PART 3: THE DANGERS OF "DEPLETION"
In my previous post concerning chronic severe hyponatremia, I explained how over corrections of serum sodium of large magnitude required a dilute large volume diuresis, often precipitated by resolution of a transient source of ADH secretion. In this post I will discuss two phenomena which are particularly dangerous as they carry significant risk of producing large volume water diuresis.
1. Subclinical Volume Depletion: As mentioned in my previous post, we noticed during our review of a large number of cases of severe hyponatremia treated with 3% saline that most of the patients whose serum sodium eventually overcorrected responded to small volumes of 3% saline as if they were volume depleted, with sudden emergence of water diuresis. Interestingly, most of these patients were initially considered to be euvolemic by experienced nephrologists.
This very interesting paper reviewed the literature concerning the value of physical examination in diagnosing volume depletion. The conclusion, rather humbling, was that other than in cases of severe volume depletion our physical exam was quite inaccurate in diagnosing volume depletion. This is especially concerning considering that establishing a patient's volume status forms the major decision point in the ubiquitous diagnostic algorithm for hyponatremia.
According to the paper, reliable signs of volume depletion usually are visible with the loss of about 20% of the intravascular volume. The ADH secretion and response to volume depletion starts with volume losses as low as 5-8% of the effective intravascular volume. This implies that the patient may have significant ADH secretion, contributing to the relative excess water retention causing hyponatremia, while clinically appearing euvolemic. It also means small volume bolus may switch off this ADH secretion, causing water diuresis and sudden rise in serum sodium.
Subclinical volume depletion as a contributor to hyponatremia should always be considered a possibility especially when starting therapy with 3% saline.
2. Solute Depletion Hyponatremia: The so called "Tea and Toast Diet " hyponatremia and "Beer Potomania" are examples of solute depletion hyponatremia. As nicely described by Dr. Berl, our solute intake limits our ability to excrete free water. Even with a maximally dilute urine of around 50 mOsm/L, a person consuming a 300 mOsm/d diet can only excrete 6 L of urine (300/50=6). Such a person will become hyponatremic with drinking more than 6 L of fluids a day because any water in excess of 6 L per day excretory capacity will be retained in the body. It is important to note that this water retention is not due to ADH secretion. ADH is often suppressed in such patients. The renal danger of this pathophysiological mechanism is that whenever such patient is "presented" with solute (IV normal saline, high-protein meal which would generate BUN or even 3% saline!), without a high ADH level to prevent it, the added solute is used to rapidly excrete free water that has been "trapped" in the body.
As an example, consider the case of the 26-year-old female that I briefly alluded to in the previous post. She presented with a serum sodium of 108 mEq/L after being on an exclusively alcohol diet for the last 2 weeks. She received 2 L of normal saline in the ER (154 mEq x2 = 308 mEq of Na). Using the Edelman equation (see figure) and an initial total body water of 32 L, if we do not account for urine output, that amount of added NaCl would have raised the serum sodium to about 111 mEq/L. But the actual rise of serum sodium was to 131 mEq/L in about 5 hours accompanied by almost 7 liters of dilute urine output. Her kidneys used the roughly 300 mEq of sodium in the NS bolus to excrete more than 6 liters of maximally dilute urine (300/50=6 L, remember the earlier calculation?) and almost perfectly accounts for the 23 mEq/L rise in serum sodium (by reducing the denominator, TBW).
This would have also happened if she had received the same amount of NaCl in the form of 3% saline as in such cases the volume of infusate matters less than the amount of solute delivered.
I hope this case illustrates how dangerous solute depletion hyponatremia can be and how easy it can be to precipitate an overcorrection of serum sodium in such patients. This raises a very important question: if even treatment with 3% saline is so unreliable in patients with chronic severe solute depletion hyponatremia, how can we safely treat such patients? That will be the subject of my next post.
In conclusion, subclinical volume depletion and solute depletion pose a particularly tricky challenge in the management of chronic hyponatremia as sudden rises in serum sodium level can happen rather easily in these patients with, what would otherwise seem to be, rather innocuous treatment with saline solutions.