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Published in: Neurosurgical Review 4/2013

01-10-2013 | Original Article

Intraventricular fibrinolysis for severe aneurysmal intraventricular hemorrhage: a randomized controlled trial and meta-analysis

Authors: Stephane Litrico, Fabien Almairac, Thomas Gaberel, Rohan Ramakrishna, Denys Fontaine, Jacques Sedat, Michel Lonjon, Philippe Paquis

Published in: Neurosurgical Review | Issue 4/2013

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Abstract

The aim of this study was to assess the safety and efficacy of intraventricular fibrinolysis (IVF) for aneurysmal subarachnoid hemorrhage (aSAH) with severe intraventricular hemorrhage (IVH). In this randomized controlled trial, between 2005 and 2009, patients with aSAH and severe IVH were randomly assigned into two groups: one treated with external ventricular drainage (EVD) combined with intraventricular recombinant tissue plasminogen activator (rt-PA) and the second with EVD alone. The primary end-point was mortality rate within the first 30 days. We performed meta-analysis including all published articles that compared IVF + EVD to EVD alone in patients with aSAH IVH. Eleven patients were included in the rt-PA group, eight in the control group. At 30 days, mortality rate was lower in the rt-PA group (45.5 vs. 62.5 %), but results were not statistically significant (p = 0.65). Clearance of third and fourth ventricles was obtained previously in the rt-PA group (4.25 days) compared to the control group (10.67 days) (p = 0.001). There was no statistically significant difference concerning the occurrence of complications. The meta-analysis showed a better survival rate with IVF without raised statistical significance (odds ratio = 0.32 [95 % confidence interval, 0.10–1.03]). This study shows that IVF is as safe as EVD alone for aSAH with severe IVH. It accelerates blood clot resolution in the ventricular system. Mortality rate could be improved by IVF but without significant results. Because of the severity and rarity of this pathology, a multicenter study is required.
Clinical Trial Registration Information: www.​clinicaltrials.​gov (NCT00823485)
Literature
1.
go back to reference Akdemir H, Selcuklu A, Pasaoglu A, Oktem IS, Kavuncu I (1995) Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase. Neurosurg Rev 18(2):95–100PubMedCrossRef Akdemir H, Selcuklu A, Pasaoglu A, Oktem IS, Kavuncu I (1995) Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase. Neurosurg Rev 18(2):95–100PubMedCrossRef
2.
go back to reference Ducruet AF, Hickman ZL, Zacharia BE, Grobelny BT, Narula R, Guo KH, Claassen J, Lee K, Badjatia N, Mayer SA, Connolly ES Jr (2010) Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. Neurosurgery 66(4):648–655. doi:10.1227/01.NEU.0000360374.59435.60 PubMedCrossRef Ducruet AF, Hickman ZL, Zacharia BE, Grobelny BT, Narula R, Guo KH, Claassen J, Lee K, Badjatia N, Mayer SA, Connolly ES Jr (2010) Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. Neurosurgery 66(4):648–655. doi:10.​1227/​01.​NEU.​0000360374.​59435.​60 PubMedCrossRef
3.
go back to reference Findlay JM, Grace MG, Weir BK (1993) Treatment of intraventricular hemorrhage with tissue plasminogen activator. Neurosurgery 32(6):941–947, discussion 947PubMedCrossRef Findlay JM, Grace MG, Weir BK (1993) Treatment of intraventricular hemorrhage with tissue plasminogen activator. Neurosurgery 32(6):941–947, discussion 947PubMedCrossRef
4.
go back to reference Findlay JM, Jacka MJ (2004) Cohort study of intraventricular thrombolysis with recombinant tissue plasminogen activator for aneurysmal intraventricular hemorrhage. Neurosurgery 55(3):532–537, discussion 537–538PubMedCrossRef Findlay JM, Jacka MJ (2004) Cohort study of intraventricular thrombolysis with recombinant tissue plasminogen activator for aneurysmal intraventricular hemorrhage. Neurosurgery 55(3):532–537, discussion 537–538PubMedCrossRef
5.
6.
go back to reference Graeb DA, Robertson WD, Lapointe JS, Nugent RA, Harrison PB (1982) Computed tomographic diagnosis of intraventricular hemorrhage. Etiology and prognosis. Radiology 143(1):91–96PubMed Graeb DA, Robertson WD, Lapointe JS, Nugent RA, Harrison PB (1982) Computed tomographic diagnosis of intraventricular hemorrhage. Etiology and prognosis. Radiology 143(1):91–96PubMed
8.
9.
go back to reference Mayfrank L, Hutter BO, Kohorst Y, Kreitschmann-Andermahr I, Rohde V, Thron A, Gilsbach JM (2001) Influence of intraventricular hemorrhage on outcome after rupture of intracranial aneurysm. Neurosurg Rev 24(4):185–191PubMedCrossRef Mayfrank L, Hutter BO, Kohorst Y, Kreitschmann-Andermahr I, Rohde V, Thron A, Gilsbach JM (2001) Influence of intraventricular hemorrhage on outcome after rupture of intracranial aneurysm. Neurosurg Rev 24(4):185–191PubMedCrossRef
10.
go back to reference Morgan T, Awad I, Keyl P, Lane K, Hanley D (2008) Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl 105:217–220PubMedCrossRef Morgan T, Awad I, Keyl P, Lane K, Hanley D (2008) Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl 105:217–220PubMedCrossRef
11.
go back to reference Naff N, Williams MA, Keyl PM, Tuhrim S, Bullock MR, Mayer SA, Coplin W, Narayan R, Haines S, Cruz-Flores S, Zuccarello M, Brock D, Awad I, Ziai WC, Marmarou A, Rhoney D, McBee N, Lane K, Hanley DF Jr (2011) Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial. Stroke 42(11):3009–3016. doi:10.1161/STROKEAHA.110.610949 PubMedCrossRef Naff N, Williams MA, Keyl PM, Tuhrim S, Bullock MR, Mayer SA, Coplin W, Narayan R, Haines S, Cruz-Flores S, Zuccarello M, Brock D, Awad I, Ziai WC, Marmarou A, Rhoney D, McBee N, Lane K, Hanley DF Jr (2011) Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial. Stroke 42(11):3009–3016. doi:10.​1161/​STROKEAHA.​110.​610949 PubMedCrossRef
12.
go back to reference Naff NJ, Hanley DF, Keyl PM, Tuhrim S, Kraut M, Bederson J, Bullock R, Mayer SA, Schmutzhard E (2004) Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial. Neurosurgery 54(3):577–583, discussion 583–574PubMedCrossRef Naff NJ, Hanley DF, Keyl PM, Tuhrim S, Kraut M, Bederson J, Bullock R, Mayer SA, Schmutzhard E (2004) Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial. Neurosurgery 54(3):577–583, discussion 583–574PubMedCrossRef
13.
go back to reference Nieuwkamp DJ, de Gans K, Rinkel GJ, Algra A (2000) Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: a systematic review of the literature. J Neurol 247(2):117–121PubMedCrossRef Nieuwkamp DJ, de Gans K, Rinkel GJ, Algra A (2000) Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: a systematic review of the literature. J Neurol 247(2):117–121PubMedCrossRef
14.
go back to reference O'Kelly CJ, Kulkarni AV, Austin PC, Urbach D, Wallace MC (2009) Shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage: incidence, predictors, and revision rates. Clinical article. J Neurosurg 111(5):1029–1035. doi:10.3171/2008.9.JNS08881 PubMedCrossRef O'Kelly CJ, Kulkarni AV, Austin PC, Urbach D, Wallace MC (2009) Shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage: incidence, predictors, and revision rates. Clinical article. J Neurosurg 111(5):1029–1035. doi:10.​3171/​2008.​9.​JNS08881 PubMedCrossRef
15.
go back to reference Rainov NG, Burkert WL (1995) Urokinase infusion for severe intraventricular haemorrhage. Acta Neurochir (Wien) 134(1–2):55–59CrossRef Rainov NG, Burkert WL (1995) Urokinase infusion for severe intraventricular haemorrhage. Acta Neurochir (Wien) 134(1–2):55–59CrossRef
16.
go back to reference Ramakrishna R, Sekhar LN, Ramanathan D, Temkin N, Hallam D, Ghodke BV, Kim LJ (2010) Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 67(1):110–117. doi:10.1227/01.NEU.0000370920.44359.91, discussion 117PubMedCrossRef Ramakrishna R, Sekhar LN, Ramanathan D, Temkin N, Hallam D, Ghodke BV, Kim LJ (2010) Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 67(1):110–117. doi:10.​1227/​01.​NEU.​0000370920.​44359.​91, discussion 117PubMedCrossRef
17.
go back to reference Rohde V, Schaller C, Hassler WE (1995) Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry 58(4):447–451PubMedCrossRef Rohde V, Schaller C, Hassler WE (1995) Intraventricular recombinant tissue plasminogen activator for lysis of intraventricular haemorrhage. J Neurol Neurosurg Psychiatry 58(4):447–451PubMedCrossRef
18.
go back to reference Rosen DS, Macdonald RL, Huo D, Goldenberg FD, Novakovic RL, Frank JI, Rosengart AJ (2007) Intraventricular hemorrhage from ruptured aneurysm: clinical characteristics, complications, and outcomes in a large, prospective, multicenter study population. J Neurosurg 107(2):261–265. doi:10.3171/JNS-07/08/0261 PubMedCrossRef Rosen DS, Macdonald RL, Huo D, Goldenberg FD, Novakovic RL, Frank JI, Rosengart AJ (2007) Intraventricular hemorrhage from ruptured aneurysm: clinical characteristics, complications, and outcomes in a large, prospective, multicenter study population. J Neurosurg 107(2):261–265. doi:10.​3171/​JNS-07/​08/​0261 PubMedCrossRef
19.
go back to reference S.F.A.R. (2004) Hémorragie sous-arachnoidienne grave. Conférence d'experts. Société Française d'Anesthésie et de Réanimation, Paris S.F.A.R. (2004) Hémorragie sous-arachnoidienne grave. Conférence d'experts. Société Française d'Anesthésie et de Réanimation, Paris
21.
go back to reference Shen PH, Matsuoka Y, Kawajiri K, Kanai M, Hoda K, Yamamoto S, Nishimura S (1990) Treatment of intraventricular hemorrhage using urokinase. Neurol Med Chir (Tokyo) 30(5):329–333CrossRef Shen PH, Matsuoka Y, Kawajiri K, Kanai M, Hoda K, Yamamoto S, Nishimura S (1990) Treatment of intraventricular hemorrhage using urokinase. Neurol Med Chir (Tokyo) 30(5):329–333CrossRef
25.
go back to reference Varelas PN, Rickert KL, Cusick J, Hacein-Bey L, Sinson G, Torbey M, Spanaki M, Gennarelli TA (2005) Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: pilot study of treatment with intraventricular tissue plasminogen activator. Neurosurgery 56(2):205–213, discussion 205–213PubMedCrossRef Varelas PN, Rickert KL, Cusick J, Hacein-Bey L, Sinson G, Torbey M, Spanaki M, Gennarelli TA (2005) Intraventricular hemorrhage after aneurysmal subarachnoid hemorrhage: pilot study of treatment with intraventricular tissue plasminogen activator. Neurosurgery 56(2):205–213, discussion 205–213PubMedCrossRef
26.
go back to reference Webb AJ, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF (2012) Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: The Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Program. Stroke. doi:10.1161/STROKEAHA.112.650523 Webb AJ, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF (2012) Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: The Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Program. Stroke. doi:10.​1161/​STROKEAHA.​112.​650523
28.
go back to reference Yusuf S, Peto R, Lewis J, Collins R, Sleight P (1985) Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 27(5):335–371PubMedCrossRef Yusuf S, Peto R, Lewis J, Collins R, Sleight P (1985) Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 27(5):335–371PubMedCrossRef
Metadata
Title
Intraventricular fibrinolysis for severe aneurysmal intraventricular hemorrhage: a randomized controlled trial and meta-analysis
Authors
Stephane Litrico
Fabien Almairac
Thomas Gaberel
Rohan Ramakrishna
Denys Fontaine
Jacques Sedat
Michel Lonjon
Philippe Paquis
Publication date
01-10-2013
Publisher
Springer Berlin Heidelberg
Published in
Neurosurgical Review / Issue 4/2013
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI
https://doi.org/10.1007/s10143-013-0469-7

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