Prepared by Praveen Kandula, MD, MPH, Assistant Professor of Clinical Medicine, Southern Illinois University School of Medicine, Springfield, IL
Hospitalized patients are often found to have electrolyte abnormalities, of which sodium imbalances are the most common.1 Too much sodium in the blood is referred to as hypernatremia (>145 mEq/L), whereas too little sodium in the blood is called hyponatremia (<135 mEq/L); a sodium plasma concentration between 135 and 145 mEq/L is considered normal. Hyponatremia is more common than hypernatremia. Depending on the setting, hyponatremia is observed in 1% to 42% of hospitalized patients.2 It is essential that physicians know how to manage sodium irregularities because these conditions are associated with significant morbidity and mortality.3-6 This article answers 10 questions about commonly encountered clinical situations.
Why is normal saline called isotonic when it has 154 mEq/L of sodium, which is more than normal serum sodium plasma levels of 135 to 145 mEq/L?
Blood plasma comprises 90% water and 10% cellular material. Normal sodium plasma levels average 140 mEq/L, which is the amount of sodium found in the liquid portion of plasma. To get a true concentration of sodium in a crystalloid solution, the 10% cellular component needs to be accounted for. This means that the normal sodium level of 140 mEq/L must be increased by 10%, or 14 mEq, for a total of 154 mEq/L, which is the level of sodium found in normal saline solution.
Should normal saline be used to treat hyponatremia in patients with SIADH?
The impact of intravenous fluids in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) depends on the patient's urine osmolarity. Typically, normal saline's osmolarity of 328 mOsm/L exceeds what is found in a serum sample from a SIADH patient; however, high antidiuretic hormone (ADH) levels raise urine osmolarity in these patients. If the osmolarity level exceeds 328 mOsm/L, the kidneys excrete enough sodium in less than 1 L of urine to equal the amount contained in an entire bag of normal saline. The rest of the "free water" in the normal saline solution is reabsorbed via the ADH, which can decrease the sodium plasma concentration in a SIADH patient. Generally, normal saline should not be used to correct SIADH if the patient's urine osmolarity exceeds 500 mOsm/L.7
Does hypokalemia influence the treatment of hyponatremia?
Yes, hypokalemia needs to be corrected for hyponatremia to be corrected. Sodium (Na+) is the predominant extracellular electrolyte, and potassium (K+) is the predominant intracellular electrolyte. Their concentrations are regulated by constant exchange using sodium potassium adenosine triphosphatase (ATPase) and reflect the relative proportions of solute and water and not the absolute amount of either solute or water. Plasma sodium concentrations are represented by the following equations8,9:
As these equations demonstrate, plasma sodium levels cannot improve unless the level of plasma potassium is corrected.
Is a 4.0-gram salt diet the same as a 4.0-gram sodium diet?
No, and the answer is clear when one considers basic chemistry. The atomic weights of sodium (Na+) and chloride (Cl- ) are different, at 23.0 grams and 35.5 grams, respectively. Because 1.0 gram of salt (NaCl) comprises 1.0 gram of Na+ and 1.0 gram of Cl-, the atomic weight of salt is 58.5 grams (23.0 grams + 35.5 grams). As shown by this equation, there is 1.0 gram of Na+ in 2.5 grams of salt (58.5/23.0); hence, a 4.0-gram salt and a 4.0-gram sodium diet, both of which are commonly prescribed in the hospital, are not equal!
How many grams of sodium are found in 1 L of normal saline solution?
As mentioned in the answer to question 4, the atomic weight of sodium is 23.0 grams; thus, 1 mole of sodium has 23.0 grams of sodium and 1 mmol has 0.023 grams. As explained in the answer to question 1, normal saline solution has 154 mEq/L of sodium. Because 1 mEq equals 1 mmol of sodium (valency of 1), there are 154 x 0.023 grams ≈ 3.5 grams of sodium in 1 L of normal saline solution. It is important that clinicians know this, because many patients are kept on "maintenance fluids," which can add up to a lot of sodium when paired with the patient's normal diet.
Does normal saline solution have the same sodium content as Ringer?s lactate?
Normal saline solution has 154 mEq/L of sodium, and Ringer's lactate has 130 mEq/L of sodium. While the latter solution is used more commonly in surgical patients, the two fluids are nonetheless interchangeable for most purposes. It is important to remember that Ringer's lactate contains an additional 4 mEq/L of potassium and 28 mEq/L of lactate. Lactate is converted to bicarbonate in the liver and primarily helps in combating acidosis.
How can one be sure that a cirrhotic patient?s diet is truly salt-restricted?
Salt restriction and diuretics are used to treat patients who have cirrhosis and ascites. Short of actually monitoring patients all day and calculating the salt content in all food and beverages consumed, the best alternative is to monitor their urine sodium levels. As mentioned in the answer to question 5, 1 mmol (or 1 mEq) of sodium equals 0.023 grams of sodium. Thus, if a patient is in homeostasis, total intake should equal total output; if 2.0 grams of sodium are consumed, then 2.0 grams must be excreted. Per the previous calculations, this should equal 88 mEq. It is generally thought that 10 mEq of sodium is lost through nonurinary sources, such as sweating, breathing, and the gut. The goal is to have patients excrete more than 78 mEq of sodium daily so that there is net sodium loss and resultant weight loss. Therefore, if a patient's total sodium excretion exceeds 78 mEq daily yet the person is gaining weight, a 2.0-gram sodium-restricted diet is not being followed.10
How can one accurately estimate FENa in a patient on furosemide (Lasix)?
Fractional excretion of sodium (FENa) is commonly used to determine whether the etiology of a case of acute renal insufficiency is prerenal or intrinsic; however, this calculation can have limited usefulness in patients who are on diuretics because these drugs interfere with sodium reabsorption. Several alternative calculations can be used, including calculating the fractional excretion of urea, uric acid, or lithium. All follow the same principle, which is that patient's in prerenal states demonstrate avid salt and water reabsorption at the proximal tubule. Lithium, urea, and uric acid are also absorbed in the proximal tubule, but these are not affected by furosemide. The equivalents of FENa levels below 1% for lithium, uric acid, and urea are values lower than 15%, 12%, and 35%, respectively. Similarly, the equivalent of FENa levels above 1% for lithium, uric acid, and urea are values higher than 25%, 20%, and 35%, respectively. The fractional excretion of urea is thought to be the most sensitive and specific calculation in patients receiving diuretics.11,12
When do we use normal saline to treat hypernatremia?
Hypernatremia frequently develops in hospitalized patients, and almost all cases are attributable to the loss or lack of free water. Iatrogenic salt excess due to intravenous fluids is commonly overlooked. When treating hypernatremia, hypotonic fluids like dextrose 5.0% in water (D5W), 0.2% normal saline, or 0.45% normal saline, are preferred unless the patient is hemodynamically unstable secondary to true volume depletion. If possible, oral supplementation or tube feeding of free water is preferable.13
How effective are newer medications at treating SIADH?
Traditional management of euvolemic hyponatremia has included restricting free water intake and correcting the underlying cause of the condition. Newer medications that aid in aquaresis (loss of free water only, without affecting urinary sodium or potassium excretion) are now available. These new drugs are called vaptans, and only the intravenous form, conivaptan (Vaprisol), is available in the United States; however, oral formulations have been developed and are being used in other countries. Although vaptans have been found to be effective,14 further large-scale studies are needed. When administering vaptans, clinicians must closely monitor the rate at which their patient's sodium level rises so that inadvertent rapid correction can be avoided.