Agreement between whole blood and plasma sodium measurements in profound hyponatremia,☆☆,,★★

https://doi.org/10.1016/j.clinbiochem.2015.03.001Get rights and content

Highlights

  • We compare three methods of sodium measurement in profound hyponatremia.

  • Radiometer ABL-827© and plasma (Roche Cobas c502©) sodium values agreed closely.

  • Abbott iSTAT© values showed a positive bias relative to plasma sodium values.

  • In practice, both plasma and whole blood methods are often used at different times.

  • Clinicians may consider our results when selecting a whole blood measurement method.

Abstract

Objectives

We compared two different methods of whole blood sodium measurement to plasma sodium measurement using samples in the profoundly hyponatremic range (Na < 120 mmol/L).

Design and methods

Whole blood pools with a range of low sodium values were generated using combinations and dilutions of pooled electrolyte-balanced lithium heparin samples submitted for arterial blood gas analysis. Each pool was analyzed five times on a Radiometer 827 blood gas analyzer and iSTAT analyzer. Pools were centrifuged to produce plasma, which was analyzed five times on a Roche Cobas c501 chemistry analyzer. An additional 40 fresh (analyzed on day of collection) excess lithium heparin arterial blood gas samples from 36 patients were analyzed on the Radiometer 827, iSTAT, and Cobas c501 as described above. The setting was a tertiary referral center. Blood samples were collected from a combination of patients in the intensive care unit, operating theaters and emergency room.

Results

All methods demonstrated excellent precision, even in the profoundly hyponatremic measurement range (Na < 120 mmol/L using a plasma reference method). However, agreement between the methods varied with the degree of hyponatremia. In the profoundly hyponatremic range, Radiometer whole blood sodium values were nearly identical to plasma reference sodium, while iSTAT whole blood sodium showed a consistent positive bias relative to plasma sodium in this range.

Conclusion

If whole blood direct sodium measurements are compared with plasma sodium in profoundly hyponatremic patients consideration should be given to the use of Radiometer blood gas analyzers over iSTAT since the latter shows a positive bias relative to a plasma comparative method.

Introduction

Hyponatremia is a common electrolyte abnormality in hospitalized patients [1] and dysnatremia is an independent risk factor for hospital mortality [2]. Profound hyponatremia (sodium < 120 mmol/L) can lead to cerebral edema and correction of the hyponatremia is necessary to prevent or treat associated neurological complications or death [3]. However, excessively rapid correction of profound hyponatremia is well established to be associated with a risk of osmotic demyelination syndrome (ODS), which may itself cause substantial morbidity or mortality [4].

Targeted rates of sodium correction are often difficult to achieve in profound hyponatremia and expert opinion has consistently emphasized the unpredictability of response to treatment [5], [6]. Early identification or anticipation of non-optimal correction is important because there is convincing evidence from animal models that minimizing the duration of non-optimal correction reduces the risk of subsequent ODS and mortality [7]. Despite significant attention to the diagnostic workup in profound hyponatremia, there is little evidence-based guidance on how clinicians should monitor response to treatment.

Many investigators have recommended very frequent monitoring of electrolytes during therapy [8], [9], and others have even suggested the monitoring of sodium as frequently as every one to 2 h during acute therapy [5]. This raises the challenge of determining the optimal method and frequency of monitoring. Surprisingly, this issue has not attracted significant attention. While the use of indirect ion-selective electrodes (indirect ISE) for testing sodium levels is the most common method for laboratory sodium measurement, direct (undiluted) ion-selective electrode (direct ISE) whole blood methods have advantages in that they require smaller blood sample volumes and may be performed at or near the point of care, which may eliminate delays in specimen collection/processing, as well as communication of results to the treating physician [10]. Several small studies have investigated the agreement between direct and indirect ISE sodium measurements [11], [12], [13], [14], [15]. However, none have assessed the precision of the individual methods and the agreement between various methods in the profoundly hyponatremic range. Thus, our object was to assess the precision of indirect (plasma) and direct (whole blood) sodium measurements in the profoundly hyponatremic range and also assess the agreement between whole blood and plasma methods.

Section snippets

Creation of low sodium pools for bias and precision studies

Electrolyte-balanced lithium heparin samples submitted for arterial blood gas (ABG) analysis from patients in the intensive care unit, operating theaters, or emergency department were pooled and allowed to sit at 4 °C for 1 to 3 weeks to create a pool of lithium heparin whole blood with a sodium concentration of approximately 90 mmol/L. Patient samples were allowed to sit at 4 °C to reduce sodium values due to cellular redistribution of water and sodium in the samples. Lithium heparin whole blood

Sodium bias and precision from pooled and manufactured samples

The sample pools at various sodium concentrations were prepared and analyzed as described under Materials and methods section. The precision of each method was very good, with an observed coefficient of variation (CV)  1.3% for all the sample pools (with the exception of one low sodium pool on the Radiometer), spanning sodium concentrations of 104 to 133 mmol/L (Table 1).

Using ANOVA to test differences between the platforms for individual pools, for sodium concentrations of < 130 mmol/L (pools 1,

Discussion

In this study we describe the bias (compared to a comparative plasma measurement) and the precision of two whole blood sodium methods across a wide range of sodium levels. Both the whole blood and plasma methods demonstrated very good precision (around 1% CV), even in the profoundly hyponatremic measurement range (Na < 120 mmol/L on plasma method). Thus method imprecision is not the cause of ≥ 3 mM discrepancies between whole blood and plasma sodium observed in this and previous (see below) studies

Conclusion

When measuring sodium trajectories in the profoundly hyponatremic range (< 120 mmol/L), clinicians should be aware that there are limitations to using different measurement methods interchangeably, since agreement between the methods is not perfect. Ideally, a single method of measurement should be used and, in general, all these methods will be acceptably precise in this range. However, if the turnaround times or other concerns will result in both direct and indirect sodium measurements being

Acknowledgments

The authors gratefully acknowledge the entire M.E.T.R.I.C. research group for their support, which made this project possible. We also thank Mayo Clinic's Center for Translational Science Activities, Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), for their support. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

References (16)

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Cited by (4)

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    Each 1 g/dL [10 g/L] increase in Hb independently decreased DNa by approximately 0.15 mmol/L relative to INa. Although this estimate remained consistent in sensitivity analyses, its confirmation is obviously necessary, with the expectation that the effect size might vary when other analytic platforms and blood gas samplers are tested [12–14]. Incidentally, the inclusion of Hb into the model altered the point estimate of the TP effect slightly to 0.8 mmol/L per 1 g/dL [10 g/L] (Table 2).

  • Comparison of serum sodium levels measured by blood gas analyzer and biochemistry autoanalyzer in patients with hyponatremia, eunatremia, and hypernatremia

    2016, American Journal of Emergency Medicine
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    The authors found a mean difference of 3.36 mmol/L. Some studies included patients with hyponatremia or hypernatremia by biochemistry autoanalyzer; however, sample sizes were relatively small, and the authors did not report biases in hyponatremia or hypernatremia groups separately [3,11]. One of the largest studies conducted in this field by Mirzazadeh et al [8] evaluated records of approximately 11 000 paired samples.

Institution: This work was performed at Mayo Clinic in Rochester, MN.

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Financial support: None.

Conflicts of interest: None.

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MeSH headings: Hyponatremia, blood gas analysis.

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