Analgesia for the cirrhotic patient: A literature review and recommendations

Abstract

The choice of analgesic agent in cirrhotic patients is problematic and must be individualized taking into account several factors including severity of liver disease, history of opioid dependence, and potential drug interactions. With a cautious approach including slow dose up-titration and careful monitoring, effective analgesia can be achieved in most cirrhotic patients without significant side effects or decompensation of their liver disease. Paracetamol is safe in patients with chronic liver disease but reduced doses of 2-3 grams daily is recommended for long-term use. Non-steroidal anti-inflammatory drugs are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Opioids have an increased risk of toxicity particularly in patients with hypoalbuminaemia, and immediate-release as opposed to controlled-release formulations are advised. Co-prescription of laxatives is mandatory to avoid constipation and encephalopathy. Adjuvant analgesics such as tricyclic antidepressants and anti-convulsants may be used cautiously for cirrhotic patients with neuropathic pain. Gabapentin or pregabalin may be better tolerated in cirrhosis because of non-hepatic metabolism and a lack of anticholinergic side effects.

The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis

“…NSAIDs can also cause new-onset ascites in patients with compensated cirrhosis or makes it difficult to control existing ascites. As a rule, NSAIDs should be used cautiously in patients with cirrhosis (2). …”

“…Although analgesic are commonly used and can affect the natural course of disease in patients cirrhosis, there are few recommendations regarding the proper use of analgesics in this population (234). To our knowledge, there are only a few reports such as physician opinions or prescription patterns related to analgesics and these reports were based on the survey of a small number of patients (56).…”

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

“…Interestingly, the renal synthesis of prostaglandin E2 is increased in cirrhotics to counteract the water-retaining effect of AVP and hence Non Steroid Anti-Inflammatory Drugs may worsen the renal excretion of solute-free water in these patients [14,15] . As previously stated, the clinical consequence of solute-free water excretion impairment is the development of hyponatremia.…”

Perioperative Risk Assessment and Management of Cirrhotic Patients

“…Induction agents, with the exception of ketamine and propofol, decrease HBF [63,149] without a change in clearance [140]. Care should be taken with benzodiazepines and paralytics, due to a reduction in both CYP-3A4 metabolism and PBP resulting in prolonged duration [1,[140][141][142]144,147,150,151], whereas atracurium, lorazepam, oxazepam, and temazepam undergo non-hepatic conjugation [140,152]. Opioids in LC have significantly reduced metabolism [141,147,153] and prolonged half-lives, potentially exaggerating sedative and respiratory depressant effects, in contrast to fentanyl [1,141,147].…”

“…Although the uptake and onset of anesthetic drug action is unaffected, hepatic clearance is dependent upon volume of distribution, functional hepatic blood flow (HBF), hepatic extraction ratio, hepatic microsomal and cytochrome-P450 enzyme activity, decreased plasma-binding proteins (PBP), and decreased biliary excretion (Table 3) [63, [140][141][142][143][144][145][146][147]. In general, short to intermediate halflive drugs at lower doses with longer dose intervals should be used [140,141].…”