Anesthesia for Bariatric Surgery

Metabolic Syndrome

The clustering of a group of defined metabolic and physical abnormalities is now referred to as the metabolic syndrome. Patients with metabolic syndrome commonly have abdominal obesity, reduced levels of high-density lipoprotein (HDL), hyperinsulinemia, glucose intolerance, hypertension, and other characteristic features as listed in Box 58.1 . Specific criteria for diagnosing metabolic syndrome are included in Table 58.4 . The diagnosis requires that at least three of the following be present: abdominal obesity, elevated fasting glucose, hypertension, low HDLs, and hypertriglyceridemia. Weight gain with visceral obesity is a major predictor of the metabolic syndrome. The clinical approach uses waist circumference, rather than BMI, to define the adipose mass component contributing to the metabolic syndrome since BMI has been shown to be a relatively insensitive indicator of the risk for obesity-associated metabolic and cardiovascular diseases. Waist circumference, but not BMI, reflects abdominal subcutaneous adipose tissue as well as abdominal visceral adipose tissue and is therefore a better index of central, or truncal, fat mass.

In the United States, approximately 34% of the adult population have metabolic syndrome. Of these, more than 83% meet the criterion of abdominal obesity. The incidence of metabolic syndrome increases with age, with more than 40% of the U.S. population affected by the age of 60 years. Men are affected more commonly than women, and Hispanics and South Asians appear to be particularly susceptible. Its frequency is lower in African American men than in Caucasians. Metabolic syndrome may result from use of some commonly prescribed drugs, including corticosteroid, antidepressant, and antipsychotic agents. Protease inhibitors used to treat human immunodeficiency virus (HIV) infection can induce metabolic syndrome secondary to insulin resistance.

Patients with metabolic syndrome have an increased risk for cardiovascular disease events and are at increased risk for all-cause mortality. Metabolic syndrome increases the risk of type 2 diabetes, which itself is an important risk factor for atherosclerotic disease and may be considered as a coronary heart disease equivalent. Metabolic syndrome is also associated with a variety of other conditions, such as polycystic ovary syndrome, nonalcoholic fatty liver disease, gallstones, sleep disturbances, sexual impotence, and numerous forms of cancer including breast, endometrial, pancreatic, colon, and liver cancer, as detailed in Table 58.3 . In multiple trials involving nearly 1900 patients, morbidly obese individuals had much greater weight loss following bariatric surgery than after nonsurgical therapy, with amelioration of most of the diseases associated with morbid obesity in a year’s time. Metabolic syndrome is resolved by bariatric surgery in over 95% of patients who achieve the expected weight loss, making it clear that bariatric surgery is a metabolic intervention and not simply a weight management procedure.

Inflammatory processes appear to play an important role in the metabolic syndrome. Adipose tissue has two major functions: storage and release of energy-rich fatty acids and secretion of proteins required for endocrine and autocrine regulation of energy metabolism. Adipocytes exert their metabolic effects by release of free fatty acids, whose release is enhanced by the presence of catecholamines, release of glucocorticoids, increased beta-receptor agonist activity, and reduction of lipid storage mediated by insulin. Visceral adipose tissue has been identified as an important source of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as antiinflammatory cytokines such as adiponectin. Increased levels of proinflammatory cytokines likely contribute to the etiology of insulin resistance primarily by obstructing insulin signaling and contributing to downregulation of peroxisomal proliferator-activated receptor-γ, which are fundamentally important regulators of adipocyte differentiation and control. Additionally, insulin resistance may promote inflammation through diminution of insulin’s antiinflammatory effects. Lastly, oxidative stress is increased with obesity, primarily as a result of excessive intake of macronutrients and a concomitant increase in metabolic rate. These factors may also contribute to the inflammatory response noted with obesity.

Native immune responses act aberrantly in obese individuals. Natural killer (NK) cell cytotoxic activity is depressed with obesity, as are plasma levels of cytokines such as IL-12, IL-18, and interferon-γ known to regulate NK cell function. Other cytokines (primarily IL-6 and TNF-α) and adipokines (leptin, adiponectin, adipose-derived resistin) are two additional major groups of inflammatory proteins produced and released by adipose and adipose-associated tissue. Both serum and adipose tissue obtained from obese subjects consistently have elevated levels of IL-6 and TNF-α, and circulating levels of IL-6 are consistently increased in individuals having either type 2 diabetes or impaired glucose tolerance. Proteins such as leptin and adiponectin, which are produced primarily by adipocytes, are classified as adipokines. Although leptin is primarily involved in appetite control, its immunologic effects include protection of T lymphocytes from apoptosis and regulation of T-cell activation and proliferation. Reduced leptin levels may increase appetite and slow metabolism, but may also increase susceptibility to the toxicity of proinflammatory stimuli, such as endotoxin and TNF-α. Elevated leptin levels are proinflammatory, and this likely plays an important role in the progression of heart disease and diabetes, especially in obese patients. Serum levels of adiponectin correlate with insulin sensitivity and do not rise in obesity. Significantly reduced adiponectin levels are found in patients having type 2 diabetes. Adiponectin reduces both TNF-α production and activity. It also inhibits IL-6 production. Resistin, an adipokine that induces insulin resistance, is induced by endotoxin and cytokines. Resistin acts at the cellular level to upregulate production of proinflammatory cytokines, most likely through the nuclear factor κB (NFκB) pathway. Resistin appears to present a molecular link among metabolic signaling, inflammatory processes, and the development of cardiovascular disease. Resistin levels have been associated with inflammatory markers apparently independent of BMI in humans.

An understanding of the role of NFκB in insulin resistance is required to fully appreciate the links between obesity and inflammation. Both free fatty acids and TNF-α act via intracellular inflammatory cascade pathways to arrest insulin signaling. This process is mediated by activation of transcription factors present within the cell cytoplasm. Following their translocation to the nucleus, they eventually bind to transcription factors regulating the inflammatory process. The cytoplasm also contains NFκB, another transcription factor whose activation is implicated in a number of diseases, including diabetes. NFκB is also induced by hypoxia, and it increases production of proinflammatory cytokines TNF-α and IL-6, both of which are frequently increased in patients with OSA syndrome. Therefore inflammation provides the common linkage underlying the association between obesity, metabolic syndrome, and OSA.

Obstructive Sleep Apnea—Hypopnea Syndrome

OSA is a condition characterized by recurrent episodes of partial or complete upper airway collapse occurring during sleep. An obstructive apneic event is defined universally as the complete cessation of airflow during breathing lasting 10 seconds or longer despite maintenance of neuromuscular ventilatory effort. The definition of an obstructive hypopneic event however may vary depending on the criteria being used for scoring. The Centers for Medicare and Medicaid Services (CMS) defines a hypopneic event as the partial reduction of airflow of 30% or more lasting at least 10 seconds, accompanied by a decrease of at least 4% in the oxygen saturation (SpO ₂ ) as opposed to the American Academy of Sleep Medicine (AASM), which accepts a 3% drop in SpO ₂ or a terminal cortical arousal. Additionally, the AASM recommends scoring a third type of respiratory event in which flow limitation is detected and is associated with a cortical arousal. These events are designated respiratory effort related arousals (RERAs).

The diagnosis of OSA can only be made in patients who undergo polysomnography, or a home sleep study. Results of polysomnography are reported as the apnea-hypopnea index (AHI), which is derived from the total number of apneas and hypopneas divided by the total sleep time or the respiratory disturbance index (RDI) which includes RERA. A normal lower limit for AHI has not yet been defined in an epidemiologic study of healthy subjects. Most sleep centers commonly use an AHI between 5 and 10 events per hour as a normal limit. The severity of obstructive sleep apnea/hypopnea syndrome (OSAHS) is arbitrarily defined, but recommendations for disease classification are as follows :

• Mild Disease: AHI of 5 to 15 events per hour

• Moderate Disease: AHI of 15 to 30 events per hour

• Severe Disease: AHI of greater than 30 events per hour

Due to the risks of developing systemic and pulmonary hypertension, left ventricular hypertrophy, cardiac arrhythmias, cognitive impairment, persistent daytime somnolence, and other factors, treatment is recommended for patients with either moderate or severe disease. Treatment partly depends on the severity of the sleep-disordered breathing, but the consensus view is that patients with moderate or severe disease should be treated with continuous positive airway pressure (CPAP) during sleep. Other conservative treatment measures may include weight loss, avoidance of alcohol prior to bedtime, and sleeping on one’s side.

Numerous studies have confirmed that obesity is the greatest risk factor for OSAHS, with about 70% of patients (up to 80% of males and up to 50% of females) with OSAHS being obese. Severe sleep apnea disease is more common in men until women reach the age of menopause, and a strong negative correlation between the AHI and minimum SpO ₂ has been observed. Importantly, the diagnosis of OSAHS may be missed until the patient presents for surgery. In one study of 170 patients presenting for surgery, only 15% had already been diagnosed with sleep apnea, but on preoperative testing, 76% were found to have OSAHS. A STOP-Bang questionnaire ( Box 58.2 ) can be used to screen patients for OSA, with a score of 5 to 8 identifying patients at risk for moderate to severe disease. We believe it is important for obese patients presenting for bariatric surgery to undergo preoperative polysomnography testing for OSAHS. Preoperative diagnosis and appropriate interventional management can have the following benefits: less postoperative sleep deprivation, improved response to analgesic and anesthetic drugs, and normalization of cardiovascular disturbances.

Anatomically, obese patients with OSAHS typically have increased amounts of adipose tissue deposited into oral and pharyngeal tissues including the uvula, tonsils, tonsillar pillars, tongue, aryepiglottic folds, and lateral pharyngeal walls. An inverse relationship exists between the degree of obesity and pharyngeal area. Deposition of fat in the lateral walls decreases the size of the airway and changes the shape of the oropharynx into an ellipse with a short transverse and long anteroposterior axis. This configuration can contribute to both the development and severity of airway obstruction and can also increase the expectation that it will be more difficult to maintain airway patency during mask ventilation and to perform direct laryngoscopy for endotracheal intubation with general anesthesia. Neuromuscular blockade should be fully reversed prior to extubation, and low tidal volumes or lung protective ventilation should be employed.

Additionally, airway obstruction following extubation is likely to be complicated by the use of opiate and sedative drugs needed for postoperative pain management because these drugs tend to decrease pharyngeal dilator tone and increase the likelihood of upper airway collapse.

OSA also plays an important role in inflammation and the metabolic syndrome. The hypopneic and apneic events that occur in OSAHS are part of the cycle of events that involves both arousal from sleep and oxyhemoglobin desaturation. Sympathetic nervous system activation results as patients with untreated OSA undergo cyclic episodes of hypoxia and reoxygenation. This process leads to elevation of proinflammatory cytokines and may also induce oxidative stress of vascular endothelium, thus inducing an even more heightened state of systemic inflammation in obese patients with OSA. Levels of many different inflammatory mediators, including IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin, TNF-α, IL-1, reactive oxygen species, and adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are increased in patients with OSAHS. Thus obesity, the metabolic syndrome, and OSAHS are interrelated diseases that significantly alter a patient’s inflammatory disease profile and increase multiple health risks, particularly those of cardiovascular and airway origin. Importantly, surgical intervention to cause weight loss has been shown not only to improve obesity-related respiratory disease, but it also can lead to significant and sustained increases in plasma adiponectin levels while decreasing both IL-6 and hs-CRP levels as well as improve NK cell function and increase IL-12, IL-18, and interleukin-γ plasma levels.

Behavioral Interventions and Modification

Behavioral interventions and behavioral modification are essential for obese patients to change their learned habits related to eating and physical activity in order to produce weight loss and long-term weight reduction. This applies both for nonsurgical and surgical approaches to weight loss. The key features of typical behavioral programs include self-monitoring, goal setting, nutrition and exercise education, stimulus control, problem solving, cognitive restructuring, and relapse prevention. Patients often benefit from referral to multidisciplinary weight loss programs that incorporate diet, physical activity, and behavioral interventions to achieve their weight loss goals because these combined interventions provide the best weight loss and weight maintenance results without pharmacologic or surgical intervention. However, it is essential to identify and treat patients with eating disorders or major psychiatric disorders who require specialized psychiatric and psychological treatment to achieve meaningful weight loss.

Pharmacotherapy for Weight Loss

Recommendations for pharmacotherapy as a treatment of obesity, first and foremost, stress lifestyle and behavioral modifications as the initial approaches to initiate weight loss. Patients who do not reach their established reasonable weight loss goals by a combination of diet and exercise may be directed to pharmacotherapy to increase weight loss. There are weight loss drugs that have been approved by the Food and Drug Administration (FDA) and are currently prescribed for long-term use. These are typically used adjunctively with diet and exercise for patients having a BMI of 30 or greater (≥27 for patients with obesity-related risk factors or comorbid diseases). In current practice, there are only two categories of weight loss drugs: appetite suppressants and lipase inhibitors. Three drugs are currently available for the specific indication of weight loss: phentermine, lorcaserin, and orlistat. Phentermine, an adrenergic reuptake inhibitor, augments adrenergic signaling within the central nervous system and peripheral tissues. Phentermine decreases appetite and food intake and increases resting metabolic rate to promote weight loss. Its side effects include tachycardia and hypertension. Lorcaserin is a selective 5-HT _2C receptor agonist that reduces food intake through the activation of pro-opiomelanocortin. Due to its selectiveness for the 5-HT _2C receptor, lorcaserin has a better safety profile than the previous serotonin agonists for weight loss that have since been removed from the U.S. market due to increased risk of stroke and acute coronary syndrome. Lorcaserin should not be used in patients on selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs) due to the risk of serotonin syndrome, which can be life threatening. Orlistat, a lipase inhibitor, reversibly binds to lipase and prevents both absorption and digestion of certain dietary fats. Because orlistat also interferes with the absorption of fat-soluble vitamins, patients using this drug need to supplement fat-soluble vitamins A, D, E, and K. It has significant gastrointestinal side effects including diarrhea, steatorrhea, flatulence, fecal incontinence, and oily rectal discharge.

Alternative Pharmacologic Options

Allison and colleagues reviewed the literature on dietary and herbal medications for weight loss. These agents are marketed as “food supplements,” thereby escaping the purview of the FDA. Even though these supplements cannot legally claim to treat a disease, they can claim to reduce the risk of a disease. According to the review, claims for weight loss have been made for multiple products such as chitosan, chromium picolinate, conjugated linoleic acid, ephedra alkaloids (ma huang), and Garcinia cambogia . Most of the reports involving these compounds are from poor quality studies without any randomization, control groups, or blinding, thereby placing in question both efficacy and safety of these compounds. The only studies involving herbals that have consistently demonstrated weight loss involve combinations of ephedrine and caffeine. Pharmacologically, this is expected because ephedrine, an adrenergic agonist, is known to be an appetite suppressant and a thermogenic agent. For this reason, ma huang , a natural source of the ephedra alkaloid, is added to most, if not all, dietary supplements marketed for weight loss. The success of ephedrine as a weight loss agent in combination with caffeine and or aspirin is well established. Unfortunately, multiple cases of cardiac and neurological issues, including hypertension, stroke, seizure, and even death have been reported, possibly related to the inconsistent doses in the preparations and the lack of medical supervision in people consuming these products for weight loss. Consequently, the National Institutes of Health has banned these products from any recommended weight loss regimen.