Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage

Andrew F. Ducruet, Zachary L. Hickman, Brad E. Zacharia, Bartosz T. Grobelny, Reshma Narula, Kuang Hua Guo, Jan Claassen, Kiwon Lee, Neeraj Badjatia, Stephan A. Mayer, E. Sander Connolly

Research output: Contribution to journalReview article

34 Citations (Scopus)

Abstract

OBJECTIVE: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 ± .55; control, 1.00 ± 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 ± 0.80; control, 2.25 ± 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 ± 0.14 vs 0.70 ± 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. CONCLUSION: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalNeurosurgery
Volume66
Issue number4
DOIs
StatePublished - Apr 1 2010

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Cerebral Hemorrhage
Tissue Plasminogen Activator
Meningitis
Edema
Hemorrhage
Drainage
Length of Stay
Glasgow Coma Scale
Brain Edema
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Ducruet, Andrew F. ; Hickman, Zachary L. ; Zacharia, Brad E. ; Grobelny, Bartosz T. ; Narula, Reshma ; Guo, Kuang Hua ; Claassen, Jan ; Lee, Kiwon ; Badjatia, Neeraj ; Mayer, Stephan A. ; Connolly, E. Sander. / Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. In: Neurosurgery. 2010 ; Vol. 66, No. 4. pp. 648-655.
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title = "Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage",
abstract = "OBJECTIVE: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 ± .55; control, 1.00 ± 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 ± 0.80; control, 2.25 ± 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 ± 0.14 vs 0.70 ± 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46{\%} vs 12{\%}; P = .049) and a trend toward shunt dependence (38{\%} vs 6{\%}; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. CONCLUSION: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.",
author = "Ducruet, {Andrew F.} and Hickman, {Zachary L.} and Zacharia, {Brad E.} and Grobelny, {Bartosz T.} and Reshma Narula and Guo, {Kuang Hua} and Jan Claassen and Kiwon Lee and Neeraj Badjatia and Mayer, {Stephan A.} and Connolly, {E. Sander}",
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Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. / Ducruet, Andrew F.; Hickman, Zachary L.; Zacharia, Brad E.; Grobelny, Bartosz T.; Narula, Reshma; Guo, Kuang Hua; Claassen, Jan; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A.; Connolly, E. Sander.

In: Neurosurgery, Vol. 66, No. 4, 01.04.2010, p. 648-655.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage

AU - Ducruet, Andrew F.

AU - Hickman, Zachary L.

AU - Zacharia, Brad E.

AU - Grobelny, Bartosz T.

AU - Narula, Reshma

AU - Guo, Kuang Hua

AU - Claassen, Jan

AU - Lee, Kiwon

AU - Badjatia, Neeraj

AU - Mayer, Stephan A.

AU - Connolly, E. Sander

PY - 2010/4/1

Y1 - 2010/4/1

N2 - OBJECTIVE: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 ± .55; control, 1.00 ± 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 ± 0.80; control, 2.25 ± 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 ± 0.14 vs 0.70 ± 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. CONCLUSION: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

AB - OBJECTIVE: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. METHODS: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. RESULTS: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 ± .55; control, 1.00 ± 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 ± 0.80; control, 2.25 ± 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 ± 0.14 vs 0.70 ± 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. CONCLUSION: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

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JO - Neurosurgery

JF - Neurosurgery

SN - 0148-396X

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