Urokinase Is Safe and Effective in Reducing Recurrence in Chronic Subdural Hematoma After Burr-Hole Drainage.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of subdural urokinase in reducing the recurrence of chronic subdural hematoma (cSDH). METHODS: Consecutive adults with cSDH and burr-hole drainage from 1 January 2013 to 31 December 2017 were retrospectively analyzed. Clinical records, radiologic images, laboratory data, and medication records were reviewed. The primary outcome was the recurrence rate of cSDH in patients with or without urokinase instillation. Secondary outcomes included complication rates such as infection and acute intracranial hemorrhage. Univariate and multivariate analyses were conducted to identify independent factors associated with cSDH recurrence. RESULTS: A total of 297 consecutive patients were identified for analysis. The average dosage of urokinase instillation via the subdural drain into the subdural space was 15,800 units (5000-60,000 units) over a mean duration of 2 days (1-6 days). The symptomatic recurrence rate of cSDH was significantly lower with urokinase at 3.0% versus 11.7% with no urokinase (odds ratio: 0.234; P = 0.022). Univariate analysis and multivariate analysis showed that bilateral cSDH and the presence of underlying liver disease were significantly associated with higher recurrence, while the instillation of urokinase was significantly and independently associated with lower recurrence (odds ratio = 0.311; P = 0.005). Complication rates including infection and hemorrhage were comparable with patients with or without urokinase and had no significant difference. CONCLUSIONS: Instillation of urokinase was safe for patients with cSDH. The recurrence rate of cSDH was significantly lower with urokinase.

High-dose simvastatin for aneurysmal subarachnoid hemorrhage: a multicenter, randomized, controlled, double-blind clinical trial protocol.

BACKGROUND: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage. However, no clinical data are available to answer whether a high-dose regimen is more effective than a normal-dose regimen, even though the biochemical actions and related neuroprotective mechanisms are thought to be dose related. OBJECTIVE: To determine whether 80 mg simvastatin daily (high dose) over 3 weeks initiated within 96 hours of the ictus will reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with 40 mg simvastatin daily (normal dose), leading to improvements in clinical outcomes and thus cost-effectiveness. METHODS: The study design is a randomized, controlled, double-blind clinical trial (www.ClinicalTrials.gov; identifier: NCT01077206). Two hundred forty patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers are being recruited over 3 years. The primary outcome measure is the presence of delayed ischemic deficits. Secondary outcome measures include modified Rankin Disability Score at 3 months and cost-effectiveness analysis. EXPECTED OUTCOMES: This will be the first study to clarify whether high-dose simvastatin is better than normal-dose simvastatin for patients with acute aneurysmal subarachnoid hemorrhage in terms of neurological outcomes and cost-effectiveness. DISCUSSION: In the present trial, we compare high-dose and normal-dose simvastatin; we know that another ongoing phase III multicenter trial (Simvastatin in Aneurysmal Subarachnoid Haemorrhage; http://www.stashtrial.com/home.html) is comparing normal-dose and no simvastatin. When the results are interpreted together, the research question of a possible beneficial effect of high-dose simvastatin in acute aneurysmal subarachnoid hemorrhage could be answered.