

Acknowledgements

The Area Committee on Clinical Chemistry and Toxicology extends its appreciation to Paul D’Orazio, Ph.D., Co-Chairholder of the former Subcommittee on Electrolytes, for his help in preparing the second edition of this approved-level guideline, especially his advice on appropriate revisions and responses to the comments.

In addition, the area committee would also like to recognize the valuable contributions of the members and advisors of the Subcommittee on Electrolytes that developed the first approved edition of this guideline.

Paul D’Orazio, Ph.D., Co-Chairholder Gary Graham, Ph.D., Co-Chairholder Carolyn Bergkuist, M.S.

Ioannis Laios, Ph.D.

Alan Cormier, Ph.D.

Sharon Ehrmeyer, Ph.D.

Arthur Malenfant, Ph.D.

Richard R. Miller, Jr.

John Toffaletti, Ph.D.

Jesper Wandrup, M.D.

Advisors

George Bowers, Jr., M.D.

Richard A. Durst, Ph.D.

Neil Greenberg, Ph.D.

Jack Ladenson, Ph.D.

Robert F. Moran, M.S., Ph.D., FCCM, FAIC Kathleen M. O'Connell, Ph.D.

James Seago, Ph.D.

Paul Van Dreal, Ph.D.

viii ix

Active Membership (as of 1 October 2000)

Sustaining Members

Abbott Laboratories American Association for Clinical Chemistry Bayer Corporation Beckman Coulter, Inc.

BD and Company bioMérieux, Inc.

College of American Pathologists Dade Behring Inc.

Nippon Becton Dickinson Co., Ltd.

Ortho-Clinical Diagnostics, Inc.

Pfizer Inc Roche Diagnostics, Inc.

Professional Members

American Academy of Family Physicians American Association of Blood Banks American Association for Clinical Chemistry American Association for Respiratory Care American Chemical Society American Medical Technologists American Public Health Association American Society for Clinical Laboratory Science American Society of Hematology American Society for Microbiology American Society of Parasitologists, Inc.

American Type Culture Collection, Inc.

Asociación Española Primera de Socorros (Uruguay) Asociacion Mexicana de Bioquimica Clinica A.C.

Assn. of Public Health Laboratories Assoc. Micro. Clinici Italiani- A.M.C.L.I.

Australasian Association of Clinical Biochemists British Society for Antimicrobial Chemotherapy Canadian Society for Medical Laboratory Science—Société Canadienne de Science de Laboratoire Médical Canadian Society of Clinical Chemists

Clinical Laboratory Management Association College of American Pathologists College of Medical Laboratory Technologists of Ontario College of Physicians and Surgeons of Saskatchewan Commission on Office Laboratory Accreditation Fundación Bioquímica Argentina International Association of Medical Laboratory Technologists International Council for Standardization in Haematology International Federation of Clinical Chemistry Italian Society of Clinical Biochemistry Japan Society of Clinical Chemistry Japanese Association of Medical Technologists (Tokyo) Japanese Committee for Clinical Laboratory Standards Joint Commission on Accreditation of Healthcare Organizations National Academy of Clinical Biochemistry National Society for Histotechnology, Inc.

Ontario Medical Association Laboratory Proficiency Testing Program RCPA Quality Assurance Programs PTY Limited Sociedade Brasileira de Analises Clinicas Sociedade Brasileira de Patologia Clinica Sociedad Espanola de Quimica Clinica

Government Members

Armed Forces Institute of Pathology BC Centre for Disease Control Centers for Disease Control and Prevention Chinese Committee for Clinical Laboratory Standards Commonwealth of Pennsylvania Bureau of Laboratories Department of Veterans Affairs Deutsches Institut für Normung

(DIN)

FDA Center for Devices and Radiological Health FDA Center for Veterinary Medicine FDA Division of Anti-Infective Drug Products Health Care Financing Administration/CLIA Program Health Care Financing Administration Iowa State Hygienic Laboratory Massachusetts Department of Public Health Laboratories National Association of Testing Authorities – Australia National Center of Infectious and Parasitic Diseases (Bulgaria) National Institute of Standards and Technology Ohio Department of Health Ontario Ministry of Health Saskatchewan Health-Provincial Laboratory Scientific Institute of Public Health;

Belgium Ministry of Social Affairs, Public Health and the Environment South African Institute for Medical Research Swedish Institute for Infectious Disease Control Thailand Department of Medical Sciences

Industry Members

AB Biodisk Abbott Laboratories Abbott Laboratories, MediSense Products Accumetrics, Inc.

Amersham Pharmacia Biotech Ammirati Regulatory Consulting Asséssor AstraZeneca Aventis Avocet Medical, Inc.

Bayer Corporation - Elkhart, IN Bayer Corporation - Middletown, VA

Bayer Corporation - Tarrytown, NY Bayer Corporation – West Haven, CT

Bayer Medical Ltd.

BD

x

BD Biosciences – San Jose, CA BD Biosciences – Sparks, MD BD Consumer Products BD Italia S.P.A.

BD VACUTAINER Systems Beckman Coulter, Inc.

Beckman Coulter, Inc. Primary Care Diagnostics Beckman Coulter K.K. (Japan) Bio-Development SRL Bio-Inova Life Sciences International Biolog, Inc.

bioMérieux, Inc.

Biometrology Consultants Bio-Rad Laboratories, Inc.

Biotest AG Bristol-Myers Squibb Company Canadian Reference Laboratory Ltd.

Capital Management Consulting, Inc.

CASCO•NERL Diagnostics Checkpoint Development Inc.

Clinical Design Group Inc.

COBE Laboratories, Inc.

Combact Diagnostic Systems Ltd.

Community Medical Center (NJ) Control Lab (Brazil) Copan Diagnostics Inc.

Cosmetic Ingredient Review Cubist Pharmaceuticals Cytometrics, Inc.

Dade Behring Inc. - Deerfield, IL Dade Behring Inc. - Glasgow, DE Dade Behring Inc. - Marburg, Germany Dade Behring Inc. - Sacramento, CA Dade Behring Inc. - San Jose, CA

DAKO A/S

Diagnostic Products Corporation Eiken Chemical Company, Ltd.

Enterprise Analysis Corporation Fort Dodge Animal Health Gen-Probe Glaxo-Wellcome, Inc.

Greiner Meditech, Inc.

Health Systems Concepts, Inc.

Helena Laboratories Home Diagnostics, Inc.

Hycor Biomedical Inc.

I-STAT Corporation Instrumentation Laboratory International Technidyne Corporation Kendall Sherwood-Davis & Geck Labtest Diagnostica S.A.

LifeScan, Inc. (a Johnson & Johnson Company)

Lilly Research Laboratories Medical Automation Systems Medical Device Consultants, Inc.

Medical Laboratory Automation Inc.

Medtronic, Inc.

Merck & Company, Inc.

mvi Sciences (MA) Nabi Neometrics is.

Nichols Institute Diagnostics (Div. of Quest Diagnostics, Inc.)

Nissui Pharmaceutical Co., Ltd.

Nippon Becton Dickinson Co., Ltd.

Norfolk Associates, Inc.

Ortho-Clinical Diagnostics, Inc.

(Raritan, NJ) Ortho-Clinical Diagnostics, Inc.

(Rochester, NY) Oxoid Inc.

Pfizer Global R & D Pfizer Inc Pharmacia & Upjohn Premier Inc.

Procter & Gamble Pharmaceuticals, Inc.

The Product Development Group Quest Diagnostics Incorporated Quintiles, Inc.

Radiometer America, Inc.

Radiometer Medical A/S David G. Rhoads Associates, Inc.

Roche Diagnostics GmbH Roche Diagnostics, Inc.

Roche Laboratories (Div.

Hoffmann-La Roche Inc.)

The R.W. Johnson Pharmaceutical Research Institute Sanofi Diagnostics Pasteur Sarstedt, Inc.

SARL Laboratoire Carron (France) Schering Corporation Schleicher & Schuell, Inc.

Second Opinion SenDx Medical, Inc.

Showa Yakuhin Kako Company, Ltd.

SmithKline Beecham, S.A.

Streck Laboratories, Inc.

Sysmex Corporation (Japan) Sysmex Corporation (Long Grove, IL) The Toledo Hospital (OH) Trek Diagnostic Systems, Inc.

Vetoquinol S.A.

Visible Genetics, Inc.

Vysis, Inc.

Wallac Oy Wyeth-Ayerst Xyletech Systems, Inc.

YD Consultant Yeongdong Pharmaceutical Corporation

Trade Associations

AdvaMed Association of Medical Diagnostic Manufacturers Japan Association Clinical Reagents Ind. (Tokyo, Japan) Medical Industry Association of Australia

Associate Active Members

67th CSH Wuerzburg, GE (NY) 121st General Hospital (CA) Academisch Ziekenhuis-VUB (Belgium) Acadiana Medical Laboratories, LTD (LA)

Advocate Laboratories (IL) The Aga Khan Hospital & Medical College, Karachi (Pakistan) Albany Medical Center Hospital

(NY)

Albemarle Hospital (NC) Allegheny General Hospital (PA) Allegheny University of the Health Sciences (PA) Allina Laboratories (MN) Alton Ochsner Medical Foundation (LA) American Medical Laboratories

(VA)

Anzac House (Australia) Arkansas Department of Health Armed Forces Research Institute of Medical Science (APO, AP) Asan Medical Center (Korea) Associated Regional & University Pathologists (UT) Aurora Consolidated Laboratories (WI) Bay Medical Center (MI) Baystate Medical Center (MA) Boulder Community Hospital (CO) Brantford General Hospital (Brantford, ON, Canada) Brazileiro De Promocao (Brazil) Brookdale Hospital Medical Center (NY) Brooke Army Medical Center (TX) Brooks Air Force Base (TX) xi

Broward General Medical Center

(FL)

Calgary Laboratory Services Carilion Consolidated Laboratory

(VA)

CB Healthcare Complex (Sydney, NS, Canada) Central Kansas Medical Center Centralized Laboratory Services

(NY)

Centro Diagnostico Italiano (Milano, Italy) Champlain Valley Physicians Hospital (NY) Chang Gung Memorial Hospital (Taiwan) Children’s Hospital (LA) Children’s Hospital (NE) Children’s Hospital & Clinics (MN) Children’s Hospital King's Daughters (VA) Children’s Hospital Medical Center (Akron, OH) Children’s Hospital of Philadelphia (PA) Clarian Health–Methodist Hospital

(IN)

Clendo Lab (Puerto Rico) CLSI Laboratories (PA) Columbus County Hospital (NC) Commonwealth of Kentucky Commonwealth of Virginia (DCLS) CompuNet Clinical Laboratories

(OH)

Consolidated Laboratory Services (CA) Covance Central Laboratory Services (IN) Danish Veterinary Laboratory (Copenhagen, Denmark) Danville Regional Medical Center

(VA)

Deaconess Hospital (MO) Dean Medical Center (WI) Delaware Public Health Laboratory Department of Health & Community Services (New Brunswick, Canada) Detroit Health Department (MI) Diagnostic Laboratory Services, Inc. (HI) Duke University Medical Center

(NC)

Durham Regional Hospital (NC) Duzen Laboratories (Turkey) Dynacare Laboratories - Eastern Region (Ottawa, ON, Canada) Dynacare Memorial Hermann Laboratory Services (TX) E.A. Conway Medical Center (LA)

East Side Clinical Laboratory (RI) Elyria Memorial Hospital (OH) Emory University Hospital (GA) Esoterix Center for Infectious Disease (TX) Fairfax Hospital (VA) Fairview-University Medical Center (MN) Foothills Hospital (Calgary, AB, Canada) Fort St. John General Hospital (Fort St. John, BC, Canada) Fox Chase Cancer Center (PA) Franklin Square Hospital Center

(MD)

Fresenius Medical Care/Life Chem

(NJ)

Fresno Community Hospital and Medical Center Gambro Healthcare Laboratory

(FL)

GDS Technology, Inc (IN) Geisinger Medical Center (PA) Grady Memorial Hospital (GA) Guthrie Clinic Laboratories (PA) Harris Methodist Fort Worth (TX) Harris Methodist Northwest (TX) Hartford Hospital (CT) Health Alliance Laboratory (OH) Health Network Lab (PA) Health Sciences Centre (Winnipeg, MB, Canada) Heartland Health System (MO) Hinsdale Hospital (IL) Hoag Memorial Hospital Presbyterian (CA) Holmes Regional Medical Center

(FL)

Holy Spirit Hospital (PA) Holzer Medical Center (OH) Hospital for Sick Children (Toronto, ON, Canada) Hospital Israelita Albert Einstein (Brazil) Hotel Dieu Hospital (Windsor, ON, Canada) Huddinge University Hospital (Sweden) Hurley Medical Center (MI) Indiana State Board of Health Indiana University Instituto Scientifico HS. Raffaele (Italy) International Health Management Associates, Inc. (IL) Jacobi Medical Center (NY) Jersey Shore Medical Center (NJ) John C. Lincoln Hospital (AZ) John Peter Smith Hospital (TX)

John Randolph Hospital (VA) Johns Hopkins Medical Institutions

(MD)

Kaiser Permanente (CA) Kaiser Permanente (MD) Kaiser Permanente (NC) Kantousspital (Switzerland) Keller Army Community Hospital

(NY)

Kern Medical Center (CA) King Fahad National Guard Hospital (Saudi Arabia) Kings County Hospital Center (NY) Klinicni Center (Slovenia) LabCorp (NC) Laboratoire de Santé Publique du Quebec (Canada) Laboratório Fleury S/C Ltda.

(Brazil) Laboratory Corporation of America (MO) LAC and USC Healthcare Network (CA) Lakeland Regional Medical Center

(FL)

Lancaster General Hospital (PA) Langley Air Force Base (VA) LeBonheur Children’s Medical Center (TN) Lewis-Gale Medical Center (VA) Libero Instituto Univ. Campus BioMedico (Italy) Licking Memorial Hospital (OH) Louisiana State University Medical Center Magee Womens Hospital (PA) Magnolia Regional Health Center

(MS)

Martin Luther King/Drew Medical Center (CA) Massachusetts General Hospital (Microbiology Laboratory) Massachusetts General Hospital (Pathology Laboratory) Mayo Clinic Scottsdale (AZ) MDS Metro Laboratory Services (Burnaby, BC, Canada) Medical Center of Southern Indiana Medical College of Virginia Hospital Medicare/Medicaid Certification, State of North Carolina Memorial Hospital (CO) Memorial Medical Center (Napoleon Ave., New Orleans, LA) Memorial Medical Center (N. Jefferson Davis Pkwy., New Orleans, LA) Memorial Medical Center (IL) xii

Mercy Health System (PA) Mercy Hospital (NC) Mercy Medical Center Des Moines (IA) Mescalero Indian Hospital (NM) Methodist Hospital (TX) Methodist Hospitals of Memphis

(TN)

Michigan Department of Community Health Mississippi Baptist Medical Center Monte Tabor – Centro Italo - Brazileiro de Promocao (Brazil) Montreal Children’s Hospital (Canada) Montreal General Hospital (Canada) Morton Plant Mease Health Care

(FL)

Mount Sinai Hospital (NY) Mount Sinai Medical Center (FL) MRL Reference Laboratory (CA) National University Hospital (Singapore) Naval Surface Warfare Center (IN) New Britain General Hospital (CT) New England Fertility Institute (CT) New England Medical Center Hospital (MA) New York Hospital Medical Center of Queens New York State Department of Health NorDx (ME) North Carolina Laboratory of Public Health North Mississippi Medical Center North Shore – Long Island Jewish Health System Laboratories (NY) Northridge Hospital Medical Center (CA) Northwestern Memorial Hospital

(IL)

Ohio Valley Medical Center (WV) Olin E. Teague Medical Center (TX) O.L. Vrouwziekenhuis (Belgium) Ordre professionnel des technologists médicaux du Québec Ospedali Riuniti (Italy) The Ottawa Hospital (Ottawa, ON, Canada) Our Lady of Lourdes Hospital (NJ) Our Lady of the Resurrection Medical Center (IL) Pathology and Cytology Laboratories, Inc. (KY) Pathology Associates Laboratories

(CA)

The Permanente Medical Group

(CA)

Pocono Hospital (PA) Presbyterian Hospital (NC) Presbyterian Hospital of Dallas

(TX)

Providence Health System (OR) Providence Seattle Medical Center

(WA)

Queen Elizabeth Hospital (Prince Edward Island, Canada) Queensland Health Pathology Services (Australia) Quest Diagnostics, Incorporated

(AZ)

Quest Diagnostics Incorporated

(CA)

Quintiles Laboratories, Ltd. (GA) Regions Hospital Research Medical Center (MO) Rex Healthcare (NC) Rhode Island Department of Health Laboratories Riyadh Armed Forces Hospital (Saudi Arabia) Royal Columbian Hospital (New Westminster, BC, Canada) Saint Mary’s Regional Medical Center (NV) St. Alexius Medical Center (ND) St. Anthony Hospital (CO) St. Barnabas Medical Center (NJ) St. Boniface General Hospital (Winnipeg, Canada) St. Elizabeth Hospital (NJ) St. John Hospital and Medical Center (MI) St. John Regional Hospital (St.

John, NB, Canada) St. Joseph Hospital (NE) St. Joseph Medical Center (MD) St. Joseph Mercy – Oakland (MI) St. Joseph’s Hospital – Marshfield Clinic (WI) St. Luke’s Hospital (PA) St. Luke’s Regional Medical Center (IA) St. Mary Medical Center (IN) St. Mary of the Plains Hospital

(TX)

St. Mary’s Hospital & Medical Center (CO) Ste. Justine Hospital (Montreal, PQ, Canada) Salina Regional Health Center (KS) San Francisco General Hospital

(CA)

Santa Cabrini Hospital (Montreal, PQ Canada)

Santa Clara Valley Medical Center

(CA)

Seoul Nat’l University Hospital (Korea) Shanghai Center for the Clinical Laboratory (China) Shands Healthcare (FL) SmithKline Beecham Clinical Laboratories (GA) South Bend Medical Foundation

(IN)

Southern California Permanente Medical Group South Western Area Pathology Service (Australia) Speare Memorial Hospital (NH) Speciality Laboratories, Inc. (CA) Stanford Hospital and Clinics (CA) State of Washington Department of Health Stormont-Vail Regional Medical Center (KS) Sun Health-Boswell Hospital (AZ) Sunrise Hospital and Medical Center (NV) Touro Infirmary (LA) Tri-City Medical Center (CA) Trident Regional Medical Center

(SC)

Tripler Army Medical Center (HI) Truman Medical Center (MO) Tulane Medical Center Hospital & Clinic (LA) UCSF Medical Center (CA) UNC Hospitals (NC) Unilab Clinical Laboratories (CA) University Hospital (Gent) (Belgium) University Hospital (TX) The University Hospitals (OK) University of Alberta Hospitals (Canada) University of Chicago Hospitals (IL) University of Florida University of Medicine & Dentistry, NJ University Hospital University of the Ryukyus (Japan) University of Texas M.D. Anderson Cancer Center University of Virginia Medical Center University of Washington UPMC Bedford Memorial (PA) UZ-KUL Medical Center (Belgium) VA (Dayton) Medical Center (OH) VA (Denver) Medical Center (CO) VA (Martinez) Medical Center (CA) VA (San Diego) Medical Center

(CA)

xiii

VA (Tuskegee) Medical Center

(AL)

VA Outpatient Clinic (OH) Vejle Hospital (Denmark) Virginia Department of Health Viridae Clinical Sciences, Inc.

(Vancouver, BC, Canada) Warde Medical Laboratory (MI) Washoe Medical Center (NV)

Watson Clinic (FL) Wilford Hall Medical Center (TX) William Beaumont Hospital (MI) Williamsburg Community Hospital

(VA)

Winchester Hospital (MA) Winn Army Community Hospital

(GA)

Wishard Memorial Hospital (IN) Womack Army Medical Center

(NC)

Yan Chai Hospital (P.R. China) Yonsei University College of Medicine (Korea) York Hospital (PA) Zale Lipshy University Hospital

(TX)

OFFICERS BOARD OF DIRECTORS

F. Alan Andersen, Ph.D., President Cosmetic Ingredient Review

Donna M. Meyer, Ph.D., President Elect CHRISTUS Health

Robert F. Moran, Ph.D., FCCM, FAIC

Secretary mvi Sciences

Gerald A. Hoeltge, M.D.

Treasurer The Cleveland Clinic Foundation

William F. Koch, Ph.D., Immediate Past President National Institute of Standards and Technology

John V. Bergen, Ph.D., Executive Director

Susan Blonshine, RRT, RPFT, FAARC

TechEd

Kurt H. Davis, FCSMLS, CAE Canadian Society for Medical Laboratory Science

Robert L. Habig, Ph.D.

Cytometrics, Inc.

Thomas L. Hearn, Ph.D.

Centers for Disease Control and Prevention

Elizabeth D. Jacobson, Ph.D.

Food and Drug Administration

Carolyn D. Jones, J.D., M.P.H.

Health Industry Manufacturers Association

Tadashi Kawai, M.D., Ph.D.

International Clinical Pathology Center

J. Stephen Kroger, M.D., FACP

COLA

Barbara G. Painter, Ph.D.

Bayer Corporation

Emil Voelkert, Ph.D.

Roche Diagnostics GmbH

Ann M. Willey, Ph.D.

New York State Department of Health

Judith A. Yost, M.A., M.T.(ASCP) Health Care Financing Administration xiv xv

Contents

Abstract..............................................................................................................................................i

Committee Membership.....................................................................................................................v

Active Membership ..........................................................................................................................ix

Foreword ....................................................................................................................................... xvii

1 Introduction

2 Scope

3 Definitions/Terminology

3.1 Abbreviations

4 Standard Precautions

5 Purpose

5.1 Whole Blood and Undiluted Plasma or Serum

5.2 "Normal" Specimens

5.3 Characteristics of a "Normal" Specimen

6 Background

6.1 Preanalytical Effects on Patient Sample Results: Influences of Specimen Choice, Collection, and Handling

6.2 Analytical Issues

6.3 Reporting Results

7 Standardization of Result Reporting

7.1 Materials

7.2 Sample Analysis and Data Reduction

7.3 Validation Protocol Using Patient Samples (Optional)

References

Appendix A. Specifications for a Human Serum Certified Reference Material (CRM) for the ISE Measurement of Sodium and Potassium in Blood

Appendix B. Estimated Number of Replicates for Demonstrating Equality of Flame and ISE Determination

Appendix C. An Example of Normalization of Linear Regression Data for Sodium to 140 mmol/L and Adjustment of the Slope to One and Intercept to Zero

Appendix D. Determination of Plasma Water Mass Concentration

Summary of Comments and Subcommittee Responses

Summary of Delegate Comments and Responses

Related NCCLS Publications xvi xvii

Foreword

Analysis of electrolytes in whole blood is becoming increasingly common, and instruments that perform these analyses (ion-selective electrodes that do not require diluted samples, i.e., direct ISE) are available from a number of manufacturers. In many clinical laboratories, instruments that use a diluted specimen [flame photometry or indirect ion-selective electrodes (ISEs)] are also still in use. Direct ISE results are not equivalent to those results obtained by the technology employing dilution for a number of reasons, foremost of which are those relating to the variation in plasma water. To avoid confusion, we recommend that results obtained by direct potentiometry be adjusted to resemble those obtained by procedures that measure concentration in plasma. Most instruments using direct ISEs have built-in conversion algorithms that can be utilized by putting the instrument in "flame" mode. However, it is clear from work performed at the National Institute of Standards and Technology (NIST) that a number of direct potentiometric systems from a variety of manufacturers do not give identical results when assaying identical specimens even in the "flame" mode.

The results of determinations of sodium and potassium ions in physiological fluids have been expressed in terms of (substance) concentration (mmol/L) for many years. The use of concentrations of both sodium and potassium and their reference intervals is firmly established in clinical interpretation and practice. Analytical systems that report concentration, such as flame atomic emission spectrometry (FAES) and ion-selective electrode systems using diluted samples, will continue to be used alongside direct ion-selective electrode determinations in the foreseeable future. Consequently, to introduce a new system of reporting results of sodium and potassium determinations by ion-selective electrodes in terms of ion activity carries significant risks of confusing clinical interpretation.

2,3

A more fundamental problem also exists. Ion-selective electrodes respond to the thermodynamic activity of ions in solution. By theory, they do not sense concentration which, in fluids such as plasma, is related in a complex way to activity.

4, 2 Therefore, results should be expressed in terms of ion activity. Many practical difficulties exist with this approach, however. Because the activity of these ions cannot, at present, be determined with certainty, particularly in a fluid as complex as plasma, the accuracy of any determination of activity cannot be verified.

The convention recommended in this standard represents a pragmatic compromise that facilitates the introduction of ion-selective electrode determinations of sodium and potassium ion concentrations in whole blood or undiluted plasma into routine clinical practice, while minimizing the risk of clinical misinterpretation.

Key Words

Direct potentiometry, flame photometry, ion-selective electrode (ISE), potassium, sodium xviii

An NCCLS global consensus standard. ©NCCLS. All rights reserved. 1

Standardization of Sodium and Potassium Ion-Selective Electrode Systems to the Flame Photometric Reference Method; Approved Standard—

Second Edition

1 Introduction

The objective of this standard is to describe a method to standardize direct ion-selective electrode analyzers for determination of sodium and potassium in blood plasma to units of concentration (mmoI/L) in “normal” plasma, as reported by flame atomic emission spectrometry (flame photometry). This standardized method will allow clinical laboratories to use the same reference intervals, regardless of instrumentation or principle of the methodology.

2 Scope

This document addresses the determination of sodium and potassium in undiluted plasma in routine clinical practice using ion-selective electrodes.

3 Definitions/Terminology a

Calibration material//Calibrator, n - A material or device of known, or assigned quantitative characteristics (e.g., concentration, activity, intensity, reactivity, responsiveness) used to adjust the output of a measurement procedure or to compare the response obtained with the response of a test specimen and/or sample.

Direct analysis, n - Measurement made directly on an undiluted specimen, e.g., whole blood, plasma, or sweat.

Flame mode, n - In the flame mode, a factor can be applied to results generated by direct ISE systems that makes the results comparable to those generated by indirect systems for patient specimens normal in protein and lipid content.

Heparinized, adj - Specimens anticoagulated with a heparin salt(s).

Indirect analysis, n - Systems that require dilution of the sample; NOTE: These include some ion-selective, electrode-based systems, as well as flame emission photometry and atomic absorption.

Plasma, n - The liquid part {of whole blood} remaining after the separation of the cellular elements ... in a receptacle containing an anticoagulant, or separated by continuous filtration or centrifugation of anticoagulated blood in an apheresis procedure.

Primary standard, n - A standard that is designated or widely acknowledged as having the highest metrological qualities and whose value is accepted without reference to other standards of the same quantity.

a Some of these definitions are found in NCCLS document NRSCL8C Terminology and Definitions for Use in NCCLS Documents. For complete definitions and detailed source information, please refer to the most current edition of that document.

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3.1 Abbreviations

Sectionb

ACD Acid citrate dextrose A2.1

CRM/SRM Certified reference material/standard reference material 7.1/App. A

CV Coefficient of variation 7.2.2

EP-BGpH/IFCC Expert Panel on Blood Gas/pH of the IFCC A3

FAAS Flame atomic absorption spectrometry A2.3

FAES Flame atomic emission spectroscopy A2.1(4)

FP Flame photometer 6.2.2

HIV Human immunodeficiency virus A2.1

IFCC International Federation of Clinical Chemistry A3

ISE Ion-selective electrode 3

NIST National Institute of Standards and Technology 7.1

NRSCL National Reference System for the Clinical Laboratory A1.3

4 Standard Precautions

Because it is often impossible to know what might be infectious, all human blood specimens are to be treated as infectious and handled according to “standard precautions.” Standard precautions are new guidelines that combine the major features of “universal precautions and body substance isolation” practices. Standard precautions cover the transmission of any pathogen and thus are more comprehensive than universal precautions which are intended to apply only to transmission of blood-borne pathogens.

Standard precaution and universal precaution guidelines are available from the U.S. Centers for Disease Control and Prevention (Guideline for Isolation Precautions in Hospitals. Infection Control and Hospital Epidemiology. CDC. 1996;Vol 17;1:53-80.), [MMWR 1987;36(suppl 2S):2S-18S] and (MMWR 1988;37:377-382, 387-388). For specific precautions for preventing the laboratory transmission of blood-borne infection from laboratory instruments and materials; and recommendations for the management of blood-borne exposure, refer to NCCLS document M29—Protection of Laboratory Workers from Instrument Biohazards and Infectious Disease Transmitted by Blood, Body Fluids, and Tissue.

5 Purpose

The purpose of this standard is to recommend a procedure for the standardization of reported, direct ion-selective electrode determination of sodium and potassium in serum, plasma, or whole blood.

b Section where abbreviation first appears in text.

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A convention for reporting results of ion-selective electrode determinations of sodium and potassium is proposed whereby, for routine clinical purposes:

5.1 Whole Blood and Undiluted Plasma or Serum

Results of ion-selective electrode determinations of sodium and potassium in whole blood and undiluted

5.2 "Normal" Specimens

Results of measurements on "normal" specimens should conform with those obtained by flame atomic emission spectrometry on the same specimens.

5.3 Characteristics of a "Normal" Specimen

"Normal" plasma specimens are herein defined as having mass concentration of plasma water of 0.93 ±

0.01 kg/L; plasma total CO2 of 24 ± 2 mmol/L; plasma pH of 7.40 ± 0.05; and concentrations of albumin, total protein, cholesterol, and triglycerides as specified in Section 7.3.

6 Background

6.1 Preanalytical Effects on Patient Sample Results: Influences of Specimen Choice, Collection, and Handling

Electrolyte results, especially for potassium, may be affected by cellular transfer that occurs either during patient preparation, sample collection, or sample handling.

Because the sodium concentration in erythrocytes is one-tenth that of plasma, hemolysis has little effect on the sodium concentration. For example, hemolysis resulting in a plasma hemoglobin of 5 g/L would decrease a 140-mmol/L plasma sodium concentration by only 0.4%. Sodium concentrations are markedly affected only by extremely severe (>10 g/L Hb) hemolysis.

Because the intracellular potassium concentration is about 23 times higher than that in plasma, cellular disruption or cellular leakage of potassium can markedly alter the potassium concentration of plasma.

6.1.1 Cellular Disruption

For example, hemolysis resulting in a plasma hemoglobin of 5 g/L would increase plasma potassium concentration by 0.5 mmol/L. Because platelets are ruptured during coagulation, serum potassium is increased by 0.1 to 0.7 mmol/L, or even higher, in patients with thrombocytosis.

5 Therefore, plasma is preferred for determination of potassium.

6.1.2 Cellular Leakage

Potassium movement through intact cell membranes can also alter plasma potassium by several mechanisms during specimen collection.

6.1.2.1 Extracellular Acidosis

Extracellular acidosis due to tourniquet application with forearm exertion leads to exchange of hydrogen ion for potassium resulting in a 10 to 20% increase in plasma potassium.

7 The tourniquet should not be released until the collection is completed.

plasma or serum (see Section 3) should be reported in terms of concentration (mmol/L).

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6.1.2.2 Intracellular Glucose Depletion

Intracellular glucose depletion by glycolysis induces glucose entry into cells. This entry is accompanied by potassium, decreasing extracellular potassium. This mechanism is an early and limited process, especially evident in patients with leukocytosis (leukocyte count above 100 x 109/L).

6.1.2.3 Sodium/Potassium Pump

Cellular leakage is dependent upon the sodium/potassium pump. Its efficiency is temperature- and energy-dependent. When temperature decreases, the pump slows down, causing the potassium to leak out of the cell. The rise in plasma potassium is about 0.15 mmol/L per hour at 25"C and about 0.25 mmol/L per hour at 4"C6 (for example, after storage of a syringe in ice water). Some anticoagulants, which inhibit glycolysis, can also increase plasma potassium.

6.1.3 Collection and Handling

To summarize the practical recommendations for collection and handling:

• Prolonged tourniquet application (in excess of 2 minutes) and forearm exertion by the patient should be avoided.

• Blood should be collected with Li heparin as an anticoagulant.

• Samples should be kept at room temperature (20 to 25"C).

• Plasma should be separated from cells within 60 minutes after collection.

6.2 Analytical Issues

6.2.1 Direct Measurement

In a properly designed direct ion-selective electrode system, differences in sodium and potassium measurements between heparinized plasma and whole blood should be minimal. The differences seen are attributed primarily to changes in the liquid-junction potential due to the erythrocytes and can be minimized with the use of properly designed systems and electrolyte solutions to form the liquid junction.

6.2.2 Indirect Methods

The traditional methods measure the concentration of Na, K in plasma (e.g., FP and "diluting" ISE instruments.) The FP measures the intensity of light emitted by the sodium and potassium atoms excited by the flame. This light intensity is directly proportional to the number of sodium and potassium atoms, which, in turn, is directly proportional to the concentration of these ions in the sample. Instruments using diluted ISE specimens also measure the plasma sodium/potassium concentration, because the sample is diluted such that both the activity coefficient of sodium and potassium and the volume fraction of water in the sample is nearly equal to the activity coefficient of sodium and potassium and the volume fraction of water in the calibrating solutions. Under these conditions, activity is directly proportional to concentration with the same proportionality constant from sample to sample.

6.2.3 Analytical Comparison: Direct versus Indirect

About 47% of the participants in the 1994 C-A Comprehensive Chemistry Survey of the College of American Pathologists9 used diluted ISE methods for determining sodium. Another 1% of the

An NCCLS global consensus standard. ©NCCLS. All rights reserved. 5 participants used the FP. Diluted ISE methods are referred to as "indirect" methods. The difference in the sodium and potassium results between the direct and indirect methods is mainly due to the electrolyte plasma. Sodium ions are almost exclusively associated with the water phase of plasma. Because the volume fraction of plasma water in normal specimens is approximately 93%, indirect ISEs and FPs will produce results that are about 7% lower than direct ISE methods. All methods that measure the concentration of sodium in plasma are related to the total volume of sample and not the water phase of that sample. As the volume fraction of plasma water is altered by disease, the difference between the direct and indirect methods will also change (see Section 6.2.4). Another source of differences between direct and indirect methods is the binding of these ions by inorganic and organic ligands, primarily bicarbonate. This binding is minimal (1 to 2%) as compared to the influence of plasma water (7%).

6.2.4 Abnormal Specimens

In all samples with abnormal lipid and protein levels, diluted methodologies give results that are biased from measurements on undiluted samples. For specimens with abnormal concentrations of plasma water, bicarbonate, or hydrogen ions, the results reported by ion-selective electrodes on undiluted samples and by flame atomic emission spectrometry diverge. Results obtained by ion-selective electrodes on undiluted samples more accurately reflect the pathophysiological status of these ions in plasma water and thus may be more relevant clinically than those reported by flame atomic emission spectrometry.

11,12

Difference in sodium values due to protein concentration can be as high as 17 mmol/L (total protein ~160 g/L), 13 while differences due to lipid concentration (triglyceride ~113,000 mg/L) were reported to be 26 mmol/L.

6.3 Reporting Results

If results by both techniques are available, it should be made clear whether they are derived from measurements with ISEs on undiluted specimens or with diluted specimens by ISE or FP. This is necessary, because certain samples with abnormalities in lipid, protein, or bicarbonate concentration can give clinically important differences in electrolytes depending on the analytical procedure. The risk for clinical misinterpretation is present if results from ISE using sample dilution or FP only are reported for samples with these abnormalities. In these cases, the direct ISE result is to be regarded as the more clinically relevant result.

7 Standardization of Result Reporting

The objective of this standard is to describe a method to standardize direct ion-selective electrode analyzers for determination of sodium and potassium in blood plasma to units of concentration (mmol/L) in "normal" plasma, as reported by flame atomic emission spectrometry (flame photometry). Bias of the ISE analyzer to flame photometry after this standardization process should be within ±2%. This is the maximum allowable population difference, irrespective of the sodium or potassium concentration, within the 120- to 160-mmol sodium/L or 2- to 6-mmol potassium/L plasma ranges. Therefore, clinical laboratories will be able to use the same reference intervals, regardless of instrumentation or principle of the methodology.

7.1 Materials

Three serum pools should be included in this method. Three reference materials, formulated for the purpose of standardizing ion-selective electrode analyzers to flame photometry, are available from NIST [Gaithersburg, MD; telephone (301) 975-OSRM] and are recommended (SRM 956a). The sodium and potassium concentrations (mmol/L) of these pools are as follows:

exclusion effect. This effect is caused by the solvent -displacing effect of lipids and proteins in the

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Level 1 Level 2 Level 3

Sodium 120 ± 2 140 ± 2 160 ± 2 Potassium 6.0 ± 0.2 4.0 ± 0.2 2.0 ± 0.2

As an alternative to purchasing these materials, the serum pools may be prepared using the method described in Appendix A. Alternative materials from other countries may be acceptable upon verification by the user according to specifications listed in Appendix A.

7.2 Sample Analysis and Data Reduction

The following protocol may be used with SRM 956a or with serum pools. If SRM 956a is used, then the label values assigned by NIST should be used below in lieu of the flame photometric concentrations. The Subcommittee on Electrolytes believes that the most practical method for standardization and/or verification of the standardization of ISE instruments is to use the NIST standard reference material.

7.2.1 Calibration and Analysis

The ISE instrument should be calibrated according to the manufacturer's instructions and operated in the flame mode when this option is available. The FP should be calibrated according to the NIST reference method.

15,16 Each of the three serum pools should be analyzed by alternating determinations on the ISE analyzer and FP. They should be run in random order with respect to concentration, for a total of 15 replicates on each instrument for each concentration.

Example: Individual determinations might…