The Link Between Acute Liver Failure And Bariatric Surgery

M M
on 11/12/12 3:29 pm

 

Tylenol, a no-no after gastric bypass?  Maybe.  Down the road, if confirmed in future large study -

Screen Shot 2012-11-11 at 8.40.24 AM
 

Among patients with acetaminophen-induced acute liver failure (ALF), bariatric surgery was 25 times more common than in the general population.

This is slightly terrifying to me, a nearly nine-year roux-en-y patient who left the bariatric surgery hospital taking acetaminophen melted in a one-ounce dose cup of warm water.  I have depended on Tylenol caplets, capsules and liquids for nine years along with my re-routed-intestines husband who also depends on the stuff for aches and pains. 

Those who DRINK alcohol BE WARNED.

Wikipedia -

Paracetamol INN (play /ˌpærəˈstəmɒl/ or /ˌpærəˈsɛtəmɒl/), or acetaminophen USAN Listeni/əˌstəˈmɪnəfɨn/, chemically named N-acetyl-p-aminophenol, is a widely used over-the-counter analgesic(pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, paracetamol can also be used in the management of more severe pain such as post-surgical pain and providing palliative care in advanced cancer patients.[4] The onset of analgesia is approximately 11 minutes after oral administration of paracetamol,[5] and its half-life is 1–4 hours. Though acetaminophen is used to treat inflammatory pain, it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity.

While generally safe for use at recommended doses (1,000 mg per single dose and up to 4,000 mg per day for adults),[6] acute overdoses of paracetamol can cause potentially fatal liver damage and, in rare individuals, a normal dose can do the same; the risk may be heightened by chronic alcohol abuse, though it is lessened by contemporary alcohol consumption.Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand

We depend on acetaminophen because We Have Been Trained Not To Touch NSAIDS!  What then if acetaminophen is off the table for use?  What do we use for over the counter pain medication?  It's hard enough that pain medications after gastric bypass DO NOT WORK THE SAME and it is hard to find something that TAKES THE EDGE OFF OF any pain.  Even just something as simple as menses and cyst pain is not touched by NSAIDS (not that I would know, I promise... a little) or acetaminophen. 

Screen Shot 2012-11-11 at 9.03.16 AM
 

What do we do when there are no options?

Sigh.

American Association for the Study of Liver Diseases (AASLD)

Among patients with acetaminophen-induced acute liver failure (ALF), bariatric surgery was 25 times more common than in the general population.

Tylenol
Researchers at California Pacific Medical Center (CPMC) reported an alarming rate of bariatric surgery among patients with ALF from acetaminophen poisoning.  They studied 101 patients with ALF between 2009 and 2011, of whom 54 had acetaminophen-induced ALF. Of those 54 patients 9 – or 16.7 percent – had prior bariatric surgery, as compared to none of the 47 patients with ALF from other causes. The prevalence of bariatric surgery in the American population is approximately 0.66 percent.

When asked about the large percentage of patients with acetaminophen-induced ALF who had bariatric surgery, Dr. Edward Holt said, "While it is possible that this percentage could be lower in a study with a larger sample size, it is not likely that a difference this large would disappear.  To the best of our knowledge, this is the first report of bariatric surgery in acetaminophen-induced ALF."

In the United States more than one million adults between the ages of 18 and 75 years have had bariatric surgery. "If these patients are predisposed to liver injury from acetaminophen, then clinical management and drug advertising should immediately be updated to reflect this risk," said Dr. Holt.

When asked about future directions of research in this area, Dr. Holt said "We would like see these findings reproduced in a larger, multi-center study, and we want to look at the pharmacokinetics of acetaminophen in patients with and without bariatric surgery."

The CPMC researchers called attention to previously reported associations between bariatric surgery and suicide, and between alcohol abuse and acetaminophen-induced ALF.  They showed that patients in their study with prior bariatric surgery and acetaminophen-induced ALF did not have higher rates of depression, alcohol abuse, or intent to cause self-harm when compared to patients with other causes of ALF.

The authors concluded that prior bariatric surgery may place patients at higher risk for acetaminophen poisoning, similar to the increased risk seen in patients who chronically abuse alcohol.  "Patients with chronic alcohol abuse who take 4 grams of acetaminophen each day can inadvertently poison themselves and even develop acetaminophen-induced ALF.  Based on our results, we suspect that bariatric surgery may also render patients more susceptible to acetaminophen-induced liver injury.  However, before an official warning is issued further research should be conducted." concluded Dr. Holt.

CONTROL ID: 1423621
PRESENTATION TYPE: Oral or Poster
CURRENT CATEGORY: Acute Liver Failure and Artificial Liver Support
CURRENT DESCRIPTORS: A01. Acute Liver Failure and Artificial Liver Support
TITLE: Prior Bariatric Surgery Increases the Risk of Acute Liver Failure from AcetaminophenPoisoning
AUTHORS (FIRST NAME, LAST NAME): Edward W. Holt1, Timothy J. Davern1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Department of Transplantation, Division of Hepatology, California Pacific Medical Center, San Francisco, CA, United States. 

ABSTRACT BODY: Background: Bariatric surgery (BS) is an effective therapy for morbid obesity, a major public health problem in the U.S. Previous reports suggest that following BS, higher peak serum concentrations of ethanol (ETOH) after a challenge, and a higher rate of suicide compared to matched controls are observed. We hypothesized that prior BS might also predispose patients to an increased risk of acetaminophen (APAP)-related liver injury.

Purpose: To report the prevalence of BS in a cohort of patients with APAP-induced acute liver failure (APAP-ALF) and to compare this to both the prevalence among patients with non APAP-ALF and to the estimated national prevalence of BS. Differences between groups were compared using Fischer’s exact test, chi-square test and Student’s t-test.

Methods: Patients with ALF were prospectively identified between 2009 and 2011 using standard criteria (Larson et al. Hepatology 2005). The population prevalence of BS was estimated from the published literature, including the National Hospital Discharge Survey.

Results: 101 patients with ALF were identified; 54 with APAP-ALF and 47 with non APAP-ALF. 9 of 54 (16.7%) with APAP-ALF had prior BS (8 roux-en-Y gastric bypass; 1 duodenal switch, mean 5.9 (±2.8) years before presentation) compared to 0 of 47 with non APAP-ALF (p=0.003). The prevalence of BS in the APAP-ALF cohort was roughly 30-fold higher than the estimated prevalence (0.5%) in the general U.S. population (p = 0.0001). In the APAP-ALF cohort there were no differences in age, gender or need for liver transplantation between patients with and without prior BS (p>0.05 for all), but the group with prior BS had a lower prevalence of depression and ETOH abuse (p=0.04 and p=0.03, respectively). Importantly, BS patients did not have a higher rate of intent to self-harm (22.2% with prior BS vs. 35.6% without prior BS, p=0.4). In the APAP-ALF cohort, no patients with prior BS died compared to 8 patients (17.8%) without prior BS (p=0.16).

Conclusions: In a cohort of patients with ALF the prevalence of prior bariatric surgery was dramatically higher in patients with APAP-ALF compared to non APAP-ALF patients and to the general U.S. population. Importantly, patients with APAP-ALF and BS in our cohort did not have a higher incidence of depression, ETOH abuse or intentional overdose than in APAP-ALF patients without BS. These data suggest that bariatric surgery is a risk factor for severe liver injury from APAP.

This novel finding, if confirmed in a larger multi-center cohort, should lead to specific warnings for APAP use in bariatric patients similar to those already in place for patients who drink excessive alcohol.


 

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CarolF3
on 11/12/12 3:35 pm - Albany, NY
RNY on 12/17/12

Glad I don't drink alcohol. 

So, then what would be considered safe to take after surgery if Liquid or otherwise other ways of Tylenol have this link?

Carol

Cicerogirl, The PhD
Version

on 11/12/12 3:48 pm - OH
That pretty much just leaves us with prescription pain meds.

Lora

 6 years out and maintaining 190 pounds lost!  

“You don't drown by falling in the water.  You drown by staying there.”

 

Cicerogirl, The PhD
Version

on 11/12/12 3:48 pm - OH
It doesn't surprise me at all that the incidence is much higher in bariatric surgery patients since almost everyone I know who has NOT had RNY uses NSAIDs far more than Tylenol. WE are the ones *****ly on Tylenol. (Well, not me... It has never touched any kind of pain I have ever had for any reason so I don't waste my time.)

Perhaps another reason for people to consider VSG...

Thanks for sharing. I have several friends who take a lot of acetaminophen who should see this.

Lora

 6 years out and maintaining 190 pounds lost!  

“You don't drown by falling in the water.  You drown by staying there.”

 

noftessa0401
on 11/13/12 9:42 am - San Diego, CA
RNY on 12/27/12

Tylenol has never helped me no matter what kind of pain I've had.  Sucks.

HW: 274 | SW: 232 | CW: 137 | Goal: 145 (ticker includes a 42 pound loss pre-op) | Height: 5'4"

M1: -24 (205) | M2: -14 (191) | M3: -11 (180) | M4: -7 (173) | M5: -7 (166) | M6: -8 (158) | M7: -11 (147) | M8: -2 (145) | M9: -3 (142) | M10: -2 (140) | M11: -4 (136) | M12: -2 (134) | M13: -0 (134) | M14: -3 (131) | M15: +4 (135) | M16: +2 (137)

jiaguy
on 11/12/12 3:58 pm, edited 11/12/12 3:59 pm
RNY on 10/03/12

Tylenol is metabolized in the liver, as a drug it is very toxic beyond a certain daily dose (and your liver's ability to process it). I would possibly believe that a increased amount is absorbed due to lack of stomach acids. 

Look up the molecular structure of tylenol and Phenacetin (Removed off the market due to renal toxicity). Phentacin is metabolized into tylenol in a first pass through the liver and tylenol, without being modified by the liver is likely toxic. Once your body cannot metabolize anymore you start on your liver. Watch how much total tylenol you take on a day to day basis it used to be 3grams max ( but i understand that has been lowered?)

SarahLee1969
on 11/12/12 4:03 pm - NY
Ill have to double check but it says post RNY patients who consume alcohol and take 4gms of acetominophin... I recall the max daily dosage being 2gms...
Either way, I will, as always try to reserve medications for only when I feel I REALLY need it. I rarely use acetaminophen other than for a fever. Im very fortunate I do not have any serious aches and pains!
(deactivated member)
on 11/12/12 4:20 pm
RNY on 08/31/12 with

Thank you for your posting. I'm going to talk to my surgeon about this in January at my next visit. I had to go off of my higher dose of Meloxicam prior to surgery. It was a wonderful drug for my chronic back, foot, neck, and arthritis issues. I've been using half doses of Vicodin 5/500's once or twice a day to take the edge off. The surgery did help considerably with the nerve/bone issues in my foot but my back is a bear still. Surgeon said only the RNY would help the back because more weight needs to be gone to relieve the pain. I still have about 35 lbs to go but I strongly feel that I'll need long term pain management (mild-moderate) and don't ever want to make the mistake of getting too much acetaminophen. Luckily, I'm a non-drinker.

julia_b5
on 11/12/12 4:38 pm
Tylenol is a risk for everyone. Many pre-op RNY patients already show signs of fatty liver disease so I wonder if they see a trend with people who are morbidly obese that don't have surgery. My surgeon puts in all his paperwork RNY with possible liver biopsy in case it looks like your liver is already diseased he can check it while he's in there.
Citizen (USA & Brit)
Kim

on 11/12/12 4:39 pm, edited 11/12/12 4:42 pm - Castle Rock, CO

Basic pharmacology being part of my degree a gazillion years ago, I would NEVER take Tylenol on a daily basis - none of this information is new and anyone needing regular pain relief should seriously consider what surgery they propose having.

If we already have an RNY,  and we need to manage our pain on a daily basis, we need to be doing it in a much safer way than daily Tylenol!!!

   10 years post RNY

Success - one day at a time    

Proud Feminist, Atheist, LGBT friend, and Socialist Liberal 

Want to join the new R&R 3.0?    PM me for an invite!

M M
on 11/12/12 4:57 pm

I would reconsider taking any pain meds at this point.  "Do I REALLY need this?"

Dolores L.
on 11/12/12 7:08 pm - FL
Revision on 08/14/12
Occasional, low dose use of acetaminophen shouldn't put an otherwise healthy post-bariatric patient at risk. As a general rule of thumb, for adults, the max daily dose is 75 mg/kg/24 hrs up to 4gm/24 hrs, but that shouldn't be taken on a regular basis either.

APAP is not a benign drug. Many healthcare providers don't think it should be OTC, and I've gone back and forth with how I feel about it. Whatever the med, use the lowest dose possible to treat the problem. And bottom line, if you don't need it, don't take it. Those of us who are s/p WLS have to be especially careful of everything we put in our mouth, right?

         

        
BugdocMom
on 11/12/12 8:17 pm - CA
RNY on 05/31/11 with

Many studies have shown that oral medications are absorbed at different rates and amounts in bypass folks than in "regular" people. Most are absorbed at a faster rate but a lower amount. However, acetaminophen is absorbed by bypass patients at almost twice the efficiency as in normal folks. These absorption differences can pose a lot of problems since the guidelines for safe dosing come from studies in unaltered systems AND since so many drugs simply haven't been examined in bypass patients. I happened to just run across this paper (below) last night while doing some research to give to my Orthopedic surgeon to help him understand which meds and dosages to consider for my upcoming hip replacement. My major concerns were 1. Opioids seem to hit quickly and wear off almost as quickly and require MUCH higher doses than pre-op (they used to knock me flat out but post-op barely touch the pain-- unfortunately, despite all the anecdotal evidence that we absorb them differently, I have not found any studies investigating opioid absorption after bypass) and 2. oral Warfarin and Coumadin (blood thinners) don't work well for bypass patients so injectable thinners will need to be used. During my research, I was surprised to see that tylenol is absorbed at 100% higher efficiency in bypass folks. This scared the crap out of me since I have been taking narcotics with APAP quite a bit recently and was already concerned about my acetaminophen intake IF I absorbed it like a normal person. Yikes!

Anyway, the increased acetaminophen absorption rate and levels have been shown in multiple studies and we know alcohol is also metabolized differently in bypass patients so I am not surprised that studies are now seeking to tie increased risk of  liver failure to bypass. I am sure more investigations into other drugs would show many have the ability to contribute to the increased risk. 

This is a review of several studies and below is a part about acetaminophen absortion:

Drug Therapy-Related Issues
in Patients *****ceived
Bariatric Surgery by Chan 2010

 

Acetaminophen absorption
kinetics, a marker to estimate gastric emptying
rate, was performed in a study of patients who underwent
gastrectomy for malignancy. In these patients, an
esophageal jejunostomy was constructed using the
Roux-en-Y technique. The results showed that the rate
of acetaminophen absorption (administered as oral
powder, mixed with a liquid meal) was significantly
shortened in patients receiving this procedure, compared
with healthy subjects (14). This observation was
confirmed in our recently completed study in obese
patients *****ceived RYGB. Acetaminophen kinetics
were determined preoperatively, as well as 3 months
and 1 year after surgery. Acetaminophen was administered
as oral liquid. We found that the mean peak
acetaminophen concentration was nearly doubled (p < 0.01) following RYGB, and the mean time to peak
concentration was significantly shortened, from about
45 minutes to around 10 minutes in both postoperative
study visits (15).

 

14. Ueno T, Tanaka A, Hamanaka Y, et al. Serum drug concentrations
after oral administration of paracetamol to patients with surgical
resection of the gastrointestinal tract. Br J Clin Pharmacol.
1995;39(3):330-2.
15. Chan, L-N, Lin YS, Horn, JR, et al. The Effect of Proximal Rouxen-
Y Gastric Bypass Surgery on Upper Gastrointestinal Transit
Time: A Pilot Study. [Abstract]. J Parentr Ent Nutr (JPEN)
2010;34(2).

Dolores L.
on 11/13/12 4:02 am - FL
Revision on 08/14/12

You can always have a blood level drawn if you were curious. But sounds like we need to stick to half as much as what would be recommended for non WLS patients, just to be safe. Good to know. I'm going to ask my surgeon what he thinks about this study when I see him next month.

         

        
BugdocMom
on 11/13/12 9:42 am - CA
RNY on 05/31/11 with

Yes, I will certainly restrict my intake while I am navigating this hip replacement.

You may find that your surgeon has no idea about this study. There seems to be a huge disconnect between practicing bariatric surgeons and active researching surgeons. If your surgeon knows you are keeping up with the literature, it may provide the much needed impetus to get involved with the current literature again (if he is not already-- if he is, that's wonderful!).

Dolores L.
on 11/13/12 3:31 pm - FL
Revision on 08/14/12

He may know something about it. Or he may assign me to find out more, LOL!! He runs the program in Bariatrics at University of South Florida. They are actively involved in research and teaching, so he's pretty up on his stuff. His NP is also great about sharing what they are studying. 

         

        
Cicerogirl, The PhD
Version

on 11/13/12 12:42 pm - OH

Odd about the blood thinners... I have been on Coumadin almost continuously since 1979 and have been on the same dose for about 10 years.  My dose did not change after my RNY (although it is more subject to brief variations based on my food choices).

 

Lora

 6 years out and maintaining 190 pounds lost!  

“You don't drown by falling in the water.  You drown by staying there.”

 

cajungirl
on 11/13/12 6:27 am

This doesn't surprise me at all.  It's known even amongst the non-WLS community that too much Tylenol will tax the liver.  Since we aren't allowed NSAIDS, Tylenol is what is usually recommended for common pains.  It's not meant to be taken long-term for anyone.

I am not worried about it for me I probably haven't taken more than 8-10 tylenol in the 7 years since surgery.  I have taken Alieve about 3 times (under doctors orders)......I just don't have many ailments that require medications (THANKFUL I AM).

Proximal RNY Lap - 02/21/05

 9 years committed ~  100% EWL and Maintaining

www.dazzlinglashesandbeyond.com

 

M M
on 11/13/12 6:44 am

I think when I pass - they'll do an autopsy and find a tumor filled with Tylenol, Splenda and anti-epileptic medications.

cajungirl
on 11/13/12 6:49 am

LOL Beth, now Splenda is a different story.  I'm sure I use way to much Splenda.

Proximal RNY Lap - 02/21/05

 9 years committed ~  100% EWL and Maintaining

www.dazzlinglashesandbeyond.com