Prevention of delayed ischaemic deficits after aneurysmal subarachnoid haemorrhage by intrathecal bolus injection of tissue plasminogen activator (rTPA)

Summary

Among a series of 224 patients with aneurysmal subarachnoid haemorrhage (SAH) admitted over a period of three years, 52 patients were prospectively treated with intrathecal tissue plasminogen activator (rTPA). All of these patients were admitted and operated on within 72 h after SAH. SAH was confirmed by CT scan and the volume of blood accumulated in the basal cisterns was graded according to Fisher's scale. All patients had a SAH according to Fisher's grade III, as a prerequisite for inclusion into the study. In 21 patients additional intraventricular bleeding was detectable on CT scan. The diagnosis of a single intracerebral aneurysm as the bleeding source was established by pan-angiography, which also excluded additional cerebro-vascular malformations.

The control group consisted of 68 patients, which were also treated within 72 h after SAH. Age and sex distribution as well as the clinical patterns were comparable to the rTPA group.

In all patients the aneurysm was clipped using standard microsurgical techniques. After the aneurysm had been excluded from the parent vessel, 10 mg of rTPA, dissolved in 10 ml of its solution fluid, were slowly instilled into the basal cisterns in the treatment group. In patients with additional severe intraventricular bleeding, 5–10 mg of rTPA were injected into the ventricles via an intraventricular catheter at the end of the operation. Apart from the intrathecal application of the thrombolytic substance, the surgical protocol was identical in the patients of the control group.

During the postoperative period, the patients in both groups were examined neurologically and by transcranial Doppler on a daily basis. CT scans were performed on days 1, 2, 5, 10 postoperatively and immediately prior to discharge. Final clinical grading for this study was performed three months after surgery and the patients were graded according to the Glasgow Outcome Scale. The occurrence of clinical signs of delayed ischaemic deficits (DID), attributable to the occurrence of cerebral vasospasm, was the only defined endpoint of the study. Radical blood clot removal, verfied by serial CT scans was achieved in all patients treated using the intrathecal thrombolytic agent.

Overall results in the rTPA group at three months postsurgery were as follows: 39 patients (75%) were in grade I, 7 in grade II (13.5%), and 6 patients (11.5%) were in grade III GOS. Delayed ischaemic deficits, attributable to the occurrence of vasospasm were apparent in 4 patients (8%), in whom clinical symptoms were moderate in two patients and severe in another two. Three patients responded well to moderate hypertensive-hypervolaemic treatment resulting in an increase of their systolic arterial pressure up to 160 mm Hg. In none of these three patients cerebral infarction and/or permanent neurological deficits developed. In one patient with spasmogenic infarction of the middle cerebral artery territory in complete hemiparesis persisted. The overall results in the control group were as follows: 44 patients (64%) were in grade I GOS postoperatively, 6 in grade II (9%), 14 in grade III (21%), 1 in grade IV (1.5%), and three patients (4%) had died. DID attributable to the development of vasospasm developed in 16 patients (23.5%). DID were transient in 9 patients (13%) resolving completely after induction of hypertensive and hypervolaemic therapy. In four patients (6%) neurological deficits persisted despite vigorous treatment, and 3 patients (4%) died from spasmogenic cerebral infarction.

From the results of this first prospective study of a single bolus injection of rTPA in patients with aneurysm rupture, it is concluded, that intrathecal thrombolysis is an effective and safe method for removal of intracisternal blood accumulations after SAH resulting in a significant reduction of symptomatic vasospasm and DID. With regard to the radicality of blood clot removal achievable by the use of rTPA it is furthermore concluded, that conversion of a SAH according to Fisher grade III into a SAH of Fisher grade II is sufficient for significant reduction of the incidence of posthaemorrhagic DID, avoiding the necessity of complete pharmacological blood clot evacuation and the use of higher concentrations of rTPA or continuous irrigation of the subarachnoid space.