Pain management in the cirrhotic patient: the clinical challenge

Abstract

Pain management in patients with cirrhosis is a difficult clinical challenge for health care professionals, and few prospective studies have offered an evidence-based approach. In patients with end-stage liver disease, adverse events from analgesics are frequent, potentially fatal, and often avoidable. Severe complications from analgesia in these patients include hepatic encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding, which can result in substantial morbidity and even death. In general, acetaminophen at reduced dosing is a safe option. In patients with cirrhosis, nonsteroidal anti-inflammatory drugs should be avoided to avert renal failure, and opiates should be avoided or used sparingly, with low and infrequent dosing, to prevent encephalopathy. For this review, we searched the available literature using PubMed and MEDLINE with no limits.

FIGURE 1.

Acetaminophen metabolism. At therapeutic doses, 90% of acetaminophen is metabolized to glucuronide and sulfate compounds and ultimately excreted via the renal system. Of the remaining acetaminophen, 50% is excreted unchanged in the urine, and the remainder is metabolized by the cytochrome P450 system; a hepatotoxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), is subsequently produced. Hepatic glutathione conjugates with NAPQI to produce nontoxic metabolites that are renally excreted. With a toxic ingestion of acetaminophen, the glucuronidation and sulfation pathways become overwhelmed, and glutathione stores diminish, resulting in hepatocyte necrosis due to NAPQI.

FIGURE 2.

A pharmacological approach to analgesia in patients with cirrhosis who have no renal failure, active alcoholism, or active substance abuse. Starting doses are used unless otherwise indicated. Doses should be carefully titrated as tolerated. Minimize total acetaminophen to less than or equal to 2 to 3 g/d. Avoid polypharmacy and monitor for adverse drug events.