Thread by @AdamRodmanMD

It's time for me to channel my inner @tony_breu -- which means it's Tweetorial time!

So let's talk about azotemia (elevated blood urea nitrogen) after an upper gastrointestinal bleed!

It’s a well-known phenomenon on the medical wards that after an upper gastrointestinal bleed, the blood urea nitrogen will rise considerably more than the creatinine. In fact, it’s a common teaching “pearl”

But why does the urea nitrogen rise?

The traditional teaching is that the elevation in urea nitrogen comes from digestion of blood and its high protein content. This actually dates back to the original study in 1934.

Sanguinetti first noted azotemia in 9 patients with massive hemorrhage for a duodenal ulcer. He attributed this to catabolic breakdown of blood, and tested his theory by feeding three of his colleagues pig’s blood.

He was so concerned that the azotemia might prove fatal that he actually advocated cecostomy to remove the blood!

Several other small case series in the 1930s confirmed these findings, though Clausen in 1936 noticed that patients with pre-existing kidney disease had higher degrees of azotemia.

No matter the cause, Schiff and Stevens in 1939 performed a review of 53 patients that suggested higher BUN was associated with both higher degrees of anemia and shock.

This led Gregory et al in 1945 to run a series of dog experiments to test the dominant theory of blood catabolism.

They took 66 dogs and designed four intervention groups -- controls, blood feeding, hypotension via bleeding, and then combined blood-feeding/hypotension. They then measured serial urea nitrogens.

Medical history has not been good to doggos.

Their conclusions:

✔️ Hypotension caused a significant and persistent rise in BUN
✔️ Blood feeding caused a small transient rise in BUN
✔️ Anemia alone DID NOT cause an elevated BUN
✔️ Hypotension AND blood-feeding cause a higher and longer uremia than either alone.

A wonderful follow up study was done by Cohn and colleagues in 1956. He recruited five healthy men for a series of studies in which they were given either blood, protein concentrate, or beefsteak.

They found that there was a small rise in BUN (~25%) with blood that rapidly resolved within 24 hours. However, both the protein concentrate and the beefsteak had a considerably higher rise (up to 247%) and lasted greater than 24 hours.

They concluded that while blood can cause a small, transient increase in urea nitrogen, it’s far less than other sources of protein.

In 1980, Stellato and colleagues performed a systematic review and concluded that azotemia in gastrointestinal hemorrhage may have a small and transient effect from blood digestion, but that hypovolemia was the major contributing factor (ncbi.nlm.nih.gov/pubmed/6968509)

Since the 1930s, it’s been noted that azotemia in UGIB is associated with sicker patients.

In 2017, Kumar and colleagues performed a retrospective cohort study looking at patients with azotemia and nonvariceal UGIB to test this hypothesis (ncbi.nlm.nih.gov/pubmed/28377105)

They found that an elevated BUN was associated with an increased risk of an adverse event, including death.

Their conclusion?

“Increasing BUN at 24 hours likely reflects under resuscitation and is a predictor of worse outcomes in patients with acute nonvariceal UGIB.”

So let’s revisit the original question again. Why does the urea nitrogen rise in gastrointestinal hemorrhage?

I think the most important takeaway here is that if you have a patient with a GIB and azotemia, don’t just think, “oh, that’s interesting.”

You should carefully evaluate their need for volume resuscitation.

Okay, let me know what you think! I just finished a block of wards attending, and every evening I go home and try to answer as best I can a clinical question that came up on rounds ("Angry Adam E-mails" I call them). This one in particular surprised me.

And a special thanks to @melhoenig who first told me about this controversy!

If you like this kind of stuff, I host a podcast on medical history and storytelling in partnership with @ACPInternists called Bedside Rounds at bedside-rounds.org or itunes.apple.com/us/podcast/bed….

And if you’re a member of the ACP you can get CME/MOC points for listening!

Go to acponline.org/BedsideRounds after you listen and take a brief quiz!