Falsely elevated sodium levels during thiopental treatment in the ICU: technical interference on a laboratory device with important clinical relevance.

INTRODUCTION: Thiopental is a cornerstone in the treatment of refractory status epilepticus and intractable intracranial hypertension. In our center we observed that thiopental might cause falsely elevated serum sodium levels. METHODS: Triggered by a recent case experience of extremely elevated serum sodium levels during thiopental treatment, we retrospectively identified 53 patients treated with thiopental in our intensive care unit between 2007 and 2011 and evaluated electrolyte changes. We differentiated the analysis before and after introduction of a new device for sodium assays (Dimension Vista, Siemens) in the central laboratory in April 2010. Standardized in vitro laboratory tests were performed to study the effect of thiopental on sodium analysis. RESULTS: Before April 2010, serum sodium levels determined in the central laboratory showed a good agreement with the bedside point-of-care (POC) device during thiopental therapy with [sodium](laboratory) - [sodium](POC) of only 1.08 mmol/L (P = .0517). After April 2010, a strong discrepancy between laboratory values and POC values was observed with [sodium](laboratory) - [sodium](POC) = 11.57 mmol/L (P < .0001). Standardized in vitro testing confirmed that thiopental induced a dose-dependent false hypernatremia (P = .002). CONCLUSIONS: Thiopental treatment can result in falsely elevated serum sodium. This is a critical finding since high sodium levels preclude administrating mannitol or hypertonic saline for the treatment of elevated intracranial pressure. Moreover, a false high sodium level might lead to the inappropriate administration of hypotonic fluids potentially resulting in increased brain edema and even higher intracranial pressure. To our knowledge, this is the first paper describing this clinically relevant phenomenon.

Usefulness of early rule-in and rule-out biomarker protocols to estimate ischemia-induced myocardial injury in early chest pain presenters.

Protocols to minimize the time between 2 measurements of troponin or a combination with copeptin have been developed to rapidly rule-in or rule-out myocardial injury (MI) in patients with chest pain. These fast track protocols to rule-in and rule-out MI are not sufficiently validated for early chest pain presenters. The "early presenter" model was tested in 107 stable patients after a short period of myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI), and copeptin were measured at the start and 90, 180, and 360 minutes after stent implantation. MI was defined as a troponin level more than the upper limit of normal (ULN) and an absolute increase of >50% ULN on the 360-minute sample. A single combined measurement of troponin and copeptin 90 minutes after the onset of ischemia has a low diagnostic value. This increases when serial measurements with 90-minute intervals are included. For ruling in MI, the highest positive predictive value (with a 95% confidence interval [CI]) can be obtained when focusing only on the increase in troponin level, with a positive predictive value of 86% (70, 93) and 80% (67, 90) for hsTnT and hsTnI, respectively. For ruling out MI, a combined absence of any troponin more than the ULN and any significant increase in troponin level perform best with a negative predictive value of 75% (55, 89) and 75% (55, 89) for hsTnT and hsTnI, respectively. In conclusion, in early presenters, rapid biomarker protocols underestimate MI. A standard biomarker assessment after 3 hours is required to adequately rule-in or rule-out myonecrosis.

Use of likelihood ratios improves clinical interpretation of IgA anti-tTG antibody testing for celiac disease.

BACKGROUND: We investigated whether taking into account IgA anti-tissue transglutaminase antibody concentration (IgA anti-tTG) and total IgA concentration could improve clinical interpretation of serologic testing for celiac disease (CD). METHODS: We retrospectively identified 43 consecutive newly diagnosed CD patients and 545 consecutive disease control patients who had an IgA anti-tTG request during the 42-month study period and for whom intestinal biopsy results were available. RESULTS: Sensitivity and specificity of the IgA anti-tTG assay from Genesis was 95.3% and 92.7%, respectively, with a likelihood ratio (LR) of 12.4. The LR for CD markedly increased with increasing IgA anti-tTG concentration (from 2.0 for results between 7 and 20 U/ml up to 319 for results >100 U/ml). The LR for CD was also higher in patients with a normal IgA concentration (0.82-4.53 g/L) compared to patients with an increased IgA concentration (15.3 vs. 3.1, respectively). These observations were confirmed with a second IgA anti-tTG assay from BioRad. CONCLUSION: Sensitivity of IgA anti-tTG was good. Specificity, however, was reduced when IgA anti-tTG was weak positive or when the IgA concentration was increased. Taking into account IgA anti-tTG concentration and IgA concentration improves clinical interpretation of serologic testing for CD.

Technical and diagnostic performance of 6 assays for the measurement of citrullinated protein/peptide antibodies in the diagnosis of rheumatoid arthritis.

BACKGROUND: Several anticitrullinated protein/peptide antibodies (ACPA) assays have been reported to be of diagnostic value for rheumatoid arthritis (RA). We evaluated the technical performance and diagnostic accuracy of 6 ELISAs for the detection of antibodies to citrullinated protein/peptide antigens. METHODS: ACPA were determined in 298 serum samples using 6 commercially available ACPA assays. One hundred two samples were from RA patients, including patients with early and established RA, and 196 were from controls, including patients with psoriatic arthritis, connective tissue diseases, organ-specific autoimmune diseases, and a group of consecutive patients for whom a rheumatologist ordered anticyclic citrullinated peptide (CCP) antibodies. The ELISA reagent sets under study were Citrullinated Protein Antibodies (Genesis), Anti-MCV (Orgentec), Immunoscan RA (Euro-Diagnostica), Anti-CCP IgG ELISA (Euroimmun), EliA CCP (Phadia), and Quanta Lite CCP3 IgG ELISA (Inova). Technical performance (imprecision, linearity, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. RESULTS: Variable technical performance was noted among the different ACPA assays, with some assays displaying poor reproducibility and bad linearity. ACPA results were well correlated among assays with the same antigen specificity, but the numerical values reported for each assay differed widely. Using cutoff values proposed by the manufacturer, diagnostic sensitivities ranged between 69.6% and 77.5% and specificities between 87.8% and 96.4%. The areas under the ROC curves were comparable among the different assays. CONCLUSIONS: Overall diagnostic performance of ACPA assays is comparable among the different assays, but standardization is needed. For some assays, analytical characteristics could be improved.