Hyponatremia and Mortality

Abstract

For those who are not electrolyte enthusiasts, hyponatremia can be a frustrating disorder. Dealing with hyponatremia means considering various and often opposite scenarios. Does the patient have hypovolemic, euvolemic, or hypervolemic hyponatremia? Is it acute or chronic? Symptomatic or asymptomatic? Do I want to correct rapidly or more slowly? Shall I give normal saline, hypertonic saline, or water restriction? And-every resident's nightmare-which of the impossible formulas shall I use to calculate the correction rate? These challenges may be the reason that the management of hyponatremia is still suboptimal (1-3). This is worrisome not only because hyponatremia counts as the most common electrolyte disorder in hospitalized patients but also because it is associated with increased mortality. The association between hyponatremia and mortality has been demonstrated in numerous studies (4 -9), but causality has been difficult to prove. Therefore, two possibilities remain ( Figure 1): (1) Hyponatremia is a direct cause of death, or (2) severe underlying disease is the cause of death and hyponatremia is merely another complication of this underlying disease.In this issue, Chawla et al. (10) elegantly rephrase the issue of hyponatremia and mortality as, "Do patients die with or from hyponatremia?" The investigators first show mortality rates in a large sample of hospitalized patients with hyponatremia (serum sodium Ͻ135 mmol/L). Similar to previous observations (9), mortality rose as serum sodium dropped. Surprising, however, this trend reversed when serum sodium reached values of Յ120 mmol/L, when mortality rates started to decrease again. The final result was a parabolic relationship between serum sodium and mortality. On the basis of these observations, Chawla et al. formulate an interesting hypothesis (10): That patients with moderate hyponatremia have more severe underlying disease than those with severe hyponatremia and therefore higher mortality rates. The patients with severe hyponatremia, they argue, were likely admitted because their serum sodium was so low, not because they were so ill.In the remainder of the article, the authors seek to confirm this hypothesis by performing a detailed chart review of 53 fatal cases with serum sodium Ͻ120 mmol/L and 35 survivors with serum sodium Ͻ110 mmol/L. Indeed, the authors note that more than half of the fatal cases had severe conditions associated with high mortality rates, including sepsis and acute kidney injury. These disorders were largely absent in survivors, whose more severe hyponatremia was largely attributed to the use of thiazides and antidepressants. Importantly, hyponatremia's most dangerous and potentially fatal complications, cerebral edema and the osmotic demeylination syndrome, were rarely observed. Thus, the authors conclude that patients die with and not from hyponatremia. This is an interesting conclusion that will definitely stir debate on the value of actively treating hyponatremia. The study is also an interesting example of how detailed chart...

Clinical practice guideline on diagnosis and treatment of hyponatraemia

“…Whether this reflects disease severity or has a direct contributory effect remains unclear (58). Systemic vasodilation and arteriovenous shunting of blood may reduce the effective arterial blood volume.…”

Prevalence of Hyponatremia and Its Associated Morbimortality in Hospitalized Patients Receiving Parenteral Nutrition

“…However, in this current study, the identification of the independent association between sustained HN and mortality suggests that persistently low SNa levels, rather than transitory HN, could play a role in increasing the death rate. In fact, HN could directly contribute to the worsening of the basal disease and to organ dysfunction due to adverse metabolic alterations associated with HN, such as negative inotropic response, reduction of liver gluconeogenesis, increased insulin resistance, and impaired bone remodelling [25,26]. Our results suggest that the study of mortality in patients with HN should take into account SNa values dynamically, and not be limited to a single laboratory determination.…”

Hyponatremia and bone: an emerging relationship

“…This possibility is reminiscent of an ongoing discussion in the hypo natremia literature, namely whether the increased mortality that is consistently observed in hyponatremic patients is causal or merely an epi phenomenon. 39 This question is still unresolved, with the latest two studies showing data argu ing in favor 40 and against 41 direct effects of hyponatremia on mortality.…”