with postoperative delayed gastric emptying.

STRESS GASTRITIS

7 Major trauma accompanied by shock, sepsis, respiratory failure, hemorrhage, or multiorgan injury is

often accompanied by acute stress gastritis. Acute stress gastritis is particularly prevalent after thermal

injury with greater than 35% total surface area burned.29 Multiple superficial ulcerations and erosions

are noted in the proximal, acid-secreting portion of the stomach, with fewer lesions in the antrum and

only rare ulcerations in the duodenum.

The most sensitive diagnostic test for stress ulceration is endoscopic examination. If patients are

examined within 12 hours of the onset of injury, acute mucosal ulcerations may be observed that appear

as multiple, shallow areas of erythema and friability, often accompanied by focal hemorrhage. The

lesions are progressive during the first 72 hours after injury. When lesions are examined histologically,

they are seen to consist of coagulation necrosis of the superficial endothelium with infiltration of

leukocytes into the lamina propria. Chronic disease, characterized by fibrosis and scarring, is not

observed. With resolution of the underlying injury or sepsis, healing is accompanied by mucosal

restitution and regeneration.

Clinical observations and a large number of experimental studies suggest that mucosal ischemia is the

central event underlying the development of stress gastritis. In clinical practice, most patients who

contract stress gastritis do so after an episode of sepsis, hemorrhage, or cardiac dysfunction

accompanied by shock. Experimental studies that cause depletion of high-energy phosphate compounds

such as ATP predispose to the development of stress gastritis. Luminal gastric acid secretion, although

not the sole cause of stress gastritis, appears to be a necessary concomitant process. A number of

experimental observations suggest that a critical concentration of luminal acid is required to initiate

injury in the setting of mucosal ischemia. The fall in mucosal energy supply permits proton backdiffusion into the mucosa; the resultant decrease in mucosal pH exacerbates ischemic damage.

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Figure 45-7. Conversion of Billroth II gastrojejunostomy to Roux-en-Y gastrojejunostomy. The afferent limb is divided (A) and

intestinal continuity is reestablished by anastomosis 50 to 60 cm downstream from the original gastrojejunostomy (B).

Clinical risk factors that predict development of stress gastritis include adult respiratory distress

syndrome, multiple long-bone fractures, a major burn over 35% of the body surface, transfusion

requirement above 6 units, hepatic dysfunction, sepsis, hypotension, and oliguric renal failure. Scoring

systems of critical illness, exemplified by the Acute Physiology and Chronic Health Evaluation

(APACHE) system, accurately predict risk for acute stress gastritis.

The major complication of stress gastritis is hemorrhage. Admission to an intensive care unit is not an

independent risk factor for bleeding. However, the development of respiratory failure or coagulopathy

(platelet count less than 50,000/mm3, international normalized ratio (INR) >1.5, or partial

thromboplastin time (PTT) greater than two times normal) imparts the greatest risk for hemorrhage.

Diagnosis

Clinical studies that use bloody nasogastric discharge as a sign of stress gastritis probably underestimate

its incidence in critically ill patients. Conversely, studies based on endoscopy overestimate the incidence

of clinically important stress gastritis. In one endoscopically controlled study, 100% of patients with

life-threatening injuries had evidence of gastric erosions by 24 hours. Severely burned patients have

endoscopic evidence of gastric erosions in greater than 90% of cases, whereas significant upper

gastrointestinal hemorrhage occurs in between 25% and 50% of patients with burn wound infection.

Treatment and Prophylaxis

Critically ill patients are at risk for development of acute stress gastritis. Because hemorrhage associated

with stress gastritis significantly increases mortality, these patients should be treated

prophylactically.29–31 Seven randomized, controlled trials have compared H2

-receptor antagonists with

proton pump inhibitors in prophylaxis of bleeding from stress ulceration.29 The consensus of these

studies is that proton pump inhibitors are more effective at maintaining gastric pH above 4.0, but no

convincing data exist that one agent is superior to the other in prevention of clinically important

bleeding. Stress ulcer prophylaxis with these agents is associated with colonization of the upper GI tract

with potentially pathogenic gram-negative organisms. No statistically significant differences in

incidence of pneumonia have been noted between H2

-receptor antagonists and proton pump inhibitors

when used for stress ulcer prophylaxis. H2

-receptor antagonists are involved in more drug-drug

interactions due to inhibitory effects on the cytochrome oxidase system. Prolongation of protime may

be noted in patients receiving coumadin. Increased plasma concentrations of diazepam, propranolol,

nifedipine, and several antibiotics may also be noted in patients receiving H2

-receptor antagonists.

Early enteral feeding was first introduced as a component of burn care. Enteral feeding was designed

to address the hypermetabolic state that develops after burn injury and to prevent visceral protein loss

due to catabolic metabolism. Enteral nutrition has also been demonstrated to prevent bacterial

translocation across the intestinal wall. In addition, enteral nutrition has been noted to maintain

intragastric pH >3.5, suggesting that this modality may be used to prevent gastric hemorrhage from

stress ulceration. In burn patients, early enteral feeding decreases upper GI hemorrhage, effects that are

not potentiated by the addition of H2

-receptor antagonists. It seems likely that early enteral feeding will

become widely employed in critically ill surgical patients, beyond those with thermal injury, as a

primary modality for stress ulcer prophylaxis.

References

1. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic

ulcer disease. Aliment Pharmacol Ther 2009;29:938–946.

2. Sanchez-Delgado J, Gene E, Suarez D, et al. Has H. pylori prevalence in bleeding peptic ulcer been

underestimated? A meta-regression. Am J Gastroenterol 2011;106;398–405.

3. Shiota S, Suzuki R, Yamaoka Y. The significance of virulence factors in Helicobacter pylori. J Dig Dis

2013;14:341–349.

4. Reyrat JM, Rappouli R, Telford JL. A structural overview of the Helicobacter cytotoxin. Int J Med

Microbiol 2000;290:375–379.

5. Wu J, Xu S, Zhu Y. Helicobacter pylori CagA: a critical destroyer of the gastric epithelial barrier.

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Dig Dis Sci 2013;58:1830–1837.

6. Censini S, Lange C, Xiang Z, et al. Cag, a pathogenicity island of Helicobacter pylori encodes type Ispecific and disease-associated virulence factors. Proc Natl Acad Sci U S A 1996;93:1259–1264.

7. Gillen D, El-Omar EM, Wirz AA, et al. The acid response to gastrin distinguishes duodenal ulcer

patients from Helicobacter pylori-infected healthy subjects. Gastroenterology 1998;114:50–57.

8. Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection.

Gastroenterology 2008;134;306–323.

9. Cid TP, Fernandez MC, Martinez SB, et al. Pathogenesis of Helicobacter pylori infection.

Helicobacter 2013;18:12–17.

10. Lanas A, Perex-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital

admission due to severe gastrointestinal events and those associated with nonsteroidal

antiinflammatory drug use. Am J Gastroenterol 2005;100:1685–1693.

11. Pilotto A, Franceshi M, Leandro G, et al. NSAID and aspirin use by the elderly in general practice:

effect on gastrointestinal symptoms and therapies. Drugs Aging 2003;20:701–710.

12. Lanas A, Garcia-Rodriguez LA, Arroyo MT, et al. Risk of upper gastrointestinal ulcer bleeding

associated with selective cyclooxygenase-2 inhibitors, traditional non-aspirin non-steroidal antiinflammatory drugs, aspirin and combinations. Gut 2006;55;1731–1738.

13. O’Connor A, Molina-Infante J, Gisbert JP, et al. Treatment of Helicobacter pylori infection 2013.

Helicobacter 2013;18(suppl 1):58–65.

14. Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe

and its relationship to antibiotic consumption. Gut 2013:62:34–42.

15. Zullo A, Hassan C, Campo SM, et al. Bleeding peptic ulcer in the elderly: risk factors and

prevention strategies. Drugs Aging 2007;24:815–828.

16. Zeiton JD, Rosa-Hezode I, Chryssostalis A, et al. Epidemiology and adherence to guidelines on the

management of bleeding peptic ulcer: a prospective multicenter observational study in 1140

patients. Clin Res Hepatol Gastroenterol 2012:36:227–234.

17. Rosenstock SJ, Moller MH, Larsson H, et al. Improving quality of care in peptic ulcer bleeding:

nationwide cohort study of 13,498 consecutive patients in the Danish clinical register of emergency

surgery. Am J Gastroenterol2013;108:1449–1457.

18. Imperiale TF, Kong N. Second-look endoscopy for bleeding peptic ulcer disease: a decisioneffectiveness and cost-effectiveness analysis. J Clin Gastroenterol2012;46;e71–e75.

19. Hepworth CC, Swain CP. Mechanical endoscopic methods of haemostasis for bleeding peptic ulcers:

a review. Baillieres Clin Gastroenterol 2000;14:467–476.

20. Sharma VK, Sahai AV, Corderi FA, et al. Helicobacter pylori eradication is superior to ulcer healing

with or without maintenance therapy to prevent further ulcer haemorrhage. Ailment Pharmacol Ther

2001;15:1939–1947.

21. Boey J, Choi SK, Alagaratnam TT, et al. Risk stratification for perforated duodenal ulcers: a

prospective validation of predictive factors. Ann Surg 1987;205:22–28.

22. Moller MH, Engebjerg MC, Adamsen S, et al. The peptic ulcer (PULP) score: a predictor of

mortality following peptic ulcer perforation. A cohort study. Acta Anaesthesiol Scand 2012;56:655–

662.

23. Lunevicius R, Morkevicius M. Systematic review comparing laparoscopic and open repair for

perforated peptic ulcer. Br J Surg 2005;92:1195–1207.

24. Sanabria AE, Morales CH, Villegas MI. Laparoscopic repair for perforated peptic ulcer disease.

Cochrane Database Syst Rev 2005;(4):CD004778.

25. Antoniou SA, Antoniou GA, Koch OO, et al. Meta-analysis of laparoscopic versus open repair of

perforated peptic ulcer. J Soc Laparoendo Surg 2013;17:15–22.

26. Hemmer PH, de Schipper JS, van Etten B, et al. Results of surgery for perforated gastroduodenal

ulcers in a Dutch population. Dig Surg 2011;28:360–366.

27. Burge N, Barton RG, Enniss TM, et al. Laparoscopic versus open repair of perforated

gastroduodenal ulcer: a national surgical quality improvement program analysis. Am J Surg

2013;206:957–963.

28. Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal disease. Annu Rev

Pathol 2006;1:63–96.

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29. Greenwood JE, Pilkington KB, Wagstaff MJ. Prevention of gastrointestinal bleeding due to stress

ulceration: a review of current literature. Anaesth Crit Care 2012;40:253–259.

30. Alhazzani W, Alenezi F, Jaeschke RZ. Proton pump inhibitors versus histamine 2 receptor

antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and metaanalysis. Crit Care Med 2013;41:693–705.

31. Reveiz L, Guerrero-Lozano R, Camacho A, et al. Stress ulcer, gastritis, and gastrointestinal bleeding

prophylaxis in critically ill pediatric patients: a systematic review. Pediatr Crit Care Med

2010;11:124–132.

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Chapter 46

Management of Obesity

Robert W. O’Rourke

Key Points

1 Obesity is defined and categorized using body mass index (BMI, weight [kg]/height [m]2) based on

World Health Organization definitions.

2 BMI directly correlates with the risk of multiple metabolic diseases and long-term mortality.

3 Lifestyle interventions as treatment for obesity, including diet, exercise, and psychological therapy,

are of limited efficacy; evolving strategies directed toward environmental manipulation demonstrate

potential.

4 Current pharmacotherapy for obesity includes a wide range of agents that act via multiple

mechanisms, are prone to side effects, and are of limited efficacy; active research in

pharmacotherapy for obesity holds significant promise.

5 Bariatric surgery is highly efficacious in treating obesity and metabolic disease, and includes a wide

range of procedures that have evolved over decades.

6 Current dominant bariatric surgery operations include gastric bypass, sleeve gastrectomy, and

gastric banding.

7 Classic mechanisms of action of bariatric surgery include restriction of caloric intake and

malabsorption of ingested calories, but evolving data suggest that other mechanisms predominate,

including but not limited to alterations in gut and satiety hormone homeostasis, bile acid

metabolism, and enteroenteric and enterocentral nervous systemic communications.

DIAGNOSIS AND EPIDEMIOLOGY

Obesity and Metabolic Disease

Excess adipose tissue is the defining feature of obesity, and metabolic disease arises in adipose tissue.

Metabolic disease is diverse, involving every organ system. The correlation between obesity and

metabolic disease, while strong, is not perfect – some patients develop metabolic disease at low body

weight, while others who are very obese are protected. Visceral adiposity imparts greater risk than

subcutaneous adiposity, and heterogeneity of visceral and subcutaneous adiposities partly explains the

imperfect correlation between obesity and metabolic disease. Lean patients also develop metabolic

disease, albeit less frequently than the obese, demonstrating that nonadipose tissue-based mechanisms

contribute to metabolic disease as well. It is beyond the scope of this chapter to discuss the wide

spectrum of specific treatment strategies for individual metabolic diseases. Rather, we will discuss the

treatment of obesity itself, the goal of which is reduction in adipose tissue mass, because despite the

variable relationship between body weight and metabolic dysfunction, in the vast majority of patients,

regardless of initial weight, weight loss has beneficial effects on virtually all metabolic diseases.

Treatment options for obesity may be broadly divided into medical and surgical approaches.

Diagnosis

1 Body mass index (BMI, weight [kg]/height [m]2) is the primary metric used to define obesity.

Originally devised in the 19th century as a general measure of human body habitus, BMI was coopted in

the 1940s by the insurance industry and used to stratify humans into high- and low-risk subpopulations

based on actuarial data for the purpose of setting life insurance rates. The medical community

subsequently used BMI to estimate risk of morbidity and mortality. Much debate exists regarding the

appropriate BMI cutoff points for optimal health, with various health and professional organizations

setting different values. World Health Organization (WHO) definitions, set in 1995 and agreed upon by

the U.S. Centers for Disease Control (CDC), are most commonly utilized and define overweight as BMI

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>25 and <30 and obesity as BMI ≥30, and categorize obesity into classes 1 (BMI 30 to 34.9), 2 (BMI

35 to 39.9), and 3 (BMI ≥40).1

2 BMI correlates with long-term mortality and metabolic disease in a J-shaped curve, the nadir of

which is debated, but may be as low as 20 or as high as 25.2 BMI in the obese range (≥30) is clearly

associated with an increased risk in long-term mortality and multiple metabolic diseases relative to BMI

<30. For individuals with BMI 40 to 50, this risk translates into a 10-year decrease in life expectancy.

In contrast to obesity, data demonstrating a correlation between overweight BMI and health risk are

conflicting. Analyses are complicated by numerous confounding variables including but not limited to

gender, age, ethnicity, smoking, cancer, and diabetes. In addition, the choice of control/referent group

alters outcomes; for example, the correlations between overweight BMI and clinical outcomes weaken

significantly and may be masked when referent groups span a larger BMI range (e.g., 18 to 25) relative

to comparison with referent groups spanning a narrow BMI range (e.g., 21 to 23). Despite these

conflicting data, the preponderance of evidence suggests that BMI in the overweight range is associated

with an increased risk of long-term mortality, albeit lower than the risk associated with BMI in the

obese range.3 Furthermore, mortality aside, compelling data demonstrate that overweight BMI is

associated with an increased risk of cardiovascular disease, diabetes, and other metabolic diseases, and

is associated with an increased risk of future progression to frank obesity with its attendant risks. Taken

together, these observations suggest that overweight should be considered a serious health risk and a

predecessor to obesity.

These complex data demonstrate that BMI is not a perfect measure of adiposity. Indeed, muscular

athletes may have BMI within the obese range despite low body fat levels and an absence of metabolic

disease, while elderly people with a paucity of muscle mass may have low BMI despite increased

adiposity and metabolic disease. Ethnic differences further confound the predictive power of BMI, as

certain ethnicities, for example Asians, develop metabolic disease at lower BMI, prompting the WHO in

2004 to propose BMI cutoffs of 23 and 27.5 for overweight and obesity respectively in Asians. In certain

subpopulations, including patients with heart failure, renal failure, and other chronic diseases,

overweight and obesity are associated with decreased mortality, a phenomenon termed the “obesity

paradox.”4

These observations have led to a search for other measures of adiposity. Waist circumference and

waist–hip ratio are easily measured and in many studies correlate more accurately with metabolic

disease than BMI, reflecting the disproportionate effect of visceral adiposity on metabolic disease.5

Water displacement, dual-energy x-ray absorptiometry scanning, double-labeled isotope water

measurement, bioelectrical impedance analysis, and quantitative magnetic resonance imaging may

provide more accurate measures of adiposity and better predict metabolic disease, but have not gained

widespread acceptance due to cost and complexity. Despite its limitations, BMI remains the most

commonly used metric for obesity.

Epidemiology, Disease Burden

Human obesity has existed for millennia as evidenced by prehistoric figurines of obese humans (e.g.,

Venus of Willendorf) and periodic concerns regarding past obesity “epidemics” over the past two

centuries. Nonetheless, the worldwide prevalence of overweight and obesity has increased dramatically

over the past 50 years. BMI, like many clinical characteristics, spans a bell curve. Three large US

epidemiologic datasets, the National Health and Nutrition Examination Survey (NHANES), the National

Health Interview Survey (NHIS), and the Behavioral Risk Factor Surveillance System (BRFSS),

demonstrate similar trends, with a rightward shift of the BMI bell curve over the past three decades,

mean BMI increasing from 25.5 in the 1970s to 28.5 in 2005, and the prevalence of obesity more than

doubling in the same interval.6 The CDC reports that as of 2010, 69% of US adults were overweight or

obese, and 36% of US adults and 17% of US children were obese.7 Evidence suggests that the prevalence

of obesity has plateaued in the past 2 to 3 years in industrialized countries including the US, but

continues to rise in developing countries. Gender, ethnic, and regional differences complicate obesity

epidemiology. The rate of increase is higher in women compared to men, and while rates of increase are

similar across ethnicities, mean BMI is highest in Blacks, followed by Hispanics, then Caucasians. Data

regarding the association between obesity and socioeconomic status are conflicting; evidence suggests

an inverse correlation between low socioeconomic status and obesity in low- and middle-income

countries but a positive correlation in industrialized countries. Obesity prevalence is increased in rural

compared to urban environments in the United States, although this relationship is inverted in

developing countries.

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