Hyponatremia—Current Treatment Strategies and Perspectives for the Future
hospital inpatients (which occurred in 14.5 % of those studied) increased mortality at one year and five years.12
A recent analysis of the American
National Health and Nutrition Examination Survey III (NHANES III) database has revealed that mild (mean 133 mmol/l) chronic hyponatremia is associated with osteoporosis at the femoral neck.13 These recent data have challenged the traditional view of mild hyponatremia as an asymptomatic condition and renewed interest in the treatment of hyponatremia of all levels of severity.
Differential Diagnosis of Hyponatremia The first step in the treatment of hyponatremia is correct diagnosis of the underlying etiology. There are a number of classifications of the pathogenesis of hyponatremia. Some authorities use a classification based on whether hyponatremia is dilutional, depletional, or redistributional in nature.14
In routine clinical practice, we classify
hyponatremia based on clinical and biochemical estimation of extracellular volume status. This divides hyponatremia into hypovolemic, euvolemic, and hypervolemic etiologies (see Table 1). Although the clinical features of the three categories are quite distinct, in practice it can be difficult to distinguish mild hypovolemia from euvolemia. The causes of hyponatremia are numerous and diverse, and so accurate diagnosis is essential to enable correct management. Hypovolemic hyponatremia can be difficult to diagnose as serum urea may be low in hypovolemic elderly patients and urinary sodium may be low in SIAD due to anorexia. In these cases, an isotonic saline infusion can be helpful.15
Euvolemic hyponatremia, usually caused by the syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatremia in hospitalized patients. However, it is important that SIAD is not diagnosed erroneously as a number of other pathologies can result in euvolemic hyponatremia, for which the management is markedly different. For example, hyponatremia may occur as a direct result of surgical procedures—bladder irrigation during transurethral resection of the prostate gland can lead to direct absorption of water from the bladder, producing euvolemic dilutional hyponatremia,16,17
and
inappropriate fluid replacement may also cause dilutional hyponatremia.18
Adrenocorticotrophic hormone (ACTH) deficiency, which leads to cortisol but not aldosterone deficiency, can cause euvolemic hyponatremia with a biochemical picture identical to SIAD. This is due to the fact that plasma cortisol is necessary to excrete free water.19
This distinction is especially important to make in patients with neurosurgical conditions, who commonly develop hyponatremia.6
50 % of patients with acute subarachnoid hemorrhage develop hyponatremia, most of which has been attributed to SIAD.7
Over Some of
the hyponatremia attributed in the immediate post-hemorrhage period to SIAD may actually represent acute ACTH deficiency. This is as yet unproven; however, 16 % of patients with acute traumatic brain injury develop ACTH deficiency20 severe hyponatremia.21
and some of these patients develop very
Current Treatment of Hyponatremia As outlined above, the management of hyponatremia is critically dependent on an accurate estimation of the patient’s extracellular volume status, and the accurate diagnosis of the underlying cause (see Table 1). Incorrrect diagnosis of the patient’s volume status could lead to harmful or even fatal mistakes in treatment.
US ENDOCRINOLOGY
Fluid restriction is regarded as the first-line treatment for hyponatremia due to SIAD (in the majority of cases apart from patients with severe symptomatic hyponatremia). It is well established and safe. Fluid restriction of 800–1,200 ml per day is generally advised, according to severity of hyponatremia. However, strict fluid restriction is extremely difficult to maintain, especially in the community, as thirst in SIAD is inappropriately normal due to a downward resetting of the osmotic thirst threshold.24
Furthermore, intravenous antibiotic or
cytotoxic therapy alone can push patients over their allotted fluid restriction. As a result, fluid restriction is often insufficient to reverse hyponatremia and is rarely quick enough to manage symptomatic hyponatremia.
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Euvolemic hyponatremia is usually, but not always, due to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), and therefore the most important element in diagnosis is the recognition of other causes, especially glucocorticoid deficiency. Glucocorticoid therapy has been shown to suppress arginine vasopressin (AVP) secretion,22
which allows free water
excretion and the normalisation of plasma sodium concentrations in patients with ACTH deficiency.23
Hypervolemic Peripheral, Raised JVP Underlying illness
ACTH = adrenocorticotrophic hormone; JVP = jugular venous pulse; Na = sodium; SIAD = syndrome of inappropriate antidiuresis.
Table 1: Differential Diagnosis of Hyponatremia Clinical Signs
Urinary Na+ <20 mmol/l
Hypovolemic Dry mucous membranes
Decreased turgor Pancreatitis
Tachycardia Sodium depletion Hypotension post diuretics (orthostatic)
Raised urea, renin
Euvolemic Underlying illness Hypothyroidism SIAD with ongoing
fluid restriction Primary polydipsia Inappropriate fluid replacement Cirrhosis
pulmonary edema Cardiac failure Ascites
SIAD ACTH deficiency
Urinary Na+ >40 mmol/l
Gastrointestinal losses Diuretics Mucosal losses
Addison’s disease Cerebral salt wasting Salt-wasting nephropathy
Cardiac failure or cirrhosis
Nephrotic syndrome on diuretic therapy
In hypovolemic hyponatremia, the aim is to correct plasma sodium and simultaneously restore intravascular volume. Most cases will respond to the intravenous infusion of 0.9 % isotonic saline. Diuretic therapy should be discontinued, and an underlying cause sought and treated. Co–existent Addison’s disease is suggested by history, examination, and the presence of hyperkalemia. Although the biochemical abnormalities of Addison’s disease will respond to high-dose corticosteroids, patients usually need intravenous saline to expand blood volume and replace body sodium; intravenous dextrose may also be needed if the patient is hypoglycemic.
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