Current treatment practice and outcomes. Report of the hyponatremia registry

Abstract

Current management practices for hyponatremia (HN) are incompletely understood. The HN Registry has recorded diagnostic measures, utilization, efficacy, and outcomes of therapy for eu- or hypervolemic HN. To better understand current practices, we analyzed data from 3087 adjudicated adult patients in the registry with serum sodium concentration of 130 mEq/l or less from 225 sites in the United States and European Union. Common initial monotherapy treatments were fluid restriction (35%), administration of isotonic (15%) or hypertonic saline (2%), and tolvaptan (5%); 17% received no active agent. Median (interquartile range) mEq/l serum sodium increases during the first day were as follows: no treatment, 1.0 (0.0-4.0); fluid restriction, 2.0 (0.0-4.0); isotonic saline, 3.0 (0.0-5.0); hypertonic saline, 5.0 (1.0-9.0); and tolvaptan, 4.0 (2.0-9.0). Adjusting for initial serum sodium concentration with logistic regression, the relative likelihoods for correction by 5 mEq/l or more (referent, fluid restriction) were 1.60 for hypertonic saline and 2.55 for tolvaptan. At discharge, serum sodium concentration was under 135 mEq/l in 78% of patients and 130 mEq/l or less in 49%. Overly rapid correction occurred in 7.9%. Thus, initial HN treatment often uses maneuvers of limited efficacy. Despite an association with poor outcomes and availability of effective therapy, most patients with HN are discharged from hospital still hyponatremic. Studies to assess short- and long-term benefits of correction of HN with effective therapies are needed.

Figures

Figure 1

Consort diagram showing patient flow. The 3087 patients in bottom row constitute the per-protocol group. All analyses are based on this group. Note: patients reporting multiple comorbidities were counted in the “Other” group. See Materials and Methods section and Supplementary Table S4 online for description of the adjudication process. CHF, congestive heart failure; HN, hyponatremia; [Na+], sodium concentration; SIADH, syndrome of inappropriate antidiuretic hormone secretion.

Figure 2

Initial therapy of hyponatremia. Bars show percentages of patients receiving specified therapy. Lines show cumulative proportions of patients receiving therapies shown. CHF, congestive heart failure; FR, fluid restriction; HN untreated, no specific treatment targeted at hyponatremia at any time during hospitalization; HS, hypertonic saline; NS, isotonic saline; SIADH, syndrome of inappropriate antidiuretic hormone; TO, tolvaptan. aTherapies given to ⩾1% of patients; b7.6.0%, c9.3%, d5.2%, and e3.1% of patients received other unique therapies.

Figure 3

Choice of initial therapy according to baseline serum sodium concentration: all patients.P-values shown for comparisons where P<0.05; all other intergroup comparisons did not reach statistical significance. Dotted lines indicate P-value comparisons for <120- vs. 126–130-mEq/l groups. FR, fluid restriction; HN, hyponatremia; HS, hypertonic saline; NS, isotonic saline. aNo prescribed therapy specifically targeting HN.

Figure 4

Change in serum sodium concentration from baseline by initial monotherapy. FR, fluid restriction; HN, hyponatremia; NS, isotonic saline.

Figure 5

Outcomes and the use of second therapies in patients with baseline serum sodium concentrations <130 mEq/l initially treated with fluid restriction alone. The decision to initiate a second treatment or not and the selection of any such treatments were made by the patients' treating physicians without input from the investigators. All serum sodium concentration [Na+] values are median (IQR) in mEq/l. HS, hypertonic saline; NS, isotonic saline; TO, tolvaptan. aPretreatment value; bsuccess defined as proportion of patients with [Na+] increase by 5 mEq/l or more from baseline.