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Intraarterial Thrombolysis (PowerPoint)


									           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)
•   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)]

•   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].

•    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
   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)
• 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.

• 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
• 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.
                    GA or sedation?
General anaesthesia (GA)
• Patient does not retch
• Airway secure
• Head stable and access better

• 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
•   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?

• 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)
            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
•   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

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