Which manifestation is associated with a dilutional hyponatremia

Additionally, a loop diuretic may be combined with IV 0. Lasting correction depends on successful treatment of the underlying disorder. When the underlying disorder is not correctable, as in metastatic cancer, and patients find severe water restriction unacceptable, demeclocycline to mg orally every 12 hours may be helpful by inducing a concentrating defect in the kidneys.

However, demeclocycline is not widely used due to the possibility of drug-induced acute kidney injury Acute Kidney Injury AKI Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood azotemia with or without reduction in amount of urine IV conivaptan , a vasopressin receptor antagonist, causes effective water diuresis without significant loss of electrolytes in the urine and can be used in hospitalized patients for treatment of resistant hyponatremia.

Oral tolvaptan is another vasopressin receptor antagonist with similar action to conivaptan. Tolvaptan use is limited to less than 30 days due to the potential for liver toxicity and should not be used in patients with liver or kidney disease.

In diuretic-induced hyponatremia, elimination of the diuretic may be enough; some patients need some sodium or potassium replacement. Similarly, when mild hyponatremia results from inappropriate hypotonic parenteral fluid administration in patients with impaired water excretion, merely altering fluid therapy may suffice.

In patients with neurologic symptoms eg, confusion, lethargy, seizures, coma , treatment is more controversial. The debate primarily concerns the rate and degree of hyponatremia correction. Acute hyponatremia with known rapid onset ie, within Rapid-onset hyponatremia is problematic because the cells of the central nervous system have not had time to remove some of the intracellular osmolar compounds used to balance intracellular and extracellular osmolality.

Thus, the intracellular environment becomes relatively hypertonic compared to the serum, causing intracellular fluid shifts that can rapidly cause cerebral edema, potentially progressing to brain stem herniation and death. In these patients, rapid correction with hypertonic saline is indicated even when neurologic symptoms are mild eg, forgetfulness. The patient should be monitored in an intensive care unit and serum sodium levels monitored every 2 hours.

In some situations, hypertonic saline may be used with a loop diuretic. Equations are available to help predict the sodium response to a given amount of hypertonic saline, but these formulas are only rough guidelines and do not decrease the need to monitor electrolyte levels frequently.

For instance, in hypovolemic hyponatremia the sodium level can normalize too quickly as volume is replaced and thus removes the hypovolemic stimulus for vasopressin secretion, causing the kidneys to excrete large amounts of water. Another recommendation includes administration of desmopressin 1 to 2 mcg every 8 hours concurrently with hypertonic saline. The desmopressin prevents an unpredictable water diuresis that can follow the abrupt normalization of endogenous vasopressin that can occur as the underlying disorder causing hyponatremia is corrected.

After the sodium has been corrected at the appropriate rate for 24 hours, desmopressin is stopped. Hypertonic saline can then be stopped, or, if required for continuing correction of hyponatremia, continued.. For patients with rapid-onset hyponatremia and neurologic symptoms, rapid correction is accomplished by giving mL of hypertonic saline IV over 15 minutes. This dose can be repeated once if neurologic symptoms are still present.

This amount in mEq OR mmol may be calculated using the sodium deficit formula as. Adjustments may be needed based on serum sodium concentrations, which are monitored closely during the first few hours of treatment. Patients with seizures, coma, or altered mental status need supportive treatment, which may involve endotracheal intubation Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal tube inserted through the mouth Nasotracheal tube inserted through the nose Patients meeting the criteria for cerebral salt wasting should not be fluid restricted because fluid restriction can cause brain vessel vasospasm.

Although isotonic saline should correct the cause of hyponatremia, use of hypertonic saline is recommended to prevent more severe hyponatremia if indeed SIADH is present.

The selective vasopressin V2 receptor antagonists conivaptan IV and tolvaptan oral are treatment options for severe or resistant hyponatremia. These drugs are potentially dangerous because they may correct serum sodium concentration too rapidly; they are typically reserved for severe Conivaptan is indicated for treatment of hypervolemic and euvolemic hyponatremia.

It requires close monitoring of patient status, fluid balance, and serum electrolytes and so its use is restricted to hospitalized patients. A loading dose is given followed by a continuous infusion over a maximum of 4 days.

It is not recommended in patients with advanced chronic kidney disease estimated glomerular filtration rate Tolvaptan is a once daily tablet indicated for hypervolemic and euvolemic hyponatremia. Close monitoring is recommended especially during initiation and dosage changes. Tolvaptan use is limited to 30 days because of the risk of liver toxicity. Tolvaptan is not recommended for patients with advanced chronic kidney disease or liver disease.

Its effectiveness can be limited by increased thirst. Tolvaptan use is also limited by high cost. Both of these drugs are strong inhibitors of CYP3A cytochrome P, family 3, subfamily A and as such have multiple drug interactions.

Other strong CYP3A inhibitors eg, ketoconazole , itraconazole , clarithromycin , retroviral protease inhibitors should be avoided. Clinicians should review the other drugs the patient is taking for potentially dangerous interactions with V2 receptor antagonists before initiating a treatment trial.

Fluid restriction alone is frequently not enough to prevent recurrence of hyponatremia. Oral salt NaCl tablets can be used with dosage adjusted to treat mild to moderate chronic hyponatremia in these patients. Oral urea is a very effective treatment for hyponatremia, but it is tolerated poorly by patients due to its taste. A newer oral formulation of urea has been developed to enhance palatability. Osmotic demyelination syndrome previously called central pontine myelinolysis may follow too-rapid correction of hyponatremia.

Demyelination classically affects the pons, but other areas of the brain can also be affected. Malnutrition also includes overnutrition. Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss Flaccid paralysis, dysarthria, and dysphagia can evolve over a few days or weeks after a hyponatremic episode. The classic pontine lesion may extend dorsally to involve sensory tracts and leave patients with a "locked-in" syndrome an awake and sentient state in which patients, because of generalized motor paralysis, cannot communicate, except by vertical eye movements controlled above the pons.

Damage often is permanent. In such cases, inducing hyponatremia with hypotonic fluid may mitigate the development of permanent neurologic damage. Hyponatremia is potentially life threatening. The degree, duration, and symptoms of hyponatremia are used to determine how quickly to correct the serum sodium.

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Common Health Topics. Videos Figures Images Quizzes Symptoms. Symptoms and Signs. Exclusion of translocational hyponatremia and pseudohyponatremia Identification of the cause. Mild to moderate hyponatremia Severe hyponatremia Rapid-onset hyponatremia Hypertonic saline solution Selective receptor antagonists Chronic hyponatremia Osmotic demyelination syndrome.

Key Points. When this happens, your body's water levels rise, and your cells begin to swell. This swelling can cause many health problems, from mild to life-threatening. Hyponatremia treatment is aimed at resolving the underlying condition. Depending on the cause of hyponatremia, you may simply need to cut back on how much you drink.

In other cases of hyponatremia, you may need intravenous electrolyte solutions and medications. Seek emergency care for anyone who develops severe signs and symptoms of hyponatremia, such as nausea and vomiting, confusion, seizures, or lost consciousness.

Call your doctor if you know you are at risk of hyponatremia and are experiencing nausea, headaches, cramping or weakness. Depending on the extent and duration of these signs and symptoms, your doctor may recommend seeking immediate medical care. Sodium plays a key role in your body. It helps maintain normal blood pressure, supports the work of your nerves and muscles, and regulates your body's fluid balance. In chronic hyponatremia, sodium levels drop gradually over 48 hours or longer — and symptoms and complications are typically more moderate.

In acute hyponatremia, sodium levels drop rapidly — resulting in potentially dangerous effects, such as rapid brain swelling, which can result in a coma and death. Premenopausal women appear to be at the greatest risk of hyponatremia-related brain damage. This may be related to the effect of women's sex hormones on the body's ability to balance sodium levels. It differentiates true, pseudo or translocational hyponatremia [ Figure 1 ]. Calculated serum osmolality may not reflect serum osmolality if other osmotically active solutes are present in the plasma.

Hence, serum osmolality should be measured by osmometer, IB. If osmometer is not available, random blood sugar, serum triglyceride and serum protein should be helpful in differentiating the three types.

Urine osmolality can be used to distinguish between impaired water excretion and hyponatremia with normal water excretion [ Table 5 ]. Values above this level indicate an inability to normally excrete free water, most commonly because of persistent secretion of ADH.

This is done by measuring the urinary sodium losses. If initial urine sodium concentration is equivocal, it could be difficult to differentiate true hypovolemia or euvolemic hyponatremia. In this situation serial monitoring of the urine osmolality and urine sodium concentration in response to the administration of 1litre 0. If the patient is hypovolemic, 0.

In both disorders, the urine sodium concentration will increase with saline therapy, although the increase in hypovolemic patients will not be seen until the hypovolemia is corrected. It is the sum of the urine sodium plus potassium concentrations divided by the serum sodium concentration.

Fractional excretion of sodium FENa provides an accurate assessment of volume status than the urine sodium alone because it corrects for the effect of variations in urine volume on the urine sodium. Stimulation of the vasopressor V1a receptor also contributes to the uric acid wasting. Water retention also causes low BUN. Thiazide diuretic-induced hyponatremia similar reductions in uric acid and urea levels can occur in patients with thiazide diuretic-induced hyponatremia where thiazides are used for water overload.

Evaluation of acid-base and potassium balance may be helpful in some patients. Metabolic acidosis and hyperkalemia - primary adrenal insufficiency in patients without renal failure.

Mild metabolic alkalosis and normal K- is seen in hypopituitarism because of higher plasma aldosterone levels. In case of doubt, one can initiate 0. Hypovolemic hyponatremia improves with 0.

Etiology of hyponatremia. Acute hyponatemia is generally symptomatic. The risk of brain herniation is high and rapid correction is needed. Acute hyponatremia is common in marathon runners, patients with primary polydipsia and users of ecstasy. These patients have not had time for the brain adaptations to occur. Chronic hyponatremia- It is generally asymptomatic or has mild symptoms. However; it may present with seizures if hyponatremia is very severe.

Patients with mild symptoms eg, dizziness, forgetfulness, gait disturbance should be treated with less aggressive therapy. Among patients with urine to serum electrolyte ratio greater than 1, in whom fluid restriction will not be sufficient to achieve the desired goal, additional therapy includes salt tablets and if necessary, a loop diuretic.

An alternative approach is the initiation of a vasopressin antagonist without fluid restriction. Rate of correction: In chronic hyponatremia the brain undergoes adaptation and hence the risk of cerebral herniation is very low unlike the risk in acute hyponatremia. Instead very rapid correction can lead to osmotic demyelination syndrome ODS.

Hence, chronic hyponatremia generally needs gradual correction. High risk of ODS is seen esp. Osmotic demyelination-It is a rare, but severe and sometimes irreversible disorder. It presents with locked in syndrome i. This disorder was formerly called central pontine myelinolysis CPM , but the name was changed because demyelination is more diffuse and does not necessarily involve the pons and. Recently, it has been shown that ODS can be reversed by relowering sodium and giving desmopressin.

Potassium added to the solution should be included in the formula i. However, these formulae have limitations and cannot be used to accurately predict the magnitude of change in serum sodium and frequent measurements are necessary.

In the current guidelines these formulae are not used. In addition water restriction, salt, urea, demeclocycline and vaptans are used according to the etiology. In cases of chronic hyponatremia or mild symptoms water restriction is the main cornerstone of treatment. Diurectics and vaptans are the other drugs used. The cation concentration of the administered fluid must exceed the cation concentration of the urine. Careful monitoring of the serum sodium is essential to prevent very rapid correction.

Fluid restriction: The effectiveness of fluid restriction can be predicted by the urine to serum electrolyte ratio as described above. All fluids, not only water, must be included in the restriction; several days of restriction are usually necessary before a significant increase in plasma osmolality occurs; and only fluid, not sodium, should be restricted.

Thirst, can be ameliorated by substituting hard candy or ice chips for drinking fluids. Thiazides should not be used. Demeclocycline: Causes a nephrogenic form of diabetes insipidus, thereby decreasing urine concentration even in the presence of high plasma AVP levels. Treatment must be continued for several days to achieve maximal diuretic effects; one should wait 3 to 4 days before deciding to increase the dose.

Demeclocycline can cause reversible azotemia and sometimes nephrotoxicity, especially in patients with cirrhosis and should be discontinued if increasing azotemia occurs. Fluid restriction is warranted in hyponatremic patients with primary polydipsia in whom increased fluid intake is the primary problem.

Glucocorticoid deficiency should be excluded by proper tests. Treatment consists of Glucocorticoids for adrenal insufficiency suppress ADH. As risk of ODS is high general guidelines for chronic hyponatremia should be followed. Low solute intake should be corrected. Risk of ODS is small. Presentation may be acute or chronic. Mostly it is chronic. Sodium chloride, usually as 0. K may be added if required. Gastrointestinal losses- may be acute or chronic. Urine Cl is a better marker for volume status in patients with vomiting instead of Urine Na.

Both K and bicarbonate deficits should be corrected along with volume correction. CSW may present acutely. Moslty 0.

Thiazides induced hyponatremia is usually chronic and should be corrected slowly as risk of ODS is high. K should also be supplemented. Patients with thiazide-induced hyponatremia are at high risk for a recurrence and should not be rechallenged with a thiazide. Mineralocorticoid deficiency associated hyponatremia is chronic and responsds to 0.

Fludrocortisone may be need for long term treatment. Water restriction is the mainstay of therapy. Vaptans act on vasopressin receptors as antagonists. The V2 receptors cause antidiuresis, while V1a and V1b receptors cause vasoconstriction and adrenocorticotropic hormone ACTH release, respectively.

The vasopressin receptor antagonists produce a water loss aquaresis without affecting sodium and potassium excretion. Vaptans are the most appropriate physiological approach to treat hyponatremia as they do not deplete electrolytes and restriction of fluids is not needed. They do not stimulate the neurohormonal system and cause no renal impairment.

Treatable causes of Euvolemic Hyponatremia should be excluded e. Vaptans are useful for chronic hyponatremia. Vaptans are used in addition to fluid restriction and sodium chloride administration. Tolvaptan significantly increased serum sodium concentration. Even with modest sodium improvement there was significant increase in mental scores. But the effect was not clinically significant and long-term efficacy was doubtful as the patients were followed up for only 30 days.

Thus liver function tests should be performed initially and LFT should be repeated three to four months after initiating therapy and then again at six-month intervals. If liver injury is suspected, tolvaptan should be discontinued. Recently FDA has recommended Tolvaptan use but not for greater than 4 wks. Fluid restriction should not be used during the active phase of correction, thereby allowing the patient's thirst to compensate for vigorous aquaresis. Appropriate caution should be exercised in patients treated with tolvaptan for hyponatremia for extended periods e.

Patients who are refractory to or unable to tolerate or obtain other therapies for hyponatremia and in whom the benefit of tolvaptan treatment outweighs the risks, remain candidates for long- term therapy with tolvaptan; but in such cases, liver function tests should be monitored carefully and serially i. Conivaptan is FDA approved for euvolemic hyponatremia in hospitalized patients. It is available only as an intravenous preparation and is given as a mg loading dose over 30 min, followed by a continuous infusion.

Generally, the mg continuous infusion is used for the first 24 h. Therapy is limited to a maximum duration of 4 days because of drug-interaction effects with other agents metabolized by the CYP3A4 hepatic isoenzyme. Hyponatremia in CHF is chronic and should be corrected till serum Na is normal and symptoms improve.

The level of serum Na should be normalized so that diuretic therapy for CHF can be optimised. In some studies, hyponatremia was associated with increased mortality and increased rate of re-hospitalization in patients of acute heart failure. Further studies of the Vaptans are necessary to determine whether serum sodium normalization will be translated into a better long-term prognosis in patients with CCF.

However Tolvaptan has been found to be hepatotoxic and hence USFDA has limited their use only in those hyponatremic patients with end-stage liver disease who are awaiting imminent liver transplantation, who are at little risk of added hepatic injury and will benefit from correction of hyponatremia before surgery to decrease the risk of ODS postoperatively.

In earlier studies the patients with cirrhosis were found to have improved serum sodium levels with vaptans however therewas no clear difference between Vaptans and control groups regarding mortality, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, or renal failure. Hence is contraindicated in cirrhosis. Satvaptan was found to maintain sodium levels long term in cirrhotics however it's use is also limited.

Contraindications to vaptans-Vasopressin receptor antagonists should not be used in hyponatremic patients who are volume depleted. Vaptans should not be used to treat the type of euvolemic hyponatremia caused by emetic stimuli or secondary adrenal insufficiency and they are ineffective in the vasopressin-independent form of SIADH caused by an activating mutation of the V 2 receptor.

They are ineffective where AVP levels are appropriate, for example, cerebral salt wasting and psychogenic polydipsia.