Survival From Acute Hepatorenal Syndrome Following Splenorenal Shunt JOSEF E. FISCHER, M.D.* GERALD S. FOSTER, M.D.
From the Departments of Surgery and Medicine, Massachusetts General Hospital and the Harvard Medical School, Boston, Massachusetts 02114
Acute aggravation of chronic hepatorenal syndrome following angiography is described in a patient with recovery and long-term survival following splenorenal shunt. It is believed that this patient represents a type of hepatorenal syndrome which can be expected to tolerate shunt and recover from hepatorenal syndrome. Possible mechanisms of the pathophysiology are discussed and recommendations made on this basis for the selection of such patients for portal decompression.
chronic liver disease in whom the additional stress of angiography resulted in acute renal shutdown in an aggravated state of "hepatorenal syndrome." After a period of 8 days of oliguria, splenorenal shunt and left renal denervation resulted in prompt diuresis and survival. This patient met several of the criteria which have been used in the past to separate out two types of renal impairment with co-existent liver disease. In the discussion, an approach to the problem of selection of patients for portal systemic shunt in "hepatorenal syndrome" is suggested.
THE RENAL FAILURE which constitutes the terminal event in many patients with liver disease is considered a functional disorder, a supposition suggested by the prompt function of cadaver renal transplants taken from patients dying with so-called "hepatorenal syndrome.'"14 The syndrome usually ends fatally, although recovery has been reported, both spontaneously2'10 or following successful hepatic transplantation.15 It has been recently suggested that there may be more than one type of the so-called "hepatorenal syndrome" and that these may be differentiated on clinical and hemodynamic grounds, and that one group of patients might respond to portal decompression.8'9'20 One long-term apparent cure of the hepatorenal syndrome following portacaval shunt has been reported.18 In another patient, prompt diuresis occurred, but the patient succumbed following a perforated ulcer.4 Some have proposed portal decompression for hepatorenal syndrome in all patients who might tolerate the procedure,13 but as has been pointed out, an indistinguishable syndrome develops after portacaval shunt.4 The advantages of being able to select those patients who will benefit from portal systemic shunt are obvious. The following case report represents, we believe, chronic functional renal impairment in a patient with
Case Report Patient R.M. (MGH #133-57-15), a 54-year-old woman, had a history of excessive alcoholic intake since age 20. She had been well and working until between 6 and 8 months prior to admission when she noted increasing abdominal swelling without leg swelling. She was admitted to another hospital, placed on a salt and fluid restriction and a diuretic program consisting of aldactozide and ethacrinic acid. Her weight declined from 114 lb to 98 lb. She was discharged from the hospital one week prior to her first MGH admission on 50 mg of ethacrinic acid daily. She did not limit her fluid or salt intake at home, rapidly reaccumulated abdominal fluid, and was admitted at the request of her family. On physical examination, blood pressure was 100/60, pulse 88, respirations 28, temperature 380 and weight 108. She was a pleasant, chronically emaciated, wasted female with a massively protuberant abdomen. The skin was dry with flaking, and spider angiomata were distributed on the upper torso. Palmar erythema was present as well as an early Dupuytren' s contracture. The abdomen was distended with tense ascites and measured 363/4 inches in circumference. Liver was about 8 cm below the right costal margin without
Submitted for publication February 7, 1975. Supported in Part By Public Health Service Grant #AM-15347.
*
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23
tween 400 and 800 cc/day in spite of Prednisone and diuretic agents. On January 13th, paracentesis was performed removing 4,240 cc of clear yellow fluid. This was "replaced" with salt poor albumin. She tolerated the procedure well with weight decreasing from 125h to 114h. Girth decreased to 40 inches and then to 38. Paracentesis was complicated by streptococcal cellulitis which responded to penicillin. Following paracentesis, a rather hard irregular liver could be felt, but the spleen was not palpable. It was thought that the nodule in her liver, although most likely "regenerating" might represent a hepatoma. a-Fetoglobulin was negative. On 1/21/72, she was hydrated and underwent angiography, revealing a small splenic and open portal vein. Wedged hepatic vein pressure was 40 cm of water. There was a gradient between the inferior vena cava and the right atrium, with a pressure of 17 cm H20 in the vena cava and 4 cm H20 in the right atrium. On anteroposterior view, there was narrowing of the inferior vena cava at the level of the hepatic vein, but no diaphragm was present.3 Following angiography, renal shutdown occurred despite colloid and the fact that she had been well hydrated before her angiogram. At that time, sodium was 120, potassium 5.7, BUN rose to 54 on 1/23, albumin was 4.0. Urine osmolality was 330, urinary sodium varied between I and 4 and potassium varied between 49 and 81 mEq/liter. L-Essential amino acids plus hypertonic glucose were begun by subclavian catheter.' In spite of this, by 1/28/72, BUN was 75 and creatinine had risen to 7.0 with urine output varying 100 and 333 cc/day. Cardiac index was 3.5 liters/min/m2 and in spite of the fact that the hemodynamic criteria did not suggest that L-Dopa would be successful,59 in desparation a trial of L-Dopa was undertaken for 36 hours without success. On 1/29/72, she underwent a splenorenal shunt and denervation of the left renal artery through a left thoracoabdominal incision. The splenic vein was approximately 1 cm in diameter. Following opening of the shunt, pressure in an omental vein fell to 30 cm water. Within the first 3 hours following removal of the clamps
splenomegaly. Stool guaiac was positive. On mental testing, Grade I encephalopathy was present, although there was no asterixis. Laboratory values showed a hematocrit of 26.6, WBC 12,400 with 81 polys. Sodium 137, potassium 2.7, BUN 31, creatinine 1.2, total protein 6.3 with an albumin of 3.4 and globulin of 2.9. Bilirubin 0.7 and 1.0, cholesterol 199, cholesterol esters 117, ammonia 50 to 75. SGOT was 35, LDH 75, alkaline phosphatase 5.9 Bodansky Units. PPD was negative. Paracentesis revealed clear yellow fluid with a negative cell block, with a total protein of 2.6 (albumin 1.0, globulin 1.6). Peritoneal fluid amylase was 10 units. Urine osmolality remained between 360 and 380 mosm/liter with a sodium of 1 or 2 mEq/ liter, potassium ranging between 60 and 80 mEq/liter. The patient remained weak and unsteady. Over the next 4 weeks in the hospital, she continued to have guaiac positive stools without any obvious source on barium enema or upper GI series. Potassium replacement and nutritional therapy were carried out and diuretic therapy was increased to Furosemide 80 mg daily. On this regimen, her BUN and potassium rose, and she was changed to 80 mg of Furosemide qod. Over the next two months in an extended care facility, she did well gaining strength, but with little improvement in her diuretic resistant ascites, although she had added muscle mass. Prednisone4 and ethacrinic acid were added to the regimen without relief from ascites, which remained tense. She was readmitted to the hospital in January of 1972. Weight was 129½h and abdominal girth had increased from 36 to 46 inches. Hct was 33, white count 6,600 with normal platelets. Prothrombin time was normal. Sodium 142, potassium 3.4, BUN 25 creatinine 1.1, total protein 6.1 with albumin 2.8 and globulin 3.3, bilirubin was 0.5, SGOT 23, and alkaline phosphatase 2.6 Bodansky Units. Urine osmolality was 422, urinary sodium 3, potassium 49. A central venous pressure catheter was placed and over the next several weeks, she was given massive amounts of salt poor albumin without ever raising her venous pressure. Urine output remained be-
Intractable Ascites 133 5745 R. M. 54 9
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FIG. 1. Composite chart of t4?INARrA*+ patient, R. M. Initial admis(AiqiLI sion shows inability to provoke diuresis and rising BUN and creatinine when diuresis is too vigorous. fIM/IOOA,IJ Renal shutdown followed angiography which was O?EA77NIAE performed 8 days following paracentesis. Urgent splenorenal shunt was undertaken when oliguria per- SERUM ALBUMINI sisted for 8 days. Note im(gf/00/l mediate diuresis and natriuresis. (Ibsi
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FISCHER AND FOSTER
and even while the patient was on the operating table, diuresis of 1000 cc of urine with a urinary sodium of 195 mEq/liter occurred (Fig. 1). Over the next several days, urinary sodium varied between 18 and 71 mEq/liter without diuretics. BUN fell to 52, and on February 5th, to 38 with creatinine to 2.0. During the second postoperative week, she accumulated some ascites, but this responded to 40 mg of Lasix qod. On discharge from the hospital, weight was 104½/2 and girth 371/2. She was tolerating 70 gm of protein daily without asterixis and 500 mg of sodium. She was readmitted several months later with upper gastrointestinal bleeding (not requiring transfusion) and some re-accumulation of ascites. No source was found, and it was presumed she bled from gastritis. Following this, she continued to diurese spontaneously and at present is on no salt restriction, has no ascites and is back at work. She has abstained from alcohol in the interim, except for one brief period. Recent chemistries indicate that liver function has been stable, there is no evidence of hepatic encephalopathy.
Discussion While it is not completely clear that this patient's renal failure represented the acute hepatorenal syndrome, certainly this appeared related to angiography and presumably represents the increased toxicity of angiogram dye to patients whose renal function is already compromised on a hepatic basis. The urinary electrolytes, notably a low urinary sodium and relatively high potassium, suggested that in fact this was not acute tubular necrosis, but merely an aggravation of the patient's already present renal dysfunction. The duration of the renal shutdown 8 days, suggested that reversal was not likely, since most cases where shutdown follows angiogram dye have diuresed by 3 to 6 days. Recovery was dramatic in that diuresis occurred within one-half hour after removal of shunt clamps, and the urinary sodium of 195 suggests preferential perfusion of renal cortical nephrons. The hepatorenal syndrome, for want of a better definition, has been described as renal failure in the presence of cirrhosis. Even after attempts have been made to rule out all of the causes which may lead to the "pseudo hepatorenal syndrome"'4 a sizeable group of patients remain in whom no therapy avails and whose situation ends fatally. Over the past several years, it has become clear that this group is heterogeneous and contains at least two types of patients. The initial attempt of classification on the basis of both plasma volume and cardiac output by Tristani and Cohn20 suggested that in one group, plasma volume was diminished and the cardiac output low with a normal or increased peripheral vascular resistance. In this group, volume infusions were of temporary benefit in increasing urine output as well as increasing cardiac index. In the other group, plasma volume appeared normal and cardiac index was elevated, often with a diminished peripheral vascular resistance.8'9'20 Unfortunately, a number of studies using both renal arteriography and 133Xenon scans have attempted to unify all patients in the hepatorenal syndrome into one
category.6'13
Ann. Surg. * July 1976
Recently one of us has suggested a classification for differentiating these two types of patients based on basically hemodynamic5'8'9"13 criteria similar to that proposed by Tristani and Cohn,20 in which the Type I patients consist of those patients, generally stable, without an acute insult, with a diminished plasma volume, decreased cardiac index and normal or increased peripheral vascular resistance. The other, those with an elevated cardiac index, decreased peripheral vascular resistance, and increased or normal plasma volume, generally occurs following an acute insult, is often associated with hepatic encephalopathy and recent deterioration in hepatic function. It has recently been proposed that portacaval anastomosis be considered as therapy for the hepatorenal syndrome in those patients who can tolerate the surgical procedure.13'18 It is our contention that portal-systemic decompression is only suitable in patients who are essentially hypovolemic and whose plasma volume is decreased with diminished cardiac indices, and that pharmacological therapy, which at present is unsatisfactory5'8'9,1215'16"19 be recommended for the other group as portacaval anastomosis is likely to result in the death of the patient. The case herein reported is offered as an example of the Type I hepatorenal syndrome, where portal systemic decompression may succeed. This patient manifested a normal cardiac index, approximately 3.5 1/min/ m2, which in our experience, using the indocyanine green indicator method has suggested classification as a "Type I patient.' 5,8,9,13,20 Similarly, there was no mild hypotension, usually associated with a Type II hepatorenal syndrome, except in respect to hypovolemia. In spite of infusions of salt poor albumin, urinary output increased only transiently, and diuretic and Prednisone therapy was without benefit. Associated findings here were narrowing of the inferior vena cava at the point of entrance of the hepatic vein, and although a diaphragm was not seen, this has been reported by others.3 Hepatic vein wedge pressure was markedly elevated, suggesting severe post-sinusoidal block and marked portal hypertension. This patient's acute deterioration was undoubtedly due to the effects of angiogram dye, perhaps aggravated by paracentesis, although the patient had been hydrated and a number of days had elapsed to allow equilibration following paracentesis. The pathophysiology in such patients, who admittedly are rare, may be on the basis of pooling of the blood volume within the splanchnic circulation as suggested by Tristani and Cohn,20 with the loss of a high volume of protein rich ascites (total protein in the ascites was 2.6 gr/100ml) from a severely congested liver secondary to high degree outflow block or as previously suggested by Schumaker and his colleagues17 and recently reemphasized by Gordon and her co-workers,11 a "porto-
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renal reflex." As such, the improvement of this patient whether secondary to portal decompression alone or portal decompression in association with left renal denervation must remain a moot point. In her present state of health, the patient refuses to undergo further angiographic studies and since there is a possibility of sensitivity to iodinated dyes, we have been reluctant to press the issue. Since, however, the "portorenal reflex," if it is at the root of such disordered pathophysiology, is mediated via the sympathetic nerves,16 the relief of portal congestion is probably sufficient and renal denervation is not required. Moreover, in most cases of hepatorenal syndrome, the infusion of phenoxybenzamine or dibenzyline directly into the kidney has been without effect, although the type of patient in whom this was attempted has not been clearly defined.6 The diuresis in this patient occurred within half an hour of removal of the shunt clamps and suggested that the portal decompression was distinctly related to the diuresis. The extraordinarily high urinary sodium seen within the first four hours after diuresis suggests that the renal cortical nephrons were being almost preferentially perfused. The reasons for this are not clear. The patient received a trial of L- Dopa prior to operation, however, this was terminated approximately 24 hours before the operative procedure, and it is unlikely that the natriuretic effect of L-Dopa7 persisted. Subsequently, however, urinary sodium returned towards normal and has remained in the 30 to 40 mEq/liter range. The ultimate outcome in this patient following one episode of ascites reaccumulation associated with mild gastrointestinal bleeding suggested that the relief of altered pathophysiology was not total and that during a period of hepatic decompensation and gastrointestinal bleeding, the tendency towards the hepatorenal syndrome persisted as it was provoked by gastrointestinal bleeding. It is to be emphasized, however, the patient is now on an unrestricted salt intake without diuretics and remains ascites free.
Addendum When last seen on 4/8/76, she had developed a superficial lesion of the right tonsillar pillar, biopsy-squamous cell carcinoma, treated with radiation, there were no neck nodes. Chemistries were as follows: BUN 21 mg/100 ml, creatinine 0.7 mg/100 ml, total protein 7.8 with albumin 4.2 gm/100 ml, globulin 3.6 gm/100 ml, bilirubin 0.3/0.8 mg/100 ml, SGOT 24, alkaline phosphatase 4.1 Bodansky Units. Na 143, K 4.3, C 198, CO2 25.
References 1. Abel, R. M., Beck, C. H., Jr. et al.: Improved Survival from Acute Renal Failure Following Treatment with Intravenous
25
Essential L-Amino Acids and Glucose. N. Engl. J. Med., 288:695, 1973. 2. Baldus, W. P., Reichter, R. N. and Summerskill, W. H. J.: The Kidney in Cirrhosis. I. Clinical and Biochemical Features of Azotemia in Hepatic Failure. Ann. Intern. Med. 60:353, 1964. 3. Chuji, K., Matsuda, S., Hoie, H. and Hirocka M.: Membranous Obstruction of the Hepatic Portion of the Inferior Vena Cava. Clinical Study of Nine Cases. Surgery, 72:551, 1972. 4. Conn, H. O.: A Rational Approach to the Hepatorenal Syndrome. Gastroenterology, 65:321, 1973. 5. Dodsworth, J., James, J. H., Cummings, M. G. and Fischer, J. E.: Diagnosis and Therapy of the Hepatorenal Syndrome, A Tentative Classification. Surg. Forum, 24:396, 1973. 6. Epstein, M., Berk, D. P., Hollenberg, N. K. et al.: Renal Failure in the Patient with Cirrhosis. Am. J. Med., 49:175, 1970. 7. Finlay, G. D., Whitsell, T. L., Cucinell, E. A. and Goldberg, L. I.: Augmentation of Sodium and Potassium Excretion Glomerular Filtration Rate and Renal Plasma Flow by LevoDopa. N. Engl. J. Med., 284:866, 1971. 8. Fischer, J. E.: Neurotransmitters and Hepatic Failure. Conn. Med., 36:575, 1972. 9. Fischer, J. E.: Acute Hepatic Failure. In The Liver-The Molecular Biology of Its Disease. Frederick F. Becker, Ed. New York, Marcel Dekker. (1975) Part B 725. 10. Goldstein, H. and Boyle, J. D.: Spontaneous Recovery from the Hepatorenal Syndrome. Report of Four Cases. N. Engl. J. Med. 272:895, 1965. 11. Gordon, S. J., Bazzato, G., Oresti, G. and Kowlesar, 0. D.: Experimental Portal Hypertension: Effect on Renal Function. Gastroenterology, 53:735, 1973. 12. Gornel, D. L., Lancestremere, R. G., Papper, S. and Lowenstein, L. M.: Acute Changes in Renal Excretion of Water and Solute in Patients with Laennec's Cirrhosis Induced by the Administration of the Pressor Amine, Metaraminol. J. Clin. Invest., 41:594, 1962. 13. Kew, M. C., Limbrick, C., Varma, R. R. and Sherlock, S.: Renal and Intrarenal Blood Flow in Non-Cirrhotic Portal Hypertension. Gut, 13:763, 1972. 14. Koppel, M. H., Coburn, J. W., Mims, M. M. et al.: Transplantation of Cadaveric Kidney from Patients with Hepatorenal Syndrome: E-vidence for The Functional Nature of Renal Failure in Advanced Liver Disease. N. Engl. J. Med., 280: 1367, 1969. 15. Iwatsuri, S., Popotzer, M. M., Corman, J. L. et al.: Recovery from Hepatorenal Syndrome After Transplantation. N. Engl. J. Med., 289:1155, 1973. 16. Nori, M., Austen, W. G. and McDermott, W. V., Jr.: Role of Hepatic Arterial Blood Flow and Hepatic Nerves on Renal Circulation and Function. I. Acute Studies in the Dog. Ann. Surg., 162:849, 1965. 17. Onnis, M., Schumacker, H. B., Jr. and Bounous, G.: Response to Occlusion of the Portal Vein: Blood Pressure and Renal Blood Flow. Arch. Surg., 85:897, 1962. 18. Schroeder, E. T., Numann, P. J. and Chamberlain, B. E.: Functional Renal Failure in Cirrhosis. Recovery After Portacaval Shunt. Ann. Intern. Med., 72:923, 1970. 19. Sugerman, J. H., Berkowitz, H. D., Davidson, D. T. and Miller, L. D.: Treatment of the Hepatorenal Syndrome with Metaraminol. Surg. Forum, 21:359, 1970. 20. Tristani, F. E. and Cohn, J. J.: Systematic and Renal Hemodynamics in Oliguric Hepatic Failure: Effect of Volume Expansion. J. Clin Invest. 46:1894, 1966.
From the Departments of Surgery and Medicine, Massachusetts General Hospital and the Harvard Medical School, Boston, Massachusetts 02114
Acute aggravation of chronic hepatorenal syndrome following angiography is described in a patient with recovery and long-term survival following splenorenal shunt. It is believed that this patient represents a type of hepatorenal syndrome which can be expected to tolerate shunt and recover from hepatorenal syndrome. Possible mechanisms of the pathophysiology are discussed and recommendations made on this basis for the selection of such patients for portal decompression.
chronic liver disease in whom the additional stress of angiography resulted in acute renal shutdown in an aggravated state of "hepatorenal syndrome." After a period of 8 days of oliguria, splenorenal shunt and left renal denervation resulted in prompt diuresis and survival. This patient met several of the criteria which have been used in the past to separate out two types of renal impairment with co-existent liver disease. In the discussion, an approach to the problem of selection of patients for portal systemic shunt in "hepatorenal syndrome" is suggested.
THE RENAL FAILURE which constitutes the terminal event in many patients with liver disease is considered a functional disorder, a supposition suggested by the prompt function of cadaver renal transplants taken from patients dying with so-called "hepatorenal syndrome.'"14 The syndrome usually ends fatally, although recovery has been reported, both spontaneously2'10 or following successful hepatic transplantation.15 It has been recently suggested that there may be more than one type of the so-called "hepatorenal syndrome" and that these may be differentiated on clinical and hemodynamic grounds, and that one group of patients might respond to portal decompression.8'9'20 One long-term apparent cure of the hepatorenal syndrome following portacaval shunt has been reported.18 In another patient, prompt diuresis occurred, but the patient succumbed following a perforated ulcer.4 Some have proposed portal decompression for hepatorenal syndrome in all patients who might tolerate the procedure,13 but as has been pointed out, an indistinguishable syndrome develops after portacaval shunt.4 The advantages of being able to select those patients who will benefit from portal systemic shunt are obvious. The following case report represents, we believe, chronic functional renal impairment in a patient with
Case Report Patient R.M. (MGH #133-57-15), a 54-year-old woman, had a history of excessive alcoholic intake since age 20. She had been well and working until between 6 and 8 months prior to admission when she noted increasing abdominal swelling without leg swelling. She was admitted to another hospital, placed on a salt and fluid restriction and a diuretic program consisting of aldactozide and ethacrinic acid. Her weight declined from 114 lb to 98 lb. She was discharged from the hospital one week prior to her first MGH admission on 50 mg of ethacrinic acid daily. She did not limit her fluid or salt intake at home, rapidly reaccumulated abdominal fluid, and was admitted at the request of her family. On physical examination, blood pressure was 100/60, pulse 88, respirations 28, temperature 380 and weight 108. She was a pleasant, chronically emaciated, wasted female with a massively protuberant abdomen. The skin was dry with flaking, and spider angiomata were distributed on the upper torso. Palmar erythema was present as well as an early Dupuytren' s contracture. The abdomen was distended with tense ascites and measured 363/4 inches in circumference. Liver was about 8 cm below the right costal margin without
Submitted for publication February 7, 1975. Supported in Part By Public Health Service Grant #AM-15347.
*
22
ACUTE HEPATORENAL SYNDROME
Vol 184 . No. I
23
tween 400 and 800 cc/day in spite of Prednisone and diuretic agents. On January 13th, paracentesis was performed removing 4,240 cc of clear yellow fluid. This was "replaced" with salt poor albumin. She tolerated the procedure well with weight decreasing from 125h to 114h. Girth decreased to 40 inches and then to 38. Paracentesis was complicated by streptococcal cellulitis which responded to penicillin. Following paracentesis, a rather hard irregular liver could be felt, but the spleen was not palpable. It was thought that the nodule in her liver, although most likely "regenerating" might represent a hepatoma. a-Fetoglobulin was negative. On 1/21/72, she was hydrated and underwent angiography, revealing a small splenic and open portal vein. Wedged hepatic vein pressure was 40 cm of water. There was a gradient between the inferior vena cava and the right atrium, with a pressure of 17 cm H20 in the vena cava and 4 cm H20 in the right atrium. On anteroposterior view, there was narrowing of the inferior vena cava at the level of the hepatic vein, but no diaphragm was present.3 Following angiography, renal shutdown occurred despite colloid and the fact that she had been well hydrated before her angiogram. At that time, sodium was 120, potassium 5.7, BUN rose to 54 on 1/23, albumin was 4.0. Urine osmolality was 330, urinary sodium varied between I and 4 and potassium varied between 49 and 81 mEq/liter. L-Essential amino acids plus hypertonic glucose were begun by subclavian catheter.' In spite of this, by 1/28/72, BUN was 75 and creatinine had risen to 7.0 with urine output varying 100 and 333 cc/day. Cardiac index was 3.5 liters/min/m2 and in spite of the fact that the hemodynamic criteria did not suggest that L-Dopa would be successful,59 in desparation a trial of L-Dopa was undertaken for 36 hours without success. On 1/29/72, she underwent a splenorenal shunt and denervation of the left renal artery through a left thoracoabdominal incision. The splenic vein was approximately 1 cm in diameter. Following opening of the shunt, pressure in an omental vein fell to 30 cm water. Within the first 3 hours following removal of the clamps
splenomegaly. Stool guaiac was positive. On mental testing, Grade I encephalopathy was present, although there was no asterixis. Laboratory values showed a hematocrit of 26.6, WBC 12,400 with 81 polys. Sodium 137, potassium 2.7, BUN 31, creatinine 1.2, total protein 6.3 with an albumin of 3.4 and globulin of 2.9. Bilirubin 0.7 and 1.0, cholesterol 199, cholesterol esters 117, ammonia 50 to 75. SGOT was 35, LDH 75, alkaline phosphatase 5.9 Bodansky Units. PPD was negative. Paracentesis revealed clear yellow fluid with a negative cell block, with a total protein of 2.6 (albumin 1.0, globulin 1.6). Peritoneal fluid amylase was 10 units. Urine osmolality remained between 360 and 380 mosm/liter with a sodium of 1 or 2 mEq/ liter, potassium ranging between 60 and 80 mEq/liter. The patient remained weak and unsteady. Over the next 4 weeks in the hospital, she continued to have guaiac positive stools without any obvious source on barium enema or upper GI series. Potassium replacement and nutritional therapy were carried out and diuretic therapy was increased to Furosemide 80 mg daily. On this regimen, her BUN and potassium rose, and she was changed to 80 mg of Furosemide qod. Over the next two months in an extended care facility, she did well gaining strength, but with little improvement in her diuretic resistant ascites, although she had added muscle mass. Prednisone4 and ethacrinic acid were added to the regimen without relief from ascites, which remained tense. She was readmitted to the hospital in January of 1972. Weight was 129½h and abdominal girth had increased from 36 to 46 inches. Hct was 33, white count 6,600 with normal platelets. Prothrombin time was normal. Sodium 142, potassium 3.4, BUN 25 creatinine 1.1, total protein 6.1 with albumin 2.8 and globulin 3.3, bilirubin was 0.5, SGOT 23, and alkaline phosphatase 2.6 Bodansky Units. Urine osmolality was 422, urinary sodium 3, potassium 49. A central venous pressure catheter was placed and over the next several weeks, she was given massive amounts of salt poor albumin without ever raising her venous pressure. Urine output remained be-
Intractable Ascites 133 5745 R. M. 54 9
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XMT 1000 INTAKE (a//241r/ 500_
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FIG. 1. Composite chart of t4?INARrA*+ patient, R. M. Initial admis(AiqiLI sion shows inability to provoke diuresis and rising BUN and creatinine when diuresis is too vigorous. fIM/IOOA,IJ Renal shutdown followed angiography which was O?EA77NIAE performed 8 days following paracentesis. Urgent splenorenal shunt was undertaken when oliguria per- SERUM ALBUMINI sisted for 8 days. Note im(gf/00/l mediate diuresis and natriuresis. (Ibsi
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FISCHER AND FOSTER
and even while the patient was on the operating table, diuresis of 1000 cc of urine with a urinary sodium of 195 mEq/liter occurred (Fig. 1). Over the next several days, urinary sodium varied between 18 and 71 mEq/liter without diuretics. BUN fell to 52, and on February 5th, to 38 with creatinine to 2.0. During the second postoperative week, she accumulated some ascites, but this responded to 40 mg of Lasix qod. On discharge from the hospital, weight was 104½/2 and girth 371/2. She was tolerating 70 gm of protein daily without asterixis and 500 mg of sodium. She was readmitted several months later with upper gastrointestinal bleeding (not requiring transfusion) and some re-accumulation of ascites. No source was found, and it was presumed she bled from gastritis. Following this, she continued to diurese spontaneously and at present is on no salt restriction, has no ascites and is back at work. She has abstained from alcohol in the interim, except for one brief period. Recent chemistries indicate that liver function has been stable, there is no evidence of hepatic encephalopathy.
Discussion While it is not completely clear that this patient's renal failure represented the acute hepatorenal syndrome, certainly this appeared related to angiography and presumably represents the increased toxicity of angiogram dye to patients whose renal function is already compromised on a hepatic basis. The urinary electrolytes, notably a low urinary sodium and relatively high potassium, suggested that in fact this was not acute tubular necrosis, but merely an aggravation of the patient's already present renal dysfunction. The duration of the renal shutdown 8 days, suggested that reversal was not likely, since most cases where shutdown follows angiogram dye have diuresed by 3 to 6 days. Recovery was dramatic in that diuresis occurred within one-half hour after removal of shunt clamps, and the urinary sodium of 195 suggests preferential perfusion of renal cortical nephrons. The hepatorenal syndrome, for want of a better definition, has been described as renal failure in the presence of cirrhosis. Even after attempts have been made to rule out all of the causes which may lead to the "pseudo hepatorenal syndrome"'4 a sizeable group of patients remain in whom no therapy avails and whose situation ends fatally. Over the past several years, it has become clear that this group is heterogeneous and contains at least two types of patients. The initial attempt of classification on the basis of both plasma volume and cardiac output by Tristani and Cohn20 suggested that in one group, plasma volume was diminished and the cardiac output low with a normal or increased peripheral vascular resistance. In this group, volume infusions were of temporary benefit in increasing urine output as well as increasing cardiac index. In the other group, plasma volume appeared normal and cardiac index was elevated, often with a diminished peripheral vascular resistance.8'9'20 Unfortunately, a number of studies using both renal arteriography and 133Xenon scans have attempted to unify all patients in the hepatorenal syndrome into one
category.6'13
Ann. Surg. * July 1976
Recently one of us has suggested a classification for differentiating these two types of patients based on basically hemodynamic5'8'9"13 criteria similar to that proposed by Tristani and Cohn,20 in which the Type I patients consist of those patients, generally stable, without an acute insult, with a diminished plasma volume, decreased cardiac index and normal or increased peripheral vascular resistance. The other, those with an elevated cardiac index, decreased peripheral vascular resistance, and increased or normal plasma volume, generally occurs following an acute insult, is often associated with hepatic encephalopathy and recent deterioration in hepatic function. It has recently been proposed that portacaval anastomosis be considered as therapy for the hepatorenal syndrome in those patients who can tolerate the surgical procedure.13'18 It is our contention that portal-systemic decompression is only suitable in patients who are essentially hypovolemic and whose plasma volume is decreased with diminished cardiac indices, and that pharmacological therapy, which at present is unsatisfactory5'8'9,1215'16"19 be recommended for the other group as portacaval anastomosis is likely to result in the death of the patient. The case herein reported is offered as an example of the Type I hepatorenal syndrome, where portal systemic decompression may succeed. This patient manifested a normal cardiac index, approximately 3.5 1/min/ m2, which in our experience, using the indocyanine green indicator method has suggested classification as a "Type I patient.' 5,8,9,13,20 Similarly, there was no mild hypotension, usually associated with a Type II hepatorenal syndrome, except in respect to hypovolemia. In spite of infusions of salt poor albumin, urinary output increased only transiently, and diuretic and Prednisone therapy was without benefit. Associated findings here were narrowing of the inferior vena cava at the point of entrance of the hepatic vein, and although a diaphragm was not seen, this has been reported by others.3 Hepatic vein wedge pressure was markedly elevated, suggesting severe post-sinusoidal block and marked portal hypertension. This patient's acute deterioration was undoubtedly due to the effects of angiogram dye, perhaps aggravated by paracentesis, although the patient had been hydrated and a number of days had elapsed to allow equilibration following paracentesis. The pathophysiology in such patients, who admittedly are rare, may be on the basis of pooling of the blood volume within the splanchnic circulation as suggested by Tristani and Cohn,20 with the loss of a high volume of protein rich ascites (total protein in the ascites was 2.6 gr/100ml) from a severely congested liver secondary to high degree outflow block or as previously suggested by Schumaker and his colleagues17 and recently reemphasized by Gordon and her co-workers,11 a "porto-
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renal reflex." As such, the improvement of this patient whether secondary to portal decompression alone or portal decompression in association with left renal denervation must remain a moot point. In her present state of health, the patient refuses to undergo further angiographic studies and since there is a possibility of sensitivity to iodinated dyes, we have been reluctant to press the issue. Since, however, the "portorenal reflex," if it is at the root of such disordered pathophysiology, is mediated via the sympathetic nerves,16 the relief of portal congestion is probably sufficient and renal denervation is not required. Moreover, in most cases of hepatorenal syndrome, the infusion of phenoxybenzamine or dibenzyline directly into the kidney has been without effect, although the type of patient in whom this was attempted has not been clearly defined.6 The diuresis in this patient occurred within half an hour of removal of the shunt clamps and suggested that the portal decompression was distinctly related to the diuresis. The extraordinarily high urinary sodium seen within the first four hours after diuresis suggests that the renal cortical nephrons were being almost preferentially perfused. The reasons for this are not clear. The patient received a trial of L- Dopa prior to operation, however, this was terminated approximately 24 hours before the operative procedure, and it is unlikely that the natriuretic effect of L-Dopa7 persisted. Subsequently, however, urinary sodium returned towards normal and has remained in the 30 to 40 mEq/liter range. The ultimate outcome in this patient following one episode of ascites reaccumulation associated with mild gastrointestinal bleeding suggested that the relief of altered pathophysiology was not total and that during a period of hepatic decompensation and gastrointestinal bleeding, the tendency towards the hepatorenal syndrome persisted as it was provoked by gastrointestinal bleeding. It is to be emphasized, however, the patient is now on an unrestricted salt intake without diuretics and remains ascites free.
Addendum When last seen on 4/8/76, she had developed a superficial lesion of the right tonsillar pillar, biopsy-squamous cell carcinoma, treated with radiation, there were no neck nodes. Chemistries were as follows: BUN 21 mg/100 ml, creatinine 0.7 mg/100 ml, total protein 7.8 with albumin 4.2 gm/100 ml, globulin 3.6 gm/100 ml, bilirubin 0.3/0.8 mg/100 ml, SGOT 24, alkaline phosphatase 4.1 Bodansky Units. Na 143, K 4.3, C 198, CO2 25.
References 1. Abel, R. M., Beck, C. H., Jr. et al.: Improved Survival from Acute Renal Failure Following Treatment with Intravenous
25
Essential L-Amino Acids and Glucose. N. Engl. J. Med., 288:695, 1973. 2. Baldus, W. P., Reichter, R. N. and Summerskill, W. H. J.: The Kidney in Cirrhosis. I. Clinical and Biochemical Features of Azotemia in Hepatic Failure. Ann. Intern. Med. 60:353, 1964. 3. Chuji, K., Matsuda, S., Hoie, H. and Hirocka M.: Membranous Obstruction of the Hepatic Portion of the Inferior Vena Cava. Clinical Study of Nine Cases. Surgery, 72:551, 1972. 4. Conn, H. O.: A Rational Approach to the Hepatorenal Syndrome. Gastroenterology, 65:321, 1973. 5. Dodsworth, J., James, J. H., Cummings, M. G. and Fischer, J. E.: Diagnosis and Therapy of the Hepatorenal Syndrome, A Tentative Classification. Surg. Forum, 24:396, 1973. 6. Epstein, M., Berk, D. P., Hollenberg, N. K. et al.: Renal Failure in the Patient with Cirrhosis. Am. J. Med., 49:175, 1970. 7. Finlay, G. D., Whitsell, T. L., Cucinell, E. A. and Goldberg, L. I.: Augmentation of Sodium and Potassium Excretion Glomerular Filtration Rate and Renal Plasma Flow by LevoDopa. N. Engl. J. Med., 284:866, 1971. 8. Fischer, J. E.: Neurotransmitters and Hepatic Failure. Conn. Med., 36:575, 1972. 9. Fischer, J. E.: Acute Hepatic Failure. In The Liver-The Molecular Biology of Its Disease. Frederick F. Becker, Ed. New York, Marcel Dekker. (1975) Part B 725. 10. Goldstein, H. and Boyle, J. D.: Spontaneous Recovery from the Hepatorenal Syndrome. Report of Four Cases. N. Engl. J. Med. 272:895, 1965. 11. Gordon, S. J., Bazzato, G., Oresti, G. and Kowlesar, 0. D.: Experimental Portal Hypertension: Effect on Renal Function. Gastroenterology, 53:735, 1973. 12. Gornel, D. L., Lancestremere, R. G., Papper, S. and Lowenstein, L. M.: Acute Changes in Renal Excretion of Water and Solute in Patients with Laennec's Cirrhosis Induced by the Administration of the Pressor Amine, Metaraminol. J. Clin. Invest., 41:594, 1962. 13. Kew, M. C., Limbrick, C., Varma, R. R. and Sherlock, S.: Renal and Intrarenal Blood Flow in Non-Cirrhotic Portal Hypertension. Gut, 13:763, 1972. 14. Koppel, M. H., Coburn, J. W., Mims, M. M. et al.: Transplantation of Cadaveric Kidney from Patients with Hepatorenal Syndrome: E-vidence for The Functional Nature of Renal Failure in Advanced Liver Disease. N. Engl. J. Med., 280: 1367, 1969. 15. Iwatsuri, S., Popotzer, M. M., Corman, J. L. et al.: Recovery from Hepatorenal Syndrome After Transplantation. N. Engl. J. Med., 289:1155, 1973. 16. Nori, M., Austen, W. G. and McDermott, W. V., Jr.: Role of Hepatic Arterial Blood Flow and Hepatic Nerves on Renal Circulation and Function. I. Acute Studies in the Dog. Ann. Surg., 162:849, 1965. 17. Onnis, M., Schumacker, H. B., Jr. and Bounous, G.: Response to Occlusion of the Portal Vein: Blood Pressure and Renal Blood Flow. Arch. Surg., 85:897, 1962. 18. Schroeder, E. T., Numann, P. J. and Chamberlain, B. E.: Functional Renal Failure in Cirrhosis. Recovery After Portacaval Shunt. Ann. Intern. Med., 72:923, 1970. 19. Sugerman, J. H., Berkowitz, H. D., Davidson, D. T. and Miller, L. D.: Treatment of the Hepatorenal Syndrome with Metaraminol. Surg. Forum, 21:359, 1970. 20. Tristani, F. E. and Cohn, J. J.: Systematic and Renal Hemodynamics in Oliguric Hepatic Failure: Effect of Volume Expansion. J. Clin Invest. 46:1894, 1966.
