Prospective, Randomized, Open-Label Phase II Trial on Concomitant Intraventricular Fibrinolysis and Low-Frequency Rotation After Severe Subarachnoid Hemorrhage

Abstract

This was a randomized, prospective, open-label, treatment as usualcontrolled phase II study, investigating feasibility, safety, and efficacy. The study was reviewed and approved by the local institutional ethics committee (ID#: 3062) of the Medical Faculty of the Heinrich-HeineUniversity, Düsseldorf, Germany. Sixty patients experiencing aneurys mal SAH, that is, World Association of Neurological Surgeons (WFNS) grade II to V and Fisher grade III to IV, were randomized into experimental or control treatment. 8,9Participants Eligible patients were allocated into the 2 treatment groups in accordance with the randomization sequence after informed consent was obtained. Inclusion criteria were (1) aneurysmal SAH WFNS grade II to V and Fisher grade III to IV; (2) patients aged ˃18 years; (3) admission <24 hours after ictus; (4) no history of anticoagulative or plateletinhibiting drugs; (5) informed consent by a legal representative; and Background and Purpose-The goal of this randomized, open-label phase II study was to investigate the effect of concomitant low-frequency head-motion therapy and intraventricular fibrinolysis in patients after surgical or endovascular treatment for aneurysmal subarachnoid hemorrhage.

Intraventricular Fibrinolysis with Tissue Plasminogen Activator is Associated with Transient Cerebrospinal Fluid Inflammation: A Randomized Controlled Trial

“…4,8,38 It is now well established by randomized trials that pharmacological use of intraventricular TPA accelerates hematoma clearance, both from the ventricles and basal cisterns. 12,13,38 Although the removal of blood is thought to be potentially beneficial in reducing the risk of complications, such as hydrocephalus and delayed cerebral ischemia, our findings suggest that the sudden, rapid release of hematoma breakdown products may transiently perpetuate injury and induce inflammation.…”

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain

“…Local administration of tissue plasminogen activator (TPA) accelerates clearance of intraventricular and subarachnoid blood [3][4][5]. Although the administration of TPA into the ventricles is thought to be safe, rare cases of iatrogenic intracranial hemorrhage have been reported [5,6].…”

“…Local administration of tissue plasminogen activator (TPA) accelerates clearance of intraventricular and subarachnoid blood [3][4][5]. Although the administration of TPA into the ventricles is thought to be safe, rare cases of iatrogenic intracranial hemorrhage have been reported [5,6]. Moreover, intraventricular TPA may have other adverse effects, including direct neurotoxicity, the promotion of inflammation, and worsening cerebral edema [7][8][9][10].…”

“…Clinical trials and case series have used regimens ranging from 0.3 to 8 mg, administered every 6-24 h [3][4][5][11][12][13][14][15][16][17]. Some studies suggest that smaller doses are as effective as larger ones and are associated with a lower bleeding risk [15][16][17][18][19].…”

Drug treatment of cerebral vasospasm after subarachnoid hemorrhage following aneurysms

“…Intracisternal administration of low-dose rt-PA for the prevention of CVS after SAH has been demonstrated safe and effective [78]. Recently, a randomized, openlabel phase II study on concomitant low-frequency head-motion therapy and intraventricular rt-PA has been administrated in patients after surgical or endovascular treatment for aSAH, with effective subarachnoid clot reduction, despite a poor effect on radiographic vasospasm, cerebral infarction, or neurological outcome [79]. Though clearance of subarachnoid clots to prevent CVS has been accepted, optimal administration and dosage of fibrinolysis still need to be established.…”