hyponatremia

Classification

• hypertonic
  • serum osmolality > 295 mOsm/kg H2O
• isotonic
  • serum osmolality 275-295 mOsm/kg H2O
• hypotonic
  • serum osmolality < 275 mOsm/kg H2O
  • hypervolemic, isovolemic, or hypovolemic

Etiology

edema-forming states (hypotonic, hypervolemic)

• mechanism
  • decreased effective arterial blood volume
  • sodium & water retention by the kidney
    • water retention exceeds sodium retention in pregnancy
  • excessive total body sodium
  • excessive extravascular fluid (3rd spacing)
• congestive heart failure (CHF)
• nephrotic syndrome
• hepatic cirrhosis
• acute or chronic renal failure

volume depletion (hypotonic. hypovolemic)

• mechanism
  • renal salt loss
  • extrarenal salt loss
  • replacement with hypotonic fluid
  • stimulation of ADH despite hypotonicity (hypovolemia overrides hyponatremia)
• urine Na+ < 10 meq/L
  • gastrointestinal loss from vomiting or diarrhea
  • 3rd space loss
    • peritonitis
    • pancreatitis
  • skin losses
  • lung & respiratory tract losses
• urine Na+ > 20 meq/L
  • pharmacologic agents
    • diuretics: thiazide diuretics more commonly than loop diuretics*
    • mannitol
    • enemas
  • hypoaldosteronism
    • Addison's disease
    • hyporenin hypoaldosteronism
  • salt-losing nephritis
  • osmotic diuresis
  • renal tubular acidosis (RTA)
  • obstruction

* in the elderly mainly associated with diabetes mellitus & diuretics

normal extracellular volume (hypotonic, normovolemic)

• syndrome of inappropriate antidiuretic hormone secretion (see SIADH)
  • malignancy (carcinoma causing ectopic production of ADH)
  • CNS disease
  • pulmonary disorders
  • pharmacologic agents
  • postoperative after orthopedic surgery, hypophysectomy
• pharmacologic agents that potentiate renal effect of ADH
  • chlorpropamide
  • carbamazepine
  • NSAIDs
  • cyclophosphamide
• pharmacologic agents that produce ADH-like effect
  • oxytoxin
  • desmopressin
• administration of hypotonic fluids (urine Na+ < 10 meq/L)
  • postoperative
  • psychogenic polydipsia
• low salt intake (anorexia)
• severe hypothyroidism
• cortisol deficiency or panhypopituitarism
• pregnancy (mild hyponatremia due to changes in ADH response to osmolality)
• most common 60%

hyponatremia with hypertonicity or hyperosmolarity (hypertonic)

• mechanism:
  • osmotically active substance causes movement of intracellular fluid extracellularly
• hyperglycemia (a decrease of 1.6 meq/L for each 100 mg/dL increase in plasma glucose)*
• increased serum urea, alcohols, mannitol, sorbitol, glycine

* in the elderly mainly associated with diabetes mellitus & diuretics

pseudohyponatremia (isotonic hyponatremia)*

• isotonic hponatremia occurs because of non-aqueous volume occupied by lipid in hypertriglyceridemia & perhaps protein in monoclonal & polyclonal gammopathies
• ion-specific electrodes used in most modern instruments measures may be falsely low when plasma contains < 93% H2O
  • flame photometry may be more reliable measure of sodium
• see Laboratory (below) for expected serum sodium in the presence of hyperglycemia

* distinguish from true hyponatremia caused by hyperosmolarity by measuring serum osmolality

Epidemiology

• most common electrolyte abnormality in hospitalized patients
• more common in elderly patients

Clinical manifestations

• symptoms related to etiology of hyponatremia
  • orthostasis associated with volume depletion, but not edema-forming states
• symptoms related to degree of hyponatremia & acute vs chronic nature of the disorder
  • symptoms do not appear until:
    • serum sodium drops below 125 meq/L suddenly
    • much lower if hyponatremia is chronic
  • overt neurologic symptoms are most often due to serum sodium levels < 115 mEq/L
• neurologic manifestations predominate
  • headache
  • lethargy, apathy, muscle weakness, muscle cramps
  • agitation/irritability
  • nausea/vomiting
  • dysgeusia
  • cognitive impairment
    • disorientation
    • confusion
  • decreased level of consciousness
  • decreased deep tendon reflexes
  • muscle twitching
  • grand mal seizures
  • Cheyne-Stokes respirations
  • coma & death may occur with [Na+] < 110 meq/L

Laboratory

• serum osmolality & urine osmolality
  • serum osmolality is decreased except in hyperosmolar conditions, i.e. diabetes & pseudohyponatremia (isotonic hyponatremia)
  • urine osmolality
    • < 100 mOsm kg H2O suggests appropriately suppressed ADH
      • primary polydipsia
      • decreased solute intake (anorexia)
    • > 100 mOsm kg H2O suggests ADH excess (SIADH)
      • elderly may not be able to dilute urine < 150 mOsm/kg H2O, thus > 150 mOsm kg H2O may suggest ADH excess (SIADH) in the elderly
      • also consistent with volume depletion
    • adrenal insufficiency & hypothyroidism may present similarly to SIADH (see below)
• serum chemistries
  • electrolytes
    • serum sodium
      • mild hyponatremia, serum Na+ < 136 meq/L
      • severe hyponatremia, serum Na+ < 125 meq/L
    • serum K+:
      • hypokalemia if volume depletion with fluid loss secondary to renal or GI etiology
      • normal in SIADH
    • serum bicarbonate: normal in SIADH
    • serum chloride: normal in SIADH
  • serum glucose
    • a decrease in serum Na+ of 1.6 meq/L for each 100 mg/dL increase in serum glucose
  • serum urea nitrogen:
    • BUN/creatinine ratio > 20 with volume depletion
  • serum creatinine
  • serum uric acid
• urine chemistries
  • urine sodium
    • urine sodium < 20 meq/L in:
      • edema-forming states - cirrhosis - CHF - nephrotic syndrome
      • hypovolemia of extrarenal origin
      • decreased solute intake (anorexia)
    • urine sodium > 20 meq/L in:
      • renal failure
      • hypovolemia of renal origin
      • SIADH
  • urine creatinine
• fractional excretion of sodium (FENA)
• thyroid function tests if indicated
• adrenal function tests if indicated
  • adrenal insufficiency
    • serum cortisol 8 AM, plasma ACTH
    • hyperkalemia, acidosis, history of autoimmune disease, weight loss
  • first diagnostic tests after serum sodium & serum K+ in a patient with history of opioid abuse & symptoms of secondary adrenal insufficiency
• see ARUP consult

Diagnostic procedures

• geriatric assessment tools* demonstrate worse function it elderly patients with hyponatremia & improvement with improvement of serum sodium

* the geriatric assessment tools used included

• Hindi mental status examination
• Barthel's index of activities of daily living,

* timed get-up-&-go test

* dynamometer hand grip strength

Complications

• increased risk of myocardial infarction & death (mild hyponatremia, serum Na+ < 136 meq/L)
• increased risk of perioperative mortality (even mild hyponatremia, serum Na+ < 135 meq/L)
• seizures, coma
• high mortality associated with severe hyponatremia (< 125 meq/L)
  • mortality > 50% if serum sodium is < 105 meq/L
  • mortality is higher among alcoholics
  • rapid overcorrection of hyponatremia is common;
    • osmotic demyelination (central pontine myelinolysis) is rare

Management

• establish urgency of treatment
  • brain edema, uncontrolled seizures & herniation are
  • acute onset of hyponatremia, seizures, & stupor/coma indicate urgent treatment
• urgent treatment for symptomatic patients
  • normal saline to restore euvolemia in hypovolemic patients (NEJM)
    • infusion of normal saline can result in worsening of hyponatremia
  • IV furosemide (Lasix) may be given for volume overload
  • 3% saline*
    • 100 mL bolus for acute symptomatic isovolemic hypotonic hyponatremia (polydipsia or administration of hypotonic fluids)
    • increase serum sodium 1.0-2.0 meq/L/hour; 0.5 meq/L/hour
      • total increase of 4-6 meq/L/24 hours to max of 8 meq/L/24 hours
      • 6-10 meq/L/24 hours aligns with guidelines (2023)
      • maintain this serum sodium for 24 hours
      • rapid correction of severe hyponatremia (> 12 mEq/L per 24 hours) is associated with lower mortality without excess risk for osmotic demyelination syndrome
    • central pontine myelinolysis is a rare complication of too rapidly correcting serum sodium
    • desmopressin with 3% saline for safer increase in serum sodium
    • D5W +/- desmopressin for overcorrection of hyponatremia;
      • ref recommends D5W + desmopressin
    • 3% saline bolus 2 mL/kg every 6 hours during 1st 24 hours safe
  • serum Na+ is usually corrected to 120 meq/L
  • conivaptan or tolvaptan IV for life-threatening euvolemic & hypervolemic hyponatremia in hospitalized patients
• asymptomatic patients
  • water restriction unless patient is volume contracted
    • 500 to 1000 mL/day (restriction of all fluids)
    • indicated for patients with cirrhosis when serum Na+ < 120 meq/L
  • normal saline for hypovolemia
  • hypervolemia
    • chronic heart failure, cirrhosis, chronic renal failure
    • fluid restriction
    • loop diuretic
    • tolvaptan 15-60 mg PO QD
  • SIADH
    • free water restriction alone is not sufficient
    • demeclocycline
      • do NOT use in patients with cirrhosis
    • tolvaptan 15-60 mg PO QD
    • increase solute intake (urea 15 g BID mixed with fruit juice) for low plasma osmolality & high urine osmolality not responding to fluid restriction
• address underlying disease processes
• unless hyponatremia is indicated as acute, treat a chronic hyponatremia

* 3% saline also indicated for serum Na+ < 130 meq/L immediately preceding liver transplantation

More general terms

• electrolyte disorder
• sign/symptom

Additional terms

• drugs associated with hyponatremia
• fractional excretion of sodium (FENA)
• hypernatremia
• sodium (Na+) in serum

Patient information

hyponatremia patient information