I get some great letters, here is one of the best from a woman with SIADH

An e-mail I received last month:

I love your blog.  I have had SIADH for a zillion years.  I only found out what I had when I went with 5 girlfriends to a fancy spa hotel  in Tucson for a mini-vacation/ 4th of July Weekend in 1997 where the heat increased to an uncomfortable 117 degrees.

Healthcare workers in the hotel kept handing out bottles of water at each hotel exercise location with orders to “hydrate, hydrate, hydrate” and I stupidly followed their directions.  I drank myself into a 6 day coma.

The only time that sentence has been used for water, not alcohol.

Very non-traumatic for me. Very traumatic for my family. I woke up on day 6 saying, “I am STARVING!  Will someone go get me a taco?” which was very anxiety-relieving for all of them; they’d been sure I’d wake up cognitively impaired.  I wasn’t.  This “taco” sentence sounded JUST like me.  And I have continued to be not cognitively impaired despite interesting lab numbers.

My dad (who is a physician too) has SIADH as well, though his was diagnosed after mine.  I was mis-diagnosed for 9 years prior to my coma as having a “seizure disorder.”  The excellent care I received when my mental status went to heck in a handbasket was truly life-saving.  I remain a very grateful nephrology patient.  And I really do love your blog.

Thought you should know this.

She wrote back a few days later giving me permission to post her letter:

I am dying (well not literally dying) to start an SIADH group on Facebook.  We are so not connected to one another, and each of our nephrologists only have a handful of patients and of course the doctors can't introduce us to eachother because of HIPAA. 

• For those of us that have the Syndrome without lung cancer and so on and have to live our lives thirsty
• and our summers avoiding the sun through our sunroofs (Demeclocycline)
• and have to, if we're female, find inventive ways to paint our nails to avoid Demeclocycline making our nailbeds ugly colors
• and have to fear that Otsuka Pharmaceutical will convince the ONE manufacturer who makes Demeclocycline to stop making it and force us into buying Tolvaptan even though they never tested it in 3rd stage human trials on people that weren't already cognitively impaired (I know because I volunteered for every single US trial), 

Well, we NEED each other.  We need tips on nail polish, tips on drinking our fluids out of 1 ounce shot glasses, tips on rolling ice cubes around our mouths during the days our sodium is tanking, and your website is a GREAT place for us to meet up!  

You have my non-dying thanks and permission to reprint/repost any or all of my statements!

Reminder of a great case from the archives

Last year I had one of the most severe cases of hyponatremia I had ever seen. Last night I was flipping through iPhoto (looking for the drawings Margret Atwood did of my alter ego, Kidney Boy) and found this photo...

Just looking at the labs gives me chills. Here is the whole story.

Outpatient hyponatremia

Almost all of the hyponatremia I see is inpatient, but this week a woman was referred to my clinic with a sodium of 128. She has a sharp family doctor who ordered all the right tests. Here are the key pieces:

• Plasma sodium 128
• Plasma osmolality 277
• Urine osmolality 180
• Urine SpGrav 1.005
• Urine sodium 14

She has a history of hypothyroidism but her TSH was over suppressed, no hint of hypothyroidism. She was not taking any diuretics. She was on an SSRI that could cause SIADH but the low urine osmolality and low specific gravity argue against excessive ADH activity.

The case hinges on the low urine osmolality. This is a rare case of ADH-independent hyponatremia. All of the major causes of hyponatremia (volume depletion, diuretics*, heart failure, SIADH, etc) are driven by ADH which prevents the kidney from clearing free water. The low urine osmolality indicates the kidney is not under the influence of ADH and doing what it needs to in order to correct the sodium, i.e. excreting excess water in the form of dilute urine.

I believe there are only a few causes of ADH-independent hyponatremia, and only two occur with any regularity:

• Psychogenic polydipsia
• Tea and toast syndrome
• Reset osmostat (rare)

When the kidney is making dilute urine and the patient has hyponatremia the problem is not in the quality of the urine, which is appropriate, but in the quantity of urine, which is inadequate.

She described her diet as a peanut butter and jelly sandwich for breakfast, some fruit and juice with some nuts for lunch and nothing for dinner. Her fluid intake was high (4-5 cups of coffee, a large water bottle of water, some juice, some soda, and a couple of additional glasses of water) but no where near enough for psychogenic polydipsia.

I suspect she has tea and toast syndrome. I am checking a 24-hour urine osmolality to gauge her daily osmolar load and then plan to have her increase the amount of protein and minerals in her diet while trying to taper her fluid intake.

More on tea and toast syndrome here

A well done case report on a healthy patient wih reset osmostat can be found here (pdf)

* if the diuretics are still active the urine osmolality could be low but once the drug wears off the urine osmolality will climb

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.

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

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.

Must see photo

Check out Joshua Schwimmer's photo of a foley bag.

Great shot, highly illustrative of vaptans effect on urine osmolality.

Happy July 1st.

For the third year in a row a I had the honor to present the first morning report of the academic year. Fluids, diuretics and dysnatremia:

Fluids And Electrolytes July1

View more presentations from Joel Topf.

Dysnatremia chapters (chapters 6-9) of Fluids

Chapters 6 and 7: Hyponatremia

06 and 07 Hyponatremia

Chapter 8: Hypernatremia

08 Hypernatremia

Chapter 9: Polyuria/Polydipsia

09 Polydipsia Polyuria

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.

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.

Electrolyte Free Water Clearance

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Lecture to medical students July 17th

Lecture on IV Fluids and sodium

I had eight 3rd year medical students. I did a quick pole and 6 of the 8 had or were planning on getting an iPhone/iPod touch. One student had an Android G1. No Blackberries, no Windows Mobile.

Is it too early to declare a winner in the medical smart phone arena?

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.

William Schwartz, the co-discoverer of SIADH has died

William Schwartz has died.

Every Monday at noon during fellowship we had the fluid and electrolyte conference with Dr. Fred Coe. Dr. Coe has extra-sensory powers for electrolytes. When you presented, you would give just the electrolytes and he would re-create the entire case from the metabolic panel. During the lecture he would ask you to explain a certain pathophysiology and then excoriate you if your thoughts were lazy and poorly organized.

If you ever blamed a poorly characterized hyponatremia on SIADH, Dr. Coe would look at you and ask "If Bartter and Schwartz were here, at this table, right now, and were looking at the same data that you have provided, would they agree that this is SIADH? Would they?"

JASN re-printed the original 1957 article describing SIADH in 2001.

Goodbye Dr. Schwartz, yours are the shoulders we stand-on in the daily grind of clinical nephrology.

Fluid and Electrolyte lecture at Providence from Friday

Third in the series of interesting fluid and electrolyte cases.

I would add a slide on where I was going in potassium before the anorexia section.

SlideSpace botches the torn paper frames I used through out the lecture so if you have Keynote, download and look at the native file.

Here is a link to the Keynote file.

Electrolyte Vignette

View more presentations from Joel Topf. (tags: alcoholism magnesium)

Internal Medicine Board Review: Fluids, Electrolytes and Acid Base

The chief resident at Providence asked me to do a board review class for the third-years. They have small sessions weekly (?) in the physician lounge. This afternoon we went over fluids, electrolytes and acid-base. We did the first 14 questions. Seems like it went pretty well.

Board Review Questions and Answers

iPhone Medical Applications

I have four medical applications on my iPhone, of which I use two. Here is a quick review.

To show how the iPhone equipped physician approaches clinical problems I will use the DB's Medical Rants most recent acid-base problem. He presents a case with the following information:

49-year-old man, previously in good health, presents after a few weeks of progressive weakness and dizziness. He admits to polyuria. Your job is to extensively discuss his lab tests.

The first step in my mind is to fully interpret the ABG. To do this we will use the application ABG.

ABG

This simply named program is an ABG calculator that runs through the standard algorithms for detecting multiple primary acid-base abnormalities. Can't remember Winter's Formula. As long as you don't have boards coming up you can just plug'n chug and turn DB's ABG into the following:

This does two of the calculations that DB describes at length:

1. Winter's formula (16 * 1.5 + 8 ±2) shows that the predicted pCO2 is 30-34. The patient's CO2 is 33 so the patient has isolated and appropriately compensated pCO2 of 33. ABG displays this information in the second line when it describes the acid-base disorder as "Compensated metabolic acidosis." It does not describe a second primary condition such as respiratory acidosis or alkalosis.
   
2. Gap-Gap or delat-delta. The patient has a dramatically elevated anion gap at 27 (15 over the upper limit of normal of 12) but his bicarb of 16 is only 8 below normal. The difference between the delta gap and the delta anion gap is 7 (15-8) when this is added to the normal bicarbonate you get 31; so the patient had a pre-existing metabolic alkalosis with a bicarbonate of 31. ABG displays this information as the corrected bicarbonate.

The next step is adjusting his sodium for the hyperglycemia. To do this we will use Mediquations though Medical  Calc works just as well.

Mediquations

DB, in his discussion, states that he has unpublished data proving that no formula is effective at adjusting the serum sodium for the hyperglycemia. For those of us without his unpublished data should adjust the sodium using Katz's traditional conversion (pdf of a letter to JAMA discussing adjusting sodium for hyperglycemia in DKA. Katz's original conversion was discussed in a letter to the NEJM) of a drop in Na of 1.6 for every 100 the glucose is over 100 mg/dL. Nephrology fellows should additionally be aware of Hillier's data showing the sodium falling 2.4 for every 100 of glucose. Both Mediquations and Medical calculator adjust the sodium using Katz's conversion.

Of coarse you wouldn't know it was Katz's conversion because even if you tap on "More Info," Mediquation does not provide the reference. Likewise you will not get the reference with Medical Calc.

Though DB did not explore free water defecits in his discussion of the case this is a clinically relevent point. You can use Mediquation to calculate the water deficit.

I feel that using ABG and Mediquations will make you a more effective physician without forcing you to memorize equations used only periodically.

July first lecture on IVF, Diuretics and dysnatremia

Today I gave the first lecture of the '08-'09 Academic Year. This was morning report for internal medicine. I did a lecture on IVF, diuretics, total body water and dysnatremia. It was a good lecture but Powerpoint only. I am about half-way done with the killer handout I am working on and am disapointed that I didn't finish it. Hopefully will have it done for the next lecture in two weeks.

Fluids And Electrolytes July1

View SlideShare presentation or Upload your own. (tags: diuretics sodium)

Dysnatremia handout

One of my (soon to be former) fellows wanted a copy of this work-sheet handout on electrolyte free water clearance.

Hyponatremia and Marathons

I love it when some of the arcane nephrology knowledge makes headlines. When I heard NPR covering hyponatremia I almost cried. I am training for a half marathon in October and so I have been thinking about this topic.

Almond, Et al's study published in the NEJM looked at 488 blood samples from 766 runners recruited from the 2002 Boston Marathon. They found post-race:

• Average sodium 140±5 mmol/L
  
• 13% had a sodium <>
  • 22% of woman
  • 8% of men
    
• 3 runners had Na <>

When they looked at predictors of hyponatremia, univariate predictors included:

• Female gender (p<0.001)
• Lower BMI
• Fewer prior marathons (p=0.008)
• Slower training pace (p<0.001)
• Longer race duration (p<0.001)
• Hydration frequency (p<0.001)
• Hydration volume (p=0.01)
• Urination during the race (with more frequent voiding having a higher risk of hyponatremia) (p=0.047)
• Weight gain during the race (p<0.001)

Of note use of sport drinks compared to pure water made no difference. In the multivariate analysis, hyponatremia was associated with:

• weight gain
• longer racing time
• body-mass index of less than 20

Of note the female gender falls out in the multivariate analysis as it likely was accounted for both by the longer running time and lower BMI.

In the discussion the authors mention that most sport drinks have only 18 mmol/L of Na.