Tag: hyponatremia

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Fellow-Level Lecture on Hyponatremia

Today I did a noon conference on sodium for the neph fellows. Instead of a comprehensive sodium lecture I focused on a number of different elements and interesting aspects of hyponatremia. Mostly a deeper dive into aspects that you don’t have time to cover in standard sodium lecture.

I opened with 17 quick slides on free water clearance. These slides are old and I think I could do better. Definitely due for an update.

Download the slides here.

Then I used a slide deck which covers:

  • mannitol as a cause of an osmolar gap and pseudohyponatremia
  • glycine induced pseudohyponatremia
  • a bit of data on rapid correction of sodium by hemodialysis
  • exercise induced hyponatremia
  • use of FeNa and FeUrea and FeUric acid to distinguish between salt depletion and SIADH
download the slides here
It was a fun lecture and everyone participated in a casual and interactive freewheeling learning session. Great stuff.
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Renal week day 4: The case for DDAVP in severe hyponatremia

Today I went to see Richard Stern talk about Therapeutic Considerations in the Hyponatremic Patient. It was an excellent talk. One of the concepts he introduced, at least to me, was the use of DDAVP in the patient with severe hyponatremia.

His argument was that the biggest threat to to these patients is the overly rapid correction of sodium due to the sudden suppression of endogenous ADH in the middle of therapy. This is exactly what I was worried about when I was treating that severe case of hyponatremia a couple of weeks ago. My solution up to now is to write an order for the nurse to call me if the patient’s urine output rises over 100 mL an hour. Unfortunately this is an unusual call order and nurse compliance with it is questionable.

He proposes using DDAVP to essentially lock, or hold constant urinary losses. Then you use 3% saline and the increases in plasma sodium should be more predictable.

This maneuver has a high degree of difficulty but I think it solves an important problem. I’m going to try this on my next case of extreme hyponatremia.

Has anyone else used this technique?

– Posted using BlogPress from my iPad

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Lowest sodium I have ever seen

I’m not sure if it is really the lowest sodium but it definately was among the lowest.

I received a call regarding a consult for a patient with a sodium of 105.

The patient is a 60 year old caucasian woman who had been started on chlorthalidone 3 days prior to admission. Her physician had been wrestling with hypertension and changed her from 25 mg of hydrochorothiazide to 50 mg of chlorthalidone. (The internist was keeping up with her American Journal of Hypertension. Though 50 mg is a whole lotta chlorthalidone.)

Both figures are from Ernst Et al. Hypertension 2006

After one or two days of the new diuretic the patient started vomiting and developed diarrhea. The only thing she was able to keep down was water. When she came to the ER she hadn’t eaten anything solid for two days.

She was admitted with hypovolemic hyponatremia. She was given a bolus of 500 mL of normal saline in the ER and the sodium went up to 108. Additionally her potassium was 2.7 and her magnesium and phosphorous were low. She was started on potassium chloride and sodium phosphate prior to being transferred to the ICU. When I called the nurse I was told the intensivist  planned on starting her on 3% saline.
I was immediately worried about overcorrecting her sodium and developing osmotic demyelination syndrome from 3% saline and aggressive correction of her potassium. Tom Berl had come and spoken to our fellow and had put the fear of potassium in me by discussing a case that was triggered by potassium repletion. From the case report:

This patient was at risk of overcorrection because she had two of the most common clinical settings in which such overcorrection occurs: thiazide use and hypovolemia.

Patients with hypovolemic hyponatremia send conflicting signals to the hypothalamus regarding ADH release. The volume deficiency stimulates ADH (if the body volume deficient, let’s not lose any water via the kidneys) and low osmolality surpresses ADH (the body is too diluted so let’s lose some water to bring the concentration up). In the case of this conflict, volume rules. As I tell my medical students,

Remember the ABC’s, Airway, breathing and circulation. O for osmoregulation is way down in the alphabet.

The problem of rapid correction occurs when you correct the volume deficiency and all of the sudden the hypothalamus asks itself, why am I releasing any ADH with an osmolality of 260?

Then the kidney starts producing urine that you could probably bottle and sell as organically filtered water. Electrolyte free water clearance begins to approach the urine output and the sodium also starts to climb and climb fast.

To protect this patient I told the nurse to decrease the normal saline to 100 mL per hour and to call me if the urine output goes over 200 per hour. We also started checking the sodium every six hours and I ordered urine osmolality, sodium and potassium.

Her sodium started to rise slowly, the urine output increased but never resembled Niagra. After two days her sodium was in the 120s her urine still appeared volume depleted and volume status began to look wet. She developed wheezes and she had a few rales. We had to abandon the normal saline. We started tolvaptan. She received 30 mg once and then 15 mg the next day after she had a brisk response. After that her urine electrolytes resembled SIADH.

Once the sodium crossed 130 I stopped the tolvaptan, restricted her free water, and added a gram of sodium chloride twice a day. Her sodium stabilized around 130.

Around this time I sent a renin aldo ratio. I usually order these before I start a patient on aldactone, because after you start it you need to wash them out for weeks prior to checking for primary hyperaldosteronism. Our patient had difficult to treat hypertension and hypokalemia on admission, so I checked it. I just found out that it came back positive. The high aldosterone was after we had corrected her volume deficiency. I think it is primary, and this may explain why she had persistently low urine sodiums despite successful volume resuscitation.

We looked for a cause of the SIADH, but couldn’t find anything. No narcotics, no pulmonary disease, no malignancy, normal TSH and cortisol, no anti-depressants. She had a normal non-contrast head CT scan on admission. I even ordered a contrasted CT scan of the chest to make sure she didn’t have a cancer in there. Nothing. Idiopathic SIADH hiding behind, at least initially, volume depletion and in the background of primary hyperaldosteronism. Strange case.

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Pharma and Medical Education

Jose Arruda, Chief of Nephrology, UIC Medical Center
I was excited to see Dr. Arruda on the schedule to speak at our fellowship. This is one of the best aspects of being an academic nephrologist; we get prominent nephrologists from around the country to speak to our department.
When I saw the title of his lecture was A New Approach to Hyponatremia, I knew we were going to get the vaptan story (PDF).

Otsuka is pushing tolvaptan (Scamsca™) hard. We are getting detailed a lot, and I hear that the cardiologists are also getting an earful. Honestly, the data looks a little thin to me. The drug is the most reliable method for tackling persistent SIADH. But that’s rare. In my experience, usual care fixes almost every case of hyponatremia within a day or two. There are a minority of cases that don’t respond quickly. These episodes of persistent hyponatremia worry me. Unfortunately, tolvaptan doesn’t feel like a good option for these patients. We know from the SALT studies that a week after you stop the drug the sodium equals the control group and the drug costs $300 per day (average wholesale price (PDF), retail price). I find it hard to prescribe a $9,000 per month drug for chronic therapy. I’ll stick with salt tablets, furosemide and water restriction.

Arruda’s lecture was on tolvaptan and the first slide was giving some background on hyponatremia and he commented that “I hate this slide.” I can’t imagine putting together a presentation and flying 500 miles to present it and loathing the very first slide.
It is illustrative of what is wrong with academic nephrology. Dr. Arruda hates the first slide in his deck. Why doesn’t he remove/fix/change the slide? Because the slide deck has been vetted by the FDA and Otsuka’s lawyers. He can’t change it. He has signed a contract saying he won’t change it. Dr. Arruda gave a solid, thoughtful lecture to our department, but he did that in spite of the materials he was using. He spent considerable time just talking about the pathophysiology of sodium and did a better job than most at avoiding being a mere shill for Otsuka.
Our nephrology program, and I suspect others (most?) rely on the generosity of pharma companies to bring scientists to our program but we pay by letting the drug companies supply the slides. Tragically, those slides are vetted by people uninterested in education and devoted to meeting the conflicting demands of both the marketing and legal departments.
Dr. Arruda seems like a good guy and is a highly respected nephrologist but the only way we could get him to come to Detroit was on Otsuka’s dime and they were able to control the message.
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Crazy numbers: lowest creatinine

The consult team is now taking care of a patient with what I think is the lowest creatinine I have ever seen: 0.29 mg/dL. I’m not a bench nephrologist but I think that is a pretty typical mouse creatinine.

Update: some commenters asked about the BUN: 6 mg/dL. FYI today the Cr is down to 0.28 and the BUN fell to 3!

The patient has SIADH and low creatinines are a usual finding. She also has a crazy low uric acid of 1.4. Not quite Uricase low but getting close. Her admission sodium was 108, her urine sodium today was a whopping 156 with a urine potassium of 34. So if you calculate her electrolyte free water clearance (the amount of her urine which is electrolyte free water):

You get a negative 826 mL. A negative electrolyte free water is not unusual in SIADH and distinguishes it from the hyponatremia seen with heart failure (or other conditions of decreased effective circulating volume).
In this case the negative clearance means that for every liter of urine this patient makes it is as if she drank 826 mL of fluid. The very act of urinating lowers the sodium further by diluting the plasma sodium.
This throws a wrench in the standard plan of adding the urinary output to the insensible losses and setting the fluid restriction to be 200-500 mL below that. This works in conditions like heart failure where the electrolyte free water is positive but with a negative free water clearance you need to account for the negative free water clearance by adding it to the water intake, not the renal losses.
See this presentation on electrolyte free water clearance for further details.
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What causes hyponatremia in marathon runners

Me, running the NYC Marathon

One of the first blog posts ever on PBFluids was a review of Almond Et al’s study of hyponatremia. With this year’s Boston Marathon now complete I have re-reviewed the subject.

The Almond study was high profile and did a good job of demonstrating the risk factors for marathon induced hyponatremia. (See this post for a review) However some of the findings were self evident: increased weight gain was associated with hyponatremia. What is not answered is, why those who developed hyponatremia gained 3 liters of water. Why didn’t these patients just urinate the excess water? Normally, a falling sodium, shuts down ADH like a bordello on Easter. The retention of water is indirect evidence of ADH. Could it be that marathon running and ultra-endurance events could be added to the list of causes of the Syndrome of Anti Diuretic Hormone (SIADH).

It would have been nice to see a U/A or urine osmolality in Almond’s data to confirm this.

Siegel et al. (PDF) has done the most detailed study I am aware of on exercise induced hyponatremia. They did detailed biochemical assessments on 39 runners in the 2001 Boston Marathon. They drew pre-race (day before) and post-race (within 2 hous of finishing) samples for:

  • CPK
  • IL-6
  • ADH (vasopressin)
  • cortisol
  • prolactin
  • CRP

They also looked at 308 runners who collapsed during the 2004 Boston Marathon and measured:

  • IL-6
  • ADH (vasopressin)

Additionally they did some blood tests on 2 runners who had died of cerebral edema from exercise induced hyponatremia. One from the 2002 Marine marathon and the other from the 2002 Boston Marathon.

The normal patients had spikes in their CPK from 150 to 2,323. They also had a doubling of cortisol and prolactin but no change in ADH levels. The rise in CPK was matched by increases in IL-6 followed by an increase in CRP.

Of the 308 collapsed runners only 16 had hyponatremia. All of the hyponatremic runners reported a lack of urination during the race. 7 of the 16 had inappropriately high ADH levels in the blood. The authors concluded that lack of urination (though only driven by ADH in half the patients) rather than fluid loading was the predominant cause of hyponatremia.

The article then describes the laboratory and clinical scenario surrounding the two deaths in 2002. The data is summarized in the following table:

Importantly, both patients were initially treated with 150 mL/hr of normal saline without improvement. Two years later, two patients presented with similar symptoms and responded well to 3% saline:
The primary conclusions from this study, which admittedly is a bit schizophrenic with numerous anecdotal reports from various populations, is that exercise induced hyponatremia is not due to sodium loss but rather from fluid retention. Some of this fluid retention is driven by ADH and hence introduces exercise induced hyponatremia as a novel cause of SIADH. The diagnosis of SIADH is backed up by elevated urine sodium, elevated urine osmolality and normal (or high in the case of cortisol) cortsiol and TSH levels.

The elevated urinary sodium levels (consistent with SIADH) are a critical fact in the etiology of hyponatremia. If we were dealing with hypovolemia (commonly, but erroneously, referred to as dehydration), a cause of hyponatremia, one would expect a low urine sodium (usually less than 10 but always less than 20). The high urine sodium means that these patients were not volume depleted, It was not loss of sodium through the sweat which lead to the low sodium. This means that changing the sodium content of sport drinks is unlikely to prevent the complication.

The authors point out NSAIDs (ibuprofen, Motrin, Advil, naproxen) enhance renal response to ADH and should be avoided in the 24-hours prior to a race.

The authors recommend treating acute symptomatic hyponatremia from a marathon with 3% saline 1 mL/kg/hr to raise serum sodium 4-6 mEq/L and then to slow the rate to target 12 mEq/L in the first 24 hours of therapy. Just as is in all cases of SIADH 0.9% saline may not improve the serum Na.