Management of the infected arterial pseudoaneurysm secondary to groin injecting drug use and outcomes: a systematic review protocol

Abstract

Introduction

People who inject drugs are at risk of a range of injecting-related infections and injuries, which can threaten life and limb. In parallel to escalating rates of drug-related deaths seen in Scotland and the UK, there has also been an increase in hospital admissions for skin and soft tissue infections related to injecting drug use. One such injecting complication is the infected arterial pseudoaneurysm, which risks rupture and life-threatening haemorrhage. Surgical management options for the infected arterial pseudoaneurysm secondary to groin injecting drug use remain contentious, with some advocates for ligation and debridement alone, whilst others promote acute arterial reconstruction (suture or patch repair, bypass or, more recently, endovascular stent-graft placement). Rates of major lower limb amputations related to surgical management for this pathology vary in the literature. This review aims to evaluate the outcomes of arterial ligation alone compared with arterial reconstruction, including open and endovascular options, for the infected arterial pseudoaneurysm secondary to groin injecting drug use.

Methods and analysis

The methods will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Three electronic databases will be searched and the resultant papers screened according to the study inclusion and exclusion criteria (detailed in the Population, Intervention, Comparison, Outcomes and Study design statement). Grey literature will be excluded. All papers at each stage will be screened by two independent authors, with disagreements arbitrated by a third. Papers will be subject to appropriate standardised quality assessments.

Primary outcome

Major lower limb amputation.

Secondary outcomes

Reintervention rate, rebleeding rate, development of chronic limb-threatening ischaemia 30-day mortality and claudication.

Ethics and dissemination

This is a systematic review based on previously conducted studies, therefore, no ethical approval is required. The results of this work will be published in a peer-reviewed journal and presented at relevant conferences.

PROSPERO registration number

CRD42022358209.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The study design comprises a comprehensive search strategy and selection criteria, with double-screening of all studies to reduce selection bias and data collection errors.

• The inclusion of primary endovascular stent-graft placement as a treatment modality for this pathology.

• The use of proportional meta-analysis to optimise inclusive incorporation of outcomes from non-comparator studies in quantitative analysis.

• Limitations of the study are excluding non-English language papers and grey literature.

Introduction

In recent years, drug-related deaths have been rising across countries such as the UK, most markedly in Scotland, and the USA, reflecting increases in drug-related harms.^1–3 In parallel to these drug deaths, there has also been an observed increase in hospital admissions for skin and soft tissue infections related to injecting drug use.^{4 5} People who inject drugs (PWID) are at risk of range of injecting-related infections and injuries, some of which may threaten life and limb.^{6 7}

One such injecting injury is the infected arterial pseudoaneurysm. A pseudoaneurysm (or false aneurysm) represents a defect in the arterial wall with haemorrhage contained by the surrounding soft tissues, compressed thrombus and not lined by endothelium.⁸ It is distinct from a true aneurysm, which involves dilatation of the arterial wall. Continued extravasation and expansion of a pseudoaneurysm ultimately risks free rupture.⁹ The arterial wall in PWID can also be further compromised by the severity of surrounding infection present, as well as the caustic acidifying agents injected.^9–12

A pseudoaneurysm is the most commonly described arterial complication of injecting drug use. In the context of PWID, they can develop from direct, typically infective, trauma to an artery, usually when attempting to inject intravenously, or during intentional arterial injecting. Given the probable non-sterile injecting technique, this can lead to the formation of an intramural abscess/haematoma complex.8 9 13 14 Arterial pseudoaneurysms may also occur as a result of malignant local infective invasion with destruction of arterial integrity from perivascular soft tissue sepsis.9 10 12 13 A further aetiology is septic metastases, for example, from infective endocarditis.^{10 14} Arterial pseudoaneurysms in the groin are the most frequently reported in PWID resultant from injecting into this anatomical region. However, arterial pseudoaneurysms may occur anywhere throughout the arterial vasculature, usually where injecting has been undertaken.^{13 14} If untreated they may rupture causing catastrophic, life-threatening haemorrhage.

Management options for arterial pseudoaneurysms secondary to injecting drug use remain contentious.^{10 13–15} The options for initial operative management include: arterial ligation and debridement alone or arterial reconstruction with debridement.10 13 14 16 Arterial reconstruction comprises primary repair of the defect with a suture or patch repair, or a bypass of the ligated pseudoaneurysm to compensate for the reduced distal blood supply.10 13 14 17 18 Such bypasses can be routed either extra-anatomically (circumventing the infected field) or anatomically (in situ). More recently, endovascular reconstructions with stent-grafts have also been reported.^{19 20}

However, reticence exists regarding arterial reconstruction due to the degree of pathogenic contamination common to these cases, which can risk infection of the reconstruction and predispose to life-threatening haemorrhage.¹⁵ Autologous vein would usually be the preferred conduit for reconstruction, especially in an infected field, although this is often not available in PWID due to venous damage and destruction from injecting.^{15 18} Use of the internal iliac artery as an autologous conduit has also been described.¹⁸ Prosthetic grafts are high risk for infection, particularly in this setting. Biosynthetic and biological (encompassing cadaveric) conduits are alternatives, but also risk infection.^20–22 An additional concern is continued injecting, introduction of further infection and also use of any reconstruction for drug-using vascular access.^{15 23} Moreover, arterial reconstruction may not be required due to adequate residual perfusion of the limb postligation, and thus may pose more risk to the patient.^{15 16} Rates of major lower limb amputation following ligation vary in the literature from 0% to 3.3% to 33%.^{16 24–30} The purpose of this systematic review is to analyse published specific outcome following the different surgical management options for the infected arterial pseudoaneurysm secondary to groin injecting drug use. The timing of interest for these management options is immediate (at the index procedure) or during the acute admission episode (non-immediate). To our knowledge, this is the first systematic review on this topic to incorporate endovascular reconstructions in addition to open management.

Objectives

This systematic review aims to evaluate the outcomes of arterial ligation alone compared with arterial reconstruction, including endovascular management, for the infected arterial pseudoaneurysm secondary to groin injecting drug use. Arterial reconstructions of interest will be those performed at the index operation and during the acute admission episode for this pathology. The primary outcome will be major lower limb amputation. Secondary outcomes will be reintervention rate, rebleeding rate, development of chronic limb-threatening ischaemia (CLTI), 30-day mortality and claudication.

Methods and analysis

This systematic review will include all studies that meet the Population, Intervention, Comparison, Outcomes and Study design (PICOS) statement (table 1) and eligibility criteria.

Table 1.

PICOS statement

Population	Adults (aged ≥18 years) with an infected arterial pseudoaneurysm secondary to groin injecting drug use (this may involve the common femoral, superficial femoral, profunda femoris, external iliac or common iliac arteries)
Intervention	Arterial reconstruction by way of repair (suture or patch repair), bypass operation (if ligation performed) or endovascular stent-graft placement±debridement and undertaken immediately (at the index surgical intervention) or during the acute admission episode
Comparison	Ligation of the infected arterial pseudoaneurysm±debridement alone at index surgical intervention
Outcomes	Primary outcome: major lower limb amputation Secondary outcomes: reintervention rate; rebleeding rate; development of chronic limb-threatening ischaemia; 30-day mortality and claudication
Study design	Randomised controlled trials, prospective and retrospective observational cohort studies and case series (four or more patients)

Eligibility criteria

The search will be performed in relevant electronic databases. Only full published papers in English will be included. The grey literature, encompassing conference abstracts, will be excluded. The anatomical location of the pseudoaneurysm, the corresponding intervention executed and related outcomes must be reported clearly in the paper or else it will be excluded (ie, if the management and outcomes of pseudoaneurysms in different anatomical locations are described cumulatively along with each intervention and outcome, rendering those specifically related to the groin indistinguishable). Papers that detail only some of the outcomes of interest, however, distinctly report the related management method for the correct anatomical area will be included with documentation of the outcomes reported on, and ‘not reported’ or ‘unclear’ as applicable.

Population

The population of interest are PWID who have developed infected arterial pseudoaneurysms secondary to groin injecting drug use (ie, infected arterial pseudoaneurysms related to the groin, typically due to injecting drug use in this anatomical region and can involve the following vasculature: the common femoral, superficial femoral, profunda femoris, external iliac or common iliac arteries). The case definition will be any arterial pseudoaneurysm secondary to groin injecting drug use. Cases will be ascertained on radiological findings (if imaging performed) and clinically, including at the time of operation. All arterial pseudoaneurysms in this review will be considered infected due to the aetiology. Non-sterile injecting predominantly precipitates the ensuing pathophysiology in these cases, which is typically infective rather than simply traumatic.⁹ PWID are defined as individuals who inject drugs, which may be illicit or prescribed, with the latter not being used in conduct with the prescription, for example, injection of methadone or crushed tablets in solution originally intended for oral consumption.

Interventions

The intervention consists of any arterial reconstruction undertaken to surgically manage an infected arterial pseudoaneurysm secondary to groin injecting drug use. This may be a suture or patch repair (the patch material may be autologous, prosthetic, biosynthetic or biologic). It also includes a bypass operation to compensate for arterial ligation of an infected arterial pseudoaneurysm (this may be performed prior to the ligation at the index intervention through an extra-anatomical route in an attempt to try and limit contamination of the reconstruction). The bypass operation may be routed extra-anatomically or anatomically and the conduit may be autologous, prosthetic, biosynthetic or biologic. Endovascular management through placement of a stent-graft across anatomically suitable pseudoaneurysms will also be incorporated into the review.

Comparison

Arterial ligation alone with no arterial reconstruction will be considered to be the comparator.

Outcomes

The studies should report on the primary outcome: major lower limb amputation. Secondary outcomes of interest are: reintervention rate, rebleeding rate, development of CLTI, 30-day mortality and claudication.

Study design

Primary studies, which may be prospective or retrospective, in English will be included. There will be no restrictions to geographical location of the study.

Patient and public involvement

There was no direct patient and public participation in this study as it is a protocol for a systematic review.

Information sources and search strategy

The electronic databases to be systematically searched are: EMBASE; MEDLINE and Scopus. There will be no time restriction to the search (running from 1974 to search date in EMBASE, 1946 in MEDLINE and 1960 in Scopus). The search strategy was devised to fulfil the PICOS statement and employed free search terms (search strategy for each database detailed in online supplemental material, appendix 1). Papers produced from the search will be limited to the English language and any grey literature identified will be excluded. Authors of recent publications may be contacted for missing data.

Data

Data selection and coding

All studies resultant from the search will be exported to EndNote V.20 (Clarivate) and duplicates removed. These studies will then be transferred to Rayyan, a web-based platform to facilitate collaborative systematic literature review screening.³¹ Titles and abstracts will be independently screened by two authors (CSM and DS) in accordance with the selection criteria. Any differences during the screening process will be arbitrated by a third author (JN/SS/AR) in order to reach a final decision.

The study selection process will be recorded in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.³² The papers from the title and abstract screening will be then be subject to the PICOS criteria, with those not meeting these elements excluded and the reason recorded.

Data extraction

Data will be extracted from all studies that meet the inclusion criteria and it will be undertaken independently by two authors (CSM and DS). Any disagreements in extraction will be reviewed and decided on by a third author (JN/SS/AR). Data to be extracted are: study design, population size and basic demographics (age, gender), anatomical location of the arterial pseudoaneurysm, presentation with rupture, surgical intervention details (ligation and number of arteries ligated and information on reconstruction if performed), major lower limb amputation, need for further intervention; rebleeding rate, development of CLTI, 30-day mortality, claudication, wound management, wound complications and follow-up duration. For the arterial reconstructions, graft infections and thromboses will also be recorded. If reported, the clinical status of the patient at presentation and influence of this on management will also be documented.

Risk of bias (quality) assessment

The appropriate assessment tool will be used for the design of each study included: the Cochrane Collaboration’s risk of bias tool for randomised studies (randomised controlled trials), the Newcastle-Ottawa Scale for cohort studies and the Joanna Briggs Institute critical appraisal tool for case series.^33–35 Evaluation using these tools will again be performed independently by two authors (CSM and DS). Divergences in scoring will be settled by a third author (AR/JN/SS).

Synthesis and analysis

Data to be quantitatively synthesised are: major lower limb amputation rate, reintervention rate, rebleeding rate, development of CLTI, 30-day mortality and claudication. Data for each outcome will be quantitatively pooled and assessed using suitable statistical tools and models (ie, proportional and conventional comparative meta-analyses). The robustness of the resultant evidence will be subject to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework by two authors (CSM and DS), with any differences reviewed by a third author (AR/JN/SS).³⁶ Heterogeneity will also be assessed using an appropriate statistical tool when the number of identified studies and the amount of variation between trials can be defined. If the data allow, there will also be subgroup analyses of ligation and debridement alone, compared with open and endovascular reconstructions, respectively.

This systematic review protocol has also been written in accordance with the PRISMA-Protocol checklist (online supplemental material, appendix 2).^{37 38}

Potential implications

There is no current consensus on the surgical management of the infected arterial pseudoaneurysm secondary to groin injecting drug use. This review aims to give a comprehensive and contemporary overview of the literature and relevant outcomes to aid in informing practice.

Ethics statements

Patient consent for publication

Not applicable.