Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

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Brief Title

Brain Aneurysms: Utility of Cisternal Urokinase Irrigation

Official Title

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

Brief Summary

      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

      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

      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.

Study Type


Primary Outcome


Secondary Outcome

 Aneurysm regrowth


Subarachnoid Hemorrhage, Aneurysmal



Study Arms / Comparison Groups

 No treatment
Description:  Those are the patients that do not receive any treatment for the aneurysm, neither endovascular nor surgical


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 1, 2007

Completion Date

December 31, 2020

Primary Completion Date

December 31, 2020

Eligibility Criteria

        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

          -  past medical history of bleeding disorders or liver diseases altering the coagulation

          -  anticoagulation

          -  platelet count <10x109/L

          -  prothrombin time >15 seconds




18 Years - N/A

Accepts Healthy Volunteers



Teresa V Moratal, Nurse, , 

Location Countries


Location Countries


Administrative Informations



Organization ID

CEIm 17-07-2019

Responsible Party


Study Sponsor

University of Valencia

Study Sponsor

Teresa V Moratal, Nurse, Study Chair, Hospital General Universitario Valencia

Verification Date

March 2021