Hypervolemic hyponatremia

Hypotonic hyponatremia, the most common form of hyponatremia, can be further classified as hypovolemic, euvolemic, or hypervolemic hyponatremia. 

Hypervolemic hyponatremia is associated with an elevated total body sodium content and an expanded ECF volume. 

In a 5-day, double-blind, randomized, placebo-con-trolled study in 74 patients with euvolemic or hypervolemic hyponatremia, oral conivaptan (40 or 80 mg/day) significantly increased serum sodium concentrations (2). The most common adverse events were headache, hypotension, nausea, constipation, and postural hypotension. 

In 84 patients with euvolemic or hypervolemic hyponatremia randomized to intravenous placebo or conivaptan 20 mg over 30 minutes followed by a 96-hour infusion of either 40 or 80 mg/day, conivaptan increased serum sodium concentrations (3). Infusion site reactions led to withdrawal of one and four of the patients who were given conivaptan 40 and 80 mg/day respectively. 

In two multicenter, randomized, double-blind, placebo-controlled studies of tolvaptan in 448 patients with euvolemic or hypervolemic hyponatremia, tolvaptan 15-60 mg/day increased serum sodium concentrations significantly compared with placebo (6). The main adverse effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. 

Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N Conivaptan Study Group. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 2007 27(5) 447-57. 

Due to the dual renal and vascular action of AVP, scientists at Yamanouchi Pharmaceuticals became interested in the identification of dual Vla/V2 vasopressin receptor antagonists, particularly because such agents were anticipated to be of unique utility in the treatment of congestive heart failure (CHF), where aberrant AVP secretion appeared responsible for both the onset of hypervolemic hyponatremia and deleterious increases in vascular resistance.14 The resulting drug discovery program ultimately lead to the identification of conivaptan HCl (1). 

On the basis of these studies, conivaptan HCl (1) has been approved by the FDA for the treatment of hospitalized patients with euvolemic and hypervolemic hyponatremia but is not currently indicated for the treatment of congestive heart failure.28 Due to its aquaretic effects, conivaptan use is contraindicated in patients with hypovolemic... 

In two randomized placebo-controlled trials of tolvaptan 15-60 mg in patients with either euvolemic or hypervolemic hyponatremia, adverse events were similar to those with placebo [43 ]. The most common adverse reactions were thirst (14% versus 5%) and dry mouth (13% versus 4%). Death rates were similar 14 of 223 patients who took tolvaptan compared with 13 of 220 patients who took placebo. Four patients who took tolvaptan had an increased serum sodium concentration to over 146 mmol/1, and in four patients the rate of increase of sodium was more rapid than clinically appropriate. Close moiutor-ing of serum sodium concentrations and plasma volume status is essential. Fluid restriction is not required. Polyuria is common. 

Patients with hypervolemic hypotonic hyponatremia should be treated with 3% saline and prompt initiation of fluid restriction. Loop diuretic therapy will also likely be required to facilitate urinary excretion of free water. 

Treatment of asymptomatic hypervolemic hypotonic hyponatremia involves correction of the underlying cause and restriction of water intake to less than 1,000 to 1,200 mL/day. Dietary intake of sodium chloride should be restricted to 1,000 to 2,000 mg/day. 

Hyponatremia is caused by an excess of total body water relative to total body sodium and can result from a number of underlying conditions, including the syndrome of inappropriate antidiuretic hormone secretion (SIADH), cirrhosis, and congestive heart failure (CHF). In each of these conditions, inappropriate production of arginine vasopressin (AVP) [also known as vasopressin or antidiuretic hormone (ADH)], a neurohormone that regulates renal electrolyte-free water reabsorption, contributes to enhanced renal water retention, leading to decreased serum sodium concentrations.7 Hyponatremia can be characterized as hypervolemic, euvolemic, or hypovolemic... 

Laboratory testing (such as osmolality) is important to help distinguish between hypervolemic or hypovolemic hyponatremia or hypernatremia. 

Hypervolemic hypotonic hyponatremia— increase in water without an equal increase in sodium. Occurs with cirrhosis, hypoproteinemia (low albumin), heart failure, and nephrotic syndrome. 

In 84 adults with hyponatremia (euvole-mic or hypervolemic) who were randomized to a bolus of conivaptan 20 mg followed by a 4-day continuous infusion of 40 mg/day (n = 29) or 80 mg/day (n = 26) compared with placebo (n = 29), the main adverse reactions were infusion site reactions [41 ]. 

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