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Hyponatremia

Last updated: January 18, 2021

Summary

Hyponatremia is a state of low sodium levels (< 135 mEq/L). Sodium is the most important osmotically active particle in the extracellular space and is closely linked to the body's fluid balance. Causes of hyponatremia include dehydration, excessive free water intake (e.g., primary polydipsia), and increased release of ADH causing reabsorption of free water in the kidneys (e.g., SIADH, CHF). The onset can be acute or chronic and symptoms are predominantly neurological and often nonspecific (e.g., nausea, headache, confusion). Investigating the cause of hyponatremia requires consideration of the patient's volume status and renal ability to retain sodium. Some conditions with very high protein (e.g., multiple myeloma) or lipid levels (e.g., DKA) in the blood may result in a laboratory artifact of falsely low serum sodium concentrations (pseudohyponatremia). Treatment involves careful correction of the sodium deficit and/or fluid imbalance. A rapid increase of the serum sodium concentration can have damaging osmotic effects, as seen in osmotic demyelination syndrome.

Definition

  • Hyponatremia: reduced serum sodium concentration (< 135 mEq/L)
  • Classification [1]
    • Severity [2]
      • Mild hyponatremia: 130–135 mEq/L
      • Moderate hyponatremia: 125–129 mEq/L
      • Severe hyponatremia (profound): < 125 mEq/L
    • Disease onset [2]
      • Acute hyponatremia: < 48 hours [3]
      • Chronic hyponatremia: ≥ 48 hours or duration unknown [2]
    • Plasma osmolality (see “Etiology”)

Etiology

Hypotonic hyponatremia [1][4]

Causes of hypotonic hyponatremia
Hypovolemic hypotonic hyponatremia Euvolemic hypotonic hyponatremia Hypervolemic hypotonic hyponatremia
Description
Renal causes
Extrarenal causes

Hypertonic hyponatremia [1][4]

Isotonic hyponatremia [1][4]

Isotonic hyponatremia should always be excluded as a cause of hyponatremia to avoid unnecessary aggressive treatment.

Pathophysiology

Fluid compartment changes in hyponatremia

Defined by Changes
Tonicity Volume status
Serum osmolality Total body water Total body sodium
Hypotonic hyponatremia Hypovolemic hypotonic hyponatremia

↓↓

Euvolemic hypotonic hyponatremia

↓ Or normal
Hypervolemic hypotonic hyponatremia ↑↑
Isotonic hyponatremia (pseudohyponatremia)

Normal

Normal

Hypertonic hyponatremia

Normal

Clinical features

Clinical features depend on the onset, duration, and severity of hyponatremia. Most patients with chronic hyponatremia are asymptomatic and symptoms typically only occur with serum sodium concentration < 120 mEq/L. [4][7]

Severely symptomatic hyponatremia [4]

Symptoms usually develop acutely (onset < 48 hours). The severity tends to correlate with the extent of cerebral edema.

Mild and moderately symptomatic hyponatremia [4]

Symptoms usually develop slowly (onset > 48 hours) and are typically nonspecific (patients can also be asymptomatic).

Clinical assessment of volume status [1][2]

Evaluation of the volume status is useful to further determine the cause. See also “IV fluids.”

Hypovolemic hyponatremia resulting from extrarenal causes typically manifests with oliguria due to hypovolemia while hypovolemic hyponatremia resulting from renal causes manifests with hypovolemia due to polyuria.

Diagnostics

Diagnostic approach to hyponatremia [1][2][4][9]

  1. Confirm hyponatremia: Repeat BMP.
  2. Exclude hyperglycemia: Check serum glucose.
  3. Check the serum osmolality (SOsm): first step in the evaluation of confirmed hyponatremia
  4. Perform focused diagnostic evaluation based on serum osmolality.

If the patient has acute hyponatremia or severe symptoms, proceed directly to treatment.

After confirming hyponatremia, serum osmolality is the most appropriate initial laboratory test to assess the etiology.

Diagnostic evaluation based on serum osmolality

Hypotonic hyponatremia [2][4][9]

The distinction between hypovolemia and euvolemia is usually difficult to make on examination alone; examination findings have low sensitivity and specificity. Many authors recommend focusing on urinary sodium rather than clinical features to distinguish between the two. [1][2][9]

  • Interpretation of UNa and/or FENa : to determine if the cause is renal or extrarenal [9]
Interpretation of diagnostic evaluation in hypotonic hyponatremia [1][4][9]
Volume status Hypovolemic Euvolemic Hypervolemic
Urine sodium
  • < 20–30 mEq/L
  • ≥ 20–30 mEq/L
  • < 20–30 mEq/L
  • ≥ 20–30 mEq/L
  • < 20–30 mEq/L
  • ≥ 20–30 mEq/L
FENa
  • < 1%
  • ≥ 1%
  • < 1%
  • ≥ 1%
  • < 1%
  • ≥ 1%
Urine osmolality
  • > 100 mOsm/kg H2O
  • ≤ 100 mOsm/kg H2O
  • > 100 mOsm/kg H2O
  • > 100 mOsm/kg H2O
Causes (See “Etiology” for more information.)

In patients taking diuretics, urinary sodium concentrations should be interpreted with caution. A FEUa < 12 % can provide more diagnostic accuracy than UNa to differentiate hypovolemia from euvolemia. [9]

Laboratory findings that suggest hypovolemia

Additional tests [1][2][9]

Consider the following based on clinical suspicion:

Hypertonic hyponatremia [4]

Isotonic hyponatremia (pseudohyponatremia) [11][12]

If pseudohyponatremia is suspected, confirm or exclude hyponatremia using direct potentiometry.

Formulas for hyponatremia

Hyponatremia formulas [4]
Formula
Serum osmolality
  • (2 x Na+) + (glucose/18) + (BUN/2.8) + (ethanol/4.6)
Corrected serum sodium concentration for hyperglycemia [14][15]
  • Katz formula: measured Na+ concentration + [0.016 × (serum glucose concentration - 100)]
  • Hillier formula: measured Na+ concentration + [0.024 × (serum glucose concentration - 100)]
Fractional excretion of sodium (FENa) [9][10]
  • (SCreatinine × UNa)/(UCreatinine x SNa) × 100%
Fractional excretion of urea (FEUrea) [16]
  • (UUrea x SCreatinine)/(UCreatinine x SUrea) x 100%
Fractional excretion of uric acid (FEUA) ) [2][9][17]
  • (UUA × SCreatinine)/(UCreatinine × SUA) × 100%
Urine to serum electrolyte ratio [18]
  • (UNa + UK)/SNa
Total body water (TBW) [19]
  • Weight (kg) x k
    • k depends on the age and sex:
      • 0.6 in males
      • 0.5 in females and elderly males
      • 0.45 in elderly females
  • Watson formula
    • Males: 2.447 - 0.09156 x age (years) + 0.1074 x height (in cm) + 0.3362 x weight (in kg)
    • Females: -2.097 + 0.1069 x height (in cm) + 0.2466 x weight (in kg)
Change in sodium concentration [20]
  • Δ [Na+] = [(Sodium infusate + potassium infusate) - Serum Na+)]/(TBW + 1)
    • Sodium infusate is the amount of sodium present in 1 L of the given solution.
    • See “Crystalloid solutions” for the sodium (and potassium) mEq contained in each fluid.
IV fluid rate for correction of hyponatremia (mL/hour) [20]
  • 1000 x (Na+ correction rate in mEq/L/hr)/(change in sodium concentration)

Treatment

General principles [1]

Alleviate Acute hyponatremia Aggressively and Correct Chronic hyponatremia Carefully!

Once specific treatment is given (e.g., discontinuation of diuretics, corticosteroids for hypocortisolism), there is a high risk of rapid autocorrection causing a dangerous increase in sodium.

Acute hyponatremia and severely symptomatic hyponatremia [1]

The goal of treating acute and/or severely symptomatic hyponatremia is the rapid correction of serum sodium with hypertonic saline to reverse neurological symptoms and prevent brain herniation. Early specialist consultation (intensive care, nephrology) is advised.

  • Indications [1]
  • Initial sodium goal: ↑ serum sodium 1–2 mEq/L/hour until an increase of 4–6 mEq/L has been reached within six hours [1]
  • Regimens for rapid correction
    • Severe symptomatic hyponatremia: hypertonic saline bolus (e.g., 3% NaCl ) [1]
    • Mild to moderate symptomatic hyponatremia: hypertonic saline infusion (e.g., 3% NaCl infusion ) [1]
    • Consider adding desmopressin to prevent overcorrection in patients with sodium < 120 mEq/L [22]
  • Further management and sodium goals: Once the acute sodium goal has been reached, start cause-specific treatment.
  • Monitoring
    • Serial serum sodium measurement
      • While receiving hypertonic saline bolus: every 20 minutes until symptoms resolve [9]
      • After the initial goal is reached: every 2–4 hours, then every 6–12 hours after stabilization [9][18]
    • Monitor urine output closely (e.g., every hour).

If there is any uncertainty about the chronicity of the hyponatremia, maximum sodium correction rates for chronic hyponatremia should not be exceeded in order to avoid the risk of ODS. [1]

Rapid sodium correction of 4–6 mEq/L should be achieved in the first 6 hours of therapy for patients with acute hyponatremia and/or severely symptomatic hyponatremia. [1]

Six in Six hours for Severe Symptoms and Stop [1]

Chronic hyponatremia without severe symptoms [1]

The goal of treating chronic hyponatremia is a slow correction of serum sodium levels to prevent overcorrection and subsequent osmotic cell damage. Treatment depends on the underlying cause (see “Cause-specific treatment” below).

  • Goal: The goal correction rate depends on the risk of ODS (see table).
  • Monitoring: Monitor patients closely for signs of overcorrection (see “Management of sodium overcorrection” below).
    • Monitor urine output closely (e.g., every hour): > 100 mL/hour is concerning for overcorrection. [1]
    • Check serum sodium frequently (at least every 4–6 hours until serum sodium is ≥ 125 mEq/L). [1]
Recommended sodium correction rates for chronic hyponatremia [1][2]
Patients at normal risk for ODS Patients with high-risk factors for ODS
Minimum correction rate (goal)
  • 4–8 mEq/L within 24 hours
  • 4–6 mEq/L within 24 hours
Maximum correction rate (limit)
  • 10–12 mEq/L within 24 hours
  • 18 mEq/L within 48 hours
  • 8 mEq/L within 24 hours

Rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome! Do not exceed hourly or daily maximum correction limits.

In patients with chronic hyponatremia, urine output > 100 mL/hour suggests sodium overcorrection and risk of impending osmotic damage.

Cause-specific treatment [1]

Hypovolemic hyponatremia [1]

Euvolemic hyponatremia [1]

Serum sodium should be monitored every 6–8 hours in patients receiving vaptan therapy in order to identify overcorrection. [1]

Hypervolemic hyponatremia [1]

If hyponatremia persists after diuretic use has been stopped, consider other causes. [9]

Management of sodium overcorrection [1]

  • Initial serum Na+ ≥ 120 mEq/L: Management of overcorrection is probably not necessary. [1]
  • Initial serum Na+ < 120 mEq/L: If the increase in sodium exceeds sodium correction limits (e.g., > 8 mEq/L/24 hours in a patient at high risk for ODS), start treatment to lower serum sodium.
  • Monitor urine output and fluid balance closely (typically every hour).
  • Check serum sodium frequently (e.g., hourly) until sodium goals and limits are achieved. [1]

Complications

Correcting hyponatremia too rapidly may cause two complications: From low to high, your pons will die (osmotic demyelination syndrome); from high to low, your brain will blow (cerebral edema).

We list the most important complications. The selection is not exhaustive.

Osmotic demyelination syndrome (ODS)

Correcting hyponatremia too rapidly can cause osmotic damage to the axonal myelin sheath in the CNS.

The symptoms and imaging findings of osmotic demyelination syndrome (ODS) first appear several days after the correction of hyponatremia!

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References

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