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Harish Seethapathy @BetterCallSeeth

Dr. Harish Seethapathy is a Clinician-Educator in the Division of Nephrology at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School in Boston, MA. His clinical interests lie in glomerular disease, onconephrology and hyponatremia. He is one of the Program Directors for the GlomCon Fellowship, was co-chair of the Education Committee for the American Society of Onconephrology (2022 & 2023), and serves as the Director of Education for the BWH/MGH Nephrology Fellowship Program.

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.

As nephrologists, we have an inherent passion for delving into intricate discussions and spirited debates. Our ardor for argumentation extends beyond a mere pastime; it constitutes a dynamic pursuit that pushes the boundaries of knowledge and elevates the bar for patient care. A standout contender in our roster of memorable kidney debates is perhaps the enduring question that has sparked impassioned discourses for the last 50 years: “What is the optimal correction rate for patients with severe hyponatremia?”

However, as in many long running debates, we often get lost in the weeds and forget both where the question began and the outcome that we have been trying so hard to prevent. The first time the question was asked, it was simple: “What is the cause of central pontine myelinolysis (CPM)?” The answer: A rapidly evolving paralytic disease with striking pseudobulbar symptoms manifested by dysarthria and dysphagia, accompanied by (here is the key) pathology or imaging findings. In one of the first large series of autopsy proven CPM cases, the authors noted severe hyponatremia (Na<120 mEq/L) in only one-fourth of the cases, with sodium values ranging between 96 and 202! Half of the patients were noted to have alcoholism as the main risk factor. Of course as nephrologists, other than when we occasionally veer into uncharted territories (like offering unexpected commentary on anemia for a bit of excitement) we tend to focus on kidney related matters. With the kidney kingdom as our well-charted domain, why explore other medical realms?

Over the next three decades, armed with sparse data, we decided to shift the spotlight and turn a disease with multiple risk factors into a sodium-centric phenomenon, because in our nephrology world sodium takes center stage, and we’re determined to make it the star of the show. We even went the extra mile, removed the imaging/autopsy criteria, rebranded it and gave it a new name (circa 1986): “osmotic demyelination syndrome (ODS)”. But why did we have to stick to this route? Initial studies between 1986 and 1995 (the largest with 255 patients) suggested that the incidence of ODS with rapid correction was extremely high (11%-23%). It was also suggested that ODS is associated with high mortality, that imaging findings of the disease can appear weeks to months later (or never, hence making it a clinical diagnosis), and crucially, that it was entirely preventable by correcting the sodium slowly. The 24 hour correction rate became our obsession; animal studies showed that 15-20 was too fast, so we went <15..then emerged reports of ODS with correction rates of 12-15, so <12 became the norm… then cases of ODS with 10… you get the gist. Most recent guidelines recommend a 24-hour correction rate of 4-6 mEq/L in high risk patients to prevent a syndrome that may occur days/weeks or months after a single episode of rapid sodium correction, with or without accompanying imaging findings. That’s like predicting next day snowfall in my beloved Boston; anywhere from 1-20 inches of snow, starting between 6 AM and 6 PM, lasting for a while, maybe not, sometimes rain, sometimes never!

Recent literature backed by data from thousands of patients is informing us that:

• Despite our best efforts, rapid correction (>10 mEq/L/24 hours) is extremely common, occurring in one-third of patients with severe hyponatremia.
• Clinically diagnosed ODS or Imaging related CPM is extremely rare (<0.1%), can occur with slow or rapid correction, and is often accompanied by other notable risk factors such as alcohol use, malnutrition, hypophosphatemia and hypokalemia.
• Slow correction may have negative downstream consequences such as increased length of hospital stays.
• The long-term neurological prognosis for most patients with CPM is excellent &
• Surprisingly, the majority of imaging proven CPM occurs in patients without hyponatremia.

So where do we go from here? A clinical trial on correction rates will never be approved. But even if it were, what would be the studied outcome? After extensive debate, it’s doubtful we truly grasp what we are trying to prevent.

Is ODS always a devastating disease? What is the timeline between rapid sodium correction and neurological findings (clinical or imaging)? Can neurological findings in a high-risk patient population (eg. alcoholism), be labeled ODS without CPM on imaging?

Is this intense focus on sodium correction justified? Is it even preventable in high-risk patients, if CPM can occur in these patients even with very low correction rates and even normal sodium levels?

Proponents of slow correction who are skeptical of new data should realize that the evidence backing current guidelines is as sturdy as a paper umbrella in a hurricane. The premise that rapid correction causes ODS is as flimsy as the belief that slow correction is its foolproof prevention. CPM is a complex disease and the degree of osmotic change required to cause it remains unclear.

You should back Team Rapid Correction not because you believe that is the answer to the correction question but because you champion questioning the status quo when compelling data is presented, you are able to critically think through new data, and are unafraid to ask the important challenging non-simplistic questions. And you are ready to embrace your identity as the nerdy, curious & debate loving water balance expert.

Copyright: fuyu liu/Shutterstock

– Guest Post written by Harish Seethapathy @BetterCallSeeth

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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