Fischer, John P. M.D.; Sieber, Brady B.A.; Nelson, Jonas A. M.D.; Cleveland, Emily B.A.; Kovach, Stephen J. M.D.; Wu, Liza C. M.D.; Kanchwala, Suhail M.D.; Serletti, Joseph M. M.D.
Free autogenous breast reconstruction is considered by many as the standard of care for postoncologic reconstruction because of its reliability and superior patient satisfaction.1–4 However, microsurgical breast reconstruction entails a lengthy operation, significant recovery, and risk of flap loss, with major complications.5 Free tissue transfer can be performed with success rates as high as 97 percent as defined by flap survival, but complications rates can approach 20 to 50 percent.6,7
Despite the robust body of literature evaluating complications after free tissue transfer, there are limited data separately accounting for early and late complications or for associated medical complications.8–10 Complications can exert a significant impact on recovery time, patient satisfaction, and health care system costs.2,11,12 Thus, a more comprehensive investigation of postoperative complications and their economic impact on the health care systems is warranted. In this study, we aim to elucidate identifiable risk factors associated with surgical and medical complications following free autologous tissue transfer, and to quantify the fiscal impact of such complications.
PATIENTS AND METHODS
We reviewed our prospectively maintained free flap database and identified all oncologic breast reconstruction patients from 2005 to 2011 who underwent reconstruction at the Hospital of the University of Pennsylvania performed by the senior author (J.M.S.). This study was institutional review board approved. Variables examined included patient characteristics, oncologic history, reconstructive details, and intraoperative and postoperative surgical complications. Complications were categorized as minor (wound healing, seroma, infection, transfusion, partial flap loss, and fat necrosis), immediate major (any thrombosis and complete flap loss), and delayed major (hernia or donor-site dehiscence requiring intervention). We also evaluated medical complications derived from a hospitalwide database query. Financial data were used to derive costs associated with complications during free tissue transfer. Complication rates were uniformly calculated as a rate per patient, not per number of flaps, such that the denominator was consistent across all complications.
A detailed review of hospital and office records included the following: preoperative history and physical examination, operative reports, anesthesia records, postoperative nursing records, discharge summaries, outpatient clinic notes, and laboratory data. In addition, the institutional hospital database was queried for medical complications and costs associated with each patient's initial reconstructive hospitalization.
Specific variables examined included baseline patient characteristics/comorbidities (age, body mass index, hypertension, chronic obstructive pulmonary disease, hyperlipidemia, active smoking, coronary artery disease, peripheral arterial disease), oncologic history (mastectomy type, preoperative and postoperative chemotherapy, and prior irradiation), reconstructive details (immediate versus delayed, unilateral versus bilateral, thrombotic events, flap type, and recipient vessel), intraoperative complications (venous or arterial thrombosis), postoperative surgical complications [any thrombosis, flap loss, delayed breast or donor-site wound complications, early infection (during hospitalization), delayed infection (outpatient infection), seroma, and blood transfusion]. Obesity was defined using the World Health Organization obesity classification system: class I obesity, body mass index of 30 to 34.9 kg/m2; class II obesity, body mass index of 35.0 to 39.9 kg/m2; and class III obesity, body mass index greater than 40 kg/m2.
Surgical complications were characterized as immediate major (any thrombosis or complete flap loss), delayed major (hernia or major wound complications requiring return to the operating room), or minor (delayed wound healing, seroma, infection, partial flap loss, transfusion, and fat necrosis). Delayed wound healing at the abdominal donor site and mastectomy flap were defined as skin necrosis or wound breakdown necessitating topical care or dressing changes for more than 3 weeks. Fat necrosis was defined as a palpable firmness greater than 1 cm in diameter present at follow-up but not related to cancer recurrence. Partial flap loss was defined as flap loss or atrophy of up to 50 percent but not requiring immediate return to the operating room. Superficial infection was defined as incisional cellulitis at either the donor site or breast that occurred within 30 days, only involved skin and subcutaneous tissue structures, was treated with antibiotics, and was documented as such by a physician. We also evaluated and analyzed medical complications occurring during the inpatient recovery period, including arrhythmia, congestive heart failure, myocardial infarction, deep venous thrombosis, pulmonary embolism, acute renal failure, urinary tract infection, respiratory failure, and infectious pneumonia.
Financial data were obtained from the Department of Finance at the Hospital of the University of Pennsylvania. These data were used to derive costs associated with complications after free tissue transfer during the initial hospital admission for reconstruction. We obtained several cost figures for each patient, including total hospital charges, total hospital cost, direct variable cost, and operative room costs during primary admission. These cost figures did not include professional service fees or charges. Cost data were compared based on complication subtypes.
All data were entered into an Excel workbook (Microsoft Corp., Redmond, Wash.). Statistical analyses included chi-square and Fisher's exact tests for categorical variables and the Wilcoxon rank sum test and Kruskal-Wallis test for continuous variables. All variables and endpoints found to be significant in the univariate analyses were included in a multivariate logistic regression model in an effort to determine independent predictors of surgical and medical complications. All tests were two-tailed, and statistical significance was defined as p < 0.05. All analyses were performed using STATA IC 11.0 (StataCorp, College Station, Texas).
Eight hundred forty-nine patients underwent 1303 free tissue transfers (395 unilateral and 454 bilateral flaps). Average follow-up was 7.5 months (range, 1 to 36 months). There was a zero percent mortality rate. All complications were reported as a per-patient incidence. Flaps included muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) (66.8 percent), deep inferior epigastric perforator (DIEP) (22.4 percent), superficial inferior epigastric artery (5.4 percent), gluteal artery perforator (3.8 percent), and transverse gracilis myocutaneous (1.6 percent). Overall, complete flap loss occurred at a rate of 2.1 percent per study patient. We evaluated surgical and medical complications, including major immediate surgical complications [n = 34 (4.0 percent)], major delayed surgical complications [n = 54 (6.4 percent)], minor surgical complications [n = 404 (47.6 percent)], and medical complications [n = 50 (5.9 percent)].
Patients who experienced a major immediate surgical complication were compared with those who did not (Table 1). This univariate analysis demonstrated that obesity (p = 0.03), smoking (p = 0.06), flap type (p = 0.005), and recipient vessels (p < 0.001) were associated with major immediate postoperative events. When a vessel other than the internal mammary or thoracodorsal artery was needed, there was a corresponding increased rate of early major complications likely related to technical difficulty, but this was not significant in a multivariate regression. A similar comparison was performed for delayed major surgical complications (Table 2). We determined that obesity (p < 0.001), chronic obstructive pulmonary disease (p < 0.001), and hypertension (p < 0.001) were associated with major delayed surgical complications. A separate analysis was performed for minor surgical complications (Table 3). Minor complications were associated with race (p = 0.038), diabetes mellitus (p = 0.001), obesity (p < 0.001), hypertension (p < 0.001), hyperlipidemia (p = 0.01), and active smoking (p = 0.002).
We separately analyzed risk factors for the following medical complications: arrhythmia, congestive heart failure, myocardial infarction, deep venous thrombosis, pulmonary embolism, acute renal failure, urinary tract infection, respiratory failure, and infectious pneumonia (Table 4). Medical complications overall were associated with chronic obstructive pulmonary disease (p < 0.001), diabetes mellitus (p = 0.01), increased body mass index (p = 0.048), and bilateral flaps (p = 0.006).
Risk Factor Analysis
To characterize independent risk factors for each subtype of surgical and medical complications, a separate multivariate regression analysis was performed on each subgroup (Table 5). This analysis demonstrates that flap choice (OR, 1.44; p = 0.024) was the one factor independently associated with major immediate surgical complications. In contrast, the regression analysis for major delayed complications showed that patient comorbidities including chronic obstructive pulmonary disease (OR, 10.1; p = 0.001) and obesity (OR, 1.71; p < 0.0001) were associated with major delayed complications (Table 6). Minor surgical complications were independently associated with diabetes mellitus (OR, 1.87; p = 0.03), hypertension (OR, 1.19; p = 0.03), and current smoking status (OR, 1.16; p = 0.07). Medical complications were independently associated with chronic obstructive pulmonary disease (OR, 17.2; p < 0.001), body mass index (OR, 1.04; p = 0.025), and bilateral flaps (OR, 2.37; p = 0.01).
We performed a separate cost analysis to determine the financial impact of surgical and medical complications on the health system (Table 7). Patients who experienced a major immediate surgical complication experienced longer hospital stay (6.1 days versus 4.2 days; p < 0.0001), higher operating room cost ($1459 versus $1044; p < 0.001), and greater hospital cost ($28,261 versus $19,106; p < 0.001). Patients experiencing medical complications consumed greater health care resources as well, including length of stay (5.9 days versus 4.8 days; p < 0.001) and hospital cost ($26,445 versus $19,045; p < 0.0001).
Experience over Time
We compared the incidence of complication between surgeons with more than 5 years of experience to those with less than 5 years of experience at the time of surgery (Table 8). This comparison revealed several interesting findings. First and somewhat counterintuitively, the intraoperative thrombosis rate was higher with greater experience (5.6 percent versus 2.5 percent; p = 0.025). Importantly, this increased intraoperative thrombosis rate did not translate into a higher flap loss rate (1.7 percent versus 2.7 percent; p = 0.28). We also compared complications by year and found that our rates of complication were relatively stable with time (Table 9). There was a trend toward fewer delayed major complications (p = 0.24). There were also fewer minor complications with time (p = 0.006) and fewer venous thrombotic events (p = 0.02).
The data provided in this study represent a comprehensive, longitudinal analysis of complications in over 1300 free tissue transfers for breast reconstruction. Importantly, we describe a separate set of risk factors for early and late major surgical complications. We show that early major complications are related to flap selection8, whereas late major complications are associated with patient comorbidities (e.g., obesity and chronic obstructive pulmonary disease). Overall, complications lead to significantly longer hospitalizations and greater health care costs.
To date, there is a paucity of literature describing the financial impact of surgical complications in autologous breast reconstruction. Several studies have compared cost-efficacy between DIEP and muscle-sparing TRAM flaps, and the use of a pedicled TRAM flap compared with a free TRAM flap, but there are limited data regarding the added cost of complications across these reconstructive modalities.13–15 Thus, one of the aims of this study was to evaluate the financial impact of medical and surgical complications. In our analysis, we determined that immediate major surgical complications added approximately 2 hospital days and over $9000 in direct costs. Similarly, medical complications added close to 2 hospital days and approximately $7000 in cost. These findings emphasize the impact complications exert on health care cost, patient morbidity and, likely by association, satisfaction.11 Overall, complications after microsurgical breast reconstruction can result in a significant burden to both the patient and health care system because of the associated added cost of care, need for further surgery, increased length of hospital stay, greater resource use, and higher morbidity.16 Our experience and results have remained consistent over time and likely relate to adherence to a protocolized management pathway and the use of consistent microsurgical technique regardless of surgeon.
Our study reports a low rate of major complications (5 to 7 percent), but the financial impact is clinically and economically significant. During the study period, the total added direct cost of immediate surgical complications was approximately $306,000 compared with $350,000 for medical complications. Preventative strategies geared toward reducing either major surgical or medical complications might translate into significant health care savings. In addition, these data may prove useful in guiding flap selection, counseling patients, using identifiable risk factors for preoperative screening, and improving health care resource consumption.
One of the critical findings of our study is that gluteal artery flaps are associated with a higher flap loss rate than abdominally based flaps. Gluteal artery flaps have been described for breast reconstruction but are known to be associated with higher flap loss rates and greater technical difficulty because of the shorter pedicle and vessel size discrepancy.17–19 We tend to use gluteal artery based flaps only as a secondary or tertiary option in free autologous reconstructions because of their higher complication rates and required intraoperative repositioning.
Another important set of findings provided by these data are that patient comorbidities were also independent predisposing risk factors for medical complications. There is little in the literature about medical complications after autologous breast reconstruction, and we feel this is an important consideration and addition to the literature. Patients who developed medical complications consumed more health care resources, had longer inpatient stays, and experienced greater morbidity. Not surprisingly, patients who experienced medical complications had various comorbidities at baseline. In such patients with multiple comorbid conditions, it may be advantageous to have a high level of suspicion for medical complications postoperatively.
As an example, in patients with chronic obstructive pulmonary disease, initiating early aggressive incentive spirometry and pulmonary toilet or considering preoperative pulmonary evaluation may be of benefit. In obese patients, ensuring appropriate venous thromboembolic prophylaxis and encouraging early ambulation and counseling regarding added risk of postoperative surgical and medical complications may be of benefit.
Obesity has been shown to be associated with overall higher rates of flap complications, including flap loss, hernia, seroma, and wound healing complications.4,20–23 In our study, obesity was independently associated with major delayed complications. These results agree with previously published reports that delayed complications tend to be associated with patient comorbidities.24 One of the critical findings presented in this study is the strong association between major surgical and medical complications and chronic obstructive pulmonary disease. Patients with chronic obstructive pulmonary disease were at 10-fold greater risk for delayed surgical complications and 17-fold greater risk for medical complications. These findings suggest that free tissue transfer should be carefully considered and discussed with the chronic obstructive pulmonary disease patient. The significantly increased risk is not necessarily attributable to the chronic obstructive pulmonary disease itself but is more likely secondary to the other comorbid conditions that coexist in this patient population. However, it should be noted that although these findings were significant, the overall prevalence of chronic obstructive pulmonary disease in our surgical population was very low.
The results presented in this study provide the practicing breast microsurgeon with useful risk-stratifying data and cost-efficiency results that can be implemented to enhance and optimize outcomes through careful patient selection and counseling (Table 10). As an institution and health system, the plastic surgery team has implemented infrastructural and pathway protocols to standardized care and management of our free flap patients. Briefly, some of these include anesthesiologists intimately familiar with free flap physiology and intraoperative management. This strategy continues as patients are transferred to the microsurgical stepdown unit where a free flap protocol is initiated. We feel that our success has largely been dictated by consistent microsurgical technique, intraoperative collaboration and open communication with anesthesia, close clinical observation of flap performance in a stepdown unit, and early recognition and treatment of vascular complications. A better understanding of complications and risk factors has allowed us to better preoperatively counsel our patients. This open discussion has facilitated patient autonomy and enhanced our management of complications, which in turn has created greater patient satisfaction.
Despite the large number of patients included in our study, there remain several limitations. First, it is a retrospective study and may be prone to observer bias, recording bias, and selection bias overall. However, there are few preoperative patient variables or comorbidities that our surgeons would consider as contraindications for performing autologous reconstruction in patients. This helps to decrease the possibility of selection bias. Conclusions that we have drawn are not yet supported by prospective data, and at this point we are only able to associate variables with outcomes. In addition, our cost data are based on the University of Pennsylvania Health System cost figures and direct variable cost, which does not include labor or overhead costs. It is also important to recognize that these cost figures only reflect one component of the economic impact of breast reconstruction. This analysis does not take into account lost productivity or work days missed secondary to a prolonged recovery or for additional physician visits. Such costs are much more difficult to directly quantify. Overall, surgical and medical complications after autologous breast reconstruction, although infrequent in our study, are independently linked to identifiable patient risk factors and associated with significant morbidity and cost.
We show that free tissue transfer is safe and effective, but several critical patient-related comorbidities and intraoperative factors are associated with postoperative patient morbidity. Early major complications tend to be related to flap selection and technical factors, whereas late major complications were associated with patient comorbidities. Overall, complications were associated with an added 2 days of hospitalization and an additional $9000 in hospital charges per patient. Careful patient selection, counseling, and preventative measures can optimize postoperative performance, minimize surgical and medical morbidity, and conserve health care resources.
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24. Scheer AS, Novak CB, Neligan PC, Lipa JE. Complications associated with breast reconstruction using a perforator flap compared with a free TRAM flap. Ann Plast Surg. 2006;56:355–358.