Thrombolytic therapy after intraventricular hemorrhage: Do we know enough?

Abstract

Intraventricular hemorrhage (IVH) complicates subarachnoid (SAH) and intracerebral (ICH) hemorrhage in 15% and 40% of patients, respectively [ [1] Daverat P. Castel J.P. Dartigues J.F. Orgogozo J.M. Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis. Stroke. 1991; 22: 1-6 Crossref PubMed Scopus (315) Google Scholar ]. The only available treatment for this condition includes the use of external ventricular drainage (EVD) in the form of intraventricular catheters (IVC) if acute obstructive hydrocephalus develops. This type of therapy, however, faces several limitations: (1) There is no uniform correlation between ventricular enlargement and elevated intracranial pressure after IVH, (2) there is no consistent association between intracranial pressure (ICP) normalization (when elevated) and clinical improvement [ [2] Adams R.E. Diringer M.N. Response to external ventricular drainage in spontaneous intracerebral hemorrhage with hydrocephalus. Neurology. 1998; 50: 519-523 Crossref PubMed Scopus (118) Google Scholar ], (3) cerebrospinal fluid (CSF) drainage via an IVC does not enhance the intrinsic lytic CSF activity and therefore does not enhance intraventricular clot resolution, (4) the presence of intraventricular catheters are risk factors for bacterial ventriculitis, which seems more prevalent after IVH [ [3] Lozier A.P. Sciacca R.R. Romagnoli M.F. Connolly E.S. Ventriculostomy-related infections: a critical review of the literature. Neurosurgery. 2002; 51: 170-182 Crossref PubMed Scopus (427) Google Scholar ], and (5) these devices are prone to occlusion when large volumes of blood occupy the ventricles. If IVC occlusion occurs, the need for repeated catheter insertions and their associated risks, such as tissue contusion along the catheter tract, increase the overall morbidity and mortality of this condition. All these reasons have driven the interest in efficiently and rapidly removing intraventricular clots in an attempt to minimize the risks of the complications mentioned. Furthermore, recognition and extrapolation of other nonmechanical forms of secondary neuronal damage such as “hemotoxicity” have also increased the interest in the rapid evacuation of blood and its degradation products from the ventricular system in patients with IVH [ 4 Figueroa B.E. Keep R.F. Betz A.L. Hoff J.T. Plasminogen activators potentiate thrombin-induced brain injury. Stroke. 1998; 29: 1202-1207 Crossref PubMed Scopus (51) Google Scholar , 5 Gong C. Boulis N. Qian J. Turner D.E. Hoff J.T. Keep R.F. Intracerebral hemorrhage-induced neuronal death. Neurosurgery. 2001; 48: 875-882 PubMed Google Scholar , 6 Hua Y. Xi G. Keep R.F. Wu J. Jiang Y. Hoff J.T. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. J. Cereb. Blood Flow Metab. 2002; 22: 55-61 Crossref PubMed Scopus (64) Google Scholar , 7 Lee K.R. Kawai N. Kim S. Sagher O. Hoff J.T. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood–brain barrier permeability, and cell survival in a rat model. J. Neurosurg. 1997; 86: 272-278 Crossref PubMed Scopus (337) Google Scholar , 8 Lee K.R. Betz A.L. Kim S. Keep R.F. Hoff J.T. The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage. Acta Neurochir. (Wien.). 1996; 138: 396-400 Crossref PubMed Scopus (126) Google Scholar , 9 Lee K.R. Colon G.P. Betz A.L. Keep R.F. Kim S. Hoff J.T. Edema from intracerebral hemorrhage: the role of thrombin. J. Neurosurg. 1996; 84: 91-96 Crossref PubMed Scopus (317) Google Scholar , 10 Lee K.R. Betz A.L. Keep R.F. Chenevert T.L. Kim S. Hoff J.T. Intracerebral infusion of thrombin as a cause of brain edema. J. Neurosurg. 1995; 83: 1045-1050 Crossref PubMed Scopus (118) Google Scholar , 11 Masada T. Hua Y. Xi G. Yang G.Y. Hoff J.T. Keep R.F. Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist. J. Neurosurg. 2001; 95: 680-686 Crossref PubMed Scopus (93) Google Scholar , 12 Xi G. Keep R.F. Hua Y. Hoff J.T. Thrombin preconditioning, heat shock proteins and thrombin-induced brain edema. Acta Neurochir., Suppl. 2000; 76: 511-515 PubMed Google Scholar , 13 Xi G. Wagner K.R. Keep R.F. Hua Y. de Courten-Myers Broderick J.P. et al. Role of blood clot formation on early edema development after experimental intracerebral hemorrhage. Stroke. 1998; 29: 2580-2586 Crossref PubMed Scopus (278) Google Scholar , 14 Xi G. Keep R.F. Hoff J.T. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J. Neurosurg. 1998; 89: 991-996 Crossref PubMed Scopus (289) Google Scholar , 15 Yang G.Y. Betz A.L. Hoff J.T. The effects of blood or plasma clot on brain edema in the rat with intracerebral hemorrhage. Acta Neurochir., Suppl. (Wien.). 1994; 60: 555-557 PubMed Google Scholar ].