Crossing the Bridge Into the 21st Century

Ezra Steiger, MD
Vice Chairman, Department of General Surgery; Head, Section of Surgical Nutrition
The Cleveland Clinic Foundation, Cleveland, Ohio



The history of parenteral nutrition can be traced back to the 1600s when Sir Christopher Wren infused ale, wine and opium into the veins of dogs and first reported his experience with that intravenous type of feeding, a little over 300 years ago. The actual first use of an intravenous feeding solution for the treatment of a specific disease process was that of Dr. Latta, when he described his experience with the use of an IV solution and the treatment of cholera in a letter to the Lancet in 1832. His prescription included two drachmas of muriate, two scruples of carbonative soda and 60 ounces of water. This essentially gave the patient a saline solution that was invaluable in treating the great fluid losses associated with cholera and helped to save many lives.


There have been some side-steps along the way in the historical evolution of the use of parenteral nutrition, including a report in Philadelphia in 1902, about the use of nutrient enemas. This was two case reports of patients nourished exclusively by rectum, with a determination of their ability to absorb nitrogen products.


The modern day era of the history of parenteral nutrition began in 1937, when Elman and Weiner, in a Journal of The American Medical Association article reported on their experience with the use of carbohydrates and protein hydrolysates for intravenous feeding in man. They published a book with photographs on the benefits of intravenous feeding, but this work became difficult to apply because of the difficulty in providing the large amounts of calories and protein required by intravenous feeding through peripheral IV sites in the hands and arms.


Dr. Harry Vars worked to perfect a technique of intravenous feeding in adult dogs that he described in the 1940s and 1950s, working out of The Harrison Department of Surgical Research at The University of Pennsylvania. Dr. Vars' work in intravenous nutrition became waylaid by the Korean War and the emphasis of treating shock and blood substitutes. He devoted a lot of his attention to this area and it wasn't until Dr. Jonathan Rhoads, as Head of the Department of General Surgery at the Hospital of the University of Pennsylvania re-emphasized the importance of nutrition, was there further work done in this area. Dr. Rhoads' work included the use of 5 liters a day of 10 percent dextrose solution with protein hydrolysates. In that way, sufficient calories along with protein, could be delivered to patients in need of intravenous nutrition support. The down-side risk of that program related to the large volumes of fluid that had to be infused to deliver the nutrients.


Dr. Stanley Dudrick, as a resident in General Surgery, working with Drs. Rhoads and Vars, perfected a technique of intravenous feeding in beagle puppies that showed normal growth and development could be achieved working with intravenous feeding in a growing mammalian system. Dr. Wilmore joined the team and reported subsequent experience in the use of this technique, not only in dogs, but in infants or babies who were born with catastrophic gastrointestinal (GI) conditions that did not allow them to adequately absorb nutrients that they took in through their GI tract. Dramatic growth and development was noted with the intravenous feeding and soon this technique became applicable for use in adult patients with a variety of gastrointestinal tract disease states and difficulties that did not allow for adequate nutrition.


It was not long afterwards, in the middle to late 1960s, that the use of intravenous feeding became very popular in many hospitals throughout the country and was adapted for use in the home setting for patients who had permanent bowel dysfunction. With this technique, patients could be maintained indefinitely, as long as they had a central venous access line through which to infuse the nutrient solutions.


In the beginning days of home parenteral nutrition, the patients would make their own solutions by adding 10 or more ingredients to the bottles, mixing the solutions at home in a miniature pharmacy setup and refrigerating and hanging the bottles that same night. The patients often had to go to their local hospitals to pick up a truck full of supplies that they would cart home for use for one month at a time and at the end of that month had to go back to the hospital to get another truck full of nutrient solutions, additives, and paraphernalia to make the solutions as well as self administer them. The pumps that were used to infuse the nutrient solutions were often very big and bulky and were not mobile at all. There were even some contraptions set up for gravity delivery of the nutrient solutions and an IV pole that the patient had strapped to their back to give some mobility to it. This is a far cry from what has happened subsequently. The modern era of home parenteral nutrition has seen the introduction of ready-made TPN bags, smaller, portable pumps and systems that truly can be worn like a vest or backpack so that patients can get their intravenous feeding while remaining fully mobile.


Where We Are Now


In looking ahead into the 21st Century, the problems of infection, vascular access, enhanced intestinal adaptation and small bowel transplantation remain in the forefront. We will be examining specifically the results of the use of oral rehydration therapies in trying to minimize the use of TPN, and the results of short bowel syndrome treatment with intestinal transplantation. It is important in all of this to recognize the contributions that have been made by the Oley Foundation and the American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.) that have generated a lot of valuable information.


The measures of home parenteral nutrition therapy outcome were well documented by Dr. Lyn Howard and her co-workers in the journal Gastroenterology in 1995. A number of disease states, including Crohn's disease, motility disorders, radiation enteritis, cancer and AIDS were looked at as far as home parenteral nutrition therapy outcome. Hospital readmissions occurred about twice per year, in most of those categories of Crohn's disease, motility disorder and radiation enteritis and four to five times a year in patients with cancer and AIDS. The rehabilitation status at the end of one year was very good, including complete rehabilitation for 60 percent of the Crohn's patients, partial rehabilitation for 38 percent of the patients and only 2 percent having minimal rehabilitation. Similarly, in the motility disorder and radiation enteritis group, complete or partial rehabilitation occurred in more than 80 to 90 percent of the patients. Rehabilitation rates were a little lower in the cancer patients and much lower in the AIDS groups of patients. Most patients with Crohn's disease were able to resume full oral nutrition at the end of one year, whereas in the motility disorder, radiation enteritis, cancer and AIDS groups, most patients still needed to be maintained on home parenteral nutrition. The survival at one year was 96 percent for the Crohn's patients and 87 percent for the motility disorder and radiation enteritis patients, only 20 percent for the cancer patients and 10 percent for the patients with AIDS. It is important to keep in mind that the one year survival is around 90 percent or a little bit more in the Crohn's patients and for people on home parenteral nutrition therapy for non-malignant or non-lethal disease entities, so we can compare these result against the results of subsequent modalities of therapy such as small bowel transplantation (see chart at end of article).


Rehospitalization for home parenteral nutrition patients occurs in about half the patients over the number of years that they are on parenteral nutrition. Most of the rehospitalization was related to their underlying diagnosis, another large part was related to home parenteral nutrition and a smaller percentage for other reasons. Of the home parenteral nutrition causes for rehospitalization, infection or catheter problems accounted for well over two-thirds of those reasons. The risk factors for recurrent sepsis in home parenteral nutrition patients was reported by O'Keefe and coworkers in The Journal of Parenteral and Enteral Nutrition in 1994. They compared their home parenteral nutrition patients who had no infection versus a group of patients who had frequent infections. They found that the younger age group of patients, patients with Crohn's disease, patients with jejunostomies and patients with venous thrombosis were significantly more likely to get in trouble with sepsis or infection. The environmental factors felt to be responsible for increased sepsis or recurrent sepsis in the home, including poor catheter care technique and tobacco smoking, were also more likely to be associated with patients who had more trouble with their catheters.


Looking Ahead


Future research for short bowel syndrome includes looking at growth factors to increase residual gut mass and absorption, improving small bowel transplantation results and slowing transit time. The Nutritional Restart Center has supplied us with some valuable information about the use of their special diet considerations along with glutamine and growth hormone in trying to enhance intestinal absorption in patients on home parenteral nutrition. In their treatment reports, growth hormone was given at a dose of 0.1 mg/kg per day and glutamine was given at a dose of 0.16 gram per kg/day intravenously or 30 grams per day orally. Generally their diet was high in carbohydrates and low in fat, provided six feedings daily and contained no simple sugars. Only drinks containing electrolytes were allowed. Their initial response to treatment showed that many patients were able to come off TPN and of those patients who were able to come off TPN, the jejunal ilial length was about 27 centimeters. Those people who remained on TPN had an average jejunal ilial length of 19 cm. The predictors of successful outcome, as far as weaning off TPN included body weight, bowel length and the growth hormone dosage. There was no significant correlation with age, gender, duration of TPN, or colonic length. The oral rehydration fluid given to patients in an attempt to enhance absorption of both sodium and water from the gastrointestinal tract is important for its therapy. There are a number of oral rehydration solutions that are available and most contain 50 to 90 mEq per liter of sodium and 20 to 25 mEq per liter of potassium, 45 to 80 mEq per liter of chloride and 20 to 30 gram per liter of glucose. Most of them have an osmolality between 240 and 330 mg. (See: "Fluid and Electrolyte Balance: A Must with TPN" in the March/April 1997 Issue of the LifelineLetter, for more information about oral rehydration solutions.)


Small bowel transplantation started by Alexis Carrel in 1902, where intestinal segments were implanted in the necks of dogs. Lilliehei in 1959, autotransplanted cold preserved small bowel. Seven human intestinal recipients were recorded in the 1960s, all of whom died. In the 1970s, TPN was emphasized. In the 1980s rejection or infection led to loss of most grafts. The International Intestinal Transplant Registry polled 24 programs from 1985 through June of 1995, and reported the results in the Lancet in 1996 (Volume 347, page 1801). Most of the small bowel transplants were a combination of intestine and liver. Fewer numbers were isolated small bowel, plus or minus colon, and 16 percent were multivisceral. The patient survival at the end of one year with small bowel transplant only was 57 percent; small bowel and liver was 44 percent and multivisceral was 41 percent. The use of FK506, however, improved these early results so that after one year the results of small bowel transplantation patient survival was up to 83 percent, small bowel and liver survival was up to 66 percent and multivisceral survival was up to 59 percent. However, these number still do not measure up to the 90 percent survival for Crohn's patients on home parenteral nutrition.


To summarize the International Intestinal Transplant Registry through 1995, there were 170 patients, 51 percent were survivors and 39 percent were able to come off home TPN. The conclusions of this study were that small bowel transplantation is a life-saving option for patients who can't be maintained on TPN and for patients who need massive abdominal evisceration for locally aggressive tumors. Most patients on TPN do well and transplantation is too risky for these patients today. Most patients on TPN do well and transplantation is too risky for these patients today.

 

HomePN vs. Intestinal Transplant

Survival

 Year 1

 Year 3

 HPN for Benign Conditions*

87-96%

70-90%

Small Bowel Transplant**

83%

47%

Small Bowel & Liver Transplants**

66%

40%


Copyright 1995 The Oley Foundation