Impact of Body Mass Index on Perioperative Outcomes of Endoscopic Pituitary Surgery

Abstract

Background

Endoscopic pituitary surgery (EPS) is increasingly being used for the treatment of pituitary lesions. Obesity is a growing epidemic in our nation associated with numerous comorbidities known to impact surgical outcomes. We present a multi-institutional database study evaluating the association between body mass index (BMI) and postsurgical outcomes of EPS.

Methods

Patients who underwent EPS from 2005 to 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Preoperative variables, comorbidities, and postoperative outcomes, such as 30-day complications, morbidity, and mortality, were analyzed.

Results

A total of 789 patients were analyzed, of which 382 were obese (BMI ≥ 30) (48.4%). No difference in reoperation rate (P = .928) or unplanned readmission rates (P = .837) was found between the obese versus nonobese group. A higher overall complication rate was observed in the obese group compared to the nonobese counterparts (P = .005). However, when separated into surgical complications (3.7% vs 1.5%, P = .068) and medical complications (7.6% vs 3.9%, P = .027), only medical complications, specifically pneumonia, remained significantly different. EPS on obese patients was also associated with prolonged operating time (154.8 min vs 141.0 min, P = .011).

Conclusions

EPS may be a safe treatment option for pituitary lesions in the obese population. Although obese patients undergoing EPS are at increased risk of medical complications and prolonged operating times, this did not influence mortality, reoperation, or readmission rate.

Keywords

body mass index obesity endoscopic pituitary surgery National Surgical Quality Improvement Program 30-day complications outcomes morbidity mortality

Introduction

Obesity has become an increasing public health concern in the United States, where more than 72 million U.S. adults are obese,¹ equating to a prevalence of 36.5%. Body mass index (BMI) has traditionally been used as a measure of obesity and overweight status. The Centers for Disease Control and Prevention (CDC) defines obesity in adults as a BMI greater than or equal to 30 kg/m².² Obesity has also created a financial burden on society, carrying an estimated annual medical cost of $147 billion in 2008 U.S. dollars.¹ Some health conditions such as heart disease, stroke, and type 2 diabetes have been linked to obesity.¹ Historically, obesity has also been viewed as a significant risk factor for negative postoperative outcomes following nonbariatric surgery because it is associated with apnea, obesity hypoventilation syndrome, and pulmonary embolism (PE).^3–7 Furthermore, obesity is associated with excess visceral adipose tissue, which contributes to profound metabolic disturbances and a prothrombotic, pro-inflammatory state.⁴ Obesity has also been demonstrated to increase postoperative cardiac arrhythmias, wound dehiscence, and infectious complications.⁴

Excessive weight gain can be one of the first clinical signs suggesting Cushing’s Disease, a condition characterized by hypercortisolism due to a pituitary adenoma.^8,9 Surgical resection of pituitary adenomas such as those in Cushing’s Disease has become the gold standard of treatment.¹⁰ With continued advancement in endoscopic surgery and improvements in both technique and technology, this approach has gained increasing popularity and has become the ideal method in surgical treatment of pituitary adenomas.^11,12 To date, there has been one retrospective review that reported obesity to be an independent predictor of postoperative cerebrospinal fluid (CSF) leak after endoscopic transsphenoidal surgery.¹³ In regard to neurologic/neurosurgical disorders, obesity has been associated with idiopathic intracranial hypertension and spontaneous CSF rhinorrhea.^14,15 Within the realm of otolaryngologic surgery, the relationship between BMI and outcomes of cervical endocrine procedures such as thyroidectomy and parathyroidectomy has been studied.^16–18 One study demonstrated that morbid obesity is associated with longer operation times, a more difficult airway and longer stay in the postanesthesia care unit.¹⁸ A large multi-institutional study showed that those with higher BMI undergoing thyroid and parathyroid surgery were at increased risk of wound complication, had longer operation times, and were more likely to require general anesthesia compared to nonobese patients. The impact of obesity on outcomes following endoscopic pituitary surgery (EPS) has been rarely studied. We aim to conduct the first large-scale, multi-institutional analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to examine the effect of obesity on postoperative medical complications, surgical complications, reoperation rates, unplanned readmission rates, and other variables in EPS patients.

Materials and Methods

The 2005–2013 NSQIP user files were queried in June 2016 in order to isolate patients who had undergone EPS. This was accomplished through the use of Current Procedural Code 62165. The isolated patients were separated into 2 groups based on weight status, with an obese group (BMI ≤ 30) and a nonobese group (BMI < 30). The NSQIP database allowed us to compare these two groups on the basis of demographics, comorbidities, and 30-day postoperative outcomes. Secondary to the de-identified nature of the NSQIP dataset, this analysis was deemed exempt from the Rutgers New Jersey Medical School Institutional Review Board.

Comorbidities analyzed included diabetes, smoking (<1 year prior to surgery), dyspnea, current alcohol use, chronic obstructive pulmonary disease, congestive heart failure, previous percutaneous coronary intervention, previous myocardial infarction (MI), hypertension (requiring medication), previous transient ischemic attack, previous cerebrovascular accident (CVA), systemic sepsis, functional status (independent/dependent), and American Society of Anesthesiologists (ASA) class (Table 1).

Table 1.

Overall Patient Demographics and Characteristics in Endoscopic Pituitary Surgery.

	Obese(N = 382)	Non-obese (N = 407)	P
Age cohorts (%)
≤40 years	21.5	22.4	.762
41–60 years	44.0	36.4	.029*
61–80 years	32.7	36.6	.252
>80 years	1.8	4.7	.026*
Sex (%)
Male	47.9	51.1	.369
Female	52.1	48.9	.369
Race (%)
White	63.6	54.1	.013*
Black	15.7	12.5	.250
Other	13.4	23.8	<.001
Unknown	7.3	9.6	.257
Comorbidities (%)
Diabetes	22.8	8.4	<.001*
Smoking	16.5	12.5	.114
Dyspnea	7.9	3.7	.012*
Alcohol	0.9	1.9	.458
COPD	2.4	1.5	.365
CHF	0.5	0.2	.613
PCI	2.7	3.1	.789
MI	0.0	0.0	—
Hypertension	56.0	37.3	<.001*
TIA	1.8	1.5	1.000
CVA	1.8	1.9	1.000
Systemic sepsis	1.6	0.7	.274
Functional status
Independent	97.0	96.6	.734
Totally or partially Dependent	3.0	3.4	.734
ASA class (%)
1 and 2	33.5	54.4	<.001*
3 and 4	66.5	45.6	<.001*

Abbreviations: ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; CVA, cerebrovascular accident; MI, myocardial infarction; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; TIA, transient ischemic attack.

*Statistically significant.

Postoperative outcomes included overall complications, surgical complications, and medical complications. Surgical complications included superficial, deep, and organ/space surgical site infections, wound disruption, and severe bleeding (requiring blood transfusion within 72 hours of the postsurgical period). Surgical complications more specific to EPS such as CSF leak, diabetes insipidus (DI), and syndrome of inappropriate anti-diuretic hormone (SIADH) are not explicitly tracked in the database and thus could not be analyzed. Medical complications consisted of pneumonia, PE, ventilator use for >48 hours, unplanned reintubation, urinary tract infection (UTI), renal insufficiency (increase in creatinine >2mg/dL above preoperative value), acute renal failure, CVA with neurological deficit, nerve injury, cardiac arrest requiring cardiopulmonary resuscitation, MI, and sepsis. Other outcomes analyzed included rates of mortality, reoperation, readmission, and unplanned readmission as well as operating time and length of stay (Table 2).

Table 2.

Postoperative Complications in Endoscopic Pituitary Surgery.

	Obese (N = 382)	Non-obese (N = 407)	P
Overall complications	10.2	4.9	.005*
Surgical complications overall (%)	3.7	1.5	.068
Superficial SSI	0.8	0.0	.113
Deep SSI	0.3	0.0	.484
Organ/space SSI	0.8	0.0	.113
Wound disruption	0.0	0.2	1.000
Severe bleeding	2.1	1.2	.408
Medical complications overall (%)	7.6	3.9	.027*
Pneumonia	1.8	0.2	.033*
Unplanned reintubation	2.9	2.2	.551
Urinary tract infection	2.4	1.0	.130
Renal insufficiency	0.5	0.0	.234
Pulmonary embolism	1.0	0.0	.055
Ventilator > 48 hours	2.4	1.0	.130
Acute renal failure	0.0	0.0	—
CVA with neurological deficit	1.8	0.5	.098
Nerve injury	0.0	0.0	—
Cardiac arrest requiring CPR	0.5	0.7	1.000
Myocardial infarction	0.3	0.0	.484
Sepsis	1.0	0.7	.718
Mortality	1.6	0.7	.328
Total operating time, mean, minutes	154.8 ± 79.3	141.0 ± 73.6	.011*
Length of stay, mean, days	5.1 ± 7.6	4.2 ± 9.6	.133
Return to operating room	3.8	3.7	.928
Readmission	8.7	8.5	.944
Unplanned readmission	5.2	4.9	.837

Abbreviations: CPR, cardiopulmonary resuscitation; CVA, cerebrovascular accident; SSI, surgical site infection.

*Statistically significant.

All statistical calculation for this analysis was accomplished via the use of SPSS version 22 (IBM, Armonk, NY). Both groups were compared to one another through the use of Pearson's χ², Fisher’s Exact, and independent 2-tailed t-tests. Variable differences between the groups were deemed to be statistically significant if the P value was less than .05. Statistically significant postoperative complications were analyzed through the use of a multivariable logistic regression (which accounts for age, gender, race, and statistically significant demographical differences) to determine the independent impact of obesity on postoperative outcomes (Table 3).

Table 3.

Multivariate Logistic Regression for Postoperative Complications Following Endoscopic Pituitary Surgery.

	Odds Ratio (95% Confidence Interval)	P
Overall medical complications	2.188 (1.116–4.290)	.023*
Pneumonia	10.985 (1.285–93.925)	.029*
Overall complications	2.305 (1.269–4.187)	.006*

*Statistically significant.

Results

A total of 810 patients who underwent EPS were identified from NSQIP between 2005 and 2013. Patients without BMI data were excluded and a total of 789 patients were included in the final analysis. Of these, 382 (48.4%) were classified as obese (BMI ≥ 30) and 407 were classified as nonobese.

Demographics and Comorbidities

Statistical analysis of the demographics (Table 1) demonstrated that the obese patient population was more likely to be within the 41- to 60-year age-group (44.0% vs 36.4%, P = .029), while the nonobese group was more likely to be greater than 80 years of age (4.7% vs 1.8%, P = .026). A higher percentage of obese patients were white when compared to the nonobese group (63.6% vs 54.1%, P = .013). There were no significant differences in other races or in gender between the two cohorts.

When looking at comorbidities (Table 1), the obese population was significantly more likely to have diabetes (22.8% vs 8.4%, P < .001), dyspnea (7.9% vs 3.7%, P = .012), and hypertension requiring medication (56.0% vs 37.3%, P < .001). Similarly, the obese cohort had a significantly higher percentage of patients within the ASA class 3 and class 4 classifications (66.5% vs 45.6%, P < .001).

Postoperative Outcomes

Upon analysis of postoperative outcomes (Table 2), we determined that the obese patients were more likely to suffer overall complications (10.2% vs 4.9%, P = .005). Upon more specific inquiry, we can see that obese patients had higher rates of surgical (3.7% vs 1.5%, P = .068) and medical (7.6% vs 3.9%, P = .027) complications, although the elevation in surgical complications is not statistically significant. When analyzing specific medical complications, it was shown that obese patients had significantly increased rates of pneumonia (1.8% vs 0.2%, P = .033). There were no significant differences among the other medical complications or between any of the specific surgical complications.

Upon analysis of other postoperative outcomes (Table 2), we can see that pituitary surgery on obese patients is associated with prolonged operating time (154.8 min vs 141.0 min, P = .011) and nonsignificant elevations in length of stay (5.1 days vs 4.2 days, P = .133). Obese patients similarly had elevated rates in mortality (1.6% vs 0.7%, P = .328), reoperation (3.8% vs 3.7%, P = .928), and unplanned readmission (5.2% vs 4.9%, P = .837); however, none of the differences were statistically significant.

Logistic Regression

Binary logistic regression (Table 3) controlling for age, gender, race, and the four statistically significant comorbidities (diabetes, dyspnea, hypertension, and ASA class) shows that obesity is an independent predictor of the previously mentioned significant outcomes: overall medical complications (odds ratio [OR] 2.188, P = .023), pneumonia (OR 10.985, P = .029), and overall complications (OR 2.305, P = .006).

Discussion

Pituitary tumors constitute 10% to 15% of all intracranial tumors and are diagnosed over 10,000 times each year in the United States.¹⁹ Currently, EPS is considered to be a relatively safe treatment option for pituitary tumors with an overall mortality rate of 0.24% and low risk of complications.²⁰ Although many studies have focused on the efficacy of EPS, few have assessed the impact of patient characteristics on surgical outcomes.

BMI is a universally accepted measure used to define and quantify obesity.^21–23 When the classification was first defined, it was used to differentiate death rates above a certain normal cutoff point and has been closely associated with risk of mortality.

Obesity has a significant impact on mortality and has been linked to numerous comorbidities known to impact surgical outcomes.^24–26 These comorbidities can lead to higher rates of serious hospital-acquired complications (HACs) related to wound healing, deep vein thrombosis/PE, and UTI.²⁷ Postoperative complications have been found to be the strongest indicator of increasing healthcare cost and a major economic burden on the healthcare system.^28,29 Furthermore, policies set by the Center for Medicare and Medicaid Services allow hospital providers to be financially penalized when patients experience certain HACs.³⁰ Thus, identifying risk factors associated with, as well as finding treatment options that may reduce postoperative complications, is imperative.

Our study uses the ACS-NSQIP database to examine the effect of obesity on the postoperative outcomes of EPS as a treatment for pituitary lesions. To our knowledge, this study is the first to explore the relationship between BMI and postoperative complications in EPS on a large, multi-institutional scale.

Obese patients were found to have higher overall rates of complications after EPS. However, when stratified into medical and surgical complication type, the increase in medical complications remained significant (7.6 vs 3.9%, P = .27), whereas the increase in surgical complications was not significant (3.7 vs 1.5%, P = .068). Previous studies have also demonstrated increased medical complication risk in the obese patient population. Safaee et al. confirmed reports that obesity is an important risk factor for thromboembolic events after meningioma resection.³¹ Studies have also shown significant risk of MI, UTI, and hemorrhage in obese patients compared with nonobese patients undergoing noncardiac surgery.³² However, in this study, these trends in complications were not implicated in EPS.

Although the obese cohort experienced a greater percentage of overall medical complications as compared to the nonobese cohort, a more detailed analysis of the various possible medical complications showed that only the incidence of pneumonia was statistically increased. This increased incidence of pneumonia in the obese cohort remained significant even after accounting for significant comorbidities including diabetes, dyspnea, and hypertension (OR 11, 95% confidence interval 1.29–93.9). These results are consistent with those in previous studies. A study by Baik et al. examining the association of age and lifestyle factors with pneumonia also showed that obese patients have a higher risk of developing pneumonia, a leading cause of mortality in hospitalized patients and worldwide.^33,34 Obesity has been often accompanied by conditions such as gastroesophageal reflux disease, obstructive sleep apnea, diabetes, and asthma, all of which are associated with increased incidence of aspiration and community-acquired pneumonia.^35–38 In addition, excess adiposity around the thorax, under the diaphragm, and within the abdomen contributes to decreased chest wall compliance, which favors postoperative pneumonia and atelectasis.³⁹ Interestingly, obesity has also been associated with increased survival advantage in hospital-acquired pneumonia^40–42—a phenomenon known as the “obesity paradox” coined to describe the inverse relationship between obesity and mortality.^43–45 Nie et al. point to more aggressive treatments for obese patients, adipose tissue release of soluble tumor necrosis factor-α receptors, and decreased levels of C-reactive protein as possible explanations for this paradox.⁴⁶ In our study, no significant differences were found between the obese and nonobese study groups for postoperative mortality (1.6 vs 0.7%), which may be related to the paradoxical survival advantage of obesity during pneumonia infection.

A significant difference was found in total operating time between the obese and nonobese groups (154.8 ± 79.3 vs 141.0 ± 73.6, P =.011). Traditionally, increased BMI has been associated with increased total operating time.^47–52 Stevens et al. suggest that impaired monitoring, hemodynamic lability, and positioning difficulties may contribute to increased operation time in neurotological and otological procedures, and that large shoulders and relatively short neck in the obese habitus could increase the technical difficulty of any procedure.⁵³ This could also explain the lengthened operating time of EPS in obese patients. In addition, EPS patients are usually fitted with image guidance hardware, and adjustment of the gear may be hindered by the aforementioned factors.

The increased risk of surgical complications with increased BMI has been implicated across many surgical specialties. Increased incidence of wound infections in obese patients undergoing cardiac surgery,^54,55 open and minimally invasive surgical treatment of endometrial cancer,⁵⁶ as well as cervical endocrine surgery has been demonstrated.¹⁶ The association of obesity with microvascular impairment and poor wound healing may contribute to these higher rates of surgical wound complications.^57,58 However, our study demonstrated that those with increased BMI undergoing EPS did not experience an increased incidence of surgical complications. This could be explained by the minimally invasive nature of the procedures, which require smaller incisions and less damage to the soft tissue.^17,59

The perioperative outcome of those with increased BMI undergoing EPS is much better, with fewer complications than those with increased BMI undergoing other surgical procedures such as coronary artery bypass graft, endometrial cancer resection, and thyroid and parathyroid surgery. Although our study demonstrated that obese EPS patients are at increased risk of postoperative pneumonia and experience longer operation times, we found that these factors had no significant effect on the overall mortality rate. Therefore, EPS remains a safe surgical approach for the treatment of pituitary lesions in those with increased BMI.

This study is not without limitations. Although the WHO classifies obesity using BMI, it may not reflect true obesity, which could be better marked by waist-to-height ratio or waist circumference.^60–64 Call for alternative measurements of general and abdominal obesity in ACS-NSQIP has been noted in previous studies.⁶⁵ There are biases inherent to ACS-NSQIP and any retrospective data analysis, mainly selection bias and the inability to adjust for confounding variables. This analysis only includes patients treated at hospitals voluntarily participating in ACS-NSQIP and may not be representative of other hospitals not participating in data collection. Because of the limited number of participating hospitals, a relatively low number of patients undergoing EPS were identified, which may not reflect the commonality of this procedure and may reduce the power of the study. Furthermore, ACS-NSQIP is primarily a general surgery database, and this could also contribute to the lower than expected number of EPS. Due to the nature of the database, rates of complications typical after pituitary surgery, such as CSF leak, DI, and SIADH, are not available, which causes potential for limited validity. There is also no follow-up beyond 30 postoperative days of initial operation, which limits our ability to assess any long-term effects of EPS beyond this period. Intraoperative events are not available on the database, and thus we were unable to assess the role of such events in the outcome of EPS. In addition, variables such as size and type of tumor (secreting vs nonsecreting) are unavailable in NSQIP and could have significantly impacted the outcome of the analyses, especially considering the increased risk of pneumonia identified in our study.

Despite these limitations, the ACS-NSQIP is a large, multi-institutional database which provides standardized definitions for patient characteristics and clinical outcomes and allows for the analysis of robust clinical data that have been audited for inter-rated reliability.⁶⁶ The results of this study demonstrate that patients with BMI greater than 30 kg/m² are more likely to suffer medical complications following EPS, specifically pneumonia, but that they did not have a statistically significant increase in risk of surgical complications. EPS in the obese cohort was also associated with increased total operating time but did not impact morbidity or mortality, length of hospital stay, reoperation rate, or readmission rate. Therefore, EPS remains a safe surgical approach for the treatment of pituitary lesions in those with increased BMI. Preoperative modification of patient risk factors and careful planning of perioperative management is essential in reducing operating times and improving outcomes in obese patients.

Conclusion

EPS is a safe surgical approach in patients with BMI greater than 30 kg/m². The increase in medical complications and total operating time seen in the obese cohort did not significantly influence mortality or contribute to length of hospital stay, reoperation, or readmission rates. Patient education remains important for the obese patient, with discussion regarding these additional complication risks. The role of obesity should be considered in the perioperative management of the patient.

Footnotes

Authors’ Note

This article was presented as an oral presentation at the 2017 Triological Society Combined Sections Meeting, New Orleans, LA, on January 19–21, 2017.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Centers for Disease Control and Prevention. Overweight and obesity. https://www.cdc.gov/obesity/data/adult.html. Accessed December 26, 2016.

Centers for Disease Control and Prevention. Overweight and obesity. https://www.cdc.gov/obesity/adult/defining.html. Accessed December 26, 2016.

Brooks-Brunn

JA.

Predictors of postoperative pulmonary complications following abdominal surgery.

Chest. 1997; 111:564–571.

Doyle

Lysaght

Reynolds

JV.

Obesity and post-operative complications in patients undergoing non-bariatric surgery.

Obes Rev. 2010; 11:875–886.

Eichenberger

Proietti

Wicky

et al . Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg. 2002; 95:1788–1792, table of contents.

Hall

Tarala

Hall

Mander

A multivariate analysis of the risk of pulmonary complications after laparotomy.

Chest. 1991; 99:923–927.

Merkow

Bilimoria

McCarter

Bentrem

DJ.

Effect of body mass index on short-term outcomes after colectomy for cancer.

J Am Coll Surg. 2009; 208:53–61.

Buliman

Tataranu

Paun

Mirica

Dumitrache

Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

J Med Life. 2016; 9:12–18.

Arnaldi

Angeli

Atkinson

et al . Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003; 88:5593–5602.

10.

Wong

Eloy

Liu

JK.

The role of bilateral adrenalectomy in the treatment of refractory Cushing's disease.

Neurosurg Focus. 2015; 38:E9.

11.

Koutourousiou

Winstead

WI.

Endoscopic endonasal surgery for remission of Cushing disease caused by ectopic intracavernous macroadenoma: case report and literature review. World Neurosurg. 2017; 98:870.e5–870.e10

12.

Kelly

DF.

Transsphenoidal surgery for Cushing’s disease: a review of success rates, remission predictors, management of failed surgery, and Nelson’s syndrome.

Neurosurg Focus. 2007; 23:E5.

13.

Dlouhy

Madhavan

Clinger

et al . Elevated body mass index and risk of postoperative CSF leak following transsphenoidal surgery. J Neurosurg. 2012; 116:1311–1317.

14.

Dunn

Alaani

Johnson

AP.

Study on spontaneous cerebrospinal fluid rhinorrhoea: its aetiology and management.

J Laryngol Otol. 2005; 119:12–15.

15.

Kupersmith

Gamell

Turbin

Peck

Spiegel

Wall

Effects of weight loss on the course of idiopathic intracranial hypertension in women.

Neurology. 1998; 50:1094–1098.

16.

Buerba

Roman

Sosa

JA.

Thyroidectomy and parathyroidectomy in patients with high body mass index are safe overall: analysis of 26,864 patients.

Surgery. 2011; 150:950–958.

17.

Duke

White

Waller

Terris

DJ.

Endoscopic thyroidectomy is safe in patients with a high body mass index.

Thyroid. 2014; 24:1146–1150.

18.

Norman

Aronson

Outpatient parathyroid surgery and the differences seen in the morbidly obese.

Otolaryngol Head Neck Surg. 2007; 136:282–286.

19.

Couldwell

Simard

Weiss

Norton

Pituitary and Adrenal. New York, NY: McGraw-Hill; 1999.

20.

Tabaee

Anand

Barron Y et al . Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg. 2009; 111:545–554.

21.

James

WP.

The epidemiology of obesity: the size of the problem.

J Intern Med. 2008; 263:336–352.

22.

World Health Organization. Physical Status: The Use and Interpretation of Anthropometry. Geneva, Switzerland: World Health Organization; 1995. Technical Report Series.

23.

Consultation

WE.

Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.

Lancet. 2004; 363:157–163.

24.

Baskin

Ard

Franklin

Allison

DB.

Prevalence of obesity in the United States.

Obes Rev. 2005; 6:5–7.

25.

Must

Spadano

Coakley

Field

Colditz

Dietz

WH.

The disease burden associated with overweight and obesity.

JAMA. 1999; 282:1523–1529.

26.

Greenberg

JA.

Obesity and early mortality in the United States.

Obesity (Silver Spring). 2013; 21:405–412.

27.

Sood

Abdollah

Sammon

et al

. The effect of body mass index on perioperative outcomes after major surgery: results from the National Surgical Quality Improvement Program (ACS-NSQIP) 2005–2011.

World J Surg. 2015; 39:2376–2385.

28.

Vonlanthen

Slankamenac

Breitenstein

et al . The impact of complications on costs of major surgical procedures: a cost analysis of 1200 patients. Ann Surg. 2011; 254:907–913.

29.

Patel

Bergman

Moore

Haglund

The economic burden of complications occurring in major surgical procedures: a systematic review.

Appl Health Econ Health Policy. 2013; 11:577–592.

30.

Services CfMaM. Hospital-acquired conditions. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/HospitalAcqCond/Hospital-Acquired_Conditions.html. Accessed December 26, 2016.

31.

Safaee

Sun

, et al. Use of thrombin-based hemostatic matrix during meningioma resection: a potential risk factor for perioperative thromboembolic events. Clin Neurol Neurosurg. 2014; 119:116–120.

32.

Bamgbade

Rutter

Nafiu

Dorje

Postoperative complications in obese and nonobese patients.

World J Surg. 2007; 31:556–560; discussion 561.

33.

Baik

Curhan

Rimm

Bendich

Willett

Fawzi

WW.

A prospective study of age and lifestyle factors in relation to community-acquired pneumonia in US men and women.

Arch Intern Med. 2000; 160:3082–3088.

34.

Bjarnason

Asgeirsson

Baldursson

Kristinsson

Gottfredsson

Mortality in healthcare-associated pneumonia in a low resistance setting: a prospective observational study.

Infect Dis (Lond). 2015; 47:130–136.

35.

Lagergren

Influence of obesity on the risk of esophageal disorders.

Nat Rev Gastroenterol Hepatol. 2011; 8:340–347.

36.

Almirall

Bolibar

Serra-Prat

et al . New evidence of risk factors for community-acquired pneumonia: a population-based study. Eur Respir J. 2008; 31:1274–1284.

37.

Kornum

Thomsen

Riis

Lervang

Schonheyder

Sorensen

HT.

Diabetes, glycemic control, and risk of hospitalization with pneumonia: a population-based case-control study.

Diabetes Care. 2008; 31:1541–1545.

38.

Liu

Wang

et al . Sleep apnea and risk of pneumonia: a nationwide population-based study. CMAJ. 2014; 186:415–421.

39.

Tait

Voepel-Lewis

Burke

Kostrzewa

Lewis

Incidence and risk factors for perioperative adverse respiratory events in children who are obese.

Anesthesiology. 2008; 108:375–380.

40.

King

Mortensen

Bollinger

et al . Impact of obesity on outcomes for patients hospitalised with pneumonia. Eur Respir J. 2013; 41:929–934.

41.

Kahlon

Eurich

Padwal

et al . Obesity and outcomes in patients hospitalized with pneumonia. Clin Microbiol Infect. 2013; 19:709–716.

42.

Singanayagam

Chalmers

JD.

Obesity is associated with improved survival in community-acquired pneumonia.

Eur Respir J. 2013; 42:180–187.

43.

Lavie

Alpert

Arena

Mehra

Milani

Ventura

HO.

Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.

JACC Heart Fail. 2013; 1:93–102.

44.

De Schutter

Lavie

Milani

RV.

The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease-the obesity paradox.

Prog Cardiovasc Dis. 2014; 56:401–408.

45.

Carnethon

De Chavez

Biggs

et al . Association of weight status with mortality in adults with incident diabetes. JAMA. 2012; 308:581–590.

46.

Nie

Zhang

Jee

Jung

Xiu

Obesity survival paradox in pneumonia: a meta-analysis.

BMC Med. 2014; 12:61.

47.

Gholson

Shah

Gao

Noiseux

NO.

Morbid obesity and congestive heart failure increase operative time and room time in total hip arthroplasty.

J Arthroplasty. 2016; 31:771–775.

48.

Sanford

Kadry

Brodsky

Macario

Bariatric surgery operating room time–size matters.

Obes Surg. 2015; 25:1078–1085.

49.

St Julien

Aldrich

Sheng

et al . Obesity increases operating room time for lobectomy in the society of thoracic surgeons database. Ann Thorac Surg. 2012; 94:1841–1847.

50.

Gadinsky

Manuel

Lyman

Westrich

GH.

Increased operating room time in patients with obesity during primary total knee arthroplasty: conflicts for scheduling. J Arthroplasty. 2012; 27:1171–1176.

51.

Wang

Gadinsky

Yeager

Lyman

Westrich

GH.

The increased utilization of operating room time in patients with increased BMI during primary total hip arthroplasty.

J Arthroplasty. 2013; 28:680–683.

52.

Bradley

Griffiths

Stewart

Higgins

Hockings

Isaac

DL.

The effect of obesity and increasing age on operative time and length of stay in primary hip and knee arthroplasty.

J Arthroplasty. 2014; 29:1906–1910.

53.

Stevens

O'Connell

Meyer

TA.

Obesity related complications in surgery.

Curr Opin Otolaryngol Head Neck Surg. 2015; 23:341–347.

54.

Birkmeyer

Charlesworth

Hernandez

et al . Obesity and risk of adverse outcomes associated with coronary artery bypass surgery. Northern New England cardiovascular disease study group. Circulation. 1998; 97:1689–1694.

55.

Loop

Lytle

Cosgrove

et al . J. Maxwell Chamberlain memorial paper. Sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care. Ann Thorac Surg. 1990; 49:179–186; discussion 186–177.

56.

Uccella

Bonzini

Palomba

et al . Impact of obesity on surgical treatment for endometrial cancer: a multicenter study comparing laparoscopy vs open surgery, with propensity-matched analysis. J Minim Invasive Gynecol. 2016; 23:53–61.

57.

Levy

Schiffrin

Mourad

et al . Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 2008; 118:968–976.

58.

Labropoulos

Wang

Lanier

Khan

SU.

Factors associated with poor healing and recurrence of venous ulceration.

Plast Reconstr Surg. 2012; 129:179–186.

59.

Santana

Reyna

Grana

Buendia

Lamas

Lamelas

Outcomes of minimally invasive valve surgery versus standard sternotomy in obese patients undergoing isolated valve surgery.

Ann Thorac Surg. 2011; 91:406–410.

60.

Ashwell

Gunn

Gibson

Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis.

Obes Rev. 2012; 13:275–286.

61.

Markovic-Jovanovic

Stolic

Jovanovic

AN.

The reliability of body mass index in the diagnosis of obesity and metabolic risk in children.

J Pediatr Endocrinol Metab. 2015; 28:515–523.

62.

Zeng

Dong

et al . Optimal cut-off values of BMI, waist circumference and waist: height ratio for defining obesity in Chinese adults. Br J Nutr. 2014; 112:1735–1744.

63.

Bener

Yousafzai

Darwish

Al-Hamaq

Nasralla

Abdul-Ghani

Obesity index that better predict metabolic syndrome: body mass index, waist circumference, waist hip ratio, or waist height ratio.

J Obes. 2013 ;2013:269038.

64.

Yoo

EG.

Waist-to-height ratio as a screening tool for obesity and cardiometabolic risk.

Korean J Pediatr. 2016; 59:425–431.

65.

Al-Refaie

Parsons

Henderson

et al . Body mass index and major cancer surgery outcomes: lack of association or need for alternative measurements of obesity? Ann Surg Oncol. 2010; 17:2264–2273.

66.

Shiloach

Frencher

Jr Steeger

et al . Toward robust information: data quality and inter-rater reliability in the American College of Surgeons National Surgical Quality Improvement Program. J Am Coll Surg. 2010; 210:6–16.