Saltiest Sodium. Dumbest Dude.

My work-shop on sodium includes a bit on all the cases of hyponatremia due to fraternity hazing.

• Mathew Carrington
• Walter Dean Jennings
• Braylon Curry

I also include the crazy case of Jennifer Strange.

But I had never heard of idiot induced hypernatremia until this case report:

A nineteen year old male drank a quart sized bottle of soy sauce on a bet.

Two hours later he was brought to the ER comatose and seizing. His sodium was 177. They initiated hypotonic fluids and arranged transfer to a tertiary care center. At the tertiary care center the sodium was still higher at 191. The doctors then changed the fluids to D5W at 12,000 mL per hour. They gave 6 liters of D5W in 30 minutes.

After the infusion he opened his eyes and regained spontaneous movement. He was discharged on hospital day four neurologically intact with only some minor abnormalities on the head MRI, all attributed to postictal changes.

How high is a sodium of 191? MedCalc will not even accept it as a possible sodium concentration:

A couple items of note:

• The infusion of D5W raised his serum glucose from 365 (hyperglycemia causes insulin resistance) to 1,116 mg/dL.
• The authors do not comment on what access they used to infuse D5W at a liter every five minutes.
• In addition to the hyperglycemia, the D5W infusion dropped the potassium from 5.1 to 2.5 in 30 minutes! That is kind of terrifying.
• The authors use the Katz correction for hyperglycemia, (eat it Hillier).
• The authors do not discuss how they decided on 6 liters of D5W. Full correction down to 140 would by roughly 12 liters, so perhaps they decided on 12 liters in an hour with continuous neurologic assessment and when he began to have spontaneous motor movement after 30 minutes they slowed down.

Some nerdery about the sodium exposure: He drank a quart of soy sauce. A quart is 946 mL. The article states that soy sauce is 17-18% sodium chloride. Here are some meta calculations, in case you are interested:

Read the article, it's a good read and it has the highest urinary sodium I have ever seen, 270 mmol/L (almost twice as salty as normal saline). They discuss other extreme hypernatremic conditions, and theories on rapid or slow correction.

Hat Tip Skeptical Scalpel

Slides for Keynote | PDF

Update from Twitter:

@kidney_boy I would guess they used a pressure bag or infuser (e.g. Trauma 1) to get in a L every 5 min
— Seth Trueger (@MDaware) June 10, 2013

@mdaware @kidney_boyA good 14 ga 1.75 inch peripheral IV can do 333 cc/min with a 1 meter pressure head to gravity.
— philroman (@philroman) June 11, 2013

@kidney_boy I've seen 216 before. Started at 196, rose more with initial NS administration. Kid with ichthyosis, and bad dehydration.
— Ken Tegtmeyer (@pccm_doc) June 11, 2013

Salty dog, the highest sodium I ever saw.

A series of sodiums from 176-188 mmol/L

Those are not glucoses. They are Sodiums. And, except for maybe an infant with congenital adrenal hyperplasia when I was a resident, those are the highest sodiums I have ever seen.

The primary management concern was the speed of correction. The first Na at 188 was drawn at 4:32 pm. Four hours later it was 177, a change of 11 mEq. Too fast. Here is the salient section from UpToDate:

Rate of correction in chronic hypernatremia — There are no definitive clinical trials, but data in children (particularly infants) suggest that the maximum safe rate at which the serum sodium concentration should be lowered in patients with chronic hypernatremia is 12 meq/L per day. To be safe, we suggest a maximum rate of correction of the serum sodium of 10 meq/L per day in patients who have had hypernatremia for at least 24 hours. The following findings provide support for this conclusion:

• A retrospective case control study included 97 children with hypernatremia and dehydration; the mean baseline serum sodium was 165 meq/L. The rate of reduction in serum sodium was significantly faster in the children who developed cerebral edema compared with children who had no complications following correction of the hypernatremia (1.0 versus 0.5 meq/L per hour).
• Similar findings were noted in another report in which the rate of reduction in serum sodium was 1.0 meq/L per hour in the nine infants who developed seizures compared with 0.6 meq/L per hour or less in 31 infants who did not develop seizures.

So Bud Rose, the dean of electrolytes, says 12 mEq per day.

Burton Rose

My patient moves 11 mEq in 4 hours after receiving 500 mL of normal saline. Now what? I was convinced that continuing normal saline would perpetuate the overly rapid correction of the sodium and put the patient at risk of cerebral edema. But since the patient was still in hypovolemic shock, I couldn't just stop the fluids.

I ordered 3% saline. I ran it at 100 mL/hour and 5 hours later the sodium was back up to 186. I was going in circles. I then changed back to normal saline and over the subsequent 48 hours we corrected the sodium at roughly 0.5 mEq/l/hr. The whole time I was going through this I was wondering is it all necessary? Is rapid correction of hypernatremia as dangerous as Rose said it was? Is half a miliequivalent/L/hr a real evidence based speed limit?

I put this question to a fourth year medical student and he did an excellent job diving into the evidence (or lack there of) on the topic. Here is his analysis:

docx | pdf 

I think he is a little hard on Rose's guidelines. The student's analysis criticizes one of 4 references that are provided in UpToDate (though his criticism is appropriate and is the sole reference in Rose's landmark Clinical Physiology of Acid Bas Disorders) to support of the 0.5 mEq/L/hr speed limit.

The four UpToDate references are:

1. Rose's own textbook, Clinical Physiology of Acid Bas Disorders. The page to look at in my 5th edition is 777.
2. Kahn et al. Controlled fall in natremia and risk of seizures in hypertonic dehydration. Intensive Care Med (1979) vol. 5 (1) pp. 27-31
3. Fang et al. Fluid management of hypernatraemic dehydration to prevent cerebral oedema: a retrospective case control study of 97 children in China. Journal of Paediatrics and Child Health (2010) vol. 46 (6) pp. 301-3
4. Blum et al. Safe oral rehydration of hypertonic dehydration. J Pediatr Gastroenterol Nutr (1986) vol. 5 (2) pp. 232-5

I will look at each reference in detail.

The section in Rose's text is very similar to the UpToDate card. The relevant paragraph is on page 777 in my 5th edition (black cover). The sole reference in this paragraph, is the 1986 Blum article (number 4 from the above list).

iPhone, a surprisingly effective photocopier.

Kahn retrospectively looked at the care of infants. They used half normal saline and gave it at 160 mL/kg/day (6.7 mL/kg/hr). All of the patients were 0-5 months, so maintenance fluids would have been 4 mL/kg/hr.

What book did this great page on maintenance fluids come from?

Nine of the first 47 patients developed seizures that could not be explained by other etiologies (fever, hypocalcemia, hypoglycemia) and so were ascribed to rapid fluid restoration, Group I. They matched these nine to 22 age-matched children who were treated contemporaneously but did not have a seizure, Group II. The investigators then changed the protocol for treating infants with hypernatremia to 120 mL/kg/day and included data on 9 patients under 5 months who were treated this way, Group III.

Here is the primary data on the three groups:

All three groups had similar sodiums but Group I had significantly higher BUNs than Group II, with I +II vs III and I vs III being non-signifigant.

The protocol called for patients in Group I and II to get only 160 mL/kg/day. Both groups significantly exceeded this. Group III hit its fluid goal nearly on the nose. They blamed the excess fluid on oral replacement and volume resuscitation with sodium bicarbonate.

The net result was a wide spread in the rate of correction of sodium:

• The kids that seized: 1.02 mEq/L/hr
• The kids that did not seize but were on the same treatment protocol: 0.62 mEq/L/hr
• The kids on the conservative protocol, also without seizures: 0.35 mEq/L/hr

Fang looked at 97 children with hypernatremia. Mean sodium was 164.5. Mean age 13 months. He performed a case-control study with the cases being patients who developed cerebral edema. Manifestations included seizures, eyelid edema, papilledema in all the patients and bulging fontanel in 36 and pupillary abnormalities in 9 cases.

The data shows cerebral edema was more common with bolus therapy, especially when the bolus was faster, higher sodiums were associated with cerebral edema but much of that disappeared in multivariate analysis as higher sodiums were also associated with increased rate of correction and ind increased bolus rates. Using ROC the investigators found a rate of fluid administration of 6.8 ml/kg/hr was safest. And the average decrease in serum sodium in the cerebral edema group was 1 mEq/L/hr and 0.5 mEq/L/hr without cerebral edema.

The final reference is Blum's study of oral rehydration, this is the reference my med student was upset with. As he outlined, this was a study of oral rehydration rather than a study of rates of treatment. The cohort was composed of eighteen infants, 6 months or younger admitted with hypernatremia (Na > 150) and treated with oral fluid resuscitation. They compared the hypernatremia outcomes to a second cohort of 26 infants who received IV rehydration for hypernatremia. Average sodium for both groups was 160.

In both groups the reduction of sodium was slow (0.3 mEq/L/hr) and no patient developed seizures.

In Burton Rose's Clinical Physiology of Acid-Base and Electrolyte Disorders this observational study with no seizures is the sole reference behind the recommendation for a slow restoration of normal sodium. Weak sauce. Of note Androgue's review of hypernatremia in the NEJM from 2000 references the same Blum and Khan articles to support its recommendation of slow treatment.

So in the end, the recommendation for slow normalization of sodium is based on a handful of studies in infants with no randomized or even prospective studies. What is unbelievable to me is no one references a study that reviews the functional/neurological outcomes of patients with the highest sodiums admitted to a large hospital based on the speed of correction. Seems like an easy study and in its absence we are left to trust in the physiology of babies.

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

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Lecture for the St John Residents

I have been doing a monthly fluid and electrolyte conference for the residents at St. John. Today we did a case of hypernatremia initially due to hypercalcemia and then due to nephrogenic diabetes insipidus.

Hypernatremia Hypercalcemia Case Vignette

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

Things have been coming in pairs: electrolyte free water and hypernatremia

First we had the highest creatinine followed by the lowest creatinine.

Then we had a case of hyponatremia/SIADH that we evaluated with the concept electrolyte free water and now we have a case of hypernatremia that we also evaluated with electrolyte free water.

I have a special fondness for dysnatremia formulas that work with either hyper- or hyponatremia because there is an elegance in using a model that works at both extremes.

Both the change of sodium formula and electrolyte free water calculation work as well with hypernatremia as they do with hyponatremia.

The case: 56 year old African American nursing home resident with a history of bipolar disease. She presents with altered mental status and initial labs reveal acute kidney injury and hypernatremia.

Body weight 70 kg

Na 177

Cr 4.18

On exam the patient had obvious hypovolemia and the elevated sodium reveals dehydration. The primary team appropriately uses half normal saline to correct both of these deficiencies.

The sodium came down to 167 the following day and after that they have been unable to further correct it. The patient remained in the ICU for 4 days prior to us being consulted for persistant hypernatremia. The creatinine rapidly corrected over four days to 1.6.

Additional data:

Admission urine sp grav 1.011

Admission urine Na 10

Admission urine osmolality 330

On the fourth day of the admission the urine output was 1,500 over the prior 8 hours

The primary team had been using the water deficit formula to estimate the amount of fluid to give the patient to correct the sodium over 2 days:

The water deficit equation asks how much water will be needed to dilute all the solutes to some ideal. In many books and programs the ideal sodium is fixed at 140 mmol/L. I usually use 145 mmol/L, which is the least amount of change in sodium to get a normal sodium. I do this because the downside of correcting sodium is all on the side over correction and inducing cerebral edema.

The equations often wont let you determine the % body water and fill in 60%. This is a large source of error because in the United States we're all fat and fat people are relatively anhydrous. Also, since typical internal medicine patient is about 100, and old people are likewise anhydrous 60% is a over estimation of total body water. My fellow estimated the total body water to be 35 liters.

The calculated free water water deficit is 7.7 liters. I usually administer half of that in the first 24 hours unless the sodium is very high, as in this case, and then I would have given about a third of the volume in the first day and correct the sodium over three days. I shoot for a change of about 12 mmol/l per day.

The equation worked well initially with the sodium going from 177 to the mid 160's but after that they stalled. The reason the sodium stopped improving was that they cured the patient of her renal failure and the urine output increased. Neither the team nor the water deficit formula accounted for this.

We can account for the urine output by replacing the electrolyte free water clearance:

So one would have to add 2.8 liters of electrolyte free water to the free water deficit calculation to account for urinary loss of electrolyte free water. If one were to recalculate the water formula using the partially corrected sodium of 167 you get:

If you plan to give half that in the first day that is 2.65 liters. Compare that to the electrolyte free water loss of 2.8 liters and it immediately becomes obvious why the sodium remained stable for days.

Teaser: An elevated electrolyte free water clearance in the presence of hypernatremia is presumptive evidence of diabetes insipidis. I will save that discussion for my next post.

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

Lecture at Providence Hospital on Electrolytes

I am trying to do a monthly lecture for the Providence internal medicine residents on electrolytes. I gave my second one last Friday. It was an interesting case we had of hypernatremia on the consult service last summer.

I did this lecture in Keynote and I am blown away by how good it presents through SlideShare. Really impressive.

Hypernatremia Hypercalcemia Case Vignette

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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.

Polyuria, polydipsia

The set up

Patient is the ICU, you receive a consult for hypernatremia resistant to therapy for three days.

Na 174

Cl 128

BUN 38

K 3.2

HCO3 27

Cr 1.6

glucose 128

urine lytes:

Na 56

K 12

Body weight 45 kg

urine output 2,800

Step one

Calculate the fluid deficit:

We assume the increase in sodium is entirely due to loss of water. If the patient is hypotensive, tachycardic orthostatic or has other clues that he maybe volume depleted, the situation is more complex. We calculate the percentage that the sodium is elevated above an imagined "ideal sodium." Many equations use 140 as the idealized sodium, I tend to use 145. The percentage the sodium is above the ideal is identical to the percentage of the total body water that is needed to lower the sodium to the target level.

174-145 / 145 = 0.2 (the sodium is 20% above 145)

Multiple that by the estimated total body water (weight x % body water) = 5.4 liters

I used 60% for estimated total body water. The patient looks like a young boy. Rose suggests lowering the estimated % body water by 10% so 50% would be okay also. In the elderly and obese this number can go below 50%. 

Step two

Going from 174 to 154 is too much change in 24 hours. The speed limit is 12 mmol/L/day so we will target a change from 174 to 162.

I use a modified water deficit formula. I divide 12 (the change in sodium we are looking for) by the target sodium (current sodium minus 12):

12/(174-12) = 0.08 x total body water = 2.0 liters or just over 80 mL/hour

Step three

Calculate the electrolyte free water clearance. The reason the ICU team repeatedly failed to correct the sodium is that they corrected the deficit without accounting for the ongoing water losses. In this case it is renal losses. If you just add the urine volume to the water deficit you will over estimate the amount of water needed because the urine contains sodium and potassium. To account for the electrolyte content of the urine we calculate the free water clearance.

Urine Na + K divided by the serum Na will give the ratio of urinary electrolytes to serum solute. 

56 + 12 / 174 = 39%
The urine has 39% electrolyte content of plasma, another way of thinking about this is that 39% of the urine volume is isotonic and the remainder (61%) is pure water. The 61% is what we are interested in; multiply the urne output by 61% this is the volume of water we need to give the patient to account for his ongoing renal losses. 

Then multiply this by the urine output (2,800) to get the electrolyte free water clearance, 1705 ml. This is another 71 mL/hour

Wrap up

Final fluid orders: 154 mL/hour of water, this can be given as D5W in the IV or preferably oral flushes. This calculation does not insensible losses.