What's the deal with pain control in #cirrhosis?
A #meded #tweetorial with QI undertones

Aims:
Tylenol
NSAIDs (mostly)
Pharmacokinetics in ESLD
Tramadol

If this is a confusing topic for you, you are not alone!
Join me as we try 2 sort a few things out
#livertwitter

Let's start with a real world scenario:

Your patient has cirrhosis with well controlled ascites, HE, and unfortunately comes in with MSK back pain from raucously cheering in vain 4 the Winnipeg Jets.
They ask for advice/treatment. In addition to stretching/PT, you recommend...

Although APAP OD is, @ lower doses it's safest analgesic
Speed limit=2-3g/d (I use 2g)
Wouldnt push it but take solace in:
Fig1: Tylenol tox=NAPQI>Glutathione (CYP2E1)
Fig2: Tho ppl assume cirrhosisglutathione, normal metabolism preserved
Fig3: 1 reason:cirrhosisCYP2E1

Patients with #cirrhosis often receive NSAIDs
This is prob ok in (short term) -ONLY IF they don’t have portal HTN

NSAIDs can
1. trigger diuretic resistance(fig1)
2. Provoke variceal bleed(fig2)
3. precipitate HRS(Throback2 https://twitter.com/ebtapper/status/1048894657852297217)
So:nsaids if ascites/varices

Actual recorded conversation:

Patient: tylenol isn't cutting it. What else do you have for me?
Data:

The time has come to address the elephant in the room: Opioids

1st, r they safe?
Fig1: Dame Sherlock gave morphine 2 ppl w/'impending HE' (BAD IDEA)
Fig2: But later study suggest NO EEG change s/p morphine
Fig3: Patwardhan showed that morph metabolism is PRESERVED in #cirrhosis

Face the facts: drug metabolism in #cirrhosis is COMPLICATED

#cirrhosis takes what u know about PK/PD & FLIPS THE SCRIPT (Fig1-2)

Think u know CYPP450? Wrong!
Each CYP varies w/stage, etiology, & the presence of cholestasis(Fig3)
How about glucuronidation? Jacked!(Fig4))

Morphine metabolism data hilights challenges in predicting the response & risks of anyin #cirrhosis

Don’t use opioids if you can avoid them. But sometimes u need em (e.g.fractures, hcc w/mets)
Start low/go slo. Choose med w/care.
Fig1: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/cld.711
Fig2: Thoughts

This brings me to #tramadol

Whenever I have used it, I found it led to resentment, encephalopathy, or both.

What's up?
Nothing better can be said about this drug that is variably converted 2 SNRI & opioid than was said by @DavidJuurlink: https://twitter.com/DavidJuurlink/status/921768456114135040

#cirrhosis and #tramadol

Review articles suggest it. But what evidence is cited for its safety/efficacy?
There is one study
Ref: https://www.ncbi.nlm.nih.gov/pubmed/18557166 
Fig1: Details about the pts enrolled are lacking
Fig2: W/o such data, the PK/PD data is

#cirrhosis & tramadol, part 2

The opioid effect of tramadol depends on CYP2D6
1. CYP2D6 activity varies widely @ baseline https://ascpt.onlinelibrary.wiley.com/doi/full/10.1038/sj.clpt.6100152
2. 2D6 activity may in ESLD (opioid effect, Fig1)
3. Then again, 2D6 may inHCC(Fig2)
Unpredictable @ getgo, ESLD makes it worse

Summary:
Tylenol (2g/d)
nsaids if ascites/varices
If u reach for an opioid: choose wisely, low/slo, constipation
Cirrhosis makes pain control challenging, but we cant shy away. We can all do better when managing pain for persons w/ #cirrhosis

Well this concludes a #tweetorial on pain control in #cirrhosis. Hope u enjoyed.
There's lots more to this topic of course but I hope it starts a productive conversation
Lots of opportunity to improve care for #livertwitter's allstars of PallCare (@nneka_ufere, @ArpanPatelMD)!