SEVERE CHRONIC HYPONATREMIA: A Pathophysiological Rumination (Part 1)

INTRODUCTION:

Severe chronic hyponatremia (<120 mEq/L) remains the #1 reason nephrologists lose sleep on call nights and rightly so.  The fear of overcorrection and the risk of central pontine myelinolysis (CPM) or osmotic demyelination syndrome (ODS), however uncommon they actually might be, has been drilled into our brains since the beginning of medical school.

In this post and the few that follow, I will attempt to address some aspects of chronic severe hyponatremia which have traditionally not been included when hyponatremia is taught or written about or have only recently been backed by some evidence and have not yet made their way into the textbooks. The recently released guidelines also did not address some of these issues. While this is not, by any means, an exhaustive discussion of the topic, I hope that these posts will not only help the readers enhance their understanding of the pathophysiology of severe hyponatremia but also help them manage it more effectively with a lot less stress and mental anguish.

PART 1: THINK OUTSIDE THE ALGORITHM

The Schrier-Berl algorithm for diagnosis of hyponatremia has been used successfully for decades for teaching, and for reasoning through the differential diagnosis at the bedside.  It is an integral part of every medicine textbook and pocket handbook. It takes us to our diagnosis through 3 decision points: Plasma osmolarity, volume status and urine sodium sequentially.  While the algorithm holds true for the garden variety mild to moderate hyponatremia, it almost invariably breaks down in case with very severe hyponatremia.

During our extensive review of cases of severe hyponatremia treated with 3% saline, we seldom came across a case in which there was only one isolated cause for hyponatremia.  Rather, they were almost always two or more possible etiologies.  In addition, many patients that were initially considered to be euvolemic by experienced nephrologists, responded to 3% saline as if they were volume depleted.  Lastly, the clinical course of these patients during the hospitalization seemed to suggest many of these causes of inappropriate release of ADH were transient and reversible (SSRIs, acute nausea, postop state etc.). The patients' physiology seemed to change from time to time, with overcorrection of sodium invariably accompanied by large-volume water diuresis as these transient sources of ADH were "switched off."

It was, however, the paper by Sood et al that finally looked at the possible different etiologies for cases of severe hyponatremia as shown in the table (see image), which I consider the single most important table in all of recent hyponatremia literature.  They showed for the first time for multiple etiologies and processes are at play, some fixed and some transient in generating severe hyponatremia.

It is of paramount importance, that in the workup of hyponatremia, especially severe cases, we do not limit our reasoning through the differential diagnosis to comply with the algorithm that we have so familiar with but constantly look for multiple etiologies and transient causes of SIADH, especially subclinical volume depletion (low urinary sodium can be helpful here), as often it is the resolution of these causes that leads to the large-volume water diuresis and overcorrection. 

Posted by Hashim Mohmand