Design and prototype of an external quality assurance program for urine bicarbonate

This dissertation validates a Beckman-Coulter DxC R © assay for total bicarbonate in urine and then proceeds to design, prototype and cost an interlaboratory comparison (ILC) program for the above urine bicarbonate based on the validation. Furthermore, this work serves as a case study for how to establish proficiency testing – and thereby achieve accreditation – for tests without external quality assurance because of analyte instability. Urine bicarbonate analysis forms part of the diagnostic workup of renal tubular acidosis (RTA). The differential diagnosis of wasting and stunting includes RTA. Given an incidence of wasted and stunted children of 250 000 per annum in South Africa, one should anticipate that at least this many appropriate urine bicarbonates should be requested per annum – thus establishing a need for urine bicarbonate analysis. The provision of urine bicarbonate analysis as an accredited clinical laboratory test requires validation and quality assurance. The absence of proficiency testing for urine bicarbonate diminishes this quality assurance and establishes a problem. The dissertation also reviews the pathophysiology and diagnosis of RTA. Furthermore, it compares and contrasts the traditional and physicochemical clinical acid-base theories and introduces non-protoncentric acid-base theories. The study shows that the Beckman-Coulter DxC R © assay for total bicarbonate in urine has a functional sensitivity of 5mmol/L. The intralaboratory coefficient of variation at 10mmol/L is 18%. The reference range was calculated to be 2− 4mmol/L. The ILC program is based on the recovery of total carbon dioxide from urine spiked with sodium bicarbonate. The results are analysed using standard deviation index plots and Youden plots. For the ILC administering body, the marginal cost of producing the quality control samples and analysing the laboratory results is R4, 64 per ILC cycle – this is the minimum subscription to the ILC. For the laboratory being evaluated, the marginal cost of the ILC is the subscription plus the marginal cost of analysis. On an arterial blood gas analyser, the marginal cost of analysis is zero and thus the marginal cost of the ILC is R4, 64. The marginal cost of analysis on the Beckman-Coulter DxC R © is R13, 00 per quality control cycle and thus (for the laboratory being evaluated) the minimum marginal cost of the ILC is R17, 64. Acknowledgements I wish to thank the enthusiastic staff of Chemical Pathology at Red Cross Children’s War Memorial hospital for their assistance and tolerating my humour. Credit for the idea of this project should go to Cylene Seaton. I also wish to thank Ruth Brown for showing me the tricks of the trade. Last but certainly not least Lisa Ungerer – the go to woman. I should like to acknowledge the National Health Laboratory Service for providing both funding and facilities. I should also like to thank the University of Cape Town for providing the infrastructure and opportunity to perform this work which should be of benefit to clinical laboratories and consequently to patients. I thank my supervisors – Judy King and Pete Berman – for their guidance and assistance. In particular, I should like to thank Judy for her unwavering support and courage against seemingly insurmountable obstacles. This document was written in LATEX using MikTEX, Geany and TEXnicCenter on both MS windows R © and linux operating systems. Images were produced using XFig and Gimp. Graphs are from OpenOffice. Statistics was performed on R. This document was referenced with BibTEX and JabRef. This dissertation is dedicated to my parents Eric and Marda Benjamin – whose sacrifices (for more than three quarters of a century) are appreciated. Dissertation notation All equations are scalar and, where numbered, are identified by chapter name and number where the latter is chronological. Equation references are placed in brackets. Thus the 5th equation in section D1 will be designated (D1−5). The symbols in all equations are italicised. Similarly, all numbered reactions are identified by chapter and number but are placed in angled brackets. Thus the 2nd reaction in chapter B would be < B−2 >. The symbols within chemical reactions are also italicised. In Appendix D1, in an attempt to explain various acid-base theories, two vocabularies are constructed. The first vocabulary relates to the description of a phenomenon and the second relates to the explanation of a phenomenon. Consequently, acid-base phenomena are separated into description and explanation. A patient sample is collected from an individual. The aliquots from a patient sample are specimens. A sample consists of several specimens. Furthermore, a sample represents a collection of specimens from the population such that if a specimen was collected from every individual, within the population, that sample would be the population. The Road Not Taken Two roads diverged in a yellow wood, And sorry I could not travel both And be one traveler, long I stood And looked down one as far as I could To where it bent in the undergrowth; Then took the other, as just as fair, And having perhaps the better claim, Because it was grassy and wanted wear; Though as for that the passing there Had worn them really about the same, And both that morning equally lay In leaves no step had trodden black. Oh, I marked the first for another day! Yet knowing how way leads on to way, I doubted if I should ever come back. I shall be telling this with a sigh Somewhere ages and ages hence: Two roads diverged in a wood, and I – I took the one less traveled by, And that has made all the difference. Robert Frost