Chapter 16: Disorders of Serum Sodium Concentration in the Elderly Patient Michael F. Michelis Division of Nephrology, Lenox Hill Hospital, New York, New York HYPONATREMIA tory that can produce information implicating drugs that facilitate sodium excretion or stimulate Disorders of serum sodium concentration are the AVP secretion. In addition, a thorough physical ex- most common electrolyte abnormalities seen in the amination, including orthostatic BP changes, is es- sential for the accurate determination of the pa- geriatric population.1 Furthermore, the develop- ment of serum sodium abnormalities is associated tient’s body fluid status. This determination may be with increased morbidity and mortality in affected especially difficult in elderly patients who may have chronic changes in skin turgor that are more asso- patients.2 Often, however, the severity of the pri- mary process contributing to the development of ciated with aging than they are with the state of the abnormal serum sodium is responsible for the hydration. unsatisfactory outcome. The most common disor- der of serum sodium concentration in the geriatric Laboratory Diagnosis and Therapy When the history and physical are completed, as- population is hyponatremia. Factors contributing sessment of laboratory data are essential (Figure 1). to the development of hyponatremia in the elderly First, a plasma osmolality must be obtained to include age-associated decreases in GFR and free ensure that one is dealing with hypo-osmolar hypo- water clearance, as well as sodium losses from de- natremia. Normo-osmolar hyponatremia as can creased activity of the renin-angiotensin-aldoste- occur with certain compounds such as mannitol, rone system and increased activity of natriuretic which can also cause hyperosmolality in normon- hormones. The latter, however, may reflect the atremic patients, and hyperosmolar hyponatremia early development of fluid retention as may occur caused by hyperglycemia must be ruled out. Fur- with excessive sodium intake from processed foods thermore, other serum studies are important to de- or subclinical cardiac disease. In addition, studies cide whether levels of substances such as blood urea have suggested increased vasopressin activity in nitrogen and uric acid are elevated and thereby con- some elderly patients. sistent with volume depletion or whether these lev- Patients in outpatient settings exhibit hypona- els seem to be diluted as would be seen with water tremia in about 5% of those tested, with occurrence excess occurring in the syndrome of inappropriate rates increasing to as high as 20% in hospitalized antidiuretic hormone secretion (SIADH). Finally, geriatric patients and 30% in patients seen in inten- urine sodium concentration and urine osmolality sive care units.3 The most common cause of hypo- natremia in this population involves abnormalities must be measured to ascertain the endocrine and of secretion of the pituitary hormone arginine va- renal responses to the hypo-osmolar state. sopressin (AVP), also called antidiuretic hormone In dehydrated patients, levels of urine sodium (ADH). can be considered low (i.e., sodium conservation) when the spot urine sodium concentration is Ͻ20 mEq/L; in older patients, where sodium conserva- Clinical Diagnosis 4 Successful evaluation of serum sodium abnormali- tion may be limited, levels up to 30 mEq/L may also ties in the elderly depends on obtaining a careful history especially noting reports of weight loss that Correspondence: Michael F. Michelis, Director, Division of Ne- can be associated with neoplastic disease, changes phrology, Lenox Hill Hospital, 100 East 77th Street, New York, NY in the level of daily activities that can be associated 10075. E-mail: [email protected] with endocrine abnormalities, and medication his- Copyright ᮊ 2009 by the American Society of Nephrology American Society of Nephrology Geriatric Nephrology Curriculum 1 HYPONATREMIA (DIFFERENTIAL DIAGNOSIS) Confirm Hypoosmolality Volume Assessment (Physical Examination) and Urine Sodium Measurement Hypovolemia Euvolemia Edema Urine Na Urine Na >30 mEq/L <20 mEq/L Urine Na Urine Na Congestive Heart Failure SIADH <20-30 mEq/L >20-30 mEq/L Cirrhosis Diuretic Use - Water Replacement Nephrotic Syndrome Vomiting Addison’s Disease Endocrine Deficiency Diarrhea Polycystic Kidneys Hypoalbuminemia Pancreatitis Bicarbonaturia Diuretic Use Figure 1. Hyponatremia (differential diagnosis). be considered indicative of some degree of conservation of generally treated by addressing the primary underlying abnor- sodium. These urine sodium levels will often be associated with mality and using diuretic regimens. urine osmolality values at least 1.5 times that of the plasma, In elderly hyponatremic patients who appear euvolemic suggesting attempts at water conservation in response to fluid and have elevated urine sodium concentrations (Ͼ20 or 30 deficits. Such patients generally respond to the replacement of mEq/L) and elevated urine osmolalities suggesting inappropri- intravascular volume with normal saline. Patients who appear ate water retention, a diagnosis of SIADH is often made.6 Here dehydrated but who have elevated urine sodium levels (Ͼ30 it is important to rule out endocrine abnormalities such as mEq/L) often have urine osmolalities closer to that of the hypoadrenalism and hypothyroidism. In addition, a careful plasma levels and should be considered to have renal salt wast- search for drugs that stimulate AVP or facilitate the effects of ing in the face of intravascular volume contraction. They AVP in the kidney should be undertaken. If these consider- should also be treated with normal saline while attempts to ations are eliminated from diagnostic possibilities, the patient diagnose the underlying abnormality are made. Various for- should be evaluated for other causes of SIADH. Table 1 lists mulas such as the Adrogue´-Madias formula (Figure 2) have some of the commonly associated central nervous system dis- been used in an attempt to predict the increase in serum so- orders, tumors, and drugs associated with inappropriate AVP dium that can occur when various concentrations of sodium secretion. Certain drug therapies such as SSRIs may pose a replacement therapy are employed.5 If more or less than1Lof special risk for the development of hyponatremia in the el- replacement fluid is used, the change in serum sodium will derly, especially those who are older and smaller in body size.7 vary directly in proportion to the amount of fluid adminis- tered. Table 1. Common causes of SIADH When patients appear to be fluid overloaded or edematous, Central nervous system disease they may have one of several edema-forming states, including Trauma congestive heart failure, nephrotic syndrome, and cirrhosis. Stroke The poor renal perfusion associated with any of these states is Infection generally associated with urine sodium concentrations in the Tumor Intracranial bleeding lower ranges (Ͻ20 to 30 mEq/L) and a tendency to urine os- Neoplasms molalities closer to that seen in the plasma. These disorders are Lung Pancreas ADROGUÉ-MADIAS FORMULA Prostate Throat Lymphoma Infusate sodium concentration – Drugs Patient serum concentration Change in serum sodium concentration with 1L of infusate = SSRIs Total body water + 1L Carbamazepine Figure 2. The Adrogue´ -Madias Formula for the prediction of the Opiates change in serum sodium that can occur following intravenous Cyclophosphamide sodium replacement therapy. Mirtazapine 2 Geriatric Nephrology Curriculum American Society of Nephrology If primary causes of the syndrome SIADH cannot be imme- conservative manner. Current recommendations are that se- diately eliminated, patients should be treated with therapies rum sodium should not increase Ͼ12 mEq/L over a 24-h pe- that can reverse the hyponatremia.8 In patients with a history riod and no more than 18 mEq/L over a 48-h period. with confounding factors such as the possible prior use of di- uretic agents, a trial of normal saline administration may be Complex Clinical Syndromes used. In patients with severe hyponatremia, i.e., serum sodium Finally, complicated situations have been described in which concentrations Ͻ110 mEq/L, it may be appropriate to use patients are hyponatremic and seem to have excess AVP activ- multiple 100-ml intravenous aliquots of hypertonic (3%) sa- ity as well as sodium depletion syndromes.10 On attempts at line to improve the serum sodium levels to avoid more serious correction with saline, including hypertonic saline, patients complications of hyponatremia such as seizures or profound may exhibit a response in which volume correction shuts off coma. In patients with serum sodium concentrations in the AVP secretion and causes a profound water diuresis with rapid 111- to 120-mEq/L range, therapies may include lesser increases in the serum sodium concentration and a tendency amounts of hypertonic saline, and greater reliance on fluid toward too rapid correction. When this occurs, reversal ther- restriction and agents that interfere with AVP effect, such as apy may be required with the administration of free water demeclocycline and the new AVP receptor antagonists. With and/or AVP (usually as the AVP agonist desmopressin). In lesser degrees of hyponatremia, i.e., serum sodium 121 to 129 addition, patients on drugs that stimulate AVP secretion may mEq/L, fluid restriction, demeclocycline, and AVP receptor have the effects of these drugs wear off during the period that antagonists can be used. therapies are undertaken, also