Thomas H. Frazier

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.

Micronutrient-Related Neurologic Complications Following Bariatric Surgery

Nearly two thirds of American adults are either overweight or obese. Accordingly, bariatric surgery experienced explosive growth during the past decade. Current estimates place the worldwide volume of bariatric procedures at greater than 300,000 cases annually. Micronutrient deficiencies are well-described following bariatric surgery, and they may present with devastating and sometimes irreversible neurologic manifestations. Clinical symptoms range from peripheral neuropathy to encephalopathy, and are most commonly caused by thiamine, copper, and B12 deficiencies.

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.

Pharmaconutrition for the Obese, Critically Ill Patient

Obesity is an epidemic that affects approximately 30% of the adult population in the United States. The prevalence of obesity in the critically ill seems to correlate with the rise in obesity in the general population. Delivery of standard enteral nutrition (EN) to patients in the intensive care unit (ICU) has been shown to decrease infectious complications. Obese ICU patients may be at increased risk for infections, ICU length of stay, and ventilation requirements compared to the nonobese. Pharmaconutrition has been shown to decrease many of these negative ICU outcomes. Because of obesity-associated increased ICU risk, provision of certain pharmaconutrients should be considered in obese patients requiring EN therapy. This review examines the evidence for specific nutrients such as green tea, curcumin, sulforaphane, poly-unsaturated fatty acids, L-arginine, L-citrulline, L-leucine, protein, probiotics, magnesium, medium-chain triglycerides, and zinc for the treatment of obesity. These nutrients could potentially be added to current EN formulas or provided as supplements.

Targeted Physician Education Positively Affects Delivery of Nutrition Therapy and Patient Outcomes Results of a Prospective Clinical Trial

BACKGROUND Malnutrition is a continuing epidemic among hospitalized patients. We hypothesize that targeted physician education should help reduce caloric deficits and improve patient outcomes. MATERIALS AND METHODS We performed a prospective trial of patients (n = 121) assigned to 1 of 2 trauma groups. The experimental group (EG) received targeted education consisting of strategies to increase delivery of early enteral nutrition. Strategies included early enteral access, avoidance of nil per os (NPO) and clear liquid diets (CLD), volume-based feeding, early resumption of feeds postprocedure, and charting caloric deficits. The control group (CG) did not receive targeted education but was allowed to practice in a standard ad hoc fashion. Both groups were provided with dietitian recommendations on a multidisciplinary nutrition team per standard practice. RESULTS The EG received a higher percentage of measured goal calories (30.1 ± 18.5%, 22.1 ± 23.7%, P = .024) compared with the CG. Mean caloric deficit was not significantly different between groups (-6796 ± 4164 kcal vs -8817 ± 7087 kcal, P = .305). CLD days per patient (0.1 ± 0.5 vs 0.6 ± 0.9), length of stay in the intensive care unit (3.5 ± 5.5 vs 5.2 ± 6.8 days), and duration of mechanical ventilation (1.6 ± 3.7 vs 2.8 ± 5.0 days) were all reduced in the EG compared with the CG (P < .05). EG patients had fewer nosocomial infections (10.6% vs 23.6%) and less organ failure (10.6% vs 18.2%) than did the CG, but these differences did not reach statistical significance. CONCLUSION Implementation of specific educational strategies succeeded in greater delivery of nutrition therapy, which favorably affected patient care and outcomes.

Obesity, inflammation, and pharmaconutrition in critical illness

It should be no surprise to clinicians that in the middle of the current national and global epidemic of obesity, the incidence of obesity would be mirrored in the population of critically ill patients in the intensive care setting. More than one-third of patients hospitalized in the intensive care unit (ICU) have a body mass index (BMI) >30 kg/m2, and 17% of children in the critical care setting are obese [1]. An unfortunate consequence of obesity is the confounding factor of inflammation, which may directly or indirectly contribute to adverse sequelae and poor outcomes [2]. Many of the lifestyle habits that lead to an increase in BMI likewise contribute to increasing inflammation, such as inactivity; ingestion of trans-fats, saturated fats, and u-6 fatty acids; increased leptin levels; high plasma triacylglycerols; and hyperglycemiawith production of advanced glycation end products [2]. Evidence of increased inflammation is seen by the association of central adiposity and increased inflammatory cytokines, such as interleukin (IL)-1 and IL-6, a relationship that is not seen with truncal obesity [3,4]. Even some patients with a normal BMI, but an increased waist-to-hip circumference, will show evidence of increased inflammation [4]. In the ICU, the inflammation that accompanies obesity sets the critically ill patient up for a classic one-/two-hit model of hyperdynamic immune response. Because of the central adiposity, immune responses are already upregulated to a physiological state that resembles a low-grade systemic inflammatory response syndrome. The baseline inflammation associated with obesity represents the first immunologic hit. The subsequent event that leads to critical illness (trauma, burn, pneumonia, sepsis, stroke, myocardial infarct, etc.) represents the second hit and results in an exaggerated metabolic response. The clinical consequences of this overzealous immune response contribute to poor outcomes and possibly increased mortality.

Novel Nonsurgical Endoscopic Approaches for the Treatment of Obesity

Globally, obesity is a leading cause of preventable death and is associated with >60 comorbid medical conditions, including 10 types of cancer that are strongly associated with body mass index. There are a number of traditional obesity treatments—for example, lifestyle management (eg, decreased caloric intake and increased expenditure), pharmacotherapy, and bariatric surgery. Recently, endoscopic approaches have emerged as a viable alternative for weight loss. Endoscopically placed intragastric balloons were introduced in the early 1980s for the treatment of medically complicated obesity but, unfortunately, had high rates of complications, such as premature deflation leading to obstruction. Despite these shortcomings, these devices have experienced a renewal, with a second generation of improved devices being approved for clinical use in 2015. In addition to the intragastric balloons, there are a number of other endoscopic approaches to weight loss that are either Food and Drug Administration approved or undergoing evaluation (aspiration therapy, duodenal jejunal bypass sleeve). The current review examines the literature available and discusses the practical clinical considerations involved.

Pharmaconutrition for the Treatment of Obesity

Obesity is rapidly becoming the leading cause of preventable death with the incidence of obesity doubling over the past 30 years. There are at least 60 known obesity-associated comorbid medical conditions in addition to 12 different types of cancer. Despite the rising trend of obesity, there are very few FDA-approved pharmacological treatments for weight reduction. Patients often turn to alternative therapies including dietary supplements, nutraceuticals, and pharmaconutrition. The purpose of this chapter is to describe the clinical evidence for a number of pharmaconutritional supplements for the treatment of obesity. These supplements include green tea, green coffee extract, protein, and L-leucine.