Tpn Nutrition Articles & Resources

The concept of feeding patients parenterally by injecting nutrient substances or fluids subcutaneously or even infusing them directly by IV was advocated and attempted long before its successful achievement. The realization of this seemingly fanciful dream required centuries of fundamental investigation and discovery, coupled with technological developments and judicious applications. The prerequisites to rational clinical studies in this challenging but vital area included knowledge of the anatomy and physiology of the circulation; knowledge of the basic biochemical nature of nutrient substrates; the interrelationships of these substrates with microbiology, immunology, asepsis, and antisepsis; and some knowledge of the complex interactions of food substances with metabolism, pharmacologic agents, and pathophysiologic processes.

Although PN has been available as a useful clinical adjunct for almost 50 years, the modern development of this mode of therapy was initiated in the fourth decade of the last century and crystallized by the work of Elman in the late 1940s. However, the practical clinical use of PN did not emerge until the 1960s. Robert Elman performed original experiments and was instrumental in developing protein substrates that would have led him inevitably to the development of a safe and reliable technique of PN. However, his work was initially interrupted by the events related to World War II in which this nation's priorities were shifted dramatically and drastically away from basic scientific medical efforts to war efforts. After his return from the war, Robert Elman compiled his efforts in a classic tome entitled Parenteral Alimentation in Surgery with Special Reference to Proteins and Amino Acids, and this monograph was awarded the quinquennial Samuel D. Gross Prize of the Philadelphia Academy of Surgery in 1945 and was published by Hoeber, Inc in It is a classic dissertation that should be read by anyone interested in the field of nutrition support, especially in surgical patients. Although Elman resumed his investigative work, his health failed, and he never regained the momentum he had achieved earlier in his career. I frequently tell my students that there are very few entirely unique new ideas but only new techniques, technology, and data that allow the full definition and validation of ideas expressed previously. Evidence for this hypothesis is manifested by the fact that the recorded history of this field of endeavor dates back almost 400 years. The adage that we "make progress by standing on the shoulders of our predecessors" is obvious from the number of important contributions that was essential to the eventual development of PN and that is outlined briefly in Table I.

Although most clinicians in the 1950s were aware of the negative impact of malnutrition on morbidity, mortality, and outcomes, only a relatively small percentage of practicing physicians and surgeons understood the necessity for providing optimal nutrition support for their malnourished patients if optimal clinical results were to be obtained. However, the prevailing dogma in the 1960s was that feeding entirely by vein was impossible; even if it were possible, it would be impractical; and even if it were practical, it would be unaffordable. PN was considered a "holy grail" or "Gordian knot" pursuit by most physicians and surgeons of that time. This formed the wall of ignorance, prejudice, and indifference that had to be penetrated by first developing all of the substrates in a compatible form that could be delivered to a seriously ill patient by IV to provide adequate nourishment; second, demonstrating in the experimental laboratory that such a solution, together with an appropriate safe and effective delivery system, could provide all essential nutrients in quality and quantity sufficient to support animals for long periods of time; and third, if the animal experiments were successful, applying the techniques and technology to safe effective use in human beings.

Many of my colleagues and friends were astounded that I would undertake such a difficult and possibly foolish project that would waste my allotted laboratory time during my residency training and not result in the desired reward of acquiring data that would merit peer-reviewed presentation and publication. However, I had absolutely no doubt that it would be possible to provide all required nutrient substrates to support cellular metabolism entirely by vein because ultimately the vascular circulation is the route by which the body cell mass receives nutrients. Fundamentally, to me, the gastrointestinal tract represented a hollow tube that extends from the mouth to the anus and consists of a specialized lining of endothelial cells, together with the attached salivary glands, biliary tree, and pancreas, which digests and modifies the food substances ingested into the alimentary tract, preparing them suitably for absorption into the portal and lymphatic systems for assimilation into the body cell mass for energy, synthesis, and other functions. Accordingly, the fundamental problem was to provide all nutrient substances required by the body in a form that could be infused directly into the peripheral bloodstream for distribution to all cells and tissues without the necessity of passage initially through the gastrointestinal tract. Before undertaking this daunting and challenging project, I attempted to overcome my own ignorance of nutrition by spending almost 2 years of my "free time" teaching myself the fundamentals of nutrition and metabolism and reading >600 papers related more specifically to PN, primarily to learn what had been tried and accomplished successfully and what had not. The most valuable publication for my purposes at that time was the monumental summation of the field by Robert P. Geyer, entitled Parenteral Nutrition and published in Physiologic Reviews by the American Physiologic Society in January It is a 37-page masterpiece citing 659 references and is the most comprehensive review of published works on PN to that date. It is "must reading" for all students, investigators, clinicians, and advocates of PN. The following is an excerpt from the introduction and summary of Geyer's paper, which defines the status of PN at the onset of our experiments better than I could present it:

Introduction

Within the last 2 decades, PN has progressed from a regimen of dextrose and salt solutions to one that encompasses all essential nutrients. Experimentally, this affords the means of performing nutrition and biochemical studies in vivo without the direct mediation of the gastrointestinal tract. Its practical importance obtains from the numerous instances when enterai feeding is partially or wholly inadequate. Much of the impetus to the growth of this field stems from the realization that proper nutrition constitutes a crucial aspect of treatment and convalescence. Thus, the surgeon has taken an active and often leading role in the development of this field. Because of the breadth of the subject and the wealth of the available data, emphasis will be. placed on those nutrients most directly concerned with nitrogen and caloric balance. This in no way implies a lesser role for other substances that also are required for health and normal function. Although subcutaneous, intramuscular, and intraperitoneal administration has been used, IV infusions are by far the most common and form the basis for most of the studies herein reported.

Considered from the standpoint of cellular nutrition, there is little reason to doubt that the needs for various nutrients both in kind and amount are fairly similar whether provided by enterai or parenteral means. The latter differs mainly in that problems concerned with toxicity and availability are accentuated, and in addition the requirements of sterility and nonpyrogenicity are imposed. The fundamental challenge has therefore not been to discover what nutrients are required but rather how to provide them in suitable forms and amounts. From both experimental and practical standpoints, this involves all necessary nutrients, although whether all are used in practice is a matter of judgment in each particular application.

Summary

Supplying balanced PN for either experimental or practical purposes can be achieved by the judicious use of properly prepared forms of amino acids, carbohydrates, fats, alcohol, vitamins, and electrolytes. Given moderate quantities of amino acids and adequate calories in the form of carbohydrate, alcohol, or fat emulsions, nitrogen equilibrium or positive balance can be achieved by the IV route in animals and patients under a variety of conditions, including the immediate postoperative period. Various techniques, including tracer studies, have shown rapid and extensive use of parenterally administered nutrients. The problems of choosing the optimum, kinds, amounts, and ratios of nutrients are by no means settled, and the particular needs of each experimental study or patient must be considered. Planned nutrition programs will accomplish far more than haphazard feeding programs, whether by enterai or parenteral means. Reactions are still encountered, though continued improvements in materials and in the understanding of their proper usage will undoubtedly eliminate these as important considerations. Although oral feeding is still to be preferred whenever possible, PN has achieved a permanent place in both therapeutic and experimental

An orderly, rational description and discussion of the resources, techniques, technology, hindrances, data collection, and eventual clinical applications was presented at the 27th ..N. Clinical Congress in 2003 as part of the Jonathan Rhoads Symposium, entitled "Early Developments and Clinical Applications of Total Parenteral Nutrition," and has been published in the July-August 2003 issue of JPEN in the usual condensed and sanitized In this presentation, I would like to share, especially with the younger members of the Society, some of the many aspects of the laboratory and clinical research that are not described in formal presentations or printed in the final publications. However, some of these "outtakes" are often interesting and sometimes valuable parts of the total picture to other investigators and clinicians in this field of endeavor. Initially, Dr Rhoads felt that it was essential to infuse nutrients by peripheral vein if any technique of PN was to be accepted by clinicians for use in patients. Accordingly, we increased the concentration of the nutrient solutions to 10% or 15%, knowing that these solutions would be irritating to the veins and thrombogenic and that the quantity of water used as a vehicle for infusing the nutrients would be 2-3 times greater than that ordinarily tolerated by a patient. Therefore, the first approach to validate this technique was to infuse such solutions into adult dogs and to use the available intramuscular diuretics to aid in the excretion of the excess administered water. However, the standard available diuretics, primarily mercurials, were not adequately effective and posed the risk of being nephrotoxic. Moreover, with this technique, weight gain justifiably could be attributed to retention of salt and water rather than to synthesis of tissue. Therefore, this model was abandoned in the animal laboratory but found a new life clinically in 1962 with the clinical availability of IV chlorothiazide. Within a short time, several other new classes of IV diuretics became available, and Dr Rhoads and I designed a protocol in which 5 L of nutrient solution containing 10%-15% concentrations of protein hydrolysate (fibrin), dextrose, electrolytes, and water-soluble vitamins, together with added chlorothiazide, were infused continuously over 24 hours into a group of preterminal cancer Nitrogen equilibrium was achieved in most of the patients, and positive nitrogen balance was achieved in some of the patients. To minimize venous thrombosis and thrombophlebitis, addition of pharmacologie agents to the regimen, including heparin, procaine, hydrocortisone, did not yield any measurable benefit; moreover, most clinical surgeons were not enamored with infusing these substances into their postoperative patients, nor were they comfortable with the high quantities of water infused intravenously. Although these studies provided important evidence for the validity of the hypothesis that practical PN support was possible, further modifications of the technique were obviously indicated.

Others had attempted to grow puppies fed entirely by IV, but they were unsuccessful for a variety of reasons. First, their nutrient formulas were not complete; second, the infusions were given by peripheral vein; third, the infusions were carried out for only 8-10 hours of each day and for only 5 or 6 days a week, thus limiting the nutrition ration to a suboptimal level; and fourth, the infusion apparatus used was that designed by Drs Rhode and Vars for use in adult animals, and it was not adequate to withstand the rigorous treatment to which it was subjected by the active and restive For these reasons, and possibly others, all previous attempts to support normal growth and development in puppies had failed. Therefore, the first order of business was to correct or overcome the deficiencies of the previous experiments, which had not been successful. The essential components of PN included the development of: (1) all required nutrient substrates to support normal growth and development, specifically in beagle puppies; (2) appropriate sterilization of the components of the solution and the maintenance of long-term sterility in the final formulation; (3) safe, stable, nonreactive, inert, central venous catheters; (4) safe long-term central venous catheterization and infusion techniques, and (5) dependable safe infusion pumps and a durable, counterbalanced, swiveled delivery apparatus that would withstand the rigors of hyperactive puppies in cages.

The first chore was to determine the nutrient requirements for dogs, more specifically for beagle dogs, and most specifically for beagle puppies. The optimal nutrient requirements for St. Bernard dogs are obviously different from those of a Chihuahua. The misconception that dog food was the same for all dogs had to be corrected, and the precise oral nutrient requirements for support of growth and development in beagle puppies was available in the veterinary literature, primarily because the beagle species was chosen as one of the experimental animals by the Atomic Energy Commission for studies relevant to the detonation of the atomic bomb on Bikini Atoll. The next challenge was to estimate the IV parenteral nutrient requirements relative to the recommended oral daily allotments. Beagle puppies also were chosen for the experiments because of their standard purebred characteristics, even temperament, innate cleanliness, and short coat.

Initially, we attempted to feed the puppies entirely IV from birth until their full development into adults. This required my acquisition of pregnant beagles a few days before their estimated delivery date and then monitor them almost continuously in a special holding room in the Harrison Department of Surgical Research Laboratories, so that I could ensure that the puppies received no nourishment from their mother by breast after being whelped. I spent as many as 72 consecutive hours in the animal quarters in order to accomplish this goal, and, especially at night, I shared the company of the quarters with various cockroaches, mice, and rats who inhabited the laboratory and seemed to enjoy snuggling against my body on the Army surplus cot set up in the room. After a few nights, I suspended the cot from the rafters with 4 piano wires to thwart the invasion of my privacy by these rascals, but I was only partially successful in keeping the resourceful varmints off me. Attempting to feed the newborn beagle puppies intravenously required housing them in special chambers controlled for climate and humidity, which I acquired from the newborn nursery at the hospital. Despite my best efforts, the animals survived for only about a week, and it became obvious to me that I would require the skills of a neonatologist, or perhaps even a veterinary neonatologist, in order to achieve our goal. I did enlist the services of veterinarians at the University of Pennsylvania School of Veterinary Medicine to assist me in attempting to identify the cause of death at autopsy of these 250-g puppies. Much to my surprise, their bladders had uniformly ruptured, and free urine was present in the peritoneal cavity, together with traces of blood. This did not surprise the veterinarians at all, and they pointed out to me that the tiny urethra of a beagle puppy very easily becomes obstructed by the crystallization of urinary salts at its meatus, and this can result in obstructive uropathy and bladder rupture. By using a warm, wet cotton swab to wash the urethral meatus about every 4 hours (which was the most civilized substitution for the licking of the area which the puppy's mother ordinarily does), I was able to nurse the puppies along for up to 3 weeks, supported by PN. However, because the endeavor was so labor intensive and required virtually continual intensive care type attention, I found it necessary to modify the original protocol to achieve more realistic goals. I rationalized that the primary aim of the experiment was not to grow puppies by vein from birth but rather to demonstrate in an immature animal (puppy) that normal growth and development could be supported by PN and thereby validate our hypothesis. Thus, the adequacy of the parenteral feeding technique would be more obvious than could be documented by radioisotopic body composition studies or weight gain.

Accordingly, the decision was made to allow the beagle puppies to be whelped and nourished by their mother for the 8 weeks that beagle puppies usually breast feed before the mother discontinues her feeding services to them. A decision was also made to study only the male members of each litter in order to maintain gender standardization. Four males in each of 3 litters received breast feeding for the first 8 weeks and then were fed an optimal oral beagle puppy diet for an additional 4 weeks. At that point, 2 animals of each litter were chosen to serve as orally fed controls. The 2 others (who were paired as closely as possible with the controls, based on their growth and development characteristics) had a central venous catheter inserted into the superior vena cava via a jugular vein in order to receive all nourishment thereafter entirely by vein, while comparing them with their littermates who continued to receive the optimal oral daily puppy ration.

During a 3-month period before beginning the IV nutrient infusions of the beagle puppies, a labor-intensive exercise in quantitative physical chemistry was carried out in order to determine the nature and compatibility of the various anions and cations which were deemed essential for the growth and development of the puppies. Various combinations and forms of the salts were added to the base solution of fibrin hydrolysate and hypertonic dextrose repetitively and tediously until precipitation could be avoided and maximal solubility could be achieved. Subsequently, all of the components were necessarily sterilized initially by passing them through a Seitz filter and ultimately through a filter for cold sterilization because heat sterilization inevitably resulted in precipitation and caramelization of the nutrient solution. This was initially accomplished in a chemical hood in the laboratory, but because of a 25% contamination rate of the solution, manifested by fever in the dogs and confirmed by microbiological smear and culture studies, a laminar flow, filtered-air hood was obtained for formulation of the solutions in the pharmacy of the Hospital of the University of Pennsylvania. It was learned that solutions so prepared could be used safely and effectively after refrigeration for up to 30 days. Microprecipitates and microbial contaminants could be identified in the solutions after that period of time.

Simultaneously with the development of the initial solution, studies were carried out to determine the compatibility of every available plastic tubing that might be used as infusion catheters implanted into the veins of the puppies. All medical-grade catheters or infusion tubings were tested by placing them subcutaneously in dogs and rats under sterile conditions to determine the animals' tolerance to them. Every available medical-grade tubing or catheter tested resulted in an inflammatory subcutaneous response that rendered it undesirable as an IV infusion catheter according to the assumption that it would be thrombogenic and initiate thrombophlebitis when inserted intravenously. In attempting to acquire small-diameter plastic tubing used for commercial purposes, I purchased a roll of Irvington Brand polyvinyl tubing (designed for use as insulation for monofilament wire) at the Pep Boys store (Manny, Moe and Jack) a few blocks away from the university campus. Much to my delight, the tubing did not cause an inflammatory response and had almost all of the desirable other characteristics for use as an indwelling central venous catheter. Because the infusion apparatus, which Drs Vars and Rhode had designed for use in adult dogs several years earlier, was not suitable for the puppies, he and I (mostly Dr Vars) designed a swiveled delivery apparatus that was machined and created by our colleagues in the Towne School of Engineering at Penn. The final apparatus was completed with scavenged Luer fittings, microphone jacks, speedometer cables, and aluminum and stainless steel scraps that Dr Vars had squirreled away in his fantastic laboratory over the previous 30 years. The infusion apparatus was supported on top of 2 cages by standard laboratory piping and connectors and fitted with pulleys and weights to counterbalance the apparatus and the animals in the cages below, while infusing continuously via a heavy duty Harvard pump. Subsequently, a micropore membrane filter was incorporated into the infusion apparatus at the swivel to minimize the infusion of particulate matter, including bacteria and fungi.

The animals were fitted with harnesses that were custom made from soft canvas initially by me and later by my wife. The harness secured a support apparatus on the animal's back by which the lower end of the infusion apparatus was connected to the central venous catheter that exited between the puppy's scapulae. The harness required adjustment with safety pins and adhesive tape on a regular basis because, as the animal grew and developed, the harness would otherwise become too restrictive and uncomfortable. Indeed, new, larger harnesses were custom made approximately monthly and actually served indirectly to verify the growth and development of the puppies.

Although the recommended protein requirement for growing beagle puppies was an impressive g/kg body weight/d, the puppies were unable to tolerate >4 g/kg/d of their ration of fibrin hydrolysate because angioneurotic edema of the ears and face developed at doses of g/kg/d. Therefore, the carbohydrate dose was raised in the IV-fed puppies from the recommended g/kg/d to 25 g/kg/d to compensate for the decreased protein calories and to induce protein sparing. It is important to emphasize that the exact requirement for fat was infused in the first set of puppies as cottonseed oil emulsion, thus providing essential nutrients to the puppies in a complete or Total PN regimen. When the commercially available emulsion (Lipomul, Upjohn, Kalamazoo, MI) was withdrawn from the market, the daily fat emulsion ration was reduced to g/kg/d, which was calculated to provide all of the essential fatty acids required for growth and development in beagle puppies. It was only in the third set of experiments that the 2 IV animals received no IV fat emulsion, because it was no longer available in this country and would not be available until 1975. I am hopeful that this will clear up misconceptions and misunderstandings that I encounter in the literature from time to time from some of our nutritionist colleagues who are not aware of these important facts and assume that all the puppies received a fat-free IV diet.

The puppy solution evolved during the experimental process in other ways also. We learned that biotin and paraaminobenzoic acid were essential vitamins in growing beagle puppies, and these were added to the original formulation. Moreover, although vitamin C is not essential for growth in beagle puppies, it was administered because it was a constituent of the commercial vitamin B/vitamin C formulation that was available to us. Vitamin K, a fat-soluble vitamin, was available individually for IV infusion, but the requirement for it in beagle dogs was unknown and was simply estimated. There was no IV form of fat-soluble vitamins A, D, and E available at the beginning of our experiments. Accordingly, in desperation, I obtained a pediatric liquid vitamin formulation that contained these fat-soluble vitamins, cold sterilized them by passing them through a micropore membrane filter, and added them to the IV nutrient formulation. No adverse effect could be discerned by this unorthodox approach; indeed, the first set of animals appeared to thrive without any evidence of any vitamin deficiency. This prompted me to impose upon the US Vitamin Corporation to develop a water-soluble and compatible form of vitamins A, D, and E for use in our puppy experiments with the idea that such vitamins would be required ultimately in the application of our laboratory experiments to human patients. Within a few months, I was rewarded in my efforts by having 25 vials of the fat-soluble vitamins in aqueous solution for IV use delivered to my laboratory. This vitamin mixture was the prototype for the development of multiple vitamin infusion (MVI), which has undergone some modifications throughout the years but is still in widespread use today as the primary PN vitamin mixture.

I might add that, initially, there was resistance on the part of the pharmaceutical company to respond to my request because there was no apparent market at that time for such an investment in a new product. I learned that the parent company was Revlon, a cosmetics company, and I knew that Lance Revson, son of the founder of Revlon, was a risk taker, according to the fact that he raced in an Indianapolis-class race car. When I was fortunate enough to make telephone contact with him, he expressed an interest in what I was attempting to do in the laboratory, and eventually for patients, and apparently used his influence in the company to produce the vitamin mixture I sought.

Maintaining long-term sterility of all components of the infusion technique was essential to the success of our experiments. The area of the skin of the back around the exit site of the catheter was shaved with a scalpel blade carefully on a regular basis, and triple antibiotic ointment was placed around the catheter once or twice daily to minimize entry of microorganisms along the catheter tract into the central venous system. When one of the first animals developed a fungemia documented by our veterinary colleagues, it became apparent that antibiotic ointment might not be adequate and that an antifungal cream or ointment would also be necessary. However, a single antimicrobial ointment that might be lethal for all bacteria and fungi would be ideal. Iodine tincture is lethal for all unicellular microorganisms; however, an inorganic iodine ointment can be very irritating and cause dermatitis and skin eruptions. I learned that another company, Purdue Frederick, was interested in developing an antimicrobial cream or ointment, and I discussed with their medical staff the possibility of producing an ointment that contained an organic form of iodine that would be released over time to kill all surface microorganisms. Their scientists responded with the development of povidone-iodine (Betadine) ointment, which not only satisfied our needs in the animal experiment but has become a mainstay in the long-term antiseptic maintenance of central venous catheters in patients for about 3 decades.

Because we were also concerned about contamination of the nutrient solution itself, we modified the infusion swivel to incorporate a 1-inch-in-diameter micropore membrane as a "final filter" of the solution in case inadvertent contamination had occurred during its formulation or administration. This idea was actually obtained from the Amoco oil Company, which had incorporated a final filter in its gasoline nozzles to filter out particulate matter that might block the fuel injection system of the high-performance automobiles in this country. A few months later, I met with representatives of the Millipore Corporation (an engineer, a marketing analyst, and financial expert) to attempt to interest them and their company in producing a new product, a bacterial and particulate-matter filter for incorporation into IV infusion tubing, especially that used with PN solutions. They listened to me politely but a week later informed me that they would not be able to honor my request because no market for such a product was apparent. I found myself in a "chicken or egg" situation because I sincerely thought that the market would be created by our work. I subsequently learned that the chairman of the board of Millipore Corporation also served on the board of trustees of Haverford College. At that time, Dr Rhoads, an alumnus of Haverford College, was not only a member of the board of trustees of his alma mater but its chairman. Therefore, I asked Dr Rhoads if I could impose upon him to ask his friend, colleague, and fellow alumnus if he could help me in this situation. Two days later, I received a telephone call from the chairman and CEO of Millipore Corporation, who informed me that he would be sending some of his representatives to see me in the laboratory a few days hence in response to Dr Rhoads' request. The same 3 individuals who had met with me a few weeks earlier returned to visit me with a much more receptive attitude. Within a few weeks, I had a prototype final filter for PN that evolved into a useful clinical adjunct during the early days of PN support of patients. From this experience, I received a memorable lesson in the value and power of seeking help from trusted contacts in achieving otherwise seemingly impossible goals.

To test our initial nutrient solution and infusion apparatus, 2 inexpensive mongrel puppies were obtained, and after hematologic, biochemical, and body weight measurements were obtained, central venous catheters were inserted into the puppies. They were fed entirely by IV thereafter for 24 days, during which time they both grew, developed, and gained weight steadily. At that point, Dr Rhoads visited the laboratory after a research meeting, and I dutifully showed him the puppies and the data obtained to that point. He congratulated me on this early success but then asked me which peripheral veins I had been using for infusion of the nutrient solution. With great trepidation, and expecting to be severely reprimanded for not following his admonishment against using a central venous catheter for infusion, I told him that I was using the external jugular vein for access, but that the tip of the catheter was threaded down into the superior vena cava. I feared the worst, but he simply authorized me to carry on and continue with our original plan to obtain the much more expensive standard pedigreed beagle puppies for our experiments.

Another common misconception about our development of PN is that the first clinical application of the puppy experiments was to human infants. Actually, the first clinical applications of our laboratory experiences were made to 6 seriously ill and malnourished adult surgical patients at the Hospital of the University of Pennsylvania. The first patient was a 52-yearold man with regional enteritis and multiple fistulas who weighed 80 pounds and had lost almost half his body weight over the previous year. We learned some valuable lessons during his treatment. After a few days of receiving PN by the standard gravity-drip-infusion technique, he became increasingly lethargic, listless, and apathetic. He became obtunded almost to the point of coma, and his respirations were depressed, irregular, and disordered. His serum phosphorus level, which had been in the normal range before the PN, had dropped precipitously to zero, and his signs and symptoms were compatible with severe hypophosphatemia. As a result, we increased the phosphate in the PN solution thereafter. Subsequently, the interrelationships between glucose and phosphate and the effects of phosphate levels on the levels of 2,3-diphosphoglycerate were studied in a series of patients receiving During his treatment, this same patient also experienced some episodes of severe hyperglycemia, glycosuria and hyperosmolar, hyperglycemic, nonketotic dehydration, and hypovolemia. These bouts always occurred in the early morning, and we discovered that it was related to the fact that the gravity-drip infusion by which the patient was receiving his hypertonic PN solution had fallen behind schedule during the night shift, and shortly before the morning report, the rate of infusion was increased by the nursing staff in order to comply with the ordered volume of infusion for that 8-hour period. On one of these occasions, the patient experienced a bout of status epilepticus that alarmed the nursing staff. We reiterated to them the crucial importance of maintaining a constant rate of the continuous 24-hour infusion in order to ensure maximal metabolic use to avoid a recurrence of the problem. I brought a pump from the laboratory to the hospital to help the nurses maintain the proper rate of infusion more easily. When the director of nursing learned of this, she interpreted my action as an insult to her nurses and to the entire nursing profession by my implying that a pump was required for nurses to maintain ordered rates of infusion. Indeed, she appealed to the medical board that I be fired, but Dr Rhoads interceded on my behalf, and, furthermore, the medical board ruled that pumps could be used for infusing PN solutions in order to maximize safety and efficacy. This introduced an entirely new era of development of a variety of sophisticated pumps for infusion of IV fluids in critically ill patients.

In our first few patients, we inserted the central venous catheters into the superior vena cava percutaneously via an external jugular vein. This technique was unsatisfactory for several reasons. The first is that the catheter was unable to be threaded into the central vein in about 25% of patients. The second was that the patient felt uncomfortable, often with a stiffness in the neck, because of the presence of the catheter exit site in the neck and its restriction of normal neck movements. The third and most important reason was that it was difficult to maintain long-term asepsis and antisepsis in the neck because of motion of the catheter and difficulty in maintaining an occlusive dressing in this mobile area. Moreover, in men, beard growth in the affected area was an added impediment. Therefore, I began to explore the possibility of using percutaneous subclavian vena puncture for access to the superior vena cava for long-term infusion of the PN solution.

We had been using long catheters inserted into the antecubital vein and threaded into the subclavian vein for monitoring central venous pressure in our cardiac patients for years. However, they were never used for infusion and were usually removed after 1-3 days. Although I had not known about Aubaniac's description of percutaneous subclavian catheterization for emergency transfusion in critically injured battle casualties, I knew that Dr Dominic DeLaurentis had been inserting central venous catheters percutaneously via the subclavian vein in order to monitor central venous pressure in his seriously ill cardiac and vascular patients at Temple University in Philadelphia. When I called him to ask if I could observe him placing one of these catheters, he informed me that one of his previous resident associates who had expertise in the technique was now a urology resident at the University of Pennsylvania Hospital. When I was consulted to evaluate our next PN candidate, an 80-year-old malnourished surgical patient, Dr Robert Mogil stood by while I followed his instructions, and I luckily was successful in achieving needle and catheter access via the subclavicular subclavian vein on my first attempt. We subsequently refined the technique, increasing the safety and efficacy of both initial access and maintaining long-term safe central venous catheterization by this route.

In August 1967, I was asked to examine a 1-monthold infant at Children's Hospital of Philadelphia who had severe short bowel syndrome and was dying of starvation after a massive intestinal resection for atresia. It was our first opportunity to apply what we had learned in feeding beagle puppies directly to a human infant. No one had ever fed an infant sufficiently by IV to support long-term normal growth and development. Her course and management have been described elsewhere in '72 However, we learned some interesting things in her management that have not been widely reported. Because there was no medically approved central venous catheter for newborn infants, we actually used our polyvinyl chloride puppy catheters initially for infusion of her PN solution. Although we had brought a peristaltic pump from our laboratory to her bedside to ensure accurate continuous 24-houra-day infusion, she always fell short of receiving her full ordered fluid allotment during the night shift from 11 PM to 7 AM. Despite our efforts to discern the cause of this recurrent discrepancy, it was not readily apparent. Then, as I was examining her later than usual one night (because of a long operative schedule), I perceived that the lights in her room blinked and that the tone of the pump motor had changed similar to the Doppler effect of a passing train. I asked the nurse if she had perceived the same changes. She answered that it must be 1 AM because the lights always blink and are slightly dimmer at that time every night. I called the hospital engineer on duty to ask him for an explanation, and he informed me that the hospital shifted from 2 generators to 1 generator at night in order to save electricity. When I asked him what effect that had on the voltage, he stated that the voltage dropped about 10%. I then counted the drops per minute of the infusion in the drip chamber, and, indeed, the drip count had dropped by 10% without changing the settings on the pump. I called the pump manufacturer the next day to inquire if the pump could be modified internally to guard against voltage drops, and within a few days I had a new pump fitted with an internal resistor that guaranteed flow rates with up to a 15% drop in voltage. As a result of that experience, most pumps for medical infusions today are equipped with that built-in safeguard.

After a few months of PN, the infant developed rickets, with classic signs of that disorder. Upon the advice of some noted pediatric nutritionists, we had not been giving the full dose of vitamin D to the patient because it was generally thought that vitamin D was only necessary to enhance absorption of calcium across the intestinal mucous membrane. Because we were giving adequate amounts of calcium by vein, our expert consultants initially advised against the need for therapeutic doses of vitamin D, fearing that the calcium might be deposited harmfully in organs and soft tissues. When we doubled the dose of vitamin D in the PN solution, the rickets resolved rather dramatically and quickly. From this experience, we concluded that vitamin D is obviously necessary for more than absorption across the mucous membrane of the gut and that it was likely also necessary for transport of calcium into the bony matrix.

Because an approved IV fat emulsion was no longer available in the United States, we were concerned about the development of essential fatty acid deficiency (EFAD) in the infant. She had already not received any fat for the first month of her life, when she was receiving standard peripheral dextrose and salt solutions, and her body stores of fat were woefully depleted. By infusing high doses of all of her other required nutrients without fat, we were quite certain that a fatty acid deficiency would manifest itself within a few weeks. We rubbed safflower oil onto her skin, hoping that some absorption of linoleic acid would occur transdermally. However, she did develop changes in skin color and character consistent with EFAD, which was subsequently confirmed biochemically. Because the patient, her mother, and her father all had an O-positive blood type, we decided to allow the patient's parents to create a physiologic fat emulsion for their daughter. Accordingly, we fed the parents a breakfast high in fat and drew a unit of blood from each of them an hour later. After centrifuging their donated blood, we drew off the creamy plasma and divided it into 30to 60-mL plastic blood-product bags. We then reinfused their red cells back into the parents. Adding 1 packet of the fatty plasma to the PN regimen of the infant daily was sufficient to correct both the clinical and biochemical EFAD she had demonstrated temporarily and to prevent her from developing EFAD thereafter. Thus, the patient was really receiving complete PN.

In 1968, a 36-year-old woman with extensive intraperitoneal metastatic ovarian carcinoma became the first patient to be fed entirely by vein at home. She had received maximum hospital benefit and wanted to be discharged to her home about 120 miles north of Philadelphia in order to spend as much of her remaining life as possible with her husband and 4 young children. The logistics of maintaining her with PN at home at this early stage in the development of the PN technique were challenging, but with the help of the pharmacists at the Hospital of the University of Pennsylvania and some of our alumni physicians in the patient's home town, we were able to help fulfill the patient's wishes successfully and safely for the final 6 months of her life.

In 1968, I convinced Dr Rhoads that we had to assemble a formal team to support our PN patient activities. We already had an interested group of surgeons, pharmacists, and basic scientists working together informally on various aspects of this project. However, I felt strongly that we needed a designated nurse on the team to ensure continuity, standardization of safe principles and practices, and quality assurance, in addition to helping the staff nurses with the actual care and monitoring of the patients. The existing model in the hospital was a chemotherapy nurse who had pioneered the nurse practitioner concept at our hospital. I was successful in convincing the best emergency department nurse, Joanne Nallinger, to join what we called the hyperalimentation team. Subsequently, the name evolved to the PN team, the nutrition support team, etc. As our vista in the field of nutrition support grew, we added a dietitian, psychiatrist, psychologist, social worker, financial advisor, and even later, gastroenterologists, nephrologists, and other medical specialists. This multidisciplinary approach to the nutrition support of patients formed the grass roots that led eventually to the conception and formation of ..N.

In 1970, I received a telephone call from Dr Crohn, who absolutely astounded me by asking me for my help in caring for one of his long-term patients with Crohn's disease, which had resulted in short-bowel syndrome and malnutrition. He said that he had been caring for her for a long time and that he had done everything he possibly could do for her. It was now his opinion that the only way to continue to keep her alive was for me to accept her as a patient and treat her with PN. It was a memorable experience for a young surgeon to have the opportunity to engage this surgical hero in a lengthy dialogue that day, considering the magnitude of his contributions to the management of inflammatory bowel disease and his worldwide stature.

The patient was a 52-year-old woman having only about 18 inches of small bowel and about half of her colon in continuity. She was obviously emaciated and required intensive nutrition rehabilitation. After receiving PN for a few months in the hospital, she regained not only about 20 pounds but also her energy, strength, and zest for life. We had made arrangements with her pharmacist in her home town in Verona, NJ, to manufacture her PN solution and to provide her with all of the equipment and supplies that she might need at home to cope with this new modality. For the next 15 years, she was nourished at home with PN while she maintained communications long distance with both Dr Crohn and myself, and she made many important contributions to the development and advancement of this neophyte technique. A byproduct of her care was that HNS, a home nutrition support company, was formed by her pharmacist and his partner son and served the needs of patients and physicians and surgeons for many years before being acquired by a larger company.

In 1974, at Hermann Hospital in Houston, I had accumulated a service of 36 patients who were receiving PN and had no other reason for being in the hospital. It was obvious that our efforts should be directed toward establishing the means for such patients to be returned to their homes and to society in order to enjoy a reasonable lifestyle while being fed adequately by vein. We actually started the first home PN company, TPN, Inc, in the Hermann Professional Building. Working together with a variety of pharmacists and pharmaceutical and medical device companies, we were able to patch together an effective embryonic ambulatory home PN service. Subsequently, a home PN center was established in Hermann Hospital through the generosity of McGaw Laboratories and served our patients well for several years.

Working with our pharmacists and seamstresses, we pioneered various ambulatory PN vests, pumps, tubing, and other devices in order to improve the quality of the lives of our patients as they received continuous IV feeding (Table II).8 By 1983, we had acquired >100 patient-years of ambulatory home PN experience, and by that time, the home-care industry nationally had undergone explosive growth, becoming a billion-dollar industry. Indeed, the entire home-care establishment that exists today owes its beginnings primarily to the successful accomplishment of ambulatory home PN. If such a seemingly complex technique could be mastered at home by such compromised patients as those who required PN, virtually any patient could receive required health care at home.

Some special accomplishments with people receiving home PN include our having supported 2 patients from birth continuously to >18 and >20 years of age, and 1 adult patient for 30 years. Multiple and varied infusion devices in the forms of implanted catheters, administration systems, and pumps have been devised to assist in the comfort, effectiveness, and safety of home PN. They will continue to evolve further in the future. One of our patients had a functioning implanted Broviac catheter in his superior vena cava for 11 years 9 months and 3 days without infection until the catheter required replacement because it literally was deteriorating. The second catheter inserted into this same patient was in place for more than 5-and-a-half years so that the patient had experienced a sepsis-free life for >17 years, with only 2 implanted central venous feeding catheters. The strength, courage, and perseverance of these patients, together with their spirit, optimism, and compassion for each other, is manifested in many ways but most noteworthy by their participation in support programs throughout the country, especially by the Oley Foundation, with their invaluable services, their many activities, and their Lifeline Letter.

The most important organizational outgrowth of the burgeoning interest and activity in PN, enteral nutrition, and all forms of nutrition support was the founding of ..N., which occurred on June 5, 1975, almost 30 years ago at the Hyatt Regency O'Hare Hotel in Chicago. The genesis and early evolution of ..N. have been described quite comprehensively by one of its founding members and presidents, Murray H. ..N. was really the brainchild of Mitchell V. Kaminski Jr., who was also the driving force behind its conception. Although he was a surgery resident in the Army at Walter Reed Hospital, he established a hyperalimentation team there and organized a District of Columbia conference on PN and special diets in June 1972. This led to the adoption of goals similar to those that exist today for ..N. Working together with John Grant, he founded the American Hyperalimentation Society in Washington the following year, and Drs Kaminski and Grant sponsored an important program at the National Institutes of Health in the Department of Surgery, which gave great impetus to the movement to organize those throughout the nation interested in nutrition and generalized nutrition support of patients. As Seltzer recalls the founding meeting in 1975, he relates that, "There was a growing restlessness and frustration among those who were to become the founders of the American Society for Parenteral and Enteral Nutrition, ..N. They knew the new treatment modalities of patenteral and enteral nutrition were effective, and they were disappointed that the nation and the world were not adopting these techniques as rapidly as anticipated. It was felt that a multidisciplinary organization was needed to ignite an enthusiasm worldwide for the proper utilization of these specialized nutrition support materials and techniques.

"The services to be provided by the organization were as follows: to coordinate for the membership pertinent information, therapeutic advances and technical innovations related to parenteral and enterai nutrition; to provide an open forum for involvement and exchange of information of all members of the nutrition team including physicians, doctors of nutrition, nurses, pharmacists, dietitians and appropriate industry members; transfer knowledge and experience from those who possess the high degree of competency in the practice of parenteral and enterai nutrition support to those seeking such expertise via the use of seminars, guest speakers, and various other information exchange devices; provide an abstract service to review existing information; provide literature and on-site technical assistance to institutions establishing new programs; and to provide a basis for future scientific collaboration between investigators. Such an ambitious list of goals necessitated ..N.'s rapid growth; the organization barely had time to have an infancy."1 We are all most grateful to the organizing committee for their extraordinary and innovative contributions to the founding of ..N. and for their leadership and stewardship thereafter in its early growth and development (Table III).1

In the 1980s, a devastating blow was dealt to nutrition support teams primarily as a result of the Diagnosis Related Groups, which significantly changed the way that medicine is practiced and reimbursed to this day. Certainly, little or no provision was made by the planners of this form of health care for reimbursement of nutrition support. I am hopeful that ..N. will continue in its efforts to restore the former prominent role of nutrition support services and teams in the provision of optimal nutrition support for all patients in the future. PN and other forms of specialized nutrition support have revolutionized the manner in which neonatology and pediatric surgery are practiced today. Indeed, I am told by my pediatric surgical colleagues that approximately one-third of all major operative procedures in their specialty would be impossible or would fail without the successful application of PN and enterai nutrition. A major challenge today, and for the foreseeable future, is the provision of optimal nutrition support to our increasing geriatric population. More people are living so much longer now that the geriatric patient really requires redefinition. During my career in general surgery, a geriatric patient was one between 50 and 65 years of age. Today, I virtually regard that age group as middle-aged, and the true geriatric patient is one whose age lies between 65 and 100 years of age.

As a general surgeon, I am well aware that maintenance of good nutrition status is essential for optimal geriatric care, particularly in acute situations in which malnutrition is clearly associated with increased complications and other adverse health outcomes. Forty to fifty percent of noninstitutionalized older adults are at moderate to high risk for nutrition problems, and 40% of noninstitutionalized older adults ingest diets deficient in 3 or more nutrients according to the National Health and Nutrition Examination Surveys (NHANES). Additionally, all of the following have 1 or more nutrition inadequacies: 9%-15% of older adults in outpatient clinics, 12%-50% of hospitalized elderly patients, and 25%-85% of older adults residing in institutions. Protein energy malnutrition (PEM) is the most common nutrition inadequacy in the geriatric population and occurs or exists when insufficient energy or protein is available to meet the metabolic needs of the body. The clinical significance of PEM in older patients is that it is associated with altered immunity, impaired wound healing, reduced functional status, increased healthcare use, and increased morbidity and mortality.

Although confounding effects of nonnutrition factors cannot be completely ruled out, many studies have shown that poor nutrition is an independent determinant of increased morbidity and mortality after adjusting for nonnutrition factors. Furthermore, although the efficacy of nutrition support is unproven in many circumstances, data are available to suggest that clinical outcomes can be improved by interventions to correct or prevent nutrition deficits. Moreover, physician recognition of malnutrition in the elderly is often lacking despite its apparent clinical importance, and a number of studies suggest that even when malnutrition is recognized, appropriate attempts to correct the condition are not made. Optimally, effective care of frail or ill elderly patients mandates evaluation of nutrition status for early recognition of malnutrition and consideration of appropriate supportive nutrition interventions. The nutrition assessment of elderly patients includes, as always, a careful history and physical examination; a proportional weight change from usual to current; serum total protein and albumin concentrations; immunologic indices including lymphocyte counts; and anthropometries, including mid arm muscle circumference, skin fold thickness, and BMI (body mass index). A >5% decrease in weight is accompanied by definitely increased morbidity and mortality, a >10% decrease results in functional abnormalities and poor outcomes to therapy, and a >15%0 -20% decrease is considered severe malnutrition, which can be highly lethal. Severe malnutrition in geriatric patients is defined as a weight loss exceeding 20% of premorbid weight, a serum albumin level

Although elderly patients seem to have worse outcomes after operations than younger patients, age itself is not an independent risk factor for increased mortality, and when corrected for comorbid disorders, including malnutrition, age alone has little influence on prognosis. It is well known that despite aggressive nutrition support (oral, enteral, parenteral) of the elderly patient, it is often difficult to attenuate the catabolic response to illness or injury. Anthropometric measures indicate that when body weight does increase with nutrition support of the elderly patient, gains are mostly in fat and extracellular water, whereas gains in lean body mass might result in better functional and clinical outcomes. In considering geriatric surgical risks, mortality for emergency operations of all types in elderly patients is at least 3 times greater than for the comparable procedure performed under elective conditions. Nutrition status predictors of morbidity in geriatric patients include the KATZ Index of ADL (activities of daily living) Score, serum albumin level, usual weight percentage, presence of decubitus ulcers, presence of dysphagia, and midarm muscle circumference, according to a recent Veterans Affairs Unfortunately, in general, decisions regarding surgery in elderly patients often are made according to speculation and unfounded prejudice rather than on data, knowledge, and experience.

To summarize my thoughts on the status of geriatric nutrition support, I submit the following: comprehensive geriatric health care should include the maintenance of normal nutrition status in those who are in good health, and provision of adequate nutrition for the sick. The elderly may be at risk for development of malnutrition because of a variety of physiologic and socioeconomic factors. Hospitalized elderly patients are a heterogeneous population, but they are at significant risk for presenting to the hospital with or developing both protein-energy and micronutrient deficiencies. Nutrition assessment should be routine at admission and at regular intervals thereafter. In elderly patients requiring nutrition support, PN is indicated when the early establishment of effective enterai nutrition cannot be relied upon, and it should be initiated early in the hospital course. Peripheral PN can be a valuable interim solution when the clinical course and volitional or enterai intake are uncertain. Dietary counseling and nutrition support are just 2 of the many interventions required for the optimal care of this important and rapidly increasing segment of our society. Finally, further research in basic and clinical areas is necessary to define more clearly the many nutrition events that occur with aging and to define optimal management of these changes. I am hopeful the membership of ..N. will rise to this challenge to provide optimal nutrition to all patients under all conditions at all times, especially in our geriatric patients.

In reflecting upon the past 45 years of my obsession and passionate pursuit of providing optimal nutrition support to all patients, I have compiled a rather lengthy list of what I consider the significant contributions of the development and successful clinical application of PN to our fund of useful knowledge. They include the following. (1) The demonstration that all nutrients required for normal growth and development in animals and human beings could be provided long term entirely by IV for the first time. (2) The demonstration that positive nitrogen balance, weight gain, wound healing, reduced morbidity and mortality, and many other desirable clinical outcomes could be accomplished in critically ill patients nourished entirely by IV as long as required. (3) The development of a wide variety of parenteral macronutrient and micronutrient substrates for standard and special nutrition and metabolic support of serious ill patients of all ages. (4) The development of safe, effective central venous catheterization and long-term IV infusion techniques for nutrition support, resuscitation, and pharmacotherapy. (5) The stimulation of a technological revolution in the development of infusion pumps, alarms, safety features, servomechanisms, miniaturization, portability, precision, dependability, etc. (6) The stimulation of the development of IV fluid bags, reservoirs, infusion tubing, administration apparatus, etc, tailored to specific individual patient requirements, situations, and infusates. (7) The stimulation of a technological revolution in pharmacy with automated, computerized preparation and admixture apparatus, filtered laminar-airflow areas, cold sterilization by filtration, nutrient:nutrient and nutrientimedication interactions and compatibilities, etc. (8) The stimulation of the specialty of clinical pharmacology and nutrition support among pharmacists and solution preparation technicians in the pharmacy profession. (9) The demonstration of the multidisciplinary scope of clinical nutrition and the initiation and organization of nutrition support teams. (10) The subsequent inspiration and stimulation for the establishment of multidisciplinary professional, scientific, educational, and clinical societies for the advancement of nutrition support worldwide, such as ..N., ESPEN, PENSA, POLSPEN, etc. (11) The demonstration of the utility of inducing a period of "bowel rest" together with PN in the management of selected conditions or disorders of the gastrointestinal tract. (12) The establishment, beyond a doubt, of the relevance of adequate nutrition support in achieving optimal results, minimizing morbidity and mortality, and improving outcomes in the adjunctive or primary therapy of critically ill patients. (13) The stimulation of the subsequent accentuated interest and advancement in enterai nutrition support as an adjunctive, additional, or alternative technique of nutrition support of patients with an adequately functioning alimentary tract. (14) The stimulation of the study and analysis of cost:benefit, risk:benefit, outcomes, policies and procedures, standards, regulatory legislation, and oversight, credentialing, reimbursement, medical-legal and ethical issues, etc, of nutrition support. (15) The stimulation of the development of nutrient solutions for specific metabolic needs, such as renal failure, hepatic failure with encephalopathy, pulmonary insufficiency, immunomodulation, etc. (16) The stimulation of the concept of nutrients, either individually or in various combinations, as medical foods for use in the therapeutic management of a medical disorder, disease, or condition ("nutriceutical prescription foods"). (17) The development and advancement of the concept that the practice of clinical nutrition support is not merely the provision of foodstuffs but is the modulation of cellular biochemistry, biology, immunology, and function. (18) The development of the concept, apparatus, expertise, and system of ambulatory home nutrition support leading to the "explosion" in the home care industry and outpatient therapy. (19) The demonstration of the essentiality for fundamental, integrated, and continuing nutrition education in the professional school curriculum, postgraduate training programs, and for lifelong learning.

Before concluding this presentation, I would like to express one of my continuing major "pet peeves" or disappointments during my lengthy career. It is that I feel rankled every time I hear the expression "total PN vs TEN" or "parenteral vs enterai," especially among my colleagues who should know better. Anyone interested and competent in providing optimal nutrition to their patients knows that it is essential that knowledge, judgment, and competency must prevail in choosing what are the best diet constituents and how they might best be provided for the patient under virtually any situation or with any adverse condition. Not to use every tool in our clinical toolbox optimally detracts from our education and training, our professionalism, and our morals and ethics. The practice of nutrition support should not be adversely influenced by ambition, self-interest, prejudice, financial gain, ignorance, etc. Practitioners who "always treat their patients with enterai nutrition" and those who "always treat their patients with PN" are both likely to be practicing lessthan-optimal nutrition support. The use of the most appropriate modality in every conceivable situation requires versatility, experience, judgment, and wisdom. As an analogy, one can insert a screw with a pair of pliers, but it would be more suitable and efficacious to use a screwdriver; similarly, one can pound a nail into a board with a wrench, but it would be better to use a hammer. Another analogy in this regard is that some of our colleagues, like some of their Hollywood counterparts, seem to be more interested in the superficial sartorial and tonsorial aspects of the annual Academy Awards ceremony than in the excellence of the performances that earned the actors their Oscars. It would be a noble endeavor for the members of ..N. to direct our efforts, talents, and limited resources to perfecting nutrition support to the point that clinicians could nourish their patients by the most efficacious methods and techniques to provide substrates sufficient in quality and quantity to allow the maximum number of cells in the body cell mass to perform optimally the functions for which they were designed. I am hopeful that the members of this society will take the lead and set the example in the future in advancing each and every method and technique of nutrition support to its full capacity and potential and integrating their use in the most rational and effective manner. We owe it to our patients to do so.

In closing, I would like to share a few philosophical thoughts that have influenced me throughout my career. The first is that there are 3 stages of a new idea: the first stage is that it will never work; the second stage is that it will be too expensive; and the third stage is that "I knew it was a great idea all along." That certainly has applied to the development of PN, enteral nutrition, and even ..N. Thomas Alva Edison, in responding to a question about how he conceived and invented the incandescent light bulb, stated, "Any other bright-minded fellow can accomplish as much if he will stick like hell and remember [sic] nothing that's any good works by itself. You got [sic] to make the damn thing work." This expresses my thoughts regarding the development of PN better than I could. A third lasting axiom, which I attribute to Arthur Burke, PharmD, one of the founders of ..N., is that treating malnutrition is 10% science, 10% experience, 10% skill, 20% patience, but most importantly, 50% attitude. No good can ever possibly result from an indifferent or bad attitude regarding nutrition support. My final thought to the ..N. membership is one that had been expressed more than 12 years ago by one of my early mentors in surgery, Dr James C. Thompson, who stated that "The medicine of today is successful largely because of the research of yesterday, and if we fail today to vigorously pursue research, the medicine of tomorrow will be the medicine of today." I can think of no more profound message to leave with the ..N. membership on this most special occasion in my life as your 28th Jonathan E. Rhoads Lecturer. Thank you very much for this signal honor and privilege, and good luck in your continuing obsessive and passionate pursuit of providing optimal nutrition support to all patients, under all conditions, at all times.

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Stanley J. Dudrick, MD, FACS

From the Yale University School of Medicine, Department of Surgery, Program in Surgery, St. Mary's Hospital/Yale Affiliate, Waterbury, Connecticut

Readers will note the use of "total parenteral nutrition" and "TPN" throughout this article. In the April 2004 issue ?ι Nutrition in Clinical Practice (NCP), ..N. published the "Definition of Terms, Style, and Conventions Used in ..N. Guidelines and Standards" document, which endorsed the use of "parenteral nutrition/ PN" over "total parenteral nutrition/TPN" to avoid confusion regarding the meaning of TPN as total nutrients or feeding totally by parenteral nutrition. To remain true to the history of this aspect of clinical nutrition, however, the term "TPN" was preferred.

Received for publication February 10, 2005.

Accepted for publication April 4, 2005.

Correspondence: Stanley J. Dudrick, MD, FACS, St. Mary's Hospital, Department of Surgery, 56 Franklin Street, Waterbury, CT 06706. Electronic mail may be sent to .