Ryan T. Hurt

Obesity, inflammation, and the potential application of pharmaconutrition

Obesity is an emerging problem worldwide. Hospitalized obese patients often have a worse outcome than patients of normal weight, particularly in the setting of trauma and critical care. Obesity creates a low-grade systemic inflammatory response syndrome (SIRS) that is similar (but on a much smaller scale) to gram-negative sepsis. This process involves up-regulation of systemic immunity, is characterized clinically by insulin resistance and the metabolic syndrome, and puts the patient at increased risk for organ failure, infectious morbidity, and mortality. Through lipotoxicity and cytokine dysregulation, obesity may act to prime the immune system, predisposing to an exaggerated subsequent immune response when a second clinical insult occurs (such as trauma, burns, or myocardial infarction). Specialized nutrition therapy for such patients currently consists of a hypocaloric, high-protein diet. However, this approach does not address the putative pathophysiologic mechanisms of inflammation and altered metabolism associated with obesity. A number of dietary agents such as arginine, fish oil, and carnitine may correct these problems at the molecular level. Pharmaconutrition formulas may provide exciting innovations for the nutrition therapy of the obese patient.

Nutrition Therapy of the Severely Obese, Critically Ill Patient: Summation of Conclusions and Recommendations

This report compiles the conclusions and recommendations for nutrition therapy of the obese, critically ill patient derived by the group of experts participating in this workshop on obesity in critical care nutrition. The recommendations are based on consensus opinions of the group after review of the current literature. Obesity clearly adds to the complexity of nutrition therapy in the intensive care unit (ICU). Obesity alters the incidence and severity of comorbidities, tolerance of the prescribed regimen, and ultimately patient outcome through the course of hospitalization. Although the basic principles of critical care nutrition apply to the obese ICU patient, a high-protein, hypocaloric regimen should be provided to reduce the fat mass, improve insulin sensitivity, and preserve lean body mass. The ideal enteral formula should have a low nonprotein calorie to nitrogen ratio and have a variety of pharmaconutrient agents added to modulate immune responses and reduce inflammation.

Obesity epidemic: overview, pathophysiology, and the intensive care unit conundrum.

Obesity is one of the leading causes of preventable death in the United States, second only to smoking. The annual number of deaths attributed to obesity is estimated to be as high as 400,000. Nearly 70% of the adult U.S. population is overweight or obese. The historical viewpoint toward obesity has deemed it to be a lifestyle choice or characterological flaw. However, given the emerging research into the development of obesity and its related complications, our perspective is changing. It is now clear that obesity is a heterogeneous disease with many different subtypes, which involves an interplay between genetic and environmental factors. The current epidemic of obesity is the result of an obesogenic environment (which includes energy-dense foods and a lack of physical activity) in individuals who have a genetic susceptibility for developing obesity. The pathophysiology associated with weight gain is much more complex than originally thought. The heterogeneous nature of the disease makes the development of treatment strategies for obesity difficult. Obesity in general is associated with increased all-cause mortality and cause-specific mortality (from cardiovascular, diabetic, hepatic, and neoplastic causes). Yet despite increased overall mortality rates, current evidence suggests that when these same patients are admitted to the intensive care unit (ICU), the obesity provides some protection against mortality. At present, there is no clear explanation for this obesity conundrum in critical illness.

Volume-Based Feeding in the Critically Ill Patient

INTRODUCTION Critically ill patients placed on enteral nutrition (EN) are usually underfed. A volume-based feeding (VBF) protocol designed to adjust the infusion rate to make up for interruptions in delivery should provide a greater volume of EN than the more common fixed hourly rate-based feeding (RBF) method. METHODS This single-center, randomized (3:1; VBF/RBF) prospective study evaluated critically ill patients on mechanical ventilation expected to receive EN for ≥ 3 days. Once goal rate was achieved, the randomized feeding strategy was implemented. In the VBF group, physicians used a total goal volume of feeds to determine an hourly rate. For the RBF group, physicians determined a constant hourly rate of infusion to meet goal feeds. RESULTS Sixty-three patients were enrolled in the study with a mean age of 52.6 years (60% male). Six patients were excluded after randomization because of early extubation. The VBF group (n = 37) received 92.9% of goal caloric requirements with a mean caloric deficit of -776.0 kcal compared with the RBF group (n = 20), which received 80.9% of goal calories (P = .01) and a caloric deficit of -1933.8 kcal (P = .01). Uninterrupted EN was delivered for 51.7% of all EN days in VFB patients compared with 54.5% in RBF patients. On days when feeding was interrupted, VFB patients overall received a mean 77.6% of goal calories (while RBF patients received 61.5% of goal calories, P = .001). No vomiting, regurgitation, or feeding intolerance occurred due to VBF. CONCLUSIONS A VBF strategy is safe and improves delivery to better meet caloric requirements than the standard more commonly used rate-based strategy.

Physician-delivered malnutrition: why do patients receive nothing by mouth or a clear liquid diet in a university hospital setting?

BACKGROUND Traditional practices of placing patients nil per os (NPO) or on clear liquid diet (CLD) deter delivery of optimal nutrition care and are not always supported by sound physiologic principles. OBJECTIVE This perspective survey evaluated the incidence of this practice, the reasons for such orders, and the response to intervention by the Multidisciplinary Nutrition Team (MNT). METHODS All patients admitted to University of Louisville Hospital were monitored by MNT dietitians and were candidates for the study if they were placed NPO upon CLD for ≥ 3 days. The MNT determined appropriateness of diet orders. RESULTS Out of 1192 admissions, 22.6% of the patients (n = 262, 61% male, mean age 46.1 years) were found to be NPO or on CLD for ≥ 3 days (mean 5.2 days NPO, 1.04 days CLD), and were entered in the study. Uncertainty regarding the reason for the specific diet order occurred more often when patients were placed on CLD than when made NPO (32.1% vs. 15.0% of cases, respectively, P < 0.05). NPO diet orders were more often deemed appropriate by the MNT than were orders for CLD (58.6% vs. 25.6%, respectively, P < 0.05). Compliance with MNT recommendations was low at 40.0%. CONCLUSIONS Despite an active MNT, 22% of patients were made NPO or placed on CLD for a prolonged period of time. More than a third of diet orders for NPO and two thirds of orders for CLD were inappropriate and poorly justified. Improving the adequacy of nutrition therapy is hampered by noncompliance with MNT recommendations.

Stress prophylaxis in intensive care unit patients and the role of enteral nutrition.

Use of acid-suppressive therapy (AST) to prevent stress gastropathy in the intensive care unit has grown rapidly over the past 20 years. The primary indications for such use of AST include need for mechanical ventilation, overt gastrointestinal bleeding, severe burn, and head trauma. Despite this limited list of indications, proton pump inhibitors (PPIs) often are overprescribed for purposes of stress prophylaxis. Decreased mucosal blood flow with subsequent tissue ischemia is thought to be the mechanism responsible for stress-induced gastropathy. Subsequent activation of inflammatory and vasoconstrictive mediators determines the severity of the gastropathy. Numerous basic science studies suggest that enteral nutrition (EN) can improve mucosal blood flow and reverse the generation of these inflammatory mediators. Clinical studies evaluating the effectiveness of EN vs acid-suppressive medications, however, have shown variable results (and there are no randomized controlled trials to date). In hypersecretory states (such as head trauma and burns), AST should be given, even in patients who are tolerating EN. In the absence of a hypersecretory state, pharmacologic AST may be avoided or discontinued in patients who are tolerating EN. Stress prophylaxis medications also should be discontinued in patients who do not have a clear indication for their use. Overt bleeding in a patient receiving EN for stress prophylaxis should prompt the initiation of a PPI. Randomized controlled studies investigating the efficacy of EN for stress ulcer prophylaxis are needed. Protocols should be developed to alert healthcare teams to consider discontinuation of AST, especially when tolerance of EN is achieved.

The Outcomes of Obese Patients in Critical Care

The severity and prevalence of obesity continue to rise throughout the world. A similar rise in the prevalence of obesity is seen in the population of patients admitted to the intensive care unit (ICU). In the ICU setting, nearly every aspect of care is made more difficult by obesity. This review highlights the challenges in the care of obese ICU patients. Multiple statistical reviews have suggested improved outcomes for obese ICU patients. This article critically evaluates published outcome studies and highlights potential confounders that may result in misleading results. Body mass index (BMI) has been traditionally used to stratify risk in obese populations. Other factors that may be more predictive of poor outcomes in obese populations are further discussed. Further research in these factors has the potential to guide therapy in high-risk critically ill obese populations.

Geriatric Obesity: Evaluating the Evidence for the Use of Flavonoids to Promote Weight Loss

Obesity is a rapidly growing epidemic that now affects approximately 30% of the adult population in the United States. The prevalence of obesity in the geriatric population makes it one of the fastest growing groups due to aging baby boomers. Because of the limited number of available treatments for obese adults, they often turn to supplements and alternative medicine sources to help them lose weight. One such group of supplements contains plant metabolites flavonoids, which includes catechins from tea, quercetin from fruits and vegetables, and isoflavones from soy products. Some flavonoids such as catechins and soy isoflavones can modestly reduce weight. This review examined the clinical evidence for catechins, quercetin, and soy isoflavones for the treatment of obesity and explored the mechanisms of action as related to obesity. Furthermore, flavonoids were evaluated for the treatment of obesity in geriatric populations as well as for safety concerns.

Immune-enhancing enteral diet increases blood flow and proinflammatory cytokines in the rat ileum

BACKGROUND Enteral feeding improves outcome following surgery. Benefits depend on timing, route (enteral vs parenteral), and nutrient composition (standard vs immune-enhancing diets; IED). IED augments intestinal immunity and stimulates gut blood flow during absorption in a nutrient-specific manner. We hypothesize that a mechanism for the gut protective effect of IED is augmentation of blood flow to the gut-associated lymphoid tissue (GALT) in the terminal ileum. METHODS Male Sprague-Dawley rats (200-230 g) were fed for 5 days either an IED (Impact, Novartis) or an isocaloric, isonitrogenous control diet (CD, Boost, Mead-Johnson) matched to the daily caloric intake (rat chow). Rats were then anesthetized and cannulated for microsphere determination of whole organ blood flow. Blood glucose levels and blood flow to abdominal organs were determined at baseline and 30, 60, 90, and 120 min after gastric gavage (2 ml) with IED or CD. Intestinal tissues were harvested for cytokine levels (ELISA: IL-4, IL-10, IFN-gamma, and IgA). RESULTS Chronic IED increased baseline blood flow in the distal third of the small intestine compared to chow-fed and CD. Baseline blood flow was comparable between IED and CD in all other organs. CD and IED produced different blood flow patterns after gavage. CD increased blood flow compared to baseline and IED in antrum, duodenum, and jejunum. Ileal blood flow remained elevated in IED rats for 2 h, perhaps suggesting maximal blood flow. IED increased blood glucose compared to CD. Chronic IED increased IL-4 and decreased IL-10 in the terminal ileum. CONCLUSIONS Chronic IED exposure increases and sustains ileal blood flow compared to CD with altered proinflammatory cytokine expression. Our data suggest that a mechanism for the IED effect involves the selective perfusion of the terminal ileum and contiguous GALT during IED nutrient absorption.

Critical Care Nutrition

The surgical critically ill patient is subject to a variable and complex metabolic response, which has detrimental effects on immunity, wound healing, and preservation of lean body muscle. The concept of nutrition support has evolved into nutrition therapy, whereby the primary objectives are to prevent oxidative cell injury, modulate the immune response, and attenuate the metabolic response. This review outlines the metabolic response to critical illness, describes nutritional risk; reviews the evidence for the role, dose, and timing of enteral and parenteral nutrition, and reviews the evidence for immunonutrition in the surgical intensive care unit.