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Propagating Relationship of Cerebral Oximetric Volume and the Clinical Outcome of Recombinant Tissue Plasminogen Activator (r-TPA) Therapy on Acute Cerebral Ischemic Stroke Patients.

ABSTRACT: Introduction:Currently, the most available treatment for acute ischemic stroke (AIS) is thrombolytic therapy with recombinant tissue plasminogen activator (r-TPA). A challenge in r-TPA therapy is the prediction of recovery in each case. Objective:The aim was to find a possible relationship between the cerebral oximetry indexes and the clinical outcome of r-TPA therapy to assess the cerebral oximetry as a non-invasive monitoring agent for therapy. Methods:The inclusion criteria were all patients with AIS who received r-TPA. The neurologic status was evaluated based on the national institutes of health stroke scale (NIHSS) score at arrival, and after a period of 24 hours. In addition, the levels of brain oxygenation in both hemispheres were measured before and continuously over the first 24 hours after r-TPA injection, using an oximetric sensor in the frontal lobes. The clinical success was defined as a 4-point improvement from the baseline NIHSS. Results:Total 44 patients with the mean age of 58.2 ± 2.18 years were enrolled, of whom 68.18% were male. Twenty-eight patients remained clinically unimproved and 16 patients were improved. A significant difference was found in the mean surface area under the brain oximetric curve in the 24 hour, in the affected hemisphere in the improved group, compared to the unimproved group (P = 0.007). There was a significant difference between the mean increase in brain oxygenation within 24 hours in the improved and unimproved groups (P = 0.002). Conclusion:It is likely that, The cerebral oximetry could contribute to predict the likelihood of r-TPA prognosis in patients with AIS.

SUBMITTER: Paybast S

PROVIDER: S-EPMC6955029 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Propagating Relationship of Cerebral Oximetric Volume and the Clinical Outcome of Recombinant Tissue Plasminogen Activator (r-TPA) Therapy on Acute Cerebral Ischemic Stroke Patients.

Paybast Sepideh S Ashraf Ali A Sarshad Hakimeh H Shakiba Maryam M Moadabi Yasser Y

Advanced journal of emergency medicine 20190817 1

<h4>Introduction</h4>Currently, the most available treatment for acute ischemic stroke (AIS) is thrombolytic therapy with recombinant tissue plasminogen activator (r-TPA). A challenge in r-TPA therapy is the prediction of recovery in each case.<h4>Objective</h4>The aim was to find a possible relationship between the cerebral oximetry indexes and the clinical outcome of r-TPA therapy to assess the cerebral oximetry as a non-invasive monitoring agent for therapy.<h4>Methods</h4>The inclusion crite ...[more]

PMID: 31938776

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Project description:Background and Purpose- Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods- Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results- Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions- The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

Project description:Background and Purpose- Telemedicine is increasingly utilized for intravenous tPA (tissue-type plasminogen activator) delivery. The comparative safety of leaving tPA-treated patients at a presenting (spoke) hospital (drip-and-stay) or transferring patients to a central treating (hub) hospital (drip-and-ship) is not established. We sought to compare outcomes between drip-and-ship and drip-and-stay patients treated with tPA via telemedicine. We hypothesized that there would be no differences in short-term outcomes of in-hospital mortality, length of stay, or discharge disposition or in 90-day outcomes between groups. Methods- We retrospectively identified patients treated with tPA at 17 spoke hospitals between September 2015 and December 2016. Demographic, clinical, and outcome data were obtained from a prospective telemedicine registry. We used negative binomial, multinomial, and logistic regression analyses to evaluate length of stay, discharge disposition, and inpatient mortality, respectively. We compared the proportion of patients with 90-day modified Rankin Scale score <2 by group. Results- Among 430 tPA-treated patients, 232 (53.9%) were transferred to the hub after treatment. The median arrival National Institutes of Health Stroke Scale score was higher for drip-and-ship (10; interquartile range, 5-18) compared with drip-and-stay patients (6; interquartile range, 4-10; P<0.001). Unadjusted length of stay was longer in drip-and-stay patients (incidence rate ratio, 0.82; 95% CI, 0.71-0.95). There were no significant differences in adjusted length of stay, hospital mortality, or discharge disposition. Among the 64% of patients with complete 90-day modified Rankin Scale score, the proportion with good outcomes (modified Rankin Scale score <2) did not differ between groups. Conclusions- We found no differences in measured outcomes between drip-and-ship and drip-and-stay patients treated in our network, although our study may be underpowered to detect small differences.

Project description:Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ?3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ?1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ?8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

Dataset Information

Propagating Relationship of Cerebral Oximetric Volume and the Clinical Outcome of Recombinant Tissue Plasminogen Activator (r-TPA) Therapy on Acute Cerebral Ischemic Stroke Patients.

Publications

Propagating Relationship of Cerebral Oximetric Volume and the Clinical Outcome of Recombinant Tissue Plasminogen Activator (r-TPA) Therapy on Acute Cerebral Ischemic Stroke Patients.

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