Hyponatremia
Hyponatremia—Current Treatment Strategies and Perspectives for the Future Mark J Hannon, MB, BCh, BMedSc, MRCPI1
and Christopher J Thompson, MB, ChB, MD, FRCPI, FRCP(Edin)2
1. Endocrinology Research Fellow; 2. Professor, Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland Medical School
Abstract
Hyponatremia is the commonest electrolyte abnormality found in hospital inpatients and is associated with a greatly increased morbidity and mortality. The management of hyponatremia is predicated on correct diagnosis of the underlying cause, which relies on accurate assessment of the patient’s volume status. The syndrome of inappropriate antidiuresis (SIAD) is the most common cause of hyponatremia and current treatments for this syndrome are poorly effective. Hypervolemic hyponatremia is also difficult to manage. The emergence of a new class of medications—the selective vasopressin-2 receptor antagonists or vaptans—gives clinicians an opportunity to target the underlying pathophysiology of these conditions, and represent an exciting new development in the management of hyponatremia. In this article we review the differential diagnosis of hyponatremia, current treatment strategies, and emerging management options.
Keywords Hyponatremia, mortality, differential diagnosis, syndrome of inappropriate antidiuresis (SIAD), vaptans
Disclosure: The authors have no conflicts of interest to declare. Received: February 28, 2011 Accepted: May 16, 2011 Citation: US Endocrinology, 2011;7(2):116–20 Correspondence: Christopher J Thompson, MB, ChB, MD, FRCPI, FRCP(Edin), Academic Department of Endocrinology, Beaumont Hospital, Dublin 9, Ireland. E:
christhompson@beaumont.ie
Hyponatremia is by far the most common electrolyte imbalance found in hospital inpatients,1
and patients with symptomatic hyponatremia have a vastly increased mortality compared with normonatremic controls.2 Therefore, it is essential that hyponatremic patients receive effective and targeted therapy. However, hyponatremia has many pathophysiological causes, each of which needs to be managed differently, making accurate diagnosis essential to enable the commencement of therapy to reduce morbidity and mortality. The recent emergence of the vaptan class of aquaretic agents is an exciting new development in the management of euvolemic hyponatremia, but hyponatremia remains poorly managed. In this article, we review the diagnosis of hyponatremia, current management strategies, and emerging therapeutic options.
Prevalence and Effects of Hyponatremia Hyponatremia is by far the most common electrolyte abnormality in hospital inpatients, and is also common in healthy patients in the community. The prevalence of mild hyponatremia (<135 mmol/l) was quoted as 4 % in a recent Belgian study,3
which looked at a healthy,
elderly population. The incidence of new hyponatremia in hospitalized patients is far higher—a recent study showed that 8 % of patients admitted with pneumonia developed hyponatremia during the course of hospital admission,4
admitted with subarachnoid hemorrhage develop hyponatremia.5
These high prevalence rates are important due to almost universal findings of higher morbidity and mortality in patients with low plasma sodium concentrations. Gill’s study of hospitalized patients with plasma sodium concentration <125 mmol/l showed an overall mortality of 28 %, significantly higher than in eunatremic controls (9 %).7
Mortality
although at least some of this excess mortality was attributed to the illnesses which precipitated hyponatremia, such as cardiac failure, liver disease, and small cell carcinoma of the lung. However, hyponatremia itself has recently been shown to be implicated in the mortality suffered by these patients, with higher mortality rates in hyponatremic patients who did not receive specific treatment for hyponatremia compared with those who did (37 versus 13 %).9
in this study increased exponentially as plasma sodium fell. This excess mortality has also been shown to persist for months after discharge from hospital,8
It has
also been shown that of commonly measured clinical and biochemical parameters in acute hospital admissions, plasma sodium concentration was most strongly associated with in-hospital mortality, with an odds ratio of 4.4.10
Hyponatremia has also been associated with increased duration of hospital stay with resultant increased hospital costs.5,7
and our own data shows that 56 % of patients Other
neurosurgical patients also have high rates of hyponatremia, with between 10–20 % of patients with intracranial tumours, hematomas undergoing pituitary surgery developing hyponatremia.6
116
The adverse outcomes outlined above associated with hyponatremia are not confined to patients with plasma sodium <125 mmol/l. Patients with mild hyponatremia in the community,3 intensive care11
with pneumonia,4 and in
have all been shown to have excess mortality compared with patients with normal plasma sodium concentrations. The largest study to date on this topic showed that even mild hyponatremia in
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