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Richard H. Sterns

Dr. Sterns is a Professor Emeritus of Medicine at the University of Rochester School of Medicine and Dentistry. He is the author of several papers and book chapters on disorders of water balance and is the section editor for fluids and electrolytes for UpToDate.

Competitors for the Hyponatremia Correction Region

Team 1: Rapid Correction vs Team 2: Slow Correction

Image generated by Evan Zeitler using Image Creator from Microsoft Designer, accessed via https://www.bing.com/images/create, January, 2024. After using the tool to generate the image, Zeitler and the NephMadness Executive Team reviewed and take full responsibility for the final graphic image.

Let’s say you wanted to do a study to see if motorcycle helmets prevent brain damage.  You put helmets on everyone in your city for a whole year – men, women, and children, pedestrians, bicycle riders, Sunday drivers, as well as motorcycle enthusiasts.  After a year, you tabulate the results.  Brain damage is rare and when it occurs, it usually has nothing to do with head trauma (Helmets don’t prevent strokes or brain tumors). You conclude: motorcycle helmets are unnecessary.

Ridiculous right?  Take a look at the “disrupter papers” and the blogs praising them. If you want to know if osmotic demyelination syndrome (ODS) is prevented by limiting the rate of correction of hyponatremia, you should study a population likely to be affected by the disorder, look for the right disorder, and do a good job of finding patients who develop it.

Sweden has a nation-wide electronic health record that lends itself to population studies.  A survey of that country’s health system provides a good road map to investigators interested in valid answers. The study showed that 86.7% of patients with an MRI diagnosis of central pontine myelinolysis (CPM) had been hyponatremic. Among them, the median serum sodium concentration was 104 mEq/L and 75% of patients had a serum sodium ≤110 mEq/L. Clearly, if you want to find enough cases of ODS to determine how best to avoid it, you need to study patients with very low serum sodium concentrations.  The Swedish study found that in the vast majority of cases, hyponatremia was corrected at rates now considered excessive.  The median rate was 0.7 mEq/L/hr and 90% of affected patients were corrected by >8 mEq/L in 24 hours – a rate accepted in Sweden as the appropriate limit.  As only 1.3% of patients were treated with hypertonic saline, excessive correction was almost always due to excretion of dilute urine once the cause of hyponatremia was eliminated.

The Swedish study was limited to MRI-documented cases.  In patients who develop pontine and/or extrapontine myelinolysis after correction of hyponatremia, images are usually negative at the onset of neurological symptoms and patients with “milder” but distressing injury may never develop a positive MRI.  Call me fussy, but if I or a family member went into a prolonged, catatonic stupor three days after rapid correction of mildly symptomatic but biochemically severe hyponatremia, I would NOT be reassured to know that the MRI remained negative. Nor would I dismiss the complication as trivial because it seemed to resolve.  That’s one of the reasons why the term “osmotic demyelination syndrome” was introduced in 1986 and why most authors recommend correction limits considerably slower than rates likely to result in severe, permanent brain damage. 

The question for a nephrologist should NOT be, “What is the cause of central pontine myelinolysis (CPM)?”  Rather, it should be, “What is the best way to avoid neurological complications when we treat severe hyponatremia?”  Rapid correction of hyponatremia is a cause of CPM, not the cause, and ODS should not be equated with CPM. The syndrome is characterized by a gradual onset of symptoms that can include paralysis, swallowing dysfunction and dysarthria, seizures, movement and behavioral disorders beginning a few days and NOT (as asserted by a NephMadness blogger) “weeks or months” after sodium correction; if the MRI becomes positive a week or two later, lesions are NOT limited to the central pons.

For those arguing that ODS is rare, I would ask, “What is the evidence that patients with acute hyponatremia can develop life-threatening cerebral edema requiring urgent treatment with hypertonic saline?”  You won’t find it in the second “disrupter” paper’s finding that slower correction is associated with higher mortality rates. Rapid correction is far more dependent on the patient’s ability to excrete dilute urine than on the caregiver’s efforts to raise the serum sodium; most hyponatremic patients dying of advanced heart failure, cirrhosis, metastatic cancer and multi-organ failure cannot dilute their urine.  In this 20-year study that included 3274 patients, only 12% of whom were given hypertonic saline, one patient died of documented cerebral edema — a marathon runner. Does that mean we should abandon treating symptomatic acute hyponatremia with hypertonic saline because cerebral edema documented by imaging is incredibly rare? Of course not.  We do not treat acutely hyponatremic patients aggressively because they WILL die of cerebral edema but because they CAN die from it.  We should apply the same standard to our efforts to avoid osmotic demyelination in patients with chronic hyponatremia.

Copyright: DarSzach/Shutterstock

– Guest Post written by Richard H. Sterns

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

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