Morbid Obesity

Patrick J. Neligan

CASE SUMMARY

A 57-year-old man is scheduled for an open Roux-en-Y gastric bypass (RYGB). He has a body mass index (BMI) of 65. He has a history of hypertension, congestive heart failure (CHF) (he has an ejection fraction of 28%) and obstructive sleep apnea (OSA). His apnea-hypopnea index is 108, and he receives continuous positive airway pressure (CPAP) 15 cm H₂O at night. Pulmonary function tests reveal a mixed restrictive-obstructive picture. Blood gas, on room air reveals a PaO₂ of 78 mmHg and a PaCO₂ of 51 mmHg. Current medications include metoprolol and enalapril. Evaluation of his electrocardiogram (ECG) reveals left bundle branch block. His fasting blood glucose is 170 mg per dL. Other laboratory values are within normal limits. On physical examination he has central obesity, blood pressure of 150/90 mmHg, heart rate 76 bpm. There is no jugular venous distension. His neck circumference is 20.5 in. (52 cm). He has good mouth opening, with Mallampati class 2 airway, and moderate neck extension. He reports dyspnea on mild exertion and occasional orthopnea.

PART I EPIDEMIOLOGY

How Likely Am I to Encounter This Patient in My Clinical Practice?

This patient has a constellation of clinical findings commonly associated with obesity. Obesity is classified according to BMI (BMI: The weight in kilograms divided by the square of the height in meters Kg/M²). Classifying a patient as overweight represents a BMI of 25 to 29.9; obese a BMI 30 to 34 (class I obesity); morbidly obese a BMI 35 to 39.9 (class II obesity); extreme obesity a BMI 40 to 49.9 (class III obesity); super morbid obesity (MO) and super-super obesity represent BMIs of 50 to 59.9 and >60, respectively. In this chapter, MO refers to all patients with BMI >35.

We are in the midst of an epidemic of obesity. In the United States, the age-adjusted prevalence of overweight in adults increased from 46% to 65.7% between the period 1976 and 2002.¹,²,³ The prevalence of obesity increased from 14.4% to 30.6%; the prevalence of extreme obesity increased from 2.9% to 5.1%.³ This represented 3.3% to 3.9% of men and 5.6% to 7.7% of women, depending on their age (the age group 40 to 59 is most likely to be obese).³ In this group, African American women (average 13.5% with MO), Mexican Americans of all ages, individuals who did not complete high school, and those with short stature, are particularly at risk.³,⁴ MO is associated with a twofold increase in the relative risk of death (from all causes) compared with a BMI 30 to 32.⁵ Recent estimates are that $70 to $100 billion or approximately 10% of all health care costs are attributable to treating obesity and obesity-related complications.⁶

There has been a simultaneous epidemic in bariatric surgical procedures,⁷ as this represents the only effective weight loss therapy.⁸ It is estimated that 103,000 surgeries were performed in 2003 specifically for MO.⁷ This is in addition to other surgeries, such as spine or lower extremity joint procedures, related to this problem. Consequently, as anesthesiologists, we are seeing an increasing number of morbidly obese patients, with the potential for increased perioperative morbidity and mortality.

The distribution of body fat has significant impact on patient outcomes. Patients are divided into roughly two groups: those with peripheral (pear-shaped) fat
distribution, most of which are women, and those with central (apple-shaped) fat distribution, most of which are men. This is conventionally recorded in whites as waistto-hip ratio. A ratio of >1 in men, and >0.85 in women suggest central obesity.⁹

What Medical Problems Does This Patient Have?

This patient has several problems characteristic of MO. These include cardiovascular disease (characterized by hypertension, coronary heart disease [CAD], and CHF), pulmonary disease (characterized by OSA and obesity hypoventilation syndrome [OHS]), and metabolic disease (the “metabolic syndrome” characterized by central obesity, dyslipidemia, insulin resistance-hyperglycemia, and hypertension). In addition, he is likely to have undiagnosed liver disease.

MO predisposes patients to cardiovascular disease. This includes hypertension, CAD, CHF, cerebrovascular disease, varicose veins, and deep venous thrombosis.

Hypertension is seen in 50% to 60% of obese patients. There is a 3 to 4 mmHg increase in systolic blood pressure and a 2 mmHg increase in diastolic pressure per 10 kg weight gained.¹⁰ Obesity contributes to hypertension through the following:

Increased vascular tone, secondary to increased sympathoadrenal activity and reduced bioavailability of nitric oxide, due to increased oxidative stress
Increased expression of angiotensinogen by adipose tissue leading to activation of the renin-angiotensinaldosterone axis
Increased renal sodium retention secondary to hyperinsulinemia

TABLE 44.1 Criteria for Diagnosis of the Metabolic Syndrome

Clinical features	NCEP ATPIII Criteria (at least any three)	WHO Criteria Impaired glucose regulation/insulin resistance and at least two other criteria
Impaired glucose regulation/insulin resistance	Fasting plasma glucose ≥110 mg/dL	Type 2 diabetes mellitus or impaired fasting glycemia (≥6.1 mmol/L [110 mg/dL]) or impaired glucose tolerance or glucose uptake below lowest quartile under hyperinsulinemic, euglycemic conditions
Abdominal obesity	Waist circumference >102 cm (40 in.) in men, >88 cm (35 in.) in women	Waist/hip ratio >0.90 in men, >0.85 in women or body mass index >30 kg/m²
Hypertriglyceridemia	≥150mg/dL	≥1.7 mmol/L (150 mg/dL)
Low levels of HDL cholesterol	<40 mg/dL in men, <50 mg/dL in women	<0.9 mmol/L (35 mg/dL) in men, <1 mmol/L (39 mg/dL) in women
High blood pressure^a	≥130/85 mmHg	≥140/90 mmHg
Microalbuminuria	Not included	≥20 µg/min or albumin:creatinine ratio ≥30 mg/g
^aBlood pressure criteria generally treated operationally by researchers as ≥ (systolic blood pressure) or, ≥ (diastolic blood pressure) or, although not included in original definitions, antihypertensive treatment.
NCEP ATPIII, National Cholesterol Education Program Adult Treatment Panel III; WHO, World Health Organization; HDL, high density lipoprotein.
Data from: (1) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood pressure in adults (Adult Treatment Panel III): Final report. Circulation. 2002;106:3143 and (2) Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539.

Data from the Framingham study has revealed a significant increase in the incidence of heart failure in MO patients.¹¹ For each increment of 1 in BMI, there was an increase in the risk of heart failure of 5% for men and 7% for women. As compared with subjects with a normal BMI, obese individuals had double the risk of heart failure.¹¹

▪ METABOLIC SYNDROME

MO is associated with a significant increase in the risk of CAD. The relative risk is 2.80 for men and 2.71 for women.¹² These patients are also at risk for dyslipidemia and type 2 diabetes mellitus, with all the associated complications. The combination of central obesity, insulin resistance, hypertension, dyslipidemia, and impaired glucose tolerance has been termed the metabolic syndrome. First described by Reaven in 1988,¹³ and known by several monikers (including “Syndrome X”), this disorder has recently been defined by the National Cholesterol Education Program (NCEP)¹⁴ and the World Health Organization (WHO)¹⁵ for research and practical purposes. The definitions are slightly different (see Table 44.1).¹⁶

Depending on which definition is used, between 25.1%¹⁷ and 27% (NCEP definition)¹⁸ of the population
(WHO definition) have metabolic syndrome. Again, African American women and Mexican Americans of both genders are at particular risk. Obesity is not an essential component of metabolic syndrome; however, there is a strong correlation between visceral fat deposits and metabolic syndrome. Hence definitions of metabolic syndrome emphasize waist circumference rather than BMI. It is possible to be metabolically obese and of normal weight, or obese without metabolic syndrome (metabolically “healthy” obese).¹⁹ This distinction is important because metabolic syndrome, not BMI, predicts future cardiovascular disease in women.²⁰ Amongst Finnish men, the prevalence of metabolic syndrome ranged from 8.8% (WHO definition) to 14.3% (NCEP definition). Patients with metabolic syndrome were 2.9 to 3.3 times more likely to die of coronary arterial disease. In a posthoc analysis of two cardiovascular trials, patients with metabolic syndrome were 1.5 times more likely to have major coronary events versus those without it.²¹ The presence of diabetes worsens the risk of metabolic syndrome. In a large cohort of patients, the prevalence of coronary arterial disease was 19.2% in patients with metabolic syndrome and type 2 diabetes, 13.9% with metabolic syndrome alone, and 7.5% with diabetes alone. The presence of coronary arterial disease increases perioperative risk. Hence the metabolic syndrome should be (until prospective epidemiologic data is available) considered an independent perioperative risk factor.

Metabolic syndrome is an inflammatory disorder. Adipose tissue, and in particular visceral fat, is an endocrine, paracrine, and immunologic organ. Obesity is a state of chronic inflammation.²² Insulin is an antiinflammatory hormone. Increased circulating free fatty acids, derived from highly metabolic visceral fat, can reduce insulin activity and promote hepatic steatosis. Tissue macrophages invade adipose tissue and release tumor necrosis factor alpha (TNF-α). This, in turn, causes the release of interleukin (IL)-1, IL-6, and other cytokines. There is an alteration in the relative concentrations of adipose-derived hormones, collectively known as adiopkines. Leptin, the first adiopkine described, is involved in the control of satiety and is markedly proinflammatory. Leptin levels are raised in patients with the metabolic syndrome. Conversely, adiponectin, which is thought to be anti-inflammatory and enhances insulin sensitivity, is reduced in these patients. Resistin, an adipokine that antagonizes insulin, is elevated in the metabolic syndrome, and hence the metabolic syndrome produces an inflammatory picture analogous to low grade sepsis. Interestingly, there are preliminary data that this adipokine picture is associated with an increase in the risk of myocardial ischemia.²³ Recent studies have highlighted the contribution of inflammation to myocardial ischemia and infarction.²⁴,²⁵ Long-term therapy for metabolic syndrome includes lifestyle modification, weight loss, tight control of hypertension and diabetes, β-blockade, statin and perhaps fibrate administration, and nicotinic acid and thiazolidinedione (insulin sensitizer) therapy.²⁶,²⁷

The presence of high levels of free fatty acids in the liver, consequence of insulin resistance and high levels of fructose in the diet,²⁸ predisposes patients to nonalcoholic (fatty) liver disease. As body weight increases, there is a progressive increase in the risk of development of nonalcoholic steatohepatitis. This is an inflammatory disease that is reversible in its early stages with weight loss. However, sustained liver injury leads to fibrosis and cirrhosis in 10% to 25% of affected individuals.¹⁶

▪ OBSTRUCTIVE SLEEP APNEA

OSA-hypopnea syndrome occurs in up to 70% of morbidly obese patients undergoing bariatric surgery.²⁹ This is characterized by five or more episodes of apnea or hypopnea per hour with daytime somnolence, or 15 episodes without. Hypopnea is a 30% reduction in airflow for 10 seconds or longer, together with at least a 4% reduction in oxygen saturation. There is no direct relationship between OSA and BMI,³⁰ although there is a correlation with central obesity. OSA is caused by narrowing of the upper airway due to fat in the pharyngeal wall (at the level of the soft palate and submental area), with loss of pharyngeal dilator activity during sleep. In addition, there is an abnormality of the central control of breathing.

OSA is quantified by performing sleep studies (polysomnography). This generates either an apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). An AHI or RDI >30 signifies severe OSA. The patient described in the case summary has an AHI >100; this should be considered very high risk.

The treatment for OSA is CPAP, with or without inspiratory pressure support. CPAP is probably beneficial to postoperative patients with a history of OSA, particularly at the time of rapid eye movement (REM) sleep on day 3 or 4.³¹ Evidence that this intervention improves outcomes is lacking. The incidence and severity of OSA significantly diminishes following gastric bypass surgery.³²

In addition to OSA, this patient also has the “OHS”, which is also referred to as sleep hypoventilation syndrome. This is characterized by chronic respiratory insufficiency, with both an obstructive and restrictive pattern on pulmonary function tests, and hypercarbia in medically complicated obesity. At its extreme, the patient develops pulmonary hypertension and right ventricular dysfunction (cor pulmonale). This is colloquially referred to as Pickwickian’s syndrome, after the rotund Dickens character. Not all patients with OHS have OSA, and not all patients with OSA are obese.³³

There is little doubt that OHS results in worse intermediate term outcomes in MO.¹⁰ Although it is universally accepted that the presence of OSA increases perioperative risk, particularly in terms of postoperative airway problems (narcotic-induced obstruction of the airway), there is little published data to support this contention.³⁴ The American Society of Anesthesiologists has recently approved guidelines for the perioperative management of these patients.³⁵ (see Table 44.2)

Postoperative atelectasis, with associated hypoxemia and increased pulmonary workload is a significant
problem for morbidly obese patients. During general anesthesia, there is a significant reduction in total respiratory system compliance.³⁶ This leads to significantly lower lung volumes, higher intra-abdominal pressure, and ventilation-perfusion mismatch.³⁷ In addition, morbidly obese patients have a significantly higher airways resistance than normal.³⁶

TABLE 44.2 Meta-Analysis Summary

												Heterogeneity
Linkages				n	Fisher Chi-square	p Value	Weighted Stouffer Zc	p Value	Effect Size	Mantel-Haenszel OR	Cl	Significance	Effect Size
Preoperative evaluation
	Focused history from medical records
		OSA vs. no OSA^*
			BMI	10	116.41	0.001	15.93	0.001	0.56			0.001	0.001
			Blood pressure	6	82.05	0.001	17.50	0.001	0.85			0.001	0.001
			Hypertension	5						2.67	2.05-3.49		0.050
	Focused physical examinationcephalometric measurement
		OSA vs. no OSA^*
			Ba-SN	15	83.45	0.001	4.06	0.001	0.13			0.030	0.030
			SNA	9	53.36	0.001	2.60	0.004	0.09			0.010	0.001
			SNB	9	68.16	0.001	4.12	0.001	0.15			0.001	0.001
			MP-H	8	109.09	0.001	10.90	0.001	0.50			0.001	0.001
			PAS	8	80.56	0.001	6.99	0.001	0.27			0.001	0.001
			OPA	5	22.59	0.020	1.39	0.080	0.06			0.210	0.250
			PNS-P	12	139.54	0.001	13.28	0.001	0.56			0.001	0.001
			SPT	5	65.49	0.001	7.34	0.001	0.41			0.600	0.700
			TA	8	75.81	0.001	6.38	0.001	0.24			0.010	0.110
Preoperative preparation
	Preoperative treatment for OSA
		Pre-post CPAP^*
			AHI	10	152.02	0.001	17.84	0.001	0.98			0.005	0.001
			RDI	5	76.01	0.001	17.20	0.001	0.99			0.030	0.001
			Oxygen saturation	6	91.21	0.001	7.85	0.001	0.46			0.750	0.040
		Pre-post mandibular appliance^*
			AHI	8	97.12	0.001	9.04	0.001	0.73			0.400	0.001
Postoperative management
	Analgesic use
		Neuraxial vs. systemic opioids^†
		Respiratory depression		7						1.44	0.61-3.39		0.030
		PCA without vs. with background infusion^†
			Hypoxemia	5	42.39	0.001	3.02	0.001	0.68			0.900	0.800
	Oxygenation
		Supplemental vs. no supplement oxygen^‡
			Hypoxemia	5						5.98	3.16-11.31		0.750
	Positioning
		Patients in nonsupine vs. supine position^*
			AHI	7	88.59	0.001	10.70	0.001	0.78			0.001	0.001
^*Nonrandomized comparative studies; nonperioperative setting. ^†Data obtained from Practice Guidelines for Acute Pain Management in the Perioperative Setting³; not exclusively patients with obstructive sleep apnea (OSA). ^‡Data obtained from Practice Guidelines for Management of the Difficult Airway²: not exclusively patients with OSA.
AHI, apnea-hypopnea index; Ba-SN, cranial base flexure angle; BMI, body mass index; CI, confidence interval; CPAP, continuous positive airway pressure; MP-H, mandibular plane to hyoid bone; OPA, oropharyngeal area; OR, odds ratio; PAS, posterior airway space; PCA, patient-controlled analgesia; PNS-P, soft palate length, posterior nasal spine to palate; SNA, angle from sella to nasion to supramental point; SNB, angle from sella to nasion to submental point; SPT, soft palate thickness; TA, tongue volume/size.
From: Practice Guidelines for the Perioperative Management of Patients with Obstructive Sleep Apnea. Anesthesiology. 2006;104:1081-1093.