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Abstract
Introduction Chronic subdural haematoma (CSDH) is one of the most common neurosurgical emergencies, especially in the elderly population. Surgery is the mainstay of treatment for CSDH. Some studies have suggested that some specific surgical strategies can have potential benefits for patients with CSDH; however, the best surgical method is still controversial. For a better understanding of surgical treatment for these patients, it is necessary to conduct a network meta-analysis to comprehensively compare the effects of medical treatment and different surgical methods.
Methods and analysis This protocol has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Related studies published up to April 2023 will be searched in the following databases: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, VIP and Wanfang. Randomised controlled trials and non-randomised prospective studies comparing at least two different interventions for patients with CSDH will be included. Quality assessment will be conducted using Cochrane Collaboration’s tool or the Newcastle–Ottawa Scale based on study design. The primary outcome will be the recurrence rates, and the secondary outcome will be the functional outcome at the end of follow-up. 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 each 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 CRD42022376829.
- neurosurgery
- protocols & guidelines
- statistics & research methods
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This will be the first network meta-analysis that comprehensively compares different surgical strategies in patients with chronic subdural haematoma.
Both randomised controlled studies and non-randomised prospective 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
Chronic subdural haematoma (CSDH) is one of the most common neurosurgical emergencies, especially in the elderly population.1 CSDH may sometimes be treated conservatively, but surgical removal of the haematoma remains the primary treatment. However, the surgical management of CSDH remains controversial.2 In theory, surgical evacuation of haematomas could relieve the mass effect and secondary brain injury after CSDH; however, the high recurrence rate (approximately 25.6%) in high-risk patients is noteworthy.3 Moreover, the mortality rate for surgically treated patients increases from 11.1% to 13.5% and up to 38.4% in patients aged 90 years or older.4 5 In these studies, the surgical methods were not restricted,3 5 and different surgical methods may have various effects on patients with CSDH.
Other studies have explored whether specific surgical strategies can improve outcomes in patients with CSDH. Duerinck et al performed a multicentre prospective randomised trial including 245 patients and found that burr-hole craniostomy (BHC) leads to the lowest recurrence rate in patients with CSDH.6 Mondorf et al conducted a retrospective study examining recurrence and outcomes in 193 patients with CSDH treated with craniotomy or BHC and found that BHC was more beneficial for patients with CSDH.7 Zhang et al enrolled 73 patients with CSDH in their study and showed that endoscope-assisted BHC was superior to BHC in reducing the recurrence and morbidity rates.8 Ban et al prospectively enrolled 541 patients with CSDH and found that middle meningeal artery (MMA) embolisation was more effective than non-surgical or surgical treatment.9 These studies indicate that some specific surgical methods may have potential benefits for patients with CSDH.
Although some meta-analyses of surgical treatment in patients with CSDH have been published previously, these studies have significant limitations. For instance, BHC, craniotomy and conservative treatment were considered conventional methods and compared with MMA embolisation in Srivatsan et al’s study.10 In Sahyouni et al’s study, craniotomy with membranectomy was compared only with BHC or craniotomy without membranectomy.11 In the study by Yagnik et al, only twist-drill craniostomy and BHC were analysed.12 In another study by Guo et al, only endoscopic-assisted surgery and BHC were compared.13 Based on the methodology of network meta-analysis, the relative effectiveness of different therapies can be evaluated together and the ranking of these therapies can be estimated.14 For a better understanding of surgical treatment in patients with CSDH, a network meta-analysis comprehensively comparing the effects of conservative treatment and different surgical methods is necessary.
Objective
This study aims to compare the efficacy and safety of medical treatment, craniotomy, BHC, endoscopic surgery, MMA embolisation and twist-drill craniostomy in patients with CSDH using Bayesian network meta-analysis.
Methods and analysis
Design
This study will be conducted using 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).15 The planned start date for the study is 31 December 2022, and the anticipated completion date is 30 June 2023.
Supplemental material
Registration information
This protocol has been registered on the International Prospective Register of Systematic Review (PROSPERO). The PROSPERO registration number is CRD42022376829.
Patient and public involvement
This protocol was designed for a network meta-analysis based on the literature. Therefore, this study will not involve patients or the public.
Information source and search strategy
We will conduct a literature search for related randomised controlled trials (RCTs) and non-randomised prospective studies published up to April 2023 in the following databases: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, CNKI, VIP and Wanfang. No restrictions on language will be set. The detailed search strategy is shown in online supplemental file 2.
Supplemental material
Eligibility criteria
Type of patients
The inclusion criteria are as follows: (a) patients aged ≥18 years old; (b) patients with initial unilateral or bilateral CSDH without loculation confirmed by CT or MRI. To increase the feasibility and transferability of the study, we will also include patients with severe systemic diseases, such as chronic heart failure, coagulation disorders, thrombocytopenia, respiratory insufficiency, and liver or renal dysfunction. Patients dependent on anticoagulants or alcohol will also be included.
Type of studies
RCTs or non-randomised prospective studies will be included. We will exclude retrospective studies, case reports, case series or reviews.
Type of interventions
This study will include studies comparing at least two of the following interventions: medical treatment, craniotomy, BHC, endoscopic surgery, MMA embolisation and twist-drill craniostomy. Studies will be excluded if there is no restriction on surgical methods.
Type of outcomes
The primary outcome will be the recurrence rate. Recurrence will be defined as reoperation of same-sided CSDH during the follow-up period. The secondary outcome will be the functional outcome at the end of follow-up. Functional outcomes will be dichotomised as good or poor according to the scale and threshold in each study. For example, the Markwalder score at follow-up after operation is dichotomised as ≤1 or >1 to define favourable or unfavourable functional outcomes, respectively; the Glasgow Outcome Scale-Extended score at follow-up after operation is dichotomised as 5–8 or 1–4 to define favourable or unfavourable functional outcomes. And, the European Quality of Life, 5 dimensions, 3-level version score at follow-up was presented as a utility index score with results ranging from 1 (perfect health) to −0.62 (health state worse than death).
In addition, postoperative complications, such as intracerebral haematoma, subdural empyema/intracerebral abscess and symptomatic pneumocephalus, will be evaluated by the imaging index threshold of each study.
Study selection
As described in detail previously,16 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 will be obtained and screened by the two authors independently. Only studies meeting the eligibility criteria will be 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) will independently extract data from all included studies. The following information will be extracted: author, year of publication, country, study duration, sample size, age, the sex distribution, the time from onset to surgery, the inclusion/exclusion criteria, the detailed intervention in each group, the number of patients in each group, the recurrence rate, the follow-up period and the outcomes in each group. If some data cannot be directly obtained from the papers, we will try to contact the authors to obtain those data. Any disagreement between the two authors will be resolved by consensus and all data will be checked by another author (JZ).
Risk of bias assessment
As described in detail previously,16 we will use the Cochrane Collaboration’s tool and Newcastle–Ottawa Scale to assess all RCTs and non-randomised prospective studies, respectively. Two authors (YL and XY) will conduct quality assessment independently and any disagreement will be solved by discussion with another author (JZ).
Data synthesis
As described in our previous study,16 when quantitative analysis is feasible, we will conduct all following statistical analyses by STATA V.14 (StataCorp, College Station, Texas, USA). However, if quantitative analysis cannot be conducted, the results will be narratively described.
Direct comparisons of interventions
As described in detail previously,16 if at least two studies provide related data, conventional pairwise meta-analyses between different interventions will be performed first. We will use the DerSimonian-Laird method and random-effects model.17 The I2 statistic will be used to assess the heterogeneity of the included studies.18
Indirect and mixed comparisons of interventions
We will conduct a network meta-analysis using a random-effects model.19 Interactions among all the included studies will be indicated in the network geometry, and the contributions of direct comparisons will be shown in a contribution plot for the network.20 The effects of each intervention on both the recurrence rate and functional outcomes of patients with CSDH will be assessed using mean ranks and the surface under the cumulative ranking curve.21
Statistical inconsistency assessment
We will use global and local methods to evaluate inconsistency between direct and indirect comparisons reported in our previous study.16 Concerning the global method, the design-by-treatment model will be adopted,22 and the loop-specific method will be used to assess local inconsistency.23
Subgroup and sensitivity analyses
If possible, subgroup analyses will be performed based on age, sex, race, the time from onset to surgery, Glasgow Coma Scale scores, baseline haematoma volumes and specific surgical treatments. The specific surgical treatments will include BHC with or without drains, BHC with single or double burr holes, BHC with subperiosteal or subdural drains and craniotomy with or without opening the internal haematoma membrane. After eliminating each study, sensitivity analysis will be performed to test whether the results are stable.
Publication bias
As described in detail previously,16 in the network meta-analysis, we will use a network funnel plot 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 the treatment effect evaluations from the network meta-analyses.24
Discussion
The onset of CSDH is slow and often overlooked or misdiagnosed due to the lack of first symptoms25; however, with advances in imaging techniques, a diagnosis can be made in most cases by CT and MRI. To date, the specific pathogenesis of CSDH has not been fully elucidated. Patients with CSDH typically exhibit impaired brain health and function, such as memory loss, progressive dementia and intracranial hypertension. If CSDH is not treated promptly and effectively, serious sequelae will occur, affecting patients’ daily activities and neurological function.
Despite being a prevalent pathology in neurosurgery, the epidemiology of CSDH has not been extensively studied. However, recent research has shed light on its incidence in specific regions. Men are more commonly affected than women, accounting for at least two-thirds of patients.26 Moreover, the global incidence and median age of CSDH have been steadily increasing. The reported average age of onset varies across multiple countries, ranging from 60 years in India to 81 years in North Wales.27 28 In a cohort of 63 358 patients in Japan, individuals aged 80 years or older accounted for nearly half of the patient population.29 The increased use of antithrombotics and the ageing population may be the factors that drive these trends.30
Currently, it is widely accepted that the initial haemorrhage in CSDH originates from bleeding of bridging veins as they traverse the dural cell layer at the dural border. This can occur due to traumatic events, anatomical changes resulting in craniocerebral disproportion (ie, brain shrinkage with age), intracranial hypotension or through anatomical manipulation such as cranial surgery.31 The subsequent formation of haematoma due to venous shearing is believed to create a potential space within the dural cell border layer, which consists of flattened and elongated cells with relatively weaker junctions that provide a natural cleavage plane for membrane separation.32 As the collection of haematoma occurs in a potential space and is caused by low-pressure venous bleeding, it takes time to develop, which explains why many patients experience symptoms weeks after the initial injury.
Another proposed pathophysiological mechanism is the development of CSDH after the formation of hygromas.33 This mechanism has been proposed based on the observation that CSDH frequently occurs following subdural hygromas, and both conditions may present after cranial trauma.34 35 Although several mechanisms have been proposed, the pathophysiological process underlying this phenomenon remains incompletely understood. It is generally believed, however, that leakage of cerebrospinal fluid into the dural cell layer creates a potential space and subsequent stretching of this layer results in thin bridging veins being compromised.36 It appears that the formation of a hygroma has no effect on the manifestation of CSDH, which consistently occurs in the same dural layer region. This suggests that an atraumatic injury to this area is a common factor in the development of CSDH. The expansion of this region seems to be caused by slow venous bleeding, and cerebrospinal fluid may contribute to this process, indicating that multiple pathomechanisms are involved in CSDH development.31
Although surgery is currently the common clinical treatment for CSDH, different surgical methods may have various effects on patients with CSDH.6–9 In addition, some meta-analyses have compared different treatments, but the optimal treatment cannot be determined due to methodological limitations.10–13 Based on the methodology of network meta-analysis, the relative effectiveness of different therapies can be evaluated together and the ranking of these therapies can be estimated.14
This will be the first network meta-analysis to comprehensively compare different surgical strategies for patients with CSDH. Non-randomised controlled studies will be included to strengthen the statistical power of this network meta-analysis due to the limited number of related randomised controlled studies. We hope the results of this network meta-analysis will provide more information about the safety and efficacy of different surgical strategies for patients with CSDH and provide help for future clinical practice and study designs. Nevertheless, this network meta-analysis will also have some limitations. First, the exclusion of retrospective studies will increase potential publication bias. Moreover, some studies with inferior quality, included in this network meta-analysis, may decrease the significance of the results. Furthermore, there may be potentially high heterogeneity among different studies, which will affect the final results of this network meta-analysis.
In conclusion, this study will help to compare the effects of different surgical treatments on patients with CSDH. We hope this network meta-analysis will offer strong evidence for the surgical treatment of patients with CSDH and 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.
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, 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 Province (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.