Risk factors for postoperative thrombosis-related complications in patients who undergo meningioma surgery: A Chinese single-center, retrospective study

doi:10.21203/rs.3.rs-4991816/v1

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Risk factors for postoperative thrombosis-related complications in patients who undergo meningioma surgery: A Chinese single-center, retrospective study

https://doi.org/10.21203/rs.3.rs-4991816/v1

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ObjectiveTo explore the incidence and risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE) following surgical intervention for meningioma.

Methods In this retrospective, observational study, we enrolled 9067 patients with histologically confirmed meningiomas who underwent surgical resection at our institution between January 2019 and June 2024. Demographic data (including gender, age, and geographic region) and information on postoperative complications (e.g., intracerebral hemorrhage, DVT, and PE) were documented and analyzed. The incidences of postoperative DVT and PE were also recorded. Risk factors for DVT and PE were identified using univariate and multivariate logistic regression analyses and restricted cubic splines.

Results Among the 9067 included patients, 766 (8.4%) experienced DVT and 32 (0.35%) developed PE. Northeast China, North China, and East China were the top three regions with the highest prevalence of DVT/PE, and the three most affected provinces were Hebei, Shandong, and Inner Mongolia. Univariate logistic regression analysis and restricted cubic splines indicated that age was a significant contributing factor to the development of both DVT and PE. The risk of PE increased in patients aged 42–82 years, as follows: the odds ratio (OR) for PE increased from 1.001 (95% confidence interval [CI]: 1.000–1.002) at 42 years to 1.044 (95% CI: 1.001–1.088) at 82 years. The incidence of PE was 4.58 (95% CI: 1.37–15.33) times higher in patients aged ≥ 60 years vs < 40 years and 8.58 (95% CI, 1.02–72.03) times higher in those aged ≥ 80 years compared with the 40–60 years group. Multivariate logistic regression analysis identified age (OR: 1.07; 95% CI: 1.06–1.08) and intracerebral hemorrhage (OR: 6.98; 95% CI: 3.75–13.00) as independent risk factors for DVT. In comparison, age (OR: 1.05; 95% CI: 1.01–1.09) and DVT (OR: 20.21; 95% CI: 9.03–45.27) were risk factors for PE.

Conclusions The incidences of DVT and PE following meningioma surgery were 8.4% and 0.4%, respectively, from 2019 to 2024. In addition to the specific age threshold of > 60 years, a broader age range (42–82 years) is also a risk factor for postoperative PE.

Meningiomas are the most common benign brain tumors and are generally treated by neurosurgery.[1] Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common postoperative complication in patients who undergo meningioma surgery.[1, 2] An early study reported an incidence of VTE as high as 72%[3], while a more recent study indicated a much lower incidence ranging from 3–4%[2]. Postoperative VTE in patients with meningioma is associated with a high risk of extended hospital stays and an increased incidence of postoperative complications, such as stroke, sepsis, unexpected intubation, hospital readmission, and mortality.[4] Investigating the specific incidence and risk factors for postoperative VTE is instrumental in the prevention and management of this condition. However, most published studies evaluated older data[5–7] or were limited by small sample sizes[1]. In the present study, we performed multivariate analyses of DVT and PE in patients who had undergone meningioma surgery, using recent, large-sample data from the Tiantan Neurosurgery Center.

Patients

In this study, we enrolled 9067 patients aged ≥ 18 years who had undergone surgical procedures and were histopathologically confirmed to have meningiomas at our center between January 2019 and June 2024. Demographic data (including gender, age, and geographic region) and information on intra- and postoperative complications (e.g., intracerebral hemorrhage, DVT, and PE) were retrieved from the electronic medical records management system. All participants provided written informed consent upon admission, which also granted permission for the use of their medical data for research purposes.

The inclusion criteria were as follows: (i) complete data for the medical history, imaging studies, and perioperative records; (ii) surgical resection and a histopathological diagnosis of meningioma; (iii) radiotherapy- and/or chemotherapy-naive; (iv) age ≥ 18 years; and v) signed informed consent for data use after admission.

Patients who were reoperated on for meningioma recurrence were excluded.

DVT assessment

Bedside ultrasonography of both lower extremities was performed just prior to surgery, 48–72 hours after surgery, or whenever a patient exhibited symptoms, such as pain, swelling, and/or pitting edema in the affected limb, or with marked changes in D-dimer concentrations. Ultrasonography was performed using the HS50 color Doppler ultrasound system (Samsung, Seoul, Korea), with the probe frequency set at 5–10 MHz. During the examination, if no blood flow signal was detected within the venous lumen, the probe was applied directly to the site of the dilated vein to observe for compression. The presence of a non-compressible or only partially compressible vein indicated a positive finding for DVT.

PE assessment

PE was assessed in accordance with the Chinese Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism (2018). PE diagnosis was confirmed by imaging studies (computed tomography (CT) pulmonary angiography) on the basis of clinical symptoms, namely dyspnea, chest pain, syncope, and elevated D-dimer concentration.

Intracerebral hemorrhage (ICH) assessment

Plain head CT was routinely performed before surgery and 2–6 hours, 24 hours, and 72 hours after surgery. Additionally, repeat CT was performed whenever there was a change in the patient’s level of consciousness.

Statistical Analysis

Data analysis was performed using STATA/MP software (version 18.0; StataCorp, College Station, TX, USA). Normally distributed continuous variables are presented as mean ± standard deviation, skewed continuous data are described as median (interquartile range), and categorical variables are reported as number (percentage). The chi-square test and Kruskal–Wallis rank-sum test were used to analyze differences in the distributions of DVT and PE. Univariate and multivariate logistic regression analyses and restricted cubic splines were used to examine the associations between sex, age, region, and ICH as variables associated with the occurrence of DVT and PE. P < 0.05 was considered statistically significant.

Baseline, preoperative, and postoperative characteristics of patients with DVT/PE

A total of 9067 patients underwent surgical procedures for meningioma during the study period. Among them, 766 (8.4%) experienced DVT and 32 (0.35%) developed PE. Women comprised 72.10% of the total patient population (71.3% for those with DVT and 68.8% for those with PE). The patients’ mean ± standard deviation age was 52.63 ± 11.19 years. Patients who developed DVT or PE after surgery were significantly older compared with the overall baseline population (P < 0.001). Specifically, the mean age was 59.39 ± 9.85 years for patients with DVT and 62.22 ± 9.86 years for those with PE (Table 1). Northeast China, North China, and East China were the top three regions with the highest prevalences of DVT/PE, and the three most affected provinces were Hebei, Shandong, and Inner Mongolia. The incidence of postoperative DVT exceeded 10% in Guangdong, Guangxi, Qinghai, Shandong, Beijing, and Chongqing, with no statistically significant differences between these provinces. The incidence of postoperative PE exceeded 1.0% in Guangdong and Hubei (1.72% and 1.24%, respectively), with no statistically significant differences between these provinces (Figure 1).

ICH was identified in 49 patients (0.5%) who underwent meningioma surgery, among whom 81.6% experienced the condition after surgery (49.0% within 6 hours postoperatively). The incidence of ICH was significantly high for both DVT and PE patients (both, P<0.001): 2.5% for DVT plus ICH and 6.2% for PE plus ICH, surpassing the ICH incidence in the overall patient population (P<0.001). No significant differences were observed for the timing and duration of ICH between DVT patients and PE patients.

DVT was present in 71.9% of PE patients, which was a significantly higher proportion compared with that in the non-PE population (8.2%). The mean duration of hospitalization was 13.12 ± 6.1 days. Both DVT and PE were associated with prolonged hospital stay (P<0.001). Specifically, the average length of hospitalization was 17.72 ± 9.93 days for DVT patients and 19.50 ± 9.48 days for PE patients (Table 1).

Results of the univariate and multivariate analyses for DVT/PE

Age emerged as a risk factor for the development of DVT, with an odds ratio (OR) of 1.07 (95% confidence interval [CI]: 1.06–1.08). Restricted cubic splines revealed a nonlinear, increasing trend in the incidence of DVT with age for patients aged 18–89 years (Table 2 and Figure 2A). Similarly, age contributed to the development of PE, with an OR of 1.09 (95% CI: 1.05–1.13). Restricted cubic splines showed that the risk of PE increased in patients aged 42–82 years, as follows: the OR for PE increased from 1.001 (95% CI: 1.000–1.002) at 42 years to 1.044 (95% CI: 1.001–1.088) at 82 years (Table 2 and Figure 2B). To facilitate the comparisons, univariate logistic regression applied to artificially constructed age group models indicated that model 3 had the optimal Akaike information criterion value, and the incidence of PE in individuals aged ≥ 60 years was 4.58 times (95% CI: 1.37–15.33) higher than that in individuals aged < 40 years. Subsequent comparative results, as presented in model 1, indicated that the incidence of PE in individuals aged ≥ 80 years was 8.58 times (95% CI: 1.02–72.03) higher than that of individuals aged 40–60 years (Table 3). ICH was identified as a risk factor for both DVT and PE, with ORs of 7.01 (95% CI: 3.93–12.52) and 12.75 (95% CI: 2.96–54.88), respectively. However, neither the timing nor the duration of bleeding was statistically significant. Furthermore, DVT was a risk factor for PE, with an OR of 28.52 (95% CI: 13.15–61.86).

Multivariate logistic regression analysis identified age (OR: 1.07; 95% CI: 1.06–1.08) and ICH (OR: 6.98; 95% CI: 3.75–13.00) as independent risk factors for DVT, with an area under the receiver operating characteristic curve of 0.697. In contrast, age (OR: 1.05; 95% CI: 1.01–1.09) and DVT (OR: 20.21; 95% CI: 9.03–45.27) were risk factors for PE, with an area under the curve of 0.876 (Table 4 and Figure 3).

In our retrospective analysis of data for 9067 patients with meningiomas who underwent surgical procedures between January 2019 and June 2024, the incidence of DVT was 8.4%, while the incidence of PE was 0.4%. Univariate and multivariate analyses indicated that age and ICH were contributors to the development of DVT, whereas age and DVT were identified as risk factors for PE.

The incidence of DVT following meningioma surgery at our center was 8.4%, similar to the incidence (8.7%) reported by Rizzo et al.[1], slightly higher than the 3–4% incidence commonly cited in recent studies[4, 8, 9], and significantly lower than that (72%) described by Sawaya et al[3]. These differences may be explained by advancements in DVT diagnostic technologies and an enhanced awareness of postoperative DVT.[4] Historically, DVT was diagnosed using iodine 125-labeled fibrinogen imaging of the legs, which is less specific than current imaging methods, potentially leading to an overestimation of the incidence of postoperative DVT.[3] Recently, ultrasonography has emerged as a simple and accessible method for diagnosing DVT, with high sensitivity and specificity.[10] Nevertheless, several retrospective studies have indicated that the incidence of DVT may be underestimated using this diagnostic approach.[8, 9] Perioperative management of VTE has become a priority at our center. Ultrasonography of the lower extremity veins is performed routinely pre- and postoperatively to proactively prevent, detect, and treat DVT. As a result, the data presented in our study better represent the actual overall incidence of DVT. The incidence of PE was 0.4% in our study, which is lower than the incidence (1.7%) reported in the United States National Surgical Quality Improvement Program from 2006 to 2014[11]. This discrepancy can be attributed to the proactive assessment of preoperative DVT risk factors, intraoperative elevation of the lower limbs, postoperative monitoring for DVT, early postoperative mobilization, and active implementation of physical and pharmacological prophylactic measures. It is well recognized that the incidence of postoperative PE can be reduced by standardized regimens[12].

Age was identified as an independent risk factor for both DVT and PE in this study. A study from 1992[5] assessed the factors influencing mortality following meningioma surgery. The results indicated a lower mortality rate in patients aged < 45 years and a higher mortality rate in those aged ≥ 65 years, compared with patients in other age groups. However, the study preceded recent developments in the diagnosis and management of VTE and had a limited sample size. Another study of 275 meningioma cases in Italy indicated that age ≥ 60 years was a significant contributing factor in VTE development[4], and an analysis of a dataset of 5036 meningioma cases from the United States National Surgical Quality Improvement Program demonstrated that age ≥ 65 years was an independent risk factor for VTE[7]. The data in our study were obtained from a large number of patients from China and confirmed that age is an independent risk factor for both DVT and PE. Within the age range of 18–89 years, we observed a nonlinear increasing trend for the risk of DVT. The risk of PE increased by 4.58 times in individuals aged ≥ 60 years, and the risk for patients aged ≥ 80 years was 8.58 times higher compared with those in the 60–80 years group. Restricted cubic splines further revealed that the age range of 42–82 years was associated with a significant risk of PE. Thus, for the Chinese population, in addition to the conventionally recognized high-risk age group of ≥ 60 years, the 42–60 years group also warrants increased attention.

ICH is a significant risk factor for both DVT and PE. In patients without meningioma, DVT and PE are prevalent complications of ICH.[13] In a Chinese cohort of 314 patients with ICH, 5.7% developed DVT.[14] Variations in prevalence among different ethnic groups have been documented, with rates of 16.7% for African Americans, 8.5% for Asians, and 2.8% for Caucasians, for all patients with VTE as a complication.[15] In the present study, we found that the proportions of DVT and PE following ICH were 38.78% and 4.08%, respectively, which are higher rates than those reported in the literature. In addition to the activation of the coagulation cascade, prolonged bed rest and subsequent venous stasis may also promote DVT/PE following ICH.[14] Brain surgery, intraoperative and postoperative immobilization, and perioperative administration of high-dose corticosteroids are also contributing factors.[12]

Our study has several limitations. First, the dataset for this study comprised only hospitalized patients, which might have led to an underestimation of the incidence of postoperative DVT and PE compared with other studies that extended their data collection to 30[4], 90[1], or 120[6, 16] days postoperatively. Second, given the large volume of data, we selected specific demographic and postoperative variables. Future research will aim to expand the dataset to include additional factors, such as blood type, body mass index, smoking status, homocysteine levels, tumor location and size, operative duration, surgical technique, postoperative management, and follow-up data. The diagnostic and prognostic models for DVT following meningioma surgery should be further optimized.

This article summarizes the incidence rates of DVT and PE following meningioma surgery at a neurosurgical center over a period of 5 years, with incidence rates of 8.4% for DVT and 0.4% for PE. Age and ICH were identified as risk factors for DVT. In addition to the specific age threshold of > 60 years, a broader age range (42–82 years) is also a risk factor for postoperative PE.

Acknowledgments

We thank Jane Charbonneau, DVM, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

Authors’ contributions

K.Y., J.B., Z.Y., B.X. and L.J. had the concept for the study; K.Y., J.B., Z.Y., L.J. conducted data collection and verified all underlying date; K.Y., J.B. interpreted the results; K.Y., L.J., and B.X. wrote the first draft; All authors edited and critically revised the final version of the manuscript and agreed with the decision to submit for publication. L.J. had final responsibility for the decision to submit for publication.

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Declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study and the subject described in this report. Protocol approved by the Ethical Committee of Beijing Tiantan Hospital, Capital Medical University.

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Table 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

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Risk factors for postoperative thrombosis-related complications in patients who undergo meningioma surgery: A Chinese single-center, retrospective study

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Abstract

Figures

Introduction

Materials and methods

Patients

DVT assessment

PE assessment

Intracerebral hemorrhage (ICH) assessment

Statistical Analysis

Results

Discussion

Conclusions

Declarations

References

Tables

Additional Declarations

Supplementary Files

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