Elliot Tapper Profile picture
Sep 27, 2018 14 tweets 8 min read Read on X
Hepatic encephalopathy in the hospital (An ode to #lactulose):
A brief #livertwitter #tweetorial
Aims:
1. Share the greatest t-shirt ever made
2. Rule out infection!
3. Laxation now! But how?

keywords: #cirrhosis, paracentesis, stool pH
1. This shirt, made by a patient, reminds us:
▶️HE is horrible, unpredictable
▶️Preventing HE is hard
▶️Dont be quick 2 label pts as 'noncompliant' - there's more to the story
▶️Our patients are awesome. Hepatology is the best

#lactuloseorcomatose
2. Think of hepatic encephalopathy as a biomarker.

For what? The answers form a mandatory checklist of sorts

1. Para to r/o SBP. Delay @ your patient's peril. (Fig1)
2. GI Bleeding?
3. UA/Blood Cultures/CXR
3. What's the Cr? Na? K?
review: nature.com/articles/s4139…
#AmJGastro
3. First line therapy for hospitalized "overt" HE is lactulose

This nonabsorbable disaccharide has been used for HE for >50 years. (Fig1)
It was known even then that there had to be another mode of action beyond frequent BMs
Lactulose's mechanism of action came into focus after a 1966 trial in patients w/chronic HE
Fig1: Design - lactulose before or after sorbitol (osmotic laxative) with run-in
Fig2: HE that occurred on sorbitol could be resolved on lactulose
Fig3: The key difference: STOOL PH!
The same effect occurs after a lactulose enema.

See these data from a randomized trial of tap water vs lactulose enema in @HEP_Journal
ncbi.nlm.nih.gov/pubmed/3301614
How does lactulose lower stool pH?

The answer is that colonic bacteria metabolize the lactulose, spitting out organic acids

Check out this study from @jclinicalinvest comparing the stool output and organic acid concentration after PEG (aka golytely) vs lactulose
And here is the kicker: A little lactulose goes a long way

Even in subjects who had formed stool, lactulose still increased the organic acid concentration!
ncbi.nlm.nih.gov/pubmed/2794043
🥊 PEG vs Lactulose 🥊 The HELP RCT
ncbi.nlm.nih.gov/pubmed/25243839

This remarkable study was led by Dr. Bob Rahimi - who, as a FELLOW, enrolled 50 patients who often present in the middle of the night! #hustle

Lactulose (20-30grams TID) vs PEG Colonoscopy prep (4L)

Who wins?
PEG hastened recovery from HE (Fig1)!

Many patients also preferred the PEG to lactulose (Fig 2)
But...
Before you pop the cork on the Golytely, check out the supplement(Fig1):
84% of PEG patients got lactulose before randomization

CLEARLY you need 2 get the bowels moving (more laxative=better)
but a little lactulose goes a long way. Stool pH not measured.
Also...what's the right dose of lactulose?

When a pt comes in with acute CHF, would we give them their home diuretic dose?

Patients admitted with HE often get ~10-20cc TID
🔥Hot take 🔥 This is not enough: That is a maintenance dose

Your pt needs an induction dose!
Unlike with PEG, you dont need 4 liters, but >20cc lactulose q6-8? Definitely!
I learned how 2 treat HE from nurses when I was an intern. We took what they were doing & standardized treatment for HE. Some extra, frequent doses make a big difference(Fig1)
cghjournal.org/article/S1542-…
In summary:
- Hepatology = the best
- Do that para! Search 4 HE triggers
- Drop that stool pH! Even a little lactulose helps
- Laxation now!! Need frequent BMs on Day 0-1 to treat Overt HE. Take your pick: extra doses of lactulose or lactulose + PEG.

Thanks for stopping by!

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More from @ebtapper

Jun 9, 2023
WHAT is the deal with Milk Thistle?
WHY is it used to treat liver disease?
HOW does it work?
DOES it work?
ARE you ready for a #tweetorial?
🧵
#medtwitter #livertwitter Image
Milk Thistle, a history:
1⃣Use to treat snake bites (Dioscorides)
2⃣To carry off bile (Pliny the Elder)
3⃣Great for liver disease (1500's: Otto Brunfels)
4⃣In 19th Century 🇺🇸, the 'Eclectics' popularized herbology, especially milk thistle, for the liver ImageImageImageImage
Fast forward to today:
1⃣Herbal supplements are a multibillion dollarindustry
2⃣A quarter of the population takes an herbal supplement
3⃣~5% of the US population is using Milk Thistle, including 12% of people with liver disease

What do they get out of it? ImageImage
Read 12 tweets
Jun 4, 2023
I once did a cost effectiveness analysis comparing shotgun vs deliberate testing for elevated ALT

pubmed.ncbi.nlm.nih.gov/27717864/ @JHepatology

We found that broad testing didn’t add much costs but increased false positives, especially when pretest probability of NAFLD was high
Then, In this RCT, John Dillon comparing usual care to broad evaluation of elevated liver enzymes, the cost per incremental diagnosis was 284💷 but was def cost-effective

pubmed.ncbi.nlm.nih.gov/31226388/
I don’t know of many examples of RCTs that confirm or support cost-effectiveness analyses so

A) cool!
B) understanding the differences in the results hinges on the assumptions in the model and the design of the RCT
Read 4 tweets
Jun 4, 2023
How to read a cost-effectiveness paper

This is a powerful method. But poorly understood, often maligned. My goal is to improve critical appraisal and help good analyses get the appreciation they deserve

🧵#MedTwitter CEA: cost-effectiveness analysis
A decision must be made!

All CEA begins with a clinical decision where we are uncertain about the best path forward. Nevertheless, when we face patients we must do something, even if that something is nothing. CEA brings our dilemma to life. Helping us quantify trade offs
Usually we compare a fair description of usual care to an alternative - make sure you agree the choice is fair, realistic, and represents an actual clinical dilemma
Read 20 tweets
Jun 2, 2023
An older man comes to the ED with abrupt onset nausea, & diarrhea

He is joined by her daughter whom he is visiting from abroad

Testing is below
The diagnosis is unclear
Until his daughter got just as sick too
🧵
#livertwitter #liverstory #MedTwitter Image
ALT >1000 has a narrow differential diagnosis



There's lots of tests you can order.
But most diagnoses are made in the H+P

Like this one

In fact, in this case, my attending said the diagnosis was obvious from the beginning

Just not to me
When I meet someone with ALT>1000, I think:

1⃣Ischemic hepatitis. Right 🫀failure? 🫀-genic shock? Cool legs?
2⃣Biliary 🪨. Pain? imaging!
3⃣Drug induced liver injury. Tylenol? Run every med through livertox.gov
4⃣Viral hep. Hep A/B/C

But these weren’t the answers
Read 16 tweets
Feb 6, 2023
The correct answer is variceal bleeding

First, the lactate is up. Take this patient seriously
Second, the obvious clues are lower hemoglobin, platelet consumption.
Third, the ammonia is crazy high. This seals the deal for variceal bleeding.

Why is that?

next slide please
Ammonia is a biomarker of badness

1. Liver dysfunction
2. Portosystemic shunting
3. Dehydration, renal injury (🫘eliminates nh3)
4. Sarcopenia (💪eliminates nh3)
5. Malnutrition

6. And upper GI bleeding
Where is all that ammonia coming from?

The answer is hemoglobin and albumin are isoleucine-poor. This means that when our blood enters the gut, it is not a nutritious source of protein. It gets broken down for waste. That waste, my friends, is ammonia
Read 9 tweets
Oct 12, 2022
5 steps toward a killer talk
🧵
1️⃣practice by recording yourself on the memo app. Listen next day while walking. Refine. Repeat.
2️⃣stay on time, preferably under. If 10 min slot, 9. If 15, 12. If 30, 25.
Read 6 tweets

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