Liver Disease and Analgesia
58. A.A., a 54-year-old man with alcoholic cirrhosis, severe ascites, and mild jaundice, has been hospitalized with severe right upper quadrant abdominal pain. His stools are guaiac positive, and he occasionally has bright red blood present at the rectum secondary to hemorrhoids. He was placed on oral lactulose 30 g QID when the protein content of his diet was increased. Although he has a history of hepatic encephalopathy, he is currently alert and receiving only spironolactone 200 mg/day and prophylactic lactulose. What problems can arise when administering opioid analgesics to patients such as A.A.?
Morphine can induce electroencephalogram (EEG) changes similar to those associated with impending hepatic encephalopathy when administered to patients with hepatic cirrhosis.196 These morphine-induced EEG changes cannot be correlated with alkalosis, hypokalemia, or increased blood ammonia levels, and the mechanism is unknown.
Because most opioid analgesics are significantly metabolized in the liver, their serum levels can accumulate if dosing intervals are not adjusted in patients with decreased hepatic function.197,198 The oral bioavailability of some of the opioids also can be increased because of a decreased hepatic first-pass effect.199 The opioids with the greatest first-pass effect or a high extraction ratio have the greatest variability in bioavailability. For example, oral morphine and meperidine have a higher extraction ratio than methadone and, therefore, are more likely to be absorbed unpredictably in patients with severe liver disease. In these patients, methadone is most likely to be absorbed consistently when administered orally.
It would be reasonable to treat A.A.'s pain with a single, modest dose of parenteral morphine, but subsequent doses should await the reappearance of signs of pain to prevent the possible precipitation of hepatic encephalopathy. Careful monitoring of A.A. is essential to minimize risk while maximizing analgesia. The clinician should remember that any CNS depressant can trigger significant problems in a patient such as A.A. If an oral opioid is to be used, then methadone will be a good choice because of its more consistent bioavailability. Although methadone has a long half-life, it is still safer to use orally than morphine. All opioid analgesics should be given in small, frequent, on-demand doses in patients such as A.A. Time-contingent dosing of opioids should be avoided in patients with liver disease because of the risk of drug accumulation. A.A. can be given methadone 2.5 mg no more often than every 6 hours, as needed, accompanied by close monitoring.
0 comments:
Post a Comment