Intraarterial recombinant human tissue plasminogen activator for ischemic stroke treatment

Intraarterial recombinant human tissue plasminogen activator for ischemic stroke treatment

Mechanical thrombectomy (MT) devices have led to improved reperfusionand clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results.

Zaidi et al., evaluated the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry.

The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT.

A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02).

Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT 1).

Intraarterial recombinant human tissue plasminogen activator for ischemic stroke treatment may be the simplest endovascular technique to undertake, when compared to Stent retriever or Penumbra aspiration. However, on its own, while the recanalization rates may be better than IV tPA, they are inferior to o Stent retriever or Penumbra aspiration 2) 3).

Currently,i.a.tPA is used in conjunction with other techniques in ischemic stroke.

Intraarterial recombinant human tissue plasminogen activator may be indicated for the following situations:

● Persistent symptoms of stroke despite Intravenous recombinant human tissue plasminogen activator and adequate medical management

● Where angiography may be performed and treatment administered within 3 and 6 hours after symptom onset with an NIHSS score greater than 4, or those with an NIHSS score of greater than 20 and the ability to be treated within 6 hours

● Posterior circulation strokes may be treated endovascularly for up to 24 hrs (due to a lesser likelihood of hemorrhagic conversion of infarct)

● CTA or MRA demonstrating a diffusion-perfusion mismatch.In face of significant penumbra, it may be worthwhile to perform endovascular intervention even outside the therapeutic window. Conversely, intervention may be abandoned even within the therapeutic window, if the stroke is complete. Centers are relying more and more on neuroimaging rather than the therapeutic window

● When Intravenous recombinant human tissue plasminogen activator is contraindicated e.g., recent surgery

Contraindications to intervention

Most contraindications are relative and have to be weighed against the risk of not intervening. These contraindications include:

● Hemorrhagic infarct or,ICH

● CT demonstrating hypodensity or mass effect consistent with evolving infarct of more than one-third of middle cerebral artery territory

● Recent major surgery

● Pregnancy

● When considering stenting, contraindication to anticoagulants and/or thrombolytics

Preprocedural management

This may be under the supervision of a stroke neurologist, or the neurosurgeon. Ensure the following:

● Rapid transfer of patient to a stroke center/facility with endovascular capabilities.

● ABC’s take precedence.

● Ensure patient has two intravenous lines, preferably 18G or larger. Start monitoring BPpulse oximetry, ECG, O2 saturation, heart rate and rhythm, respiratory rate. Insert a Foley catheter.

● Verify laboratory values including Platelet countBUNCRAPTT, PT/INR. ß-HCG for females of reproductive age group.

● Maintain MAP ≥ 90mmHg.

● CT scan head: To rule out ICH.

● CTA: To assess location of the clot (hyperdense artery sign and vascular tortuosity.

● MRI head (select cases).

● If available and can be done without delay, then perfusion studies e.g., CTP or MRP. These perfusion studies will demonstrate viable brain (penumbra) vs completed stroke.

● In centers where available, CT, CTA and CTP all a reperformed during the same session on CT scanner.

● Be cognizant of renal insufficiency, diabetes, congestive heart failure etc., in which case consider diluted non-ionic contrast agent and carefully pre-plan, to maintain contrast load to minimum.

● If the patient is not responding to IV tPA or it if is contraindicated, then endovascular intervention is considered.

● The goal of intervention is to re-establish circulation, as soon as possible.



Zaidi SF, Castonguay AC, Jumaa MA, Malisch TW, Linfante I, Marden FA, Abraham MG, Chebl AB, Novakovic R, Taqi MA, Nogueira RG, Martin CO, Holloway WE, Mueller-Kronast N, English JD, Dabus G, Bozorgchami H, Xavier A, Rai AT, Froehler MT, Badruddin A, Nguyen TN, Yoo AJ, Shaltoni H, Janardhan V, Chen PR, Britz GW, Kaushal R, Nanda A, Gupta R, Zaidat OO. Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions. Stroke. 2019 Apr;50(4):1003-1006. doi: 10.1161/STROKEAHA.118.024442. PubMed PMID: 30791829.

Ernst R, Pancioli A, Tomsick T, Kissela B, Woo D, Kanter D, Jauch E, Carrozzella J, Spilker J, Broderick J. Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke. Stroke. 2000; 31:2552–2557

Intra-arterial thrombolysis. AJNR Am J Neuroradiol. 2001; 22:S18–S21

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