I
CLINICAL NUTRITION CASES
I
DIARRHEA COMPLICATING ENTERAL FEEDING AFTER LIVER TRANSPLANTATION In this case report we present in detail the complex nature of enteral feeding, diarrhea, hypoalbuminemia, and edema in a critically ill patient. We also discuss the use of a peptide-elemental formula in this patient, who suffered continuous diarrhea for 15 weeks after liver transplantation. Use of this formula was associated with cessation of the diarrhea and permitted adequate nutritional delivery. After 26 weeks of mechanical pulmonary ventilation, extubation was possible. This case illustrates the ineffectiveness of parenteral albumin infusions for treatment of enteral edema and demonstrates the restoration of normal intestinal absorptive capacity when ultrafiltration was instituted and the patient’s generalized edematous state was corrected.
Diarrhea, reported to affect as many as 68% of patients in intensive care units,‘ causes significant morbidity in the critically ill patient receiving enteral hyperalimentation. The cause of the diarrhea is probably multifactorial; many factors have been implicated, including antibiotic^,^^^ sepsis,* formula ~ s m o l a r i t y , and ~ the presence of multiple-organ f a i l ~ r e . Recent ~ reports have also identified both dietary fat content6 and low concentration of albumin in s e ~ u m ~ -as ~ Ocrucial to the pathogenesis of the diarrhea. The former is thought to cause diarrhea by an osmotic process that occurs when relative pancreatic insufficiency exists and fat is poorly digested. The later process, hypoalbuminemia, is thought to cause bowel-wall edema and thereby also to interfere with absorption. The patient in the intensive care unit, who is frequently intubated, septic, and severely malnourished, requires a diet high in both calories and protein. However, significant malabsorption occurs in this population, frustrating attempts at enteral alimentation. Peptide formulas have been designed to provide the protein required by these paThis case was prepared by Richard Benya, M.D., Prabha Damle, M.S.R.D., and Sohrab Mobarhan, M.D., of the Clinical Research Nutrition Unit, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612. 148 NUTRITION REWEWSIVOL 48,NO 3IMARCH 1990
tients in a form that is readily absorbed; however, most of these formulas are also high in fat content. Similarly, “elemental” formulas, designed to provide calories in monomeric, absorbable form, possess exceedingly high osmolarities and may cause diarrhea when used alone. In the following case report we demonstrate the benefit of an enteral diet composed of a combined peptide-elemental formula (Reabilan HN and Vivonex TEN) to a patient who, prior to starting on the combined diet, suffered near continuous diarrhea when given various other, largely polymeric, formulas. This combined formulation (Table 1) created a diet low in fat, with acceptable osmolarity, and was composed of rapidIy-abso rbed macronutrients. Use of this combined peptide-elemental diet permitted delivery of adequate calories and protein, such that marked clinical improvement occurred. We shall also discuss the effect of parenteral albumin infusions and ultrafiltration on the course of diarrhea in this case.
Case Report A 58-year-old Caucasian woman underwent orthotopic liver transplantation for end-stage primary biliary cirrhosis. She received the antibiotic cefotetan intraoperatively; atothiaprine, cyclosporin, and prednisone were given as immunosuppressive agents. Parenteral alimentation
TABLE 1 Calories, Protein, and Fat Content of Various Enteral Formulas Protein
Fat
Formula
(dl
kcmay
(g)
(g)
Percentage of kcal as Fat
mOsmflrg of Water
Osmolite Isocal Reabilan HN Vivonex TEN Reabilan (1200 mL)/ Vivonex (900 ml) combination
2400 2000 2000 2000
2544 2120 2660 2000
88 65 115 76
91 85 100 5.6
31.4 37 35 2.8
300 300 350 630
2100
2500
100
65
25
470
Volume/Day
with a formula containing 25% glucose, 4.25% amino acids, and a 10% lipid emulsion was started immediately after surgery. Enteral feeding (via feeding tube) with Ensure (Ross Laboratories, Columbus, OH) was started 10 days later. At this point the parenteral alimentation was reduced to 500 mL of 20% lipid emulsion only, and the patient continued to receive this fat supplement until postoperative week 15. Diarrhea commenced within two days of starting the Ensure (three to six copious bowel movements daily), and therapy was changed to half-strength Osmolite (Ross Laboratories, Columbus, OH); at first it was given as bolus feedings; however, since they were not tolerated, continuous delivery of Osmolite was initiated. Nevertheless, the diarrhea continued unchanged. Because the diarrhea persisted, multiple stools were checked for Clostridium difficile toxin; a positive test was obtained during postoperative week 10. A two-week course of oral vancomycin was instituted. Tests for C. difficile became negative with treatment, but the diarrhea persisted as Osmolite (half strength, 75 mUh) continued to be given. The biliary T-tube placed during the liver transplantation was noted to be producing excess bile during week 4, and a cholangiogram revealed an obstruction at the level of the ampulla. Laparotomy identified an infected hematoma, and 9 L of ascites fluid was drained. Tube-feeding with Osmolite started again after the laparotomy, and the diarrhea, which had resolved during the period in which the patient was given nothing per os, resumed. During this latter period the patient received -1 500 kcallday (via the infusion of Osmolite and 20% fat emulsion); the patient’s pulmonary status continued to require mechanical ventilation support. During week 5 the Osmolite was changed to lsocal (full strength, 50 mUh; Mead, Johnson,
Evansville, IN), but the diarrhea persisted. In an attempt to compensate for the significant rnalabsorption, tube-feeding with lsocal HCN (2 kcal/mL) was instituted during week 8. At this time qualitative stool tests for fat were positive. Quantitative studies were not done. The next week worsening of the diarrhea prompted a change to Reabilan (half strength, 50 mUh; O’Brien Pharmaceuticals, Parsippany, NJ); the patient’s diarrhea then ceased, and the defecations returned to normal. The grossly inadequate delivery of calories and protein caused the patient’s serum albumin concentration to decrease markedly to 1.5 g/dL by week I f . In addition, recurrent fevers again suggested an intra-abdominal abscess, and the patient underwent a second exploratory laparotomy during week 11. After this laparotomy and while receiving nothing per os, the patient did not suffer any diarrhea, and eight days later (during week 12) tube feedings with Reabilan HN were started again. At this time aggressive attempts were made to advance the feedings. As the amount of Reabilan was increased to 100 mUh (week 14), the diarrhea resumed. Over a five-day course during week 12, a total of 500 g of salt-poor albumin was administered. Although the concentration of albumin in serum rose to 2.6 gldL, there was no reduction in the amount of diarrhea. Kinking of the Dobhoff tube during week 14 led to cessation of the Reabilan (100 mUh) therapy, and the diarrhea again resolved. The Dobhoff tube was placed endoscopically in the third portion of the duodenum, and the patient was again given enteral feeding with Osrnolite. Despite liberal use of diphenoxylate hydrochloride with atropine, the diarrhea returned. During week 15 the Clinical Research Nutrition Unit consultation team recommended a mixture of 1200 mL of Reabilan HN with 900 mL NUTRITION REVIEWSIVOL 48,NO 3IMARCH 1990 149
of Vivonex TEN (Norwich Eaton, Norwich, NY) in order to provide adequate calories and protein at an acceptable osmolarity, with only 25% of calories provided as fat (see Table 1). The diarrhea, which at times exceeded six bowel movements per day, resolved within four days after administration of the peptide-elemental diet combination commenced. The presence of coliform bacteria in the urine (subsequently identified as Escherichia coli) resulted in parenteral therapy with vancomycin and gentamicin for two days until results of antimicrobial susceptibility tests were available. Twelve days after the diarrhea resolved with the Reabilan-Vivonex regimen, the patient became totally anuric. As the patient’s pulmonary and peripheral edema worsened, her frequency of defecation increased and diarrhea was again a problem, albeit less so than before the peptideenteral diet was started. In order to reduce the massive fluid overload, ultrafiltration was started during week 18, and a rapid reduction in the patient’s weight was achieved within a week. Simultaneous with the reduction in the patient’s weight, two events took place. First, diarrhea again resolved, never to return. Second, urine output returned as all nephrotoxic medicines (including the cyclosporin) were withdrawn. Since the patient’s nutritional needs were consistently met for the first time, a sustained increase in serum albumin concentration was achieved. With the improvement in nutritional status, the patient’s respiratory status improved, and weaning from the ventilator could be attempted. After 26 weeks the patient was finally extubated. Physical therapy and rehabilitation continued for the next three months of hospitalization in a general medicine ward, during which time the patient was able to tolerate a general diet.
Discussion This case illustrates the difficulty in meeting the nutritional requirements of a critically ill patient via the enteral route. A number of factors have been identified as responsible for the diarrhea seen during enteral alimentation; however, none of these factors have been reliably and consistently identified in all studies. Recently, a number of investigators have focused on the role of dietary fat content, suggesting that formulas low in fat are better tolerated. Gottschlich et a1.6 examined a variety of 150 NUTRITION RfflEWSlVOL 48, NO 3IMARCH 1990
diets provided to severely burned patients undergoing enteral hyperalimentation. They discovered that dietary tolerance was best achieved by use of formulations containing
CLINICAL NUTRITION CASES
I
DIARRHEA COMPLICATING ENTERAL FEEDING AFTER LIVER TRANSPLANTATION In this case report we present in detail the complex nature of enteral feeding, diarrhea, hypoalbuminemia, and edema in a critically ill patient. We also discuss the use of a peptide-elemental formula in this patient, who suffered continuous diarrhea for 15 weeks after liver transplantation. Use of this formula was associated with cessation of the diarrhea and permitted adequate nutritional delivery. After 26 weeks of mechanical pulmonary ventilation, extubation was possible. This case illustrates the ineffectiveness of parenteral albumin infusions for treatment of enteral edema and demonstrates the restoration of normal intestinal absorptive capacity when ultrafiltration was instituted and the patient’s generalized edematous state was corrected.
Diarrhea, reported to affect as many as 68% of patients in intensive care units,‘ causes significant morbidity in the critically ill patient receiving enteral hyperalimentation. The cause of the diarrhea is probably multifactorial; many factors have been implicated, including antibiotic^,^^^ sepsis,* formula ~ s m o l a r i t y , and ~ the presence of multiple-organ f a i l ~ r e . Recent ~ reports have also identified both dietary fat content6 and low concentration of albumin in s e ~ u m ~ -as ~ Ocrucial to the pathogenesis of the diarrhea. The former is thought to cause diarrhea by an osmotic process that occurs when relative pancreatic insufficiency exists and fat is poorly digested. The later process, hypoalbuminemia, is thought to cause bowel-wall edema and thereby also to interfere with absorption. The patient in the intensive care unit, who is frequently intubated, septic, and severely malnourished, requires a diet high in both calories and protein. However, significant malabsorption occurs in this population, frustrating attempts at enteral alimentation. Peptide formulas have been designed to provide the protein required by these paThis case was prepared by Richard Benya, M.D., Prabha Damle, M.S.R.D., and Sohrab Mobarhan, M.D., of the Clinical Research Nutrition Unit, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612. 148 NUTRITION REWEWSIVOL 48,NO 3IMARCH 1990
tients in a form that is readily absorbed; however, most of these formulas are also high in fat content. Similarly, “elemental” formulas, designed to provide calories in monomeric, absorbable form, possess exceedingly high osmolarities and may cause diarrhea when used alone. In the following case report we demonstrate the benefit of an enteral diet composed of a combined peptide-elemental formula (Reabilan HN and Vivonex TEN) to a patient who, prior to starting on the combined diet, suffered near continuous diarrhea when given various other, largely polymeric, formulas. This combined formulation (Table 1) created a diet low in fat, with acceptable osmolarity, and was composed of rapidIy-abso rbed macronutrients. Use of this combined peptide-elemental diet permitted delivery of adequate calories and protein, such that marked clinical improvement occurred. We shall also discuss the effect of parenteral albumin infusions and ultrafiltration on the course of diarrhea in this case.
Case Report A 58-year-old Caucasian woman underwent orthotopic liver transplantation for end-stage primary biliary cirrhosis. She received the antibiotic cefotetan intraoperatively; atothiaprine, cyclosporin, and prednisone were given as immunosuppressive agents. Parenteral alimentation
TABLE 1 Calories, Protein, and Fat Content of Various Enteral Formulas Protein
Fat
Formula
(dl
kcmay
(g)
(g)
Percentage of kcal as Fat
mOsmflrg of Water
Osmolite Isocal Reabilan HN Vivonex TEN Reabilan (1200 mL)/ Vivonex (900 ml) combination
2400 2000 2000 2000
2544 2120 2660 2000
88 65 115 76
91 85 100 5.6
31.4 37 35 2.8
300 300 350 630
2100
2500
100
65
25
470
Volume/Day
with a formula containing 25% glucose, 4.25% amino acids, and a 10% lipid emulsion was started immediately after surgery. Enteral feeding (via feeding tube) with Ensure (Ross Laboratories, Columbus, OH) was started 10 days later. At this point the parenteral alimentation was reduced to 500 mL of 20% lipid emulsion only, and the patient continued to receive this fat supplement until postoperative week 15. Diarrhea commenced within two days of starting the Ensure (three to six copious bowel movements daily), and therapy was changed to half-strength Osmolite (Ross Laboratories, Columbus, OH); at first it was given as bolus feedings; however, since they were not tolerated, continuous delivery of Osmolite was initiated. Nevertheless, the diarrhea continued unchanged. Because the diarrhea persisted, multiple stools were checked for Clostridium difficile toxin; a positive test was obtained during postoperative week 10. A two-week course of oral vancomycin was instituted. Tests for C. difficile became negative with treatment, but the diarrhea persisted as Osmolite (half strength, 75 mUh) continued to be given. The biliary T-tube placed during the liver transplantation was noted to be producing excess bile during week 4, and a cholangiogram revealed an obstruction at the level of the ampulla. Laparotomy identified an infected hematoma, and 9 L of ascites fluid was drained. Tube-feeding with Osmolite started again after the laparotomy, and the diarrhea, which had resolved during the period in which the patient was given nothing per os, resumed. During this latter period the patient received -1 500 kcallday (via the infusion of Osmolite and 20% fat emulsion); the patient’s pulmonary status continued to require mechanical ventilation support. During week 5 the Osmolite was changed to lsocal (full strength, 50 mUh; Mead, Johnson,
Evansville, IN), but the diarrhea persisted. In an attempt to compensate for the significant rnalabsorption, tube-feeding with lsocal HCN (2 kcal/mL) was instituted during week 8. At this time qualitative stool tests for fat were positive. Quantitative studies were not done. The next week worsening of the diarrhea prompted a change to Reabilan (half strength, 50 mUh; O’Brien Pharmaceuticals, Parsippany, NJ); the patient’s diarrhea then ceased, and the defecations returned to normal. The grossly inadequate delivery of calories and protein caused the patient’s serum albumin concentration to decrease markedly to 1.5 g/dL by week I f . In addition, recurrent fevers again suggested an intra-abdominal abscess, and the patient underwent a second exploratory laparotomy during week 11. After this laparotomy and while receiving nothing per os, the patient did not suffer any diarrhea, and eight days later (during week 12) tube feedings with Reabilan HN were started again. At this time aggressive attempts were made to advance the feedings. As the amount of Reabilan was increased to 100 mUh (week 14), the diarrhea resumed. Over a five-day course during week 12, a total of 500 g of salt-poor albumin was administered. Although the concentration of albumin in serum rose to 2.6 gldL, there was no reduction in the amount of diarrhea. Kinking of the Dobhoff tube during week 14 led to cessation of the Reabilan (100 mUh) therapy, and the diarrhea again resolved. The Dobhoff tube was placed endoscopically in the third portion of the duodenum, and the patient was again given enteral feeding with Osrnolite. Despite liberal use of diphenoxylate hydrochloride with atropine, the diarrhea returned. During week 15 the Clinical Research Nutrition Unit consultation team recommended a mixture of 1200 mL of Reabilan HN with 900 mL NUTRITION REVIEWSIVOL 48,NO 3IMARCH 1990 149
of Vivonex TEN (Norwich Eaton, Norwich, NY) in order to provide adequate calories and protein at an acceptable osmolarity, with only 25% of calories provided as fat (see Table 1). The diarrhea, which at times exceeded six bowel movements per day, resolved within four days after administration of the peptide-elemental diet combination commenced. The presence of coliform bacteria in the urine (subsequently identified as Escherichia coli) resulted in parenteral therapy with vancomycin and gentamicin for two days until results of antimicrobial susceptibility tests were available. Twelve days after the diarrhea resolved with the Reabilan-Vivonex regimen, the patient became totally anuric. As the patient’s pulmonary and peripheral edema worsened, her frequency of defecation increased and diarrhea was again a problem, albeit less so than before the peptideenteral diet was started. In order to reduce the massive fluid overload, ultrafiltration was started during week 18, and a rapid reduction in the patient’s weight was achieved within a week. Simultaneous with the reduction in the patient’s weight, two events took place. First, diarrhea again resolved, never to return. Second, urine output returned as all nephrotoxic medicines (including the cyclosporin) were withdrawn. Since the patient’s nutritional needs were consistently met for the first time, a sustained increase in serum albumin concentration was achieved. With the improvement in nutritional status, the patient’s respiratory status improved, and weaning from the ventilator could be attempted. After 26 weeks the patient was finally extubated. Physical therapy and rehabilitation continued for the next three months of hospitalization in a general medicine ward, during which time the patient was able to tolerate a general diet.
Discussion This case illustrates the difficulty in meeting the nutritional requirements of a critically ill patient via the enteral route. A number of factors have been identified as responsible for the diarrhea seen during enteral alimentation; however, none of these factors have been reliably and consistently identified in all studies. Recently, a number of investigators have focused on the role of dietary fat content, suggesting that formulas low in fat are better tolerated. Gottschlich et a1.6 examined a variety of 150 NUTRITION RfflEWSlVOL 48, NO 3IMARCH 1990
diets provided to severely burned patients undergoing enteral hyperalimentation. They discovered that dietary tolerance was best achieved by use of formulations containing
