gms | German Medical Science

Objective: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) represents a well-established therapy for spontaneous intracerebral hemorrhage (ICH). However some issues in clinical routine like optimal dose and timing, catheter flushing or CSF irrigation need to be answered. Previously we investigated optimal dosing and timing of this therapy in an in vitro clot model. In addition the aim of this study was to investigate a potential effect of CSF, irrigation and washout on hematoma lysis.

Methods: In vitro blood clots were produced from 25 ml of human blood by 1.5 h incubation at 37 C°. A silicone catheter connected to an irrigation-catheter-system (IRRAS CNS™), which flushes 1ml of NaCl into the clot for 1 min with a following passive gravity drainage period was placed into the clots. Different drainage periods of 15, 30 and 60 min (n=3) were tested. Four different irrigation rates were examined for 60 min of 0, 15, 90, 180 ml/h (each n=5) and. the additional effect of 1mg rtPA was evaluated for these 4 irrigation rates (n=3). Further 6 clots were treated either with 5ml healthy CSF (n=3), hemorrhagic CSF (n=3) and hemorrhagic CSF 1 h after 1 mg rtPA administration. Plasminogen values were measured at different time points during rtPA therapy. Clots were weighed before and after treatment. For statistical analysis ANOVA was used.

Results: The relative weight after 60 min drainage with the irrigation-catheter-system was 58.28%±8.41 for 0 ml/h, 46.33%±9.51 for 15 ml/h, 46.53%±7.06 for 90 ml/h, 53.26% ±4.06 for 180 ml/h. After 15 min incubation of 1 mg rtPA following relative end weights were found: 0 ml/h=42.89% ±5.34, 15 ml/h=32.14%±5.05, 90ml/h= 36.66%±5.64, 180 ml/h=41.85%±6.72. Different drainage time with a low irrigation rate of 15ml/h was evaluated and showed a significantly lowest relative weight after 1 h (49.49%±4,592) compared to 15 (62.02%±4.312; p= 0.016) and 30 min (62.90%±1.88; p=0.012) of drainage. No significant differences in the fibrinolysis and the relative clot end weights were observed between the healthy CSF (55.1%±4.9), hemorrhagic CSF (69.4%±4.7) and hemorrhagic CSF (66.38%±5.3) pretreated with rtPA could be identified. Plasminogen levels in the clots decreased from initially >82% at a not measureable level <10% after already 1 single dose of 1 mg rtPA.

Conclusions: The present study showed that irrigation in general does not lead to higher lysis-rates. Healthy or hemorrhagic CSF did not increase lysis rate. Likewise, in ICH patients a contact of the lysis catheter to the ventricular system may not increase the efficiency of ICH lysis due to lytic effects but rather due to a pressure gradient. The decrease of the rtPA binding partner Plasminogen after already 1 mg rtPA implies that higher doses of rtPA might be ineffective.