Ten Years Experience with Intravenous Hyperalimentation and Inflammatory Bowel Disease JAMES L. MULLEN, M.D., W. CLARK HARGROVE, M.D., STANLEY J. DUDRICK, M.D., WILLIAM T. FITTS, JR., M.D., ERNEST F. ROSATO, M.D.
A retrospective analysis was conducted on 74 patients with inflammatory bowel disease who were treated with intravenous hyperalimentation at the Hospital of the University of Pennsylvania between the years 1967-1976. Intravenous hyperalimentation can ameliorate the inevitable protein-calorie malnutrition present in patients with inflammatory bowel disease. Combined with complete bowel rest, intravenous hyperalimentation can effectively function as the primary treatment or as an adjunct to the surgical management of the complications of inflammatory bowel disease. Intravenous hyperalimentation can be safely administered to these severely ill patients, almost certainly improving survival rates in the patients treated. ALNUTRITION CONSISTENTLY OCCURS in patients lVi with inflammatory bowel disease (IBD). The catabolic effects of a chronic inflammatory process are combined with dysfunction of the gastrointestinal tract which impairs normal nutrient intake and absorption. These effects are readily apparent upon examination of the nutritional status of hospitalized patients with inflammatory bowel disease, particularly when complications of perforation, fistula or infection impose increased energy and caloric demands on the individual.39'2 The malnourishing effects of inflammatory bowel disease9 12 are multiple: 1) a substantial decrease in oral protein-calorie intake. This deficient intake is due to the anorexia associated with a chronic inflammatory disease and to avoidance behavior conditioned by the occurrence of gastrointestinal symptoms associated with eating; 2) a decrease in absorptive capacity secondary to extensive inflammatory disease of the intestine and to previous bowel resections. The ultimate effect of the malabsorption component will be determined by the capacity of the individual to increase his caloric and protein intake to compensate Presented at the Annual Meeting of the Southern Surgical Association, Hot Springs, Virginia, December 5-7, 1977. Reprint requests: James L. Mullen, M.D., 4th Silverstein Pavilion, Nutrition Support Service, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. Supported in part by an Educational Grant from McGraw Laboratories, Santa Ana, California.
From the Department of Surgery, University of Pennsylvania School of Medicine and the Philadelphia Veterans Administration Hospital, Philadelphia, Pennsylvania
for these absorptive losses; 3) a substantial loss of visceral protein through diseased segments of bowel, placing an increased demand on protein synthesis mechanisms and substrate availability; 4) increased energy-caloric demands generated by the hypermetabolic effects of the inflammatory process and by complications such as infection and peritonitis. In addition to the malnourishing effects of the disease process, the treatment for the primary disease significantly increases the nutritional burden of the already compromised host." A reduction in food intake and often complete bowel rest are employed during an acute exacerbation of symptoms in the patient with inflammatory bowel disease. This severely limits nutrient intake. The usual attempts at protein-calorie supplementation using specialized enteral feeding techniques are often unsuccessful in meeting nutritional needs. Corticosteroids are often administered to these patients, particularly those with severe disease. The side effects of these anti-inflammatory agents include general catabolic effects, poor wound healing and reduced host resistance to sepsis.10 Surgical procedures are often required in the treatment of inflammatory bowel disease, producing further malnourishing effects such as a decrease in absorptive surface, mandatory gastrointestinal dysfunction in the perioperative period and the hypermetabolic effects of major surgical trauma. The employment of adequate nutritional support in the patient with inflammatory bowel disease is easily justified in view of these multiple factors which lead to malnutrition.7'9"2 The adverse effects of nutritional depletion on the patient's course are substantial. Increased disease/treatment morbidity and mortality'0 and decreased therapy response rate occur in malnour-
0003-4932-78-0500-0523-0085 © J. B. Lippincott Company
523
524
MULLEN AND OTHERS TABLE 1. Disease Site, Age, Duration Hospital Stay Age Hospital Stay (Days)* # Patients (Years)*
Site
Ulcerative Colitis (UC) Regional Enteritis (RE) Granulomatous Colitis (GC) RE and GC Entire Population * Mean
+
24 17 8 25 74
44 36 31 32 37
± 3.4 z 3.8 ± 5.1 2.5 + 3.4
51.2 32.0 42.3 41.7 42.6
± 6.0 ± 2.5 ± 7.6 4.4 ± 4.7
SEM.
ished patients with inflammatory bowel disease. The repletion of nutritional deficits and the maintenance of adequate nutrition combined with complete bowel rest during an acute inflammatory episode may provide the additional benefits of avoiding surgery and reducing the length of hospitalization.7 Patients with inflammatory bowel disease and substantial decreases in voluntary oral food intake can be force-fed through two routes-enteral and parenteral. Although isolated successes13'15 have been reported via the enteral route, most nutritional support has been provided via total parenteral nutrition or intravenous hyperalimentation (IVH), particularly where complete bowel rest is a necessary component of the therapeutic regimen.7912 Since its inception at this institution,4 intravenous hyperalimentation has been utilized extensively in patients with inflammatory bowel disease. Some of the initial patients treated with IVH had extensive granulomatous disease of the intestine and early results were gratifying. This report encompasses our experiences in providing parenteral nutritional support to patients with inflammatory bowel disease during the past ten years, 1967 through 1976. The report covers the spectrum from the early years when IVH was a last resort to the more recent years when nutritional support has been instituted at an earlier stage. Clinical Material
From 1967 through 1976, adequate records were available for retrospective analysis on 293 patients who had 617 admissions to the Hospital of the University of Pennsylvania with a primary diagnosis of inflam-
UC RE
GC RE & GC Total *
Mean ± SEM.
24 17 8 25 74
Weight Loss (lbs) 20 21 16 17 19
+
3.1
± 4.2 ± 2.6 ± 2.1
± 3.0
9
May 1978
matory bowel disease (2.1 admissions per patient). Seventy-four patients (25%) were referred to the Surgical Service for nutritional evaluation and support
with intravenous hyperalimentation. These 74 patients underwent 117 courses of intravenous hyperalimentation. Twenty-four patients (32%) had ulcerative colitis and the remaining 50 patients (68%) had granulomatous disease of the small bowel, colon or combined disease of both. In certain instances, it is difficult, if not impossible, to differentiate between ulcerative colitis and granulomatous disease of the colon but the assigned diagnoses were based upon combined clinical, radiologic and pathologic criteria.1116 The mean age of the 74 patients was 37 years. The duration of hospital stay was 43 days. Patients with granulomatous disease were somewhat younger and had a shorter hospital stay (Table 1). A retrospective analysis was conducted on the records of these 74 patients to determine admission nutritional status, presenting disease severity, indications for nutritional support, effects and morbidity of IVH, specific effects of IVH on enterocutaneous fistulas, operative morbidity and mortality, indications for continued nonoperative treatment, and follow-up of postdischarge course.
Results Assessment of the nutritional status of the 74 patients referred to the Surgical Service for consideration of parenteral nutritional support revealed a moderatelyto-severely malnourished population (Table 2). This malnutrition could be classified as marasmic-kwashiorkor type with significant depletion of body-cell mass reflected in the substantial weight loss (19 + 3 lbs), and substantial depressions in the visceral protein component, as shown by serum albumin levels of 2.9 0.13 g% and serum transferrin levels of 158 13.2 mg% (Table 2). Sixty-three (82%) of the patients suffered a loss of body weight greater than 10% of their usual weight, an amount generally agreed to indicate significant malnutrition. There were no substantial differences in the various nutritional parameters between types of inflammatory bowel disease. These patients represented a selected group from ±
±
TABLE 2. Nutritional
# Patients
Ann. Surg.
Statuts
>10% Weight Loss 21 14 7 21 63
(88%) (78%) (88%) (78%) (82%)
Albumin (g%)* 2.7 3.0 2.8 3.0 2.9
+
0.14
± 0.13 ± 0.21 ± 0.09 ± 0.13
Transferrin (mg%)* 143 150 163 177 158
12.6 14.0 16.2 12.4 ± 13.2
± ± ± ±
VOl. 187 . NO. 5
INTRAVENOUS HYPERALIMENTATION TABLE 3. History of Previous Surgery
Site UC RE GC RE & GC Total
525
TABLE 5. Indications for IVH
Interval to Present # Patients Adm. (Yrs)
Indication
Site
Pre-op
Failed Med Rx
Nutritional
Infl Hem Perf Fist Obst
(8%) (33%) (25%) (56%) 25 (32%)
0% 17% 50% 40% 32%
UC RE GC RE & GC
29% 39% 25% 37%
67% 44% 88% 48%
58% 50% 25% 48%
Totals
32%
61%
48%
2 6 2 15
10.0 4.7 2.0 7.1 6.2
0 0 0 7%
4%
100% 17% 50% 33% 40%
0% 0 33% 17% 0% 0% 13% 13% 16% 12%
the total population of IBD patients seen at our hospital in that the severity of disease was greater. Twentyfive of the 74 patients (32%) had undergone a previous intra-abdominal procedure. The mean duration from the previous operation to the present admission was 6.2 years. Almost all patients (92%) who had a previous operation were individuals with granulomatous disease. Two patients with ulcerative colitis had previous emergency operations because of a perforated toxic colon. Those patients with granulomatous disease (23 of 25) were operated on previously for the following indications: intractable inflammation (32%), perforation (40%), fistula (15%), obstruction (12%) and hemorrhage (4%) (Table 3). The patients' inpatient therapy regimen before receiving IVH was often of the multiple drug variety, usually including steroids, salicylazosulfapyridine (Azulfidine), and opiates. Only 14% of these patients were not receiving any of these medications (Table 4). Twenty-five (34%) of the 74 patients had a total of 43 enterocutaneous fistulas, 20 of the 50 patients with granulomatous disease (40%) and five of the 24 patients with ulcerative colitis (2 1%). Four of the six fistulas in the ulcerative colitis group followed operations for drainage of abscesses following perforation. The indications for parenteral nutritional support were varying and often multiple. Nutritional preparation for operation was the reason in 33% of the patients, and failure of medical treatment was the indication in 61%. The poor nutritional status of the patient was cited as an indication for nutritional support in only 48% of these patients (Table 5). Intravenous hyperalimentation improved the nutritional status or prevented further deterioration in almost all patients. Seventy-seven per cent of these patients
gained weight on IVH despite the presence of an acute inflammatory process or other complications. Only eight patients lost weight and this was of little magnitude. The average duration of intravenous hyperalimentation was three and one-half weeks (26 + 3.7 days) with no substantial differences between the types of disease. The average amount of weight gain was 10 lbs during this three and one-half week period (Table 6). The beneficial effects of IVH were accomplished with minimal morbidity, no different from that experienced in the non-IBD patient population treated with IVH in our hospital. Complications occurred in eight patients (10%): three episodes of pneumothorax (4%); three instances of catheter sepsis (4%); and two episodes of metabolic complications (2%). No mortality was attributed to IVH (Table 7). Forty-six (62%) of the 74 patients had surgery during their course of intravenous hyperalimentation, 15 of 24 in the ulcerative colitis group (62%) and 31 of 50 in the granulomatous disease group (62%). Almost 40% of patients who had previously failed on a medical regimen had an IVH-induced remission compatible with hospital discharge without operation; this success rate is similar to the other series.7 An intractable inflammatory process was the most common indication for operation (Table 8). Ten patients had operative complications (22%) which were often multiple -fistula, sepsis and wound infections leading to death in four (9%) individuals (Table 9). Seventeen of the 43 fistulas (43%) were closed with IVH alone, thus avoiding any surgical procedure. Only three of these recurred, leaving an overall permanent fistula closure rate with intravenous hyperalimentation alone of 33% (Table 10). All patients (26) with fistulas that did not TABLE 6. Weight Change -IVH
TABLE 4. Medical Regimens -Admission (Pre-IVH)
None
Steroids
Azulf
Opiates
8%
50%
58%
50%
17%
39%
44%
50% 48%
37% 48%
39% 50%
RE & GC
12% 19%
Totals
14%
51%
51%
Site UC
RE GC
70%
None
Gain
Loss
Duration (Days)*
UC RE GC RE & GC
8% 11% 12% 26%
84% 83% 88% 63%
8% 6% 0% 11%
Totals
15%
77%
8%
29 + 4.4 22 2.5 19 4.6 29 3.8 26 ± 3.7
57% *
Mean ± SEM.
MULLEN AND OTHERS
526 TABLE 7. IVH Complications
UC RE GC RE & GC
Totals
TABLE 9. Operative Complications
None
Metabolic
Pneumothorax
Catheter Sepsis
87% 83% 100% 93% 90%
4% 0% 0% 4%
4% 11% 0% 0% 4%
4% 5% 0% 4% 4%
2%
close with IVH alone underwent surgical closure. All of these were successfully closed at the time of operation. However, three subsequently recurred in the postoperative period in the hospital or postdischarge (Table 11). Overall, of the 43 fistulas in 25 patients, all were closed initially with either IVH alone or as an adjunct to operation, although six recurred (three after IVH alone; three after IVH-surgery). The overall closure rate was 86% (37 of 43) (Table 12). When surgical complications were analyzed with regard to preoperative medical regimens, there were no substantial differences in the complication rates. However, when the data was analyzed according to whether the disease process was ulcerative colitis or granulomatous disease (Table 13), substantial differences were apparent. In the 15 patients with ulcerative colitis who were operated on, there was a substantial increase in the complication rate of those not on preoperative steroid medication. Conversely, in the 31 patients undergoing operation for granulomatous disease, there appeared to be little difference in complications associated with the preoperative use of corticosteroids. Almost all surgical procedures (87%) were resections; no bypass procedures were employed. Various other (13%) procedures were employed usually in emergency situations (Table 14). When discharge (post-IVH) medical regimens (Table 15) were compared with initial regimens (Table 4) substantial decreases in medication are apparent. During a six to 120 month follow-up period, 25 patients were readmitted to the hospital for recurrent disease: 20 with granulomatous disease and five with ulcerative colitis. Twelve had only one subsequent admission and 13 two or more admissions. During the TABLE 8. Surgery and IVH
# Ops
Deaths
Sepsis
Fistula
Wd Infect
RE UC GC RE & GC
9 15 3 19
0% 20% 0% 5%
11% 40% 0% 15%
11% 20% 0% 5%
20% 33%
Totals
46
9%
22%
11%
RE UC
No Surgery
0% 11%
Discussion The malnourishing effects of inflammatory bowel disease are readily apparent from this series of patients, demonstrating significant losses of body cell mass from prolonged conversion of fat and skeletal muscle fuel reserves to satisfy the energy demands in these individuals with inadequate protein and calorie intake. Particularly noteworthy is the almost uniform depression of visceral protein with its impact on immunologic competence and ultimate sepsis and mortality. This particularly lethal combination of marasmic kwahiorkor-like malnutrition is usually associated with a substantial incidence of sepsis and ultimate mortality if untreated.3"0 The severity of inflammatory bowel disease in this series is not surprising since hyperalimentation was first utilized in these patients at this institution. As with most new treatments, initial patient referrals were often critically ill patients who were treatment failures and were given intravenous hyperalimentation as a last resort. As the efficacy of intravenous hyperalimentation in inflammatory bowel disease has been documented, nutritional support has been offered to these patients at an earlier stage, ameliorating the consequences of severe protein-calorie malnutrition. Although this has occurred to some extent, it is by no means the standard therapy applied in all patients with inflammatory bowel disease who have proteincalorie malnutrition. The rationale for the use of intravenous hyperalimentation in the patient with inflammatory bowel disease is three-fold: 1) to replete the nutritional deficits commonly seen; 2) to allow complete bowel rest with adequate protein-calorie intake; TABLE 10. Fistula Rx-IVH Alone
Inflam Hemm Perf Obstr Fist
# Patients # Fistula # Closed (%) # Recurred (%)
16% 42% 37% 11%
6% 16% 0% 7%
0% 4% 0% 11%
6% 0% 0% 11%
22% 0% 0% 26%
GC
RE & GC
50% 38% 63% 34%
Totals
38%
28%
9%
5%
5%
15%
GC
11%
readmission, 16 patients underwent 43 additional courses of IVH and 18 patients had 24 operations.
Surgical Indications Site
Ann. Surg. * May 1978
RE UC RE & GC
10 5 2 8
15 6 2 20
5 (33) 5 (83) 2 (100) 5 (25)
Totals
25
43
17 (40)
1 1 0 1
(20) (20) (0) (20)
3 (18)
VOl. 187 . NO. 5
TABLE 1 1. Fistula Rx-IVH and Surgery
# Fistula
# Closed
10 1 0
10 1 0
RE UC
GC RE & GC Totals
TABLE 14. Surgical Procedures
# Recurred (%)
15
15
1 (10) 1 (100) 0 (0) 1 (7)
26
26
3 (12%)
TABLE 12. Fistula Rx-Summary # Perm # Initially Closed # Patients # Fistula Closed # Recurred (%)
RE UC GC RE & GC Totals
527
INTRAVENOUS HYPERALIMENTATION
10 5 2 8
15 6
5 6
2 (13) 2 (33)
13 (87) 4 (67)
2 20
2 20
0 (0) 2 (10)
25
43
43
6 (14)
2 (100) 18 (90) 37 (86)
and 3) to provide adequate parenteral nutritional support as an adjunct to surgical intervention.7'12 IVH should be more useful in patients with granulomatous disease than in those with ulcerative colitis because of the high incidence of recurrence, and the lack of an operation that will effect a cure, as can be accomplished in ulcerative colitis. With granulomatous disease, every reasonable effort is made to accomplish successful nonoperative treatment, and surgery is reserved for complications of the disease. In granulomatous disease, IVH combined with total bowel rest has served as an effective primary modality of treatment. With ulcerative colitis, intravenous hyperalimentation usually functions as an adjuvant nutritional support for a curative surgical resection. Intravenous hyperalimentation has revolutionalized the treatment of gastrointestinal fistulas, including those secondary to inflammatory bowel disease.9 Until adequate parenteral nutritional became a reality, early operative intervention was advocated to avoid the inevitable severe protein-calorie malnutrition."12 9 The presence of a fistula is no longer an absolute indication for surgery. IVH alone resulted in a 33% longterm fistula closure rate. It must be emphasized that intravenous hyperali-
RE UC GC RE & GC
Totals
Sepsis
0% 17%
5%
0%o
0% 33% 11% 6%
0%
80%
20%
0% 0% 0% 0%
93% 100% 84% 87%
7% 0% 16% 13%
infusions. Although the indications for surgery are somewhat different than in other series,6 this may merely reflect the selected nature of our group or differences in criteria for assignment for data analysis. These critically ill patients have a substantial operative mortality and morbidity despite adequate nutritional support. The operative complication rate of 22% in part reflects the severity of illness in the patients treated with intravenous hyperalimentation at its early beginnings. The complications of IVH itself were surprisingly low despite the significant disease severity.'4 We attribute this low complication rate to a true team approach to these patients, with meticulous attention to a standard protocol for monitoring and management of patients receiving total parenteral nutrition. When complication rates were analyzed for a relaTABLE 15. Medical Regimens -Discharge (Post-IVH)
Fistula Site
Ulcerative Colitis Steroids No Steroids Granulomatous Disease Steroids No Steroids
Other
mentation should not alter the basic surgical principles of fistula management: 1) relief of distal obstruction; 2) removal of foreign bodies; 3) removal of the epithelialized tract; and 4) drainage of adjacent intraabdominal abscesses. Using optimal timing of the surgical intervention' 2'5 combined with total parenteral nutritional support and complete bowel rest, this series of patients demonstrates that a high percentage (86%) of these fistulas can be closed permanently. Although some have advocated the use of enteral elemental diets for distal intestinal fistulas'3"15 this has not proved uniformly successful in our hands. Despite the severe nutritional deficits and increased metabolic demands in these patients,7"2 intravenous hyperalimentation has effectively improved their nutritional status, with over three-fourths of all patients showing weight gain. Serial serum albumin and serum transferrin levels were often unavailable for analysis or invalidated by intervening intravenous albumin
TABLE 13. IVH and Surgery -Surgical Complications and Steroids
Death
Resection
Bypass
0% 8%
UC RE
5% 0%
GC RE & GC Totals
None
Steroids
Azulf
Opiates
54% 39% 50% 22%
33% 28% 37% 52% 35%
29% 11% 12% 22% 20%
8% 28% 0% 52% 26%
39%
528
MULLEN AND OTHERS
tionship between the use of preoperative steroids and operative mortality and morbidity, no differences were found between the steroid treated group and those not treated with steroids, as in Jalan's series.8 However, when ulcerative colitis patients were analyzed separately from those with granulomatous disease, the preoperative use of steroids in the patient with ulcerative colitis substantially decreased the operative mortality and morbidity. Although this is an uncontrolled study with varying disease severity, the evidence is suggestive that steroids have no significant deleterious effects in patients with ulcerative colitis and may even have a beneficial effect in the preoperative control of the patient with an acutely inflammed colon.8 References 1. Aguire, A., Fischer, J. E. and Welch, C. E.: The Role of Surgery and Hyperalimentation in Therapy of Gastrointestinal -Cutaneous Fistulae. Ann. Surg., 180:393, 1974. 2. Aguire, A. and Fischer, J. A.: Intestinal Fistulas in Total Parenteral Nutrition. Fischer, J. E. (ed.) Boston, Little, Brown, 1976. 3. Clark, R. G. and Lauder, N. M.: Undernutrition and Surgery In Regional Ileitis. Br. J. Surg., 56:736, 1969. 4. 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, 64:134, 1968.
DiscUSSION
DR. FRANCIS C. NANCE (New Orleans, Louisiana): I think this is a very important study. It represents the tenth anniversary of the introduction of intravenous hyperalimentation at the University of Pennsylvania, and by definition they have the longest followup of patients managed by this technique. We have had similar observations in treating patients with inflammatory bowel disease, particularly in patients with regional enteritis and granulomatous colitis. We have been gratified to see resolution of fistulas and what we think is reduction in the severity of disease. I'd like to ask Dr. Fitts some specific questions. Have you seen any physical disappearance of the typical granulomatous lesions while the patient is on hyperalimentation? In other words, can this in any way be considered definitive therapy for regional enteritis or granulomatous colitis? Our own clinical observations are that the patients with regional enteritis and granulomatous lesions respond better than patients with ulcerative colitis. Have you seen patients with florid ulcerative colitis who have not responded at all to hyperalimentation, except in a general increase in their nutritional support? And are there times when persisting with hyperalimentation could be dangerous to the clinical course of the patient? In other words, when do you stop hyperalimenting and intervene surgically? I think it's also a legitimate question and an important question to ask something about the cost of maintaining a patient for the times that you mentioned here of 20-25 days on hyperalimentation. Is that a significant factor in hospitalization? Finally, I feel that no one who was at the University of Pennsylvania in that era can ignore the fact that there is at least one important name omitted from the list of authors, and that's my old chief, Dr. Rhoads, whose contributions to this field are obvious, but which, I think, ought to be acknowledged again.
Ann.
Surg. * May 1978
5. Edmunds, L. H., Jr., Williams, G. M. and Welch, C. E.: External Fistulas Arising From the Gastrointestinal Tract. Ann. Surg., 152:445, 1960. 6. Farmer, R. G., Hank, W. A. and Turnbull, R. P.: Indications for Surgery in Crohn's Disease (Analysis of 500 cases). Gastroenterology, 71:245, 1976. 7. Fischer, J. E., Foster, G. S., Abel, R. M., et al.: Hyperalimentation as Primary Therapy for Inflammatory Bowel Disease. Am. J. Surg., 125:165, 1973. 8. Jalan, K. N., Prescott, R. J., Smith, A. N., et al.: Influence of Corticosteroids on the Results of Surgical Treatment of Ulcerative Colitis. N. Engl. J. Med., 282: 588, 1970. 9. MacFadyen, B. V., Dudrick, S. J. and Ruberg, R.: Management of Gastrointestinal Fistulas with Parenteral Hyperalimentation. Surgery, 74:100, 1973. 10. Meakins, J. L., Pietsch, J. B., Bubenick, O., et al.: Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma. Ann. Surg, 186:241, 1977. 11. Nugent, W. F.: Medical Management of Inflammatory Disease of the Colon. Symposium on Gastrointestinal Surgery. 12. Reilly, J.: Inflammatory Bowel Disease in Total Parenteral Nutrition. Fischer, J. E., (ed.) Boston, Little, Brown, 1976. 13. Rocchio, M. A., Cha, C. J. M., Haas, K. F. and Randall, H. T.: Use of Chemically Defined Diets in the Management of Patients with Acute Inflammatory Bowel Disease. Am. J. Surg., !27:469, 1974. 14. Ryan, J. A., Abel, R. M., Abbott, W. A., et al.: Catheter Complications in Total Parenteral Nutrition. N. EngI. J. Med., 290:757, 1974. 15. Votik, A. J., Echave, V., Feller, J. H., et al.: Experience with Elemental Diet in the Treatment of Inflammatory Bowel Disease: Is This Primary Therapy? Arch. Surg., 107:329, 1973. 16. Zetzel, L.: Granulomatous (Ileo) Colitis. N. EngI. J. Med., 282:600, 1970.
DR. FRANCIS E. ROSATO (Norfolk, Virginia): I'd like to thank Dr. Fitts and the other pioneers at the University of Pennsylvania not only for the development of IVH, but for updating their informative and timely experience again. There are a lot of points in this paper that are worthy of discussion. I'm going to emphasize a few, and attach some questions to them. First of all, there has been a reported anergy in a fair percentage of patients with chronic inflammatory bowel disease, specifically in their nonreactivity to DNCB, and also in their failure to respond to the mitogen PHA. Along a similar track, there is a body of literature that supports the notion that there is a return to immune competence with intravenous hyperalimentation. I'm wondering if some of the improvement that one sees in patients with chronic inflammatory bowel disease treated by hyperalimentation might not be due partially, at least, to a restoration to immune competence. Do you have any studies, Dr. Fitts, that would relate to measured immune parameters during the course of treatment? A second point worth emphasizing, and one interprets this from the slide, is that about half the patients that were referred for hyperalimentation were referred primarily for surgery, and only about half primarily for nutritional reasons. Therefore, I assume that in the process of referral perhaps the nutritional depletion of some of these patients was not appreciated by the referring physician. What clinical, everyday parameters do you use in assessing the nutritional status of patients? Specifically, what parameters do you use to decide that a patient is nutritionally ready for operative
intervention?
A last point worth emphasizing is the impressive figure of approximately 40% IVH induced remission, and approximately a 40% rate of non-operative fistula closure with intravenous hyperalimentation. And to echo Dr. Nance's question, I would ask you again: How long do you persist at the outside in continuing the IVH, in the hope of producing a non-operative remission? How long can one safely persist in this before deciding that surgery has to be embarked upon?
A retrospective analysis was conducted on 74 patients with inflammatory bowel disease who were treated with intravenous hyperalimentation at the Hospital of the University of Pennsylvania between the years 1967-1976. Intravenous hyperalimentation can ameliorate the inevitable protein-calorie malnutrition present in patients with inflammatory bowel disease. Combined with complete bowel rest, intravenous hyperalimentation can effectively function as the primary treatment or as an adjunct to the surgical management of the complications of inflammatory bowel disease. Intravenous hyperalimentation can be safely administered to these severely ill patients, almost certainly improving survival rates in the patients treated. ALNUTRITION CONSISTENTLY OCCURS in patients lVi with inflammatory bowel disease (IBD). The catabolic effects of a chronic inflammatory process are combined with dysfunction of the gastrointestinal tract which impairs normal nutrient intake and absorption. These effects are readily apparent upon examination of the nutritional status of hospitalized patients with inflammatory bowel disease, particularly when complications of perforation, fistula or infection impose increased energy and caloric demands on the individual.39'2 The malnourishing effects of inflammatory bowel disease9 12 are multiple: 1) a substantial decrease in oral protein-calorie intake. This deficient intake is due to the anorexia associated with a chronic inflammatory disease and to avoidance behavior conditioned by the occurrence of gastrointestinal symptoms associated with eating; 2) a decrease in absorptive capacity secondary to extensive inflammatory disease of the intestine and to previous bowel resections. The ultimate effect of the malabsorption component will be determined by the capacity of the individual to increase his caloric and protein intake to compensate Presented at the Annual Meeting of the Southern Surgical Association, Hot Springs, Virginia, December 5-7, 1977. Reprint requests: James L. Mullen, M.D., 4th Silverstein Pavilion, Nutrition Support Service, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. Supported in part by an Educational Grant from McGraw Laboratories, Santa Ana, California.
From the Department of Surgery, University of Pennsylvania School of Medicine and the Philadelphia Veterans Administration Hospital, Philadelphia, Pennsylvania
for these absorptive losses; 3) a substantial loss of visceral protein through diseased segments of bowel, placing an increased demand on protein synthesis mechanisms and substrate availability; 4) increased energy-caloric demands generated by the hypermetabolic effects of the inflammatory process and by complications such as infection and peritonitis. In addition to the malnourishing effects of the disease process, the treatment for the primary disease significantly increases the nutritional burden of the already compromised host." A reduction in food intake and often complete bowel rest are employed during an acute exacerbation of symptoms in the patient with inflammatory bowel disease. This severely limits nutrient intake. The usual attempts at protein-calorie supplementation using specialized enteral feeding techniques are often unsuccessful in meeting nutritional needs. Corticosteroids are often administered to these patients, particularly those with severe disease. The side effects of these anti-inflammatory agents include general catabolic effects, poor wound healing and reduced host resistance to sepsis.10 Surgical procedures are often required in the treatment of inflammatory bowel disease, producing further malnourishing effects such as a decrease in absorptive surface, mandatory gastrointestinal dysfunction in the perioperative period and the hypermetabolic effects of major surgical trauma. The employment of adequate nutritional support in the patient with inflammatory bowel disease is easily justified in view of these multiple factors which lead to malnutrition.7'9"2 The adverse effects of nutritional depletion on the patient's course are substantial. Increased disease/treatment morbidity and mortality'0 and decreased therapy response rate occur in malnour-
0003-4932-78-0500-0523-0085 © J. B. Lippincott Company
523
524
MULLEN AND OTHERS TABLE 1. Disease Site, Age, Duration Hospital Stay Age Hospital Stay (Days)* # Patients (Years)*
Site
Ulcerative Colitis (UC) Regional Enteritis (RE) Granulomatous Colitis (GC) RE and GC Entire Population * Mean
+
24 17 8 25 74
44 36 31 32 37
± 3.4 z 3.8 ± 5.1 2.5 + 3.4
51.2 32.0 42.3 41.7 42.6
± 6.0 ± 2.5 ± 7.6 4.4 ± 4.7
SEM.
ished patients with inflammatory bowel disease. The repletion of nutritional deficits and the maintenance of adequate nutrition combined with complete bowel rest during an acute inflammatory episode may provide the additional benefits of avoiding surgery and reducing the length of hospitalization.7 Patients with inflammatory bowel disease and substantial decreases in voluntary oral food intake can be force-fed through two routes-enteral and parenteral. Although isolated successes13'15 have been reported via the enteral route, most nutritional support has been provided via total parenteral nutrition or intravenous hyperalimentation (IVH), particularly where complete bowel rest is a necessary component of the therapeutic regimen.7912 Since its inception at this institution,4 intravenous hyperalimentation has been utilized extensively in patients with inflammatory bowel disease. Some of the initial patients treated with IVH had extensive granulomatous disease of the intestine and early results were gratifying. This report encompasses our experiences in providing parenteral nutritional support to patients with inflammatory bowel disease during the past ten years, 1967 through 1976. The report covers the spectrum from the early years when IVH was a last resort to the more recent years when nutritional support has been instituted at an earlier stage. Clinical Material
From 1967 through 1976, adequate records were available for retrospective analysis on 293 patients who had 617 admissions to the Hospital of the University of Pennsylvania with a primary diagnosis of inflam-
UC RE
GC RE & GC Total *
Mean ± SEM.
24 17 8 25 74
Weight Loss (lbs) 20 21 16 17 19
+
3.1
± 4.2 ± 2.6 ± 2.1
± 3.0
9
May 1978
matory bowel disease (2.1 admissions per patient). Seventy-four patients (25%) were referred to the Surgical Service for nutritional evaluation and support
with intravenous hyperalimentation. These 74 patients underwent 117 courses of intravenous hyperalimentation. Twenty-four patients (32%) had ulcerative colitis and the remaining 50 patients (68%) had granulomatous disease of the small bowel, colon or combined disease of both. In certain instances, it is difficult, if not impossible, to differentiate between ulcerative colitis and granulomatous disease of the colon but the assigned diagnoses were based upon combined clinical, radiologic and pathologic criteria.1116 The mean age of the 74 patients was 37 years. The duration of hospital stay was 43 days. Patients with granulomatous disease were somewhat younger and had a shorter hospital stay (Table 1). A retrospective analysis was conducted on the records of these 74 patients to determine admission nutritional status, presenting disease severity, indications for nutritional support, effects and morbidity of IVH, specific effects of IVH on enterocutaneous fistulas, operative morbidity and mortality, indications for continued nonoperative treatment, and follow-up of postdischarge course.
Results Assessment of the nutritional status of the 74 patients referred to the Surgical Service for consideration of parenteral nutritional support revealed a moderatelyto-severely malnourished population (Table 2). This malnutrition could be classified as marasmic-kwashiorkor type with significant depletion of body-cell mass reflected in the substantial weight loss (19 + 3 lbs), and substantial depressions in the visceral protein component, as shown by serum albumin levels of 2.9 0.13 g% and serum transferrin levels of 158 13.2 mg% (Table 2). Sixty-three (82%) of the patients suffered a loss of body weight greater than 10% of their usual weight, an amount generally agreed to indicate significant malnutrition. There were no substantial differences in the various nutritional parameters between types of inflammatory bowel disease. These patients represented a selected group from ±
±
TABLE 2. Nutritional
# Patients
Ann. Surg.
Statuts
>10% Weight Loss 21 14 7 21 63
(88%) (78%) (88%) (78%) (82%)
Albumin (g%)* 2.7 3.0 2.8 3.0 2.9
+
0.14
± 0.13 ± 0.21 ± 0.09 ± 0.13
Transferrin (mg%)* 143 150 163 177 158
12.6 14.0 16.2 12.4 ± 13.2
± ± ± ±
VOl. 187 . NO. 5
INTRAVENOUS HYPERALIMENTATION TABLE 3. History of Previous Surgery
Site UC RE GC RE & GC Total
525
TABLE 5. Indications for IVH
Interval to Present # Patients Adm. (Yrs)
Indication
Site
Pre-op
Failed Med Rx
Nutritional
Infl Hem Perf Fist Obst
(8%) (33%) (25%) (56%) 25 (32%)
0% 17% 50% 40% 32%
UC RE GC RE & GC
29% 39% 25% 37%
67% 44% 88% 48%
58% 50% 25% 48%
Totals
32%
61%
48%
2 6 2 15
10.0 4.7 2.0 7.1 6.2
0 0 0 7%
4%
100% 17% 50% 33% 40%
0% 0 33% 17% 0% 0% 13% 13% 16% 12%
the total population of IBD patients seen at our hospital in that the severity of disease was greater. Twentyfive of the 74 patients (32%) had undergone a previous intra-abdominal procedure. The mean duration from the previous operation to the present admission was 6.2 years. Almost all patients (92%) who had a previous operation were individuals with granulomatous disease. Two patients with ulcerative colitis had previous emergency operations because of a perforated toxic colon. Those patients with granulomatous disease (23 of 25) were operated on previously for the following indications: intractable inflammation (32%), perforation (40%), fistula (15%), obstruction (12%) and hemorrhage (4%) (Table 3). The patients' inpatient therapy regimen before receiving IVH was often of the multiple drug variety, usually including steroids, salicylazosulfapyridine (Azulfidine), and opiates. Only 14% of these patients were not receiving any of these medications (Table 4). Twenty-five (34%) of the 74 patients had a total of 43 enterocutaneous fistulas, 20 of the 50 patients with granulomatous disease (40%) and five of the 24 patients with ulcerative colitis (2 1%). Four of the six fistulas in the ulcerative colitis group followed operations for drainage of abscesses following perforation. The indications for parenteral nutritional support were varying and often multiple. Nutritional preparation for operation was the reason in 33% of the patients, and failure of medical treatment was the indication in 61%. The poor nutritional status of the patient was cited as an indication for nutritional support in only 48% of these patients (Table 5). Intravenous hyperalimentation improved the nutritional status or prevented further deterioration in almost all patients. Seventy-seven per cent of these patients
gained weight on IVH despite the presence of an acute inflammatory process or other complications. Only eight patients lost weight and this was of little magnitude. The average duration of intravenous hyperalimentation was three and one-half weeks (26 + 3.7 days) with no substantial differences between the types of disease. The average amount of weight gain was 10 lbs during this three and one-half week period (Table 6). The beneficial effects of IVH were accomplished with minimal morbidity, no different from that experienced in the non-IBD patient population treated with IVH in our hospital. Complications occurred in eight patients (10%): three episodes of pneumothorax (4%); three instances of catheter sepsis (4%); and two episodes of metabolic complications (2%). No mortality was attributed to IVH (Table 7). Forty-six (62%) of the 74 patients had surgery during their course of intravenous hyperalimentation, 15 of 24 in the ulcerative colitis group (62%) and 31 of 50 in the granulomatous disease group (62%). Almost 40% of patients who had previously failed on a medical regimen had an IVH-induced remission compatible with hospital discharge without operation; this success rate is similar to the other series.7 An intractable inflammatory process was the most common indication for operation (Table 8). Ten patients had operative complications (22%) which were often multiple -fistula, sepsis and wound infections leading to death in four (9%) individuals (Table 9). Seventeen of the 43 fistulas (43%) were closed with IVH alone, thus avoiding any surgical procedure. Only three of these recurred, leaving an overall permanent fistula closure rate with intravenous hyperalimentation alone of 33% (Table 10). All patients (26) with fistulas that did not TABLE 6. Weight Change -IVH
TABLE 4. Medical Regimens -Admission (Pre-IVH)
None
Steroids
Azulf
Opiates
8%
50%
58%
50%
17%
39%
44%
50% 48%
37% 48%
39% 50%
RE & GC
12% 19%
Totals
14%
51%
51%
Site UC
RE GC
70%
None
Gain
Loss
Duration (Days)*
UC RE GC RE & GC
8% 11% 12% 26%
84% 83% 88% 63%
8% 6% 0% 11%
Totals
15%
77%
8%
29 + 4.4 22 2.5 19 4.6 29 3.8 26 ± 3.7
57% *
Mean ± SEM.
MULLEN AND OTHERS
526 TABLE 7. IVH Complications
UC RE GC RE & GC
Totals
TABLE 9. Operative Complications
None
Metabolic
Pneumothorax
Catheter Sepsis
87% 83% 100% 93% 90%
4% 0% 0% 4%
4% 11% 0% 0% 4%
4% 5% 0% 4% 4%
2%
close with IVH alone underwent surgical closure. All of these were successfully closed at the time of operation. However, three subsequently recurred in the postoperative period in the hospital or postdischarge (Table 11). Overall, of the 43 fistulas in 25 patients, all were closed initially with either IVH alone or as an adjunct to operation, although six recurred (three after IVH alone; three after IVH-surgery). The overall closure rate was 86% (37 of 43) (Table 12). When surgical complications were analyzed with regard to preoperative medical regimens, there were no substantial differences in the complication rates. However, when the data was analyzed according to whether the disease process was ulcerative colitis or granulomatous disease (Table 13), substantial differences were apparent. In the 15 patients with ulcerative colitis who were operated on, there was a substantial increase in the complication rate of those not on preoperative steroid medication. Conversely, in the 31 patients undergoing operation for granulomatous disease, there appeared to be little difference in complications associated with the preoperative use of corticosteroids. Almost all surgical procedures (87%) were resections; no bypass procedures were employed. Various other (13%) procedures were employed usually in emergency situations (Table 14). When discharge (post-IVH) medical regimens (Table 15) were compared with initial regimens (Table 4) substantial decreases in medication are apparent. During a six to 120 month follow-up period, 25 patients were readmitted to the hospital for recurrent disease: 20 with granulomatous disease and five with ulcerative colitis. Twelve had only one subsequent admission and 13 two or more admissions. During the TABLE 8. Surgery and IVH
# Ops
Deaths
Sepsis
Fistula
Wd Infect
RE UC GC RE & GC
9 15 3 19
0% 20% 0% 5%
11% 40% 0% 15%
11% 20% 0% 5%
20% 33%
Totals
46
9%
22%
11%
RE UC
No Surgery
0% 11%
Discussion The malnourishing effects of inflammatory bowel disease are readily apparent from this series of patients, demonstrating significant losses of body cell mass from prolonged conversion of fat and skeletal muscle fuel reserves to satisfy the energy demands in these individuals with inadequate protein and calorie intake. Particularly noteworthy is the almost uniform depression of visceral protein with its impact on immunologic competence and ultimate sepsis and mortality. This particularly lethal combination of marasmic kwahiorkor-like malnutrition is usually associated with a substantial incidence of sepsis and ultimate mortality if untreated.3"0 The severity of inflammatory bowel disease in this series is not surprising since hyperalimentation was first utilized in these patients at this institution. As with most new treatments, initial patient referrals were often critically ill patients who were treatment failures and were given intravenous hyperalimentation as a last resort. As the efficacy of intravenous hyperalimentation in inflammatory bowel disease has been documented, nutritional support has been offered to these patients at an earlier stage, ameliorating the consequences of severe protein-calorie malnutrition. Although this has occurred to some extent, it is by no means the standard therapy applied in all patients with inflammatory bowel disease who have proteincalorie malnutrition. The rationale for the use of intravenous hyperalimentation in the patient with inflammatory bowel disease is three-fold: 1) to replete the nutritional deficits commonly seen; 2) to allow complete bowel rest with adequate protein-calorie intake; TABLE 10. Fistula Rx-IVH Alone
Inflam Hemm Perf Obstr Fist
# Patients # Fistula # Closed (%) # Recurred (%)
16% 42% 37% 11%
6% 16% 0% 7%
0% 4% 0% 11%
6% 0% 0% 11%
22% 0% 0% 26%
GC
RE & GC
50% 38% 63% 34%
Totals
38%
28%
9%
5%
5%
15%
GC
11%
readmission, 16 patients underwent 43 additional courses of IVH and 18 patients had 24 operations.
Surgical Indications Site
Ann. Surg. * May 1978
RE UC RE & GC
10 5 2 8
15 6 2 20
5 (33) 5 (83) 2 (100) 5 (25)
Totals
25
43
17 (40)
1 1 0 1
(20) (20) (0) (20)
3 (18)
VOl. 187 . NO. 5
TABLE 1 1. Fistula Rx-IVH and Surgery
# Fistula
# Closed
10 1 0
10 1 0
RE UC
GC RE & GC Totals
TABLE 14. Surgical Procedures
# Recurred (%)
15
15
1 (10) 1 (100) 0 (0) 1 (7)
26
26
3 (12%)
TABLE 12. Fistula Rx-Summary # Perm # Initially Closed # Patients # Fistula Closed # Recurred (%)
RE UC GC RE & GC Totals
527
INTRAVENOUS HYPERALIMENTATION
10 5 2 8
15 6
5 6
2 (13) 2 (33)
13 (87) 4 (67)
2 20
2 20
0 (0) 2 (10)
25
43
43
6 (14)
2 (100) 18 (90) 37 (86)
and 3) to provide adequate parenteral nutritional support as an adjunct to surgical intervention.7'12 IVH should be more useful in patients with granulomatous disease than in those with ulcerative colitis because of the high incidence of recurrence, and the lack of an operation that will effect a cure, as can be accomplished in ulcerative colitis. With granulomatous disease, every reasonable effort is made to accomplish successful nonoperative treatment, and surgery is reserved for complications of the disease. In granulomatous disease, IVH combined with total bowel rest has served as an effective primary modality of treatment. With ulcerative colitis, intravenous hyperalimentation usually functions as an adjuvant nutritional support for a curative surgical resection. Intravenous hyperalimentation has revolutionalized the treatment of gastrointestinal fistulas, including those secondary to inflammatory bowel disease.9 Until adequate parenteral nutritional became a reality, early operative intervention was advocated to avoid the inevitable severe protein-calorie malnutrition."12 9 The presence of a fistula is no longer an absolute indication for surgery. IVH alone resulted in a 33% longterm fistula closure rate. It must be emphasized that intravenous hyperali-
RE UC GC RE & GC
Totals
Sepsis
0% 17%
5%
0%o
0% 33% 11% 6%
0%
80%
20%
0% 0% 0% 0%
93% 100% 84% 87%
7% 0% 16% 13%
infusions. Although the indications for surgery are somewhat different than in other series,6 this may merely reflect the selected nature of our group or differences in criteria for assignment for data analysis. These critically ill patients have a substantial operative mortality and morbidity despite adequate nutritional support. The operative complication rate of 22% in part reflects the severity of illness in the patients treated with intravenous hyperalimentation at its early beginnings. The complications of IVH itself were surprisingly low despite the significant disease severity.'4 We attribute this low complication rate to a true team approach to these patients, with meticulous attention to a standard protocol for monitoring and management of patients receiving total parenteral nutrition. When complication rates were analyzed for a relaTABLE 15. Medical Regimens -Discharge (Post-IVH)
Fistula Site
Ulcerative Colitis Steroids No Steroids Granulomatous Disease Steroids No Steroids
Other
mentation should not alter the basic surgical principles of fistula management: 1) relief of distal obstruction; 2) removal of foreign bodies; 3) removal of the epithelialized tract; and 4) drainage of adjacent intraabdominal abscesses. Using optimal timing of the surgical intervention' 2'5 combined with total parenteral nutritional support and complete bowel rest, this series of patients demonstrates that a high percentage (86%) of these fistulas can be closed permanently. Although some have advocated the use of enteral elemental diets for distal intestinal fistulas'3"15 this has not proved uniformly successful in our hands. Despite the severe nutritional deficits and increased metabolic demands in these patients,7"2 intravenous hyperalimentation has effectively improved their nutritional status, with over three-fourths of all patients showing weight gain. Serial serum albumin and serum transferrin levels were often unavailable for analysis or invalidated by intervening intravenous albumin
TABLE 13. IVH and Surgery -Surgical Complications and Steroids
Death
Resection
Bypass
0% 8%
UC RE
5% 0%
GC RE & GC Totals
None
Steroids
Azulf
Opiates
54% 39% 50% 22%
33% 28% 37% 52% 35%
29% 11% 12% 22% 20%
8% 28% 0% 52% 26%
39%
528
MULLEN AND OTHERS
tionship between the use of preoperative steroids and operative mortality and morbidity, no differences were found between the steroid treated group and those not treated with steroids, as in Jalan's series.8 However, when ulcerative colitis patients were analyzed separately from those with granulomatous disease, the preoperative use of steroids in the patient with ulcerative colitis substantially decreased the operative mortality and morbidity. Although this is an uncontrolled study with varying disease severity, the evidence is suggestive that steroids have no significant deleterious effects in patients with ulcerative colitis and may even have a beneficial effect in the preoperative control of the patient with an acutely inflammed colon.8 References 1. Aguire, A., Fischer, J. E. and Welch, C. E.: The Role of Surgery and Hyperalimentation in Therapy of Gastrointestinal -Cutaneous Fistulae. Ann. Surg., 180:393, 1974. 2. Aguire, A. and Fischer, J. A.: Intestinal Fistulas in Total Parenteral Nutrition. Fischer, J. E. (ed.) Boston, Little, Brown, 1976. 3. Clark, R. G. and Lauder, N. M.: Undernutrition and Surgery In Regional Ileitis. Br. J. Surg., 56:736, 1969. 4. 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, 64:134, 1968.
DiscUSSION
DR. FRANCIS C. NANCE (New Orleans, Louisiana): I think this is a very important study. It represents the tenth anniversary of the introduction of intravenous hyperalimentation at the University of Pennsylvania, and by definition they have the longest followup of patients managed by this technique. We have had similar observations in treating patients with inflammatory bowel disease, particularly in patients with regional enteritis and granulomatous colitis. We have been gratified to see resolution of fistulas and what we think is reduction in the severity of disease. I'd like to ask Dr. Fitts some specific questions. Have you seen any physical disappearance of the typical granulomatous lesions while the patient is on hyperalimentation? In other words, can this in any way be considered definitive therapy for regional enteritis or granulomatous colitis? Our own clinical observations are that the patients with regional enteritis and granulomatous lesions respond better than patients with ulcerative colitis. Have you seen patients with florid ulcerative colitis who have not responded at all to hyperalimentation, except in a general increase in their nutritional support? And are there times when persisting with hyperalimentation could be dangerous to the clinical course of the patient? In other words, when do you stop hyperalimenting and intervene surgically? I think it's also a legitimate question and an important question to ask something about the cost of maintaining a patient for the times that you mentioned here of 20-25 days on hyperalimentation. Is that a significant factor in hospitalization? Finally, I feel that no one who was at the University of Pennsylvania in that era can ignore the fact that there is at least one important name omitted from the list of authors, and that's my old chief, Dr. Rhoads, whose contributions to this field are obvious, but which, I think, ought to be acknowledged again.
Ann.
Surg. * May 1978
5. Edmunds, L. H., Jr., Williams, G. M. and Welch, C. E.: External Fistulas Arising From the Gastrointestinal Tract. Ann. Surg., 152:445, 1960. 6. Farmer, R. G., Hank, W. A. and Turnbull, R. P.: Indications for Surgery in Crohn's Disease (Analysis of 500 cases). Gastroenterology, 71:245, 1976. 7. Fischer, J. E., Foster, G. S., Abel, R. M., et al.: Hyperalimentation as Primary Therapy for Inflammatory Bowel Disease. Am. J. Surg., 125:165, 1973. 8. Jalan, K. N., Prescott, R. J., Smith, A. N., et al.: Influence of Corticosteroids on the Results of Surgical Treatment of Ulcerative Colitis. N. Engl. J. Med., 282: 588, 1970. 9. MacFadyen, B. V., Dudrick, S. J. and Ruberg, R.: Management of Gastrointestinal Fistulas with Parenteral Hyperalimentation. Surgery, 74:100, 1973. 10. Meakins, J. L., Pietsch, J. B., Bubenick, O., et al.: Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma. Ann. Surg, 186:241, 1977. 11. Nugent, W. F.: Medical Management of Inflammatory Disease of the Colon. Symposium on Gastrointestinal Surgery. 12. Reilly, J.: Inflammatory Bowel Disease in Total Parenteral Nutrition. Fischer, J. E., (ed.) Boston, Little, Brown, 1976. 13. Rocchio, M. A., Cha, C. J. M., Haas, K. F. and Randall, H. T.: Use of Chemically Defined Diets in the Management of Patients with Acute Inflammatory Bowel Disease. Am. J. Surg., !27:469, 1974. 14. Ryan, J. A., Abel, R. M., Abbott, W. A., et al.: Catheter Complications in Total Parenteral Nutrition. N. EngI. J. Med., 290:757, 1974. 15. Votik, A. J., Echave, V., Feller, J. H., et al.: Experience with Elemental Diet in the Treatment of Inflammatory Bowel Disease: Is This Primary Therapy? Arch. Surg., 107:329, 1973. 16. Zetzel, L.: Granulomatous (Ileo) Colitis. N. EngI. J. Med., 282:600, 1970.
DR. FRANCIS E. ROSATO (Norfolk, Virginia): I'd like to thank Dr. Fitts and the other pioneers at the University of Pennsylvania not only for the development of IVH, but for updating their informative and timely experience again. There are a lot of points in this paper that are worthy of discussion. I'm going to emphasize a few, and attach some questions to them. First of all, there has been a reported anergy in a fair percentage of patients with chronic inflammatory bowel disease, specifically in their nonreactivity to DNCB, and also in their failure to respond to the mitogen PHA. Along a similar track, there is a body of literature that supports the notion that there is a return to immune competence with intravenous hyperalimentation. I'm wondering if some of the improvement that one sees in patients with chronic inflammatory bowel disease treated by hyperalimentation might not be due partially, at least, to a restoration to immune competence. Do you have any studies, Dr. Fitts, that would relate to measured immune parameters during the course of treatment? A second point worth emphasizing, and one interprets this from the slide, is that about half the patients that were referred for hyperalimentation were referred primarily for surgery, and only about half primarily for nutritional reasons. Therefore, I assume that in the process of referral perhaps the nutritional depletion of some of these patients was not appreciated by the referring physician. What clinical, everyday parameters do you use in assessing the nutritional status of patients? Specifically, what parameters do you use to decide that a patient is nutritionally ready for operative
intervention?
A last point worth emphasizing is the impressive figure of approximately 40% IVH induced remission, and approximately a 40% rate of non-operative fistula closure with intravenous hyperalimentation. And to echo Dr. Nance's question, I would ask you again: How long do you persist at the outside in continuing the IVH, in the hope of producing a non-operative remission? How long can one safely persist in this before deciding that surgery has to be embarked upon?
