The Infusion Heard 'Round the WorldMayo Clinic College of Medicine, Rochester, Minnesota Correspondence: W. Frederick Schwenk II, MD, Mayo Clinic College of Medicine, Rochester, MN 55906. Electronic mail may be sent to schwenk.frederick{at}mayo.edu. "Growth and Development of an Infant Receiving All Nutrients Exclusively by Vein," by Wilmore and Dudrick1 (Figure 1) was the first case report stating that IV nutrition support could reverse cachexia and allow an infant to grow and develop normally. Although the science of nutrition support has changed dramatically over the 40 years since its publication, this pioneering work proved with just 1 case report that there needed to be a reevaluation of how nutrition was provided to hospitalized patients. Wilmore and Dudrick's report led to major changes in clinical practice, initiated new collaborations among medical disciplines, influenced the decisions of international companies, and spawned the formation of numerous nutrition societies.
It is somewhat presumptive for a "second generation" clinician to describe medical practice when this paper was first published. In 1968, I was still an undergraduate at a small Midwestern college with not the slightest interest or intent of becoming a pediatrician involved with nutrition support. What I have learned about the prevailing belief system comes from interactions with the "first generation," from their writings and from listening to their stories. I am aware of how quickly one can fall out of touch with the practice of neonatology. When I trained in pediatrics some 20 years ago, infants weighing <500 g had no chance of survival. Today, such infants not only survive, but frequently thrive. It is hard for me to imagine what it must have been like in 1968 when physicians at the University of Pennsylvania were faced with a term infant with near total atresia of her small bowel. Infants with such a profound congenital anomaly had no chance of survival beyond a few days. Had this infant been hospitalized elsewhere, there is no question what her fate would have been. At the time of Wilmore and Dudrick's landmark intervention, the child had lost >20% of her body weight and was unresponsive. But in one of the first examples of "translational research," they extrapolated from laboratory work done in conjunction with Jonathan Rhoads and Harry Vars in beagle puppies and published a year earlier.2,3 If IV nutrition support could allow beagle puppies to grow and develop normally, why couldn't such therapy give rise to similar results in human infants?
What factor or factors allowed Wilmore and Dudrick1 to become pioneers in parenteral nutrition (PN) support? Solutions of protein, carbohydrate, fat, and vitamins had been available for >20 years and had been used in animals4,5 and man.6 There even had been a report of "PN" being given to an infant, with short-term success, in 1944.7 What had changed over the preceding 20 years was the ability to provide support to critically ill patients; specifically, the availability and ease of insertion of central venous catheters.8,9 Previously, in order to provide adequate nutrition support, large volumes of fluid needed to be given. Such nutrition support often was done in conjunction with administration of diuretics. Yet congestive heart failure and pulmonary edema were still frequent complications. However, with the availability of large-bore catheters that could be inserted into the superior vena cava, more concentrated solutions of nutrients could be administered. The opportunity to provide PN safely had arrived. There can be no mistaking that Wilmore and Dudrick1 were visionaries. Their work was innovative. They recognized that IV solutions of glucose, amino acids, fat, and vitamins were commercially available. With the advances in IV access and the ability for the first time to safely provide concentrated solutions of nutrients, previous limitations to providing PN could be overcome. After first showing that they could get beagle puppies to grow and develop normally, it was a natural extension of their ideas to try such therapy in a human. The infant girl presenting to the University of Pennsylvania with near total atresia of her small bowel was the ideal candidate to try their new ideas. They had the fortitude to make the jump from laboratory to bedside.
In making this leap, Wilmore and Dudrick1 recognized a need to document scientifically the effects of their therapy. Although the ultimate measure of success in this infant was growth and development, they supplemented their observations with measurement of sodium, potassium, calcium, phosphorus, and nitrogen balance to document the effect of IV nutrition support at an elemental level. This was a well-designed, scientific study. It was also in contrast to the report of Helfric and Abelson7 in 1944, who gave alternating infusions of a lecithin–olive oil emulsification and a mixture of 50% glucose and 10% casein for 5 days to a 5-month-old child. They reported that "the fat pads of the cheeks had returned, the ribs were less prominent, the general nutritional status was much improved, and the expression of dire misery was gone." Today, either of these studies would not be quite so easy to conduct, requiring "compassionate use" approval from an institutional review board. It should also be noted that Wilmore and Dudrick1 chose the optimal clinical setting to show the benefit of PN support. Energy requirements and protein requirements of puppies and infants expressed per kg body weight are higher compared with that of adult dogs and humans. In addition, puppies and infants have limited stored energy reserves. It is therefore not surprising that their choice of subjects greatly improved their chances of success. Besides being innovative, they were wise.
The validation of the use of PN support remains an ongoing challenge. Although the American Society of Parenteral and Enteral Nutrition has developed evidence-based guidelines for the use of parenteral and enteral nutrition,10 the most recent document, entitled "Guidelines for the Use of Enteral and Parenteral Nutrition in Adult and Pediatric Patients," highlights that in many areas, there is a lack of knowledge about how to provide optimal nutrition support. Of more than 320 specific recommendations in this document, only 65 were based on prospective, randomized trials.11 Several recent meta-analyses of the use of PN in critically ill adult patients have even raised the question as to whether the therapy is beneficial in the short term in stressed, normally nourished, or only moderately malnourished patients.12,13 These data in adults are in contrast to data in children.14 After the preliminary report of Wilmore and Dudrick,1 several additional reports of the successful use of PN in low-birth-weight infants were published.15,16 Today, PN is standard therapy in neonatal intensive care units around the world. Although there may be questions about the use of PN in many groups of hospitalized patients, there seems to be consensus that in at least some groups of patients, specifically, infants and children with intractable diarrhea and infants with congenital or acquired anomalies of the gastrointestinal tract requiring multiple surgeries (such as the case described by Wilmore and Dudrick1), PN dramatically reduces mortality and morbidity.17
It is somewhat difficult to predict what specialized nutrition support will look like in the future. There have been many changes over the last 40 years since the publication of Wilmore and Dudrick's1 article in how clinicians provide such support. For example, intensive insulin therapy is being used in critically ill medical and surgical patients to tightly control blood sugars and potentially reduce morbidity and mortality.18,19 There also appears to be a trend to use more enteral than PN support.8 Such therapy provides for the administration of a greater variety of nutrients directly to the intestine and is generally less expensive than PN. On the other hand, it is likely that there will continue to exist a cadre of patients, including small premature infants, who will only survive by the judicial use of PN. There does seem to be a consensus that more randomized, controlled clinical trials using PN in hospitalized patients must be carried out to allow clinicians to optimally treat their patients.8,11,12 One unanswered question is how such studies will be financed.11 However, there are additional questions that plague the clinician who cares for infants.14 For example, despite that fact there is now nearly 40 years' experience with the use of PN in infants, why do so many of these infants develop cholestatic liver disease and subsequent liver failure? This continues to be a major limitation in the clinical management of infants with short gut receiving PN.20 Nearly every aspect of PN has been implicated as causing cholestasis. Despite cycling of the PN and specialized neonatal amino acids solutions, this problem has not been solved. In summary, it has been 40 years since the publication of this "preliminary communication" by Wilmore and Dudrick, an infusion that has been "heard'round the world." The use of PN in hospitalized patients has been clearly established; measurement of its efficacy in many patient populations awaits further randomized, controlled trials. However, just as in this first case report, there remain no questions that this therapy can be lifesaving in select patients, such as infants with short gut.
Nutrition in Clinical Practice, Vol. 22, No. 2,
155-158 (2007) This article has been cited by other articles:
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
|
 |
|
Top
Prevailing Belief System
Unique Scientific Contribution
