> Table of Contents > Hyponatremia
Hyponatremia
Ruben Peralta, MD, FACS
image BASICS
DESCRIPTION
  • Hyponatremia is a plasma sodium (Na) concentration of <135 mEq/L. Hyponatremia itself does not provide information about the “total body water” state of the patient. Patients with hyponatremia may be fluid overloaded, hypovolemic, or euvolemic.
  • System(s) affected: endocrine/metabolic
EPIDEMIOLOGY
Incidence
  • Most common electrolyte disorder seen in the general hospital population
  • Predominant age: all ages
  • Predominant sex: male = female
Prevalence
2.5% of hospitalized patients
Geriatric Considerations
The elderly have lower total body water, a decreased thirst mechanism, and decreased urinary concentrating ability; their kidneys are less responsive to antidiuretic hormone (ADH), and they show decreased renal mass, renal blood flow, and glomerular filtration rate, making them at higher risk for hyponatremia.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Hypovolemic hyponatremia: Decrease in total body water and greater decrease in total body Na; decreased extracellular fluid volume; orthostatic hypotension and other changes consistent with hypovolemia are present.
  • Euvolemic hyponatremia: Increase in total body water with normal total body Na; extracellular fluid volume is minimally to moderately increased but with no edema.
  • Hypervolemic hyponatremia: Increase in total body Na and greater increase in total body water; extracellular fluid increased markedly; edema is present.
  • Redistributive hyponatremia: shift of water from intracellular compartment to extracellular compartment with resulting dilution of Na; total body water and total body Na unchanged; occurs with hyperglycemia
  • Pseudohyponatremia: dilution of aqueous phase by excessive proteins, glucose, or lipids; total body water and total body sodium unchanged; occurs in hypertriglyceridemia or multiple myeloma
  • Low Na creates an osmotic gradient between plasma and cells and fluid shifts into cells, causing edema and increased intracranial pressure.
  • Hypovolemic hyponatremia: extrarenal loss of sodium (Na <30 mmol/L in urine)
    • GI loss: vomiting, diarrhea
    • Third spacing: peritonitis, pancreatitis, burns, rhabdomyolysis
    • Skin loss: burns, sweating, cystic fibrosis
    • Heat-related illnesses
  • Hypovolemic hyponatremia: renal loss of sodium (Na >30 mmol/L in urine)
    • Cerebral salt wasting syndrome
    • Adrenal pathology (e.g., Addison disease, hemorrhage, tuberculosis)
    • Diuretics
    • Osmotic diuresis
  • Euvolemic hyponatremia (Na >30 mmol/L in urine)
    • Hypothyroidism
    • Hypopituitarism or other cause of glucocorticoid deficiency
    • Medications (e.g., carbamazepine, clofibrate, cyclosporine, levetiracetam, opiates, oxcarbazepine, phenothiazines, SSRIs, tricyclic antidepressants, vincristine) (1)
    • Primary polydipsia
    • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
    • Iatrogenic (e.g., excess hypotonic IV fluids)
  • Hypervolemic hyponatremia (Na <30 mmol/L in urine, except chronic renal failure)
    • Nephrotic syndrome
    • Cirrhosis
    • Congestive heart failure (CHF)
    • Chronic renal failure
  • Redistributive hyponatremia
    • Hyperglycemia
    • Mannitol infusion
    • Hypertriglyceridemia
  • Multiple myeloma
Genetics
  • Polymorphisms have been demonstrated.
  • Mutations have been associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD; SIADH).
GENERAL PREVENTION
Depends on underlying condition
COMMONLY ASSOCIATED CONDITIONS
  • Hypothyroidism
  • Hypopituitarism
  • Adrenocortical hormone deficiency
  • HIV patients
  • SIADH is associated with cancers, pneumonia, tuberculosis, encephalitis, meningitis, head trauma, cerebrovascular accident, HIV infection.
  • Acute neurologic patients, brain injury
  • Marathon runners in hot environments
image DIAGNOSIS
  • Symptoms related to the rate of fall in serum Na and the degree of hyponatremia
  • Mild (130 to 135 mEq/L): usually asymptomatic
  • Moderate (120 to 130 mEq/L): nausea, vomiting, malaise
  • Severe: (115 to 120 mEq/L): headache, lethargy, restlessness, disorientation
  • Severe/rapid decreases can cause seizure, coma, and respiratory arrest and may be fatal.
  • Other signs and symptoms: weakness, muscle cramps, anorexia, hiccups, depressed deep tendon reflexes, hypothermia, positive Babinski responses, cranial nerve palsies, orthostatic hypotension
PHYSICAL EXAM
  • Volume status: skin turgor, jugular venous pressure, heart rate, orthostatic BP
  • Exam for underlying illness: signs of CHF, cirrhosis, hypothyroidism
DIFFERENTIAL DIAGNOSIS
See “Etiology and Pathophysiology.”
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Comprehensive metabolic profile (BUN, creatinine, glucose, electrolytes, liver function studies, etc.)
  • Thyroid-stimulating hormone (TSH)
  • Lipid panel
  • Serum osmolality
  • Urine sodium and osmolality
  • Chest x-ray to rule out pulmonary pathology if SIADH is diagnosed
Follow-Up Tests & Special Considerations
  • CT scan of head if pituitary problem is suspected or if SIADH from CNS problem is suspected
  • Interpretation of labs: Suspect hypovolemic hyponatremia.
    • Plasma osmolality is low.
    • BUN-to-Cr ratio > 20:1
    • If urine Na >20 mEq/L (>20 mmol/L): renal loss
    • If urine Na <10 mEq/L (<10 mmol/L): extrarenal loss
    • Serum potassium >5 mEq/L (>5 mmol/L): Consider mineralocorticoid deficiency.
  • Interpretation of labs: Suspect euvolemic hyponatremia.
    • Plasma osmolality low
    • BUN-to-Cr ratio < 20:1
    • Urine Na >20 mEq/L (>20 mmol/L)
    • TSH to rule out hypothyroidism
    • Consider 1-hour cosyntropin-stimulation test to rule out adrenal insufficiency.
  • Interpretation of labs: hypervolemic hyponatremia
    • Plasma osmolality is low.
    • Urine Na <10 mEq/L (<10 mmol/L) in nephrotic syndrome, CHF, cirrhosis
    • Urine Na >20 mEq/L (>20 mmol/L) in acute and chronic renal failure
  • Redistributive hyponatremia
    • Plasma osmolality is normal or high.
    • Glucose or mannitol levels are elevated.
  • Pseudohyponatremia
    • Plasma osmolality is normal.
    • Triglyceride, glucose, or protein levels are elevated.
P.535

image TREATMENT
GENERAL MEASURES
  • Assess all medications patient is taking.
  • Institute seizure precautions.
MEDICATION
  • Treatment tailored to clinical situation: The degree of hyponatremia, how rapidly the hyponatremia developed, and whether the patient is symptomatic influence the urgency of correction. Some general principles apply
    • Expected change in serum Na with selected infusates: &Dgr;Na = [(infusate Na+infusate K-serum Na)/(TBW+1)] where TBW = a coeff × weight (wt) as in the following text:
      Table 1. Total Body Water

      Children

      0.6 × weight

      Women

      0.5 × weight

      Men

      0.6 × weight

      Elderly women

      0.45 × weight

      Elderly men

      0.5 × weight

    • Formula to determine correction available at http://www.medcalc.com/sodium.html
  • Asymptomatic, euvolemic patients can be treated with fluid restriction; the underlying cause also must be addressed.
  • For severely hyponatremic/symptomatic patients, it is generally considered safe to increase the serum Na by 0.6 to 2 mEq/L/hr, not to exceed 8 mEq/24 hr.
  • For mild to moderate hyponatremia, use isotonic saline solution (0.9%). For moderate to severe hyponatremia, consider specialist consultation for use of hypertonic saline (3%) via central line access at a rate of 1 to 2 mL/kg body weight/hr; increasing serum sodium levels by 0.5 mmol/L/hr and monitoring frequently the plasma sodium level (~q2h).
  • In patients with severe hyponatremia (euvolemic and hypervolemic state) who do not respond to the above-mentioned approach, consider the use of vasopressin V2-receptor antagonists, such as tolvaptan or conivaptan (3)[A].
  • Treat underlying condition: heart failure, cirrhosis, and so forth.
  • Chronic hyponatremia resulting from SIADH: demeclocycline (inhibits ADH action at the collecting duct) if fluid restriction alone is not effective
    • Contraindication: can cause nephrotoxicity in patients with liver disease
    • In doses of 600 to 1,200 mg/day, the drug produces a nephrogenic diabetes insipidus.
    • Significant possible interactions: oral anticoagulants, oral contraceptives, penicillin
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Admission is mandatory if the patient has acute hyponatremia or is symptomatic; acute hyponatremia (developing over <48 hours) carries the risk of cerebral edema.
  • Admission is advised if patient is asymptomatic and has a serum Na <125 mEq/dL.
image ONGOING CARE
DIET
  • Euvolemic hyponatremia: Restrict water to 1 L/day.
  • Hypervolemic hyponatremia: water and Na restriction
PROGNOSIS
  • In hospitalized patients, hyponatremia is associated with an elevated risk of adverse clinical outcomes and higher mortality (4,5)[B].
  • Recently, in community-dwelling, middle-aged, and elderly adults, mild hyponatremia has been shown to be an independent predictor of death.
  • Associated with poor prognosis in patients with acute pulmonary embolism
  • Associated with poor prognosis in patients with liver cirrhosis and those waiting for liver transplant; it is associated with significant postop risk and short-term graft loss.
REFERENCES
1. Meulendijks D, Mannesse CK, Jansen PA, et al. Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Saf. 2010;33(2):101-114.
2. Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinolysis: a systematic review. Eur J Neurol. 2014;21(12):1443-1450.
3. Rozen-Zvi B, Yahav D, Gheorghiade M, et al. Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and metaanalysis. Am J Kidney Dis. 2010;56(2):325-337.
4. Bavishi C, Ather S, Bambhroliya A, et al. Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions. Am J Cardiol. 2014;113(11):1834-1838.
5. Basu A, Ryder RE. The syndrome of inappropriate antidiuresis is associated with excess long-term mortality: a retrospective cohort analyses. J Clin Pathol. 2014;67(9):802-806.
6. Esposito P, Piotti G, Bianzina S, et al. The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options. Nephron Clin Pract. 2011;119(1):c62-c73.
Additional Reading
&NA;
  • Abraham WT, Hensen J, Gross PA, et al. Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia. Kidney Int. 2012;82(11):1223-1230.
  • Cowtan T. Thiazide diuretics. N Engl J Med. 2010; 362(7):659.
  • De Picker L, Van Den Eede F, Dumont G, et al. Antidepressants and the risk of hyponatremia: a class-by-class review of literature. Psychosomatics. 2014 55(6):536-547.
  • Ernst ME, Moser M. Use of diuretics in patients with hypertension. N Engl J Med. 2009;361(22): 2153-2164.
  • Friedman B, Cirulli J. Hyponatremia in critical care patients: frequency, outcome, characteristics, and treatment with the vasopressin V2-receptor antagonist tolvaptan. J Crit Care. 2013;28(2):219. e1-219.e12.
  • Lim YJ, Park EK, Koh HC, et al. Syndrome of inappropriate secretion of antidiuretic hormone as a leading cause of hyponatremia in children who underwent chemotherapy or stem cell transplantation. Pediatr Blood Cancer. 2010;54(5):734-737.
  • Sood L, Sterns RH, Hix JK, et al. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis. 2013;61(4):571-578.
  • Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170(3): G1-G47.
  • Sterns RH, Hix JK, Silver SM. Management of hyponatremia in the ICU. Chest. 2013;144(2):672-679.
See Also
&NA;
Algorithm: Hyponatremia
Codes
&NA;
ICD10
E87.1 Hypo-osmolality and hyponatremia
Clinical Pearls
&NA;
  • Alcohol-dependent individuals with vitamin deficiencies, elderly women taking thiazide diuretics, and people with hypokalemia or burns are at increased risk of central pontine myelinolysis. A longer duration of hyponatremia is also a risk factor.
  • Bronchogenic carcinoma, pancreas, duodenal, prostate, thymoma, lymphoma, and mesothelioma are neoplastic diseases associated with SIADH.
  • Formulas have been developed (Adrogue and Madias) for safe correction of hyponatremia and are available online (see http://www.medcalc.com/sodium.html).