Nimesulide

Abstract

S Nimesulide Renal damage and acute liver failure: case reportAn 81-year-old woman developed renal damage and fatal acute liver failure during treatment with nimesulide [therapeutic indication not stated]; the authors stated that liver cancer metastasis may also have contributed to the fatal acute liver failure.The woman, who had no hepatitis and adequate renal and hepatic function, presented with a 2-day history of haematemesis and epistaxis; she was hospitalised. She had ingested nimesulide at therapeutic doses once a day for 6 days [dosage not stated]. Three weeks earlier, she had taken diclofenac for 7 days; this drug had been stopped 4 days before the start of nimesulide. On admission, she had numerous diffuse haematomas, bilateral epistaxis, and melaena. She had hypotension (80 x 40 mmHg), a HR of 70 beats/min, a RR of 26 breaths/min and sudoresis. Laboratory tests revealed metabolic acidosis with respiratory alkalosis, and increased lactate. Her prothrombin time, partial thromboplastin time, fibrinogen level and platelet count were low.The woman received fresh frozen plasma and platelet transfusion. Her RBC, haemoglobin and haematocrit levels were diminished, with leucocytosis. The renal profile on admission showed increased urea and creatinine levels. Her AST was 10 times above normal and her ALT level was normal. Total and direct bilirubin levels were increased, but indirect bilirubin was normal. C-reactive protein was 30 times above normal. She underwent upper GI endoscopy to exclude GI bleeding; during the procedure, she developed respiratory arrest and decreased consciousness, requiring orotracheal intubation. Her renal and hepatic damage progressed 18 hours after admission, with higher levels of urea, creatinine, AST, ALT and bilirubins (including indirect bilirubin). At this time, γglutamyl transferase and alkaline phosphatase were highly elevated. Her haematological profile continued to worsen and, after 36 hours of hospitalisation, she underwent RBC, fresh frozen plasma and cryoprecipitate transfusion. Hepatitis B and C testing was negative. Carcinoembryonic antigen and CA-19-9 levels were increased by 1000-and 10 000-fold, respectively. CA-125 was increased 13-fold and alphafetoprotein levels were normal. Shortly after her transfusion, her general state worsened and she experienced a 12-minute cardiorespiratory arrest, with subsequent asystole and death.Necropsy showed liver acute hepatitis with inflammatory infiltrate, coagulative necrosis and hepatocellular collapse. Moreover, there was metastasis of moderately differentiated carcinoma, most likely from the bile duct.Author comment: "Although the patient had taken diclofenac three weeks before developing the clinical symptoms, we believe that nimesulide played a major role in her liver injury: first, because the patient was in the at-risk group; and second, because nimesulide was the current NSAID therapy. . . Although the patient was in the group at risk of [nimesulide]-induced hepatotoxicity, the liver cancer metastasis probably also contribu...