Hyponatremia Case Review

Brief Background
Hyponatremia is one of the more common electrolyte abnormalities in clinical medicine. Some sources estimate that the number of patients who experience sodium levels of less than 135 meq/L can be as high as 30% of all hospitalized patients. Management of hyponatremia is important because severe hyponatremia can cause substantial morbidity and mortality. One article cited a 1986 study in which 27% of previously healthy women undergoing elective surgery died after developing acute hyponatremia (averaging 108 mmol/L). Morbidity and mortality from hyponatremia is significantly higher in patients with underlying disease processes.

Classification of hyponatremia may help to determine its causes. In general, hyponatremia is classified based on volume status. Causes of hypovolemic hyponatremia may include excessive sodium losses from the kidneys, the skin, or the GI tract and also includes “third spacing” of fluids. Causes of euvolemic hyponatremia may include etiologies such as SIADH and psychogenic polydipsia. Many conditions stimulate ADH production including angiotensin release, hypovolemia, increased serum osmolality, hypotension, opiates, caffeine, and stress. ADH may be inappropriately secreted due to CNS or pulmonary infections and due to multiple medications including most diuretics. Causes of hypervolemic hyponatremia may include fluid overload states such as CHF, pregnancy, cirrhosis, and nephrotic syndrome. Serum sodium levels may also be artificially low with increased levels of plasma proteins or lipids and with increased serum concentration of osmotically active chemicals such as glucose and mannitol.

Clinical manifestations of hyponatremia depend on multiple factors including the chronicity of the symptoms, the absolute level of sodium, and the patient's overall health. The most common manifestations of hyponatremia are CNS-related and include mental status changes such as lethargy, confusion, disorientation, and agitation. Other symptoms such as nausea, vomiting, and weakness can also occur.

Severe hyponatremia may result in cerebral edema, encephalopathy and death.

General management of hyponatremia
Management of hyponatremia should take into account the chronicity of the disease. When hyponatremia is acute, an osmotic shift of free water into brain cells occurs, resulting in varying degrees of cerebral edema. When hyponatremia occurs over more than 48 hours, brain cells have more time to adapt to osmotic fluid shifts and significant amounts of cerebral edema are therefore less likely.

One of the more difficult aspects of managing symptomatic hyponatremia is determining the proper rate of sodium repletion. Expert panel guidelines on the management of hyponatremia note that “optimal treatment strategies [for hyponatremia] have not been well defined.” Patients with acute hyponatremia generally exhibit more symptoms than those with chronic hyponatremia and usually tolerate more rapid correction of their sodium levels. On the other hand, patients with chronic hyponatremia often have fewer clinical symptoms are are more likely to develop complications from rapid sodium repletion. If hyponatremia is corrected too rapidly in a patient with chronic hyponatremia, the rapid osmotic shift can cause osmotic demyelination, otherwise known as central pontine myelinolysis.

Guidelines on the management of hyponatremia published in 2007 recommended sodium correction of approximately 8 mmol/L per day and approximate limits of sodium correction to less than 12 mmol/L in 24 hours and less than 18 mmol/L in 48 hours. However, these guidelines also cited one study showing that severe demyelinating brain lesions rarely occurred unless the rate of sodium correction was more than 25 mmol/L in 48 hours. Other sources recommend correcting symptomatic acute hyponatremia at rates of up to 2 mEq/L/hr and correcting symptomatic chronic hyponatremia at rates of up to 0.5 mEq/L/hr until the patient's serum sodium level reaches 120 mEq/L or rises by 10 mmol/L in 24 hours.

Case Discussion
In this case a patient presented to the emergency department with severe hyponatremia. According to the expert testimony, the patient was falling and was having difficulty with her motor function. She was unable to walk and her speech was difficult to understand. Despite these symptoms, she was also noted to be conversing with her daughter in the room.

The patient had been having “flu-like symptoms” for the previous two weeks and had been vomiting for the previous 4 days. She complained of abdominal pain on one occasion during the emergency physician's evaluation. 

  • The patient's medical history was significant for hypertension and she was taking Maxide, a diuretic medication. Routine laboratory testing was performed and the patient's sodium level was reported as 100 meq/L. After consultation with a nephrologist, hypertonic saline was started.
  • By 10:20 that morning, the patient’s sodium had risen to 107 meq/L.
  • At 11:40 AM, repeat labs were drawn. Results reported at 12:20 PM showed that the sodium level had risen to 114. An order was given at 12:40 PM to discontinue the hypertonic saline infusion. The order was not carried out until 1:40 PM.
  • By 3:00 PM, the patient's sodium level was 120 meq/L.
  • Subsequently, during the patient's hospitalization, she developed symptoms consistent with central pontine myelinolysis.

In the ensuing lawsuit, the plaintiff expert witness made several assertions which included the following

  1. Sodium repletion therapy is “straightforward” and the expert was “not aware of any controversy” in managing hyponatremia (Trial transcript, p. 44)
  2. The patient had chronic hyponatremia, not acute hyponatremia and the low sodium levels were corrected too rapidly
  3. Despite the presence of a continued alteration in the patient’s mental status, the 3% sodium infusion should have been stopped when the serum sodium reached 107 and the nephrologist should have been reconsulted at that time. (Trial, p.14; Depo, p. 32)
  4. The expert disregards standard references (e.g. Rosen), which in this situation recommends raising serum sodium by 10 mEq/L or to a level of 120-125 with hypertonic saline.
  5. The patient was suffering from mild, not severe neurological symptoms, but could not provide a reasonable definition of the term “severe,” stating that “my use of the word ‘severe’ is not the same as the word ‘severe’ in the Rosen text.” (Trial, p. 63)
  6. Orders in the emergency department must be carried out within 10 minutes (increased to 15 minutes at trial), and if the nurse cannot carry out an order within that time frame, the physician must carry out the order him/herself. (Deposition, p.39; trial p. 50)
  7. During the trial, the expert opined that the defendant physician fell below the standard of care by administering too much sodium, but was unable to calculate the amount of sodium that should have been given to the patient.
  8. The expert changed his testimony between his deposition and the trial. During his deposition, he stated that he did not base his opinions on any authoritative sources. During trial, the expert referenced multiple articles and formulas to substantiate his opinions. (Depo, p.13; Trial. p.72)
  9. Rapid sodium repletion should be performed under the supervision of a nephrologist. (Depo p. 33).

After reviewing the expert’s testimony and the available literature in this case, the Standard of Care Panel came to the following conclusions. 

  1. This case was highly complex in that the patient had multiple neurologic and gastrointestinal symptoms in addition to a critically low sodium level.
  2. Given the short onset of the patient’s symptoms, the Standard of Care Panel believed that she was most likely suffering from acute or subacute hyponatremia, although there was even disagreement among panel members regarding whether the patient’s hyponatremia may have been chronic.
  3. Multiple literature sources state that there is significant controversy in the management of hyponatremia. The Standard of Care Panel believed that the expert’s statements to the contrary were misleading.
  4. Expert consensus dictates that the rate of sodium correction should be directed by the severity and the duration of the patient’s symptoms.
  5. Aggressive treatment was warranted in this case since the patient was suffering from severe neurological findings including motor weakness, inability to stand, confusion, slurred speech, inability to move mouth, multiple episodes of falling, disorientation, and possible seizures.
  6. Because the patient’s symptoms had not improved when the patient’s sodium level had reached 107, the Standard of Care Review Panel believed that it was appropriate to continue the hypertonic saline solution at that point.
  7. The Standard of Care Review Panel found no justification for the expert’s assertion that rapid sodium repletion should be performed under the supervision of a nephrologist.
  8. During her emergency department course, the patient's sodium increased from 107 to 114 in one hour and 20 minutes, amounting to an increase of 5.25 meq/L/hour and also increased from 107 to 120 in 5 hours and 40 minutes, amounting to an increase of 2.3 meq/L/hour. The Standard of Care Panel was unable to find any published guidelines that recommend replacing sodium at a rate faster than 2 meq/L/hour.
  9. While orders in the emergency department ideally should be carried out as soon as possible, the Standard of Care Panel disagreed that there is a standard requiring that every STAT order be carried out within 10 minutes.

Marx: Rosen's Emergency Medicine: Concepts and Clinical Practice, 6th ed. 2006 Mosby, Inc.

Lien Y, Shapiro J. Hyponatremia: clinical diagnosis and management. Am J Med. 2007;120(8):653-8.

Verbalis JG, Goldsmoth SR, Greenberg A, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 Suppl 1):S1-21.

Androgue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000; 342(21):1581-9.

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