Parenteral Hyperalimentation: A Useful Surgical Adjunct

Symposium on Recent Advances in Surgery

Parenteral Hyp~ral imentation A Useful Surgical Adjunct

Joseph O. Sherman, M.D., * Thomas Egan, M.D.,** and Fidel V. Macalad,M.D. t

Few reports in the medical literature during the past decades have stirred as much interest as the work of Dudrick and associates 7 , 8, 9, 24, 25, 26 of the University of Pennsylvania which demonstrated that sufficient protein, calories, and minerals could be given intravenously to maintain positive nitrogen balance and promote normal weight gain, growth and development. The main component of the solution, protein hydrolysate, has been available for many years as a 5 per cent solution in 5 per cent dextrose in water. Until recently, protein hydrolysates enjoyed little popularity because of their inability to increase lean tissue mass when given with 5 per cent dextrose and water. It has long been known that a minimum of 120 to 150 nonprotein calories must be given with each gram of parenteral nitrogen to supply the necessary energy for protein synthesis and for the normal metabolic needs of the body.lO, 11, 16, 17, 18 When protein hydrolysate is infused without sufficient nonprotein calories, the amino acids in the hydrolysate are deaminated and oxidized for energy. Unfortunately, to supply the necessary protein and calories for positive nitrogen balance a hypertonic solution of glucose and protein hydrolysate was required and had to be infused for more than a few days. The dangers of giving this type of solution for a week or longer were well known: thrombophlebitis, sepsis, overhydration, hyperglycemia, glucosuria, osmotic diuresis, and dehydration. Dudrick et al. 8 have shown that the infusion of a solution of 3.5 per cent protein hydrolysate in 19.5 per cent dextrose in water (ratio of *Assistant Attending Surgeon, The Children's Memorial Hospital; Associate in Surgery, Northwestern University Medical School, Chicago, Illinois

** Attending Pediatrician, The Children's Memorial Hospital; Associate Professor of Pediatrics, Northwestern University Medical School, Chicago, Illinois tResearch Associate, Veterans Administration Research Hospital; Lecturer in Surgery, Northwestern University Medical School, Chicago This study was supported in part by U.S. Public Health Service Clinical Research Center Grant No. FR-199.

Surgical Clinics of North America- Vol. 51, No.1, February, 1971

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nitrogen to nonprotein calories, 1 :156) with added multivitamins and electrolytes can be tolerated for a month or longer if certain precautions are followed (see below). With this solution positive nitrogen balance with weight gain has been achieved in over 1000 patients. 5 The technique, termed parenteral hyperalimentation, has been used in a large variety of patients, including those with: preoperative malnutrition, severe burns, intractable diarrhea, gastroenteric fistulas, peritonitis, ulcerative colitis, regional enteritis, renal failure, anorexia nervosa, malabsorption syndrome, and carcinomatosis. It has also been used to restore positive nitrogen balance before major surgery.

CASE REPORTS While parenteral hyperalimentation has been applied to such problems in patients of all ages, we have found the technique particularly useful in the treatment of small infants suffering from disorders known to carry a high mortality rate. The brief histories of three such patients which follow illus.trate the useful application of parenteral hyperalimentation. PATIENT No. 1. G. J. was admitted to The Children's Memorial Hospital at 2 days of age with a history of bilious vomiting for 36 hours. Examination at the time of admission revealed a 3 pound, 14 ounce, white female who was well hydrated. There was no abnormal distention. An upright x-ray of the abdomen showed several air-fluid levels. Calcifications were noted in the right lower quadrant. At operation, multiple areas of atresia of the small bowel were found. After gastrointestinal continuity was re-established, the small intestine measured 30 cm. in length from the ligament of Treitz to the ileocecal valve. Postoperatively the patient had severe watery diarrhea whenever oral intake was started. Gastrointestinal transit time was 30 minutes. Five weeks after operation the patient's weight was unchanged from her admission weight. She was emaciated, weak, and hypothermic. Apnea and bradycardia occurred, probably from aspiration of vomitus. Resuscitation included endotracheal intubation. Although there was a question of permanent brain damage from the apnea, it was decided to start parenteral hyperalimentation. She remained on hyperalimentation for 1 month without oral feedings. During this period the diarrhea subsided; she became strong and active and gained 1.14 pounds (Fig. 1). She was then started on oral intake and parenteral hyperalimentation was slowly tapered during the following month. Three months after starting hyperalimentation, she was taking full strength Similac and her stools were seedy yellow. Transit time was still 30 minutes. At the time of discharge she weighed 6.11 pounds. Subsequent follow-up revealed severe psychomotor retardation requiring permanent nursing home placement. Comment. This baby should have been placed on parenteral hyperalimentation before she had severe inanition. Unfortunately, this was our first patient and we did not have the equipment or supplies to start

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Figure 1. Photographs of patient No.1 on the day parenteral hyperalimentation was started (above) and one month later (below). The infant received nothing by mouth dUring this month.

hyperalimentation earlier. Although the procedure was successful in treating the child's short bowel syndrome, severe mental retardation required placing the patient in a nursing home. PATIENT No.2. E. L. was transferred to The Children's Memorial Hospital at 21f2 weeks of age with an enterocutaneous fistula. The child had been operated upon at 1 day of age for a high small bowel obstruction. An area of jejunal stenosis and atresia was resected, and an end-toend anastomosis was performed. Post operatively, the bowel remained obstructed, and the abdomen was re-explored 11 days later. The jejunal anastomosis was found to be disrupted and there was a large intraabdominal abscess. The proximal and distal segments of bowel were identified and re-anastomosed. On the third post operative day, yellowgreen fluid began to drain from the wound. Several attempts to insert a hyperalimentation catheter were unsuccessful. The child was then transferred to The Children's Memorial Hospital. Physical examination at the time of admission revealed a lethargic white male infant weighing 5 pounds, 13 1/2 ounces. The abdomen was fiat, and bowel sounds were active. There was a right paramedian scar with a central opening which was draining a mucoid greenish-yellow

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fluid. On the day of admission, a hyperalimentation catheter was inserted into the right brachial vein. An upper gastrointestinal series demonstrated passage of contrast material through the fistula. Daily fistula drainage averaged about 20 to 80 ml. Stools were infrequent and small. Nine days after admission, the left brachial hyperalimentation catheter was accidentally pulled out. A right internal jugular catheter was inserted. Sixteen days after starting hyperalimentation, all fistula drainage stopped. The child was then "weaned" from hyperalimentation by slowly increasing oral intake and decreasing the hyperalimentation infusion. During the 25 days when the patient was on parenteral hyperalimentation without supplemental oral intake, he gained 1.19 pounds. His subsequent hospital course was uneventful, and he was discharged on the sixty-eighth day of hospitalization. When last seen at 4 months of age, he was eating a normal diet for his age and weighed 12 pounds. Comment. Operative closure of the enterocutaneous fistula would have been difficult and dangerous. Patients with enterocutaneous fistulas seem to be ideal candidates for parenteral hyperalimentation. They are usually in negative nitrogen balance, and most have undergone one or more major operative procedures. In all of our patients who had enterocutaneous fistulas, severe diarrhea, or excessive nasogastric drainage, treatment with parenteral hyperalimentation resulted in a rapid and marked decrease in gastrointestinal secretion and motility, with a marked diminution in losses of bowel contents. PATIENT No.3. C. H. was admitted to The Children's Memorial Hospital at 7 weeks of age with a history of diarrhea which had begun at 2 days of age. The diarrhea was often associated with non-bilious vomiting, and did not abate when various diet formulas were given, excluding milk protein, disaccharides, glucose, and galactose. She continued to have significant losses on an intake consisting of 2.5 per cent fructose in distilled water. The stools, which occasionally numbered as many as 20 each day, were foul-smelling and green. A barium enema examination was normal. After a hyperalimentation catheter was inserted into the right internal jugular vein, all oral alimentation was stopped for 38 days. During this period the child had one or two small stools each day. Weight gain during this period was almost 1 pound. Nitrogen balance studies showed a consistently positive balance of 0.75 to 1.00 gm. After 38 days the patient was "weaned" from hyperalimentation over a period of 8 days by slowly increasing oral intake and concomitantly decreasing the infusion. She was discharged on the sixtieth hospital day, 11 days after starting oral intake. Comment. Each year we treat several infants who have severe intractable diarrhea which responds to no form of conventional treatment. This child, for example, continued to have severe diarrhea even when fed oral 2.5 per cent fructose water. Cessation of diarrhea occurred promptly when all oral intake was stopped and parenteral hyperalimentation was started. All of our patients who are started on hyperalimentation for severe diarrhea are allowed nothing orally for a minimum of 4 weeks. Earlier feeding can cause a recurrence of the diarrhea. When resuming

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H YPERALIMENTATION

Table 1.

Summary of 22 Patients Treated with Parenteral Hyperalimentation LENGTH OF

PATIENT

AGE

DIAGNOSIS

TREATMENT WITHOUT ORAL INTAKE

G.V. E.S. J.D. R.D. M.L. M.L. E.S. J.H. C.S. E.L M.K KK W.C. HH. C.H. J.B. N.C. T.K M.M.'" M.H. T.O. KW.

2 months 1 month 1 month

Short bowel syndrome Gastroschisis Recurrent tracheoesophageal fistula P/2 months Annular pancreas 14 months Hirschsprung's disease 8 months Intractable diarrhea 3 months Intractable diarrhea 10 days Tracheoesophageal fistula 2 months Duodenal obstruction 21/2 weeks Enterocutaneous fistula 7 days Ruptured omphalocele 4 days Meconium peritonitis, ileal atresia Gastroschisis 2 months 10 days Tracheoesophageal fistula 2 months Intractable diarrhea Enterocutaneous fistula 2 months 7 days Jejunal atresia 8 months Adhesive small bowel o bs truction 14 months Omphalocele Intractable diarrhea 2 months 10 days Gastroschisis 17 days Duodenal obstruction

WEIGHT CHANGE

(Days)

(Pounds)

37 83 23

+1.14 +2.07 +1.23

7 14 35 56 8 15 25 20 21

+0.24 +0.37 -1.65" +2.00 +0.62 +0.31 +1.19 +0.13 +1.70

7 4 38 37 9 6

. +0.88 +0.44 +0.97 +1.98 +0.44 +1.78

5 40 4 4

+0.44 +0.26 +0.37

Average weight gain per day = 0.55 oz. ''This patient will be reported on in the near future.

oral feedings, care should be taken to challenge the digestive and absorptive mechanisms gradually. Even half-strength standard formula mixtures have led to a recurrence of diarrhea. Initial feeding usually consists of 5 per cent fructose in water. If tolerated, it has been our custom to begin oral feeding of one-quarter strength prepared milk formula, gradually increasing the strength every 2 days as tolerated. We have used parenteral hyperalimentation in more than 22 pediatric patients (Table 1). Positive nitrogen balance and weight gain were achieved in all but one patient, who was unique in that intravenous dextrose was not utilized normally. Our technique for mixing the solution,22 maintaining and caring for the catheter,6 and administering the solution9 are outlined below.

PREPARATION OF HYPERALIMENT ATION SOLUTION Three liters of 5 per cent fibrin hydrolysate':' and two empty liter bottles are placed in a laminar flow hood (Fig. 2)::":' The fibrin hydro"'Aminosol 5 per cent, Abbott Laboratories, North Chicago, Illinois ""'Clean Air Center, Model C, Abbott Laboratories, North Chicago, Illinois

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Figure 2, All hyperalimentation solution is prepared in a laminar air flow hood by a registered pharmacist to minimize the chances of bacterial and fungal contamination.

lysate is distributed equally among the 5 bottles so that each contains 600 ml. Using syringes, magnesium sulfate (8,5 ml. of a 10 per cent solution), sodium chloride (24 mEq.), and potassium chloride (12 mEq.) are added. Finally, the solution is brought to 1000 ml. by adding 50 per cent dextrose in water. Quality control consists of visual inspection for particulate matter or color change, and a check for bacterial and fungal contamination. Microbiological examination includes culturing each batch of solution in thioglycolate and Sabouraud's broth. We have had minimal problems with bacterial contamination. In fact, it is unlikely that bacteria could grow in this solution. The low pH (5.35) and high osmolarity (> 1400 mOsm. per liter) tend to inhibit bacterial growth,13 Fungal contamination can be a problem. Candida species grow well at a pH of 5.7.23 Candida fungemia has been reported as a complication of this procedure.1.3. 4.12.26 Multivitamins'~ (10 ml.) and cyanocobalamin'~* (1 ml.) are added just prior to administration because of their questionable stability when added at the time of preparation of the solution. 15 This final solution (see Table 2) has a nitrogen-calorie ratio of about 1: 180. The basic solution of fibrin hydrolysate, dextrose, magnesium sulfate, and electrolytes begins to darken after 30 days at room tempera"M.V.I., u.s. Vitamin Pharmaceutical Company, New York **Rubramin-P.C., E.R. Squibb and Company, New York

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Table 2.

Composition of Hyperalimentation Solution

pH Osmolality (mOsm. per liter) Protein (gm. per 100 ml.) Calories (per 100 ml.) Glucose (gm. per 100 mI.)

5.35 >1400 3 92 20

ture, or 120 days when under refrigeration. Since darkening of the solution may indicate the presence of undesirable products, no more than a 30 day supply is Inixed at one time. I5

INSERTION OF HYPERALIMENT ATION CATHETER In all of our infants and children, who ranged in age from 4 days to 14 months, we usually inserted the hyperalimentation catheter into the superior vena cava via the external or internal jugular vein. Occasionally a brachial vein was used. All catheters were inserted in the operating room using careful aseptic technique. We prefer to use a No. 5 French polyvinylchloride umbilical artery catheter* because it does not kink, has little tissue reactivity, and is radio opaque. We have tried using silicone catheters but find them to be too soft and easily obstructed. Marked resistance is occasionally encountered when threading the catheter from the external jugular vein through the subclavian vein and into the superior vena cava, because of the acute angle between the jugular and subclavian veins. This difficulty can be minimized by doing the jugular vein cut-down very close to the clavicle and by pulling cephalad on the jugular vein to straighten the angle between the two veins. After completion of the cut-down, the proximal end of the catheter is tunneled subcutaneously and brought out through a stab wound over the mastoid process. The position of the tip of the catheter is always checked by obtaining a chest x-ray immediately after the cut-down is performed.

INFUSION OF HYPERALIMENTATION SOLUTIONS

Iri all pediatric patients, we use a peristaltic pump*'~ to maintain a constant infusion rate despite fluctuations in central venous pressure. It has been shown that if the hyperalimentation solution is given at a steady, constant rate, so that the glucose is infused not faster than 1.2 gm. per kg. per hr., hyperglycemia, glycosuria, diuresis, and dehydration can be prevented. 9 To prevent possible contamination from the hyperalimentation solution, a 0.22 micron filter*** is inserted in series in the intravenous

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*Argyle (Cat. No. MAR 1602-5), Aloe Medical, St. Louis, Missouri "*Ivac Model 400, Ivac Corporation, La Jolla, California; or Harvard Model No. 1203, Harvard Apparatus Company, Inc., Millis, Massachusetts ***Swinnex-25 Millipore filter, Millipore Corporation, Bedford, Massachusetts

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tubing just proximal to the superior vena cava catheter. The hyperalimentation solution, tubing, and burette and filter are changed every 2 or 3 days to further minimize bacterial and fungal contamination (Fig. 3). In infants, we infuse approximately 125 mI. of hyperalimentation solution per kilogram of body weight daily. This supplies 3.75 gm. protein, 3.7 mEq. sodium, 2.7 mEq. potassium and 5.2 mEq. chloride per kilogram of body weight daily. This compares favorably with the per kilogram dietary requirements of an infant weighing less than 10 kg. (3 gm. protein, 2 to 4 mEq. sodium, 2 to 3 mEq. potassium, and 2.3 mEq. chloride).19 Normally, the infants have a glycosuria with a blood sugar of 200 to 300 mg. per 100 mI. for 2 to 3 days. After this initial period of acclimatization, the blood sugar averages 60 to 80 mg. per 100 mI., and glucosuria disappears. There is some variability in the patients' adaptation to the load of infused dextrose, and it has been necessary on occasion to adjust the infusion rate below the necessary level for the first few days in order to prevent osmolar dehydration. Careful monitoring of weight, and urinary volume, frequency, and dextrose will provide an index for correct adjustment of the infusion rate. Weekly hematocrit, serum protein, blood urea nitrogen, blood sugar, electrolytes, and bilirubin determinations are performed upon each patient. We have seen anemia in some of our patients on hyperalimentation. The explanation for this is unknown. In the absence of large extrarenal losses of fluid and electrolytes, we have noted no marked alterations in sodium, potassium, or chloride. We have not seen hypokalemia, al-

Figure 3. A peristaltic pump is used to maintain a constant rate of infusion. Note the Millipore filter just proximal to the hyperalimentation catheter.

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though theoretically the infusion of large amounts of glucose may drive potassium into the cell. 21

CARE OF THE CATHETER The site of entrance of the catheter into the scalp is cleansed every 3 days'" All tape and dressings are removed from the catheter, and ether or acetone is used to defat the skin around the catheter (Fig. 4). Povidoneiodine" is then applied to the skin and allowed to dry. About 2 to 4 ml. of antibiotic ointment'~~' is applied at the point at which the catheter enters the skin. Finally, the catheter is secured with 2 inch gauze pad and tape.

COMPLICATIONS Most of the patients selected for parenteral hyperalimentation at The Children's Memorial Hospital have been critically ill. We have not used the procedure routinely on healthy infants undergoing major operative procedures. The technique of parenteral hyperalimentation is not without danger and should be reserved for selected patients.

Figure 4. Site of entrance of polyvinylchloride catheter into scalp one month after insertion. The catheter enters the external jugular vein just above the right clavicle. *Betadine solution, The Purdue Frederick Company, Yonkers, New York **Neosporin antibiotic ointment, Burroughs Wellcome and Co. (U.S.A.), Inc., Tuckahoe, New York

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Among our first 22 patients, 3 had serious systemic infection with positive blood cultures while on hyperalimentation. Two of the cultures grew out Candida species, while the third contained Staphylococcus aureus (coagulase positive). One of the 2 patients with Candida fungemia died from sepsis. Eight other catheters, when cultured after removal, were found to grow microorganisms. In each case there was an associated infection in another part of the body. This problem of contamination of a venous catheter is similar to the infections associated with ventriculoatrial shu~ts for hydrocephalus. 20 It is now routine on our service to obtain a blood culture whenever a patient on parenteral hyperalimentation develops an elevated temperature. If sepsis is suspected, the catheter is removed and cultured. Interestingly we have not had one infection at the point where the catheter enters the skin. Several of our earlier catheters were pulled out when patients were moved. We have not had this problem since incorporating several coils of the catheter in the dressings over the scalp wound. In two patients, severe dehydration occurred when nursing personnel increased the infusion rate to "catch up." The dehydration was corrected by reducing the infusion rate and giving supplementary 5 per cent dextrose and water. Two patients developed a transitory maculopapular rash, located primarily on the torso and around the mouth. A similar case has been reported recently.21 Both patients had been on hyperalimentation for more than three weeks. Conceivably the rash could have been caused by the lack of some trace element not supplied by the hyperalimentation solution. Many of our patients on hyperalimentation exhibited a constant and progressive drop in hemoglobin and hematocrit, requiring blood transfusion. We have not been able to explain this anemia. Possibly it is caused by red blood cell hemolysis from the hypertonic solution. We have not observed a rise in indirect bilirubin, nor has clinical jaundice occurred. We have not seen obstruction of major vessels,12 metabolic acidosis,14 pulmonary edema,14 or hyperosmolar coma. 21

REFERENCES 1. Ashcraft, K. W., and Leape, L. L.: Candida species complicating parenteral feeding.

J.A.M.A., 212:454-456, 1969. 2. Beal, J. M., Cornell, G. N., and Gilder, H.: Factors influencing nitrogen metabolism in surgical patients. Surgery, 36:468-486,1954. 3. Boeckman, C. R., and Krill, C. E., Jr.: Bacterial and fungal infections complicating parenteral alimentation in infants and children. J. Pediat. Surg., 5:117-126,1970. 4. Doolas, A.: Planning intravenous alimentation of surgical patients. SURG. CLIN. N. AMER.: 50:103-112,1970. 5. Dudrick, S. J.: Weight gain via vena cava. Medical World News, 10:30-34 (June 20), 1969. 6. Dudrick, S. J., Groff, D. B., and Wilmore, D. W.: Long-term venous catheterization in infants. Surg. Gynec. Obstet., 129:805-808,1969. 7. Dudrick, S. J., Wilmore, D. W., and Vars, H. M.: Long-term parenteral nutrition with growth in puppies and positive nitrogen balance in patients. Surg. Forum, 18:356-357, 1967.

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8. Dudrick, S. J., Wilmore, D. W., Vars, H. M., and Rhoads, J. E.: Long-term total parenteral nutrition with growth, development and positive nitrogen balance. Surgery, 64:134142, 1968. 9. Dudrick, S. J., Wilmore, D. W., Vars, H. M., and Rhoads, J. E.: Can intravenous feeding as the sole means of nutrition support growth in the child and restore weight loss in an adult? An affirmative answer. Ann. Surg., 169:974-984, 1969. 10. Gilder, H., Free, E. A., Weeks, D. L , Jr., and Beal, J. M.: Effect of hormones on the metabolism of surgical patients. Surg. Forum, 7:97,1956. 11. Grant, J. A. N., Moir, E., and Fago, M.: Parenteral hyperalimentation. Amer. J. Nursing, 69:2392-2395,1969. 12. Groff, D. B.: Complications of intravenous hyperalimentation in newborns and infants. J. Pediat. Surg., 4:460-464,1969. 13. Jawetz, E., Melnick, J. L., and Adelberg, E. A.: Medical Microbiology. Los Altos, California, Lang Medical Publications, 1964. 14. Kaplan, M. S., Mares, A., Quintana, P., Strauss, J., Huxtable, R F., Brennan, P., and Hays, D. M.: High caloric glucose-nitrogen infusions in post-operative management of neonatal infants. Arch. Surg., 99:567-571, 1969. 15. Klotz, R, Egan, T., and Sherman, J. 0.: Preparation of hyperalimentation solutions for the pediatric patient. Amer. J. Hosp. Pharm., (accepted for publication). 16. Larson, P. S., and Chaikoff, 1. L.: The influence of carbohydrates on nitrogen metabolism in the normal nutritional state. J. Nutrition, 13 :287, 1937. 17. Lawson, L. J.: Parenteral nutrition in surgery. Brit. J. Surg., 52: 795-800, 1965. 18. Moore, F. D.: Metabolic Care of the Surgical Patient. Philadelphia, W. B. Saunders Co., 1959. 19. Nelson, W. E., ed.: Textbook of Pediatrics, Philadelphia, W. B. Saunders Co., 9th ed., 1969. 20. Nulsen, F. E., and Becker, D. P.: Control of hydrocephalus by valve-regulated shunt: Infections and their prevention. Clin. Neurosurg., 14:256, 1966. 21. Rea, W. J., Wyrick, W. J., Jr., McClelland, R N., and Webb, W. R: Intravenous hyperosmolar alimentation. Arch. Surg., 100:393-398, 1970. 22. Serlick, S. E., Dudrick, S. J., and Flack, H. L.: Nutritional intravenous feeding: A contribution by the hospital pharmacist. Presented at the Third Annual Mid-Year Clinical Meeting, American Society of Hospital Pharmacists. Washington, Dec. 8-11, 1968. 23. Stechen, P. G., ed.: The Merck Index. Rahway, New Jersey, Merck and Co., Inc., 8th. ed., 1968. 24. Wilmore, D. W., and Dudrick, S. J.: Growth and development of an infant receiving all nutrients exclusively by vein. J .A.M.A., 203: 140-144, 1968. 25. Wilmore, D. W., Dudrick, S. J., Vars, H. M., and Rhoads, J. E.: Long-term intravenous hyperalimentation. Fed. Proc., 27:486,1968. 26. Wilmore, D. W., Groff, D. B., Bishop, H. C., and Dudrick, S. J.: Total parenteral nutrition in infants with catastrophic gastrointestinal anomalies. J. Pediat. Surg., 4:181-189, 1969. The Children's Memorial Hospital 2300 Children's Plaza Chicago, Illinois 60614