Intraventricular thrombolysis speeds blood clot resolution

Results of a pilot, prospective, randomized, double-blind, controlled trial

Neal J. Naff, Daniel F. Hanley, Penelope M. Keyl, Stanley Tuhrim, Michael Kraut, Joshua Bederson, Ross Bullock, Stephan A. Mayer, Eric Schmutzhard, Warren R. Selman, William F. Chandler, Hugh Garton, Christopher J. Chittum, Stephen J. Haines, J. Max Findlay, Robert G. Grossman

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25,000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalNeurosurgery
Volume54
Issue number3
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Urokinase-Type Plasminogen Activator
Thrombosis
Placebos
Hemorrhage
Drainage
Ventriculostomy
Intraventricular Injections
Glasgow Coma Scale
Random Allocation
Sodium Chloride
Multicenter Studies
Half-Life
Arm
Animal Models
Head
Safety
Injections
Therapeutics
Infection

Keywords

  • Cerebrospinal fluid
  • External ventricular drainage
  • Intracerebral hemorrhage
  • Intraventricular hemorrhage
  • Thrombolysis
  • Urokinase

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Naff, N. J., Hanley, D. F., Keyl, P. M., Tuhrim, S., Kraut, M., Bederson, J., ... Grossman, R. G. (2004). Intraventricular thrombolysis speeds blood clot resolution: Results of a pilot, prospective, randomized, double-blind, controlled trial. Neurosurgery, 54(3), 577-584.

Intraventricular thrombolysis speeds blood clot resolution : Results of a pilot, prospective, randomized, double-blind, controlled trial. / Naff, Neal J.; Hanley, Daniel F.; Keyl, Penelope M.; Tuhrim, Stanley; Kraut, Michael; Bederson, Joshua; Bullock, Ross; Mayer, Stephan A.; Schmutzhard, Eric; Selman, Warren R.; Chandler, William F.; Garton, Hugh; Chittum, Christopher J.; Haines, Stephen J.; Findlay, J. Max; Grossman, Robert G.

In: Neurosurgery, Vol. 54, No. 3, 01.03.2004, p. 577-584.

Research output: Contribution to journalArticle

Naff, NJ, Hanley, DF, Keyl, PM, Tuhrim, S, Kraut, M, Bederson, J, Bullock, R, Mayer, SA, Schmutzhard, E, Selman, WR, Chandler, WF, Garton, H, Chittum, CJ, Haines, SJ, Findlay, JM & Grossman, RG 2004, 'Intraventricular thrombolysis speeds blood clot resolution: Results of a pilot, prospective, randomized, double-blind, controlled trial', Neurosurgery, vol. 54, no. 3, pp. 577-584.
Naff, Neal J. ; Hanley, Daniel F. ; Keyl, Penelope M. ; Tuhrim, Stanley ; Kraut, Michael ; Bederson, Joshua ; Bullock, Ross ; Mayer, Stephan A. ; Schmutzhard, Eric ; Selman, Warren R. ; Chandler, William F. ; Garton, Hugh ; Chittum, Christopher J. ; Haines, Stephen J. ; Findlay, J. Max ; Grossman, Robert G. / Intraventricular thrombolysis speeds blood clot resolution : Results of a pilot, prospective, randomized, double-blind, controlled trial. In: Neurosurgery. 2004 ; Vol. 54, No. 3. pp. 577-584.
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AU - Naff, Neal J.

AU - Hanley, Daniel F.

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AU - Tuhrim, Stanley

AU - Kraut, Michael

AU - Bederson, Joshua

AU - Bullock, Ross

AU - Mayer, Stephan A.

AU - Schmutzhard, Eric

AU - Selman, Warren R.

AU - Chandler, William F.

AU - Garton, Hugh

AU - Chittum, Christopher J.

AU - Haines, Stephen J.

AU - Findlay, J. Max

AU - Grossman, Robert G.

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N2 - OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25,000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.

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KW - External ventricular drainage

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KW - Urokinase

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