Thread by @ebtapper

Have you ever wondered ... how beta-blockers treat #cirrhosis?

Here's a #tweetorial featuring:
1⃣Pathophys!
2⃣controversy!
3⃣Cheap, life-saving interventions!

#livertwitter #gitwitter #meded

1/

First, why do variceal bleeds happen?

Throwback to this #tweetorial:

https://twitter.com/ebtapper/status/1185514476776443904?s=20

tl;dr

1. #cirrhosis forces blood around the liver
2. Varices are bypass routes
3. Some run in the esophagus/gut
4. They can tear/bleed
5. Tragic

2/

Imagine this scene

It's 1980:
🩸variceal bleeds=surgical disease
🚫banding not invented
👶Sclero in its infancy
💉Somatostatin⬇️portal pressure,😢1/2-life
🩸🩸Rebleeding=the norm
⚰️Mortality crazy high

We need a durable way to ⬇️portal pressure!!

3/

Enter: Lebrec et al

🤔How about propranolol? It drops portal pressure(Fig1)

🎲RCT: propranolol⬇️rebleeds(Fig2)

Game: changed

4/

Turns out propranolol is awesome

Fig 1:⬇️🩸flow in varices by ~30%
Fig 2: BB⬇️mortality after bleeding

So...Beta-blockers for all?
Case closed?

Not so fast!

5/

PLOT TWIST!

Fig 1: ~30% don't respond 2 BB
Fig 2: In RCT, BB⬇️first variceal bleeds
...but not for all

🤷‍♀️What's going on?🤷‍♀️

6/

Let's back it up for a sec.

So how do beta-blockers work?

7/

Intestinal blood🩸flow is governed by:

🩸Delivery
1⃣❤️Cardiac output &
2⃣Balance of splanchnic vasodilation/vasoconstriction (alpha, beta receptors)
🩸Outflow
3⃣Ease of passage through liver to heart

Figure: how the alpha and beta work together

8/

#cirrhosis mucks intestinal blood flow

1⃣Impeded outflow⬆️intrahepatic resistance(Fig1)
2⃣More gut delivery thru splanchnic vasodilation
3⃣🔃variable cardiac❤️output(fig2)
(most are hyperdynamic...but some are not!)

9/

Here's where the meds come in:

If you block alpha/beta, you reroute blood flow(fig1)

Block beta👉⬇️flow to varices/gut
⬇️❤️output
⬆️splanchnic vasoconstriction

Block alpha👉⬆️flow through liver

10/

But why are we using NON-SELECTIVE beta-blockers??

❓Why not cardioselective BB like atenolol/metop?
❗️Not as good!(Fig1)

❓If hepatic resistance is a prob, why not alpha blockers like prazosin?
❗️Works! But...⬆️RAAS➡️fluid retention😢(Fig2-3)

11/

If only there was a way 2 combine beta/alpha blockade?

Carvedilol can do it!(fig1)

1⃣Beta>alpha. #cirrhosis metabolism is steroselective, s-enantiomer is B>A(Fig2)
2⃣⬆️Half-life & bioavailability in cirrhosis(Fig3)
3⃣RCT:May be more effective than propranolol(Fig4)

12/

Where's the controversy you were promised⁉️

Beta-blockers were the hottest topic of #livertwitter 2010-2015!

Let me tell you what happened

13/

SHOTS FIRED @ BB

2010:⬆️mortality in bad ascites(fig1)
2012:'window theory'(fig2)
(some need xtra❤️output)
2014:⬆️HRS&mortality after SBP(Fig3)

BB strikes back
🔥apology 4BB journal-of-hepatology.eu/article/S0168-…
2015: BB⬆️Waitlist survival!(f4)
2016: Mic drop meta-analysis(f4)

14/

2017-Present: Beta-blockers run up the score

1⃣Carvedilol may improve overall survival(Fig1)
2⃣RCT: BB reduce the risk of decompensation(Fig2)
3⃣Safety: U can select who will benefit based on short-term hemodynamic changes(Fig3)

15/

Well! This concludes a #tweetorial on beta-blockers for #cirrhosis. Hope u enjoyed.

1⃣BB⬇️flow 2gut but also⬇️cardiac output
2⃣BB ⬇️mortality
3⃣BB metabolism is different in cirrhosis. Carvedilol even @ 12.5mg qHS is adequate
4⃣BB safe but caution w/low BP,sick❤️

FIN

Practice variation in nonselective beta-blocker choice/timing is fascinating

1️⃣which BB you using in Saudi Arabia @drmoutaz ? Boston @tony_breu?
2️⃣how u handling periop @aoglasser?
3️⃣which in kids @Dr_NOvchinsky ?
4️⃣ever start in icu? @AvrahamCooperMD