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Gut Instincts: My Perspective

Give ‘Em 3 Liters of Hyperal

Levine, Gary M1

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Clinical and Translational Gastroenterology: February 2015 - Volume 6 - Issue 2 - p e76
doi: 10.1038/ctg.2015.3
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More than 40 years ago, my career as a gastroenterologist unintendedly veered toward nutrition support. As a gastroenterology fellow at the Hospital of the University of Pennsylvania (HUP), I needed to find a suitable research project. Luckily, Dr Jonathan Rhoades and his colleagues at HUP had pioneered the use of intravenous (IV) feeding. Ezra Steiger, a resident in the Penn surgical research laboratory had downsized hyperal into a rat model. My research mentor, Dr Julius Deren suggested that I use “hyperal” in rats to determine whether the catabolism of fasting or the lack of luminal nutrients leads to gut atrophy. My control group received the parenteral formula through a gastrostomy. I have fond memories of taking our 18-month-old son Ari with me to the laboratory on weekends to change the “apple-juice bottles”. The experiment was a success. IV-fed rats developed gut atrophy compared with enterally fed controls. An oral presentation at the American Gastroenterological Association and a Gastroenterology paper followed. An academic career was founded and funded. Over the next two decades, working with my colleague Yih Fu Shiau and a number of excellent fellows at the Veterans Administration Medical Center and later at the Albert Einstein Medical Center in Philadelphia, my laboratory applied the rat model to study the effects of gut resection, pancreaticobiliary secretions and individual nutrients on gut mass, enzyme activities as well as in vitro and in vivo absorptive function.

My interest in human clinical nutrition emanated from the good fortune of meeting Drs James Mullen and John Rombeau both of whom encouraged me to consult and round on patients at both the HUP and the Veterans Administration Medical Center. At that time, two-in-one “hyperal” was used with IV fat piggybacked intermittently. Most of the patients received infusions through subclavian lines with its risk of pneumothorax. It was a common practice to administer parenteral nutrition broadly to patients ranging from the pre-op walking well admitted for elective surgery to severely ill malnourished intensive care unit (ICU) “shipwrecks”. The maxim, “Give ‘em three liters of hyperal” was operant, resulting in frequent problems with fluid overload, electrolyte disorders, and hyperglycemia. Central-line infections also were a common problem. I learned about our ability to sustain patients with short gut or intestinal failure.

Multiple studies showed that a large number of ICU and ill medical patients (˜40–50%) was either malnourished or became malnourished soon after admission, leading to a high risk of complications, prolonged length of stay, and death. The rapid application of IV nutrition lead to studies assessing the patient's nutritional diagnosis, defining their needs, the method of delivery, and monitoring the adequacy of nutritional support. The use of safer enteral access began to be widely advocated. The art of nutrition assessment was born, aiming to find a rapid and reproducible method of making a nutrition diagnosis so that nutrition support would be recognized and treated as soon as possible. Search for a gold-standard diagnostic test (criteria included albumin, prealbumin, transferrin, retinal binding protein, and so on) found that none was as useful as taking a diet and weight loss history, astutely coined and promulgated by Dr Khursid Jeejeebhoy as “Global Nutrition Assessment”. Multiple predictive equations were developed (or rediscovered in the case of the Harris–Benedict equation) to calculate the calorie and nitrogen (i.e., protein) needs. Specific equations were developed for infants, children, diabetics, renal insufficiency, the elderly, and obese. Ancillary measurements such as nitrogen balance and metabolic cart monitoring were available to determine whether nutritional needs were met. Overfeeding fell out of vogue, permissive underfeeding became common, especially in the obese. It soon became clear that the cognitive skill of a well-trained nutrition nurse, dietitian, or physician could accurately “eyeball” the patient's nutritional needs. “Hyperal” was out, superseded by total parenteral nutrition (TPN).

During the 1970s, the American Society of Parenteral and Enteral Nutrition (ASPEN) was founded to provide a framework for nutrition education, to develop guidelines, and to provide a forum for presenting research. John Rombeau was among the founders, and I remember, at his urging, attending one of its first meetings held during a frigid January, in Chicago (no trouble in getting a hotel room at the last minute!). ASPEN provided a multidisciplinary forum and a journal, JPEN. Nutrition support teams (NSTs) were established to develop protocols for the administration and monitoring of TPN and enteral nutrition. These teams began to carry out research comparing nutritional parenteral and enteral regimens, quality monitoring, and so on. However, during the 1980s, NSTs were threatened by a counter reformation driven by cost-containment (diagnosis related groups) strategies. NSTs had to be and were justified to hospital administrators.

As the body of nutrition research grew, troubling revelations came to light. In many studies, TPN was harmful or ineffective; specialized formulas for liver and renal disease, sepsis, and cancer failed to decrease morbidity, length of hospital stay, or mortality. The quality of much research was criticized, pointing out a lack of proper controls, poor patient ascertainment and selection practices, small sample size, and a lack of a priori endpoints. In recent years, large, well-designed multicenter studies have failed to show superiority of early or delayed TPN compared with enteral support. Unfortunately, 40 years later, we lack precision in which patients benefit from TPN and enteral nutrition. Similarly, little benefit has been reported using TPN and enteral formulas containing glutamine, arginine, antioxidants, or immune enhancements. It has been pointed out, particularly by Dr Ronald Koretz, that many studies failed to include control groups in which nutrition support was withheld.

Early on, it was clear that enteral nutrition was safer, less expensive, perhaps better than TPN, but enteral access was more difficult to establish and maintain. In the early 1980s, Dr Jeff Ponsky reported the technique of percutaneous gastrostomy (PEG). After a short learning curve, PEG became a mainstay in the treatment of malnutrition. Although 30 years have passed, it is still unclear whether intragastric feeding vs duodenal intubation and infusion is preferable in the ICU (particularly in patients with pancreatitis and other diagnoses leading to a systemic inflammatory response).

Within the past decade, a new obstacle to nutrition support has had to be surmounted: multiple shortages of parenteral nutrition products ranging from trace metals to electrolytes to macronutrients. The USA still lacks an IV lipid formula containing omega-3 fatty acids.

What should our future focus be? Certainly, we will continue to successfully support patients with gut failure with home TPN. We will better select patients who will benefit from nutrition support. We will learn more about the use of various substrates and diets.


Guarantor of the article: Gary M. Levine, MD.

Specific author contributions: Gary M. Levine is the guarantor and wrote the entire article.

Financial support: None.

Potential competing interests: None.

© 2015 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology