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BACKGROUND: Postoperative drainage after surgical evacuation of chronic subdural haematoma reduces the risk of recurrence, but the optimum drainage time is uncertain. We aimed to investigate the shortest possible drainage time without increasing the haematoma recurrence rate. METHODS: We conducted a randomised, multi-arm and multistage non-inferiority trial at four neurosurgical centres in Denmark. We enrolled adult patients (aged ≥18 years) with symptomatic chronic subdural haematoma. All patients were treated according to the national standard practice with a burr hole above the maximum width of the haematoma. Patients were randomly assigned in a 1:1:1 ratio via a centralised web server to receive 6 h, 12 h, or 24 h of postoperative passive subdural drainage. Randomisation was done by an independent on-call neurosurgeon and was masked until 6 h after surgery. The primary outcome was symptomatic haematoma recurrence at 3 months after surgery; the rate of recurrence was assessed in a regression model for non-inferiority testing, with no missing data. Personnel assessing the primary outcome were masked to group allocation. Non-inferiority was assessed with a prespecified margin of 7%, in a modified intention-to-treat population-defined as patients with randomly assigned treatment excluding those withdrawing from study participation after randomisation, or experiencing acute rebleedings or accidental drain removal. This trial is registered with ISRCTN (number 15186366); the trial was stopped after the first interim analysis on the advice of an independent safety advisory committee. FINDINGS: Between March 1, 2021, and June 30, 2022, 347 patients were enrolled and 331 were followed up to 3 months, 105 were assigned to 6 h of drainage, 111 to 12 h of drainage, and 115 to 24 h of drainage. At admission, 83 (25%) participants were women and 248 (75%) were men, mean age was 75·7 years (SD 10·5), median modified Rankin Scale score was 4 (IQR 3-5), and median Glasgow Coma Scale score was 15 (IQR 14-15). At 3 months after surgery, haematoma recurrence was reported in 28 (27%) of 105 patients who were assigned to 6 h drainage (predicted haematoma recurrence rate 27·0%, 95% CI 18·5 to 35·4), 22 (20%) of 111 assigned to 12 h drainage (19·5%, 12·0 to 27·0), and 12 (10%) of 115 assigned to 24 h drainage (10·4%, 4·8 to 16·0). The risk of haematoma recurrence was increased by 16·5 percentage points (95% CI 6·5 to 26·6) in patients drained for 6 h compared with 24 h, and by 9·1 percentage points (-0·4 to 18·5) in patients drained for 12 h compared with 24 h. Therefore, non-inferiority of 6 h and 12 h of drainage to 24 h of drainage was not established. 20 patients had died by 3 months, seven in the 6 h group, eight in the 12 h group, and five in the 24 h group. The most frequent known causes of death were haematoma recurrence (three in 12 h group), comorbidity (three in 12 h group), and pneumonia (one each in 6 h and 12 h groups, two in 24 h group). The most frequent complication was postoperative infection, reported in 20 (20%) patients in the 6 h group, 25 (23%) in the 12 h group, and 19 (17%) in the 24 h group. The most common infection source was the urinary tract. INTERPRETATION: Patients surgically treated for symptomatic chronic subdural haematoma and postoperatively drained for 6 h or 12 h had higher rates of haematoma recurrence than did patients drained for 24 h. The findings from this non-inferiority trial provide evidence to support 24 h of postoperative drainage as the standard drain time when a fixed drain time approach is used. To provide solid evidence of generalisability of the results to countries other than Denmark, a multinational randomised controlled trial will be needed. FUNDING: None.
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Drenagem , Hematoma Subdural Crônico , Humanos , Hematoma Subdural Crônico/cirurgia , Masculino , Feminino , Drenagem/métodos , Idoso , Pessoa de Meia-Idade , Dinamarca , Fatores de Tempo , Recidiva , Idoso de 80 Anos ou mais , Resultado do Tratamento , Cuidados Pós-Operatórios/métodosRESUMO
INTRODUCTION: The pathophysiology of chronic subdural hematoma (CSDH) remains to be fully understood. Basic knowledge of the composition and features of cells in the CSDH fluid may contribute to the understanding of the seemingly complex processes involved in CSDH formation and recurrence. This study is the first to examine the composition of cells and of cellular features in both systemic blood and subdural fluid from CSDH patients. We hypothesized that the cellular composition and features in the hematoma fluid may be; 1) different from that in the systemic blood; 2) different between patients with and without recurrence; 3) and different between the first and second operation in patients with recurrent CSDH. METHODS: Systemic blood and subdural hematoma fluid were collected from CSDH patients with and without recurrent CSDH at the time of primary and secondary surgery. Analyses of cells and cellular features included total number of white blood cells, erythroblasts, reticulocytes, platelets, neutrophilocytes, lymphocytes, monocytes, eosinophils, basophils, reticulocytes, immature granulocytes, mean corpuscular cell volume (MCV), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hemoglobin and hematocrit. RESULTS: Of the 85 included patients, 20 patients were operated for a recurrent CSDH within 90 days follow-up. All cells found in the systemic blood were present in the CSDH fluid, but the composition was different (p < 0.0001). MCV was higher in the hematoma fluid from the primary operation of patients later developing a recurrent CSDH compared to patients not developing recurrence (p = 0.009). Also, the percentage distribution of inflammatory cells in hematoma fluid from patients with recurrent CSDH was different between the first and second operation (p = 0.0017). CONCLUSION: This study is the first to investigate the cellular composition of CSDH fluid. Compared to systemic blood and to a reference distribution, an increased number of immune cells were present in the hematoma fluid, supporting an inflammatory component of the CSDH pathophysiology. MCV was higher in the subdural fluid at time of the first operation of CSDH patients later developing recurrence. CLINICAL TRIAL REGISTRATION: The study was approved by the Scientific Ethical Committee of the Capital Region of Denmark (Journal no. H-20051073.
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Hematoma Subdural Crônico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hematoma Subdural Crônico/cirurgia , Hematoma Subdural Crônico/patologia , RecidivaRESUMO
Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845-33,237) and significantly higher than the median systemic blood level of 789 pg/L (465-2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54-44.8) and significantly higher than the dural uPAR level of 0.81 (0.3-1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane.