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Khan MN, Russo J, Spivack J, et al. Association of Body Mass Index With Infectious Complications in Free Tissue Transfer for Head and Neck Reconstructive Surgery. JAMA Otolaryngol Head Neck Surg. 2017;143(6):574–579. doi:10.1001/jamaoto.2016.4304
Does elevated body mass index affect the outcomes of patients undergoing head and neck reconstructive surgery using free flaps?
This cohort study of 415 patients found that those with an elevated body mass index who underwent head and neck reconstruction did not have significantly worse outcomes than patients with a normal body mass index. Overall infectious outcomes were more common in patients with diabetes or those treated with an alternative antibiotic regimen, but the cohort with an elevated body mass index did not have significantly worse outcomes.
Elevated body mass index does not seem to play a role as an independent risk factor in postoperative complications in free tissue transfer in head and neck surgery.
Elevated body mass index (BMI) has been proposed as a risk factor for morbidity and mortality among patients undergoing surgery. Conversely, an elevated BMI may confer a protective effect on perioperative morbidity.
To examine whether an elevated BMI is an independent risk factor for perioperative and postoperative infectious complications after free tissue transfer in head and neck reconstructive surgery.
Design, Setting, and Participants
This cohort study included patients undergoing major head and neck surgery requiring free tissue transfer at a tertiary care center. Data were collected for 415 patients treated from January 1, 2007, through December 31, 2014.
Main Outcomes and Measures
The outcome of interest was postoperative infection and complications after head and neck surgery using free flaps. Covariates considered for adjustment in the statistical model included alcohol consumption (defined as >5 drinks per day [eg, 360 mL of beer, 150 mL of wine, or 45 mL of 80-proof spirits]), type 2 diabetes, prior radiotherapy, anesthesia time, hypothyroidism, smoking, American Society of Anesthesiologists classification, antibiotic regimen received (defined as a standard regimen of a first- or second-generation cephalosporin with or without metronidazole hydrochloride vs an alternative antibiotic regimen for patients allergic to penicillin), and primary surgeon. A multiple logistic regression model was developed for the incidence of the infection end point as a function of elevated BMI (>30.0).
Among the 415 patients included in this study (277 men [66.7%] and 138 women [33.2%]; mean [SD] age, 61.5 [13.9] years), type 2 diabetes and use of an alternative antibiotic regimen were found to be independently associated with increased infectious complications after free flap surgery of the head and neck, with estimated odds ratios of 2.78 (95% CI, 1.27-6.09) and 2.67 (95% CI, 1.14-6.25), respectively, in the multiple logistic regression model. However, a high BMI was not found to be statistically significant as an independent risk factor for postoperative infectious complication (estimated odds ratio, 1.19; 95% CI, 0.48-2.92).
Conclusions and Relevance
Elevated BMI does not seem to play a role as an independent risk factor in postoperative complications in free tissue transfer in head and neck surgery.
Elevated body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) has long been proposed as a risk factor for overall mortality and morbidity, including an increased risk for cardiovascular disease, hypertension, and diabetes.1-3 Patients with elevated BMI who undergo surgery also tend to have longer operative times and endure more blood loss when compared with patients with normal BMI who undergo comparable procedures.4-7 A prior study by Hasegawa et al8 reported that patients with high BMI had greater blood loss and operative times and a significantly greater incidence of postoperative complications after esophagectomy. This increase in postoperative morbidity was hypothesized to be owing to the stress on an already compromised cardiovascular system. Several studies examining the effect of BMI on perioperative and postoperative morbidity and mortality have found that elevated BMI did not seem to be correlated with a significantly greater rate of complications or worse outcome.9-15 However, more recent literature16-20 has suggested the existence of an obesity paradox in which elevated BMI may confer a protective effect on perioperative morbidity.
Oncologic resections for head and neck cancer with free flap reconstructions are time-consuming surgical procedures that require extensive dissection, often with contaminated wounds, and are associated with significant perioperative morbidity. Poor nutritional status has long been associated with impaired wound healing. This association is of special concern in patients undergoing major resection and reconstruction for head and neck cancer, who often present with inadequate nutritional intake. In these patients, poor wound healing after free tissue transfer has the potential for significant morbidity.21-26
Elevated BMI has been evaluated in several surgical settings and has been associated with an increased risk for surgical infections.27,28 The mechanism by which obesity may contribute to increased inflammation and infection remains an active area of research. Very little has been written regarding the effects of isolated, elevated BMI on free tissue transfer outcomes, specifically infection rates, in the patient with head and neck cancer.28,29 Diabetes is a known risk factor for infection, and patients with this diagnosis often have an elevated BMI. As such, diabetes could be a confounder when investigating the effects of an elevated BMI on infection rates.
A prior multi-institutional study by de la Garza et al30 reported their experience with free flap reconstruction and perioperative complications in patients with elevated BMI and found no effect. Hypothetically, patients with elevated BMI may have increased complication rates due to issues that include difficulty with early ambulation leading to prolonged hospital stay, cervical bulk resulting in external pressure on the pedicle, and late recognition of fistula formation or infection owing to the masking effect of obesity. In light of these issues, we hypothesized that anatomical characteristics of patients with a high BMI might predispose them to greater risk for postoperative complications after free tissue transfer. In this study, we aim to examine the effects of BMI in a population of patients undergoing free tissue transfer for head and neck reconstruction.
A retrospective cohort of patients undergoing head and neck free tissue transfer at the Mount Sinai Medical Center, New York, New York, from January 1, 2007, to December 31, 2014, yielded 427 patients. Of these, 12 were excluded owing to incomplete data, resulting in a study cohort of 415 patients with varying cohort characteristics (Table 1). This study was approved by the institutional review board of Mount Sinai Medical Center. The institutional review board waived the need for consent owing to the deidentification of data.
Obesity was analyzed as a continuous and a dichotomous variable, with elevated BMI defined as greater than 30.0. Surgical site infections were defined via the Centers for Disease Control and Prevention criteria as occurring within 30 days after the surgery and including at least 1 of the following: purulent drainage from the incision; an incision that spontaneously dehisces, is deliberately opened or aspirated by a surgeon, and has positive culture results or is not cultured, in a patient with fever (body temperature >38°C) and/or localized pain or tenderness; an abscess or other evidence of infection involving the deep tissue that is detected at gross anatomical, radiographic, or histopathologic examination; or diagnosis of a surgical site infection by the surgeon.
A logistic regression model was developed for the incidence of the end point of infection as a function of high BMI (>30.0) in an observational data set consisting of the 415 cases treated at the Mount Sinai Hospital. Of these, 46 (11.1%) experienced the infection outcome. Of the 415 patients in this study, 68 (16.4%) were found to have a BMI of greater than 30.0, and 11 of these patients had the infection outcome. The following additional covariates were considered as candidates for adjustment in the model: alcohol consumption (defined as >5 drinks per day day [eg, 360 mL of beer, 150 mL of wine, or 45 mL of 80-proof spirits]), diabetic status, use of radiotherapy, anesthesia time, hypothyroidism, smoking, flap type, defect type, cancer stage, American Society of Anesthesiologists status,31 Clavien-Dindo complication grade,32 the antibiotic regimen received (defined as standard regimen of a first- or second-generation cephalosporin with or without metronidazole hydrochloride vs an alternative antibiotic regimen for patients allergic to penicillin), and primary surgeon. To adjust for potential confounding while avoiding overfitting, we pursued the following model-building strategy: candidate covariates were first screened for marginal association with infection at P < .10 using univariate logistic regression models, and those identified as marginally associated with infection were further tested for marginal association with high BMI. Only those variables identified as marginally associated with infection and with a high BMI were included as covariates in the primary analysis model. We used SAS software (version 9.3; SAS Institute, Inc) for all statistical analyses.
We included 415 patients (277 men [66.7%] and 138 women [33.2%]; mean [SD] age, 61.5 [13.9] years) undergoing free flap reconstruction at the Mount Sinai Medical Center in this analysis. Of these, 68 were found to have a BMI of greater than 30.0. Free flap donor sites included 129 anterolateral thighs, 169 radial forearms, and 58 fibular flaps, with the remaining donor sites including the scapula, rectus, serratus, iliac crest, and latissimus. The oral cavity constituted the most common resection site, with 206 cases. Covariates demonstrating P ≤ .20 in the univariate regression models were diabetic status, smoking, and antibiotic regimen. These covariates were subsequently included in the multiple logistic regression analyses, with the results shown in Table 2.
Significant covariates at the P ≤ .05 criterion in the multiple logistic regression model included diabetic status (adjusted odds ratio [OR], 2.78; 95% CI, 0.48-2.92) and antibiotic regimen (adjusted OR, 2.67; 95% CI, 1.14-6.25). The estimated effect of smoking was counterintuitive (adjusted OR, 0.65; 95% CI, 0.32-1.34), but this effect did not reach statistical significance after accounting for other covariates and may be attributed to random variation. This finding stands in contrast to the detection of the known strong risk factors of diabetes and alternative antibiotic preparations in this analysis. The effect of a high BMI, controlled for other factors, was not found to be significant toward the infection outcome (estimated adjusted OR, 1.19; 95% CI, 0.48-2.92). We stress the importance of inclusion of diabetes as an independent risk factor in the model; high BMI, due to its known correlation with diabetic status, could otherwise function as a proxy measure of diabetic status.
These results were stable when previously excluded candidate covariates were individually incorporated into the model alongside BMI as a continuous covariate (estimated adjusted OR for a 5-U increase in BMI, 1.10; 95% CI, 0.79-1.52). An additional investigation of possible nonlinearity in the effect of BMI on the infection outcome was conducted using a spline of order 3 in the context of a generalized additive model with the above covariates included as linear terms. Evidence for the nonlinear effects of BMI was not significant.
Overall, diabetes and the use of an alternative antibiotic regimen were found to be significantly independently associated with infectious complications after free flap surgery of the head and neck. Diabetes was associated with an estimated adjusted OR of 2.78 (95% CI, 0.48-2.92), and treatment with an alternative antibiotic therapy was associated with an estimated adjusted OR of 2.67 (95% CI, 1.14-6.25). However, elevated BMI was not found to be independently associated with an increased risk for postoperative infectious complications. In addition, a BMI of less than 18.5 was not associated with an increased infection rate in this cohort, although this finding was not the primary aim of this investigation.
Obesity has long been established as a risk factor for several other comorbidities, including cardiovascular disease, hypertension, and diabetes. Obesity has also been shown to lead to increased intraoperative risk factors, such as increased operative times and blood loss, compared with a normal BMI.4-8 Resultant vascular changes in patients with an elevated BMI makes free flap surgery, where the reconstruction is at least partially dependent on the quality of peripheral vasculature, more risky for the patient.33,34 Surgery is further complicated by the body habitus of larger patients, with more soft-tissue bulk in the neck and larger subcutaneous fat pads. Finally, obese patients are often sedentary, putting them at greater risk for perioperative and postoperative complications. This association has been examined extensively in orthopedics, where lower extremity surgery may limit the ability of patients with an elevated BMI to ambulate and has been found to lead to greater complication rates.35-37 For these reasons, we were interested in examining the role of elevated BMI on head and neck microvascular surgery.
In specific situations, elevated BMI has been associated with increased hospital mortality, such as mechanical ventilation in the context of acute lung injury.38 However, other centers have reported a protective effect of an elevated BMI in critically ill patients, leading to a confusing picture of the effects of an elevated BMI in patients undergoing prolonged, major surgical procedures.39 The cardiothoracic literature has examined the effect of an elevated BMI on perioperative complications. Maurer et al13 found that an increased BMI did not increase the risk for perioperative complications from cardiovascular surgery. Wigfield et al15 also found no significant increase in perioperative and 30-day mortality in obese and extremely obese patients undergoing cardiac surgery.
Several other reports in the cardiac literature have found the same lack of effect of an elevated BMI in perioperative complications and postoperative outcomes.14,40 Weltz et al41 analyzed the effect BMI has in patients undergoing midurethral sling procedures for the treatment of stress urinary incontinence and found no difference in cure rates or complications between obese and nonobese patients. Extensive research has been performed in transplantation regarding the effect elevated BMI may have on survival of patients and grafts. Several studies42-44 have found an increase in postoperative complications and morbidity associated with obesity in recipients of liver transplants. This same effect was observed in populations undergoing kidney transplant.45,46 Additional reports indicate the survival and complication rates to be comparable between obese and nonobese patients.47-50
Another interesting observation exists in the general surgery literature with the discussion of an obesity paradox. This phenomenon is described in situations whereby being overweight or moderately obese serves a protective effect after general surgery procedures compared with a normal weight. Jackson et al19 found obesity to have a protective effect when examining the risk for stroke after carotid endarterectomy. In other studies,16,18,51 the idea of this paradox has been refined to indicate a possible protective effect of mild to moderate obesity when compared with underweight or morbid obesity. Therefore, overall review of the current literature indicates that elevated BMI may have minimal effects on surgical outcomes in certain patient populations or certain surgical procedures but may have adverse effects or even a paradoxical protective effect in other surgical populations. Therefore, the effects of BMI must be evaluated in the specific population of interest to determine the nature of the effect of elevated BMI.
The head and neck literature has examined some of the influence BMI may have on surgical outcomes. Hollander et al17 found that patients with head and neck cancer with a higher BMI had lower overall and disease-related mortality rates and an increase in overall survival when compared with underweight or normal-weight patients. Stevens et al20 examined the possible effect that elevated BMI could have on otologic surgery and did not find any proven effect of elevated BMI. Buerba et al52 found that patients with greater BMI undergoing cervical endocrine procedures seem to sustain more postoperative morbidity, specifically more wound complications. However, this finding seemed to be clinically insignificant, and they recommended treating patients with an elevated BMI similar to those with a normal weight. Other studies have also validated this stance.53 Ono et al11 determined that although elevated BMI was associated with prolonged hospital stay in a cohort of patients with mandibular fracture, it was not associated with postoperative complication rates. Lateral and anterior skull base literature54-56 have found a deleterious association between elevated BMI and elevated intracerebral pressures, leading to a predilection for postoperative and idiopathic cerebrospinal fluid leaks. Several studies57,58 have also concluded that elevated BMI does not increase the risk of morbidity after esophagectomy. Therefore, even within the head and neck literature, we must clearly define the patient population being examined to determine the effects of elevated BMI.
Reconstructive surgery of the head and neck with the use of free tissue transfer is markedly different when compared with other procedures performed in head and neck surgery. Most procedures in head and neck surgery are generally outpatient and are not associated with significant blood loss or donor site morbidity. On the contrary, free tissue transfer procedures are associated with higher complication rates in general and prolonged hospitalizations compared with other more common procedures. These procedures are far less commonly performed compared with other head and neck procedures such as thyroid surgery or sinus surgery; thus, the effect of an elevated BMI in free flap reconstruction has not been studied extensively.
In a multi-institutional study, de la Garza et al30 found no association of elevated BMI with several perioperative outcomes after free tissue transfer in head and neck surgery. In analyzing medical and surgical complications in this cohort, they found comparable complication rates and no significant difference in ORs when examining patients with a BMI of at least 30.0 vs those with a BMI of less than 30.0. Our findings appear to support these results.
In our study, patients receiving alternative antibiotic regimens were associated with increased rates of postoperative infection compared with those receiving standard antibiotic regimens. This finding has been previously reported regarding free flap reconstruction in head and neck surgery.59,60 We also noted an association with diabetes, a known risk factor in this patient population, on the rates of postoperative infection, surgical complications, and poor healing.61-69 Diabetes is associated with several physiologic changes, including deleterious effects on microvasculature, ultimately leading to difficulty with wound healing.61,62,66 Despite these results, our analysis found no statistically significant difference in the rate of overall complications, and specifically, infectious complications, when performing free flap surgery in obese (BMI>30.0) patients.
As an interesting secondary observation, we did not find any difference in infectious complications in our cohort with a low BMI. Prior studies have shown the importance of adequate nutritional support in patients undergoing cancer surgery and, more specifically, free flap procedures, in the perioperative period.70 McMahon et al71 found that low preoperative serum albumin levels were independently associated with Clavien-Dindo complications of grade III and above on multiple regression modeling. Shum et al72 found that acute malnutrition was associated with a 4-fold increased risk of flap failure compared with a normal nutritional status. Similarly, Kim et al73 found a higher rate of complications in underweight patients undergoing gastrectomy for gastric cancer. Ejaz et al9 also found this to be true among patients with gastric cancer, reporting that patients with a BMI of less than 18.5 had significantly decreased overall survival after gastrectomy. Hendifar et al74 examined the effect of BMI on perioperative and long-term clinical outcomes in resected pancreatic ductal adenocarcinoma and found that a lower BMI was associated with a longer postoperative hospital stay. Therefore, low BMI and the associated poor nutrition are clear risk factors for surgical complications in major surgical procedures. Despite this finding, our data did not indicate an increased risk for infection in patients with a BMI of less than 18.5. This result can likely be attributed to the rich blood supply to the head and neck, affording this region some resistance to surgical infections. In addition, the population with head and neck cancer is distinct from the cohorts analyzed in other surgical fields.
Limitations of this study include that this was a retrospective analysis and was dependent on chart reviews and prior documentation. The study was subject to errors in prior documentation or data gathering. In a few instances, all the data were not available. However, patients with missing relevant data were excluded from the study.
In this cohort of 415 patients undergoing free tissue transfer reconstruction for head and neck oncologic defects, an increased infection rate was noted in patients with diabetes and those who did not receive standard antibiotic prophylaxis. However, an elevated BMI (>30.0) does not seem to play a role as an independent risk factor in postoperative infectious complications in free tissue transfer in head and neck surgery.
Corresponding Author: Brett A. Miles, MD, DDS, Department of Otolaryngology–Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1189, Annenberg 10th Floor, New York, NY 10029 (firstname.lastname@example.org).
Accepted for Publication: November 13, 2016.
Published Online: March 16, 2017. doi:10.1001/jamaoto.2016.4304
Author Contributions: Drs Khan and Miles had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Khan, Spivack, Pool, Likhterov, Genden, Miles.
Acquisition, analysis, or interpretation of data: Khan, Russo, Spivack, Pool, Teng, Miles.
Drafting of the manuscript: Khan, Spivack, Pool, Genden, Miles.
Critical revision of the manuscript for important intellectual content: Khan, Russo, Spivack, Pool, Likhterov, Teng, Miles.
Statistical analysis: Khan, Spivack.
Administrative, technical, or material support: Pool, Genden, Miles.
Study supervision: Khan, Russo, Likhterov, Miles.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.