CASE Confused and weak
Mr. W, age 26, is brought to the emergency department (ED) by his parents for intermittent confusion, weakness, and increasing lethargy over the past 4 days. He is jaundiced with mild abdominal pain, nausea, and vomiting.
Mr. W has a history of alcohol use disorder, drinking as much as 1 L of vodka a day. Six months ago, he was hospitalized for alcoholic hepatitis and severe hyponatremia.
In the ED, Mr. W is awake, alert, and oriented to person, place, and time. Vital signs are: pulse 89 beats per minute; blood pressure, 117/50 mm Hg; respirations, 15 breaths per minute; and temperature, 98.5ºF. Physical examination is notable for scleral icterus, jaundice, tender hepatomegaly, and asterixis.
Mr. W is not taking any medications. He reports that his most recent drink was the day before; however, his current alcohol intake is unknown.
Laboratory tests reveal altered hepatic function, including elevated aspartate aminotransferase (251 U/L), alanine aminotransferase (56 U/L), alkaline phosphatase (179 U/L), total bilirubin (15.4 mg/dL), and ammonia (143 U/L), impaired coagulation (international normalized ratio 2.39), and decreased albumin (2.7 g/dL). Other metabolic disturbances include: sodium, 104 mEq/L; chloride, <60 mEq/L; potassium, 2.2 mEq/L; and CO2, 44.5 mEq/L.
What is your differential diagnosis for Mr. W’s altered mental status?
a) hepatic encephalopathy
b) Wernicke’s encephalopathy
c) hyponatremia
d) drug intoxication
e) head trauma
The authors’ observations
Hyponatremia is defined as a serum sodium concentration <136 mEq/L. Mr. W is considered to have severe hyponatremia because his serum sodium concentration is <125 mEq/L. Although commonly caused by an inability to suppress antidiuretic hormone, hyponatremia has several possible causes (Figure 1).1 Symptoms are nonspecific and are more visible when there is a large or rapid decrease in the serum sodium concentration. Most patients with a serum sodium concentration >125 mEq/L are asymptomatic. Mr. W, who had a serum sodium of 104 mEq/L, presented with several symptoms, including confusion, lethargy, nausea, vomiting, and weakness. Headache, muscle spasms, depressed reflexes, restlessness, and disorientation also might be observed.2
Because of Mr. W’s impaired hepatic function, elevated ammonia, and asterixis, hepatic encephalopathy could be contributing to his altered mental status. Suspect Wernicke’s encephalopathy in a patient with neurologic symptoms and a history of chronic alcohol abuse. In its classic form, Wernicke’s encephalopathy has acute onset, characterized by the triad of ataxia, global confusion, and ocular abnormalities. However, this triad is not consistently or frequently encountered.3
Which tests would you order next?
a) blood ethanol level
b) urine drug screen
c) serum osmolality
d) CT of the head
EVALUATION Sober, yet sick
To rule out intoxication as the cause of Mr. W’s altered mental status, blood ethanol level and urine drug screens are obtained and found to be negative. CT of the head is negative for acute intracranial pathology.
Mr. W is admitted to the medical intensive care unit (MICU) for severe hyponatremia and altered mental status. Serum osmolality is 220 mOsm/kg (normal range 281 to 304 mOsm/kg). To further classify his hypotonic hyponatremia, volume status is assessed, and Mr. W is determined to be euvolemic. Thyroid-stimulating hormone and cortisol are within normal limits, eliminating hypothyroidism and adrenal insufficiency as causes of his euvolemic hypotonic hyponatremia. Mr. W is treated for hyponatremia likely secondary to syndrome of inappropriate antidiuretic hormone (SIADH). SIADH is a diagnosis of exclusion that first requires ruling out hypothyroidism and glucocorticoid insufficiency (Figure 1).1
The authors’ observations
Because hypokalemia is an independent predictive factor for development of hyponatremia, it is necessary to evaluate the potassium level in all hyponatremic patients. Mr. W’s potassium level was 2.2 mEq/L on admission. Serum sodium concentration is related to total exchangeable sodium, total body water, and total exchangeable potassium. Potassium depletion causes a shift of sodium into cells with a comparable exit of potassium from cells into extracellular fluid. The reverse process occurs during potassium repletion, leading to an increase in serum sodium concentration and making hypokalemia a risk factor for developing osmotic demyelination syndrome (ODS).4
Treating hyponatremia
Hyponatremia treatment depends on its severity, presence or absence of symptoms, and whether the hyponatremia is acute (<24 hours) or chronic (>48 hours).5
Because of Mr. W’s extremely low serum sodium concentration, predisposition to hyponatremia secondary to alcoholism, and history of severe hyponatremia, it is likely he is chronically hyponatremic.
In patients with chronic hyponatremia, neurological sequelae are associated with the need for a more rapid rate of correction of serum sodium. For most patients with chronic hyponatremia, a correction rate of ≤10 to 12 mEq/L during the first 24 hours and <18 mEq/L over 48 hours is recommended to avoid ODS.6