Thread by @ebtapper, What's the deal with pain control in #cirrhosis?A #meded #tweetorial with QI [...]

What& #39;s the deal with pain control in #cirrhosis?
A #meded #tweetorial with QI undertones

Aims:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👍" title="Thumbs up" aria-label="Emoji: Thumbs up">Tylenol

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👎" title="Thumbs down" aria-label="Emoji: Thumbs down">NSAIDs (mostly)

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤯" title="Explodierender Kopf" aria-label="Emoji: Explodierender Kopf">Pharmacokinetics in ESLD

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔪" title="Küchenmesser" aria-label="Emoji: Küchenmesser">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

What& #39;s the deal with pain control in #cirrhosis?A #meded #tweetorial with QI undertonesAims:https://abs.twimg.com/emoji/v2/... draggable=

Tylenolhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="👎" title="Thumbs down" aria-label="Emoji: Thumbs down">NSAIDs (mostly)https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤯" title="Explodierender Kopf" aria-label="Emoji: Explodierender Kopf">Pharmacokinetics in ESLDhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🔪" title="Küchenmesser" aria-label="Emoji: Küchenmesser">TramadolIf this is a confusing topic for you, you are not alone!Join me as we try 2 sort a few things out #livertwitter" title="What& #39;s the deal with pain control in #cirrhosis?A #meded #tweetorial with QI undertonesAims:https://abs.twimg.com/emoji/v2/... draggable="false" alt="👍" title="Thumbs up" aria-label="Emoji: Thumbs up">Tylenolhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="👎" title="Thumbs down" aria-label="Emoji: Thumbs down">NSAIDs (mostly)https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤯" title="Explodierender Kopf" aria-label="Emoji: Explodierender Kopf">Pharmacokinetics in ESLDhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🔪" title="Küchenmesser" aria-label="Emoji: Küchenmesser">TramadolIf this is a confusing topic for you, you are not alone!Join me as we try 2 sort a few things out #livertwitter" class="img-responsive" style="max-width:100%;"/>

Let& #39;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

https://abs.twimg.com/emoji/v2/... draggable="false" alt="☠️" title="Totenkopf" aria-label="Emoji: Totenkopf">, @ lower doses it& #39;s safest analgesic
Speed limit=2-3g/d (I use 2g)
Wouldnt push it but take solace in:
Fig1: Tylenol tox=NAPQI>Glutathione (

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Augen" aria-label="Emoji: Augen">CYP2E1)
Fig2: Tho ppl assume cirrhosis

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">glutathione, normal metabolism preserved
Fig3: 1 reason:cirrhosis

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">CYP2E1

Although APAP OD ishttps://abs.twimg.com/emoji/v2/... draggable=

, @ lower doses it& #39;s safest analgesicSpeed limit=2-3g/d (I use 2g)Wouldnt push it but take solace in: Fig1: Tylenol tox=NAPQI>Glutathione (https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Augen" aria-label="Emoji: Augen">CYP2E1)Fig2: Tho ppl assume cirrhosishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">glutathione, normal metabolism preservedFig3: 1 reason:cirrhosishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">CYP2E1" title="Although APAP OD ishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="☠️" title="Totenkopf" aria-label="Emoji: Totenkopf">, @ lower doses it& #39;s safest analgesicSpeed limit=2-3g/d (I use 2g)Wouldnt push it but take solace in: Fig1: Tylenol tox=NAPQI>Glutathione (https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Augen" aria-label="Emoji: Augen">CYP2E1)Fig2: Tho ppl assume cirrhosishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">glutathione, normal metabolism preservedFig3: 1 reason:cirrhosishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">CYP2E1">

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:https://twitter.com/ebtapper/... class="Emoji" style="height:16px;" src=" https://abs.twimg.com/emoji/v2/... draggable="false" alt="🚫" title=""Betreten verboten!"-Zeichen" aria-label="Emoji: "Betreten verboten!"-Zeichen">nsaids if ascites/varices

https://twitter.com/ebtapper/status/1048894657852297217

Actual recorded conversation:

Patient: tylenol isn& #39;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/& #39;impending HE& #39; (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 any

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Tablette" aria-label="Emoji: Tablette">in #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:">https://aasldpubs.onlinelibrary.wiley.com/doi/full/... Thoughts

Morphine metabolism data hilights challenges in predicting the response & risks of anyhttps://abs.twimg.com/emoji/v2/... draggable=

in #cirrhosisDon’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/... Thoughts" title="Morphine metabolism data hilights challenges in predicting the response & risks of anyhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Tablette" aria-label="Emoji: Tablette">in #cirrhosisDon’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/... Thoughts">

This brings me to #tramadol

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

What& #39;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">https://twitter.com/DavidJuur...

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:">https://www.ncbi.nlm.nih.gov/pubmed/18... Details about the pts enrolled are lacking
Fig2: W/o such data, the PK/PD data is

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤷‍♂️" title="Achselzuckender Mann" aria-label="Emoji: Achselzuckender Mann">

#cirrhosis and #tramadolReview articles suggest it. But what evidence is cited for its safety/efficacy? There is one study Ref: https://www.ncbi.nlm.nih.gov/pubmed/18... Details about the pts enrolled are lackingFig2: W/o such data, the PK/PD data is https://abs.twimg.com/emoji/v2/... draggable=

" title=" #cirrhosis and #tramadolReview articles suggest it. But what evidence is cited for its safety/efficacy? There is one study Ref: https://www.ncbi.nlm.nih.gov/pubmed/18... Details about the pts enrolled are lackingFig2: W/o such data, the PK/PD data is https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤷‍♂️" title="Achselzuckender Mann" aria-label="Emoji: Achselzuckender Mann">">

#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.">https://ascpt.onlinelibrary.wiley.com/doi/full/... 2D6 activity may

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">in ESLD (

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">opioid effect, Fig1)
3. Then again, 2D6 may in

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">HCC(Fig2)
Unpredictable @ getgo, ESLD makes it worse

#cirrhosis & tramadol, part 2The opioid effect of tramadol depends on CYP2D61. CYP2D6 activity varies widely @ baseline https://ascpt.onlinelibrary.wiley.com/doi/full/... 2D6 activity may https://abs.twimg.com/emoji/v2/... draggable=

in ESLD (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">opioid effect, Fig1)3. Then again, 2D6 may inhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">HCC(Fig2)Unpredictable @ getgo, ESLD makes it worse" title=" #cirrhosis & tramadol, part 2The opioid effect of tramadol depends on CYP2D61. CYP2D6 activity varies widely @ baseline https://ascpt.onlinelibrary.wiley.com/doi/full/... 2D6 activity may https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">in ESLD (https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">opioid effect, Fig1)3. Then again, 2D6 may inhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">HCC(Fig2)Unpredictable @ getgo, ESLD makes it worse">

Summary:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👍" title="Thumbs up" aria-label="Emoji: Thumbs up">Tylenol (2g/d)

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👎" title="Thumbs down" aria-label="Emoji: Thumbs down">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🚫" title=""Betreten verboten!"-Zeichen" aria-label="Emoji: "Betreten verboten!"-Zeichen">nsaids if ascites/varices
If u reach for an opioid: choose wisely, low/slo,

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🚫" title=""Betreten verboten!"-Zeichen" aria-label="Emoji: "Betreten verboten!"-Zeichen">constipation
Cirrhosis makes pain control challenging, but we cant shy away. We can all do better when managing pain for persons w/ #cirrhosis

Summary: https://abs.twimg.com/emoji/v2/... draggable=

Well this concludes a #tweetorial on pain control in #cirrhosis. Hope u enjoyed.
There& #39;s lots more to this topic of course but I hope it starts a productive conversation
Lots of opportunity to improve care for #livertwitter& #39;s allstars of PallCare (

https://abs.twimg.com/emoji/v2/... draggable="false" alt="👀" title="Augen" aria-label="Emoji: Augen">@nneka_ufere, @ArpanPatelMD)!

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