Background/Aims : Inguinal incisions are a common route of access in vascular surgery. Due to anatomical challenges and a diverse bacterial flora in this area, surgical site infections (SSI) represent a common, debilitating and sometimes life-threatening complication. The INVIPS-Trial evaluates the role of Negative Pressure Wound Therapy (NPWT) on closed inguinal incisions in elective vascular surgery to prevent SSI and other wound complications . Methods: This randomized controlled trial (RCT) registered at ClinicalTrials.gov (Identifier: NCT01913132) compares the effects of a NPWT dressing (PICO, Smith & Nephew, UK) and the center’s standard wound dressing (Vitri Pad, ViTri Medical, Sweden) on postoperative wound complications, especially SSI. The study includes two distinct vascular procedures with different SSI risk profiles: endovascular aortic repair (EVAR) and open surgical approaches involving the common femoral artery (OPEN). Results: Four hundred ninety-five groin incisions in both treatment arms are anticipated to be included in the EVAR group and 147 inguinal incisions in both treatment arms in the OPEN group. Since a large percentage of inguinal vascular procedures in both groups but especially in the EVAR group are performed bilaterally, many patients can serve as their own control by randomly receiving NPWT on one and the standard dressing on the contralateral inguinal incision. Conclusions: This ongoing RCT attempts to elucidate the potential benefit of NPWT on closed inguinal incisions after different vascular procedures. Outcome and conclusions of this trial could have implications on postoperative wound care of patients in both vascular surgery and other surgical specialties.
Vascular surgery today relies heavily on inguinal access for both endovascular and open surgical procedures. Unfortunately, the inguinal region contains a high concentration of virulent bacteria [
Negative pressure wound therapy (NPWT) has been established as an alternative treatment for chronic and infected wounds. Its application on closed, clean incisions, also called ‘incisional NPWT’ (INPWT), on the other hand is a more recent development. In the latest Cochrane review [
Although the exact mechanism of action of INPWT and how it might be beneficial in the wound healing process has not yet been established, some works attempting to elucidate different factors are emerging. It has been demonstrated that INPWT decreases hematoma and seroma formation not only by removal of wound fluid across the suture line but also by locally enhancing the endogenous draining capacity of the lymphatic system [
Wilkes et al. conducted bench-top and computer modelling experiments to evaluate a INPWT device (PrevenaTM, KCI, San Antonio, TX) and showed less biomechanical stress around skin and subcutaneous suture lines. [
The relatively high frequency of SSI in the groin in combination with a well-established follow-up program at this center, represented good conditions to study interventions aimed at decreasing the inguinal SSI rate. Since a pharmacological approach with a change of the center’s antibiotic prophylaxis failed to improve SSI rates [
Single center randomized controlled clinical trial.
The study was initiated to determine whether a prophylactic negative pressure wound therapy pad (PICOTM) applied after vascular surgical procedures with inguinal incisions could reduce the surgical site infection rate as well as the frequency of other wound complications such as delayed healing, lymphorrhea, seroma and
hematoma when compared to the standard wound dressing (Vitri Pad, ViTri Medical, Sweden).
The primary endpoint is the development of SSI and other wound complications within the first 90 days postoperatively. Secondary endpoints are occurrence of SSI and other wound complications up to one year postoperatively as well as mortality in the different treatment groups.
The Vascular Center, Malmö-Lund, Skåne University Hospital, is a tertiary referral center for the southernmost part of Sweden with a primary catchment population of 800,000 inhabitants. The center possesses a well-estab- lished postoperative follow-up program for all patients undergoing vascular surgery.
All adult patients without ongoing infection undergoing elective vascular procedures with inguinal incisions are eligible to participate.
Patients scheduled for vascular surgical procedures with inguinal incisions are provided with written information before undergoing the admission procedure which takes place one to two weeks prior to scheduled surgery. During the admission process, the background and aim of the study are discussed with eligible patients, informed consent obtained and the randomization conducted by outpatient clinic nurses. In this study we apply simple randomization using an opaque randomization envelope containing equal numbers of “PICO” and “standard” notes. In bilateral groin incisions, the draw from the envelope dictates the wound dressing selection in the right inguinal incision and the contralateral incision is automatically assigned the alternate dressing. Randomization outcome and consent form are documented in the patient’s records.
The study has been approved by the regional ethical review board (Dnr 2013/322) and has been registered at ClinicalTrials.gov (Identifier: NCT01913132).
There is no difference between the surgical procedures and perioperative care between the treatment and control groups. At the end of the procedure, wounds are sutured intracutanously in case of horizontal incisions whereas vertical incisions are closed according to surgeon’s preference. Steri-StripsTM (3M, St Paul, Minnesota) are often applied in case of intracutanous sutures. PICOTM is a negative pressure system employing −80 mm∙Hg continuous suction generated through a canister-free portable pump. The PICOTM dressing eliminates fluid predominantly by evaporative loss. It is directly applied onto the closed incisions and, according to the manufacturer’s recommendation, left in place for seven days, after which it stops working and can be removed by the patients themselves or nurses at the center’s outpatient clinic.
Vitri Pad is the institution’s standard wound dressing consisting of a sterile water-proof bandage with absorbent pad. Consistent with the recommendation of the Centers for Disease Control and Prevention (CDC) [
All data is collected using SPSS for Mac, version 22.0 (SPSS Inc., Chicago, Illinois, USA). The data is collected per groin incision as opposed to per patient and stems from the patient’s electronic records, the regional microbiological laboratory, the central transfusion registry as well as content from conducted phone interviews after three and twelve months postoperatively. Visits at the outpatient clinic are scheduled in line with the clinic’s and the Swedish vascular registry’s guidelines at one and twelve months postoperatively (
Data collected preoperatively are identification number, age at operation, date of procedure, indication for procedure, gender, height (in cm), weight (in kg), body mass index (BMI, in kg/m2), ischemic heart disease (yes/no), atrial fibrillation (yes/no), arterial hypertension (yes/no), diabetes mellitus (yes/no), type of diabetes mellitus (regulated with diet only, oral anti-diabetic drugs, insulin-dependent), current smoker (yes/no), ex-smoker (yes/no) [according to the Centers for Disease Control and Prevention smoking status description: ex-smoker ≥ 100 cigarettes during lifetime [
Preoperative antibiotic treatment excluding antibiotic prophylaxis (yes/no), preoperative antibiotic prophylaxis
Variables | Preoperative | Perioperative | 1 month | 3 months | 12 months |
---|---|---|---|---|---|
Identification number | x | ||||
Age at operation | x | ||||
Date of operation | x | ||||
Indication for procedure | x | ||||
Gender | x | ||||
Height | x | ||||
Weight | x | ||||
Body mass index | x | ||||
Comorbidities | x | ||||
Past surgical history | x | ||||
Smoking status | x | ||||
Anticoagulation | x | ||||
ASA score | x | ||||
Current medication | x | ||||
Planned procedure | x | ||||
Randomization | x | ||||
Antibiotic treatment pre/postoperative | x | ||||
Antibiotic prophylaxis received | x | ||||
Blood chemistry | x | ||||
Type of anesthesia | x | ||||
Type of incision | x | ||||
Wound products used | x | ||||
Duration of procedure | x | ||||
Wound dressing received | x | ||||
Blood products transfused | x | ||||
Readmission 30 days postoperatively | x | ||||
Wound complications | x | x | x | ||
Pseudoaneurysm on CT | x | ||||
Reoperation | x | x | x | ||
SSI | x | x | x | ||
Phone interview | x | x | |||
Wound culture obtained | x | x | |||
Mortality | x |
ASA score = American Society of Anesthesiologists score, SSI = Surgical site infection, CT = Computed Tomography.
received (yes/no), preoperative anemia (yes/no), preoperative blood glucose concentration (mmol/L), preoperative albumin concentration (g/L), preoperative estimated glomerular filtration rate (ml/min), form of anesthesia (general/regional/local), groin incision performed (yes/no), bilateral incision (yes/no), vertical incision (yes/no), transverse incision (yes/no), use of wound products such as Floseal® (yes/no), Hemopatch® (yes/no), Tachosil® (yes/no) (all Baxter Healthcare Corporation, Deerfield, IL, USA), Collatamp® (EUSA Pharma, Oxford, UK) (yes/no), stent graft used (yes/no), synthetic graft used (yes/no), bovine pericardial patch used (yes/no), any patch used (yes/no), any foreign material applied in wound (yes/no), vein graft/patch (yes/no), arterial graft (yes/no), closure technique in case of EVAR (cutdown/fascia suture), duration of procedure (min), bypass (yes/no), wound dressing received (PICO/standard), postoperative antibiotic therapy (yes/no), number of transfused units of packed red blood cells, plasma and thrombocyte concentrates, postoperative treatment at intensive care unit (yes/no), inpatient length of stay (days).
Readmission within 30 days postoperatively (yes/no), surgical site infection (SSI) within 30 days (yes/no), wound culture obtained within first 3 months postoperatively (yes/no), pseudoaneurysm formation on computed tomography follow-up 30 days (yes/no), reoperation 30 days (yes/no), sought medical attention because of groin problem within 90 days (yes/no), reoperation 90 days (yes/no), SSI 90 days (yes/no), reoperation 1 year (yes/no), SSI 1 year (yes/no), wound cultures within 1 year (yes/no), 1 year mortality (yes/no), mortality due to groin infection (yes/no), type of bacterial isolate, SSI grading according to Szilagyi classification, C-reactive protein concentration at infection diagnosis (mg/L), presenting symptoms, surgical revision (yes/no), negative pressure wound therapy after surgical revision (yes/no), sepsis (yes/no), bleeding (yes/no), wound dehiscence (yes/no), seroma (yes/no), hematoma (yes/no), lymphorrhea (yes/no), amputation within 1 year (yes/no).
The diagnosis SSI is made according to the 1999 diagnostic criteria defined by the Centers for Disease Control and Prevention, USA. [
The primary analysis principle applied will be intention-to-treat. The only condition for initial inclusion is application of the correct wound dressing at the end of the procedure. Exclusion criteria are death or re-operation before reaching the primary or secondary endpoints. As a safety aspect, we will conduct a mortality analysis in the treatment groups.
We defined two main groups of vascular surgical procedures with groin incisions that carry different infection risk profiles. Infection rates and other statistics stem from a review of data collected during four consecutive months in 2013 after changing the center’s antibiotic prophylaxis from cloxacillin administered intravenously at three time points to trimethoprim/sulfamethoxazole administered orally once in the morning of the operation. [
In about 80% of cases, endovascular aortic repair (EVAR) requires a bilateral inguinal approach whereby the transverse incisions are conducted at the end of the procedure and merely serve to repair the femoral artery defect created by the introduction of endovascular material. This type of procedure carries an infection risk of about 4.4% at this center. Mortality in this group was 4.4% at three and 6.7% at twelve months.
Open inguinal procedures (OPEN) such as thrombendarterectomies (TEA) and arterial bypass operations with vertical incisions involving the femoral artery in the groin have a much higher infection rate of about 30%. Bilateral inguinal approaches were performed in 24% in this procedure category. Three and twelve-month mortality was 0%.
The different characteristics of these endovascular and open procedures have to be taken into account when conducting sample size determination and statistical analysis planning.
We used G*Power 3.1 [
EVAR
Previous data indicated an inguinal SSI rate of 4.4% when using the standard dressing. For bilateral cases, we estimated the proportion of discordant pairs to be 5%. Assuming all cases are either unilateral or bilateral, and a reduction in SSI rate from 4.4% to 1.0%, yields n1 = 750, and n2 = 340, respectively. Among all EVAR-cases, 20% are assumed to be unilateral (i.e. p1 = 0.2):
n = p1 × n1 + (1 − p1) × n2. n = 0.2 × 750 + 0.8 × 340 = 422
Taking into account the previously identified 12-month mortality of 6.7%, yields a mortality-corrected sample size of n = 452 (422/(1 − 0.067)).
In an attempt to adjust for other types of “loss to follow-up” such as missing data and re-operations on the respective side, we added an additional 10% (45 cases) resulting in a total sample size of 497.
OPEN
Previous data indicated an inguinal SSI rate of 30% when using the standard dressing. Assuming all cases are either unilateral or bilateral, and a reduction in SSI rate from 30% to 10% with a proportion of discordant pairs of 25% in bilateral cases yields n1 = 138 and n2 = 120, respectively. Among all Open-cases, 76% are assumed to be unilateral (i.e. p1 = 0.76):
n = p1 × n1 + (1 − p1) × n2. n = 0.76 × 138 + 0.24 × 122 = 134
The 12-month mortality in this group was 0%. To adjust for other types of “loss to follow-up”, we added an additional 10% (13 cases) resulting in a total sample size of 147.
EVAR | OPEN | ||||
---|---|---|---|---|---|
Bilateral | Unilateral | Bilateral | Unilateral | ||
80% | 20% | 24% | 76% | ||
Procedure characteristics1 | SSI rate | 4.4% | 30 % | ||
Orientation of incision | Mostly horizontal | mostly vertical | |||
Median operating time (Range) | 214 (536) | 178 (321) | |||
Surgical wound exposure | at end of procedure | During entire procedure | |||
1-year mortality | 6.7% | 0 % |
Power calculation2 | n assuming only bi/unilaterality | 340 750 | 120 138 |
---|---|---|---|
n as weighted average based on laterality proportion | 422 | 134 | |
n including estimated loss to follow-up due to mortality | 452 | 134 | |
n + 10% for other loss to follow-up | 497 | 147 |
1Based on earlier data collection, 2n = required number of groin incisions, EVAR = Endovascular aortic repair, SSI = Surgical site infection.
We will conduct a descriptive analysis of background data such as comorbidities, procedure-related risk factors and different operation techniques. Important differences will be accounted for in a sensitivity analysis.
The study involves both uni-and bilateral inguinal incisions. Unilateral incisions are treated with either standard or NPWT dressing according to the randomization result and analyzed with Fisher’s exact test for independent samples. In case of bilateral incisions, one is randomly designated to either standard or NPWT treatment group, the other by default to the alternate treatment group. It is important to recognize that the outcomes in the treatment groups in this scenario will most likely not be independent of one another and will therefore be analyzed with McNemar’s test for paired data. The advantage of the bilateral design is that all patient-related risk factors, such as comorbidities and hygiene factors, are exactly the same in both treatment groups and patients serve as their own control. The bilateral design thus decreases the required group size at a fixed level of statistical power, as can be seen from the assessments of n1 and n2 above. The obtained p-values from the uni- and bilateral analyses will subsequently be combined to an overall p-value using Fisher’s method of combining p-values [
Vascular surgery with inguinal incisions carries a significant risk for surgical site infections. This is true for endovascular but even more so for open procedures.
INPWT could be an important tool in the postoperative care of these anatomically and microbiologically challenging wounds. Although various mechanisms of action of this technique have been described, a central effect of INPWT in this anatomical location could simply be to provide a protective cover to the healing wound. The constant suction that is being applied by the INPWT-system provides a highly-adaptive surface that prevents kinking and a subsequent breach of the sterile barrier resulting in bacterial contamination during movements of the hip joint.
In this study, only elective procedures were included. That is partially because we observed much higher SSI rates among elective cases but also due to the fact that only elective patients are able to follow hygiene and other routines thereby limiting the amount of uncontrollable variables. In addition, there are some obvious ethical concerns linked to the inclusion of acute patients that could be avoided.
A potential limitation of this study could be that the randomization takes place before the operation, not at its end. One might argue that this could create bias since the surgeon in charge, theoretically, could be aware of the respective randomization outcome before conducting the operation. In addition, only inguinal sites that in fact are subject to surgical incisions would be randomized if randomized at the end of procedure. In the current setup, a few randomized treatment outcome results needs to be excluded postoperatively if percutaneous vascular closure devices are used instead of incision followed by fascial closure or open vascular repair or if no incision is performed on one side.
In our view, the most compelling argument against intraoperative randomization was that the large number of rotating on-duty operating room personnel would make it very difficult to achieve the necessary sense of awareness for the study and to thereby limit the amount of missed randomizations. In addition, the logistics in the operating room are not such that randomization envelopes could easily be accessible.
When conducting the three-month survey of vascular procedures with groin incisions at this center in 2013, it was noteworthy that open procedures carried a 0% one-year mortality. Because this was most likely just by chance, one could argue that the estimated sample size for the OPEN arm of the INVIPS-Trial should be corrected upwards to account for a likely higher mortality. We did however feel that a correction not based on our own data would somehow be arbitrary.
In a retrospective comparative cohort analysis, highly prone to the Hawthorne effect [
The research group has received an unrestricted unconditional research grant 15,550 USD and donation of 100 PICO dressing kits from Smith and Nephew in 2013. We have also received 12,900 USD from the Swedish SUS Stiftelser och Fonder: Grant-number 95407.
The trial is registered at ClinicalTrials.gov (Identifier: NCT01913132).
Julien Hasselmann,Tobias Kühme,Jonas Björk,Stefan Acosta, (2015) Incisional Negative Pressure Wound Therapy in the Prevention of Surgical Site Infection after Vascular Surgery with Inguinal Incisions: Rationale and Design of a Randomized Controlled Trial (INVIPS-Trial). Surgical Science,06,562-571. doi: 10.4236/ss.2015.612080