Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis.

BACKGROUND: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response. METHODS: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis. RESULTS: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR. CONCLUSION: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

BACKGROUND: Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. METHODS: A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. RESULTS: MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). CONCLUSION: MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

Prognostic value of procalcitonin in community-acquired pneumonia.

The prognostic value of procalcitonin (PCT) levels to predict mortality and other adverse events in community-acquired pneumonia (CAP) remains undefined. We assessed the performance of PCT overall, stratified into four predefined procalcitonin tiers (< 0.1, 0.1-0.25, > 0.25-0.5, >0.5 µg·L⁻¹) and stratified by Pneumonia Severity Index (PSI) and CURB-65 (confusion, urea >7 mmol·L⁻¹, respiratory frequency ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs) risk classes to predict all-cause mortality and adverse events within 30 days follow-up in 925 CAP patients. In receiver operating characteristic curves, initial PCT levels performed only moderately for mortality prediction (area under the curve (AUC) 0.60) and did not improve clinical risk scores. Follow-up measurements on days 3, 5 and 7 showed better prognostic performance (AUCs 0.61, 0.68 and 0.73). For prediction of adverse events, the AUC was 0.66 and PCT significantly improved the PSI (from 0.67 to 0.71) and the CURB-65 (from 0.64 to 0.70). In Kaplan-Meier curves, PCT tiers significantly separated patients within PSI and CURB-65 risk classes for adverse events prediction, but not for mortality. Reclassification analysis confirmed the added value of PCT for adverse event prediction, but not mortality. Initial PCT levels provide only moderate prognostic information concerning mortality risk and did not improve clinical risk scores. However, PCT was helpful during follow-up and for prediction of adverse events and, thereby, improved the PSI and CURB65 scores.