natremia always denotes hypertonicity, hyponatremia Downloaded from www. at UNIVERSITY OF NEW MEXICO on · May 25, The New . N Engl J Med. May 25;(21) Hyponatremia. Adrogué HJ(1), Madias NE. Author information: (1)Department of Medicine, Baylor College of. PDF | On Jun 1, , Horacio J. Adrogué and others published Downloaded from by HUSEIN SONARA MD on January

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Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations.

A year-old woman noted an unpleasant, sweet taste in her mouth. She otherwise felt well and was taking no medications. Because dysgeusia is a rare manifestation of hyponatremia, her serum sodium level was tested and was mmol per liter.

The serum osmolality was mOsm per kilogram of water, the urinary osmolality mOsm per kilogram of water, the urinary sodium 85 mmol per liter, and the urinary potassium 40 mmol per liter. Her thyroid function and adrenal function were normal. A computed tomographic CT scan of the thorax showed a mass in the lower lobe of the left lung, which proved to be a small-cell carcinoma. How should her hyponatremia be treated? The Clinical Problem Hyponatremia, defined as an excess of water in relation to the sodium in the extracellular fluid, is the most common electrolyte disorder in hospitalized patients.

The syndrome of inappropriate secretion of antidiuretic hormone SIADH is the most frequent cause of hyponatremia, although hyponatremia associated with volume depletion of the extracellular fluid also occurs commonly. Initial reports suggested that secretion of arginine vasopressin in SIADH was independent of plasma osmolality. Although this is the case in about one third of patients with SIADH 7 Figure 1in other patients with this condition, secretion of arginine vasopressin is fully suppressed, resulting in dilute urine, but at a serum sodium level lower than normal a “reset osmostat”.

Less commonly, plasma levels of arginine vasopressin are low or undetectable in patients with SIADH, even in the presence of hyponatremia.

In some patients, mutations of the aquaretic i. View larger version 19K: Patterns of plasma levels of arginine vasopressin AVP; also known as the antidiuretic hormoneas compared with plasma sodium levels in patients with SIAD, are shown.

The shaded area represents normal values of plasma AVP. Adapted from Robertson, 7 with the permission of the publisher. For each increase of mg per deciliter 5. A normal or elevated measured osmolality value, however, does not rule out hypotonic hyponatremia, because urea is an ineffective osmole. When diagnostic uncertainty remains, volume contraction of the extracellular fluid can be ruled out by infusing 2 liters of 0.

Measurement of the serum level of arginine vasopressin is not recommended routinely, because urinary osmolality above mOsm per kilogram of water is usually sufficient to indicate excess of circulating arginine vasopressin.

NEJM — The Syndrome of Inappropriate Antidiuresis

Most cases caused by malignant disease hypobatremia with effective antineoplastic therapy, and most of those due to medication resolve promptly when the offending agent is discontinued.

When the hyponatremia is chronic and asymptomatic, a diagnosis can be pursued before treatment is initiated. Acute Symptomatic Hyponatremia The most important factors dictating the management of SIAD are the severity of the hyponatremia, its duration, and the presence or absence of symptoms Figure 2.

View larger version 28K: Most cases of hyponatremia that occur out of the hospital are chronic and minimally symptomatic, except in marathon runners, users of 3,4-methylenedioxymethamphetamine MDMA, also known as “ecstasy”and people who drink water to excess; in these groups, severe symptoms usually indicate acute hyponatrekia and require rapid correction. The treatment of hyponatremia with an unclear duration and nonspecific symptoms or signs e. Some reports suggest a high risk if patients are not treated aggressively 29 ; others suggest that rapid correction increases morbidity or mortality.

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This disorder, which includes both central pontine and extrapontine myelinolysis, begins with lethargy and affective changes generally after initial improvement of neurologic symptoms with treatmentfollowed by mutism or dysarthria, spastic quadriparesis, and pseudobulbar palsy.

Many limit correction to 8 mmol per liter over a period of 24 hours and 18 mmol per liter over a period of 48 hours; close monitoring of the rate of correction every 2 to 3 hours 25 is recommended to avoid overcorrection. Some authorities recommend brain imaging e. Fluid restriction, estimated on the basis of levels of urinary and plasma electrolytes Figure 2is a cornerstone of therapy. Oral intake of urea 30 g per day is effective but is poorly tolerated.

Demeclocycline Declomycin, Wyeth—Ayerst to mg twice daily reduces urinary osmolality and increases serum sodium levels, but its effects can be variable and it can cause nephrotoxicity.

Vasopressin-Receptor Antagonist Therapy A more recent option for treating SIAD is conivaptan Vaprisol, Astellas Pharmaa vasopressin-receptor antagonist approved by the Food and Drug Administration in for intravenous treatment of euvolemic hyponatremia 34 and approved in for intravenous treatment of hypervolemic hyponatremia 35 Table 3.

In a double-blind, randomized trial, in patients assigned to conivaptan for 4 days, as compared with those assigned to placebo, the serum sodium levels increased by 6 mmol per liter. Although hypotension has not been reported in association with conivaptan, it is a risk, because conivaptan is a nonselective vasopressin-receptor antagonist; blocking the vasopressin V 1 receptor induces vasodilation.

Currently, conivaptan use is limited to the treatment of hospitalized patients; it might be considered particularly for those who have moderate-to-severe hyponatremia and symptoms but not seizures, delirium, or coma, which would warrant the use of hypertonic saline. One theoretical concern is that vasopressin-receptor antagonists might increase serum sodium levels too rapidly, putting patients at risk for osmotic demyelination. To date, this complication has not been reported, but trials of these agents have involved very close monitoring and minimal or no water restriction.

These agents frequently cause dry mouth and thirst, 36 which stimulate water intake, slowing the rise in serum sodium levels. Use of these agents in practice would require similarly close monitoring of serum sodium levels. Areas of Uncertainty Optimal Strategies for Correcting Serum Sodium Levels There are no data from randomized trials to guide optimal strategies for correction of serum sodium levels in patients with either acute or chronic hyponatremia, and the relative risks of osmotic demyelination and of hyponatremic encephalopathy continue to be debated.

The best method for determining an initial rate for hypertonic saline infusion is also controversial 38 ; Table 4 presents some suggested strategies. The traditional approach is to estimate a sodium deficit and is not physiologically based, because SIAD is characterized by a water excess, rather than a sodium deficit.

Another approach is to calculate the effect of 1 liter of an infusate on the serum sodium level, then estimate the volume needed for infusion; this formula predicts actual changes in the serum sodium level reasonably well, 38 but it involves two calculations, which can be confusing.

Other formulas incorporate amounts of salt and water infused and excreted 3940 ; these add precision, but at the price of complexity.

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Loop diuretics also increase the rate of increase in the serum sodium level. The rate of change in serum sodium levels must be monitored every 2 to 3 hours, and the infusion adjusted as needed. When symptoms of osmotic demyelination develop during the treatment of hyponatremia, case reports suggest that it may be possible to reverse the neurologic deficits by again lowering the serum sodium level. Cerebral Salt Wasting SIAD may be difficult to distinguish from cerebral salt wasting, a syndrome of hyponatremia and extracellular-fluid volume depletion in patients with insults to the central nervous system.

Prevention of Postoperative Hyponatremia Surgical procedures typically increase circulating levels of arginine vasopressin; nevertheless, hypotonic intravenous fluids are frequently administered perioperatively.

Summary and Recommendations The patient described in the vignette apparently has chronic hyponatremia attributable to SIAD; she has no neurologic symptoms. Treating the underlying cause in this case, small-cell lung cancer is the definitive means of correcting the hyponatremia.

In the absence of symptoms, gradual correction of the hyponatremia is appropriate and should involve adequate solute intake including salt and protein and fluid restriction, starting at ml per day of water on the basis of the formula shown in Figure 2.

If the patient were disoriented, we would recommend increasing her serum sodium level by 0. This increase can be accomplished by promoting free-water excretion with the use of furosemide and replacing sodium and potassium losses with 0. Alternatively, conivaptan might be used to increase the serum sodium level, although clinical experience with vasopressin-receptor antagonists remains very limited. Ellison reports receiving research grants from Chemica Technologies, and Dr.

Berl reports receiving consulting fees from Astellas and Sanofi-Aventis, lecture fees from Astellas, and research support from Otsuka. No other potential conflict of interest relevant to this article was reported.

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