Analgesia for Cirrhotics: A Practical Approach

November 20, 2008

liver.jpgCommentary by Albert B. Knapp MD, NYU Clinical Professor of Medicine (Gastroenterology)

THE CASE:
WS, a 49 yo year old Caucasian male with a known 35 year history of alcohol abuse, now presents with jaundice, tense ascites and a left shoulder fracture following a bar room brawl last night. He is admitted to the orthopedic service for elective pinning but is presently in great pain. You are consulted in regards to pain management….

THE QUESTION:
How should you approach the use of analgesia in patients with cirrhosis?

DISCUSSION:
The medical management of the cirrhotic patient is commonly fraught with peril and problems. Pain is a common complaint that ranges from a minor hindrance to a major impairment. The question of how and when to administer analgesia is a frequent and lively topic of ward management rounds.

Cirrhotic patients have a host of important problems that make straightforward analgesia potentially risky. These include profound impairments in synthetic and detoxification capacities, variable degrees of portal hypertension with resultant varices formation, frequent but sometimes subtle maldigestion and malabsorption, variable acute & and chronic mental status changes, and the omnipresent threats of pulmonary (hepatopulmonary syndrome, HPS) and renal compromise (hepatorenal syndrome, HRS).

The first clinical point to make is to assess the true extent of pain. The more intense the pain, the more powerful the analgesia required. One should always institute initial therapy with the mildest of medications and progress up the ladder of intensity analgesic strength should symptoms persist. Potential side effects vary by analgesic class but usually revolve around mental or hemodynamic status changes. This dovetails into clinical point number two, namely, to expect the unexpected.

The most efficacious way to think about analgesic agents is by class: The three most frequently used classes are acetaminophen (Tylenol, paracetamol), NSAIDs, and narcotics. I will also briefly discuss certain “crossover” compounds as well as non-classified drugs.

Tylenol (at low doses of 325mg PO every 4-6 hours) is eminently safe and bereft of any major CNS, hepatic, or hemodynamic side-effects. The medication is readily metabolized even in the most compromised of cirrhotic livers and no discernable changes in mental, portal, pulmonary or renal status are generally detected. Tylenol is a preferred analgesic, but unfortunately is too mild to meet the needs of most patients. “Extra strength” Tylenol (usually 650 mg per pill) must be used with caution as no patient with cirrhosis should receive more than 5-6 grams of Tylenol in a 24 hour period as this cumulative dose can result in sub-acute or even acute hepatic injury.

NSAIDs as a class offer far more relief than Tylenol but the potential side effects warrant careful thought. NSAIDs result in a host of metabolic changes including severe fluid retention, systemic and possibly portal hypertension, cytotoxic gastrointestinal mucosal injury as well as pronounced decreases in gastrointestinal and renal blood flow. To complicate matters, these effects are not always dose-dependent. Intravenous NSAIDs such as Toradol are very effective in acute situations but have significant gastric mucosal and hemodynamic complications. They are contraindicated for patients with chronic pain issues. Cirrhotics given NSAIDs must be carefully monitored and the need for these medications frequently re-assessed. As a rule, patients should be started concomitantly on either an H2-receptor antagonist or PPI to mitigate gastric mucosal damage and to thwart bleeding. Serum creatinine levels as well as a CBC should be performed on a daily basis. A small but reversible rise in serum creatinine is not unexpected while on therapy.

Narcotics are the most efficacious analgesics available and their major side effects are limited to mental status changes, constipation and hypotension. The first two are frequent and severe and hence preclude frequent use: Narcotics easily pass the blood-brain barrier and exacerbate underlying mental status changes. Constipation may result in an increased serum protein load with resultant CNS toxicity and frequently requires concomitant neomycin, lactulose or other cathartics for relief. Symptomatic hypotension is rare but readily manageable with IV fluids.

What about the combination class analgesics such as Tylenol with Codeine (Tylenol#3)? They are certainly effective and are used readily. Simply apply all pertinent rules and warnings for both classes when ordering.

Finally, let’s consider the use of a relatively novel agent, namely Neurontin (Gabapentin). Its true mode of action and metabolism are still open to debate but this has not stopped physicians from prescribing it. Its major side effects in healthy patients treated for post-herpetic neuralgia are asthenia and pronounced somnolence. Drug-mediated acute hepatitis has been described but is rare. Given the lack of safety data for cirrhotics and the plethora of already vetted analgesic agents, I personally deprecate their use.

In summary, the approach to analgesia in the cirrhotic population should be cautious, practical and incremental. Frequent monitoring and prompt discontinuation of the analgesic usually results in early detection and rapid resolution of untoward side effects. But again, remember to expect the unexpected…

THE ANSWER:
After performing both a thorough history and physical examination emphasizing prior medication usage/reactions as well as the extent of underlying liver and/or CNS disease, AND reviewing the patients admission blood & radiographic studies (CBC, SMA-20), INR, amylase/lipase levels, serum ammonia (if applicable) and CXR, I would have started the patient on Tylenol #3.

What is your opinion? Let me know….. albert@knappmd1.com

4 Responses to Analgesia for Cirrhotics: A Practical Approach

  1. gene frunkin on November 24, 2008 at 11:04 pm

    There are a number of points relevant to this case which need to be made:

    1) Someone with history of alcoholism, jaundice tense ascites and recent alcohol intake has alcoholic hepatitis and surgery should be avoided unless required to be life saving. There would be a great chance of liver failure occurring after surgery/anesthesia in this patient;

    2) NSAIDS are contraindicated in cirrhotics because of decreased renal blood flow and ensuing hepatorenal syndrome;

    3) hepatopulmonary syndrome does not enter into the choice of analgesia;

    4) extrastrength tylenol has 500 mg of tylenol and not 650mg

    In brief, the simple answer is that cirrhotics can be treated for pain like non cirrhotics except no NSAIDS.

  2. siham abdulreim on October 1, 2009 at 10:12 am

    In cirrhotics ,spinal anaethesia is better than systemic;I agree tylenol is better not NSAIDS

  3. George Butel on March 7, 2010 at 2:21 pm

    Someone who has been abusing alcohol–and who knows what else, it’s probably not going to be in your clinical history–for 35 years doesn’t sound like his mind is functioning that well to begin with. You overlook the likelihood of him taking one Tylenol, and then another, and then forgetting about the first two, and so on, as well as the probability that he is still using alcohol. ER admissions each year due to acetaminophen toxicity among those WITHOUT pre-existing liver conditions is astounding. I cannot imagine that you would allow the patient to go within 6 feet of a bottle of Tylenol. I don’t allow acetaminophen in my house.

  4. Reham on January 20, 2014 at 8:25 am

    Can i use paracetamol 2gram per day in a cirrhotic patient or not thanks

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