Intraarterial Thrombolysis

Intra-arterial thrombolysis should be given in stroke centres with the appropriate level of experience In patients who fulfil the criteria for iv thrombolysis this should be given ASAP. Potential indications for i.a. rather than iv or in addition to iv thrombolysis include: • • • Primary intraarterial thombolysis Severe disabling neurological deficit and Contraindications to iv thrombolysis (e.g. recent surgery), 3-6 h from symptom onset or Dense artery sign on the CT head scan • • • Rescue thrombolysis Severe disabling neurological deficit and No improvement (or worsening without bleed) with iv thrombolysis No recanalization or early reolclusion after iv thrombolysis • • • Brain stem stroke treatment can be delivered within 12 h of symptom onset and Occlusion of basilar artery documented on 4-vessel angiography Eligible even if consciousness impaired and or patient ventilated Shaltoni et al 2007, Arnold et al 2002, 2003, Hill et al 2002

Primary intraarterial thrombolysis (LIT)

Arnold, Mattle et al, Bern (2002 n=100 MCA, 2003 n=40 basilar)

• • • Equipment high-resolution angiography system (Toshiba CAS 500) with a matrix of 1024x1024 pixels 5.5 F-JB2 catheter (Valavanis) was inserted into the femoral artery for 4-vessel angiography LIT using a microcatheter, mostly a Fast Tracker 18 (Target Therapeutics) through the 5.5-F JB2 catheter, which was navigated into the occluded MCA • • Thrombolytic agent Urokinase (Urokinase HS Medac) in a mean dose of 863 000 IU (range 20,000 to 1,250,000 IU) [or alteplase 50% of standard iv dose (not in above papers, pers comm. 2004)] • Technique Inject as near as possible to or into the thrombus over 60 to 90 minutes • • Additional procedures In patients occlusion due to soft thrombotic material, mechanical disruption of the clot was performed in addition using a very flexible hydrophilic guidewire catheter (Silver Speed MTI 0.008 or 0.010 inch). The tip of the guidewire was formed in a J shape to avoid perforation of the vessel walls. Penetration and fragmentation of the thrombus was achieved by gently advancing and rotating the convex border of the J-shaped guidewire (n=8).

In 2 patients without recanalization after injection of 1 000 000-IU urokinase a percutaneous transluminal angioplasty was performed using a FasStealth balloon dilatation catheter (Target Therapeutics) with a balloon diameter of 2.00 mm (n=2) • Documentation of outcome control angiography immediately after thombolysis [TIMI grade 0; minimal recanalization, TIMI grade 1; partial recanalization, TIMI grade 2; complete recanalization, TIMI grade 3].

• • Aftercare heparin in a dose doubling the activated thromboplastin time immediately after LIT before IST n=18), after IST change to 250-500 mg aspirin (n=82) iv immediately after LIT and then daily po/iv instead of heparin.

pts treated on neurological intensive care ward. Standard protocols for ward care and follow-up

Rescue i.a. thrombolysis after full dose iv thrombolysis (Shaltoni et al 2007)

• N=69, age 60+- 13, NIHSS 18 (6-39) • Patients with persisting occlusion a/o lack of clinical improvement after iv thrombolysis • Iv rtPa started med 120 min, iaT med 288 min • Reteplase n=56, alteplase n=7, urokinase n=6 • Symptomatic ICH n=4( 5.8%), 3 fatal • Recanalisation in 50% • Favourable outcome (H or IP rehab) 55% • Combination safe compared with iv alone. Higher rate of recanalisation and favourable outcome Shaltoni et al , Stroke 2007;38: 80-84.

Procedures for rescue i.a. thrombolysis

(Shaltoni et al 2007)

• Control angio every 10 min • Mechanical disruption of the clot via microcatheter premitted • Neuro function assesses every 15 min • Terminate IAT if TICI flow>2a or time >6h form onset (except for basilar artery where time was not limited) or maximum dose achieved (alteplase 24 mg, reteplase 6 u urokinase 750 000 U)

Rescue ia thrombolysis after full dose IV thrombolysis

(Hill et al, Calgary n=6, Stroke 2002;33:279-282)

• • Indication Disabling (severe) ischaemic stroke

and

persistent occlusion of the symptomatic artery or clinical and CT?MR evidence of basilar artery thrombosis All patients had had standard full dose Alteplase within 3 h of symptom onset.

• • • • • • • • Procedure Femoral approach Alteplase 1 mg/ml diluted x2 with sterile water Alteplase applied to the face of the thrombus, into the thrombus, and distal to the thrombus Pulse spray technique, 3 cc per application, using 3 cc syringes Combined with mechanical clot disruption, where possible Max dose of Alteplase i.a. 20 mg IV heparin was given as 2000 IU bolus at the beginning of the procedure and in a bolus fashion intermittently throughout to a maximum of 500 iu/h (???) Angioplasty/stenitng not prospectively planned but available as ‘rescue’ procedures • Post procedure No heparin/antithrombotics for 24 h

Rescue Intraarterial Thrombolysis

IMS II Investigators 2007

• Recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg over 30 minutes) • For subjects with an arterial occlusion at angiography, additional rt-PA was administered via the EKOS micro infusion catheter or a standard microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis. • Significantly better than no thrombolysis. Trial to compare iv with combined iv/ia therapy ongoing IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007;38:2127-35.

Ongoing IAT Research IMS III

• RCT, n=900 planned, end date 2015 • 18-82 years, initiation of IV rt-PA within 3h, NIHSSS ≥ 10, occlusion seen in M1, ICA or basilar artery on CTA • Iv rt-PA alone (0.9 mg/kg) vs combined IV/IA (0.6 mg/kg over 30 min followed by immediate angiography. If clot is demonstrated, the neuro-interventionalist will then choose from currently available but trial defined intra arterial treatment approaches. IAT will be given at maximum 2 mg bolus and 10 mg/hr, max 22 mg) using standard microcathether.

http://clinicaltrials.gov/ct2/show/NCT00359424

GA or sedation?

• • •

General anaesthesia (GA)

Patient does not retch Airway secure Head stable and access better • •

Sedation

Faster time to treatment Avoids complications of GA • • • •

Preliminary Results From a Retrospective Multicenter Study.

N=980 with IAT Only large vessel anterior circulation strokes included, GA was used in 44% No differences in intracranial hemorrhage rates compared with sedation Poorer neurological outcome at 90 days (OR=2.33; 95% CI, 1.63-3.44; P<0.0001) with GA Higher mortality (odds ratio=1.68; 95% CI, 1.23-2.30; P<0.0001) with GA ABOU-CHEBL Stroke April 2010

Upper age limit for IA lysis?

• <80?

• <70 and fit for age?

Consider • anaesthetic risk • More difficult access with tortuous stiff vessels Age in ia trials • 66+/-13 (Shaltoni 2007) • <80 (IMS II investigators) • 66+/-15 (Abou-Chebl 2010 large register)

Thrombectomy Karolinska Stroke Update meeting in November 2010 The consensus statement • • • • • • • • There is still a controversy whether mechanical removal of thrombus should be used routinely or only within trials. Large artery occlusion is associated with a high morbidity and mortality if left untreated Mechanical thrombectomy achieves higher recanalization rates compared to historical controls with or without intravenous rt-PA The odds for favourable outcome in general are significantly increased with early vessel recanalization Due to the lack of evidence of randomized control trials for clinical efficacy, mechanical thrombectomy should not be used in clinical routine However, in selected patients (e.g. with indication for iv-treatment but also contraindication), endovascular approaches may be considered as part of a institutional protocol If treatment is done outside a RCT, data should be included in a multicenter registry including assessment of three months outcome Future prospective randomized controlled trials of endovascular treatment should also evaluate the impact of sedation modality on safety of the intervention, technical success, time to recanalization, and clinical outcome • For full statement http://www.strokeupdate.org/Cons_Thrombectomy_2010.aspx