I had a patient’s potassium pop from 3.1 to 5.1. It struck a half-remembered dream of a mentor teaching me that the most common cause of hyperkalemia was the treatment of hypokalemia. It is one of those internship myths that are recited mostly just to scare caution into over eager interns. So I asked Bluesky if anyone knew about this.
I then immediately, I went to Chat GPT4o and asked the same question. I hit the right domain with a correctly-worded prompt and the rock skipped clear across the lake.
Looking at my choices, I went with the middle one, because it had a DOI and I don’t have a subscription to UpToDate.
And being from 1998 made it contemporary with the pearl of wisdom in question.
The NEJM review of Hypokalemia by G. John Gennari was part of a review series on Fluids and Electrolytes the NEJM ran around the turn of the century. They were foundational articles for me as a fellow from 2001-2003. And on page 6 of an 8 page review of hypokalemia he drops this bomb.
Potassium replacement is the cornerstone of therapy for hypokalemia. Unfortunately, supplemental potassium administration is also the most common cause of severe hyperkalemia in patients who are hospitalized,53 and this risk must be kept in mind when one is initiating treatment. The risk is greatest with the administration of intravenous potassium, which should be avoided if possible. When potassium is given intravenously, the rate should be no more than 20 mmol per hour, and the patient’s cardiac rhythm should be monitored. Oral potassium is safer, because potassium enters the circulation more slowly.
Reference 53 is a study that G. John Gennari published in 1987.
In that study he combed the lab computer to find every case of hyperkalemia over 5.9 in a year. He found 300 and examined every case. Forty-eight of them were associated with new medications. Here was his list of meds that could cause hyperkalemia
Notice he doesn’t include ACEi as a group. He uses group names for beta-blockers and potassium sparing diuretics. But he lists captopril as a single agent because there were no other ACEi. This is an old study.
Of those 300, 172 had sustained hyperkalemia. He found 43 to have a single etiology of hyperkalemia (Group 1). And of those 43, potassium chloride was the sole etiology in 29 patients. Renal insufficiency was right behind at 24, followed by digoxin at 21. Did I mention this was an old study?
The whole study sounds pretty flimsy and polluted with biases. It stinks of post hoc choices and arbitrary rationalizations. Research has become much more rigorous in the last 40 years.
I don’t find this data to be cempelling but I’m also sure this was the source of the myth in question. And Chat GPT4o was instrumental in finding it and finding it fast.
That said the discussion on Bluesky was absolutely delightful. Follow the original post to see the rich conversation that bubbled up.
Post script: I do not believe that the most common cause of hyperkalemia is the treatment of hypokalemia. I think we live in a world with so much angiotensin and aldosterone inhibition that mistreatment of hypokalemia is a tiny blip on the radar.
Post-Post Script: the first reference, the review from 2017 in the NEJM by Kamel and Haperin, It doesn’t exist. The computer is pulling their book from 2016.
