I love getting e-mails from interesting people. Here is a recent one:
Dear Dr. Topf:
First of all, congratulation to your recent promotion!
I have one question regarding the treatment of acute hyperkalemia. As an avid follower of your posts and blogs, I have implemented your “bag of saline with furosemide”-approach for several years in appropriate patients and it works like a charm. I particularly like the beauty of the physiology behind this supposedly simple regime, with flow-induced recruitment of BK (FIKS) supporting the job of ROMK.
However, in my experience, this treatment is woefully underused in clinical practice and little known – even among nephrologists.
Are you aware of a publication substantiating its use? Which reference should I quote?
Looking forward to your reply!
Best wishes,
XXXXXXXXXX
Hmm? Data to support the use of loop diuretics in the treatment of hyperkalemia. Let’s see what we can find.
The first reference I found was this article from 1984
These authors looked at renal potassium excretion in patients following 40 mg of furosemide daily for three days. They did this experiment in 6 health volunteers five separate protocols:
- Furosemide with a high salt diet (270 mEq of Na per day)
- Furosemide with a low salt diet (15-20 mEq of Na per day)
- Furosemide with a high salt diet and captopril, intended to prevent increased aldosterone release with diuresis
- high salt diet and captopril, this time without furosemide
- Furosemide with a high salt diet and water load, this was intended to suppress ADH, which has a kaliuretic effect
The authors found that in the acute phase, the first 3 hours after IV furosemide, patients excreted 16 mEq of additional potassium over baseline potassium excretion with the high sodium diet, 19 mEq over baseline in the low salt group (presumably due to higher aldosterone) and 13.5 mEq in the high salt and captopril group.
Interestingly, the authors found that following this acute phase of increased potassium excretion there was a compensatory period decreased potassium excretion in the high sodium group that resulted in just about neutral potassium balance.
It makes me wonder if adding fludrocortisone would be helpful to the “bag of saline with furosemide”-approach to hyperkalemia.
I posed this question to my favorite potassium expert, Melanie Hoenig, and she suggested these references.
First was a circulation manuscript from when furosemide was the new kid and we were still trying to feel it out. These authors were playing around with weekly infusions of furosemide to treat hypertension. And it worked. (Link)
But, helpfully, they also provided information on potassium excretion, but unhelpfully they provided the data in micro Equivalents of potassium per minute.
So we have to do the math
Let’s say:
188 µEq/min from 0 to 22 minutes = 4.1 mEq
180 µEq/min from 22 to 45 minutes = 4.1 mEq
122 µEq/min from 45 to 90 minutes = 5.5 mEq
62 µEq/min from 90 to 120 minutes = 1.9 mEq
So a total of 15.6 mEq in the first two hours with an average of 63 mg of furosemide
195 µEq/min from 0 to 22 minutes = 4.3 mEq
201 µEq/min from 22 to 45 minutes = 4.6 mEq
166 µEq/min from 45 to 90 minutes = 7.5 mEq
91 µEq/min from 90 to 120 minutes = 2.7 mEq
And 19.1 mEq in the first two hours with an average of 210 mg of furosemide for you cowboys.
The next reference she sent was from the Canadian Medical Association Journal in 1968 where they took 115 male students and gave them one of three diuretics:
Hydrochlothiazide 50mg
Hydrochlorothiazide/triamterene 50/25
Furosemide 40 mg
And then tracked them for 24 hours. The results are interesting. Here are the potassium results:
73 mEq of potassium. Pretty impressive. But look how hydrochlorothiazide does just as well, though it is backloaded with most of the kaliuresis coming later in the monitoring period. Hydrochlorothiazide actually resulted in more sodium excretion, over 24 hours than a single dose of furosemide.
The last reference she sent was a 1964 manuscript from Circulation where the authors were playing with the, then novel furosemide. They were using it in edematous patients resistant to available diuretics (acetazolamide, spironolactone, meralluride, and thiazides) as well as normal patients. Here are the daily electrolyte losses with various doses of oral furosemide, from 50 to 600(!) mg.
Good to know that doses beyond 100 mg don’t seem to add much kaliuresis.
So to answer the question, a slug of furosemide seems to be good for 15 mEq of potassium removal acutely, given that the extracellular volume of 70 kg man is about 17 liters, this should drop the serum potassium by a little less than 1 mEq/L.
None of these studies look at patients with hyperkalemia, so I would really like to see any experimental evidence with that, so if you know of any, hit me up on socials.