Current treatment practice and outcomes. Report of the hyponatremia registry

Greenberg, Arthur; Verbalis, Joseph G.; Amin, Alpesh; Burst, Volker; Chiodo, Joseph; Chiong, Jun R.; Dasta, Joseph F.; Friend, Keith; Hauptman, Paul J.; Peri, Alessandro; Sigal, Samuel H.

doi:10.1038/ki.2015.4

Cited by 152 publications

(131 citation statements)

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“…However, the recommended set of laboratory tests [23,24,25,26] including the Schwartz-Bartter criteria as well as cortisol and TSH were performed in only about 20% of all patients in either group. These findings demonstrate that the potentially deleterious impact of this disorder is often not appreciated and that the diagnostic management of hyponatremia in general is poor as has been shown repeatedly in the past [21,27]. …”

Section: Resultsmentioning

confidence: 77%

“…The study design has been described previously in detail [21,22]. The study protocol was approved by individual IRB at each participating institution, and informed consent (or waiver) was obtained prior to data collection.…”

Section: Methodsmentioning

confidence: 99%

“…Patients were excluded if they were less than 18 years old, hypovolemic, severely hyperglycemic, or receiving renal replacement therapy. A complete listing of inclusion and exclusion criteria has been published previously [21,22]. …”

Section: Methodsmentioning

confidence: 99%

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Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

et al. 2017

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Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na⁺] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na⁺] change (Δ_daily[Na⁺]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δ_daily[Na⁺] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

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Section: Resultsmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

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Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

et al. 2017

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“…Fluid restriction was effective at increasing PNa in patients with hyponatremia but did not have any advantage in improving outcomes (36). Furthermore, in data obtained in a recent registry of .3000 subjects with hyponatremia, the increase in PNa observed with fluid restriction in the first 24 hours was not significantly different from that observed in untreated patients (37). PNa usually increases slowly and only by 1-2 mEq/L with fluid restriction alone.…”

Section: Limitation Of Water Intakementioning

confidence: 86%

Mild Chronic Hyponatremia in the Ambulatory Setting

Rondon‐Berrios

Berl

2015

Clinical Journal of the American Society of Nephrology

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Mild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.

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“…It is likely that a more active management of hyponatraemia by experts in the field had more impact than the implementation of water restriction. The authors cite the lack of impact of water restriction in the observational setting of the hyponatraemia registry [14], and in routine clinical practice [15][16][17][18], but perhaps in the setting of a small intervention trial, their efforts and expertise produced more effective implementation of water restriction. In addition, the range of secondary interventions used was very varied, so remain in the position that we are unclear what the most effective intervention-water restriction, vaptans or saline infusion-was.…”

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confidence: 99%

Syndrome of inappropriate antidiuresis should it be managed by specialised endocrinologists?

Garrahy

Thompson

2017

Endocrine

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The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia in hospitalised patients, accounting for 43% of patients with a plasma sodium concentration of <130 mmol/l [1]. Although there are virtually no data on mortality in SIAD, mortality in all-cause hyponatraemia has been reported to be elevated in almost every paper on the subject [2][3][4]. Hyponatraemic patients are also vulnerable to morbidity related to falls [5], fractures [6] and osteoporosis [7]. In the absence of separate studies in SIAD, it is widely accepted that patients who have hyponatraemia due to SIAD are vulnerable to the same risk of the morbidities and mortality associated with all-cause hyponatraemia. This has prompted considerable interest in whether treatment of hyponatreamia can improve outcomes in SIAD.Unfortunately, there is little data in the literature upon which to construct evidence based guidelines for the management of hyponatraemia due to SIAD. In the absence of a solid evidence base, there are controversial differences between the US recommendations [8] and the European guidelines [9] on treatment of SIAD. The US recommendations acknowledge that second-line treatment of SIAD, after failure of water restriction can be vaptans, urea or frusemide with sodium chloride supplementation, whereas the European Guidelines specifically advise against vaptans. So where are the gaps in our knowledge in the literature? The mortality in SIAD separately from that due to all-cause hyponatraemia is not known. Mortality studies have assessed the effects of hyponatraemia on death rate, without separating out the relative mortality of SIAD from other causes of hyponatraemia. In addition, as very few studies have firmly ascertained the full diagnostic criteria for SIAD in their study cohorts [10], the accuracy of data from many SIAD studies is questionable.The situation is complicated by the lack of studies on the response of plasma sodium to established treatments for SIAD. There are no prospective randomised-controlled trials which have reported the effects of water restriction, and many second-line treatments, in SIAD. There is however firm data on the response of SIAD-related hyponatraemia to treatment with vaptans; the randomised, placebocontrolled SALT studies showed that a mixed population of patients with SIAD and hypervolaemic hyponatraemia demonstrated a larger rise in plasma sodium concentration in response to tolvaptan than to placebo [11], and a later subgroup analysis confirmed that similar biochemical responses were consistent in the SIAD subgroup [12]. However, we still await the results of trials which compare the proven benefits of vaptans with first-line treatment with water restriction.It is therefore timely to see the results of an intervention study in SIAD patients in this journal [13]; the paper reported the effects of specialised endocrine care on outcomes in SIAD. The authors have a proven track record in the field, and as a group who have highlighted the poor ascertainment of basic diagnosti...

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Current treatment practice and outcomes. Report of the hyponatremia registry

Cited by 152 publications

References 38 publications

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

Mild Chronic Hyponatremia in the Ambulatory Setting

Syndrome of inappropriate antidiuresis should it be managed by specialised endocrinologists?

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