A multimodal concept in patients after severe aneurysmal subarachnoid hemorrhage: results of a controlled single centre prospective randomized multimodal phase I/II trial on cerebral vasospasm.
OBJECTIVE
Recent publications suggest that a combination of head-shaking and cisternal irrigation might reduce symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). The present clinical prospective randomized phase I/II study was initiated in order to analyze the prophylactic effect of intracisternal lysis in combination with kinetic treatment followed by intrathecal nimodipine lavage.


METHODS
Twenty patients with aneurysmal SAH, WFNS grade 2 to 5 (GCS 13-3) and Fisher grade 3 or 4 were included in this prospective randomized study which had been approved by the local Ethics Research Committee. Following insertion of a ventricular drain, securing of the aneurysm by a microsurgical or endovascular route and the insertion of two lumbar catheters, intracisternal lysis with urokinase 120 000 IU/d was performed for 48 h in the patients of the study group. Intrathecal pressure was monitored by the second lumbar catheter. After intracisternal lysis, intrathecal nimodipine lavage was applied for 7 d. For comatose patients kinetic head-rotation was also performed. Vasospasm was clinically identified with a focus on delayed neurological deficits (DINDs) by daily transcranial Doppler (TCD), computerized tomography (CT), perfusion CT (pCT) and cerebral angiography (DSA).


RESULTS
There was no DIND in the study group among the patients who were awake, while two DINDs occurred in the control group. The pooled TCD flow velocities over an average period of 14 d revealed no statistically significant difference between the groups. Vasospasm-related infarction on CT was seen in two patients of the control group. Evident vasospasm on DSA appeared in three patients of the study group compared with 7 patients in the control group. Moreover there was a neurological improvement in the study population as measured by mRS at 3-month follow-up (P=0.266). In two consecutive patients randomized to the study group a paresis of the lower extremities of unknown origin occurred. As a result of these complications the study was stopped in accordance with the local Ethics Research Committee guidelines.


CONCLUSIONS
A multimodal approach with translumbar lysis in combination with kinetic therapy followed by intrathecal nimodipine lavage proved to be effective against cerebral vasospasm and for clinical outcome. However, due to the observed complications with the occurrence of paraparesis in two patients of the study group the trial was stopped. Nevertheless, the promising preliminary results suggest a further development of the clinical protocol using a modified multimodal concept to prevent and treat cerebral vasospasm after severe SAH.
Hänggi
D
D
Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany. Daniel.Haenggi@uni-duesseldorf.de
Eicker
S
S
Beseoglu
K
K
Behr
J
J
Turowski
B
B
Steiger
H-J
HJ
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D026201:Musculoskeletal Manipulations; D009553:Nimodipine / Q000008:administration & dosage; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D007507:Therapeutic Irrigation; D015912:Thrombolytic Therapy; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage; D020301:Vasospasm, Intracranial / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*
D002121:Calcium Channel Blockers; D009553:Nimodipine; D014568:Urokinase-Type Plasminogen Activator