Hyponatremia

Description

Hyponatremia describes a serum sodium (Na⁺) concentration <135 mmol/L (Exact value depends on laboratory assay used.)
In addition to being the most common electrolyte derangement, hyponatremia has been associated with increased morbidity and mortality.

Epidemiology

Incidence

Hyponatremia is the most commonly encountered electrolyte disorder in hospitalized patients

Prevalence

1–2% in hospitalized patients
4.4% of postoperative patients
Nearly 30% of critically ill patients

Morbidity

Hyponatremia is associated with prolonged durations of stay in the intensive care and hospital, and associated with a higher rate of discharge to a long-term care facility.

Mortality

Associated with an increased all-cause mortality in hospitalized patients
It is an independent risk factor for death in cirrhosis, heart failure, and following acute myocardial infarction.

Etiology/Risk Factors

Hypoosmolar Hyponatremia. Describes an increase in plasma water in excess of plasma sodium.

Increased endogenous antidiuretic hormone (ADH)
- Hypovolemic
  - Intravascular volume depletion.
  - GI losses (diarrhea, vomiting)
  - Skin losses (burns, sweat)
  - Renal losses (diuretics, cerebral salt wasting, ketonuria, bicarbonaturia)
  - Third spacing into a "nonfunctional" space (edema, tissue trauma)
  - Adrenal insufficiency (may also be euvolemic). Decreased aldosterone results in volume contraction due to renal loss; ADH is released in response. Cortisol insufficiency also stimulates ADH release.
- Hypervolemic
  - Decreased effective circulating volume (heart failure, cirrhosis, nephrotic syndrome). In addition to increases in ADH, arterial underfilling is detected by baroreceptors in the aortic arch, carotid sinus, and afferent renal arterioles that then activate the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) resulting in avid sodium and water retention.
- Euvolemic
  - Syndrome of inappropriate ADH secretion (SIADH). Increased levels of ADH cause water retention (decreased serum osmolality).
  - Reset osmostat. A type of SIADH where ADH release is stimulated by a lower osmolality than would be expected in a normal patient. Seen in pregnancy and chronic malnutrition.
  - Hypothyroidism. Mechanism is not completely understood. Possibly due to reduced cardiac output or SIADH.
Increased exogenous ADH (usually euvolemic)
- Desmopressin or vasopressin use
- Oxytocin infusion during the induction of labor or postpartum
Appropriately suppressed ADH (usually euvolemic but may be hypervolemic)
- Insufficient solute to excrete excess free water. In beer drinker's potomania, excessive hypotonic fluid intake results in an overwhelmed capacity to excrete free water.
- Intake of hypotonic fluids
- Polydipsia
- Excessive hypotonic IV fluids
- Absorption of glycine or sorbitol solutions during hysteroscopy or trans-urethral resection of the prostate (TURP) (may be associated with normal or elevated osmolality)

Hyperosmolar hyponatremia. May be referred to as redistributive hyponatremia because water shifts from the intracellular to the extracellular compartment with a resultant dilution of sodium. The total body water and total body sodium are unchanged.

Mannitol. This effect is sometimes harnessed during increased intracranial pressure to decrease cerebral volume. Similarly, for neurosurgical cases, mannitol may be administered prior to opening the dura to decrease brain volume and protrusion.
Hyperglycemia
Maltose (IVIg)
Pseudohyponatremia. The plasma is diluted by excessive proteins or lipids. The total body water and total body sodium are unchanged.
- Hyperproteinemia
- Hyperlipidemia

Physiology/Pathophysiology

Antidiuretic hormone (ADH). Excessive exogenous or endogenous ADH prevents the excretion of maximally dilute urine.
- ADH results in free water absorption as water moves passively down its concentration gradient from the tubules to the hypertonic medullary interstitium via aquaporin-2 channels in the medullary collecting ducts.
- Endogenous ADH release from the posterior pituitary gland is normally stimulated by an increase in serum osmolality thereby maintaining normal serum osmolality between 280 and 300 mOsm/kg. Sodium, along with its anion (mostly chloride or bicarbonate) account for the vast majority of serum osmoles.
- ADH release may be enhanced despite a low serum osmolality in the following situations (described above under etiology):
  - Decreased intravascular volume (in an attempt to maintain serum volume)
  - Decreased effective circulating fluid volume
  - SIADH and reset osmostat
- Exogenous ADH acts in the same way as endogenous ADH with resultant free water absorption and hyponatremia.
- In polydipsia and beer drinker's potomania, patients excrete maximally dilute urine; however, their excessive intake of hypotonic fluid overwhelms the renal diluting capacity resulting in hyponatremia.
Neurological effects
- Hyponatremia increases free water movement into the intracellular space and cellular edema. Because of the fixed space of the cranium, symptoms manifest from increased intracranial volume and can result in herniation and death. When chronic, the cells are able to compensate by moving solutes out and into the extracellular space (water moves extracellularly as well); this decreases the pathological effects.

The history and physical exam should be focused on searching for the underlying cause, assessing volume status, and determining if the derangement is acute (present <48 hours) or chronic (present >48 hours or if uncertain of time onset) causes
History
- Fluid loss from diarrhea, burns, vomiting
- Cardiac, renal, and hepatic disorders
- Medications (desmopressin, thiazide diuretics, oxytocin, carbamazepine, SSRIs)
- IV fluids
- Surgical history
Symptoms
- Mild and chronic cases are often asymptomatic
- Acute or more severe cases may have nausea, malaise, lethargy, headache, or seizures
Signs/physical exam
- May have altered mental status or be obtunded
- Assessment of intravascular volume status: Jugular venous pressure, capillary refill, edema, dry mucous membranes, hypotension, and tachycardia
Laboratory investigations: Serum osmolality, urine osmolality, urine sodium
Additional studies such as creatinine, urea, liver function panel, cortisol, and TSH can further aid with the diagnosis.

Differential Diagnosis

Measurement of serum osmolality and serum glucose will rule out hyperosmolar hyponatremia.
- Hyperglycemia: Na⁺ is decreased by 1.6 mEq/L for every 100 mg that glucose exceeds 100 mg. True [Na⁺] = [Na⁺] + [1.6 (glucose-100)/100]
Clinical exam to assess the volume status is important in differentiating between hypervolemic, euvolemic, and hypovolemic hyponatremia.
Patients with intravascular volume depletion and decreased effective circulating fluid volume tend to avidly retain sodium and therefore have a low urine [Na⁺].
- Urine [Na⁺] is typically <20 mEq/L
- Fractional excretion of sodium (FENa) is a more accurate way to determine sodium excretion.
- FENa = ([Na⁺]_urine × Cr_plasma)/([Na⁺]_plasma × Cr_urine) × 100; a FENa <1–2% is consistent with avid sodium retention.
- An exception is when renal sodium loss leads to volume contraction (e.g., diuretics and cerebral salt wasting).
  - [Na⁺]_urine and FENa are usually >20 mEq/L and >2%, respectively.
  - In these circumstances, a FEurea <30% suggests avid renal reabsorption
- Because of high levels of ADH, urine osmolality will be high (>400 mOsm/L).
Patients with hyponatremia from SIADH or exogenous ADH do not avidly retain sodium. Typically, [Na⁺]_urine is >20 mEq/L and FENa >2%.
- Urine osmolality is inappropriately high (exact value depends on degree of excess ADH secretion/administration).
Polydipsia and beer drinker's potomania present with maximally dilute urine (<100 mOsm/L).
- These patients do not avidly retain sodium.
- FENa is typically >2% but [Na⁺]_urine may be low due to high urine volumes.

Identify and manage acute symptomatic hyponatremia before proceeding with the operation. In addition, when specific causes can be identified they should be treated accordingly:
- Intravascular depletion from GI or renal losses, as well as insensible and third spacing, should be repleted.
- Congestive heart failure: Volume overload should be treated with diuresis and/or optimization of cardiac function (may require inotropic agents). Sodium and water restriction are imperative.
- Volume overload states such as cirrhosis should be managed with water and sodium restriction, diuresis, and treatment of underlying disorder.
- SIADH is managed with water restriction and management of the underlying disorder (see SIADH chapter). Other possible therapies include demeclocycline or vasopressin antagonists.
- Polydipsia is managed with water restriction
Sodium correction. Prevent excessive rises in [Na⁺] in patients with documented chronic hyponatremia (>48 hours).
- Maximum rate of change <0.5 mmol/L/hour (<10 mmol/L in 24 hours, <18 mmol/L in 48 hours)
- Rapid increases in [Na⁺] in chronic hyponatremia can lead to osmotic demyelination.
Avoid intraoperative exacerbation of hyponatremia. Worsening hyponatremia may lead to cerebral edema, seizures, and possibly death.

Repeat serum electrolytes
Consider medicine or nephrology consultation

Bagshaw SM , Townsend DR , Mcdermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anesth. 2009;56:151–167.
Wald R , Jaber BL , Price LL , et al. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294–302.
Sterns R , Cappuccio J , Silver S , et al. Neurologic sequelae after treatment of severe hyponatremia: A multicenter perspective. J Am Soc Nephrol. 1994;4:1522–1530.
Adrogué , HJ , Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–1589.

See Also (Topic, Algorithm, Electronic Media Element)

TURP Syndrome
Hypernatremia
Urine Osmolality
Plasma Osmolarity
Hypothyroidism
Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

ICD9

276.1 Hyposmolality and/or hyponatremia

ICD10

E87.1 Hypo-osmolality and hyponatremia

Hyponatremia should not be ignored.
To proceed or delay? Elective surgeries should be delayed for a [Na⁺] <130 mmol/L in order to complete a full workup and begin treatment. Proceeding with urgent or emergent surgeries must be done with caution while weighing the risk–benefit ratio of delay.
Perioperatively, worsening of hyponatremia or a rapid rise of serum [Na⁺] in chronic hyponatremia should be avoided.

Adam Romanovsky , MD

Sean M. Bagshaw , MD, MSc, FRCPC

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Basics ⬇

Incidence

Prevalence

Morbidity

Mortality

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Follow-Up ⬆ ⬇

References ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆ ⬇

Clinical Pearls ⬆ ⬇

Author(s) ⬆