Effect of Postoperative Tranexamic Acid on Recurrence Rate and Complications in Chronic Subdural Hematomas Patients: Preliminary Results of a Randomized Controlled Clinical Trial

doi:10.21203/rs.3.rs-2469052/v1

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Research Article

Effect of Postoperative Tranexamic Acid on Recurrence Rate and Complications in Chronic Subdural Hematomas Patients: Preliminary Results of a Randomized Controlled Clinical Trial

https://doi.org/10.21203/rs.3.rs-2469052/v1

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Journal Publication

published 18 Apr, 2023

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Introduction. Chronic subdural hematoma (CSDH) is a frequent neurosurgical disease, which mainly affects elderly patients. Tranexamic acid (TXA) has been hypothesized as an oral agent to avoid CSDH progression and/or recurrence. We performed an evaluation to determine whether the postoperative use of TXA reduces recurrence rate.

Method. A prospective, randomized and controlled trial. Patients with unilateral or bilateral chronic subdural hematoma undergoing surgical treatment by burr-hole were randomized as to whether or not to use TXA in the postoperative period. We evaluated image and clinical recurrence of CSDH at follow up of 6 months and potential clinical and/or surgical complications impact of TXA.

Results. Twenty-six patients were then randomized to the control group (52%) and twenty-four patients to the TXA group (48%). Follow-up ranged from 3 months to 16 months. There were no significant difference between baseline data in groups regarding to age, gender, use of antiplatelet or anticoagulants, smoking, alcoholism, systemic arterial hypertension, diabetes mellitus, hematoma laterality, hematoma thickness and drain use. Clinical and radiological recurrence occurred in 3 patients (6%), being 2 cases in TXA group (8.3%) and 1 in control group (3.8%). Postoperative complications occurred in 2 patients during follow-up (4%), being both cases in TXA group (8.3%), and none in the control group.

Discussion and Conclusion. Although TXA group had a higher recurrence rate (8.3%), there was no statistically significant difference between the two groups. Moreover, TXA group had 2 complications while control group had no complications. Although limited by experimental nature of study and small sample, our current data suggest that TXA should not be used as a potential agent to avoid recurrences of CSDH and might increase complication odds.

chronic subdural hematoma

treatment

tranexamic acid

surgery

Chronic subdural hematoma (CSDH) is a frequent neurosurgical disease, which mainly affects elderly patients¹. Its incidence has increased considerably due to population aging², reaching 58 patients per 100,000 people in those aged 65 years old or more³. Most patients have complete remission of symptoms when diagnosed and treated early^4–6.

Main risk factors for the development of CSDHs are: age, gender, alcoholism and coagulopathies (including the use of anticoagulants or antiplatelets). Treatment can be conservative or surgical, depending on the symptoms and clot size. As a general rule, surgery is indicated for hematomas thicker than 10 mm or for symptomatic patients².

In surgical cases, some techniques can be used: one or two trepanations, twist-drill craniostomy, craniotomy, mini-craniotomy, endoscopic trepanation⁶. Although there is no consensus in the literature as to the best surgical technique, burr-hole surgery has been the most used method, and is considered the first-line treatment for CSDH^6–8.

Recurrence rate after surgical treatment ranges from 5–30%, with an approximate average of 10%⁷. Main factors associated with recurrence are: male gender, diabetes mellitus, bilateral hematoma, hyperdense hematoma, thickness of the hematoma^9–11.

There is much debate about the risk factors for recurrence, and no preventive measure has been definitively established so far^9–11. In order to reduce recurrence rates, some medications have been studied. Trans-4-(aminomethyl)-cyclohexane-1-carboxylic acid, also known as tranexamic acid (TXA), induces anti-fibrinolysis, and it is believed that it may promote hemostasis in microbleeding¹². There are reports reduction in recurrence rate with the use of TXA in the postoperative period^13–15. We conducted a prospective, randomized, controlled study to determine whether the postoperative use of oral tranexamic acid reduces the risk of recurrence after CSDH treatment by burr-hole and to evaluate any associated complications.

Design of Study

Study was a randomized controlled clinical trial with a parallel design. The allocation ratio was 1:1. Patients were users of the medical facility (one single institution) and met the eligibility criteria. This study was conducted and reported according to CONSORT guidelines.

Participants

Patients with unilateral or bilateral chronic subdural hematoma undergoing surgical treatment by burr-hole. Patients operated on between March 1, 2021 and August 15, 2022, at the Hospital do Servidor Público Estadual de São Paulo, were randomized as to whether or not to use tranexamic acid in the postoperative period, after approval by the ethics committee.

Criteria for indication of surgery: symptomatic unilateral or bilateral chronic subdural hematoma or thicker than 10 mm.

Inclusion criteria: Patients aged over 18 years, diagnosed with unilateral or bilateral chronic subdural hematoma and submitted to surgical drainage by trepanation and consent to participate in the study.

Exclusion criteria: patients with malignant diseases, history of acute myocardial infarction, stroke, severe peripheral arterial disease, or any other condition that contraindicated the use of tranexamic acid. Patients who needed to be reoperated due to acute rebleeding in the immediate postoperative period were also excluded from the study.

Interventions

After surgery for CSDH, patient was randomized (using the software: miniwebtool-https://miniwebtool.com/br) to the control group (without TXA) or to the intervention group (use of TXA at a dose of 750mg/day in 3 daily doses for 3 months).

All operated patients underwent control computed tomography (CT) on the first postoperative day.

Recurrence rate was used as the primary outcome, defined as the return of symptoms or the need for surgical intervention due to recurrence of the chronic subdural hematoma. Recurrences were also divided in early (before 1 month) and late recurrences (after 1 month).

Pre and postoperative clinical and surgical evaluation were performed by the same care team composed of 8 resident physicians and 3 senior neurosurgeons. Standard surgery adopted by our institution consists of one or two burr-hole surgery. Procedures were performed under general anesthesia in the operating room. Burr-holes were made in the frontal or parietal region or both according to anatomical distribution of CSDH. In all procedures, irrigation with saline solution was performed until cleaning blood clot. A subdural drain was placed when possible, with the tip located in the frontal region.

A control CT scan was performed on the first postoperative day. Subdural drain was maintained for 24–48 hours, at a level below the head. During the drain maintenance period, the patient was restricted to the bed, without raising the headboard. After removal of the drain, patient was encouraged to walk with the help of the physical therapy team.

Radiological evaluation of CSDH was done with skull CT in axial and coronal slice, focusing in the thicker section (Fig. 1).

Once morphology of CSDH may differ among patients we used Nakaguchi classification¹⁶ to facilitate understanding and comparing morphological aspects among both groups of patients. Figure 2 illustrates each type of architecture: Type 1 - homogeneous architecture, Type 2 - laminar architecture, Type 3 - separated architecture, and Type 4 - trabecular architecture.

Outcomes

Our hypothesis is that tranexamic acid treatment in postoperative period of CSDH patients is superior compared to control.

Primary Outcome

We evaluated image and clinical recurrence of CSDH at follow up of 6 months.

Secondary Outcomes

We evaluated the potential clinical and/or surgical complications impact of tranexamic acid during follow-up.

Sample Size

Once there are no previous studies concerning the question of this manuscript and defining ideal sample size and we have no idea of differences between groups and respective variances, we opted to perform a pilot study trying to reach at least 30 patients in each group.

Initially we have reached over 60 patients, but after exclusion criteria application final number was twenty six (26) patients to control group and twenty-four (24) to experimental group.

Randomization

Assignment of participants was performed after surgery, to avoid intraoperative bias. After standard surgery and following inclusion criteria, patients were then randomized with software application and then started immediate post operative TXA. There were no blinding procedures, once both researchers, physicians and patients knew their study groups and medication applied.

Patients were divided into two groups: TXA Group and Control Group.

In the immediate postoperative period as well as 3 and 6 months post operation, all of the patients underwent a brain CT.

Statistical Methods

In this study, numerical data are presented as the mean with the range. Categorical data are presented as percentages. To determine the distribution of our data, the Kolmogorov-Smirnov test was performed. Student’s t-test for the paired and unpaired groups and Chi-Square tests for categorical variables were performed when appropriate. The significance level was established as p < 0.05.

Participant flow

Seventy-four (74) patients underwent surgery for chronic subdural hematoma along evaluated period. Among patients, twenty-four (32%) were excluded because they met exclusion criteria. Three patients evolved with acute subdural hematoma in the immediate post operative period and required emergency reoperation by craniotomy and the other twenty-one had contraindications to the use of TXA. Twenty-six patients were then randomized to the control group (52%) and twenty-four patients to the TXA group (48%). Follow-up ranged from 3 months to 16 months, with mean of 9.4 months. Full participant flow is shown in flowchart (Fig. 3).

Baseline Data

Among patients in TXA Group, fifteen (62.5%) were male and nine (37.5%) were female. Mean age was 75.8 ± 11.8 years old. Mean follow-up time was 9.3 months. Three (12.5%) patients reported chronic use of antiplatelets, and one (4.2%) reported chronic use of anticoagulants. Fifteen (62.5%) patients reported previous medical history of arterial hypertension, ten (41.7%) had diabetes mellitus, one (4.2%) reported chronic use of alcohol and 4 (16.6%) reported smoking. Glasgow Coma Scale (GCS) at admission ranged from 9 to 15, with a mean of 14. Presenting symptoms were: impairment of consciousness in 10 patients (41.7%), motor deficits in 12 (50%), headache in 9 (37.5%), language deficits in 1 (4.2%), gait disturbance in 1 (4.2%). Twelve (50%) patients had hematoma width larger than 20 mm in at least one side, with a hematoma width mean of 20.1 mm.

Applying Nakaguchi Classification, there were: 12 (50%) patients with homogeneous hematomas, 2 (8.3%) laminar, 1 (4.2%) separated, and 9 (37.5%) trabecular. Six (25%) patients had bilateral CSDH, and eighteen (75%) patients had unilateral CSDH. Among unilateral CSDH patients: Three (16.7%) patients were operated with a single burr hole and 15 (83.3%) were operated with two burr holes. Among patients with bilateral hematomas: four were operated with one burr hole in each side, one patient with 2 burr holes in each side and one patient was operated with one burr hole on the left side and two burr holes on the right side. Nineteen (79.2%) patients used drains and five (20.8%) did not.

Among patients in Control Group, sixteen (61.5%) were male, and ten (38.5%) were female. Mean age was 72.6 ± 11.9 years old. Mean follow-up time was 9.5 months. Three (11.5%) patients reported chronic use of antiplatelets and none reported chronic use of anticoagulant. Eighteen (69.2%) patients reported previous history of hypertension, seven (26.9%) diabetes mellitus, one (3.8%) chronic use of alcohol and 5 (19.2%) reported smoking. GCS at admission ranged from 10 to 15, with a mean of 14. Presenting symptoms were: impairment of consciousness in 10 patients (38.5%), motor deficits in 16 (61.5%), headache in 6 (23.1%), and diplopia in 1 (3.8%). Fifteen (57.7%) patients had hematoma width higher than 20 mm in at least one side, with a hematoma width mean of 20.4 mm.

Applying Nakaguchi Classification, there were: 8 (30.8%) patients with homogeneous hematomas, 2 (7.7%) laminar, 4 (15.4%) separated, and 10 (38.5%) trabecular. Seven (26.9%) patients had bilateral CSDH, and twenty (73.1%) patients had unilateral CSDH. Among unilateral CSDH patients: Four (20%) patients were operated with a single burr hole and 16 (80%) were operated with two burr holes. Among patients with bilateral hematomas: one was operated with one burr hole in each side, four patient with 2 burr holes bilaterally, and two patients were operated with one burr hole in one side and two burr holes on the opposite side. Twenty-one (80.8%) patients used drains and five (19.2%) did not.

There were no significant difference between baseline data in groups regarding to age, gender, use of antiplatelet or anticoagulants, alcoholism, systemic arterial hypertension, diabetes mellitus, hematoma laterality, hematoma thickness and drain use. No patient was lost during follow-up. Data are summarized in Table 1.

Table 1

Demographic, Clinical, and Radiological Baseline Characteristics of groups.
	TXA GROUP (n = 24)	CONTROL GROUP (n = 26)	p
Age	75.8 ± 11.8	72.6 ± 11.9	0.34
Sex = male	15 (62.5%)	16 (61.5%)	0.94
Medical history
Antiplatelet	3 (12.5%)	3 (11.5%)	0.92
Anticoagulant	1 (4.2%)	0	0.29
Etilism	1 (4.2%)	1 (3.8%)	0.95
Smoke	4 (16.6%)	5 (19.2%)	0.83
Hypertension	13 (54.2%)	18 (69.2%)	0.27
Diabetes mellitus	10 (41.7%)	7 (26.9%)	0.27
GCS at admission
Median	14.3	14.2	0.68
GCS 14–15	22 (91.7%)	22 (84.6%)	0.43
GCS 9–13	2 (8.3%)	4 (15.4%)	0.43
GCS 3–8	0	0
Symptoms at presentation
Consciousness impairment	10 (41.7%)	10 (38.5%)	0.82
Motor deficit	12 (50%)	16 (61.5%)	0.41
Headache	9 (37.5%)	6 (23.1%)	0.27
Seizure	2 (8.3%)	0	0.13
Language deficit	1 (4.2%)	0	0.29
Gait disturbance	1 (4.2%)	0	0.29
Diplopia	0	1 (3.8%)	0.33
Hematoma width in mm
Median	20.1 ± 6.1	20.4 ± 6.2	0.71
Hematoma width ≥ 20mm	12 (50%)	15 (57.7%)	0.59
Hematoma width < 20mm	12 (50%)	11 (42.3%)	0.59
Hematoma type (Nakaguchi)
Type 1	12 (50%)	8 (30.8%)	0.17
Type 2	2 (8.3%)	3 (11.5%)	0.14
Type 3	1 (4.2%)	4 (15.4%)	0.19
Type 4	9 (37.5%)	11 (42.3%)	0.73
Hematoma side
Right	8 (33.3%)	13 (50%)	0.23
Left	10 (41.7%)	6 (23.1%)	0.16
Bilateral	6 (25%)	7 (26.9%)	0.87
Postoperative drain
Yes	19 (79.2%)	21 (80.8%)	0.89
No	5 (20.8%)	5 (19.2%)

Outcomes

Clinical and radiological recurrence occurred in 3 patients (6%), being 2 cases in TXA group (8.3%) and 1 in control group (3.8%). There was no statistically significant difference between groups regarding the recurrence rate according to Chi-Square tests (p = 0.5). Data of CSDH recurrences are exposed in Table 2. Images of recurrence cases are exposed in Fig. 4.

Table 2

Recurrence rates.
Recurrences	Early (≤ 30 days)	Late (> 30 days)	Total	p
TXA GROUP (n = 24)	1	1	2 (8.3%)
CONTROL GROUP (n = 26)	0	1	1 (3.8%)
Total (n = 50)	1	2	3 (6%)	0.5

Post operative complications occurred in 2 patients during follow-up (4%), being both cases in TXA group (8.3%), and none in the control group. There was one case of oligosymptomatic pulmonary thromboembolism (demanding oral anticoagulants), and one wound infection in TXA group, treated with antibiotics. No other clinical or surgical complications were observed including no cases of acute myocardial infarction, peripheral vascular disease, stroke or allergic reactions. There was one death in TXA group, due to SARS-CoV-2 infection. This subject developed infection after hospital discharge and when was admitted to hospital due to COVID-19 he did not present any new neurological symptoms and head CT showed no recurrence. There was no statistically significant difference between groups regarding the recurrence rate and complications according to Chi-Square tests (p = 0.5). Data of complications are summarized in Table 3.

Table 3

Complications.
Complications	TXA GROUP (n = 24)	CONTROL GROUP (n = 26)	Total (n = 50)
Pulmonary thromboembolism	1 (4.2%)	0	1 (2%)
Miocardial infarction	0	0	0
Stroke/TIA	0	0	0
Infection	1 (4.2%)	0	1 (2%)
New neurological deficits	0	0	0
Mortality	1*	0	1
Total	3	0	3
* Death due to Sars-Cov-2 infection acquired after hospital discharge; TIA = transient ischemic attack

Limitations

Our main limitation is the small sample in each study arm. Surely, we will continue to reach more data to settle a more definitive result. Then, we did not apply blinding methods, which might have increased bias risks. Additionally, we understand the heterogeneity of CSDH patients, which are generally old subjects and using several medications and pre existing medical conditions which might impact in study analysis. However we believe our randomization could draw two similar groups according to their baseline data and we believe our results are coherent.

Another relevant observation is that we only applied TXA after surgery. Thus, according to data from this manuscript we are not able to make any inferences about TXA effect when used as an option to nonsurgical management of CSDH. This should be addressed in future trials.

Generalization

Chronic subdural hematomas (CSDH) remain a conceptual and management challenge in neurosurgical practice. Their complex and multifactorial pathophysiology¹⁷, divergent treatment strategies, associated morbidities, and high recurrence rates make this an intriguing chapter in neurosurgical portfolio. Several different and respectful institutions follow different guidelines in their approach especially because there is no clear and strong literature evidence of best practice. Once elder population is continuously increasing together with risk factors like trauma and medications, the prevalence of CSDH should also probably increase⁹.

CSDH treatment may be conservative or surgical, depending on symptoms and clot size². Morbidity and mortality are low; however, complications and recurrences are common^2,4, occurring in up to 30% of cases. Although there is no consensus on the best surgical technique to be employed, burr hole evacuation of hematoma has been the most frequently used procedure and is considered the first option of treatment for CSDH^6–8.

In 2009 Santarius et al performed a randomized controlled trial evaluating the use of a drain after burr-hole evacuation. They concluded that a drain was effectively associated with a lower rate of recurrence of CSDH and lower rate of patient mortality⁷. However, Gernsback et al¹⁸, Sivaraju et al¹⁹, and Heringer et al²⁰ have recently reported that their results did not match with those found by Santarius et al⁷. In these cases, the use of a drain did not affect recurrence rates^18–20.

When patients have normal conscience status, no motor deficits, and/or controlled symptoms like seizures or headache some nonsurgical treatments are being tried. There have been growing reports on the use of statins (HMG-CoA reductase inhibitors)^21–24, tranexamic acid^{12–15, 25} (antiplasminogen antifibrinolytic), a platelet-activating factor receptor antagonist (etizolam)^26,27, angiotensin-converting enzyme inhibitors^28–30, corticosteroids^31–35, goreisan^13,25,36,37 and antiangiogenic endovascular procedures like embolization of the distal middle meningeal artery (MMA)^38–43. All medications used until now share a potential role on inflammatory processes underlying CSDH formation.

Most studies on pharmacological treatment of CSDH are based on case series and single-center reports. Tranexamic acid is also being evaluated for CSDH treatment as a stand-alone method or used together with surgery. Kageyama et al¹² have reported improvement in a case series. Since then, other studies have pointed divergent results. Yang et al¹⁵ presented animating results in their sample, while Yamada et al²⁵ carried out a randomized clinical trial with a treatment protocol similar to the one in this study and found no benefit from tranexamic acid in terms of recurrence avoidance²⁵.

Interpretation

In this study, we tried to assess whether TXA can reduce recurrence of CSDH when used after burr-hole evacuation of CSDH. There was no statistically significant differences in baseline data between groups. Furthermore, surgical technique and perioperative care were barely the same for all patients.

Although TXA group had a higher recurrence rate (8.3%), there was no significant difference between both groups. This result is in agreement with the only randomized clinical trial ever published on the subject²⁵.

Moreover, TXA group had 2 complications while control group had no complications. One complication was potentially related to the use of TXA (pulmonary thromboembolism) and the other was more sporadic (surgical site infection). Although there was no statistically significant difference, the presence of complications in this group points to a possible clinically significant difference and the need for enhanced and close surveillance of such patients.

Although with the limitations exposed above, our current data suggest that TXA should not be used as a potential agent to avoid recurrences of CSDH and might increase complication odds. Continuing current study is mandatory to draw stronger inferences about this theme. Other similar reports from worldwide centers are also welcome to improve discussion.

Our current data suggest that TXA should not be used as a potential agent to avoid recurrences of CSDH and might increase complication odds.

Future multicenter studies with larger sample sizes are expected to confront current literature and address any issues about CSDH nonsurgical treatment.

Ethical Approval

Our study project was approved by Ethics and Research Committee of our institution (IAMSPE).

Competing interests

There are no competing interests to be disclosed

Authors' contributions

All authors designed paper;

Marcus Torres, Marina Melo, Bernardo Ribeiro and Pedro de Freitas collected data; Marcus Torres, Marina Melo, Bernardo Ribeiro, Pedro de Freitas, Matheus Oliveira and Felix Pahl analyzed data;

Marcus Torres, Matheus Oliveira and Felix Pahl wrote the paper;

Marcus Torres, Marina Melo, Bernardo Ribeiro, Pedro de Freitas, Matheus Oliveira, Felix Pahl and Jose Rotta revised paper draft and submitted

Funding

Study was carried out without funding

Availability of data and materials

We have all data collected and analysed available if necessary.

Toi H, Kinoshita K, Hirai S, et al. Present epidemiology of chronic subdural hematoma in Japan: analysis of 63,358 cases recorded in a national administrative database. J Neurosurg. 2018 Jan;128(1):222–228.
De Oliveira MF. Chronic subdural hematomas and pursuit of nonsurgical treatment alternatives. World Neurosurg. 2019 Jun;126:481–483.
Liu W, Bakker NA, Groen RJ. Chronic subdural hematoma: a systematic review and meta-analysis of surgical procedures. J Neurosurg. 2014 Sep;121(3):665–673.
Guilfoyle MR, Hutchinson PJ, Santarius T. Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma. Acta Neurochir (Wien). 2017 May;159(5):903–905.
Kolias AG, Chari A, Santarius T, et al. Chronic subdural haematoma: modern management and emerging therapies. Nat Rev Neurol. 2014 Oct;10(10):570–8.
Baschera D, Tosic L, Westermann L, et al. Treatment standards for chronic subdural hematoma: results from a survey in austrian, german, and swiss neurosurgical units. World Neurosurg. 2018 Aug;116:e983-e995.
Santarius T, Kirkpatrick PJ, Ganesan D, et al. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009 Sep;374(9695):1067–73.
Teles AR, Kraemer JL. Management of chronic subdural hematoma in Brazil. Arq Neuropsiquiatr. 2018 Aug;76(8):570–571.
Zhu F, Wang H, Li W, et al. Factors correlated with the postoperative recurrence of chronic subdural hematoma: an umbrella study of systematic reviews and meta-analyses. EClinicalMedicine. 2021 Dec 20;43:101234.
Miah IP, Tank Y, Rosendaal FR, et al; Dutch Chronic Subdural Hematoma Research Group. Radiological prognostic factors of chronic subdural hematoma recurrence: a systematic review and meta-analysis. Neuroradiology. 2021 Jan;63(1):27–40. Erratum in: Neuroradiology. 2020 Nov 5; PMID: 33094383; PMCID: PMC7803717.
Blaauw J, Jacobs B, den Hertog HM, et al. Neurosurgical and perioperative management of chronic subdural hematoma. Front Neurol. 2020 Jun 19;11:550.
Kageyama H, Toyooka T, Tsuzuki N, et al. Nonsurgical treatment of chronic subdural hematoma with tranexamic acid. J Neurosurg. 2013 Aug;119(2):332–7.
Wakabayashi Y, Yamashita M, Asano T, et al. [Effect of gorei-san with tranexamic acid for preventing recurrence of chronic subdural hematoma]. No Shinkei Geka. 2012 Nov;40(11):967–71.
Tanweer O, Frisoli FA, Bravate C, et al. Tranexamic acid for treatment of residual subdural hematoma after bedside twist-drill evacuation. World Neurosurg. 2016 Jul;91:29–33.
Yang K, Kim KH, Lee HJ, et al. Role of adjunctive tranexamic acid in facilitating resolution of chronic subdural hematoma after surgery. J Korean Neurosurg Soc. 2022 Nov 3.
Nakaguchi H, Tanishima T, Yoshimasu N. Factors in the natural history of chronic subdural hematomas that influence their postoperative recurrence. J Neurosurg. 2001 Aug;95(2):256–62.
Edlmann E, Giorgi-Coll S, Whitfield PC, et al. Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy. J Neuroinflammation. 2017 May 30;14(1):108.
Gernsback J, Kolcun JP, Jagid J. To drain or two drains: recurrences in chronic subdural hematomas. World Neurosurg. 2016;95:447–450.
Sivaraju L, Moorthy RK, Jeyaseelan V, et al. Routine placement of subdural drain after burr hole evacuation of chronic and subacute subdural hematoma: a contrarian evidence based approach. Neurosurg Rev. 2018;41: 165–171.
Heringer LC, Sousa UO, Oliveira MF, et al. The number of burr holes and use of a drain do not interfere with surgical results of chronic subdural hematomas. Arq Neuropsiquiatr. 2017 Nov;75(11):809–812.
Tang R, Shi J, Li X, et al. Effects of atorvastatin on surgical treatments of chronic subdural hematoma. World Neurosurg. 2018 Sep;117:e425-e429. Erratum in: World Neurosurg. 2018 Nov;119:529.
Qiu S, Zhuo W, Sun C, et al. Effects of atorvastatin on chronic subdural hematoma: a systematic review. Medicine (Baltimore). 2017 Jun;96(26):e7290. Erratum in: Medicine (Baltimore). 2017 Jul 21;96(29):e7616.
Jiang R, Zhao S, Wang R, et al. Safety and efficacy of atorvastatin for chronic subdural hematoma in chinese patients: a randomized clinicaltrial. JAMA Neurol. 2018 Nov 1;75(11):1338–1346.
Guidry BS, Kelly KA, Yengo-Kahn AM, et al. Statins as a medical adjunct in the surgical management of chronic subdural hematomas. World Neurosurg. 2021 May;149:e281-e291.
Yamada T, Natori Y. Prospective study on the efficacy of orally administered tranexamic acid and goreisan for the prevention of recurrence after chronic subdural hematoma burr hole surgery. World Neurosurg. 2020 Feb;134:e549-e553.
Hirashima Y, Kurimoto M, Nagai S, et al. Effect of platelet-activating factor receptor antagonist, etizolam, on resolution of chronic subdural hematoma–a prospective study to investigate use as conservative therapy. Neurol Med Chir (Tokyo). 2005 Dec;45(12):621–6; discussion 626.
Hirashima Y, Kuwayama N, Hamada H, et al. Etizolam, an anti-anxiety agent, attenuates recurrence of chronic subdural hematoma–evaluation by computed tomography. Neurol Med Chir (Tokyo). 2002 Feb;42(2):53–5; discussion 56.
Bartek J Jr, Sjåvik K, Schaible S, et al. The role of angiotensin-converting enzyme inhibitors in patients with chronic subdural hematoma: a scandinavian population-based multicenter study. World Neurosurg. 2018 May;113:e555-e560.
Neidert MC, Schmidt T, Mitova T, et al. Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: associations with initial presentation and clinical outcome. J Clin Neurosci. 2016;28:82–86.
Poulsen FR, Munthe S, Søe M, et al. Perindopril and residual chronic subdural hematoma volumes six weeks after burr hole surgery: a randomized trial. Clin Neurol Neurosurg. 2014 Aug;123:4–8.
Hutchinson PJ, Edlmann E, Bulters D, et al; British Neurosurgical Trainee Research Collaborative; Dex-CSDH Trial Collaborators. Trial of dexamethasone for chronic subdural hematoma. N Engl J Med. 2020 Dec 31;383(27):2616–2627.
Shi M, Xiao LF, Zhang TB, et al. Adjuvant corticosteroids with surgery for chronic subdural hematoma: A systematic review and meta-analysis. Front Neurosci. 2021 Dec 8;15:786513.
Mebberson K, Colditz M, Marshman LAG, et al. Prospective randomized placebo-controlled double-blind clinical study of adjuvant dexamethasone with surgery for chronic subdural haematoma with post-operative subdural drainage: interim analysis. J Clin Neurosci. 2020 Jan;71:153–157.
Henaux PL, Le Reste PJ, Laviolle B, et al. Steroids in chronic subdural hematomas (SUCRE trial): study protocol for a randomized controlled trial. Trials. 2017;18:252.
Miah IP, Herklots M, Roks G, et al. Dexamethasone therapy in symptomatic chronic subdural hematoma (DECSA-R): a retrospective evaluation of initial corticosteroid therapy versus primary surgery. J Neurotrauma. 2020 Jan 15;37(2):366–372.
Fujisawa N, Oya S, Yoshida S, et al. A prospective randomized study on the preventive effect of japanese herbal kampo medicine goreisan for recurrence of chronic subdural hematoma. Neurol Med Chir (Tokyo). 2021 Jan 15;61(1):12–20.
Goto S, Kato K, Yamamoto T, et al. Effectiveness of goreisan in preventing recurrence of chronic subdural hematoma. Asian J Neurosurg. 2018 Apr-Jun;13(2):370–374.
Waqas M, Vakhari K, Weimer PV, et al. Safety and effectiveness of embolization for chronic subdural hematoma: systematic review and case series. World Neurosurg. 2019 Jun;126:228–36.
Link TW, Boddu S, Paine SM, et al. Middle meningeal artery embolization for chronic subdural hematoma: a series of 60 cases. Neurosurgery. 2019 Dec 1;85(6):801–807.
Ban SP, Hwang G, Byoun HS, et al. Middle meningeal artery embolization for chronic subdural hematoma. Radiology. 2018 Mar;286(3):992–999.
Catapano JS, Ducruet AF, Nguyen CL, et al. Middle meningeal artery embolization for chronic subdural hematoma: an institutional technical analysis. J Neurointerv Surg. 2021 Jul;13(7):657–660.
Court J, Touchette CJ, Iorio-Morin C, et al. Embolization of the middle meningeal artery in chronic subdural hematoma - a systematic review. Clin Neurol Neurosurg. 2019 Nov;186:105464.
Kim E. Embolization therapy for refractory hemorrhage in patients with chronic subdural hematomas. World Neurosurg. 2017;101:520–527.

No competing interests reported.

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Journal Publication

published 18 Apr, 2023

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Editorial decision: Major revision
05 Mar, 2023
Reviews received at journal
18 Jan, 2023
Reviewers agreed at journal
16 Jan, 2023
Reviewers invited by journal
16 Jan, 2023
Editor assigned by journal
16 Jan, 2023
Submission checks completed at journal
13 Jan, 2023
First submitted to journal
11 Jan, 2023

You are reading this latest preprint version

Effect of Postoperative Tranexamic Acid on Recurrence Rate and Complications in Chronic Subdural Hematomas Patients: Preliminary Results of a Randomized Controlled Clinical Trial

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Method

Design of Study

Participants

Interventions

Outcomes

Sample Size

Randomization

Statistical Methods

Results

Participant flow

Baseline Data

Outcomes

Discussion

Limitations

Generalization

Interpretation

Conclusion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1