Factors Associated with Recurrence in Chronic Subdural Hematoma following Surgery

Introduction

Chronic subdural hematoma (CSDH) is a frequent condition among the elderly. From a population-based study, the incidence of CSDH was reported between 8.2 and 17.6 per 100,000 persons per year.¹ The prevalence of CSDH is currently rising due to an aging population and the increased use of antiplatelet and anticoagulant medicines.² The treatment of choice for symptomatic patients is surgery, including craniotomies, twist drills, and burr holes.³⁴ However, recurrence rates following surgery have been observed to range from 10.1 to 29% in prior studies.⁵⁶⁷⁸

In recent years, several risk factors for the recurrence of CSDH have been identified as follows age, seizure, coagulopathy, type of CSDH, the thickness of the hematoma, postoperative midline shift, postoperative subdural air collection, and postoperative re-expansion.^910111213 However, risk factors for recurrence are still the subject of controversy, and there is no universal consensus. Moreover, previous studies analyzed the factor as a binary outcome with various time points for recurrence that have been inconsistent. Time-to-event analysis has been used to investigate factors that may have an impact on the outcomes during follow-up, especially neuro-oncology.¹⁴¹⁵

Therefore, the purpose of this study was to describe the recurrent rate of CSDH after surgery. Additionally, a secondary objective was to evaluate factors associated with the recurrence of CSDH after surgery by time-to-event analysis.

Materials and Methods

Results

Cutoff Points of the Continuous Covariates for Protective Effect to Recurrence

Following that, the effect of the significant continuous covariates (operative time and amount of saline irrigation) was estimated by the hazard plots, as shown in Fig. 1. As a result, the cutoff points of these covariates that led to the HR of less than 0 for the protective effect of recurrence were 90 minutes for operative time and 3,200 mL for the amount of saline irrigation. For simplifying the final model, operative time and amount of saline irrigation were categorized into binary classifiers as their cutoff points. Therefore, the cumulative Kaplan–Meier curves was shown in Fig. 2A–D. Finally, the effect of the predictors related to the recurrent event and the final model that comprised the categorical variables were shown in Fig. 3A–D.

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Fig. 1 Hazard plot of continuous variables for recurrence of chronic subdural hematoma. (A) Operative time. (B) Amount of saline irrigation.

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Fig. 2 Cumulative Kaplan–Meier curves for recurrence after surgery. (A) Overall cumulative Kaplan–Meier curves. (B) Clopidogrel, (C) Operative time. (D) Amount of saline irrigation.

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Fig. 3 Forest plots of the hazard ratio of each covariate. (A) Clopidogrel with univariate analysis. (B) Operative time (incision-closure wound time) with univariate analysis. (C) Amount of saline irrigation with univariate analysis. (D) Multivariable model.

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Discussion

The natural courses of CSDH following surgery were either resolved or recurrent. The recurrent rate of CSDH was found at 22% in this study. From prior studies, Oh et al⁶ investigated the postoperative course of CSDH and reported that 12% of patients had recurrent CSDH, while Schwarz et al⁷ observed a recurrent rate of CSDH after burr hole operation in 29%. In addition, recurrence rates following surgery have been reported from other prior studies to range from 8.9 to 29.1%.²⁰²¹

Because various criteria for the recurrence were used, there are different recurrent rates from each other. Moreover, several time endpoints for recurring criteria varied between 3 and 6 months.¹⁷²² Therefore, we proposed to use time-to-event statistical analysis to evaluate the postoperative course of CSDH that is a challenge because previous studies estimated outcomes by binary logistic regression that had various time endpoints and led to various results. When there are several time endpoints, a time-to-event analysis may better capture the natural course of CSDH and be more appropriate than binary logistic regression.¹⁴¹⁵

Risk factors related to the recurrence of CSDH following surgery have still been discussed and are uncertain from prior studies. As result, preoperative clopidogrel usage and the amount of saline irrigation were potentially associated with the recurrence of CSDH in this study.

The use of antithrombotic drugs, either antiplatelets or anticoagulants, has increased due to the patient's underlying disease.²³²⁴ Around 35% of patients with CSDH in this study had preoperative antithrombotic drug usage and we found clopidogrel was significantly associated with recurrence. These drugs have been debated as a risk factor for recurrence from prior studies. Leroy et al²³ reported that preoperative anticoagulant usage was the predictor of CSDH recurrence, while other prior studies found that antithrombotic therapy did not affect the recurrent event.¹⁰¹³²⁴ Discontinuation of antithrombotic drugs was performed before surgery, but there are variations in the recommencing time of antithrombotic drugs in the postoperative period.²⁵ Early recommence of antithrombotic drugs may lead to a recurrence of CSDH. However, the optimal time of restart should be further studied in the future. Moreover, aspirin, which is another antiplatelet, was not associated with the recurrence of CSDH in this study that is explained by the different mechanisms of action between aspirin and clopidogrel. Aspirin irreversibly inhibits platelet cyclooxygenase-1,²⁶ while clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.²⁷ However, more research about the impact of various antiplatelet or anticoagulant medications has to be conducted in the future.

Intraoperative saline irrigation has been reported to significantly reduce CSDH recurrence compared with no irrigation in prior studies.²⁸²⁹³⁰ Moreover, the amount of saline irrigation has noteworthy importance for reducing recurrent rates when at least 3,200 mL of saline was used by the HR plot. Initially, we analyzed this variable as a continuous variable and found that the amount of saline irrigation significantly affected a reduction of risk of recurrence (HR: 0.99, 95% CI: 0.992–0.998 in multivariable analysis). However, the continuous variable was dichotomized to make it easier to use in general practice and the HR plot is the one of cutoff optimization methods that have been used.³¹³² As a result, the amount of saline irrigation was dichotomized at 3,200 mL of saline and it was discovered that HR was less than zero and had a protective effect against the recurrence of CSDH.

Irrigation washes out several inflammatory cytokines and fibrinolytic factors; this procedure may help reduce postoperative recurrence.³⁰ In addition, operative time was related to a low recurrent rate in univariate analysis, but this factor did not significantly associate with CSDH recurrence. From multivariable analysis, operative time had influent less than other factors. To the author's knowledge, this is the first study to report that amount of saline irrigation is significantly related to the recurrence of CSDH following surgery. The findings of this study lend credence to the idea that inflammatory cytokines and fibrinolytic agents wash out to lower the recurrence rate.

Moreover, the use of postoperative drains has been studied and the results of this intervention still have been inconclusive for the predictor of recurrence. Weigel et al reviewed publications and reported that drainage reduces the risk of recurrence,⁴ while studies by Gernsback et al and Nath and Fotedar found that recurrence rates of CSDH do not appear to be affected by either the number of burr holes or the number of drains.³³³⁴ According to the findings in this study, the use of a drain was not associated with the recurrence of CSDH, which is consistent with previous research.

There are certain limitations to the study that should be pointed out. This study was limited by its single-center design and retrospective nature, which may have led to bias. However, we tried to adjust the confounders by multivariable analysis.³⁵³⁶ In addition, another limitation was relatively small of cases overall. Thus, prospective or randomized controlled research is required for a larger sample size and a homogenous protocol to confirm the effect of predictors.

Conclusion

In summary, preoperative clopidogrel and saline irrigation were found to be associated with the recurrence rate of CSDH. Factors associated with CSDH recurrence should be developed and validated as the clinical prediction tool for implication in general practice.