Management of pain in patients with advanced chronic liver disease or cirrhosis
- James P Hamilton, MD
James P Hamilton, MD
- Assistant Professor of Medicine
- Johns Hopkins University School of Medicine
- Eric Goldberg, MD
Eric Goldberg, MD
- Associate Professor of Medicine
- University of Maryland School of Medicine
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
- Section Editor
- Bruce A Runyon, MD
Bruce A Runyon, MD
- Section Editor — Cirrhosis and Its Complications
- Clinical Professor of Medicine
- University of New Mexico, Division of Gastroenterology and Hepatology
- Special Hepatology Consultant to the Indian Health Service
- Northern Navajo Medical Center, Shiprock, New Mexico
Patients with liver disease may develop acute or chronic pain from a variety of causes. In addition to causes common in the otherwise healthy population, those with advanced liver disease may have ascites (leading to abdominal and lower back pain) and gynecomastia (leading to mastalgia).
Management of pain in patients with liver disease raises special concerns. The choice of appropriate analgesic agents requires a thorough understanding of their pharmacokinetic and side effect profiles (table 1).
As a general rule, patients with mild liver disease can be treated with a similar choice of drugs as those who are otherwise healthy. Susceptibility to adverse effects increases with worsening liver function due to altered pharmacokinetics and hemodynamic changes. (See "Tests of the liver's capacity to transport organic anions and metabolize drugs".)
The exact cutoff at which drug doses and the selection of drugs should be altered is uncertain. Modifications of drug-prescribing should generally be considered in patients who have developed advanced chronic liver disease (eg, bridging fibrosis on biopsy) or cirrhosis, particularly when accompanied by portal hypertension (such as those with esophageal varices, ascites, or portal gastropathy/colopathy) or renal insufficiency. Important exceptions are patients who are actively drinking alcohol and those on multiple medications, who can develop severe hepatotoxicity from concomitant use of acetaminophen regardless of the severity of liver disease.
This topic review will summarize safety considerations of nonselective nonsteroidal antiinflammatory drugs (NSAIDs), selective NSAIDs (COX-2 inhibitors), opioids, acetaminophen, and agents for neuropathic pain in patients with advanced chronic liver disease or cirrhosis. The recommendations regarding analgesic use in patients with advanced chronic liver disease are also summarized in the accompanying table (table 1). A general approach to patients with cirrhosis is presented separately. (See "Cirrhosis in adults: Overview of complications, general management, and prognosis".)
- De Lédinghen V, Heresbach D, Fourdan O, et al. Anti-inflammatory drugs and variceal bleeding: a case-control study. Gut 1999; 44:270.
- Zipser RD, Hoefs JC, Speckart PF, et al. Prostaglandins: modulators of renal function and pressor resistance in chronic liver disease. J Clin Endocrinol Metab 1979; 48:895.
- Boyer TD, Zia P, Reynolds TB. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology 1979; 77:215.
- Wong F, Massie D, Hsu P, Dudley F. Indomethacin-induced renal dysfunction in patients with well-compensated cirrhosis. Gastroenterology 1993; 104:869.
- Bosch-Marcè M, Clària J, Titos E, et al. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology 1999; 116:1167.
- Clària J, Kent JD, López-Parra M, et al. Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites. Hepatology 2005; 41:579.
- Tegeder I, Lötsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet 1999; 37:17.
- Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc 2010; 85:451.
- Mazoit JX, Sandouk P, Zetlaoui P, Scherrmann JM. Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects. Anesth Analg 1987; 66:293.
- Crotty B, Watson KJ, Desmond PV, et al. Hepatic extraction of morphine is impaired in cirrhosis. Eur J Clin Pharmacol 1989; 36:501.
- Hasselström J, Eriksson S, Persson A, et al. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol 1990; 29:289.
- Tegeder I, Geisslinger G, Lötsch J. [Therapy with opioids in liver or renal failure]. Schmerz 1999; 13:183.
- Klotz U, McHorse TS, Wilkinson GR, Schenker S. The effect of cirrhosis on the disposition and elimination of meperidine in man. Clin Pharmacol Ther 1974; 16:667.
- Pond SM, Tong T, Benowitz NL, et al. Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects. Clin Pharmacol Ther 1981; 30:183.
- Haberer JP, Schoeffler P, Couderc E, Duvaldestin P. Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis. Br J Anaesth 1982; 54:1267.
- Physican's desk reference electronic library. Thomson. 2003.
- Novick DM, Kreek MJ, Arns PA, et al. Effect of severe alcoholic liver disease on the disposition of methadone in maintenance patients. Alcohol Clin Exp Res 1985; 9:349.
- Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther 2013; 37:1132.
- Benson GD. Acetaminophen in chronic liver disease. Clin Pharmacol Ther 1983; 33:95.
- Zimmerman HJ, Maddrey WC. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology 1995; 22:767.
- Kuffner EK, Dart RC, Bogdan GM, et al. Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2001; 161:2247.
- Parfieniuk A, Flisiak R. Role of cannabinoids in chronic liver diseases. World J Gastroenterol 2008; 14:6109.
- Hézode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 2005; 42:63.
- Hézode C, Zafrani ES, Roudot-Thoraval F, et al. Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology 2008; 134:432.
- Ishida JH, Peters MG, Jin C, et al. Influence of cannabis use on severity of hepatitis C disease. Clin Gastroenterol Hepatol 2008; 6:69.
- Kelly EM, Dodge JL, Sarkar M, et al. Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/Hepatitis C Virus-coinfected Women. Clin Infect Dis 2016; 63:512.
- Brunet L, Moodie EE, Rollet K, et al. Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis. Clin Infect Dis 2013; 57:663.