Article Text
PDF
Abstract
Introduction Blood blister-like aneurysm (BBA) is a special type of intracranial aneurysm with relatively low morbidity and high mortality. Various microsurgical techniques and endovascular approaches have been reported, but the optimal management remains controversial. For a better understanding of the treatment of BBA patients, a network meta-analysis that comprehensively compares the effects of different therapies is necessary.
Methods and analysis This protocol has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Related studies in the following databases will be searched until November 2022: PubMed, Embase, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang. Randomised controlled trials (RCTs) and non-randomised studies comparing at least two different interventions in BBA patients will be included. Quality assessment will be conducted using Cochrane Collaboration’s tool or Newcastle-Ottawa Scale based on their study designs. The primary outcome is the composite of the incidences of intraoperative bleeding, postoperative bleeding and postoperative recurrence. The secondary outcome is an unfavourable functional outcome. Pairwise and network meta-analyses will be conducted using STATA V.14 (StataCorp, College Station, Texas, USA). Mean ranks and the surface under the cumulative ranking curve will be used to evaluate every intervention. Statistical inconsistency assessment, subgroup analysis, sensitivity analysis and publication bias assessment will be performed.
Ethics and dissemination Ethics approval is not necessary because this study will be based on publications. The results of this study will be published in a peer-reviewed journal.
PROSPERO registration number CRD42022383699.
- neurosurgery
- protocols & guidelines
- statistics & research methods
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
STRENGTHS AND LIMITATIONS OF THIS STUDY
This will be the first network meta-analysis that comprehensively compares different treatments in patients with blood blister-like aneurysms of internal carotid artery.
Both randomised controlled studies and non-randomised studies will be included to strengthen the statistical power of this network meta-analysis.
Based on the study designs, we will use Cochrane Collaboration’s tool or Newcastle-Ottawa Scale to conduct quality assessment.
Some included studies may have inferior quality and decrease the significance of the results in this network meta-analysis.
Potentially high heterogeneity among different studies may influence the final results of this network meta-analysis.
Introduction
Blood blister-like aneurysms (BBAs) are rare vascular lesions, accounting for 0.9%–6.5% of internal carotid artery (ICA) aneurysms.1 2 The diagnosis and treatment of BBAs are challenging, and regardless of the treatment option, the mortality rate remains high. BBAs are usually located in the non-branch part of the anteromedial supraclinoid segment of the ICA. BBAs are small in size, have a broad basal appearance or irregular protrusions, lack an identifiable aneurysmal neck and usually develop a cystic appearance within days to weeks. Their aneurysmal walls are fragile and prone to rupture, leading to subarachnoid haemorrhage (SAH).
Although a variety of microsurgical techniques and endovascular approaches have been reported, the optimal treatment remains controversial.3 4 Microsurgical treatments of BBAs include clipping, wrapping, wrapping and clipping, and ICA occlusion with or without previous protective bypass. Simple clipping and wrapping are closely related to aneurysmal regrowing and rebleeding.5 6 Moreover, studies have reported that ICA stenosis, leading to postoperative ischaemic lesions, can occur after simple clipping, and wrap-induced anterior choroidal artery occlusion may occur after ICA wrapping.7 8 The wrapping and clipping technique was regarded as the best surgical option in some studies.1 8 However, incomplete wrapping of the ICA lesion segment after this technique could be related to a high risk of aneurysmal regrowing or rebleeding.9 ICA occlusion with or without previous protective bypass is another surgical treatment. However, an ICA occlusion test is more difficult to perform in patients with SAH. Even in cases of sufficient reserve capacity on preoperative occlusion tests, ICA occlusion without bypass is associated with a poor prognosis.2 10 In addition, the technique of performing protective high flow bypass before ICA occlusion is also related to significant morbidity and mortality.11 12 Endovascular treatments for BBAs include coiling, stent-assisted coil embolisation and flow-diverter stent treatment. Some authors reported that simple coiling was associated with a high risk of intraoperative aneurysm perforation and regrowing.5 13 Similarly, the technique of stent-assisted coil embolisation is reported to be related to a significant risk of BIA rupture and regrowth.14 Additionally, perioperative antiplatelet therapy may cause bleeding.14 In recent years, flow-diverting stents (FDSs) have been recognised as a safe and feasible therapy for BBAs.15 16 However, BBAs cannot be occluded immediately, and high-dose antiplatelet therapy is required after surgery, which may cause BBA rebleeding during this period.15 17
A previous meta-analysis showed that endovascular treatment had lower morbidity and mortality and provided a better outcome than surgical approaches,18 but the authors only compared the two most common treatments (surgery and endovascular management). Another meta-analysis showed that the bypass procedure was associated with more favourable outcomes; however, only bypass and non-bypass surgical methods were compared in the study.19 Moreover, Lee et al only compared the safety and efficacy of stent-assisted coiling and FDS in the management of BBAs.20 Therefore, choosing the optimal intervention measure is essential to the treatment of the disease. However, there is no comprehensive study comparing and ranking various interventions. A network meta-analysis can compare and rank various interventions.21 For a better understanding of the treatment of BBA patients, a network meta-analysis that comprehensively compares the effects of different therapies is necessary.
Objective
The aim of this study is to compare the efficacy and safety of clipping, wrapping, wrapping and clipping, ICA occlusion, coiling, stent-assisted coil embolisation, and flow-diverter stent treatment for patients with BBAs using a Bayesian network meta-analysis.
Methods and analysis
Design
This study will be conducted using a Bayesian network meta-analysis. The protocol has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (see online supplemental file 1).22 The planned start date for the study is April 1, 2023, and the anticipated completion date is 31 July 2023.
Supplemental material
Patient and public involvement
Neither patients nor the public are involved because this protocol is designed for a network meta-analysis based on the literature.
Information source and search strategy
We will search the literature for related randomised controlled trials (RCTs) and non-randomised studies in the following databases until November 2022: PubMed, Embase, Scopus, Web of Science, Cochrane Library, CNKI, VIP and Wanfang. No restrictions on language are set. The detailed search strategy is shown in online supplemental file 2.
Supplemental material
Eligibility criteria
Type of patients
The inclusion criteria of the patients are as follows: (a) patients aged ≥18 years old and (b) BBAs of ICA confirmed by CT angiography or digital subtraction angiography. Patients with severe systemic diseases, such as chronic heart failure, coagulation disorders, thrombocytopenia, respiratory insufficiency and liver or renal dysfunction, were excluded. Patients who are dependent on anticoagulants or alcohol are also excluded.
Type of studies
Randomised controlled trials or non-randomised studies are included. We exclude case reports, case series and reviews.
Type of interventions
This study will include studies comparing at least two different interventions among the following interventions: clipping, wrapping, wrapping and clipping, ICA occlusion, coiling, stent-assisted coil embolisation and flow-diverter stent treatment. Studies will be excluded if there is no restriction on treatment methods.
Type of outcomes
The primary outcome is the composite of the incidences of intraoperative bleeding, postoperative bleeding and postoperative recurrence. Recurrence is evaluated by the imaging index threshold of each study. The secondary outcome is an unfavourable functional outcome at the end of follow-up. Functional outcome is dichotomised to good or poor according to the scale and threshold in each study.
Study selection
After removing duplicates, the titles and abstracts of all records will be independently screened by two authors (YL and XY). Any record that does not meet the eligibility criteria will be removed. Full-text papers of the remaining studies are obtained and screened by two authors independently. Only studies that meet the eligibility criteria will be finally included. If studies have duplicate data, only the study with a larger sample size and longer follow-up time will be included. Any disagreement between two authors will be resolved by another author (JZ).
Data extraction
Based on a pre-established extraction form, two authors (YL and XY) independently extract data from all included studies. Name of the first author, the origin of the report, demographic data, year of publication, study design, number of patients included, location of BBAs, detailed intervention in each group, angiographic outcomes, rebleeding, periprocedural complications, recurrence rate, inclusion criteria, exclusion criteria, follow-up period and clinical outcomes in each group will be extracted from the studies that are finally included. If some data can not be obtained from the papers directly, we will try to contact the authors to obtain those data. Any disagreement between two authors will be solved by consensus and all data will be checked by another author (JZ).
Risk of bias assessment
We will use Cochrane Collaboration’s tool and Newcastle-Ottawa Scale to assess all randomised controlled trials and all non-randomised prospective studies, respectively. Two authors (YL and XY) will assess the quality of the studies independently, and any disagreement will be solved by discussion with another author (JZ).
Data synthesis
When quantitative analysis was feasible, we will conduct all of the following statistical analyses by STATA V.14 (StataCorp, College Station, Texas, USA). However, if quantitative analysis can not be conducted, the results will be described narratively.
Direct comparisons of interventions
We will conduct conventional pairwise meta-analyses between different interventions first if at least two studies provide related data. We will use the DerSimonian-Laird method and random effects model.23 The I2 statistic is used to assess the heterogeneity of the included studies.24
Indirect and mixed comparisons of interventions
We will conduct a network meta-analysis using a random effects model.25 Interactions among all the included studies will be indicated in the network geometry, and the contributions of direct comparisons will be shown in the contribution plot for the network.26 The effects of every intervention on both the primary outcome and the secondary outcome in BBA patients will be assessed using mean ranks and the surface under the cumulative ranking curve.27
Statistical inconsistency assessment
Global and local methods will be used to evaluate the inconsistency between direct and indirect comparisons. Concerning the global method, the design-by-treatment model will be adopted,28 and the loop-specific method will be used to assess the local inconsistency.29
Subgroup analysis and sensitivity analysis
If possible, subgroup analyses will be performed based on study design (RCTs or observational studies), age, sex, race and Glasgow Coma Scale score. A sensitivity analysis will be performed to test whether the results are stable by eliminating each study.
Publication bias
In the network meta-analysis, a network funnel plot will be used to estimate potential publication bias.
Quality of evidence
Following the Grading of Recommendations, Assessment, Development and Evaluation approach, we will assess the evidence quality by rating the quality of treatment effect evaluations from network meta-analyses.30
Discussion
This is the first network meta-analysis that comprehensively compares different treatments in BBA patients. Both randomised controlled studies and non-randomised studies will be included to strengthen the statistical power of this network meta-analysis. We hope the results of this network meta-analysis will provide more information about the safety and efficacy of different treatment strategies in BBA patients and provide help for future clinical practice and studies. Nevertheless, this network meta-analysis also has some limitations. First, some studies with inferior quality, included in this network meta-analysis, may have decreased the significance of the results. Second, there may be potentially high heterogeneity among different studies, which would have affected the final results of this network meta-analysis.
In conclusion, this study will help to compare the effects of different treatments in patients with BBAs. We hope this network meta-analysis is a source of strong evidence for the treatment of BBA patients to guide future clinical practice.
Ethics and dissemination
Ethical issues
Because this network meta-analysis will be based on publications, ethics approval and patient consent are not required.
Publication plan
This protocol has been registered on PROSPERO and the final results of this study will be published in a peer-reviewed journal.
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
YL and XY are joint first authors.
YL and XY contributed equally.
LL and XH contributed equally.
Contributors YL, JZ and XY are responsible for the conception of the study. YL, JZ, HZ and HL designed this protocol. YL, JZ and XY tested the feasibility of this protocol. YL and XY wrote the original draft. XH, LL, JZ and HL revised the draft.
Funding This work was supported by the National Natural Science Foundation of China grant number 81801186, Science and Technology Department of Sichuan Provence grant number 2020YFQ0009 and Outstanding Subject Development 135 Project of West China Hospital, Sichuan University grant number ZY2016102.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.