0022-5347 /79/1214-0499$02. 00/0 Vol. 121, April
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1979 by The Williams & Wilkins Co.
BENIGN CHOLESTATIC JAUNDICE AFTER NEPHRECTOMY FOR PYONEPHROSIS AND SEPSIS ELIYAHU MUKAMEL, DAN DOVER, JACK PINKHAS
AND
CIRO SERVADIO
From the Departments of Urology and Internal Medicine D, Beilinson Medical Center, Tel-Aviv University Sackler School of Medicine, Petah Tiqva, Israel
ABSTRACT
Severe benign postoperative intrahepatic cholestatic jaundice appeared immediately after nephrectomy in a patient with nephrolithiasis and septicemia. Convalescence was uneventful and no treatment was necessary. This diagnostic possibility should be considered whenever jaundice appears postoperatively for pyonephrosis and septicemia. Postoperative jaundice mimicking bile duct obstruction occurs in some patients. The term benign postoperative intrahepatic cholestasis is used to describe this syndrome. 1- 3 Herein we report a case of benign postoperative intrahepatic cholestasis that appeared several hours after nephrectomy for urolithiasis, pyonephrosis and septicemia. CASE REPORT
A 57-year-old woman was admitted to the urological ward because of colicky pains in the right flank and temperature up to 39C 2 days in duration. History was non-contributory. The only pathological findings were a body temperature of 39C and marked tenderness in the right flank. Laboratory investigation showed a hemoglobin of 10.3 gm. per cent and a white blood count of28,000/cu. mm. Urinalysis revealed massive leukocyturia. Blood urea nitrogen (BUN) was 19 mg. per cent, creatinine 1 mg. per cent, sodium 139 mEq./1., potassium 3.9 mEq./1., chloride 102 mEq./1., bilirubin 0. 7 mg. per cent, serum glutamic oxaloacetic transaminase 31 units (normal 5 to 40 units), lactic dehydrogenase 175 IU (normal 100 to 225 IU) and alkaline phosphatase 59 IU (normal 30 to 85 IU). Excretory urography showed a poorly functioning hydronephrotic right kidney, with a large stone obstructing the pelvis, as well as many smaller stones scattered in the calices. The left kidney was normal. Urine and blood cultures repeatedly yielded Proteus vulgaris. Treatment consisted of 3 gm./24 hours ampicillin intravenously and 240 mg./24 hours gentamicin intramuscularly. The patient's condition became worse, tenderness in the right flank increased, chills appeared and the body temperature increased to 41C. An operation was done 3 days after hospitalization. No jaundice had been noted and repeated liver function tests 24 hours preoperatively were normal. General anesthesia was used, consisting of sodium thiopental, nitrous oxide and fentanyl citrate. No halothane was used. A large pyonephrotic kidney with pericapsular adhesions full of stones and pus was discovered. The renal pedicle was ligated and the kidney was dissected free. Since the ureter was severely inflamed and contained large amounts of pus a right ureterectomy also was done through a second lower abdominal incision. There was no massive bleeding and no changes in the blood pressure were noted. Two units of packed red cells were transfused during the operation. Jaundice was first noted 8 hours postoperatively and 4 hours later the serum bilirubin reached 20.3 mg. per cent, with a direct bilirubin of 15.4 mg. per cent. The serum glutamic oxaloacetic transaminase was 40 units, lactic dehydrogenase 245 IU, alkaline phosphatase 200 IU, hemoglobin 11.3 gm./100
ml. and BUN 24 mg. per cent. At this stage no urobilinogen was detected in the urine. The patient's condition was good, body temperature returned to normal 3 days postoperatively and she recovered rapidly from the operation. The bilirubin level decreased to 9.8 and 2 mg. per cent 3 and 9 days postoperatively, respectively. The hemoglobin level remained around 12 gm. per cent throughout the entire postoperative course. A liver biopsy was refused by the patient who was discharged from the hospital 2 weeks later with normal liver function tests and bilirubin. Intravenous cholangiography 3 weeks postoperatively showed no pathology whatsoever in the gallbladder or in the biliary tract.
Accepted for publication July 21, 1978. 499
COMMENT
Postoperative jaundice may be owing to various causes, such as increased pigment load resulting from hemolysis or resorption of hematomas, extrahepatic obstruction and impaired hepatocellular function after the administration of anesthetic drugs, hypotension, sepsis, hypoxia and infectious hepatitis. 3 A distinct clinical entity of postoperative jaundice simulating bile duct obstruction was described by Schmid and associates as benign postoperative intrahepatic cholestasis. 1 It may follow prolonged and difficult surgical procedures requiring blood transfusions, usually complicated by hypotension and sepsis. Direct hyperbilirubinemia reaching even 40 mg. per cent developed 1 and 10 days postoperatively, accompanied by a variable elevation of alkaline phosphatase, while serum glutamic oxaloacetic transaminase and lactic dehydrogenase values remained normal or only slightly elevated. 1-4 Usually, there is no pruritus. The course of the jaundice is benign with a duration of 2 to 30 days and it disappears without specific treatment. 2 The marked hyperbilirubinemia occurs despite the paucity of structural abnormalities as seen in liver biopsies that may disclose the presence of bile casts, as well as minimal hepatocellular necrosis and lymphocytic infiltration. 1 In our patient there was no evidence suggesting severe hemolysis or resorption ofhematomas. In addition, no hepatotoxic anesthetic drugs were administered nor was an extrahepatic obstruction or preoperative liver disease evident. The clinical course and laboratory findings suggested the diagnosis of benign postoperative intrahepatic cholestasis. The nephrectomy was done during septicemia and blood transfusions were administered for the long and difficult surgical procedure. Jaundice appeared several hours postoperatively and reached its maximal level 16 hours later. Despite the markedly elevated bilirubin level, the patient's condition was good and she recovered rapidly. The alkaline phosphatase level was elevated while serum glutamic oxaloacetic transaminase and lactic dehydrogenase levels remained normal. Hypoxia, hypotension, sepsis and massive blood transfusion have been
500
MUKAMEL AND ASSOCIATES
suggested as etiologic factors but the exact mechanism is unknown. 3 The marked hyperbilirubinemia with elevated alkaline phosphatase without pronounced morphological evidence of liver damage may suggest that the main insult is in hepatic excretory function. 2 The available evidence indicates that approximately 10 per cent of red blood cells in a 14-dayold acid-citrate-dextrose preserved blood are destroyed in the first 24 hours after transfusion 2 and, presumably, may be an additional factor for an increased pigment load. Exaggerated levels ofbilirubin were not owing to failure of excretion by the remaining left kidney since renal failure was not detected at any time during hospitalization. However, Lamont and Isselbacher stated that concomitant renal failure may increase the degree of jaundice owing to impaired renal excretion of conjugated bilirubin. 3 One may suggest that the benign postoperative intrahepatic cholestasis appeared in our patient after right nephrectomy because of manipulation in proximity to the biliary tree. However, the complication appeared after difficult surgical procedures in various organs, including the left kidney. 2 • ·' Therefore, it seems that the systemic factors, such as hypotension, hypoxia, sepsis and pigment overload,
have a major role in the pathogenesis, rather than local causes. In conclusion, this diagnostic possibility should be considered in post-nephrectomy patients, especially when pyonephrosis and septicemia are present. Since recovery is complete minimal diagnostic and therapeutic measures are necessary. REFERENCES
1. Schmid, M., Hefti, M. L., Gattiker, R., Kistler, H. and Senning,
2.
3. 4. 5.
A.: Benign postoperative intrahepatic cholestasis. New Engl. J. Med., 272: 545, 196(?. Kantrowitz, P. A., Jobes, W. A., Greenberger, N. J. and Isselbacher, K. J.: S~vere postoperative hyperbilirubinemia simulating obstructive jaundice. New Engl. J. Med., 276: 591, 1967. Lamont, J. I. and Isselbacher, K. J.: Postoperative jaundice. New Engl. J. Med., 288: 305, 1973. Morgenstern, L.: Postoperative jaundice. An approach to a diagnostic dilemma. Amer. J. Surg., 128: 255, 1974. Fahrlander, H., Huber, F. and Gloor, F.: Intrahepatic retention of bile in severe bacterial infections. Gastroenterology, 4 7: 590, 1964.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1979 by The Williams & Wilkins Co.
BENIGN CHOLESTATIC JAUNDICE AFTER NEPHRECTOMY FOR PYONEPHROSIS AND SEPSIS ELIYAHU MUKAMEL, DAN DOVER, JACK PINKHAS
AND
CIRO SERVADIO
From the Departments of Urology and Internal Medicine D, Beilinson Medical Center, Tel-Aviv University Sackler School of Medicine, Petah Tiqva, Israel
ABSTRACT
Severe benign postoperative intrahepatic cholestatic jaundice appeared immediately after nephrectomy in a patient with nephrolithiasis and septicemia. Convalescence was uneventful and no treatment was necessary. This diagnostic possibility should be considered whenever jaundice appears postoperatively for pyonephrosis and septicemia. Postoperative jaundice mimicking bile duct obstruction occurs in some patients. The term benign postoperative intrahepatic cholestasis is used to describe this syndrome. 1- 3 Herein we report a case of benign postoperative intrahepatic cholestasis that appeared several hours after nephrectomy for urolithiasis, pyonephrosis and septicemia. CASE REPORT
A 57-year-old woman was admitted to the urological ward because of colicky pains in the right flank and temperature up to 39C 2 days in duration. History was non-contributory. The only pathological findings were a body temperature of 39C and marked tenderness in the right flank. Laboratory investigation showed a hemoglobin of 10.3 gm. per cent and a white blood count of28,000/cu. mm. Urinalysis revealed massive leukocyturia. Blood urea nitrogen (BUN) was 19 mg. per cent, creatinine 1 mg. per cent, sodium 139 mEq./1., potassium 3.9 mEq./1., chloride 102 mEq./1., bilirubin 0. 7 mg. per cent, serum glutamic oxaloacetic transaminase 31 units (normal 5 to 40 units), lactic dehydrogenase 175 IU (normal 100 to 225 IU) and alkaline phosphatase 59 IU (normal 30 to 85 IU). Excretory urography showed a poorly functioning hydronephrotic right kidney, with a large stone obstructing the pelvis, as well as many smaller stones scattered in the calices. The left kidney was normal. Urine and blood cultures repeatedly yielded Proteus vulgaris. Treatment consisted of 3 gm./24 hours ampicillin intravenously and 240 mg./24 hours gentamicin intramuscularly. The patient's condition became worse, tenderness in the right flank increased, chills appeared and the body temperature increased to 41C. An operation was done 3 days after hospitalization. No jaundice had been noted and repeated liver function tests 24 hours preoperatively were normal. General anesthesia was used, consisting of sodium thiopental, nitrous oxide and fentanyl citrate. No halothane was used. A large pyonephrotic kidney with pericapsular adhesions full of stones and pus was discovered. The renal pedicle was ligated and the kidney was dissected free. Since the ureter was severely inflamed and contained large amounts of pus a right ureterectomy also was done through a second lower abdominal incision. There was no massive bleeding and no changes in the blood pressure were noted. Two units of packed red cells were transfused during the operation. Jaundice was first noted 8 hours postoperatively and 4 hours later the serum bilirubin reached 20.3 mg. per cent, with a direct bilirubin of 15.4 mg. per cent. The serum glutamic oxaloacetic transaminase was 40 units, lactic dehydrogenase 245 IU, alkaline phosphatase 200 IU, hemoglobin 11.3 gm./100
ml. and BUN 24 mg. per cent. At this stage no urobilinogen was detected in the urine. The patient's condition was good, body temperature returned to normal 3 days postoperatively and she recovered rapidly from the operation. The bilirubin level decreased to 9.8 and 2 mg. per cent 3 and 9 days postoperatively, respectively. The hemoglobin level remained around 12 gm. per cent throughout the entire postoperative course. A liver biopsy was refused by the patient who was discharged from the hospital 2 weeks later with normal liver function tests and bilirubin. Intravenous cholangiography 3 weeks postoperatively showed no pathology whatsoever in the gallbladder or in the biliary tract.
Accepted for publication July 21, 1978. 499
COMMENT
Postoperative jaundice may be owing to various causes, such as increased pigment load resulting from hemolysis or resorption of hematomas, extrahepatic obstruction and impaired hepatocellular function after the administration of anesthetic drugs, hypotension, sepsis, hypoxia and infectious hepatitis. 3 A distinct clinical entity of postoperative jaundice simulating bile duct obstruction was described by Schmid and associates as benign postoperative intrahepatic cholestasis. 1 It may follow prolonged and difficult surgical procedures requiring blood transfusions, usually complicated by hypotension and sepsis. Direct hyperbilirubinemia reaching even 40 mg. per cent developed 1 and 10 days postoperatively, accompanied by a variable elevation of alkaline phosphatase, while serum glutamic oxaloacetic transaminase and lactic dehydrogenase values remained normal or only slightly elevated. 1-4 Usually, there is no pruritus. The course of the jaundice is benign with a duration of 2 to 30 days and it disappears without specific treatment. 2 The marked hyperbilirubinemia occurs despite the paucity of structural abnormalities as seen in liver biopsies that may disclose the presence of bile casts, as well as minimal hepatocellular necrosis and lymphocytic infiltration. 1 In our patient there was no evidence suggesting severe hemolysis or resorption ofhematomas. In addition, no hepatotoxic anesthetic drugs were administered nor was an extrahepatic obstruction or preoperative liver disease evident. The clinical course and laboratory findings suggested the diagnosis of benign postoperative intrahepatic cholestasis. The nephrectomy was done during septicemia and blood transfusions were administered for the long and difficult surgical procedure. Jaundice appeared several hours postoperatively and reached its maximal level 16 hours later. Despite the markedly elevated bilirubin level, the patient's condition was good and she recovered rapidly. The alkaline phosphatase level was elevated while serum glutamic oxaloacetic transaminase and lactic dehydrogenase levels remained normal. Hypoxia, hypotension, sepsis and massive blood transfusion have been
500
MUKAMEL AND ASSOCIATES
suggested as etiologic factors but the exact mechanism is unknown. 3 The marked hyperbilirubinemia with elevated alkaline phosphatase without pronounced morphological evidence of liver damage may suggest that the main insult is in hepatic excretory function. 2 The available evidence indicates that approximately 10 per cent of red blood cells in a 14-dayold acid-citrate-dextrose preserved blood are destroyed in the first 24 hours after transfusion 2 and, presumably, may be an additional factor for an increased pigment load. Exaggerated levels ofbilirubin were not owing to failure of excretion by the remaining left kidney since renal failure was not detected at any time during hospitalization. However, Lamont and Isselbacher stated that concomitant renal failure may increase the degree of jaundice owing to impaired renal excretion of conjugated bilirubin. 3 One may suggest that the benign postoperative intrahepatic cholestasis appeared in our patient after right nephrectomy because of manipulation in proximity to the biliary tree. However, the complication appeared after difficult surgical procedures in various organs, including the left kidney. 2 • ·' Therefore, it seems that the systemic factors, such as hypotension, hypoxia, sepsis and pigment overload,
have a major role in the pathogenesis, rather than local causes. In conclusion, this diagnostic possibility should be considered in post-nephrectomy patients, especially when pyonephrosis and septicemia are present. Since recovery is complete minimal diagnostic and therapeutic measures are necessary. REFERENCES
1. Schmid, M., Hefti, M. L., Gattiker, R., Kistler, H. and Senning,
2.
3. 4. 5.
A.: Benign postoperative intrahepatic cholestasis. New Engl. J. Med., 272: 545, 196(?. Kantrowitz, P. A., Jobes, W. A., Greenberger, N. J. and Isselbacher, K. J.: S~vere postoperative hyperbilirubinemia simulating obstructive jaundice. New Engl. J. Med., 276: 591, 1967. Lamont, J. I. and Isselbacher, K. J.: Postoperative jaundice. New Engl. J. Med., 288: 305, 1973. Morgenstern, L.: Postoperative jaundice. An approach to a diagnostic dilemma. Amer. J. Surg., 128: 255, 1974. Fahrlander, H., Huber, F. and Gloor, F.: Intrahepatic retention of bile in severe bacterial infections. Gastroenterology, 4 7: 590, 1964.
![[Cholestatic jaundice after azathioprine treatment (author's transl)].](/assets/img/hold.png)
