In gratitude of the loyal support of our members, the CNS is offering complimentary 2021 Annual Meeting registration to all members! Learn more.

  • The effect of epsilon amino-caproic acid on the development of obstructive hydrocephalus following aneurysmal subarachnoid hemorrhage: A case control study

    Final Number:

    Joshua York Menendez MD; Joseph H. Miller MD; Kristen Lamb PA-C; Bonita Agee; Beverly C. Walters MD, MSc, FRCS(C), FACS; Mark R. Harrigan MD

    Study Design:
    Clinical trial

    Subject Category:
    Aneurysm/Subarachnoid Hemorrhage

    Meeting: AANS/CNS Cerebrovascular Section 2015 Annual Meeting

    Introduction: Epsilon amino-caproic acid (EACA) and other antifibrinolytic agents are used to prevent rehemorrhage following aneurysmal subarachnoid hemorrhage (SAH). Increased rates of hydrocephalus (HCP) due to EACA administration has been reported. We present a case control study investigating the relationship between EACA administration and the development of shunt-dependent HCP.

    Methods: A power analysis was performed to determine sample size. All of the patients in this study were managed by a single neurosurgeon who treated all SAH patients with EACA prior to February, 2012 and then discontinued the use of EACA after that time. From a cohort of 129 consecutive patients diagnosed with SAH who met inclusion criteria, 57 patients who required placement of a ventriculoperitoneal shunt (VPS) were identified as cases. The remaining 72 patients, who did not get a VPS, were designated as controls. Demographic data, clinical and radiographic grading scales and details of the clinical course and treatment were extracted from a retrospective review of medical charts of both groups. Cases and controls were compared to identify factors that contributed to the development of shunt-dependent HCP.

    Results: The overall rate of VPS placement was 44%. The rate of EACA treatment was in the cases was 43.9%, and 55.6% among the controls (p=0.2). Patients presenting with intraventricular hemorrhage or with a Hunt and Hess III or IV clinical exam were more likely to require a VPS (p<0.0001).

    Conclusions: The administration of EACA does not appear to increase the incidence of shunt-dependent HCP following SAH.

    Patient Care: There has been a trend towards abandoning anti-fibrinolytic therapy in the treatment of SAH due to concern for increased rates of shunt-dependent hydrocephalus. There have been no studies dedicated to elucidating any causative relationship between these two entities. Our study shows that the administration of anti-fibrinolytic agents does not cause increased rates of hydrocephalus and anti-fibrinolytic agents should not be held for this concern.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Discuss the controversy surrounding anti-fibrinolytic agents in the treatment of SAH, 2) Describe clinical factors contributing to the development of shunt-dependent hydrocephalus following SAH.

    References: 1. Auer LM, Mokry M: Disturbed cerebrospinal fluid circulation after subarachnoid hemorrhage and acute aneurysm surgery. Neurosurgery 26:804–808; discussion 808–809, 1990 2. Baharoglu MI, Germans MR, Rinkel GJE, Algra A, Vermeulen M, van Gijn J, et al.: Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 8:CD001245, 2013 3. De Oliveira JG, Beck J, Setzer M, Gerlach R, Vatter H, Seifert V, et al.: Risk of shunt-dependent hydrocephalus after occlusion of ruptured intracranial aneurysms by surgical clipping or endovascular coiling: a single-institution series and meta-analysis. Neurosurgery 61:924–933; discussion 933–934, 2007 4. Dehdashti AR, Rilliet B, Rufenacht DA, de Tribolet N: Shunt-dependent hydrocephalus after rupture of intracranial aneurysms: a prospective study of the influence of treatment modality. J Neurosurg 101:402–407, 2004 5. Dóczi T, Nemessányi Z, Szegváry Z, Huszka E: Disturbances of cerebrospinal fluid circulation during the acute stage of subarachnoid hemorrhage. Neurosurgery 12:435–438, 1983 6. Dorai Z, Hynan LS, Kopitnik TA, Samson D: Factors related to hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 52:763–769; discussion 769–771, 2003 7. Ellington E, Margolis G: Block of arachnoid villus by subarachnoid hemorrhage. J Neurosurg 30:651–657, 1969 8. Erixon HO, Sorteberg A, Sorteberg W, Eide PK: Predictors of shunt dependency after aneurysmal subarachnoid hemorrhage: results of a single-center clinical trial. Acta Neurochir (Wien):2014 9. Fodstad H, Liliequist B, Schannong M, Thulin CA: Tranexamic acid in the preoperative management of ruptured intracranial aneurysms. Surg Neurol 10:9–15, 1978 10. Graff-Radford NR, Torner J, Adams HP, Kassell NF: Factors associated with hydrocephalus after subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. Arch Neurol 46:744–752, 1989 11. Gruber A, Reinprecht A, Bavinzski G, Czech T, Richling B: Chronic shunt-dependent hydrocephalus after early surgical and early endovascular treatment of ruptured intracranial aneurysms. Neurosurgery 44:503–509; discussion 509–512, 1999 12. Harrigan MR, Rajneesh KF, Ardelt AA, Fisher WS: Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus. Neurosurgery 67:935–939; discussion 939–940, 2010 13. Hasan D, Vermeulen M, Wijdicks EF, Hijdra A, van Gijn J: Management problems in acute hydrocephalus after subarachnoid hemorrhage. Stroke J Cereb Circ 20:747–753, 1989 14. Heros RC: Acute hydrocephalus after subarachnoid hemorrhage. Stroke J Cereb Circ 20:715–717, 1989 15. Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson K-E: Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg 97:771–778, 2002 16. Inagawa T, Kamiya K, Ogasawara H, Yano T: Rebleeding of ruptured intracranial aneurysms in the acute stage. Surg Neurol 28:93–99, 1987 17. Juvela S: Rebleeding from ruptured intracranial aneurysms. Surg Neurol 32:323–326, 1989 18. Kassell NF, Torner JC, Adams HP: Antifibrinolytic therapy in the acute period following aneurysmal subarachnoid hemorrhage. Preliminary observations from the Cooperative Aneurysm Study. J Neurosurg 61:225–230, 1984 19. Kassell NF, Torner JC, Haley EC, Jane JA, Adams HP, Kongable GL: The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1: Overall management results. J Neurosurg 73:18–36, 1990 20. Kassell NF, Torner JC, Jane JA, Haley EC, Adams HP: The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results. J Neurosurg 73:37–47, 1990 21. Kazumata K, Kamiyama H, Ishikawa T, Makino K, Nakamura T, Takizawa K, et al.: Clinical study of cerebrospinal fluid dynamics using 111In-DTPA SPECT in patients with subarachnoid hemorrhage. Neurol Med Chir (Tokyo) 46:11–17; discussion 17–18, 2006 22. Knibestöl M, Karadayi A, Tovi D: Echo-encephalographic study of ventricular dilatation after subarachnoid hemorrhage, with special reference to the effect of antifibrinolytic treatment. Acta Neurol Scand 54:57–70, 1976 23. Kosteljanetz M: CSF dynamics in patients with subarachnoid and/or intraventricular hemorrhage. J Neurosurg 60:940–946, 1984 24. Leipzig TJ, Redelman K, Horner TG: Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy. J Neurosurg 86:220–225, 1997 25. Lin LF, Houng A, Reed GL: Epsilon amino caproic acid inhibits streptokinase-plasminogen activator complex formation and substrate binding through kringle-dependent mechanisms. Biochemistry (Mosc) 39:4740–4745, 2000 26. Mehta V, Holness RO, Connolly K, Walling S, Hall R: Acute hydrocephalus following aneurysmal subarachnoid hemorrhage. Can J Neurol Sci J Can Sci Neurol 23:40–45, 1996 27. Milhorat TH: Acute hydrocephalus. N Engl J Med 283:857–859, 1970 28. Milhorat TH: Acute hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 20:15–20, 1987 29. Nishioka H, Torner JC, Graf CJ, Kassell NF, Sahs AL, Goettler LC: Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: a long-term prognostic study. III. Subarachnoid hemorrhage of undetermined etiology. Arch Neurol 41:1147–1151, 1984 30. Paré L, Delfino R, Leblanc R: The relationship of ventricular drainage to aneurysmal rebleeding. J Neurosurg 76:422–427, 1992 31. Park BE: Spontaneous subarachnoid hemorrhage complicated by communicating hydrocephalus: epsilon amino caproic acid as a possible predisposing factor. Surg Neurol 11:73–80, 1979 32. Roos YBWEM, Rinkel GJE, Vermeulen M, Algra A, van Gijn J: Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev:CD001245, 2003 33. Sethi H, Moore A, Dervin J, Clifton A, MacSweeney JE: Hydrocephalus: comparison of clipping and embolization in aneurysm treatment. J Neurosurg 92:991–994, 2000 34. Sheehan JP, Polin RS, Sheehan JM, Baskaya MK, Kassell NF: Factors associated with hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 45:1120–1127; discussion 1127–1128, 1999 35. Vale FL, Bradley EL, Fisher WS: The relationship of subarachnoid hemorrhage and the need for postoperative shunting. J Neurosurg 86:462–466, 1997 36. Vermeulen M, Lindsay KW, Murray GD, Cheah F, Hijdra A, Muizelaar JP, et al.: Antifibrinolytic treatment in subarachnoid hemorrhage. N Engl J Med 311:432–437, 1984

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy