A 51-year-old woman is admitted to the hospital due to a 5-day history of increasing lethargy and confusion. The patient underwent arthroscopic knee surgery 2 weeks ago. Acetaminophen-oxycodone was prescribed with instructions to limit total acetaminophen dosage to ≤2 g/day. Medical history is significant for cirrhosis due to remote alcohol use disorder; she has abstained for several years. Temperature is 36.3 C (97.3 F), blood pressure is 92/51 mm Hg, pulse is 68/min, and respirations are 24/min. The patient is drowsy, inattentive, and unable to provide a history. Pupils are 5 mm and reactive to light bilaterally. Bilateral asterixis is present. Cardiopulmonary examination is normal. Bowel sounds are hypoactive; no fluid wave, shifting dullness, or tenderness is noted. Abdominal ultrasonography reveals minimal peritoneal fluid; liver echotexture is nodular with no suspicious masses. Complete blood count, renal function test results, serum electrolyte levels, and urinalysis are unremarkable. Liver function test results include an elevated prothrombin time, decreased albumin, and elevated total bilirubin, which are unchanged from baseline results obtained before surgery. Which of the following processes most likely precipitated the patient's current condition?

Question

A 51-year-old woman is admitted to the hospital due to a 5-day history of increasing lethargy and confusion.  The patient underwent arthroscopic knee surgery 2 weeks ago.  Acetaminophen-oxycodone was prescribed with instructions to limit total acetaminophen dosage to ≤2 g/day.  Medical history is significant for cirrhosis due to remote alcohol use disorder; she has abstained for several years.  Temperature is 36.3 C (97.3 F), blood pressure is 92/51 mm Hg, pulse is 68/min, and respirations are 24/min.  The patient is drowsy, inattentive, and unable to provide a history.  Pupils are 5 mm and reactive to light bilaterally.  Bilateral asterixis is present.  Cardiopulmonary examination is normal.  Bowel sounds are hypoactive; no fluid wave, shifting dullness, or tenderness is noted.  Abdominal ultrasonography reveals minimal peritoneal fluid; liver echotexture is nodular with no suspicious masses.  Complete blood count, renal function test results, serum electrolyte levels, and urinalysis are unremarkable.  Liver function test results include an elevated prothrombin time, decreased albumin, and elevated total bilirubin, which are unchanged from baseline results obtained before surgery.  Which of the following processes most likely precipitated the patient's current condition?

Quizplus · Accepted Answer

Explanation: 11ec2b69_bf3d_2aaf_8f63_2537cec7fa81_MD0005_00 This patient with cirrhosis has altered mental status. Given the bilateral asterixis and nonfocal neurologic examination, this presentation is most concerning for hepatic encephalopathy (HE). The pathogenesis of HE involves accumulation of neurotoxins (eg, ammonia [NH₃]) due to liver dysfunction. The underlying precipitants of HE usually involve disturbances in nitrogen (¹⁴N) metabolism: Increased nitrogenous waste production: infections such as spontaneous bacterial peritonitis (increased bacterial catabolism of proteins), gastrointestinal bleeding (breakdown of blood products in gut lumen), and metabolic triggers of glutaminolysis (hypokalemia, metabolic alkalosis) Decreased ammonia clearance: worsening liver function (eg, ischemia, hepatocyte loss), decreased renal function (ie, impaired NH₄⁺excretion), or constipation (eg, opioid-induced bowel slowing) New portosystemic shunting: surgically placed portocaval shunts that create a conduit for neurotoxins to bypass the liver and enter the CNS This patient's standard workup for HE (eg, serum chemistries, urinalysis, cultures) revealed no metabolic or infectious process. Therefore, other causes must be investigated. Constipation, an expected adverse effect of opioid therapy, is a common, underappreciated, and preventable HE precipitant because decreased bowel motility causes intestinal retention of nitrogen-producing bacteria. Patients lucid enough to provide a history should be asked about recent changes in stooling habits. Treatment and prevention involve bowel clearance (lactulose) and/or antibiotic therapy (rifaximin). (Choice A) Acetaminophen toxicity can cause acute hepatic necrosis, and the risk is higher with preexisting advanced liver disease and long-term heavy alcohol use. However, this patient is no longer drinking alcohol; her acetaminophen dosage of ≤2 g/day is safe, well tolerated, and a viable option for analgesia. Furthermore, her liver synthetic function (eg, coagulation profile, bilirubin, albumin) is unchanged from baseline, arguing against primary hepatic injury or deterioration as the precipitant of HE. (Choices C and D) Many opioids undergo hepatic metabolism. Decreased hepatic glucuronidation promotes accumulation of drug metabolites, which can lead to opioid toxicity (even at standard doses); by interfering with neurotransmitter signaling, opioid metabolites can depress cortical activity, thereby unmasking HE. However, opioid intoxication is classically accompanied by miosis and bradypnea (vs normal pupils and high-normal respiratory rate). (Choice E) In the circulation, many opioids are bound by plasma proteins (primarily albumin). Plasma protein-drug binding is usually decreased (rather than increased) in cirrhosis due to hypoalbuminemia. This leads to a greater fraction of unbound free drug, which can cross the blood-brain barrier to enhance CNS depression. Educational objective: Constipation should be considered as a possible cause of hepatic encephalopathy.

A 51-Year-Old Woman Is Admitted to the Hospital Due to a 5-Day