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Wednesday, November 9, 2016

Analgesia : In Hepatic Failure


  • 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
  • Avoid polypharmacy and monitor for adverse drug events.

Paracetamol
  • In general, for long-term use in cirrhotic patients it is recommended to reduce dosing at 2 to 3 g/d. 
  • Although such patients may eliminate paracetamol more slowly than patients without liver disease, repeated administration of the drug does not result in accumulation of hepatotoxic intermediate, NAPQI. 
  • Furthermore, there is no evidence of increased CYP enzymes activity or reduced hepatocellular glutathione stores in patients with liver disease.
NSAIDs
  • should be avoided in those with both compensated and decompensated cirrhosis, primarily because of the risk of acute renal failure due to prostaglandin inhibition.
  • An increased risk of GI mucosal bleeding, variceal hemorrhage, impaired renal function, and development of diuretic-resistant ascites is seen with use of NSAIDs in patients with cirrhosis with portal hypertension
  • Selective COX-2 inhibitors
  • inadequate data to establish the safety of selective COX-2 inhibitors in patients with advanced CLD or cirrhosis
  • If used, celecoxib product information suggests a 50% dose reduction for Child-Pugh class B cirrhosis
Opiods
  • should be administrated with a longer interval between doses and possibly lower doses, with individual titration to achieve optimal pain relief without significant adverse effects. 
  • Careful follow-up is necessary to check for signs of sedation, opioid-induced constipation and early encephalopathy. 
  • Immediate discontinuation of the opioids should be considered if any sign of these complications is appeared.
Fentanyl
  • Generally a good choice for patients with CLD or cirrhosis when opiate treatment indicated.
  • Useful option in patients with renal failure in setting of cirrhosis.
  • No dose adjustment needed for single dose.
  • With repeated dosing, reduce dose and frequency by approximately 25 to 50%.
  • Initiate transdermal patch at half usual dose. 
Morphine
  • Accumulation of metabolites with complex effects (eg, respiratory depression, analgesic tolerance, neurotoxicity) can occur in patients with cirrhosis and renal failure
  • Reduce dose and frequency by approximately 50% in advanced CLD or cirrhosis.
  • Titrate dose gradually to avoid accumulation of active drug.
  • Avoid in patients with cirrhosis and renal failure.
 Tramadol
  • Unpredictable onset, variable analgesic efficacy, and risk of accumulation in patients with cirrhosis
  • Avoid use in patients with decompensated cirrhosis.
  • Avoid use in patients at risk for seizures.
  • Based upon limited experience, a reduced dose of 25 mg every eight hours may be considered for treatment of pain in patients with advanced CLD or well-compensated cirrhosis.
References
  1.  www.uptodate.com
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861975/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250965/

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