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RECURRENT HEPATIC COMA IN A CHRONIC HEMOOIAL YSIS PATIENT: SUCCESSFUL TREATMENT BY CAPO

Marc F. Segaert Bernard Carlier and Johan Verbanck ABSTRACT A hemodialysis patient developed hepatic cirrhosis with subsequent portal-systemic encephalopathy. Switching from hemodialysis to CAPD prevented the recurrent episodes of hepatic coma. This observation suggests that, in combined chronic renal and hepatic failure with portal-systemic encephalopathy, CAPD may be the treatment of choice. This paper presents evidence to support this assumption.

Chronic hemodialysis patients frequently develop hepatitis B, which sometimes results in hepatic cirrhosis . Portal-systemic encephalopathy (PSE) may ensue. We describe a patient in whom mild PSE repeatedly progressed to full hepatic coma during hemodialysis sessions. Switching the patient from hemodialysis (HD) to continuous ambulatory peritoneal dialysis (CAPD) prevented the recurrent hepatic coma.

CASE REPORT A 60-year-old woman with chronic glomerulonephritis was started on chronic hemodialysis in February 1973. In 1974 she contracted hepatitis B. This disease ran an asymptomatic course but the serum transaminase levels never returned to normal and hepatitis B surface antigen persisted in her blood. By 1977 she had hepatic cirrhosis with signs of PSE. Her mental state deteriorated. Frequently she was agitated or depressed. There was a day-night reversal in sleep rhythm. Personal care was neglected. Her blood ammonia level was almost constantly elevated (levels between

Key words: Chronic renal failure, CAPD, hepatic cirrhosis, ammonia, portalsystemic encephalopathy From the Division of Nephrology, Department of Internal Medicine, Heilig Hart Ziekenhuis, Wilgenstraat 2, 8800 Roeselare, Belgium.

150 and 250 μg/dl). Ultrasonography showed a macronodular liver and a slight splenomegaly; there was minimal ascites and the portal vein was dilated. Liver scintigraphy demonstrated marked uptake of the isotope by the spleen and bone marrow suggesting portalsystemic shunting. She was given a protein-poor diet of 60 g per day and lactulose, which she took up to 70g daily. Between March 1977 and September 1980 the patient was admitted II times with severe PSE (Fig. I). She came in lethargic, and proceeded to stupor and coma at the end of the dialysis procedure. She was lethargic on admission perhaps because surreptitiously, she took tranquillizers or hypnotics during the night. Also apparently she did not follow dietary advice in the period between dialyses as shown by diet q uestionnaires. Blood ammonia levels almost always peaked to values between 250 and 400 μg/dl in these circumstances. We never noted severe hypokalemia or hypoglycemia during dialysis. Sharp falls in blood pressure however were not infrequent. Dialysis was performed with a flat plate I m cuprophane artificial kidney, for four hours three times weekly. The dialysate was glucose-free and contained acetate as an alkalinizing agent; the potassium concentration was at I mEq/l.

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Potassium chloride was added I. V. during dialysis to keep the serum potassium above 3.5 mEq/l. The patient always regained consciousness 24 to 48 hours after intensive treatment with cleansing enemas and lactulose given in enema and via a nasogastric tube. Between October 1980 and February 1981 the comas succeeded each other at a dramatic rate. The patient was admitted at least once monthly for treatment of hepatic coma (Fig. I) -an untenable situation. A trial with CAPD, at this time a new technique in our unit. was undertaken. On 3/3/81, a peritoneal catheter was inserted during a short general anesthesia. This precipitated hepatic coma. The first two days on CAPD the patient was unconscious and she was treated, as before, by cleansing enemas and lactulose given in enema and by gavage. This was the last time we had to perform this procedure . She has been on CAPD for almost two years. She felt much better than on HD. Her dry weight rose in 12 months from 51 to 63 kg. Severe PSE never recurred (Fig. 2). Mild PSE frequently was noted. Her EEG improved markedly. Lactulose was stopped without ill effect. Repeated questionnaires revealed that spontaneously she took in between 45 and 55 g of protein daily. Blood chemistries changed significantly. The blood urea level came down from a mean predialysis value of 181 &plusmn; 23 fig/dl (last 12-fionth period on HD) to 87 &plusmn; 18 fig/dl during CAPD (first 12 month period on CAPD) (p < 0.001). In this period mean baseline blood ammonia levels dropped from 208 &plusmn; 46 &mu;g/dl to 153 &plusmn; 33 &mu;g/dl (p < 0.001); there were no more peak levels. Total protein went down from 6.75 &plusmn; 0.19 g/dl to 5.64 &plusmn; 0.66 g/dl (p < 0.001). Exchanges were performed by her 70-yearold husband using three 2-liter bags of glucose 1.36 g/dl and one 2 -liter bag of glucose 3.86 g/dl. Peritonitis was a frequent problem. Infection was due to lapses in sterile technique rather than to the propensity of cirrhotics to develop peritonitis. The isolated bacteria were always either Staphylococcus aureus or Staphylococcus epidermidis. Never was there any growth of gram-negative bacteria. The patient was last seen for a routine checkup on November 13, 1982. She felt rather well. Her ammonia level was at 90 &mu;g/dl. A few days later at home she developed fever, diarrhea and vomiting . She was brought in the next day dehydrated, hypotensive and stuporous. Her ammonia level was at 470 &mu;g/dl, the highest ever. She died within a few hours after admission. An autopsy could not be performed.

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DISCUSSION Hepatic encephalopathy is multifactorial in origin. Synergism between toxic

and metabolic factors is well recogn ized. Metabolic abnormalities augment the role of toxins. Given an underlying state of subacute or chronic intoxication with ammonia a comparatively small increase in a single toxin or an intensification of hypoxia, hypovolemia, electrolyte depletion or acid-base imbalance may be enough to precipitate overt encephalopathy (I). Ammonia plays a central role in the pathogenesis of PSE. High levels are often associated with severe PSE. Protein, urea and amino-acids are ammonia-generating substances. An aspect of CAPD which may be beneficial for patients with hepatic encephalopathy seems to be the spontaneously poor dietary intake of protein by CAPD patients. On a free diet they seldom

ingest more than 1 g of protein per kg body weight per day (2,3). Peritoneal glucose absorption seems to interfere with appetite (3). Thus patients who were unsuccessful in observing a protein-poor diet during HD find it an easy task on CAPD. Furthermore, the lower total body urea pool also results in diminished ammonia formation. Urea is lower despite a 40% decrease in weekly urea clearance in CAPD as compared to HD (4). The lower urea level is due mainly to the protein-poor diet and the substantial losses of protein and amino acids in the peritoneal effluent (4). A second important advantage of CAPD, as compared to HD, is the absence of dysequilibrium of any kind. There are no acute changes in intra or

extracellular fluid volume or composition. Blood pressure, pH, level ofNa+ , K+ CI , Ca++ , etc. remain constant. In CAPD there is also a constant abundance of glucose, the main brain fuel, whereas during HD patients frequently do not eat and they lose glucose in the dialysate. PSE as a multifactorial event is known to be precipitated by acute drops in blood volume, serum potassium and blood glucose (I). The "uremic middle molecules" possibly contribute, as most toxins do, to the pathogenesis of PSE in chronic renal failure patients with cirrhosis. These toxic molecules pass through the peritoneal membrane more easily than through conventional dialysis membranes (5). Their weekly clearance on CAPD is about six times higher than on HD (6). One might also speculate that the chronic loss of amino acids in the peritoneal effluent may cause an alteration in plasma aminoacid metabolism, which results in alterations in

brain neurotransmitters. PSE is known to be associated with increased brain concentration of the neutral aminoacids -phenylalanine and tyrosine. They may disturb cerebral catecholamine metabolism and promote the synthesis of false neurotransmitters (7). We conclude that CAPD may be the treatment of choice in patients with combined chronic renal failure and hepatic cirrhosis with PSE. The present case adds evidence to support this conclusion.

ACKNOWLEDGEMENTS The authors thank Prof. Dr. J. Fevery, division of hepatology, University of Leuven, Belgium, for helpful suggestions in preparing this manuscript and Mrs. Sarah Reed for careful linguistic advice.

REFERENCES 1. Zieve L. The mechanism of hepatic coma. Hepatology 1981;1:360-366. 2. Randerson DH, Chapman GV, Farrell

PC. Amino acid and dietary status in CAPD patients. In: Atkins RC et al eds. Peritoneal Dialysis. Edinburgh London Melbourne & New York: Churchill Livingstone. 1981:179-191. 3. Gah1 GM, Baeyer HV, Riedinger R et al. Caloric intake and nitrogen balance in patients undergoing CAPD. In: Moncrief JW, Popovich RP eds. CAPD update. New York: Masson Publishing USA, Inc. 1981:87-93. 4. Blumenkrantz MJ, Kopple ill, Moran JK et at. Nitrogen and urea metabolism during continuous ambulatory peritoneal dialysis. Kidney Int 1981;20:7882. 5. Bergstrom J. Finding the uremic molecule(s). In: Moncrief JW, Popovich RP eds. CAPD update. New York: Masson Publishing USA, Inc. 1981:103-108. 6. Popovich RP, Moncrief JW .Nolph KD et al. Continuous ambulatory peritoneal dialysis. Ann Intern Med 1978;88: 449-456. 7. James JH. Ziparo V, Jeppson B, Fischer JE. Hyperammonaemia. plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portalsystemic encephalopathy. Lancet 1979;2: 772775.

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