Evidence map›Paper›PMID 25739904›Full record

Trial reportNeurocritical care2015

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

Andreas H Kramer, Craig Jenne, Jessalyn K Holodinsky, Stephanie Todd, Derek J Roberts, Paul Kubes, David A Zygun, Michael D Hill, Caroline Leger, John H Wong

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Neurocritical care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Thrombolysis for aneurysmal subarachnoid haemorrhage.The Cochrane database of systematic reviews · 2025
    Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Andreas H KramerDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada. andreas.kramer@calgaryhealthregion.ca.
Craig JenneDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada.
Jessalyn K HolodinskyDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada.
Stephanie ToddDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada.
Derek J RobertsDepartment of Community Health Sciences, University of Calgary, Calgary, Canada.
Paul KubesDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada.
David A ZygunDepartment of Critical Care Medicine, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W, Calgary, AB, T2N 2T9, Canada.
Michael D HillDepartment of Clinical Neurosciences, University of Calgary, Calgary, Canada.
Caroline LegerUniversity of Laval, Quebec, Canada.
John H WongDepartment of Clinical Neurosciences, University of Calgary, Calgary, Canada.
University of Calgary · CAUniversité Laval · CAUniversity of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity.

methodsTwelve patients with aneurysmal SAH and IVH, treated with endovascular coiling and ventricular drainage, were randomized to receive either 2 mg intraventricular TPA or placebo every 12 h (five doses). CT scans were performed 12, 48, and 72 h after initial administration, and blood was quantified using the SAH Sum and IVH Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12 h after the first dose using ELISA assays.

resultsMedian CSF TPA concentrations in seven TPA-treated patients were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12 h after drug administration. Peak concentrations varied markedly (401-8398 ng/ml). Two patients still had slightly elevated levels (283-285 ng/ml) when the second dose was due after 12 h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6 h, had declined by 12 h, and correlated strongly with radiographic IVH clearance (r = 0.82, p = 0.02).

conclusionsThe pharmacokinetics of intraventricular TPA administration varies between individual patients. TPA dose does not need to exceed 2 mg. The optimal administration interval is every 8-12 h.

Indexed as

Cerebral HemorrhageCerebral VentriclesFemaleFibrinolytic AgentsHumansInjections, IntraventricularIntracranial AneurysmMaleMiddle AgedPilot ProjectsSubarachnoid HemorrhageTissue Plasminogen ActivatorTreatment OutcomeFibrinolytic AgentsTissue Plasminogen ActivatorD-dimerFibrinolysisIntraventricular hemorrhagePharmacokineticsSubarachnoid hemorrhageTissue plasminogen activator

Identifiers

PMID25739904
OpenAlexW2144057132

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.