Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema

W Andrew Mould, J Ricardo Carhuapoma, John Muschelli, Karen Lane, Timothy C Morgan, Nichol A McBee, Amanda J Bistran-Hall, Natalie L Ullman, Paul Vespa, Neil A Martin, Issam Awad, Mario Zuccarello, Daniel F Hanley, MISTIE Investigators, Khaled Aziz, Jeffrey Fletcher, Bratislav Velimirovic, Daryl Warder, Gavin Britz, Carmelo Graffagnino, Inam Kureshi, Judy Huang, Byron Bailey, Dilantha Ellegala, Angela Hays, Marc LaPointe, David Sinclair, Joshua B Bederson, Henry Moyle, David Mendelow, Prokopios Panaretos, Martin Gizzi, Thomas Steineke, Lorenzo Munoz, Shaun T O'Leary, Richard E Temes, Robert Dodd, Cristanne Wijman, Paul Camarata, Jack Jallo, Christopher Loftus, Michael Weaver, Mark Harrigan, Neil Martin, Paul Vespa, Bob Carter, Issam Awad, Fernando Goldenberg, Andrew Ringer, Mario Zuccarello, E Francois Aldrich, William Ashley, Peng Roc Chen, George Lopez, Jean-Louis Caron, Daniel Haux, Berk Orakcioglu, Sven Poli, Thorsten Steiner, William C Broaddus, R Scott Graham, W Andrew Mould, J Ricardo Carhuapoma, John Muschelli, Karen Lane, Timothy C Morgan, Nichol A McBee, Amanda J Bistran-Hall, Natalie L Ullman, Paul Vespa, Neil A Martin, Issam Awad, Mario Zuccarello, Daniel F Hanley, MISTIE Investigators, Khaled Aziz, Jeffrey Fletcher, Bratislav Velimirovic, Daryl Warder, Gavin Britz, Carmelo Graffagnino, Inam Kureshi, Judy Huang, Byron Bailey, Dilantha Ellegala, Angela Hays, Marc LaPointe, David Sinclair, Joshua B Bederson, Henry Moyle, David Mendelow, Prokopios Panaretos, Martin Gizzi, Thomas Steineke, Lorenzo Munoz, Shaun T O'Leary, Richard E Temes, Robert Dodd, Cristanne Wijman, Paul Camarata, Jack Jallo, Christopher Loftus, Michael Weaver, Mark Harrigan, Neil Martin, Paul Vespa, Bob Carter, Issam Awad, Fernando Goldenberg, Andrew Ringer, Mario Zuccarello, E Francois Aldrich, William Ashley, Peng Roc Chen, George Lopez, Jean-Louis Caron, Daniel Haux, Berk Orakcioglu, Sven Poli, Thorsten Steiner, William C Broaddus, R Scott Graham

Abstract

Background and purpose: Perihematomal edema (PHE) can worsen outcomes after intracerebral hemorrhage (ICH). Reports suggest that blood degradation products lead to PHE. We hypothesized that hematoma evacuation will reduce PHE volume and that treatment with recombinant tissue-type plasminogen activator (rt-PA) will not exacerbate it.

Methods: Minimally invasive surgery and rt-PA in ICH evacuation (MISTIE) phase II tested safety and efficacy of hematoma evacuation after ICH. We conducted a semiautomated, computerized volumetric analysis on computed tomography to assess impact of hematoma removal on PHE and effects of rt-PA on PHE. Volumetric analyses were performed on baseline stability and end of treatment scans.

Results: Seventy-nine surgical and 39 medical patients from minimally invasive surgery and rt-PA in ICH evacuation phase II (MISTIE II) were analyzed. Mean hematoma volume at end of treatment was 19.6±14.5 cm(3) for the surgical cohort and 40.7±13.9 cm(3) for the medical cohort (P<0.001). Edema volume at end of treatment was lower for the surgical cohort: 27.7±13.3 cm(3) than medical cohort: 41.7±14.6 cm(3) (P<0.001). Graded effect of clot removal on PHE was observed when patients with >65%, 20% to 65%, and <20% ICH removed were analyzed (P<0.001). Positive correlation between PHE reduction and percent of ICH removed was identified (ρ=0.658; P<0.001). In the surgical cohort, 69 patients underwent surgical aspiration and rt-PA, whereas 10 underwent surgical aspiration only. Both cohorts achieved similar clot reduction: surgical aspiration and rt-PA, 18.9±14.5 cm(3); and surgical aspiration only, 24.5±14.0 cm(3) (P=0.26). Edema at end of treatment in surgical aspiration and rt-PA was 28.1±13.8 cm(3) and 24.4±8.6 cm(3) in surgical aspiration only (P=0.41).

Conclusions: Hematoma evacuation is associated with significant reduction in PHE. Furthermore, PHE does not seem to be exacerbated by rt-PA, making such neurotoxic effects unlikely when the drug is delivered to intracranial clot.

Figures

Figure 1
Figure 1
CT scan at EOT for a medical patient with (right) and without (left) the semi-automated threshold based segmentation of perihematomal edema. EOT, end of treatment scan.
Figure 2
Figure 2
BLS and EOT edema volumes for the surgical (S+rt-PA and SO) and medical cohorts. BLS, baseline stability scan, EOT, end of treatment scan.
Figure 3
Figure 3
A.) BLS and EOT edema volumes for patients separated by treatment group (medical, surgical aspiration only, and surgery plus rt-PA) and trichotimized by order of % ICH removed. BLS, baseline stability scan, EOT, end of treatment scan. B.) Percent of ICH removed as calculated by [(BLS ICH volume - EOT ICH volume)/ BLS volume] in a continuous fashion versus reduction in edema (BLS edema volume - EOT edema volume) for patients receiving medical management (blue) and MIS (red). BLS, baseline stability scan, EOT, end of treatment scan, S + rt-PA, surgery plus rt-PA, SO, surgical aspiration only. *- denotes statistical significance
Figure 4
Figure 4
Correlation between percent of ICH removed as calculated by [(BLS ICH volume - EOT ICH volume)/ BLS volume] and reduction in edema (BLS edema volume - EOT edema volume). BLS, baseline stability scan, EOT, end of treatment scan, S + rt-PA, Surgery plus rt-PA, SO, Surgical aspiration only.

Source: PubMed

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