Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

Study Overview
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Brief Summary
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Despite the efforts made in its treatment, aneurysmal subarachnoid haemorrhage continues to induce high mortality and morbidity rates. Today there are treatment protocols in all hospitals. The vast majority prefer, whenever possible, the endovascular route, given its lesser aggressiveness and morbidity. Although embolization prevents aneurysm' rebleeding, it does remove the subarachnoid blood clot. Therefore, it does not modify the evolution, incidence and severity of vasospasm. The idea is to carry out a 10-year retrospective study classifying patients into five groups based on the type of treatment received, analyzing the results' differences. The aim is to improve what is done as much as possible and to be able to propose potential areas for improvement. Besides, this study will be the basis of a future prospective study, prepared without the current one's biases and errors.

Detailed Description
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Aneurysmal subarachnoid hemorrhage continues to have very high morbidity and mortality rates, despite the years elapsed and repeated attempts to reduce it. Stabilizing the aneurysm by embolization or surgical clipping leaves unresolved the vasospasm, responsible for ischemic brain damage, causing neurological sequelae and cognitive impairment. It has long been known that the deoxyhemoglobin liberated from the extravasated red blood cells retained in the subarachnoid clot is the leading cause of vasospasm. Different routes have been tried to minimize its deleterious effects, such as copious lavage of the skull base cisterns, lysing the subarachnoid clot with urokinase or rtPA, administration of vitamin C, iron chelators, or superoxydodismutase-like drugs. The volume of subarachnoid hemorrhage was soon correlated with the vasospasm severity. Once this fact was known in the 1980s and 1990s, cisternal lavage was used extensively during aneurysms' surgical clipping. Clots located in the subarachnoid space were lysed with urokinase or rtPA (recombinant tissue plasminogen activator), showing positive effects, particularly evident for the most severe bleeds, those with Fisher's grades of 3 or higher. However, the introduction of embolization changed the treatment paradigm. As the craniotomy is not carried out, the cisterns are not usually washed, which controls the rebleeding but not the vasospasm. To date, we are not aware of any study that compares the effect on vasospasm of embolization versus clipping of aneurysms with lavage of the cisterns using thrombolytic agents. In the Neurosurgery Department of our Hospital, two periods can be identified in which the treatment of brain aneurysms has been carried out differently. In the first period between 2007 and 2011, the aneurysms were primarily subjected to embolization, and only if there was no indication for endovascular treatment, surgical clipping was performed. In the second period, between 2012 and 2018, they were operated on an emergency basis with clip application and the skull base cisterns washed with urokinase. Embolization was considered if the surgical clipping was judged too risky. The aim is to analyze these two periods and compare the mortality, morbidity, and vasospasm rates, the need for a cerebrospinal fluid diversion (temporary and definitive), and the final neurological and cognitive status for the different therapeutic approaches.

Official Title
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Cerebral Aneurysms: a Retrospective Study on the Experience in Our Hospital With a Comparative Analysis Between the Different Techniques Used in Its Treatment

Conditions
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Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Cerebral, Hydrocephalus

Intervention / Treatment
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* Drug: Urokinase
* Procedure: Endovascular treatment
* Procedure: Clipping
* Procedure: External ventricular drain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years of age harbour one or more saccular brain aneurysms with or without subarachnoid hemorrhage (SAH) multiple aneurysms Exclusion Criteria: absence of brain fusiform, traumatic or mycotic aneurysms SAH due to other causes (trauma, anticoagulation, antiplatelet medication, arteriovenous malformation, or tumor) any medical, neurological, or psychiatric condition that would impair patient's evaluation past medical history of bleeding disorders or liver diseases altering the coagulation anticoagulation platelet count <10x109/L prothrombin time >15 seconds

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No treatment<br>Those are the patients that do not receive any treatment for the aneurysm, neither endovascular nor surgical | |
| External ventricular drain only with neither embolization nor clipping<br>These patients will be treated with an external ventricular drain only with neither embolization nor clipping | Procedure: External ventricular drain<br>* Insertion of an external ventricular drain to treat acute hydrocephalus<br>|
| Embolization<br>These patients will be treated endovascularly | Procedure: Endovascular treatment<br>* Aneurysm treatment through endovascular methods<br>|
| Programmed surgical clipping<br>These patients will be treated no on an emergency basis with surgical clipping of an aneurysm that has bled | Procedure: Clipping<br>* Surgical clipping of brain aneurysms<br>|
| Emergency surgical clipping with cisternal urokinase administration<br>These patients with undergo emergency surgical clipping with cisternal urokinase administration | Drug: Urokinase<br>* Washing the subarachnoid clot induced by a subarachnoid haemorrhage aneurysmal bleeding with urokinase after aneurysm clipping<br>* Other names: Aneurysm clipping plus cisternal lavage with Urokinase;Procedure: Clipping<br>* Surgical clipping of brain aneurysms<br>|
| Patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping<br>This group will include patients with incidental brain aneurysm discovery with no SAH and programmed aneurysm clipping | Procedure: Clipping<br>* Surgical clipping of brain aneurysms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasospasm | Presence and severity of vasospasm | 21 days | 
| Cerebrospinal fluid diversion | Need for temporary or definitive cerebrospinal fluid diversion | 1 year | 
| Mortality rate | Mortality rate in each group of patients | 1 year | 
| Outcome | Glasgow Outcome Score (GOSE) at discharge, 6 and 12 months posttreatment | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aneurysm regrowth | Aneurysm regrowth on follow-up after each tipe of treatment | 10 years | 
| Aneurysm rebleed | Aneurysm rebleed on follow-up after each tipe of treatment | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysm, Subarachnoid haemorrhage, Fibrinolytic Therapy, Intracisternal fibrinolysis, Cerebral vasospasm, Delayed ischemic neurological deficit