Incidence and prevalence

Obesity is a disease that affects more than one-third of the adult U.S. population. It is the second leading cause of preventable death in the United States. Current estimates are that 65% of adults in the United States are classified as overweight or obese and more than 30% of adults are classified as obese; this means the prevalence of obesity has doubled over the past 20 years. There are an estimated 23 million persons in the United States with a BMI of no less than 35 kg/m² and 8 million with a BMI of 40 kg/m² or higher. Obesity in children and adolescents has also increased significantly since the mid-1990s. In the United States, 30% of this population is overweight, and 15% is obese.

Pathophysiology

Genetic predisposition, believed to be a primary factor in the development of obesity, explains only 40% of the variance in body mass. The significant increase in the prevalence of obesity has resulted from environmental factors that increase food intake and reduce physical activity. Other factors such as socialization, age, sex, race, and economic status affect its progression. In the United States, food consumption has risen as a result of the supersizing of portions and the availability of fast food and snacks with high fat content. Physical activity has been reduced as a result of modernization (television and computers), a sedentary lifestyle, and work activities. Cultural and lifestyle variations play an important role in the development of obesity.

Clinical manifestations

Manifestations include increased cardiac output, blood volume, oxygen consumption, minute ventilation, work of breathing, and carbon dioxide production, as listed in the following box. Obesity is associated with an increase in the incidence of more than 30 medical conditions. The risk of cardiovascular disease, certain cancers, diabetes, and disease overall is linearly related to weight gain. Type 2 diabetes, coronary heart disease, hypertension, and hypercholesterolemia are prominent conditions in overweight and obese patients. With increasing weight gain and increased adiposity, glucose tolerance deteriorates, blood pressure rises, and the lipid profile becomes more atherogenic. Hormonal and nonhormonal mechanisms contribute to the greater risk of breast, gastrointestinal, endometrial, and renal cell cancers. Psychological health risks often stem from social ostracism, discrimination, and an impaired ability to participate fully in activities of daily living. The physiologic changes associated with obesity are listed in the following box.

Diagnostic and laboratory findings

Findings include hypercholesterolemia, hypertriglyceridemia, and altered pulmonary function test results. Baseline arterial blood gases, chest radiography, electrocardiography, and echocardiography are used for diagnosis.

Treatment

A multimodal approach in the treatment of obesity includes dietary intervention, increased exercise, behavior modification, drug therapy, and surgery. Weight loss programs are individualized to each patient based on the degree of obesity and coexisting conditions. Drug therapy is initiated in patients with a BMI greater than 30 kg/m² or a BMI between 27 and 29.9 kg/m² with a coexisting medical condition. Medications that promote weight loss have limited efficacy. Despite the enormous potential market, efforts to develop effective drug therapies have been disappointing. The U.S. Food and Drug Administration’s guidance for long-term weight loss drugs recommends that a 5% weight reduction be maintained for 12 months after treatment initiation. Two drugs are available for use: orlistat (Xenical and Alli) and phentermine (Adipex-P, others). When used in combination with a comprehensive weight loss program, they can occasionally be effective in producing weight loss in the range of 4 to 5.5 kg.

Orlistat is a lipase inhibitor that decreases the absorption of fat in the gastrointestinal tract. It has recently been released as an over-the-counter medication. Side effects are minor and most related to gastrointestinal discomfort. Phentermine, a sympathomimetic agent, is approved for short term use (up to 12 weeks) as a weight loss management drug. Tolerance, dependence, abuse, and a relatively high number of side effects limit its usefulness. Several antidepressants, antiepileptic, and antidiabetic drugs may promote weight loss and are used off label for this indication.

Surgical approaches designed to treat obesity can be classified as malabsorptive or restrictive. Malabsorptive procedures, which include jejunoileal bypass and biliopancreatic bypass, are rarely used at the present time. Restrictive procedures include the vertical banded gastroplasty (VBG) and gastric banding, including adjustable gastric banding (AGB). Roux-en-Y gastric bypass (RYGB) combines gastric restriction with a minimal degree of malabsorption. VBG, AGB, and RYGB can all be performed laparoscopically. RYGB, the most commonly performed bariatric procedure in the United States, involves anastomosing the proximal gastric pouch to a segment of the proximal jejunum and bypassing most of the stomach and the entire duodenum. It is the most effective bariatric procedure to produce short- and long-term weight loss in severely obese patients. Advances in laparoscopic surgery have significantly improved surgical procedure times, morbidity, and mortality related to bariatric surgery.

Pharmacologic considerations

Obesity is associated with significant alterations in body composition and function that can alter the pharmacodynamics and pharmacokinetics of drugs. Alterations in the volume of distribution are related to the size of the fat organ, increased blood volume, increased cardiac output, increased total body weight, and alterations in protein binding and lipophilicity of the drug. Highly lipophilic drugs have an increased volume of distribution in obese persons compared with persons of normal weight. The increased volume of distribution requires higher doses of lipophilic drugs to produce the required pharmacologic effect and prolongs the elimination of certain drugs such as benzodiazepines. Factors such as protein binding and end-organ clearance affect volume of distribution.

There is no relationship for some highly lipophilic drugs (digoxin, remifentanil, and procainamide) between their solubility and distribution in obese patients. Dosing by ideal body weight is appropriate for these drugs. Drugs with weak or moderate lipophilicity are usually dosed based on ideal body weight or lean body mass. Recommendations for dosing commonly used anesthetics are listed in the table on pg. 233.

Dosing Guidelines for Intravenous Anesthetics

Anesthetic Agent	Dosing	Guidelines
Midazolam (Versed)	TBW	Increased central Vd; increase initial dose to achieve therapeutic effect; prolonged sedation
Thiopental	TBW	Increased Vd; increase initial dose; prolonged time to awakening
Propofol	TBW: Initial and infusion	Increased Vd; increase initial dose; high affinity for fat; high hepatic extraction
Fentanyl	TBW	Increased Vd; increased elimination half-life
Sufentanil	TBW	Increased Vd; increased elimination half-life
Remifentanil	IBW	Consider age and lean body mass
Cisatracurium	TBW	No difference than those with normal weight
Vecuronium	IBW	Increased Vd; impaired hepatic clearance; prolonged duration of action
Rocuronium	IBW	Faster onset and similar duration of action
Succinylcholine	TBW	Increased plasma pseudocholinesterase activity; increase dose

IBW, Ideal body weight; TBW, total body weight; V_d, volume of distribution.

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