Surgical Grand Rounds 03/10/2013 Thrombolysis never too late

Case presentation Mr X Background Hx: EVAR (AUI + R-L fem-fem crossover) Intermittent claudication L>R for the last 18 months

2013 Admitted with a 10 day hx of acute deterioration of left foot pain progressing to rest pain

Past Medical History Hypertension Dyslipidaemia Medications - Pravastatin - Amlodipine Aspirin Bisoprolol NKDA Social Hx: smoker Fam Hx : PVD

Examination Left cold, pale foot Pulses not palpable ABIS: Right : Normal Left : 0.3 Underwent full investigation for embolus source (Holter, Echo)

CT angio 2013 Thrombus in distal popliteal. Non occluding

CT angiogram 2013 Right Iliac limb. Left occluder

Fem – Fem Crossover Fem – fem crossover

Distal SFA patent

Occlusion in left distal popliteal artery

Angiogram prior to thrombolysis Distal SFA occlusion

Angiogram Post thrombolysis Highlight of this case: Even though a thrombus has been present since april 2013, thrombolysis was successful in clearing out the thrombus.

Thrombolysis Catheter-directed thrombolysis performed by vascular surgeons/interventional radiologists Plan Mechanism Indications/contraindications Technique Peri-procedural protocol/complications Evidence

MECHANISM OF ACTION ACTIVATION Prothrombin (II) Thrombin (IIa) (Converts) Platelets Fibrinogen (I) Fibrin (Ia) Clot (Binds) tPA (Converts) DEGRADATION Plasminogen Plasmin FDPs 14 14

Indications Acute limb iscahemia Acute embolus Thrombosis of a stenosis in a native artery Thrombosed arterial bypass graft 15

Relative Contra-indications Haemorrhagic diathesis Recent GI bleed Hx stroke, intracranial tumour/aneurysm, spinal surgery Pancreatitis Bacterial endocarditis Documented GI neoplasm, varices Recent surgery 16

Thrombolysis - Technique Contralateral access via common femoral artery Guidewire traversal test / Catheter tip into thrombus. Single vs multi side hole Low-Dose Infusion: 0.5-1mg tPA per hour Heparin – pericatheter thrombosis Sequential angiograms Advance catheter tip / co-axial system ? Treatable critical stenosis Accelerated Infusion Pulse Spray, Hi-dose bolus 17 17

tPA Protocol (Acute Limb Ischaemia) Overnight continuous infusion techniques using multislit catheter Surgeon/Radiologist initiating tPA to inject 5mg bolus into clot through infusion catheter Infuse via pump at 5ml/hr (1mg tPA/ hr) to cont. until rpt angiogram 18

tPA Protocol (Acute Limb Ischaemia) Cont. Sub-therapeutic heparin given through side port of the sheath in the groin (2500 IU bolus then 500 IU/hr as maintenance) Monitor aPTT to ensure < 60secs Monitor Fibrinogen levels 6 hourly to maintain > 100mg/dL Repeat angiogram the next morning Remove sheaths after waiting 1 hr post tPA termination & Activated Clotting Time < 175 Continue therapeutic heparin arm if indicated with 6 hourly monitoring of APTT between 60-90 19

MANAGEMENT OF PATIENTS ON TPA Baseline obs & Dopplers Check tPA and Heparin are correctly connected and running Infusion running Infusion NOT running CALL SURGICAL TEAM Check 1/2 hourly obs: T°, HR, BP Inspect access site of thrombolysis catheter Dopplers Causes for concern: Bleeding from site Persistant tachycardia post thrombolysis initiation Increasing groin pain Hypotension Headache Altered motor function(?TIA/CVA) Altered mental state No Change 20

Patient Guidelines on tPA Strict bed rest Urinary Catheter in situ Normal diet Bloods: FBC, U&E, Coags, Fibrinogen levels, Group & Crossmatch (2 units) Check angiogram day post procedure Infusion can only be stopped upon instructions by Surgeon/Radiology team and the team is to remove infusion catheter 21

TPA vs. Surgery 3 randomized, clinical trials in 1990’s Rochester series – urokinase vs surgery, 114 pts Limb salvage rate similar in both - 82% at 12 months Survival rate thrombolysis group (84%) vs 58% (more cardiopulmonary complications) STILE trial – rt-PA, urokinase vs surgery, 234 pts Patients with acute ischemia (0-14 days) who were treated with thrombolysis had improved amputation-free survival and shorter hospital stays, but those with chronic ischemia (> 14 days), surgical revascularisation was more effective and safer TOPAS trial - urokinase Amputation free survival Thromb: 71.8% (6/12), 65% at 1 yr Surgery: 74.8% (6/12), 69.9% Major Haemorrhage 12.5% Vs 5.5% Open procedures 315 Vs 551 at 6 months There are 3 randomized clinical trials related to TPA vs. Surgery – rocehster series, stile trial and topas 22

To summarise Rochester – Mortality Surgery > Thrombolysis, similar outcome limb STILE – acute cases better with lysis TOPAS – Similar outcome with decreased need for open surgery All showed higher risk bleeding with thrombolysis 23

Cochrane review Five trials with a total of 1283 participants Berridge C et al - Surgery versus thrombolysis for initial management of acute limb ischaemia – updated 2013 All RCTs comparing thrombolysis and surgery for the initial treatment of acute limb ischaemia Five trials with a total of 1283 participants

Results No significant difference in limb salvage or death at 30 days, six months or one year for initial surgery vs thrombolysis. At 30 days, thrombolysis patients had higher rate of stroke (1.3%) vs (0%) major haemorrhage (8.8%) vs (3.3%) distal embolisation (12.4%) vs (0%) (OR 8.35; 95% CI 4.47 to 15.58). Participants treated by initial thrombolysis underwent a less severe degree of intervention (OR 5.37; 95% CI 3.99 to 7.22) and displayed equivalent overall survival (OR 0.87; 95% CI 0.61 to 1.25).

National Audit of Thrombolysis for Acute Leg Ischemia (NATALI) Data collected over 10 years 11 centres in UK, 1133 thrombolysis Major haemorrhage rate 7.85% Stroke rate 2.3% - ½ haemorrhagic Earnshaw et al JVS 2004 26

NATALI Adverse Predictors of Amputation free survival Age, DM, Duration + Severity of Ischemia, Neurosensory deficit Poor Predictors of Patient Survival Female, Age, IHD, Native vessel occlusion and embolic etiology 27