Abstract
Introduction
Surgical site infection after saphenous vein harvest is common, with reported leg wound infection rates ranging from 2 to 24%. There have been few investigations into sex-related differences in complication rates. Moreover, varied effects of smoking have been reported. The aim of this study was to investigate risk factors such as gender and smoking, associated with surgical site infection after vein graft harvesting in coronary artery bypass grafting surgery.
Methods
We included 2,188 consecutive patients who underwent coronary artery bypass grafting surgery with at least one vein graft at our centre from 2009 to 2018. All patients were followed up postoperatively. Risk factors for leg wound infection requiring antibiotic treatment and surgical revision were analysed using logistic regression analysis.
Results
In total, 374 patients (17.1%) received antibiotic treatment and 154 (7.0%) underwent surgical revision for leg wound infection at the harvest site. Female sex, high body mass index, diabetes mellitus, longer operation time, peripheral vascular disease and direct oral anticoagulants were independently associated with any leg wound infection at the harvest site. Among surgically revised patients, female sex and insulin or oral treatment for diabetes mellitus as well as longer operation time were independent risk factors. Smoking was not associated with leg wound infection.
Conclusion
Female sex is associated with increased risk of leg wound infection. The underlying mechanism is unknown. In the current population, previous or current smoking was not associated with an increased risk of leg wound infection.
Keywords: Female sex, Leg wound infection, Smoking
Background
In coronary artery bypass grafting (CABG) surgery the saphenous vein is the most common conduit for coronary revascularization, being used in 80% of cases [1]. Surgical site infection (SSI) at the saphenous vein harvest site is more common than sternal wound infections, with reported leg wound infection (LWI) rates ranging from 2 to 24% [2–5]. Leg wound infections have a negative effect on patients’ morbidity, quality of life and wellbeing [6]; they prolong hospitalization, may require extensive debridement and surgical procedures and are an economic burden to the health care system [6, 7]. To reduce the risk of LWI, measures such as antibiotic prophylaxis, proper skin disinfection and maintaining an aseptic environment are applied [7–9]. Risk factors associated with LWI include external factors such as the vein harvesting technique [10–12], duration of surgery [13], number of vein grafts [14] and choice of sutures [15–17]. Patient-dependent risk factors for LWI include diabetes mellitus (DM), obesity, peripheral vascular disease, impaired renal function and low left ventricular ejection fraction (LVEF) [13, 14, 18].
In different surgical procedures, men are often more affected by SSI than women [19]. Studies regarding sex as a risk factor for sternal wound infection after cardiac surgery show divergent results [4, 5, 20]. However, it has been reported that leg wound complications are actually more common in female patients [14, 18, 21], although further studies are warranted to confirm this.
Smoking is a modifiable risk factor (that is, a behavioral risk factor) that has been associated with wound complications after different types of surgery [22, 23]. Studies investigating LWI after CABG surgery are sparse and no association between smoking and LWI has yet been shown [3, 14].
In conclusion, ambiguity persists regarding the understanding of some potential risk factors for LWI. This study aimed to investigate risk factors for LWI after vein graft harvesting in CABG, with focus on female sex and smoking.
Materials and methods
Study design
This was a retrospective cohort study based on prospectively collected data from a local quality register at a single cardiothoracic centre in Sweden.
Data sources
The Carath Registry is a quality register including pre-, intra- and postoperative patient data. Our study included the following variables: sex, age, body mass index (BMI), glomerular filtration rate (GFR), preoperative haemoglobin (HB), smoking status, DM, vein harvesting technique (conventional or “no-touch” technique, where the vein is harvested along with the perivascular adipose tissue) [24], number of distal anastomoses, LVEF, peripheral vascular disease, degree of urgency (elective or acute), preoperative anticoagulant treatment, type of surgery (CABG or CABG + valve) and operation time. These 15 variables, identified from the Carath Registry, were evaluated regarding their association with LWI. They were selected based on previous research and the authors’ own clinical experience, and to ensure inclusion of some less investigated factors.
Patients and perioperative routines
Follow-up data were obtained regarding consecutive patients undergoing CABG alone or CABG in combination with other cardiac surgical procedures, with at least one vein graft, between 1 January 2009 and 31 December 2018 at the Department of Vascular and Cardiothoracic Surgery, Örebro University Hospital, Örebro, Sweden [25].
Preoperatively all elective and acute patients showered with chlorhexidine gluconate (4%). Hair cutting was performed with a hair clipper at the department ward the day before surgery or directly before the operation. Vein harvesting was performed using an open surgical technique. The wound was closed with two or three layers of subcutaneous and intracutaneous monofilament sutures. Between 2009 and 2013, Biosyn 3 − 0® (Covidien, Minneapolis, MN, USA) was used; from 2014, triclosan-coated Monocryl 3 − 0® monofilament sutures (Ethicon; Johnson & Johnson, Cincinnati, OH, USA) were used. All patients were treated with perioperative intravenous antibiotic prophylaxis. During 2009–2014, patients received cloxacillin 2 g, starting 25 min before the sternal skin incision. Two hours after the initial dose, another dose of 2 g was administered. For lengthy operations, the dose was repeated every 6 h. Before sternal closure, a final intraoperative dose was given if the previous dose had been administered ≥ 2 h previously. Postoperatively, 2 g of cloxacillin was administered every 8 h for a total duration of at least 24 h. From 2015 onward, a 3 g single dose of benzyl penicillin, administered together with the preoperative dose of cloxacillin, was added. Clindamycin 600 mg was given preoperatively to patients allergic to beta-lactam antibiotics and the dose was repeated after 4 h of surgery, with further postoperative doses given every 8 h for a total of 24 h.
Definition and follow-up of surgical site infection
The study’s two outcome variables were all LWIs, and surgical revision for LWI. In this study, LWI was defined as any wound complication for which the patient had been prescribed antibiotic treatment, in accordance with the Centers for Disease Control and Prevention (CDC) classification where one single criterion for superficial surgical site infection is “diagnosis of a superficial incisional SSI by a physician or physician designee” [26]. An LWI that had been surgically revised (under local or general anaesthesia) was considered a more severe wound infection; these LWIs were analysed separately. All surgically revised LWIs also required antibiotic treatment.
A registered nurse made a postoperative follow-up call 2 months after the surgery to check for any postoperative infections. A simplified questionnaire based on the validated Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and Stay as inpatient prolonged over 14 days (ASEPSIS) score [27] was used to classify patient-reported postoperative symptoms of infection.
Statistical analysis
Categorical variables were expressed as numbers and percentages, and age as median and range. All categorical variables were compared using chi-squared test; for age, Mann-Whitney U test was used. Before the analyses, all ratio data were categorized. Age was divided into decades. Univariable and multivariable logistic regression analyses were used to analyse the relationship of the predictor variables with the outcome. Predictors with p-values ≤ 0.2 in the univariable analysis were added to the multivariable model. The results from the multivariable analysis were reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). A p-value of < 0.05 was considered statistically significant.
The statistical analyses were performed using IBM® SPSS® Statistics version 27 (IBM Corp., Armonk, NY, USA).
Ethics
The study was approved by the Swedish Ethical Review Authority (ID 2020–03103). Because of the retrospective nature of the study no informed consent was obtained.
Results
In total, 2,628 patients underwent CABG surgery during the study period. Of these, 2,188 patients with at least one vein graft were followed up. The study population consisted of 439 women (20%) and 1,749 men (80%), their ages ranging from 30 to 89 (median 70) years. Approximately 60% of the group were smokers or ex-smokers and the majority had a BMI ≥ 25. Altogether 374 (17.1%) patients received antibiotic treatment for any LWI; 154 (7.0%) also underwent surgical revision under local or general anaesthesia. Baseline characteristics are presented in Table 1.
Table 1.
Baseline characteristics of, and operative factors in, coronary artery bypass grafting (CABG) patients with or without leg wound infection (LWI) at the saphenous vein harvesting site
| Total | No LWI | Any LWI | Surgical revision | |
|---|---|---|---|---|
| n = 2,188 | n = 1,814 (82.9%) | n = 374 (17.1%) | n = 154 (7.0%) | |
| Patient factors | ||||
| Sex, n (%) | ||||
| Female | 439 (20) | 335 (18.5) | 104 (27.8) | 48 (31.2) |
| Male | 1,749 (80) | 1,479 (81.5) | 270 (72.2) | 106 (68.8) |
| Age, yrs, n (%) | ||||
| 0–50 | 65 (3.0) | 52 (2.9) | 13 (3.5) | 4 (2.6) |
| 51–60 | 305 (13.9) | 256 (14.1) | 49 (13.1) | 16 (10.4) |
| 61–70 | 821 (37.5) | 693 (38.2) | 128 (34.2) | 67 (43.5) |
| 71–80 | 843 (38.5) | 685 (37.8) | 158 (42.2) | 56 (36.4) |
| 81–100 | 154 (7.1) | 128 (7.0) | 26 (7.0) | 11 (7.1) |
| Body mass index, kg/m2, n (%) | ||||
| <18.5 | 6 (0.3) | 3 (0.1) | 3 (0.8) | 0 (0.0) |
| 18.5–<25 | 461 (21.1) | 409 (22.6) | 52 (14.0) | 19 (12.3) |
| 25–<30 | 1,052 (48.1) | 893 (49.3) | 159 (42.5) | 77 (50.0) |
| ≥30 | 668 (30.5) | 508 (28.0) | 160 (42.7) | 58 (37.7) |
| Missing | 1 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) |
| Diabetes mellitus, n (%) | ||||
| No | 1,488 (68.0) | 1,281 (70.6) | 207 (55.3) | 72 (46.8) |
| Insulin-treated | 352 (16.1) | 248 (13.7) | 104 (27.8) | 51 (33.1) |
| Tablet-treated | 276 (12.6) | 223 (12.3) | 53 (14.2) | 29 (18.8) |
| Diet-treated | 63 (2.9) | 54 (3.0) | 9 (2.4) | 2 (1.3) |
| Missing | 9 (0.4) | 8 (0.4) | 1 (0.3) | 0 (0.0) |
| Haemoglobin, g/L, n (%) | ||||
| ≤120 | 278 (12.7) | 217 (12.0) | 61 (16.3) | 31 (20.2) |
| ≥121 | 1,902 (87.0) | 1,590 (87.6) | 312 (83.4) | 122 (79.2) |
| Missing | 8 (0.3) | 7 (0.4) | 1 (0.3) | 1 (0.6) |
| Renal function, (n) % | ||||
| Normal function | 929 (42.5) | 776 (42.8) | 153 (41.0) | 60 (38.9) |
| Mild reduction | 885 (40.5) | 733 (40.4) | 152 (40.6) | 63 (41.0) |
| Moderate reduction | 337 (15.4) | 272 (15.0) | 65 (17.4) | 28 (18.2) |
| Severe reduction | 25 (1.1) | 23 (1.3) | 2 (0.5) | 2 (1.3) |
| Renal failure | 11 (0.5) | 9 (0.5) | 2 (0.5) | 1 (0.6) |
| Missing | 1 (0.0) | 1 (0.0) | 0 (0.0) | 0 (0.0) |
| Smoking, n (%) | ||||
| Smoker | 232 (10.6) | 184 (10.1) | 48 (12.8) | 25 (16.2) |
| Ex-smokera | 1,016 (46.4) | 847 (46.7) | 169 (45.2) | 62 (40.3) |
| Never smoker | 878 (40.1) | 732 (40.4) | 146 (39.0) | 59 (38.3) |
| Missing | 62 (2.9) | 51 (2.8) | 11 (3.0) | 8 (5.2) |
| LVEF, n (%) | ||||
| >50% | 1,596 (73.0) | 1,342 (74.0) | 254 (68.0) | 101 (65.6) |
| 41–50% | 324 (14.8) | 262 (14.4) | 62 (16.6) | 26 (16.9) |
| 31–40% | 162 (7.4) | 128 (7.1) | 34 (9.1) | 17 (11.0) |
| ≤30% | 95 (4.3) | 72 (4.0) | 23 (6.1) | 10 (6.5) |
| Missing | 11 (0.5) | 10 (0.5) | 1 (0.2) | 0 (0.0) |
| Anticoagulants, n (%) | ||||
| Heparin/LMWH | 482 (22.0) | 394 (21.7) | 88 (23.5) | 31 (20.3) |
| DOAC | 81 (3.7) | 60 (3.3) | 21 (5.6) | 9 (5.8) |
| No | 1,602 (73.2) | 1,343 (74.0) | 259 (69.3) | 110 (71.4) |
| Missing | 23 (1.1) | 17 (1.0) | 6 (1.6) | 4 (2.5) |
| Peripheral vascular disease, n (%) | ||||
| Yes | 149 (6.8) | 113 (6.3) | 36 (9.6) | 17 (11.0) |
| No | 2,028 (92.7) | 1,693 (93.3) | 335 (89.6) | 137 (89.0) |
| Missing | 11 (0.5) | 8 (0.4) | 3 (0.8) | 0 (0.0) |
| Operative factors | ||||
| Urgency, n (%) | ||||
| Emergency (within 24 h) | 97 (4.4) | 79 (4.4) | 18 (4.8) | 10 (6.5) |
| Urgent | 779 (35.6) | 638 (35.2) | 141 (37.7) | 57 (37.0) |
| Elective | 1,292 (59.0) | 1,082 (59.6) | 210 (56.2) | 86 (55.9) |
| Missing | 20 (1.0) | 15 (0.8) | 5 (1.3) | 1 (0.6) |
|
Type of intervention, n (%) |
||||
| CABG | 1,724 (78.8) | 1,441 (79.5) | 283 (75.7) | 121 (78.6) |
| CABG + valve | 408 (18.6) | 331 (18.2) | 77 (20.6) | 26 (16.9) |
| CABG + other surgery | 56 (2.6) | 42 (2.3) | 14 (3.7) | 7 (4.5) |
| Vein harvesting technique, n (%) | ||||
| No-touch technique | 1,633 (74.6) | 1,345 (74.1) | 288 (77.0) | 119 (77.3) |
| Conventional technique | 555 (25.4) | 469 (25.9) | 86 (23.0) | 35 (22.7) |
| Number of graft vessels, n (%) | ||||
| 1–2 | 946 (43.2) | 804 (44.3) | 142 (38.0) | 59 (38.3) |
| 3–4 | 1,167 (53.4) | 956 (52.7) | 211 (56.4) | 82 (53.3) |
| 5–6 | 75 (3.4) | 54 (3.0) | 21 (5.6) | 13 (8.4) |
| Operation time, n (%) | ||||
| <3 h | 400 (18.3) | 353 (19.5) | 47 (12.6) | 17 (11.0) |
| 3–5 h | 1,444 (66.0) | 1,200 (66.2) | 244 (65.2) | 92 (59.7) |
| >5 h | 323 (14.8) | 242 (13.3) | 81 (21.7) | 43 (28.0) |
| Missing | 21 (0.9) | 19 (1.0) | 2 (0.5) | 2 (1.3) |
BMI = body mass index; CABG = coronary artery bypass grafting; DOAC = direct oral anticoagulant; LMWH = low-molecular-weight heparin; LVEF = left ventricular ejection fraction
Peripheral vascular disease = one or more of: claudication, carotid occlusion or 50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids, or amputation for arterial disease
aEx-smoker > 1 month
The incidence of LWI at the harvest site was 23.7% in women and 15.4% in men (Table 1). Diabetes mellitus and anaemia were also more common among the women, as was impaired GFR. Moreover, there were more active smokers in the female group. The majority of the surgeries were elective but there was a tendency for the women to have more urgent operations as well as more combined interventions (CABG + valve surgery). Further differences between the sexes are described in Table 2.
Table 2.
Baseline characteristics of and operative factors in the included women and men
| Women, n = 439 | Men, n = 1,749 | P-value | |
|---|---|---|---|
| Patient factors | |||
| Age, yrs, median (min–max) | 70.0 (37–89) | 69.0 (30–87) | 0.078 |
| BMI, kg/m2, n (%)a | 0.305 | ||
| <18.5 | 2 (0.5) | 4 (0.2) | |
| 18.5–<25 | 106 (24.1) | 355 (20.3) | |
| 25–<30 | 168 (38.3) | 884 (50.6) | |
| ≥30 | 163 (37.1) | 505 (28.9) | |
| Diabetes mellitus, n (%) a, f | 0.002 | ||
| Yes | 165 (37.8) | 526 (30.2) | |
| No | 272 (62.2) | 1,216 (69.8) | |
| Haemoglobin, g/L, n (%) b, g | <0.001 | ||
| ≤120 | 137 (31.4) | 141 (8.0) | |
| ≥121 | 299 (68.6) | 1,603 (92.0) | |
| Renal function, n (%) d | <0.001 | ||
| Normal function | 123 (28.0) | 806 (46.1) | |
| Mild reduction | 190 (43.3) | 695 (39.8) | |
| Moderate reduction | 110 (25.1) | 227 (13.0) | |
| Severe reduction | 11 (2.5) | 14 (0.8) | |
| Renal failure | 5 (1.1) | 6 (0.3) | |
| Smoking, n (%) c, h | <0.001 | ||
| Smoker | 64 (15.2) | 168 (9.8) | |
| Ex-smoker1 | 160 (38.1) | 856 (50.2) | |
| Never smoker | 196 (46.7) | 682 (40.0) | |
| LVEF, n (%) d, i | 0.828 | ||
| >50% | 315 (72.0) | 1,281 (73.7) | |
| 41–50% | 74 (16.9) | 250 (14.4) | |
| 31–40% | 30 (6.8) | 132 (7.6) | |
| ≤30% | 19 (4.3) | 76 (4.3) | |
| Anticoagulants, n (%) b, j | 0.073 | ||
| Heparin/LMWH | 113 (25.9) | 369 (21.3) | |
| DOAC | 12 (2.8) | 69 (4.0) | |
| No | 311 (71.3) | 1,291 (74.7) | |
| Peripheral vascular disease, n (%) a, k | 0.817 | ||
| Yes | 31 (7.1) | 118 (6.8) | |
| No | 406 (92.9) | 1,622 (93.2) | |
| Operative factors | |||
| Urgency, n (%) e, l | 0.002 | ||
| Emergency (within 24 h) | 27 (6.2) | 70 (4.0) | |
| Urgent | 179 (41.2) | 600 (34.6) | |
| Elective | 229 (52.6) | 1,063 (61.4) | |
| Type of intervention, n (%) | 0.006 | ||
| CABG | 324 (73.8) | 1,400 (80.1) | |
| CABG + valve | 105 (23.9) | 303 (17.3) | |
| CABG + other surgery | 10 (2.3) | 46 (2.6) | |
| Vein harvesting technique, n (%) | <0.001 | ||
| No-touch technique | 298 (67.9) | 1,335 (76.3) | |
| Conventional technique | 141 (32.1) | 414 (23.7) | |
| Number of graft vessels, n (%) | 0.052 | ||
| 1–2 | 211 (48.1) | 735 (42.0) | |
| 3–4 | 212 (48.3) | 955 (54.6) | |
| 5–6 | 16 (3.6) | 59 (3.4) | |
| Operation time, n (%) b, m | 0.286 | ||
| <3 h | 78 (17.9) | 322 (18.6) | |
| 3–5 h | 284 (65.1) | 1,160 (67.0) | |
| >5 h | 74 (17.0) | 249 (14.4) |
BMI = body mass index; CABG = coronary artery bypass grafting; DOAC = direct oral anticoagulant; LMWH = low-molecular-weight heparin; LVEF = left ventricular ejection fraction
Peripheral vascular disease = one or more of: claudication, carotid occlusion or 50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids, or amputation for arterial disease
One character behind a variable indicates missing data in the men’s group; two characters indicate missing data in both groups: aMissing data on two patients, bmissing data on three patients, cmissing data on 19 patients, dmissing data on one patient, e missing data on four patients, fmissing data on seven patients, gmissing data on five patients, hmissing data on 43 patients, Imissing data on ten patients, jmissing data on 20 patients, kmissing data on nine patients, lmissing data on 16 patients, mmissing data on 18 patients
1Ex-smoker >1 month
Risk factors for any leg wound infection
In the multivariable logistic regression analysis, female sex [p<0.001; OR 1.62 (95% CI 1.22–2.16)], BMI ≥ 30 [p<0.001; OR 2.04 (95% CI 1.42–2.93)], insulin-treated DM [p<0.001; OR 2.13 (95% CI 1.58–2.85)], peripheral vascular disease [p = 0.028; OR 1.59 (95% CI 1.05–2.42)] and direct oral anticoagulants (DOACs) [p = 0.015; OR 1.98 (95% CI 1.13–3.45)] were independently associated with any LWI (Table 3). Smoking was not associated with any statistically significant increased risk for LWI when added to the multivariable risk factor analysis. For additional details, see Table 3.
Table 3.
Results of the univariable and multivariable logistic regression analysis of risk factors for any leg wound infection (LWI)
| Unadjusted analysis | Adjusted analysis# | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Characteristics | ||||||
| Sex | ||||||
| Female | 1.70 | 1.31–2.19 | <0.001 | 1.62 | 1.22–2.16 | <0.001 |
| Male | Ref | |||||
| Age, yrs | ||||||
| 0–50 | 1.08 | 0.57–2.03 | 0.803 | |||
| 51–60 | 0.83 | 0.58–1.17 | 0.298 | |||
| 61–70 | 0.80 | 0.62–1.03 | 0.089 | |||
| 71–80 | Ref | |||||
| 81–100 | 0.88 | 0.55–1.38 | 0.585 | |||
| BMI, kg/m 2 | ||||||
| <18.5 | 7.86 | 1.54–39.98 | 0.013 | 4.48 | 0.81–24.68 | 0.085 |
| 18.5–<25 | Ref | |||||
| 25–<30 | 1.40 | 1.00–1.95 | 0.048 | 1.35 | 0.95–1.91 | 0.089 |
| ≥30 | 2.47 | 1.76–3.47 | <0.001 | 2.04 | 1.42–2.93 | <0.001 |
| Diabetes mellitus | ||||||
| No | Ref | |||||
| Insulin-treated | 2.59 | 1.97–3.40 | <0.001 | 2.13 | 1.58–2.85 | <0.001 |
| Tablet-treated | 1.47 | 1.05–2.05 | 0.023 | 1.26 | 0.88–1.80 | 0.203 |
| Diet-treated | 1.03 | 0.50–2.12 | 0.933 | 0.90 | 0.42–1.96 | 0.808 |
| Haemoglobin, g/L | ||||||
| ≤120 | 1.43 | 1.05–1.95 | 0.023 | 1.10 | 0.77–1.55 | 0.592 |
| ≥121 | Ref | |||||
| Renal function | ||||||
| Normal function | Ref | |||||
| Mild reduction | 1.05 | 0.82–1.34 | 0.688 | |||
| Moderate reduction | 1.21 | 0.87–1.67 | 0.241 | |||
| Severe reduction | 0.44 | 0.10–1.89 | 0.270 | |||
| Renal failure | 1.12 | 0.24–5.26 | 0.879 | |||
| Smoking | ||||||
| Never smoker | Ref | |||||
| Ex-smoker a | 1.00 | 0.78–1.27 | 0.998 | 0.97 | 0.75–1.25 | 0.825 |
| Smoker | 1.30 | 0.90–1.88 | 0.148 | 1.12 | 0.76–1.66 | 0.554 |
| LVEF | ||||||
| >50% | Ref | |||||
| 41–50% | 1.25 | 0.91–1.70 | 0.155 | |||
| 31–40% | 1.40 | 0.94–2.09 | 0.098 | |||
| ≤30% | 1.68 | 1.03–2.75 | 0.036 | |||
| Anticoagulants | ||||||
| Heparin/LMWH | 1.15 | 0.88–1.51 | 0.280 | 1.15 | 0.86–1.52 | 0.331 |
| DOAC | 1.81 | 1.08–3.03 | 0.023 | 1.98 | 1.13–3.45 | 0.015 |
| No | Ref | |||||
| Peripheral vascular disease, n (%) | ||||||
| No | Ref | |||||
| Yes | 1.61 | 1.08–2.38 | 0.018 | 1.59 | 1.05–2.42 | 0.028 |
| Operative factors | ||||||
| Degree of urgency | ||||||
| Emergency (within 24 h) | 1.17 | 0.68-2.00 | 0.555 | |||
| Urgent | 1.13 | 0.90–1.44 | 0.278 | |||
| Elective | Ref | |||||
| Type of intervention | ||||||
| CABG | Ref | |||||
| CABG + valve | 1.18 | 0.89–1.56 | 0.234 | |||
| CABG + other surgery | 1.69 | 0.91–3.14 | 0.093 | |||
| Vein harvesting technique | ||||||
| No-touch technique | 1.16 | 0.89–1.51 | 0.247 | |||
| Conventional technique | Ref | |||||
| Number of anastomoses | ||||||
| 1–2 | 0.80 | 0.63–1.01 | 0.060 | 0.79 | 0.61–1.01 | 0.064 |
| 3–4 | Ref | |||||
| 5–6 | 1.75 | 1.04–2.98 | 0.035 | 1.24 | 0.68–2.26 | 0.466 |
| Operation time | ||||||
| <3 h | 0.65 | 0.46–0.91 | 0.013 | 0.76 | 0.54–1.08 | 0.138 |
| 3–5 h | Ref | |||||
| >5 h | 1.64 | 1.23–2.19 | <0.001 | 1.36 | 1.00–1.86 | 0.050 |
BMI = body mass index; CABG = coronary artery bypass grafting; CI = confidence interval; DOAC = direct oral anticoagulant; LMWH = low-molecular-weight heparin; LVEF = left ventricular ejection fraction; OR = odds ratio
Peripheral vascular disease = one or more of: claudication, carotid occlusion or 50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids, or amputation for arterial disease
aEx-smoker > 1 month
#The model is adjusted for sex, diabetes mellitus, BMI, haemoglobin, smoking, anticoagulants, peripheral vascular disease, number of anastomoses and operation time
Risk factors for leg wound infection requiring surgical revision
In the multivariable analysis, female sex [p = 0.007; OR 1.74 (95% CI 1.16–2.61)], insulin-treated DM [p<0.001; OR 2.95 (95% CI 1.95–4.46)], tablet-treated DM [p<0.001; OR 2.26 (95% CI 1.40–3.65)] and operation time >5 h [p = 0.009; OR 1.75 (95% CI 1.15–2.67)] were independent risk factors for surgical revision. For further details, see Table 4.
Table 4.
Multivariable logistic regression analysis of risk factors for leg wound infection (LWI) requiring surgical revision
| Unadjusted analysis | Adjusted analysis# | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Characteristics | ||||||
|
Sex Female Male Ref |
1.90 | 1.33–2.72 | <0.001 | 1.74 | 1.16–2.61 | 0.007 |
| Age, yrs | ||||||
| 0–50 | 0.92 | 0.32–2.62 | 0.878 | |||
| 51–60 | 0.77 | 0.43–1.37 | 0.390 | |||
| 61–70 | 1.24 | 0.86–1.80 | 0.238 | |||
| 71–80 | Ref | |||||
| 81–100 | 1.08 | 0.55–2.11 | 0.820 | |||
| Diabetes mellitus | ||||||
|
No Insulin-treated |
Ref 3.33 |
2.28–4.87 | <0.001 | 2.95 | 1.95–4.46 | <0.001 |
| Tablet-treated | 2.30 | 1.47–3.62 | <0.001 | 2.26 | 1.40–3.65 | <0.001 |
| Diet-treated | 0.64 | 0.15–2.69 | 0.547 | 0.69 | 0.16–2.94 | 0.625 |
| BMI, kg/m 2 | ||||||
| BMI <18.5 | NE | |||||
| BMI 18.5–<25 | Ref | |||||
| BMI 25–<30 | 1.83 | 1.09–3.07 | 0.020 | 1.83 | 1.06–3.17 | 0.028 |
| BMI ≥ 30 | 2.21 | 1.29–3.76 | 0.003 | 1.68 | 0.95–2.98 | 0.074 |
| Haemoglobin, g/L | ||||||
| ≤120 | 1.83 | 1.20–2.77 | 0.004 | 1.29 | 0.81–2.06 | 0.282 |
| ≥121 | Ref | |||||
| Renal function | ||||||
| Normal function | Ref | |||||
| Mild reduction | 1.11 | 0.77–1.60 | 0.576 | |||
| Moderate reduction | 1.31 | 0.82–2.09 | 0.254 | |||
| Severe reduction | 1.25 | 0.29–5.46 | 0.758 | |||
| Renal failure | 1.44 | 0.18–11.5 | 0.726 | |||
| Smoking | ||||||
| Ex-smokera | 0.90 | 0.62–1.30 | 0.584 | 0.88 | 0.60–1.29 | 0.526 |
| Smoker | 1.67 | 1.02–2.74 | 0.040 | 1.33 | 0.78–2.25 | 0.291 |
| Never smoker | Ref | |||||
| LVEF | ||||||
| >50% | Ref | |||||
| 41–50% | 1.29 | 0.82–2.02 | 0.264 | |||
| 31–40% | 1.73 | 1.01–2.98 | 0.046 | |||
| ≤30% | 1.74 | 0.87–3.45 | 0.113 | |||
| Anticoagulants | ||||||
| Heparin/LMWH | 0.93 | 0.61–1.4 | 0.739 | |||
| DOAC | 1.69 | 0.82–3.48 | 0.150 | |||
| No | Ref | |||||
| Peripheral vascular disease | ||||||
| Yes | 1.77 | 1.04–3.03 | 0.035 | 1.66 | 0.94–2.93 | 0.080 |
| No | Ref | |||||
| Operative factors | ||||||
| Degree of urgency | ||||||
| Emergency (within 24 h) | 1.61 | 0.80–3.21 | 0.175 | |||
| Urgent | 1.10 | 0.78–1.56 | 0.566 | |||
| Elective | Ref | |||||
| Type of intervention | ||||||
| CABG | Ref | |||||
| CABG + valve | 0.90 | 0.58–1.39 | 0.643 | |||
| CABG + other surgery | 1.89 | 0.83–4.26 | 0.124 | |||
| Vein harvesting technique | ||||||
| No-touch technique | 1.16 | 0.79–1.72 | 0.436 | |||
| Conventional technique | Ref | |||||
| Number of anastomoses | ||||||
| 1–2 | 0.88 | 0.62–1.24 | 0.470 | 0.96 | 0.66–1.38 | 0.832 |
| 3–4 | Ref | |||||
| 5–6 | 2.77 | 1.46–5.25 | 0.002 | 1.63 | 0.77–3.48 | 0.199 |
| Operation time | ||||||
| Operation time <3 h | 0.65 | 0.38–1.10 | 0.114 | 0.69 | 0.39–1.20 | 0.197 |
| Operation time 3–5 h | ||||||
| Operation time >5 h | 2.25 | 1.53–3.31 | <0.001 | 1.75 | 1.15–2.67 | 0.009 |
BMI = body mass index; CABG = coronary artery bypass grafting; CI = confidence interval; DOAC = direct oral anticoagulant; LMWH = low-molecular-weight heparin; LVEF = left ventricular ejection fraction; OR = odds ratio; NE = not estimatable
Peripheral vascular disease = one or more of: claudication, carotid occlusion or 50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids, or amputation for arterial disease
aEx-smoker > 1 month
#The model is adjusted for sex, diabetes mellitus, BMI, haemoglobin, smoking, peripheral vascular disease, number of anastomoses and operation time
Discussion
To date, only a few studies have investigated risk factors for LWI rate after CABG surgery [14]. We found female sex, medically treated DM, high BMI, DOAC treatment, and duration of surgery, as well as presence of peripheral vascular disease, to be independent predictive risk factors for LWI. The finding that female sex was an independent risk factor for LWI confirms earlier studies [14, 18, 21]. The underlying causes are unknown, but various assumptions and theories have been put forward as to why women have a higher incidence of LWI and other complications in vascular and cardiothoracic surgery. In other surgical procedures, men are more affected by SSI [19]. One theory, based on our own experiences, is that women in general have thinner skin on the legs than men, and therefore the skin is more fragile and difficult to heal. However, there are conflicting opinions about sex differences regarding the thickness of the epidermis. A recently published review article demonstrates weak evidence for this sex difference hypothesis [28]. Earlier research described the complexity of wound healing, pointing out that there is not one single explanation for all disparities [19, 29]. Wound healing is a complex physiological process. Disturbances in this process can lead to worse or delayed wound healing. Oestrogen deficiency has been shown to be detrimental for the wound healing process and postmenopausal women have an increased risk of complications as a result [30]. One hypothesis could be that the delayed wound healing process allows more time for bacteria to contaminate the wound. Oestrogen treatment could possibly reverse these effects of delayed wound healing [30]. Further, there is a theory that the different fat distribution in women and men affects both wound healing after surgery [31] and the outcome of the surgical procedure. Impaired peripheral circulation in women compared with men may be another explanation for women’s increased risk of LWI [32].
In our study, smoking was not found to be a significant risk factor for LWI. Previous research on smoking and its impact on SSIs after different types of surgery has shown conflicting results [3, 22, 23]. A large study including data on major general surgical procedures indicated that smoking increases the risk of postoperative SSI and wound disruption [22]. Regardless of sex, age, duration of surgery or anaesthetic technique, current smoking was associated with a higher risk of postoperative wound complications compared with not smoking [22]. By contrast, and in line with the results of our study, smoking has not been shown to be an independent risk factor in previous studies on LWI after CABG surgery [14, 33]. Despite this, one study pointed out that leg wound healing disturbances in the form of wound edge necrosis and dehiscence were significantly higher in smokers than in non-smokers; but there were no differences between these two groups for LWIs [3]. Based on the findings of our study, in addition to earlier research, smoking can hardly be considered an important risk factor for occurrence of LWI after CABG.
Limitations
Our study was a single-centre study, which could potentially be a limitation regarding the external validity. An earlier study including national data from all cardiothoracic surgery centres in Sweden indicated that local traditions may be among the most important factors determining which procedures are employed in the operating theatre [34]. Such traditions would likely affect the external factors (operation time, type of sutures, vein harvesting technique, suturing experience, etc.) in the vein harvesting procedure. Furthermore, there are several issues with the definition of “smokers” and “ex-smokers”, in terms of number of cigarettes per day and also of the smoke-free period for individuals to be termed “ex-smokers”. We did not have data on the smoke-free period. In other words, our ex-smokers could have stopped at any point between 1 month and 15 years previously.
The greatest strengths of this study are the high number of included patients and the quality of the registry.
Conclusion
In this study, female sex was an independent predictor for SSI at the harvest site after CABG surgery. The underlying mechanisms need to be further investigated. Previous or current smoking was not indicated as a risk factor for occurrence of LWI.
Acknowledgements
The authors would like to thank statistician Snehal Patil, for her invaluable help and statistical support to this study.
Author contributions
H.U. Conceptualization, Methodology, Formal analysis, Writing - Original Draft, Writing - Review & Editing, Visualization. M.H-N., K.F-B. and Ö.F. Conceptualization, Methodology, Formal analysis, Writing - Original Draft, Writing - Review & Editing, Supervision. All authors read and approved the final manuscript.
Funding
This study was supported by Örebro University Hospital research committee.
Open access funding provided by Örebro University.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was approved by the Swedish Ethical Review Authority (ID 2020–03103). Because of the retrospective nature of the study no informed consent was obtained.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Jessen ME. Efforts to improve bypass graft patency have not been in vein. J Thorac Cardiovasc Surg. 2015;150(4):889–90. doi: 10.1016/j.jtcvs.2015.07.099. [DOI] [PubMed] [Google Scholar]
- 2.Deb S, Singh SK, de Souza D, Chu MWA, Whitlock R, Meyer SR, et al. SUPERIOR SVG: no touch saphenous harvesting to improve patency following coronary bypass grafting (a multi-centre randomized control trial, NCT01047449) J Cardiothorac Surg. 2019;14(1):85. doi: 10.1186/s13019-019-0887-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Sharif-Kashani B, Shahabi P, Mandegar MH, Saliminejad L, Bikdeli B, Behzadnia N, et al. Smoking and wound complications after coronary artery bypass grafting. J Surg Res. 2016;200(2):743–8. doi: 10.1016/j.jss.2015.09.017. [DOI] [PubMed] [Google Scholar]
- 4.Meszaros K, Fuehrer U, Grogg S, Sodeck G, Czerny M, Marschall J, et al. Risk factors for Sternal wound infection after Open Heart Operations Vary according to type of operation. Ann Thorac Surg. 2016;101(4):1418–25. doi: 10.1016/j.athoracsur.2015.09.010. [DOI] [PubMed] [Google Scholar]
- 5.Gudbjartsson T, Jeppsson A, Sjogren J, Steingrimsson S, Geirsson A, Friberg O, et al. Sternal wound infections following open heart surgery - a review. Scand Cardiovasc J. 2016;50(5–6):341–8. doi: 10.1080/14017431.2016.1180427. [DOI] [PubMed] [Google Scholar]
- 6.Larsson H, Nyman MH, Brynhildsen KF. Patients’ experiences regarding severe leg wound infection associated with coronary artery bypass grafting: a qualitative study. J Vasc Nurs. 2022. [DOI] [PubMed]
- 7.Allegranzi B, Bischoff P, de Jonge S, Kubilay NZ, Zayed B, Gomes SM, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis. 2016;16(12):e276–87. doi: 10.1016/S1473-3099(16)30398-X. [DOI] [PubMed] [Google Scholar]
- 8.Riksföreningen för operationssjukvård & svensk sjuksköterskeförening. Kompetensbeskrivning för legitimerad sjuksköterska med specialistsjuksköterskeexamen inriktning mot operationssjukvård Stockholm: Riksföreningen för operationssjukvård & svensk sjuksköterskeförening; 2011 [cited 2019 May 22]. http://www.rfop.se/media/1254/kompbeskrivning.pdf.
- 9.Kelvered M, Ohlen J, Gustafsson BA. Operating theatre nurses’ experience of patient-related, intraoperative nursing care. Scand J Caring Sci. 2012;26(3):449–57. doi: 10.1111/j.1471-6712.2011.00947.x. [DOI] [PubMed] [Google Scholar]
- 10.Caliskan E, de Souza DR, Boning A, Liakopoulos OJ, Choi YH, Pepper J, et al. Saphenous vein grafts in contemporary coronary artery bypass graft surgery. Nat Rev Cardiol. 2020;17(3):155–69. doi: 10.1038/s41569-019-0249-3. [DOI] [PubMed] [Google Scholar]
- 11.Filip T, Schrother F, Haase R, Rudolph N, Claus T, Albes JM. Patient satisfaction and clinical complications after Endoscopic or Surgical Saphenous Vein Harvesting. Thorac Cardiovasc Surg. 2020;68(8):700–5. doi: 10.1055/s-0039-1683901. [DOI] [PubMed] [Google Scholar]
- 12.Tian M, Wang X, Sun H, Feng W, Song Y, Lu F, et al. No-Touch Versus Conventional Vein Harvesting techniques at 12 months after coronary artery bypass grafting surgery: Multicenter Randomized, Controlled Trial. Circulation. 2021;144(14):1120–9. doi: 10.1161/CIRCULATIONAHA.121.055525. [DOI] [PubMed] [Google Scholar]
- 13.Sharma M, Fakih MG, Berriel-Cass D, Meisner S, Saravolatz L, Khatib R. Harvest surgical site infection following coronary artery bypass grafting: risk factors, microbiology, and outcomes. Am J Infect Control. 2009;37(8):653–7. doi: 10.1016/j.ajic.2008.12.012. [DOI] [PubMed] [Google Scholar]
- 14.Hassoun-Kheir N, Hasid I, Bozhko M, Shaban Z, Glam R, Hussein K, et al. Risk factors for limb surgical site infection following coronary artery bypass graft using open great saphenous vein harvesting: a retrospective cohort study. Interact Cardiovasc Thorac Surg. 2018;27(4):530–5. doi: 10.1093/icvts/ivy137. [DOI] [PubMed] [Google Scholar]
- 15.Seim BE, Tonnessen T, Woldbaek PR. Triclosan-coated sutures do not reduce leg wound infections after coronary artery bypass grafting. Interact Cardiovasc Thorac Surg. 2012;15(3):411–5. doi: 10.1093/icvts/ivs266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Thimour-Bergstrom L, Roman-Emanuel C, Schersten H, Friberg O, Gudbjartsson T, Jeppsson A. Triclosan-coated sutures reduce surgical site infection after open vein harvesting in coronary artery bypass grafting patients: a randomized controlled trial. Eur J Cardiothorac Surg. 2013;44(5):931–8. doi: 10.1093/ejcts/ezt063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Stenvik M, Tjomsland O, Lien S, Gunnes S, Kirkeby-Garstad I, Astudillo R. Effect of subcutaneous suture line and surgical technique on wound infection after saphenectomy in coronary artery bypass grafting: a prospective randomised study. Scand Cardiovasc J. 2006;40(4):234–7. doi: 10.1080/14017430600812813. [DOI] [PubMed] [Google Scholar]
- 18.Olsen MA, Sundt TM, Lawton JS, Damiano RJ, Jr, Hopkins-Broyles D, Lock-Buckley P, et al. Risk factors for leg harvest surgical site infections after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg. 2003;126(4):992–9. doi: 10.1016/S0022-5223(03)00200-9. [DOI] [PubMed] [Google Scholar]
- 19.Aghdassi SJS, Schroder C, Gastmeier P. Gender-related risk factors for surgical site infections. Results from 10 years of surveillance in Germany. Antimicrob Resist Infect Control. 2019;8:95. doi: 10.1186/s13756-019-0547-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Alghamdi BA, Alharthi RA, AlShaikh BA, Alosaimi MA, Alghamdi AY, Yusnoraini N, et al. Risk factors for post-cardiac surgery infections. Cureus. 2022;14(11):e31198. doi: 10.7759/cureus.31198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Siddiqi S. Saphenous vein harvest wound complications: risk factors, identification, prevention, and management. Chronic Wound Care Manage Res. 2016;3:147–56. doi: 10.2147/CWCMR.S82601. [DOI] [Google Scholar]
- 22.Fan Chiang YH, Lee YW, Lam F, Liao CC, Chang CC, Lin CS. Smoking increases the risk of postoperative wound complications: a propensity score-matched cohort study. Int Wound J. 2023;20(2):391–402. doi: 10.1111/iwj.13887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Schmid M, Sood A, Campbell L, Kapoor V, Dalela D, Klett DE, et al. Impact of smoking on perioperative outcomes after major surgery. Am J Surg. 2015;210(2):221–9. doi: 10.1016/j.amjsurg.2014.12.045. [DOI] [PubMed] [Google Scholar]
- 24.Souza D. A new no-touch preparation technique. Technical notes. Scand J Thorac Cardiovasc Surg. 1996;30(1):41–4. doi: 10.3109/14017439609107239. [DOI] [PubMed] [Google Scholar]
- 25.Carath – ett verksamhetsinitierat kvalitetsregister och processtöd. Ger toraxkirurgin bra möjlighet att följa vårdprocessen Läkartidningen: Läkartidningen Förlag AB; 2011 [cited 2023 14 February]. https://lakartidningen.se/klinik-och-vetenskap-1/2011/06/carath-ett-verksamhetsinitierat-kvalitetsregister-och-processtod/. [PubMed]
- 26.National Healthcare Safety Network. Prevention. CfDCa. Surgical site infection (SSI) event. 2023. https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. [cited 2023 27 October].
- 27.Wilson APTT, Sturridge MF, Grüneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet. 1986;1:311–3. doi: 10.1016/S0140-6736(86)90838-X. [DOI] [PubMed] [Google Scholar]
- 28.Lintzeri DA, Karimian N, Blume-Peytavi U, Kottner J. Epidermal thickness in healthy humans: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2022;36(8):1191–200. doi: 10.1111/jdv.18123. [DOI] [PubMed] [Google Scholar]
- 29.Nurkkala J, Kauko A, Palmu J, Aittokallio J, Niiranen T. Sex differences in coronary artery bypass grafting-related morbidity and mortality. Front Cardiovasc Med. 2022;9:1021363. doi: 10.3389/fcvm.2022.1021363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Horng HC, Chang WH, Yeh CC, Huang BS, Chang CP, Chen YJ et al. Estrogen effects on Wound Healing. Int J Mol Sci. 2017;18(11). [DOI] [PMC free article] [PubMed]
- 31.Arnaoutakis DJ, Scully RE, Sharma G, Shah SK, Ozaki CK, Belkin M, et al. Impact of body mass index and gender on wound complications after lower extremity arterial surgery. J Vasc Surg. 2017;65(6):1713–e81. doi: 10.1016/j.jvs.2016.12.116. [DOI] [PubMed] [Google Scholar]
- 32.Friedman ND, Bull PLRAL, Richards MJ, Kelly H. Validation of coronary artery bypass graft surgical site infection surveillance data from a statewide surveillance system in Australia. Infect Control Hosp Epidemiol. 2007;28:812–7. doi: 10.1086/518455. [DOI] [PubMed] [Google Scholar]
- 33.Swenne CL, Borowiec J, Carlsson M, Lindholm C. Prediction of and risk factors for surgical wound infection in the saphenous vein harvesting leg in patients undergoing coronary artery bypass. Thorac Cardiovasc Surg. 2006;54(5):300–6. doi: 10.1055/s-2006-924093. [DOI] [PubMed] [Google Scholar]
- 34.Larsson H, Halleberg-Nyman M, Friberg O, Falk-Brynhildsen K. Perioperative routines and surgical techniques for saphenous vein harvesting in CABG surgery: a national cross-sectional study in Sweden. J Cardiothorac Surg. 2020;15(1):5. doi: 10.1186/s13019-020-1056-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.