Management of delayed edema formation after fibrinolytic therapy for intracerebral hematomas: Preliminary experimental data

Abstract

Fibrinolytic therapy for spontaneous intracerebral hemorrhage using recombinant tissue plasminogen activator (rtPA) is considered a viable alternative to microsurgical hematoma removal. However, experimental data suggest that rtPA is neurotoxic and evokes a late perihe-matomal edema. We present preliminary data focusing on the avoidance of late edema formation after lysis of an intracerebral hematoma in a porcine model. Twenty pigs underwent placement of a frontal intracerebral hematoma with a minimum volume of 1 mL. Half of the pigs were subjected to rtPA clot lysis and MK-801 injection for blockage of the NMDA receptor-mediated rtPA-enhanced excitotoxic pathway. The remaining 10 pigs received desmoteplase (DSPA) for clot lysis, which is known to be a less neurotoxic fibrinolytic agent than rtPA. MRI on the day of surgery and on postoperative days 4 and 10 was used to assess hematoma and edema volumes. Late edema formation could be prevented in both the MK-801/rtPA and DSPA pigs. The benefits of fibrinolytic therapy for intracerebral hematomas appear to be counterbalanced by late edema formation. MK-801 infusion as an adjunct to rtPA lysis, or the use of DSPA instead of rtPA, prevents late edema and therefore has the potential to further improve results after clot lysis. © 2008 Springer-Verlag.