Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome
A 46-year-old man with underlying liver cirrhosis and hepatocellular carcinoma (HCC) secondary to chronic hepatitis B presented with abdominal distension. The patient had undergone hepatic segmentectomy 1 year previously due to HCC. After HCC recurrence, he had been receiving transarterial chemoembolization (TACE), and fifth TACE was done 1 month previously. Abdominal computed tomography (CT) which was taken 2 weeks after the last TACE showed no viable tumor in the liver. But, increased size of lymph nodes in the portocaval space and newly developed ascites were noted. Portal vein was patent without thrombosis.\nAt admission, electrocardiography was normal and there was no evidence of cardiac dysfunction. Initial serum creatinine was 1.2 mg/dL and blood urea nitrogen (BUN) was 12 mg/dL. Albumin level was 3.6 g/dL, aspartate transaminase 136 IU/L, alanine transaminase 137 IU/L, alkaline phosphatase 215 IU/L and total bilirubin 3.8 mg/dL. Hemoglobin level was 14.3 g/dL and platelet count was 284,000/uL. Prothrombin time was 12.8 seconds. A moderate amount of ascites was noted, and urine output decreased. Diagnostic paracentesis and ascitic fluid analysis was done. Albumin was 2.2 g/dL, leukocyte count was 300/mm3 (neutrophil 61%, lymphocyte 10%, monocyte and macrophage 29%), lactate dehydrogenase was 541 IU/L, glucose was 101 mg/dL in ascites, and bacteria was not seen on gram stain and culture of ascites. Serum-to-ascites albumin gradient (SAAG) was 1.4, suggesting ascites from portal hypertension. There was no definite evidence of spontaneous bacterial peritonitis. Twenty mg of furosemide combined with 50 mg of spironolactone, was administered for three days.\nThree days after admission, serum creatinine had increased to 3.31 mg/dL and BUN had increased to 37.6 mg/dL. The fractional excretion of sodium was 0.8%. The diuretics were stopped, and a total of 80 g of albumin was administered and hydration with 1.5 L of normal saline was done for two days to rule out the possibility of pre-renal acute kidney injury. Despite such a treatment, there was no improvement of serum creatinine. No nephrotoxic drug was used and the blood pressure was generally stable. There was no evidence of parenchymal kidney disease such as marked proteinuria or hematuria. Abdominal sonography showed normal echogenicity on both kidney, and urinary tract abnormality was not noted. According to the criteria of International Ascites Club in 2007, we diagnosed the patient's renal failure as type I HRS. One mg of terlipressin was intravenously administrated every 6 hours. Because the patient complained of severe abdominal pain after 2 doses of terlipressin, it was stopped. Serum creatinine and BUN increased to 7.95 mg/dL and 84.4 mg/dL, respectively, and hourly urine volume became further decreased (). Continuous renal replace therapy was applied for supporting impaired renal function. But, the patient's abdominal pain aggravated and whole abdominal tenderness appeared. Rebound tenderness was also noted. Abdominal CT revealed that the wall of mid-ileum appeared to be thin and not enhanced with contrast. There were multiple air bubbles in the mesenteric veins and in the bowel wall, suggesting pneumatosis intestinalis (). Otherwise, there was no thrombus within vessel or free air in peritoneal cavity.\nWith these findings, the patient was diagnosed with bowel necrosis due to mesenteric ischemia induced by terlipressin. The patient received an emergency bowel resection.\nOperative findings demonstrated the small bowel segment below the Treitz ligament to be in an ischemic state. The blood flow was improved after adjusting the direction of bowel mesentery but the infarction of ileum was severe, so approximately 30 cm of it was resected. Grossly, the resected bowel also had ischemic change on serosa and mesentery, and the mucosa was atrophied and black-pigmented on the opening of the bowel lumen (). Microscopically, there were necrosis and hemorrhages in the bowel wall ().\nThere were no any immediate complications associated with surgery, but hypotension and metabolic acidosis persisted. Eventually, the patient died 2 days after operation.