E Editorial

What Is a Reference Standard? Timothy E. Morey, MD, Mark J. Rice, MD, and Nikolaus Gravenstein, MD

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his month in the journal, Carabini and colleagues observed in “A Comparison of Hemoglobin Measured by Co-Oximetry and Central Laboratory During Major Spine Fusion Surgery” that significant differences existed in measured hemoglobin concentration from 1,832 contemporaneous blood specimens depending on whether the practitioner sent the blood sample aliquots to the central laboratory auto-analyzers, complete blood count (CBC), or the arterial blood gas (ABG) “stat” laboratory.1 More specifically, the ABG hemoglobin overestimated the CBC hemoglobin by 0.4 g/dL, although 7% of measurements had a >1.0 g/dL difference. Moreover, there was only fair to moderate agreement in the range of hemoglobin where a “transfusion trigger” might be pulled. These results led the authors to conclude that CBC and ABG techniques “… cannot be used interchangeably … when managing a patient with critical blood loss.”1 It also means that the two devices should not be used interchangeably as reference standards for scientific investigations. Lord William Kelvin (1824–1907), a founder of thermodynamics, cogently noted, “In physical science the first essential step in the direction of learning any subject is to find principles of numerical reckoning and practicable methods for measuring some quality connected with it. I often say that when you can measure what you are speaking about, and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre [sic] and unsatisfactory kind; it may be the beginning of knowledge, but you have scarcely in your thoughts advanced to the state of Science, whatever the matter may be.”2 This nineteenth-century observation was illustrated by Henry Marks and still serves us well today (Fig. 1). Based on the work of Carabini and colleagues in the twenty-first century, one wonders whether the method of measurement may affect the conclusions for a variety of medical investigations that may or may not use CBC or ABG hemoglobin concentrations to

test a certain hypothesis. That is, do different “numerical reckonings” affect the conclusions? For example, Brown and colleagues published in this journal earlier this year an analysis of 20,930 patients to test their hypothesis that older patients have a greater risk of packed red blood cell transfusion than younger ones.3 They accepted their hypothesis partly based on, “When patients were stratified by lowest in-hospital hemoglobin (7.00–7.99, 8.00–8.99, 9.00–9.99, and ≥10.00 g/dL), the odds of transfusion generally increased with each additional decade of age in every stratum, except for that containing patients in whom the lowest in-hospital hemoglobin did not decrease below

What is a reference standard?

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