Intracisternal Therapy with Tissue Plasminogen Activator for the Prevention of Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage. A Review

Abstract BACKGROUND The sequelae of aneurysmal subarachnoid hemorrhage (SAH) include vasospasm and hydrocephalus. OBJECTIVE To assess whether intraventricular tissue plasminogen activator (tPA) results in less vasospasm, fewer angioplasties, or fewer cerebrospinal fluid shunting procedures. METHODS 41 patients (tPA group, Hunt and Hess 3, 4, 5) from 2007 to 2008 received intraventricular tPA and lumbar drainage for a minimum of 5 days (range 5–7 days) and were compared to a matched group of 35 patients from 2006 to 2007 (Control, HH 3, 4, 5). Statistical comparison was done by t test analysis or Fisher exact tests and data are expressed as average ± standard error of the mean. RESULTS There were no significant differences in demographic data, although the tPA group had a trend toward more surgical patients. The tPA group of patients had a significantly higher modified Fisher grade than controls (P < .001) and had a significantly better Hunt and Hess grade than controls (P < .03). The angioplasty rate was significantly lower among the tPA patients (15.0% ± 5.6) than controls (40.0% ± 8.5, P = .019). The number of days spent in severe vasospasm normalized over the 14-day monitoring period by transcranial Doppler was significantly lower in the tPA group (0.09 ± 0.02) than controls (0.17 ± 0.03). The shunt rate was significantly lower among tPA patients (17.5% ± 6.0) than controls (42.8% ± 8.6). There were 2 clinically silent tract hemorrhages in the tPA group (4.8%). CONCLUSION Intraventricular tPA is a safe and effective treatment for reducing both angioplasty and shunting rates in patients with SAH H&H Grades 3 to 5. A randomized trial is indicated.

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Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1991.75.2.0189 ◽

1991 ◽

Vol 75 (2) ◽

pp. 189-196 ◽

Cited By ~ 117

Author(s):

Joseph M. Zabramski ◽

Robert F. Spetzler ◽

K. Stuart Lee ◽

Stephen M. Papadopoulos ◽

Edwin Bovill ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Phase I ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Subarachnoid Space ◽

Phase I Trial ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Postoperative Treatment ◽

Bleeding Complications ◽

Tissue Plasminogen

✓ Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated.

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