Liver problems are increasingly frequent in the U.S. and global populations [1]. Cirrhosis is chronic liver damage caused by different liver conditions, such as hepatitis and chronic alcoholism. Today, cirrhosis is a substantial public health problem, accounting for approximately 770,000 deaths annually, and, according to autopsy studies, affecting 4.5% to 9.5% of the global population [2]. Patients with both chronic and acute liver problems require special considerations due to their decreased ability to process certain drugs, including pain medication. 

Pain management in patients with cirrhosis remains a clinical challenge for health care professionals. Only a few prospective studies have offered an evidence-based approach to address it. However, certain recommendations have been developed in order to ensure the safety of pain medications administered.

In general, the greater the progression of liver dysfunction, the greater the impairment in drug metabolism. Patients with asymptomatic liver problems without cirrhosis do not have liver dysfunction, and their analgesic metabolism is similar to that of the general population and pain medications remain safe. 

In patients with end-stage liver disease but not cirrhosis (such as severe hepatitis), drug metabolism may be altered; thus, adverse events from analgesics may occur and the least effective minimal doses should be used in order to prevent any such occurrence.

Finally, patients suffering from cirrhosis must be very careful with pain medications. Indeed, the efficiency of drug removal by the liver relies on liver enzyme capacity, blood flow and plasma protein binding – all of which are compromised by cirrhosis. Severe complications from analgesia in patients with the most severe liver problems include hepatic encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding, which can eventually be lethal.

Such adverse events are avoidable with a careful pain medication administration regimen. Some guidelines have been developed [3] but remain heuristic for now [4].

In general, reduced dosage for acetaminophen remains a safe option for pain medication for patients with liver problems. Hepatologists tend to cautiously recommend 2 to 3 grams per day of acetaminophen [5].

In patients with cirrhosis, nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen) should be entirely avoided. This is primarily because of the risk of acute renal failure due to prostaglandin inhibition. However, there is also an increased risk of bleeding and the development of diuretic-resistant ascites [6].

Opiates should also be avoided or used sparingly, with low and infrequent dosing, to prevent precipitating encephalopathy. Patients with the slightest history of encephalopathy or substance abuse should also avoid opiates all together.

This said, however, an important caveat is that the care of patients with cirrhosis must be individualized. In practice, analgesic options may vary depending on a number of factors, such as nutritional status, adherence, renal function, and liver transplant candidacy [5].

With careful planning, the right pain medication can be administered in the right way in order to prevent the occurrence of any negative side effects in patients with liver problems. However, there remains a paucity of prospective studies that have assessed the safety of various analgesics in patients with advanced liver dysfunction. Such research is required in order to best optimize their method of administration and ensure safe and efficient pain management across settings.  

References

1. Cheemerla, S. & Balakrishnan, M. Global Epidemiology of Chronic Liver Disease. Clinical Liver Disease (2021). doi:10.1002/cld.1061
2. Lim, Y. S. & Kim, W. R. The Global Impact of Hepatic Fibrosis and End-Stage Liver Disease. Clinics in Liver Disease (2008). doi:10.1016/j.cld.2008.07.007
3. Analgesic use in adults with liver disease – UpToDate. Available at: https://www.uptodate.com/contents/image?imageKey=GAST%2F90196. (Accessed: 29th September 2022)
4. Imani, F., Motavaf, M., Safari, S. & Alavian, S. M. The therapeutic use of analgesics in patients with liver cirrhosis: A literature review and evidence-based recommendations. Hepatitis Monthly (2014). doi:10.5812/hepatmon.23539
5. Chandok, N. & Watt, K. D. S. Pain management in the cirrhotic patient: The clinical challenge. Mayo Clinic Proceedings (2010). doi:10.4065/mcp.2009.0534
6. Safe Usage of Analgesics in Patients with Chronic Liver Disease: A Review of the Literature. Available at: https://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/safe-usage-analgesics-patients-chronic-liver-disease-review. (Accessed: 29th September 2022)