Abstract
Background: Upper extremity (UE) microsurgical reconstruction relies upon proper wound healing for optimal outcomes. Cigarette smoking is associated with wound healing complications, yet conclusions vary regarding impact on microsurgical outcomes (replantation, revascularization, and free tissue transfer). We investigated how smoking impacted 30-day standardized postoperative outcomes following UE microsurgical reconstruction. Methods: Utilizing the National Surgical Quality Improvement Program, all patients who underwent (1) UE free flap transfer (n = 70) and (2) replantation/revascularization (n = 270) were identified. For each procedure, patients were stratified by recent smoking history (current smoker ≤1-year preoperatively). Baseline demographics and standardized 30-day complications, reoperations, and readmissions were compared between smokers and nonsmokers. Results: Replantation/revascularization patients had no differences in sex, race, or body mass index between smokers (n = 77) and nonsmokers. Smokers had a higher prevalence of congestive heart failure (5.2% vs 1.0%, P = .036) and nonsmokers were more often on hemodialysis (15.6% vs 10.4%, P = .030). Free flap transfer patients had no differences in age, sex, or race between smokers (n = 14) and nonsmokers. Smokers had a longer length of stay (6.6 vs 4.2 days, P = .001) and a greater prevalence of chronic obstructive pulmonary disorder (COPD; 7.1% vs 0%, P = .044). Recent smoking was not associated with increased odds of any 30-day minor and major standardized surgical complications, readmissions, or reoperations following UE microsurgical reconstruction via free flap transfer or replantation/revascularization. Baseline diagnosis of COPD was also not a predictor of adverse 30-day outcomes following free flap transfer. Conclusion: Recent smoking history was not associated with any 30-day adverse outcomes following UE microsurgical reconstruction via replantation/revascularization or free flap transfer. In light of these findings, further investigation is warranted, with particular focus on adverse events specific to free flaps and replantation/revascularization.
Keywords: smoking, adverse outcomes, microsurgical reconstructive surgery, upper extremity
Abstract
Contexte: La reconstruction microchirurgicale du membre supérieur repose sur la bonne guérison de la plaie pour des résultats optimaux. Le tabagisme est associé à des complications pour la guérison des plaies; toutefois, les conclusions concernant ses répercussions sur les résultats microchirurgicaux (réimplantation, revascularisation et transfert de tissu libre) sont variables. Nous avons cherché à savoir quelles étaient les répercussions du tabagisme sur les résultats postopératoires standardisés à 30 jours après reconstruction microchirurgicale du membre supérieur. Méthodes: Utilisant le Programme national d’amélioration de la qualité de la chirurgie, tous les patients ayant subi (1) un transfert de lambeau libre du membre supérieur (n = 70) et (2) une réimplantation/revascularisation (n = 270) ont été identifiés. Pour chaque procédure, les patients ont été classés en fonction de leurs antécédents de tabagisme récent (fumeur actuel ≤ 1 an préopératoire). Les données démographiques initiales et les complications standardisées à 30 jours, les réinterventions et les réhospitalisations ont été comparées entre fumeurs et non-fumeurs. Résultats: Concernant les réimplantations/revascularisations, il n’y a pas eu de différences en termes de sexe, race ou IMC entre les fumeurs (n = 77) et les non-fumeurs. Les fumeurs avaient une plus grande prévalence d’insuffisance cardiaque congestive (5,2 % contre 1,0 %, P = 0,036) et les non-fumeurs étaient plus souvent sous hémodialyse (15,6 % contre 10,4 %, P = 0,030). Concernant les patients ayant eu un transfert de lambeau libre, il n’y a pas eu de différences en termes d’âge, de sexe ou de race entre les fumeurs (n = 14) et les non-fumeurs. La durée d’hospitalisation des fumeurs a été plus longue (6,6 jours contre 4,2 jours, P =0,001) avec une prévalence plus élevée de MPOC (7,1 % contre 0 %, P = 0,044). Le tabagisme récent n’a pas été associé à une augmentation de la probabilité de complications chirurgicales standardisées, majeures ou mineures, à 30 jours, de réhospitalisation ou reprises chirurgicales après reconstruction microchirurgicale du membre supérieur par transfert de lambeau libre ou réimplantation/revascularisation. Le diagnostic de MPOC à l’inclusion dans l’étude n’était pas non plus un facteur prédictif d’événements indésirables à 30 Jours après transfert de lambeau libre. Conclusion: Un antécédent de tabagisme récent n’a pas été associé à des résultats indésirables à 30 jours après reconstruction microchirurgicale du membre supérieur via réimplantation/revascularisation ou transfert de lambeau libre. À la lumière de ces constatations, des études supplémentaires portant particulièrement sur les événements indésirables propres aux procédures de lambeaux libres et de réimplantation/revascularisation sont justifiées.
Keywords: tabagisme, effets indésirables, microchirurgie, membre supérieur
Introduction
Microsurgical reconstructive procedures of the upper extremity (UE), including replantation, revascularization, and free tissue flap transfers, involve a multitude of technically challenging and complex microsurgical techniques that are useful in salvaging a limb in patients suffering from trauma, tumor resection, congenital malformations, and sepsis, among others. 1 -3 A wide variety of flaps have been developed to allow for reconstruction of most defects of the UE, including bony defects, lack of muscle function, neuropathies, and complex wounds. 4 These procedures require the use of microsurgical techniques to adequately connect existing and donor vasculature and tissues. 2,3 Thus, optimal wound healing is necessary for functional, sensory, and operative success. 1
Cigarette smoking within a year of surgery has been associated with adverse or suboptimal wound healing. 5,6 In addition to the known medical issues that can arise from cigarette smoking, smokers are at risk of greater postoperative complications, including wound healing issues and pulmonary compromise. 7 The most frequently implicated cigarette components in wound healing are nicotine, carbon monoxide, nitric oxide, and hydrogen cyanide. 8 The main effects of nicotine on wound healing come from its peripheral vasoconstrictive properties, which can reduce blood flow profoundly in digital arteries specifically. 9,10 And, as nitric oxide is a known relaxant of smooth muscle, it causes bronchodilation and vasodilation of pulmonary capillaries, effectively increasing the absorption of nicotine. Carbon monoxide decreases the oxygen available to tissues by shifting the oxygen–hemoglobin saturation curve, and hydrogen cyanide impairs innate cellular pathways for tissue repair. 11,12 These chemicals all work synergistically to impair wound healing. 13 In particular, smoking is known to impair microcirculation in replanted digits. 14 Currently, there is no consensus on the impact of smoking on microsurgical reconstructive procedures, and recent literature has reported contradictory conclusions regarding the effects of smoking on UE reconstruction. 15 -20 In a 2018 study, smoking was identified as a risk factor for delayed wound healing in free thigh flap reconstruction. 19 Prior studies showed that smoking did not increase risk of microvascular complications, including replant and flap failure. 16 -18,20 However, other studies have reported that smoking contributed to poor immediate replant survival rates. 15
This study aimed to evaluate the impact of current or recent smoking history on 30-day standardized postoperative outcomes following UE revascularization and/or replantation and free flap procedures. Specifically, we will compare the rates of the following between smokers and nonsmokers: (1) demographics, (2) comorbidities and (3) peri- and postoperative standardized adverse events.
Methods
Database
The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried to identify all patients who primarily underwent UE free flap transfer or replantation and/or revascularization procedures performed between 2008 and 2016. The NSQIP aggregates perioperative through 30-day postoperative patient data from over 600 American hospital institutions where data are collected from randomly assigned patient charts. 21 -23 These data on over 150 binary variables include demographics, laboratory values, comorbidities, intraoperative conditions, and surgical indications, including the Current Procedural Terminology (CPT) codes and International Classification of Disease, Ninth Revision diagnosis codes. Surgical outcomes are also reported as binary variables and include readmissions, reoperations, discharge dispositions, and patient mortalities. A certified surgical clinical reviewer collects the data from each site. 22
Study Participants
Patients who underwent UE free flap transfer were identified using CPT codes that corresponded to a principal operative procedure of free flap transfer. This included muscle, myocutaneous, skin, fascial, or osteocutaneous flaps with microvascular anastomoses (CPT codes: 15756, 15757, 15758, 20969, 20970, 20972, and 20973). This excludes CPT codes for bone flaps that do not specify the attachment of a cutaneous paddle. To ensure that only UE procedures were included, patients were only included if they had a postoperative diagnosis or associated secondary procedure pertaining to the UE. Replantation and revascularization patients were identified using CPT codes that corresponded to replantation procedures of the digit (20816, 20822), thumb (20824, 20827), hand (20808), forearm (20805), and arm (20802), or blood vessel repair of the finger, hand, or UE (35207, 35236; Table 1); codes including vascular procedures related to arteriovenous fistulae were excluded from this study. This study was exempt from review by the institutional review board (IRB) because de-identified, publicly available data were utilized. As such, this study is in accordance with the Helsinki Declaration and no informed consent was required.
Table 1.
Upper Extremity Microsurgical Reconstruction Procedures Included in This Study.
| Replantation/revascularization | Free flap transfers |
|---|---|
| Digit replantation | Musclea |
| Thumb replantation | Myocutaneousa |
| Arm replantation | Skina |
| Forearm replantation | Fasciaa |
| Hand replantation | |
| Hand and finger direct blood vessel repair | |
| UE blood vessel repair with vein graft (excluding arteriovenous fistula procedures) |
Abbreviation: UE, upper extremity.
a With microvascular anastomoses.
Outcomes
The outcome of interest in this study was any adverse event within 30 days of surgery, also categorized as a binary variable. Standardized postoperative adverse outcomes, as defined by and reported by the NSQIP, included superficial and deep surgical site infections, wound dehiscence, myocardial infarction (MI), reoperation, and readmissions, among others, and general surgical outcomes. Outcomes are recorded in NSQIP whether or not a patient had been discharged from their original admission. 23
Statistical Analysis
Patients were separated into surgical cohorts by their primary procedure as follows: (1) free flap transfer and (2) replantation/revascularization. Patients who underwent both procedures during the same anaesthesia were excluded. Subsequently, patients within each surgical cohort were stratified by history of cigarette smoking (smokers) and those without a recent smoking history (nonsmokers). Recent smoking history is recorded in NSQIP if the patient was a current smoker had smoked any number of cigarettes in the year prior to admission for surgery. 21
Baseline demographics and preoperative conditions were collected and compared between cohorts using both chi-square and independent samples t testing. Univariate analysis was employed to identify possible individual risk factors for 30-day postoperative major and minor complications, readmissions, and reoperations between smokers and nonsmokers. Major complications were defined as stroke, cardiac arrest, MI, pulmonary embolism, unplanned reintubation, ventilator dependence for more than 48 hours, acute renal failure, sepsis, and septic shock. Minor complications were defined as superficial incisional site infection, organ space infection, wound dehiscence, pneumonia, urinary tract infection, deep venous thrombosis, renal insufficiency, and postoperative transfusion. Due to the infrequent occurrence of complications, statistical analysis was not performed between 2 different surgical cohorts. Multivariate regression models were developed to evaluate the impact of smoking history as well as any potential risk factors identified from univariate analysis on 30-day outcomes for all UE microsurgical reconstructive procedures. For all statistical analysis, a P value of <.05 was set as the threshold for statistical significance. All statistical analysis was performed utilizing SPSS Statistics Version 24.0 (IBM Corporation).
Results
Replantation/Revascularization Procedures
A total of 270 patients underwent UE replantation/revascularization procedures. Of these patients, 77 (28.5%) were current smokers and had a history of cigarette smoking within 1 year prior to surgery (smokers) and 193 did not (nonsmokers). Smokers in this cohort were younger (43.8 vs 51.2 years, P < .001), with an age range of 18 to 89 years. There were no differences in terms of sex, race, or body mass index (BMI) between the groups. Replantation/revascularization smokers had a higher prevalence of congestive heart failure (5.2% vs 1.0%, P = .036), and nonsmokers were more frequently on hemodialysis at baseline (15.6% vs 10.4%, P = .030); rates of chronic obstructive pulmonary disorder (COPD) were comparable between smokers and nonsmokers (6.5% vs 3.6%, P = .302; Table 2). Preoperative laboratory values were comparable, as well as wound class, American Society of Anesthesiologists (ASA) score, operative time, and length of stay (Table 3). Major (1.3% vs 7.3%, P = .06) and total complications (13.0% vs 14.0%, P = .829) were also comparable between smokers and nonsmokers. Both smokers and nonsmokers also experienced similar 30-day reoperation (2.4% vs 6.1%, P = .350) and readmission rates (3.9% vs 3.6%, P = .916; Table 4).
Table 2.
Baseline Demographics and Comorbidities of All Patients Included in This Study Who Underwent Replantation/Revascularization (Emergency/Trauma) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Parameter | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Mean age, years | 43.8 | 51.2 | <.001 |
| Sex | |||
| Male | 28.7% | 71.3% | .948 |
| Female | 28.3% | 71.7% | |
| Race | |||
| White | 70.1% | 63.2% | .892 |
| Black | 11.7% | 14.0% | |
| Other | 18.2% | 22.8% | |
| Body mass index, kg/m2 | 27.3 | 28.5 | .193 |
| Comorbidities | |||
| Ventilator dependence | 1.3% | 2.6% | .516 |
| Recent weight loss | 0% | 1.6% | .271 |
| Hypertension | 37.7% | 43.5% | .378 |
| Diabetes mellitus | 14.3% | 21.8% | .163 |
| Chronic obstructive pulmonary disorder | 6.5% | 3.6% | .302 |
| Dialysis | 10.4% | 15.6% | .030 |
| Corticosteroid use | 5.2% | 7.8% | .455 |
| Congestive heart failure | 5.2% | 1.0% | .036 |
| Ascites | 0.0% | 0.5% | .527 |
| Disseminated cancer | 0.0% | 1.0% | .370 |
| Renal failure | 1.3% | 1.0% | .853 |
| Preoperative sepsis | 7.8% | 8.3% | .662 |
Bold face values are statistically significant values.
Table 3.
Preoperative Laboratory Values, Wound Class, and Perioperative Parameters for Replantation/Revascularization (Emergency/Trauma) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Parameters | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Preoperative laboratory values | |||
| White blood cell count, ×109/L | 9.1 | 9.1 | 1.000 |
| Hematocrit, % | 36.5 | 37.6 | .283 |
| Platelet count, ×103 | 237.9 | 222.3 | .181 |
| Creatinine, mg/dL | 1.9 | 2.5 | .108 |
| Albumin, g/dL | 3.5 | 3.6 | .659 |
| INR | 1.1 | 1.2 | . 552 |
| Operative variables | |||
| Wound class | |||
| Clean | 58.4% | 62.7% | .213 |
| Clean contaminated | 10.4% | 7.8% | |
| Contaminated | 22.1% | 14.0% | |
| Dirty | 9.1% | 15.5% | |
| ASA classification | |||
| 1 (No disturbance) | 7.8% | 22.3% | .063 |
| 2 (Mild disturbance) | 40.3% | 32.1% | |
| 3 (Severe disturbance) | 31.2% | 31.1% | |
| 4 (Life-threatening disturbance) | 19.5% | 14.0% | |
| Preoperative blood transfusions | 2.6% | 3.6% | .797 |
| Operative time, minutes | 141.3 | 158.6 | .290 |
| Length of stay, days | 3.0 | 3.7 | .278 |
| Days from admission to surgery | 1.0 | 0.8 | .691 |
Abbreviations: ASA, American Society of Anesthesiologists; INR, international normalized ratio.
Table 4.
Complications Compared Between Smokers and Nonsmokers for Replantation/Revascularization (Emergency/Trauma) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Complications | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Deep vein thrombosis | 0% | 2.1% | .203 |
| Myocardial infarction | 1.3% | 0% | .113 |
| Cardiac arrest | 0% | 0% | - |
| Stroke/cerebrovascular accident | 0% | 1.0% | .370 |
| Urinary tract infection | 1.3% | 1.0% | .853 |
| Acute renal failure | 1.3% | 0.5% | .499 |
| Progressive renal insufficiency | 0% | 0.5% | .527 |
| Pulmonary embolism | 0% | 2.1% | .217 |
| Pneumonia | 1.3% | 1.0% | .853 |
| Wound infection | 0% | 1.0% | .370 |
| Superficial infection | 1.3% | 2.1% | .670 |
| Dehiscence | 0% | 0% | - |
| Sepsis | 0.0% | 2.1% | .203 |
| Shock | 0% | 2.1% | .203 |
| Unplanned reintubation | 0% | 0% | - |
| Ventilator for >48 hours | 0% | 3.1% | .118 |
| Organ space infection | 1.3% | 0.5% | .499 |
| Transfusion | 10.4% | 5.2% | .121 |
| Minor complications | 13.0% | 12.4% | .902 |
| Major complications | 1.3% | 7.3% | .055 |
| Total complications | 13.0% | 14.0% | .829 |
| Readmissions | 3.9% | 3.6% | .916 |
| Reoperations | 2.4% | 6.1% | .350 |
Regression analysis revealed that preoperative smoking history within 1 year prior to admission for surgery was not found to be a predictor of any adverse 30-day outcomes, including major or total complications, reoperations, and readmissions, in revascularization/replantation patients.
Free Flap Transfer Procedures
A total of 70 patients who underwent UE free flap transfers were identified. Of these, 14 (20.0%) patients were current smokers and had a history of cigarette smoking within a year prior to surgery (smokers) and 56 patients without smoking history (nonsmokers). Smokers and nonsmokers had no differences in age, sex, or race distribution. Nonsmokers had a higher preoperative BMI (29.1 vs 24.7 kg/m2, P < .001). Smokers had a higher prevalence of COPD (7.1% vs 0%, P = .044), with no differences observed for other comorbid conditions, including hypertension or diabetes (Table 5). Smokers experienced lengthier hospital stays (6.6 vs 4.2 days, P = .001), although operative times, as well as distribution of wound class and ASA classification, did not differ (Table 6). Both smokers and nonsmokers experienced no 30-day postoperative major complications, and the 2 cohorts had comparable rates of transfusion (14.3% vs 8.9%, P = .550) and minor/total complications (14.3% vs 12.5%, P = .858). In addition, 30-day reoperations (0% vs 7.5%, P = .326) and readmissions (1.8% vs 7.1%, P = .282) were comparable between the smokers and nonsmokers following free flap transfer. Smokers did not experience any postoperative infections. Overall, few postoperative complications were reported for either cohort (Table 7).
Table 5.
Baseline Demographics and Comorbidities of All Patients Included in This Study Who Underwent Free Flap Transfer (Elective) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Parameter | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Mean age, years | 38.50 | 44.96 | .152 |
| Sex | |||
| Male | 64.3% | 53.6% | .470 |
| Female | 35.7% | 46.4% | |
| Race | |||
| White | 100% | 71.4% | .159 |
| Black | 0% | 12.5% | |
| Other | 0% | 16.1% | |
| Body mass index, kg/m2 | 24.7 | 29.1 | <.001 |
| Comorbidities | |||
| Ventilator dependence | 0% | 0% | - |
| Recent weight loss | 0.0% | 1.8% | .615 |
| Hypertension | 7.1% | 26.8% | .117 |
| Diabetes mellitus | 7.1% | 12.5% | .777 |
| Chronic obstructive pulmonary disorder | 7.1% | 0% | .044 |
| Dialysis | 0% | 0% | - |
| Corticosteroid use | 0% | 1.8% | 0.615 |
| Congestive heart failure | 0% | 0% | - |
| Ascites | 0% | 0% | - |
| Disseminated cancer | 0% | 0% | - |
| Renal failure | 0% | 0% | - |
| Preoperative sepsis | 0% | 0% | - |
Bold face values are statistically significant values.
Table 6.
Preoperative Laboratory Values, Wound Class, and Perioperative Parameters for Free Flap Transfer (Elective) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Parameters | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Preoperative laboratory values | |||
| White blood cell count, ×109/L | 6.9 | 7.7 | .600 |
| Hematocrit, % | 40.5 | 40.72 | .924 |
| Platelet count, ×103 | 197.5 | 240.3 | .150 |
| Creatinine, mg/dL | 0.8 | 0.9 | .329 |
| Albumin, g/dL | 4.6 | 4.2 | .325 |
| INR | 1.3 | 1.0 | .345 |
| Operative variables | |||
| Wound class | |||
| Clean | 71.4% | 89.3% | .233 |
| Clean contaminated | 21.4% | 5.4% | |
| Contaminated | 0% | 3.6% | |
| Dirty | 0% | 1.8% | |
| ASA classification | |||
| 1 (No disturbance) | 14.3% | 12.5% | .983 |
| 2 (Mild disturbance) | 57.1% | 58.9% | |
| 3 (Severe disturbance) | 28.6% | 28.6% | |
| 4 (Life-threatening disturbance) | 0% | 0% | |
| Preoperative blood transfusions | 0% | 0% | - |
| Operative time, minutes | 451.4 | 391.3 | .254 |
| Length of stay, days | 6.6 | 4.2 | .001 |
| Days from admission to surgery | 0 | 0 | - |
Abbreviations: ASA, American Society of Anesthesiologists; INR, international normalized ratio.
Bold face values are statistically significant values.
Table 7.
Complications Compared Between Smokers and Nonsmokers for Free Flap Transfer (Elective) Microsurgical Reconstruction Procedures of the Upper Extremity.
| Complications | Smokers | Nonsmokers | P value |
|---|---|---|---|
| Deep vein thrombosis | 0% | 0% | - |
| Myocardial infarction | 0% | 0% | - |
| Cardiac arrest | 0% | 0% | - |
| Stroke/cerebrovascular accident | 0% | 0% | - |
| Urinary tract infection | 0% | 0% | - |
| Acute renal failure | 0% | 0% | - |
| Progressive renal insufficiency | 0% | 0% | - |
| Pulmonary embolism | 0% | 0% | - |
| Pneumonia | 0% | 0% | - |
| Wound infection | 0% | 1.8% | .615 |
| Superficial infection | 0% | 1.8% | .615 |
| Dehiscence | 0% | 0% | - |
| Sepsis | 0% | 0% | - |
| Shock | 0% | 0% | - |
| Unplanned reintubation | 0% | 0% | - |
| Ventilator for >48 hours | 0% | 0% | - |
| Organ space infection | 0% | 0% | - |
| Transfusion | 14.3% | 8.9% | .550 |
| Minor complications | 14.3% | 12.5% | .858 |
| Major complications | 0% | 0% | - |
| Total complications | 14.3% | 12.5% | .858 |
| Reoperations | 0% | 7.5% | .326 |
| Readmissions | 7.1% | 1.8% | .282 |
| Reoperations | 0% | 7.5% | .326 |
While smokers had a greater prevalence of COPD within the free flap transfer cohort, multivariate regression analysis revealed that there neither recent smoking history nor COPD at baseline was associated with increased odds of developing major and minor complications or incurring related readmission or reoperations in the 30-day postoperative period.
Discussion
Associations between cigarette smoking within a year of surgery and adverse or suboptimal wound healing have been reported due to disruption and dysregulation of the endothelium as well as disruption of complement activation. 6,16 In particular, smoking is known to impair microcirculation in replanted digits and cutaneous vasculature. 14,24 And, while peripheral artery disease more commonly affects the lower extremity, there appears to be a consensus in the reports of the effects of smoking on outcomes following lower extremity microsurgery. 25 -30 This consensus does not seem to exist for UE microsurgery. Recent literature has reported contradictory conclusions regarding the effects of smoking on UE reconstruction specifically. 15 -18,20 In this study, we investigated the effects of smoking on 30-day postoperative outcomes following UE reconstruction procedures. While the national prevalence of cigarette smokers was 15.5% in 2016, the prevalence of smoking in our study groups, both replantation/revascularization (28.5%) and free tissue transfer patients (20.0%), was above this national average. 31 The reason behind the increased rate is beyond the scope of this article, the elevated rates of smokers in our cohort, albeit limited in sample size, may strengthen the lack of association found in this study.
Cigarette smoking was not found to be associated with postoperative complications in the 30 days following UE microsurgical reconstruction. Several studies have reported related conclusions. 16,17,19,32 He et al 16 evaluated the impact of smoking within 6 months of replantation of an UE or digits. Although they observed no difference in failure rates between smokers and nonsmokers as well as a nonsignificantly higher rate of postoperative infections among smokers, they recommended patients cease smoking following replantation. 16 In a study from Germany of nearly 1000 free flap reconstructions, Ehrl and colleagues 19 demonstrated no differences in complication (flap loss, partial flap loss, arterial thrombosis, venous thrombosis, or hematoma) rates up to 3 months postoperatively between smokers and nonsmokers between their UE cohort (N = 155) and overall cohort (N = 969; P > .05).
Among the largest studies to describe tobacco use as a nonsignificant risk factor for flap failure is the multicentre, multinational prospective study of 23 centres performed by Khouri et al 33 from 1994 to 1995, in which 493 free flap reconstruction procedures were evaluated (consisting of 81 UE flaps). Overall failure rate was reported at 4.1%, and tobacco use was not found to significantly impact flap failure, although a subgroup analysis was not specifically performed for UE flaps. Upper extremity flaps were associated with a 3.7% failure rate and 13.6% postoperative thrombosis rate, while the overall mean rate for all surgical sites was 9.9%. In 1995, smoking prevalence among adults was 29% globally, compared to 25.5% in the United States. 34 This rate has decreased since then, at 20% globally in 2014 and 18% in the United States in 2012. 34 Additionally, their study did not specify the extent or temporality of tobacco use among included patients with respect to their date of surgery nor did it evaluate replantation/revascularization procedures or assess tobacco use as a risk factor for adverse postoperative outcomes beyond flap failure.
Nishijima et al 17 found no differences in the extent of necrosis following digital replantation and revascularization between smokers and nonsmokers when all patients were treated with prostaglandin E1 after surgery. It is interesting to note that while prostaglandin E1 acts as a vasodilator, which in theory would allow for increased blood flow to a replanted extremity/digit, failure predominately arose from vasospasm rather than vasoconstriction. 17 While the benefits of prostaglandin E1 cannot be fully discerned from this particular study, it may prove to be beneficial to UE microsurgical reconstruction and warrants further investigation.
Our results differ from multiple reports that have demonstrated a negative effect of smoking on replanted digits, although this finding has been limited to patients who are heavy smokers. 14,15,35 Cigarette smoking has been implicated as an independent risk factor in adverse postoperative outcomes, including delayed wound healing. 13,36 Preoperative smoking cessation has been shown to improve the rate of postoperative complications in patients undergoing surgeries, including reconstructive procedures that rely heavily on proper vasculature for success. 24,37,38 While these studies have observed increased rates of minor postoperative complications, such as wound breakdown or delayed healing, they reported no increased overall rate of flap failure was observed. 8,13,39 In addition to the reduced blood flow that nicotine can produce due to vasoconstriction, other chemicals, such as carbon monoxide, can adversely impact healing due to impairment of oxygen delivery to local tissue. Nitric oxide allows for increased absorption of nicotine in the bloodstream, and hydrogen cyanide impairs innate cellular pathways for tissue repair. All of these cigarette components work synergistically to impair wound healing. 11 -13 Even so, studies have found no significant differences in replantation success between smokers and nonsmokers. 13
Surgeons have been reported to refuse to perform elective surgeries on patients who refuse to quit smoking. 40 However, in the case of replantation and revascularizations, these procedures are emergent, and surgeons often may not have the opportunity to fully optimize their patients. In both microsurgical reconstructive cohorts in the present study, we identified no significant differences in standardized postoperative outcomes between smokers and nonsmokers. One factor that may attribute to the similar success rates may be the stringent and comprehensive postoperative protocols that surgeons employ after such procedures, which often includes venous thromboembolism prophylaxis (ie, low-molecular-weight heparin), adequate immobilization, and suitable environmental conditions (ie, room temperature). Furthermore, monitoring typically includes, but is not limited to, frequent assessment of temperature, skin color, capillary refill, and Doppler ultrasound signal, especially in the immediate postoperative period. 41,42
Aside from the lack of association between smoking and adverse outcomes, these data revealed interesting aspects of this patient population. The data from the replantation/revascularization cohort revealed a considerable proportion of patients with preoperative hemodialysis use. Nonsmokers within this cohort were more often on dialysis (15.6% vs 10.4%, P = .030), but both of these rates are higher than the national average (approximately 0.14%). 43,44 For the purposes of this study, cohorts were designed to exclude all surgical procedures specifically related to arteriovenous fistula creation and/or revision; the CPT code corresponding to blood vessel repair with vein graft (35236) excludes all procedures related to arteriovenous fistula creation and/or revision. 45 In both the replantation/revascularization and free flap transfer cohorts, nonsmokers had a higher BMI. This difference was significant among free flap transfer patients, which is consistent with prior literature that supports the appetite suppressing characteristics of cigarette smoking. 46,47 However, smokers in this study had lower rates of preoperative comorbidities overall, which may bias this cohort in favour of better outcomes. Additionally, free flap transfer data revealed that smokers had lengthier hospital stays, possibly attributed to the increased rate of COPD among smokers, which has been found to be associated with lengthier hospital stays in previous studies. 48,49
Notwithstanding the results of the present study, there were several limitations to consider. First, the quality of data is innately limited by the standard of reporting in the NSQIP database. Such large databases often do not offer the same granularity as physician-run databases. For example, cigarette smokers are included in the database as those who smoked within a year prior to surgery; unfortunately, this did not distinguish those who continued to smoke after surgery nor did they comment on presence or absence of smoking beyond the 1-year time frame, providing insight into the extent of the patient’s smoking history, both of which may be important in studying adverse outcomes in this patient population. Additionally, the database reports postoperative complications as a set of common surgical complications and uses “other” as a catch-all for less common or more specific complications. Adverse events including, but not limited to, flap loss, replantation/revascularization failure, take-back rates, and amputation are very important complications that are specific to reconstructive surgeries and of interest to microsurgeons; unfortunately, these are not specifically identified or distinguished in the NSQIP database. However, the authors thought it is important to study the effects of smoking on general postsurgical outcomes in UE microsurgery cohorts, given the reliance on proper vasculature. Furthermore, the sample size of this study was limited. Strict inclusion criteria were followed to ensure that only flaps with cutaneous attachments and UE cases were considered. However, these reconstruction procedures may also have fallen under more general CPT and ICD codes which did not correspond to the UE and thus were not included in this data set. Notwithstanding, the strict inclusion criteria strengthen the presented findings and avoid contamination of the study population. Upper extremity reconstruction patients were selected based on a postoperative diagnosis or secondary procedure related to the UE, but secondary procedures may have been missed in some cases given that they may occur years after the primary procedure. Homogenizing the study by separating elective and emergency procedures was also not possible with the standard procedure identification codes, although replantation/revascularization procedures were defined as emergency procedures in this study, and free flap transfers were defined as elective procedures; all of these indications were verified by review of the preoperative diagnosis. Complication reports were limited to 30 days postoperatively, which may be adequate for assessing acute changes, but given the long-term nature of smoking effects may not have provided a completely accurate framework for studying this impact. Furthermore, many different surgery types were included in this study. Upper extremity reconstruction is very complex and requires adequate medical support to manage immediate complications. The differences among institutions and individual surgeons could not be highlighted in this study.
However, despite the limitations of this study, its strengths are significant. Herein, we present a large cohort of heterogeneous patients from heterogeneous institutions with unstandardized postoperative protocols. Despite the heterogeneity of the included patient population, smoking was not found to be a predictor of adverse outcomes in UE microvascular reconstruction surgeries. These results are supported by the findings of prior studies, such as Ehrl et al 19 and Khouri et al. 33 Yet, unlike the results from Ehrl et al, 19 our study presents findings from a variety of institutions, performed without standardized postoperative protocols, which we believe strengthens the findings that smoking was not a significant risk factor for microvascular failure. Similarly, Khouri et al 33 found no association between smoking and flap failure in a heterogeneous sample, but they did not perform subgroup analysis specifically examining UE microvascular reconstructions, while also presenting higher rates of flap failure in the UE. Our findings are contrary to this and support an overall conclusion that UE microvascular reconstruction is safe and effective, with low rates of 30-day complications, even in the setting of recent smoking.
Conclusion
A history of smoking within a year prior to surgery was not a predictor of commonly evaluated standardized postoperative adverse outcomes in the 30-day period following UE reconstruction procedures. These results represent a timely update on historical literature pertaining to microvascular reconstruction and risk of failure secondary to smoking, while also addressing these findings in a heterogeneous, diverse, nationally representative sample of patients. The results of this and previous studies suggest a need for more higher level of evidence studies, as well as impact on microsurgical-specific adverse events, to more definitively guide clinical practice. While our study did not find such an association, the authors of this study still recommend cessation of cigarette smoking given the overall medical benefits and prevention of future comorbidity and complications.
Footnotes
Level of Evidence: Level 1, Therapeutic
Authors’ Note: This study was exempt from review by the IRB because de-identified, publicly available data were utilized. As such, this study is in accordance with the Helsinki Declaration and no informed consent was required. The study was presented at the 88th Annual Plastic Surgery: The Meeting 2019 (as 2 podium presentations—1 as a Top 200 [Tier 1] paper and 1 as a Tier 2 paper; San Diego, California; September 20-23, 2019), at the 74th Annual Meeting of the American Society for Surgery of the Hand (as 2 poster presentations; Las Vegas, Nevada; September 5-7, 2019), at the 2020 Annual Meeting of the American Association of Hand Surgery (as 2 poster presentations; Fort Lauderdale, Florida; January 8-11, 2020). The following authors have nothing to disclose: O.O. Oleru, N.V. Shah, P.L. Zhou, D. Sedaghatpour, J.B. Mistry, B.C. Wham, and J. Kurtzman. No funding was solicited or received for any aspect of this study or article. No products, devices, or drugs are mentioned in the manuscript.
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.M. Koehler discloses personal fees (consulting) from Integra LifeScience, unpaid consulting with TriMed, research support from Collagen Matrix, Inc., and board/committee membership with the American Association for Surgery of the Hand (ASSH). S.K. Mithani discloses personal fees (presenter or speaker) from Integra LifeScience.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iD: Steven M. Koehler, MD https://orcid.org/0000-0002-7690-2401
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