Solo Sodium: Emergent Management of Symptomatic Hyponatremia

 A 62-year-old Hispanic male is brought in by EMS for altered mental status and new onset seizure. On arrival to the emergency department his initial vitals are stable with a finger stick glucose of 120 mg/dl. On exam there is no evidence of trauma. He appears incontinent of urine, post-ictal and unable to give a detailed history, but is protecting his airway. Per EMS he has no history of seizures and no pertinent medical problems. A head CT is normal, and all of his labs are unremarkable, with the exception of a serum sodium, which returns at 112 mEq/L.

Pathophysiology

The initial differential for new onset seizures is generally quite broad and includes hypoglycemia, drugs (alcohol/benzo withdrawal), stroke, and infections such as meningitis or encephalitis. Less often considered are electrolyte abnormalities, specifically hyponatremia.

An abnormal serum sodium is one of the most common electrolyte disturbances we encounter clinically, but typically it is mild and requires no acute therapy. Hyponatremia is usually defined as a serum sodium concentration of <135 mEq/L. Symptoms of hyponatremia can vary depending not only on the degree of hyponatremia but also how acutely the drop in sodium occurred. It is abrupt sodium changes over 48 hours that are most commonly associated with neurologic symptoms and risk of death from brain herniation.¹ Complaints and findings include lethargy, vomiting, headaches, hiccups, confusion, seizures, and even death.

When approaching the cause of hyponatremia, you must determine the volume status and urine characteristics. Knowing this information will help establish the etiology and guide future treatment. In general, all hyponatremia can be subdivided into four major categories based on the balance of total body water and sodium. These four categories are hypovolemic, hypervolemic, euvolemic and pseudohyponatremic hyponatremia.

Clinical Clues to Diagnosis

In the emergency department, recognizing that hyponatremia is contributing to the presenting symptoms is most important. Identifying the exact etiology can be challenging in the emergent setting, but the diagnostic approach should focus around a good history and physical exam. For hypovolemic hyponatremia the patient's total body water is decreased with a greater loss in sodium from either body fluid (vomiting, diarrhea, sweating) or renal losses. On history any acute fluid loss could be a clue; on exam the patient may appear dehydrated, so check for skin turgor, dry membranes, and orthostatic hypotension. Blood work may demonstrate an elevated creatinine, elevated BUN/Cr ratio (>20:1), decreased urine volume, and concentrated urine (specific gravity>1.015).

In clenching the diagnosis for hypovolemic hyponatremia you may win extra praise from your inpatient colleagues by ordering additional lab work including urine electrolytes (Na, K, Cl), or uric acid (if on diuretics). When interpreting these urine studies it can be helpful to think of sodium and water as conjoined twins. So if the volume loss is extra-renal, the kidney will work to conserve water (i.e., salt) resulting in a decreased urine sodium concentration (<10 meq/L, FE_NA<1%). Alternatively, if hypovolemic hyponatremia is caused by the kidneys, urine sodium will be elevated (>20 mEq/L, FE_NA>1%) with a differential including diuretics, renal tubular acidosis, or adrenal insufficiency.

Although an absolute “zebra” on the differential, adrenal insufficiency could be considered if a serum chemistry demonstrates hyponatremia with an elevated potassium. In this instance a deficiency of mineralocorticoids (specifically aldosterone) causes decreased sodium resorption and potassium excretion.² In regards to evaluating endocrine causes of hyponatremia, checking a random cortisol (excludes adrenal deficiency if >18 mg/dl), and thyroid function testing can be ordered, but again will not affect ED disposition.

On the other hand, if your hyponatremic patient has a known history of poorly controlled diabetes, be sure to review the blood glucose as the cause may be pseudohyponatremia (~1.5 meq  †“ Na per every  †‘100 mg/dl glucose).³ Just as the name “pseudo” implies, this is not a true hyponatremia but a falsely lowered lab value occurring with any osmotically active chemical including protein (multiple myeloma), lipids (hyperlipidemia), or even mannitol. So although sodium appears low, it will correct when the underlying aberrancy is corrected.

A patient with hypervolemic hyponatremia will often appear “wet,” with bilateral pulmonary crackles, jugular venous distention, and edema. In this disease state there is a greater increase of total body water relative to sodium, which can occur in heart failure, renal failure, and cirrhosis.

Lastly, the fourth subdivision of hyponatremia is euvolemic hyponatremia, and diagnosis will be largely based on historical information from the patient, as the assessment of volume status will appear normal. In cases of euvolemia, the serum sodium is decreased in relation to increased total body water. Historical clues may include increased fluid intake during a marathon run (exercise associated hyponatremia), psychiatric disorders (psychogenic polydipsia), or even illicit substances such as ecstasy (see the article “X” in this issue). If no history of increased water ingestion is obvious, then consider SIADH as a cause with possible sources including pulmonary malignancies or intracranial pathology (trauma, stroke, hemorrhage). Lab tests to distinguish the type of euvolemic hyponatremia should include a serum osmolality (which should be low given increase in the total body water) as well as urine osmolality. In cases of acute water ingestion, urine osmolality will be dilute (U_osm<100) as the kidneys try to correct for the extra volume, versus an inappropriate ADH response (SIADH) when the serum is dilute but the urine remains concentrated (U_osm>100). See Table 1.

Back to the Case

Your patient has a second seizure, but this time is increasingly altered, and failing to protect his airway. His family arrives and reports that he was recently diagnosed with a lung mass. The patient is emergently intubated, prepped for placement of a central line, and hypertonic saline is initiated.

How to Fix It

There are two indications for treating hyponatremia emergently with hypertonic saline. First, when the sodium level is <110 mEq/L regardless of symptomatology, or second, when there is symptomatic hyponatremia with sodium <120 mEq/L.⁴

In this case, the acute hyponatremia was euvolemic SIADH secondary to lung malignancy. The most common malignancy to cause SIADH is ADH-producing small cell carcinoma. When caring for a seizing patient with hyponatemia you will not win any favors from staff or family by perseverating over the underlying cause. You need to fix the sodium ASAP.

Per the updated expert panel recommendations from the American Journal of Medicine in 2013, a patient presenting with symptomatic hyponatremia should receive a 100ml bolus of 3% saline over 10 mins, repeated twice if needed.⁴ Evidence has demonstrated a 4-6 meq/L increase in serum sodium over one hour is sufficient to reverse the most serious manifestations of hyponatremia (i.e., seizure, herniation).⁵ In one prospective observational study of 58 adult patients with symptomatic severe hyponatremia, administration of 100 ml of 3% hypertonic saline resulted in a mean increase in sodium of 2 mEq/L.⁶

Additional updated recommendations suggest correction of serum sodium be limited to less than 6-8 meq/L in the first 24 hours.⁵ However, if you work in a setting where critical patients board for long hours, a slower correction rate can be estimated by multiplying the patient's body weight in kilograms by the desired rate of increase in serum sodium. For example, in a 70 kg patient, an infusion of 3% NaCl at 70 mL/h will increase serum Na+ by approximately 1 meq/L/h, while infusing 35 mL/h will increase serum Na+ by approximately 0.5 meq/L/h.⁵ Just be sure to check the serum chemistry every two hours, and adjust the rate accordingly.

In general, a conservative infusion is recommended to avoid the feared osmotic demyelination syndrome from aggressively over correcting the sodium and osmolality. This dreaded complication leads to diffuse demyelination of neurons in the brain resulting in flaccid paralysis, dysarthria, dysphagia, hypotension and often death.⁷ Patients at higher risk of demyelination include known alcoholics, patients who are malnourished, hypokalemic, elderly, patients with severe liver disease, or severe hyponatremia with sodium <105 meq/L. For completeness, when treating hypovolemic hyponatremia, if the patient is hemodynamically unstable, then aggressive volume resuscitation with normal saline is the rule, until they become more stable, at which point they can be more gently hydrated.⁴ In hypervolemic hyponatremia, the patient ideally needs volume removal with diuretics/dialysis, limited sodium intake, and water restriction to improve their care.

What About the Central Line?

For administration of hypertonic saline, the bottom line is that a large-bore peripheral vein will suffice in the emergent setting. On review of the evidence, the maximum recommended osmolarity for a solution administered into a peripheral vein is 900 mOsm/L, due to the fact that solutions with higher osmolarities may cause thrombophlebitis. In regards to 3% hypertonic saline the osmolaltity is 1026 mOsm/L, so central venous assess is preferred, given the potential for thrombophlebitis and possible tissue necrosis if extravasation occurs.⁸ However, remember: life over limb.

Table 1. Interpretation of Lab Values in Hyponatremia.
Classification of Hyponatremia by Plasma Tonicity/Urine Osmoality

Case Resolution

Hypertonic saline is continued through the central line once placed, and the patient is transferred to the intensive care unit. Overnight he remains intubated and sedated with a hypertonic infusion of 0.5 ml/k/hr of 3% saline. The following day his sodium improves to 120 mg/dl, and he is able to be safely extubated, and suffers no complications or neurologic deficits.

References

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2. Szylman P, Better OS, Chaimowitzet. al. Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. N Engl J Med. 12;294(7):361-5. 1976
3. Penne L, Thijssen S, Raimann J, et. al. Correction of sodium for glucose concentration in HD patients w/ poor glucose control. Diabetes Care. 33;(7) e91. 2010
4. Joseph V, Steven G, Arthur G et. al.Diagnosis, Evaluation and treatment of hyponatremia: Expert Panel Recommendations. Am journal of medicine. 126(10):S1-S42, Oct 2013
5. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrology. 29:282-299. 2009.
6. Bhaskar E, Kumar B, Ramalakshmi S. Evaluation of a protocol for hypertonic saline administration in acute euvolemic symptomatic hyponatremia: a prospective observational trial. Indian J Crit Care Med. 14(4):170-174. 2010.
7. Sterns RH, Riggs JE, Schochet SS Jr. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med. 314:1535-1542.1986.
8. Roche S, Velasco I, Porfirio M. Hypertonic saline resuscitation: saturated salt-dextran solutions. Crit Care Med. 18:203-207. 1990.