13 Sodium Dysregulation
Abstract
Disorders of sodium regulation leading to either hyponatremia or hypernatremia are seen frequently in the critical care setting, and have particular importance in the setting of neurologic injury, surgery, and disease. This chapter is split into two major sections: hyponatremia and hypernatremia. For each, a basic overview with important features are provided, followed by a list of possible causes, an approach to the diagnosis (with specific focus on neurologically relevant etiologies such as syndrome of inappropriate antidiuretic hormone secretion (SIADH), cerebral salt wasting (CSW), and diabetes insipidus), and finally our recommendations on the general approach to treatment. Useful terminology and equations are also provided throughout the chapter that may assist in the bedside management while rounding in the critical care unit.
Keywords: hyponatremia, hypernatremia, SIADH, cerebral salt wasting, diabetes insipidus, hypertonic saline, free water deficit
13.1 Terminology
• Tonicity: total concentration of nonpenetrating solutes (effective plasma osmolality)
• Osmolarity: total concentration of penetrating and nonpenetrating solutes (mOsm/L of solution = mmol/L)
• Osmolality: per kg of solvent (normal range: 275–290 mOsm/kg)
• Calculation: Serum Osmolality = 2 × Serum [Na] + Serum Glucose/18 + Blood urea nitrogen (BUN)/2.8
13.2 Hyponatremia Classification
Multiple factors are taken into consideration when classifying hyponatremia. In addition to serum sodium concentration, the patient’s volume status and serum and urine osmolality should be taken into consideration. Hyponatremia is defined as serum [Na+] < 135 mEq/L1 with severity based on the concentration. Hyponatremia can be found in a wide range of hospitalized patients (1–15%) but is far more common in patients with neurologic injury ranging from 15 to 30% depending on the etiology.23 Depending on the concentration, hyponatremia can be categorized by severity: Mild: 130–135 mEq/L, Moderate: 125–129 mEq/L; Severe: < 125 mEq/L. It can be broken into additional categories based on serum osmolality and urine Na + concentration (▶ Fig. 13.1).
13.2.1 Causes of Hyponatremia
There are multiple medical conditions associated with hyponatremia including surgery, critical illness, medications, and advanced age. Hyponatremia has also been associated in patients with traumatic brain injury, subarachnoid hemorrhage, meningitis, and brain tumors. ▶ Table 13.1 details various causes of hyponatremia.
13.2.2 Symptomatic Hyponatremia
Symptomatic hyponatremia typically occurs with a serum sodium concentration < 125 mEq/L. However, symptoms are more likely to occur when there is a rapid sodium change.2 In chronic conditions where the sodium concentration decreases over months, the brain is able to adapt by decreasing tonicity and subsequently the patient may remain relatively asymptomatic despite moderate to severe degree of hyponatremia.3
• Mild hyponatremia ([Na] 130–135 mEq/L): Asymptomatic
Fig. 13.1 Diagnostic approach to hyponatremia.
• Moderate hyponatremia ([Na] 124–129 mEq/L): Nausea, malaise, confusion, headache, vomiting, lethargy, and increasing disorientation as the sodium concentration drops3,22
• Severe hyponatremia (typically [Na] < 125 mEq/L): In addition to the abovementioned, seizures, coma, permanent brain damage, respiratory failure, brainstem herniation, and death3,22
Seizures typically occur with serum sodium concentrations < 120 mEq/L. Although the absolute risk of seizure ranges from 2.5 to 10% depending on the serum concentration with the higher risk related to concentrations < 110 mEq/L.4
13.3 SIADH versus CSW
13.3.1 Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Characterized by excessive antidiuretic hormone (ADH) release leading to increased renal water reabsorption, extracellular fluid (ECF) expansion, and hyponatremia. Due to a variety of causes (▶ Table 13.2), ADH is unable to be fully suppressed despite the condition of hypo-osmolality.5
• SIADH should be suspected in any patient with hyponatremia, hypo-osmolality, and a urine osmolality > 100 mOsm/kg, after the exclusion of thyroid, adrenal, and renal causes. In SIADH, the urine sodium concentration is usually above 40 mEq/L, the serum potassium concentration is normal, there is no acid-base disturbance, and the serum uric acid concentration is frequently low.6
13.3.2 Cerebral Salt Wasting (CSW)
• Hypovolemic hyponatremia observed in subarachnoid hemorrhage, head injury, neurosurgical procedures, stroke, meningitis, and neoplasms (primitive neuroectodermal tumors with intraventricular dissemination, carcinomatous meningitis, glioma, and primary CNS lymphoma).5,8
• Hyponatremia is commonly seen in stroke, and may be from either SIADH or CSW. In ischemic stroke, hyponatremia has been reported in up to 11.5% of ischemic strokes, and 15.6% of intracerebral hemorrhage (ICH).9,10 One study revealed hyponatremia to be present in 36.4% of ischemic strokes and 51.9% of ICH (over the entire hospital stay), and was attributed to CSW in 44.2% of cases.11
It is characterized by volume contraction from renal salt wasting (differentiated from the volume expanded state of SIADH). It is important to distinguish CSW from SIADH.
13.3.3 SIADH and CSW Diagnosis
Accurate determination of the patient’s volume status is crucial to differentiate these syndromes (see ▶ Table 13.3 and ▶ Fig. 13.1). Physical examination and other clinical measures can be useful to assess volume status, with evidence of a hypovolemic state increasing the likelihood of a CSW diagnosis.
Table 13.3 Differentiating SIADH from CSW
Feature | SIADH | Cerebral salt wasting |
Volume status | Euvolemia to mild hypervolemia | Hypovolemia |
Serum [Na + ] | Low | Low |
Urine [Na + ] | Increased (> 40 mEq/L) | Increased (> 40 mEq/L) |
Serum osmolality | Low | Low |
Urine osmolality | High (> 100 mOsm/kg) | High (> 100 mOsm/kg) |
Urine output | Normal | Increased |
Serum uric acid | Low | Normal or low |
Serum bicarbonate | Normal or low | Increased |
Central venous pressure | Normal or slightly elevated (6–10 cm H2O) | Low (< 6 cm H2O) |
BUN | Normal or low | Increased |
Mechanism | Water retention due to increased ADH secretion | Excess secretion of water and sodium |
Abbreviations: ADH, antidiuretic hormone; BUN, blood urea nitrogen; CSW, cerebral salt wasting; SIADH, syndrome of inappropriate antidiuretic hormone secretion. | ||
13.4 Diagnostic Approach to Hyponatremia
• Initial testing considerations: Basic metabolic panel, hepatic function panel, serum osmolality, urine sodium, urine osmolality, and thyroid stimulating hormone (TSH)
• May also consider obtaining AM cortisol if adrenal insufficiency is suspected
Additional notes on serum osmolality:
• Correction for hyperglycemia: To calculate the “corrected” serum sodium, we recommend the use of the following ratio: The sodium concentration will fall by 1.7 mEq/L for each 100 mg/100 mL (5.5 mmol/L) increase in glucose concentration.12
• Correct for azotemia: Tonicity = Measured serum osmolality – (BUN ÷ 2.8)
Dividing the BUN by 2.8 converts mg/dL of urea nitrogen into mmol/L of urea, which is required when calculating osmolality. If blood urea is measured in units of mmol/L, simply subtract without dividing by 2.8.13
13.4.1 Hyponatremia Treatment: General Principles
• Risk of osmotic demyelination (formerly known as central pontine myelinolysis)
◦ High risk: [Na] < 105 mEq/L, hypokalemia, alcoholism, malnutrition, and liver disease14
◦ Low risk: Hyperacute hyponatremia (over a few hours) as they have not had time to develop brain adaptations that increase risk of osmotic demyelination
• Goal: Increase [Na + ] by 6–8 mEq/L in 24 hours; 12–14 mEq/L in 48 hours.
• Do not correct serum Na at a rate greater than 10 mEq/L in 24 hours (and no more than 18 in first 48 hours)
• Recheck serum sodium every 4 hours for the first 24 hours, and at regular intervals thereafter until stabilized.
13.4.2 Acute Symptomatic Moderate to Severe Hyponatremia
Serum [Na] usually < 129 mEq/L with symptoms that can include confusion, nausea (without vomiting), headache, somnolence, and hallucinations. More severe symptoms include: vomiting, seizures, cardiorespiratory arrest, abnormal and deep somnolence, and coma (Glasgow coma score [GCS] < 8).
Treatment
Use 3% hypertonic saline infusion to raise the serum [Na]
• Initial emergent therapy: Over the first 4 to 6 hours, determine the rate to increase the serum [Na] by roughly 1 mEq/hour. It has been shown that a 4 to 6 mEq/L increase in Na concentration is adequate in the most seriously ill patients.15
Note: With more severe symptoms, a 100 mL bolus of 3% hypertonic saline can be considered.
• Check serum [Na] after 4 hours, and adjust rate of 3% hypertonic saline solution so that total rise in serum [Na] will not be greater than 10 to 12 mEq over the first 24-hour period.
Determining the Rate of 3% Hypertonic Saline Infusion
• Determine the desired change in serum [Na] (and thus, the desired [Na])
• Determine the desired timeframe to achieve this change
• Determine rate of 3% hypertonic saline infusion using the following approach:
Solve for the amount of fluid needed to reach the desired [Na] by using this formula:
