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Surgical site infections (SSIs) are common, costly, and associated with increased morbidity and potential mortality after lower limb revascularization surgery (ie, arterial bypass, endarterectomy, and patch angioplasty). Identifying evidence-informed risk factors for SSI in patients undergoing these surgeries is therefore important.
The aim of this study is to conduct a systematic review and meta-analysis of prognostic studies to identify, synthesize, and determine the certainty in the cumulative evidence associated with reported risk factors for early and delayed SSI after lower limb revascularization surgery in adults with peripheral artery disease.
We will search MEDLINE, Embase, the seven databases in Evidence-Based Medicine Reviews, review articles identified during the search, and included article bibliographies. We will include studies of adults (aged ≥18 years) with peripheral artery disease that report odds ratios, risk ratios, or hazard ratios adjusted for the presence of other risk factors or confounding variables and relating the potential risk factor of interest to the development of SSI after lower limb revascularization surgery. We will exclude studies that did not adjust for confounding, exclusively examined certain high-risk patient cohorts, or included >20% of patients who underwent surgery for indications other than peripheral artery disease. The primary outcomes will be early (in-hospital or ≤30 days) SSI and Szilagyi grade I (cellulitis involving the wound), grade II (infection involving subcutaneous tissue), and grade III (infection involving the vascular graft) SSI. Two investigators will independently extract data and evaluate the study risk of bias using the Quality in Prognosis Studies tool. Adjusted risk factor estimates with similar definitions will be pooled using DerSimonian and Laird random-effects models. Heterogeneity will be explored using stratified meta-analyses and meta-regression. Finally, we will use the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to determine certainty in the estimates of association between reported risk factors and the development of SSI.
The protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews). We will execute the peer-reviewed search strategy on June 30, 2021, and then complete the review of titles and abstracts and full-text articles by July 30, 2021, and September 15, 2021, respectively. We will complete the full-text study data extraction and risk of bias assessment by November 15, 2021. We anticipate that we will be able to submit the manuscript for peer review by January 30, 2022.
This study will identify, synthesize, and determine the certainty in the cumulative evidence associated with risk factors for early and delayed SSI after lower limb revascularization surgery in patients with peripheral artery disease. The results will be used to inform practice, clinical practice statements and guidelines, and subsequent research.
PROSPERO International Prospective Register of Systematic Reviews CRD42021242557; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242557
PRR1-10.2196/28759
Lower limb revascularization surgeries (ie, arterial bypass, endarterectomy, and patch angioplasty) are costly, high-risk procedures commonly performed in North America and internationally [
Surgical site infections (SSIs) are common and costly; they are also associated with a significantly increased risk of morbidity, limb loss, and potential mortality after lower limb revascularization surgery [
Identifying valid, evidence-informed risk factors for SSI after lower limb revascularization surgery is important to assist in deciding which patients may benefit most from interventions designed to prevent them. It may also help in determining the benefit-to-risk profile of performing open over endovascular revascularization in patients who are candidates for both. However, although many studies examining potential risk factors for SSI after lower limb revascularization surgery have been published, some are difficult to access because their titles may not indicate that they examined risk factors for SSI. They are also collectively difficult to interpret, as some have included potentially overlapping data and many are limited by between-study clinical heterogeneity. This heterogeneity includes the recruitment of patients with different indications for surgery (eg, intermittent vasculogenic claudication, chronic limb-threatening ischemia, or even aneurysms and vascular trauma [
We aim to conduct a systematic review and meta-analysis of prognostic studies to identify, synthesize, and determine the certainty in the cumulative evidence associated with reported risk factors for early and delayed SSI after lower limb revascularization surgery in adults with peripheral artery disease. We will also determine whether the strength of association for individual risk factors varies according to different clinical or methodological study characteristics.
We prespecified our methods according to the PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-Analyses) statement [
We formulated the study-focused clinical question using the PICOTS (Population, Index Prognostic Factor, Comparison of Prognostic Factors, Outcome, Timing, and Setting) framework for posing clinical questions for systematic reviews of prognostic factor studies [
P: in adults (aged ≥18 years) with peripheral artery disease who underwent lower limb revascularization surgery
I: which factors increase the risk of SSI or Szilagyi grade I (cellulitis involving the wound), grade II (infection involving subcutaneous tissue), or grade III (infection involving the vascular graft) SSI
C: over and above other comparator risk and confounding factors for predicting SSI
OTS: in-hospital or within ≤30 days or longer than 30 days after lower limb revascularization surgery?
We will search MEDLINE; MEDLINE Epub Ahead of Print, In-Process, and Other Nonindexed Citations; Embase; and the databases contained within Evidence-Based Medicine Reviews (American College of Physicians Journal Club; the Cochrane Central Register of Controlled Trials, the Database of Systematic Reviews, and the Methodology Register Database; the Database of Abstracts of Reviews of Effects; the Health Technology Assessment Database; and the National Health Service Economic Evaluation Database) from their first available dates without restrictions. To identify additional citations, we will also use the PubMed
A vascular and endovascular surgeon and epidemiologist with a PhD training in information science and evidence synthesis methods created the initial MEDLINE search strategy, which was refined after input from a medical librarian and information specialist and by adding additional thesaurus or indexing terms when new and relevant citations were located during iterative search strategies. Using a combination of Medical Subject Heading/Emtree terms and keywords, we constructed search filters covering the themes
Pre–Peer Review of Electronic Search Strategies database search strategies.
Search theme | Search terms | |||
|
Ovid MEDLINE, PubMed, and Evidence-Based Medicine Reviews | Ovid Embase | ||
|
Exploded MeSHa terms | Title and subject keywords | Exploded Emtree terms | Title and subject keywords |
Lower extremity revascularization surgery | Arterial occlusive disease/surgery OR endarterectomy OR ischemia/surgery OR lower extremity/surgery OR peripheral arterial disease/surgery OR peripheral vascular diseases/surgery OR vascular surgical procedures | ((iliofemoral OR femoral OR femoral artery*) adj3 (endarterectom* OR patch* OR repair*)) OR ((aortofemoral OR aortobifemoral OR femoral-distal OR femoral distal OR femoral-popliteal OR femoral popliteal OR femoral-tibial OR femoral tibial OR infrageniculate OR suprageniculate OR infrainguinal OR lower extremity OR lower limb OR peripheral vascular) adj3 (arterial surg* OR arterial bypass* OR bypass* OR bypass graft* OR bypass surg* OR graft* OR intervention* OR revascularization* OR revascularization procedure* OR vascular bypass* OR vascular bypass surg* OR vascular graft* OR vein graft* OR prosthetic graft*)) | Artery bypass OR blood vessel graft OR bypass surgery OR critical limb ischemia/surgery OR endarterectomy OR limb ischemia/surgery OR peripheral artery occlusive disease/surgery OR prosthetic vascular graft OR vascular surgery | ((iliofemoral OR femoral OR femoral artery*) adj3 (endarterectom* OR patch* OR repair*)) OR ((aortofemoral OR aortobifemoral OR femoral-distal OR femoral distal OR femoral-popliteal OR femoral popliteal OR femoral-tibial OR femoral tibial OR infrageniculate OR suprageniculate OR infrainguinal OR lower extremity OR lower limb OR peripheral vascular) adj3 (arterial surg* OR arterial bypass* OR bypass* OR bypass graft* OR bypass surg* OR graft* OR intervention* OR revascularization* OR revascularization procedure* OR vascular bypass* OR vascular bypass surg* OR vascular graft* OR vein graft* OR prosthetic graft*)) |
Infection | Infections OR surgical wound infection | infection* OR surgical site infection* OR surgical wound infection* OR wound infection* | Surgical infection OR wound infection | infection* OR surgical site infection* OR surgical wound infection* OR wound infection* |
aMeSH: Medical Subject Heading.
The titles and abstracts of citations identified during the search will be imported into EndNote X9 reference management software (Clarivate, Thomson Reuters Corporation). This software will be used to remove identical duplicate citations before exporting them into Distiller SR (Evidence Reviews). Two investigators will then independently review the titles and abstracts of the articles identified by the search and select any article deemed potentially relevant by either investigator for full-text review. Finally, 2 investigators will review the full text of all potentially relevant citations and select studies for inclusion in the systematic review. Disagreements regarding study inclusion will be resolved via consensus or arbitration by a third investigator (
Peripheral artery disease will be defined as intermittent vasculogenic claudication or chronic limb-threatening ischemia (ie, ischemic rest pain confirmed by vascular hemodynamic studies, lower limb ulceration, or gangrene) [
Population: The study included adults (aged ≥18 years) with peripheral artery disease who underwent lower limb revascularization surgery.
Index and comparison prognostic factors: The study evaluated the prognostic value of a potential risk factor over and above (ie, adjusted for or independent of) other existing or comparator risk and confounding factors for predicting postoperative surgical site infection (SSI).
Outcome, timing, and setting: The study reported odds ratios, risk ratios, or hazard ratios (and surrounding SE or 95% CIs) adjusted for the presence of other risk factors or confounding variables and relating the potential risk factors of interest to the development of SSI in patients undergoing lower limb revascularization surgery [
Study design: Observational (ie, cohort or case-control) studies or secondary analyses of randomized controlled trial data.
The primary outcomes will be early (in-hospital or ≤30 days) SSI and early Szilagyi grade I (cellulitis involving the wound), grade II (infection involving subcutaneous tissue), and grade III (infection involving the vascular graft) SSI. Secondary outcomes will be longer-term (>30 days) SSI or Szilagyi grade I (cellulitis involving the wound), grade II (infection involving subcutaneous tissue), or grade III (infection involving the vascular graft) SSI [
Two investigators will independently extract data in duplicate using a predesigned electronic data extraction spreadsheet piloted on a representative sample of five included studies. We will extract the following data from the included studies: (1) design, data source, and setting of the study; (2) patient recruitment period; (3) patient and procedural characteristics, including the number and types of procedures performed, the proportion of patients who had a groin incision (vertical or oblique), and the indication for the procedure (ie, intermittent vasculogenic claudication or chronic limb-threatening ischemia); (4) reported potential risk factors for SSI; (5) reported adjusted associations between the reported risk factors and the development of SSI and Szilagyi grade I, grade II, and grade III SSI after lower limb revascularization surgery (or different severities of SSI defined using different classification systems); (6) other prognostic or confounding factors that were adjusted for when evaluating associations between potential risk factors and SSI (crude or unadjusted associations were not extracted); and (7) whether the authors adjusted for a minimum confounder set in their analyses. This minimum confounder set was defined based on a narrative review of published studies and will include surgical urgency, age, sex, obesity, diabetes, the presence of critical or chronic limb-threatening ischemia, and whether a groin incision was used.
Two investigators will independently evaluate the study risk of bias in duplicate using the Quality in Prognosis Studies tool [
Before conducting quantitative data analyses, we will perform a narrative synthesis of candidate risk factors for SSI [
We will use the odds ratio as the summary measure of association for pooled analyses. Adjusted risk factor estimates with similar definitions will be pooled using DerSimonian and Laird random-effects models [
We will inspect forest plots, calculate Cochran Q homogeneity and I2 inconsistency statistics, and conduct tests of homogeneity (
We will evaluate for evidence of small study effects potentially due to publication bias for each potential risk factor–SSI association by visually inspecting produced funnel plots and using Begg and Egger tests
We will use the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for the assessment of evidence about prognostic factors to determine the certainty in the estimates of association between the reported risk factors and the development of SSI [
As of June 10, 2021, we have submitted the search strategy to another medical librarian or information scientist to peer review it using the Peer Review of Electronic Search Strategies guideline [
SSIs are one of the most important complications in vascular surgery [
Results will be used to help surgeons, patients, and authors of clinical practice statements and guidelines in deciding on the safety of open vascular surgery in patients with medically refractory intermittent claudication and in selecting between open and endovascular revascularization when patients with chronic limb-threatening ischemia are candidates for both. It will also assist clinicians and policy makers in deciding which patients may benefit most from interventions designed to prevent SSIs (eg, incisional negative-pressure wound therapy [
Completed PRISMA-P (Preferred Reporting Items in Systematic Reviews and Meta-Analyses-Protocols) checklist.
Operationalized list of quality domains containing the prompting items used when making risk of bias decisions.
Grading of Recommendations, Assessment, Development, and Evaluation
Population, Index Prognostic Factor, Comparison of Prognostic Factors, Outcome, Timing, and Setting
Preferred Reporting Items in Systematic Reviews and Meta-Analyses
Preferred Reporting Items in Systematic Reviews and Meta-Analysis Protocols
International Prospective Register of Systematic Reviews
surgical site infection
DJR conceived the study, and DJR, SKN, HTS, TB, VCM, LD, and DIM developed the study. DJR designed the search strategy and the qualitative and quantitative data synthesis plan, which was refined by SKN, HTS, TB, VCM, LD, and DIM. DJR wrote the draft of the protocol, which was critically revised by SKN, HTS, TB, VCM, LD, and DIM. DJR submitted the protocol to PROSPERO. All authors read and approved the final version of the protocol.
None declared.