title: The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations.
abstract: BACKGROUND
  Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs.
  
  
  METHODS
  An indexed MEDLINE search was conducted in July 2014, using keywords "analgesics", "hepatic impairment", "cirrhosis", "acetaminophen or paracetamol", "NSAIDs or nonsteroidal anti-inflammatory drugs", "opioid" for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well.
  
  
  RESULTS
  Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inﬂammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance.
  
  
  CONCLUSIONS
  No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Farnad
authors.initials: F
authors.lastname: Imani
authors.affiliation: Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IR Iran ; Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Motavaf
authors.affiliation: Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Safari
authors.affiliation: Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran ; Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
keywords: Acetaminophen; Adverse Drug Events; Hepatic Cirrhosis; Pain Management