Optimal drainage time after evacuation of chronic subdural haematoma (DRAIN TIME 2): a multicentre, randomised, multiarm and multistage non-inferiority trial in Denmark.

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.

Treatment of chronic subdural haematoma.

A further rise in chronic subdural haematoma (CSDH) prevalence is expected with an ageing population, and evidence-based guidelines are needed to direct treatment, while creating a platform for research. The Danish Chronic Subdural Hematoma Study (DACSUHS) has implemented the first Danish national CSDH guidelines in 2018 and have standardised CSDH management on a national level. Based on CSDH literature published between 2016 and 2022, these guidelines were updated in 2022. The updated guidelines are presented in this review.

Intraoperative Irrigation and Risk of Chronic Subdural Hematoma Recurrence.

BACKGROUND AND OBJECTIVES: In most neurosurgical centers, irrigation is an essential part of the surgical procedure for chronic subdural hematoma (CSDH). However, it is unknown whether the volume of irrigation fluid affects the risk of CSDH recurrence. This study aimed to investigate a potential association between the volume of irrigation fluid used during burr hole evacuation of CSDH and the risk of CSDH recurrence. METHODS: This study is a subanalysis of 2 randomized trials (Drain Time & Drain Time 2) designed to investigate the effect of drainage duration on the recurrence of CSDH. Intraoperative irrigation volume was measured, and patients were followed for 90 days for recurrent CSDH. RESULTS: A total of 525 patients with CSDH were included. There was no significant difference in the volume of irrigation fluid used between patients with recurrence (mean = 938 mL, SD = ±552) and without recurrence (mean = 852 mL, SD = ±454) ( P -value = .15). Patients with recurrent CSDH had larger primary CSDH volumes (mean = 134 cm 3 , SD = ±69) than patients without recurrence (mean = 119 cm 3 , SD = ±58) ( P = .04). Multiple logistic regression analysis revealed no association between irrigation volume and recurrence, also when stratified for hematoma size. CONCLUSION: There was no significant association between irrigation volume and recurrent CSDH within 90 days in patients undergoing burr hole surgery for CSDH.

Postoperative drainage for 6, 12, or 24 h after burr-hole evacuation of chronic subdural hematoma in symptomatic patients (DRAIN-TIME 2): study protocol for a nationwide randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common acute or subacute neurosurgical condition, typically treated by burr-hole evacuation and drainage. Recurrent CSDH occurs in 5-20% of cases and requires reoperation in symptomatic patients, sometimes repeatedly. Postoperative subdural drainage of maximal 48 h is effective in reducing recurrent hematomas. However, the shortest possible drainage time without increasing the recurrence rate is unknown. METHODS: DRAIN-TIME 2 is a Danish multi-center, randomized controlled trial of postoperative drainage time including all four neurosurgical departments in Denmark. Both incapacitated and mentally competent patients are enrolled. Patients older than 18 years, free of other intracranial pathologies or history of previous brain surgery, are recruited at the time of admission or no later than 6 h after surgery. Each patient is randomized to either 6, 12, or 24 h of passive subdural drainage following single burr-hole evacuation of a CSDH. Mentally competent patients are asked to complete the SF-36 questionnaire. The primary endpoint is CSDH recurrence rate at 90 days. Secondary outcome measures include SF-36 at 90 days, length of hospital stay, drain-related complications, and complications related to immobilization and mortality. DISCUSSION: This multi-center trial will provide evidence regarding the shortest possible drainage time without increasing the recurrence rate. The potential impact of this study is significant as we believe that a shorter drainage period may be associated with fewer drain-related complications, fewer complications related to immobilization, and shorter hospital stays-thus reducing the overall health service burden from this condition. The expected benefits for patients' lives and health costs will increase as the CSDH patient population grows. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15186366 . Registered in December 2020 and updated in October 2021. This protocol was developed in accordance with the SPIRIT Checklist and by use of the structured study protocol template provided by BMC Trials.

Effect of acute exercise on patella tendon protein synthesis and gene expression.

Evidence suggests that habitual loading can result in patellar tendon hypertrophy, especially at the proximal and distal parts of the patellar tendon. The underlying protein kinetic changes and its regulation remains controversial and human data, investigating this topic, are limited. The present study investigated how acute exercise affects growth factor production and collagen fractional synthetic rate in patellar tendon tissue from patients undergoing an anterior cruciate ligament reconstruction operation. The operation was performed by use of the bone-patellar tendon-bone method under spinal anesthesia. Twelve subjects were randomized to one of two groups: a control group or an exercise group (1-hr unilateral knee-extension 67% of Wmax 24 hours before operation). Two hours before the anterior cruciate ligament operation a flooding-dose of L-[1-(13)C]proline was given. Tissue from the most proximal part of the patellar tendon was obtained during the operation. Tendon collagen fractional synthetic rate and mRNA concentrations of TGF-ß-1, CTGF, and type I and III collagen were measured. CTGF and type I collagen expression were higher in the exercise group compared to the control group (p < 0.05). Type III collagen expression (p = 0.11), TGF-ß-1 expression (p = 0.34), and collagen fractional synthetic rate (p = 0.26) did not differ between groups. Although the expression of CTGF and type I collagen were higher, the patellar tendon collagen fractional synthetic rate was not correspondingly higher after exercise. The elevated CTGF expression in the exercise group indicates that the TGF-beta pathway could be an important link between mechanical loading and stimulation of tendon tissue type I collagen expression.