Surgical Grand Rounds03/10/2013

Thrombolysis never too late

Mr X

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

months

Case presentation

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

2013

Hypertension Dyslipidaemia

Medications

- Pravastatin - Amlodipine- Aspirin- Bisoprolol

NKDA

Social Hx: smokerFam Hx : PVD

Past Medical History

Left cold, pale foot Pulses not palpable

ABIS:Right : NormalLeft : 0.3

Underwent full investigation for embolus source (Holter, Echo)

Examination

CT angio 2013

CT angiogram 2013

Fem – Fem Crossover

Angiogram prior to thrombolysis

Angiogram Post thrombolysis

Thrombolysis Catheter-directed thrombolysis performed

by vascular surgeons/interventional radiologists

Plan◦ Mechanism◦ Indications/contraindications◦ Technique◦ Peri-procedural protocol/complications◦ Evidence

ACTIVATION

FDPs

FDPs

Prothrombin (II)

Thrombin (IIa)

ClotFibrinogen (I) Fibrin (Ia)Platelets

PlasminPlasminogenDEGRADATION

MECHANISM OF ACTION

tPA

(Binds)

(Converts)

(Converts)

Indications

Acute limb iscahemia

◦ Acute embolus

◦ Thrombosis of a stenosis in a native artery

◦ Thrombosed arterial bypass graft

Relative Contra-indications Haemorrhagic diathesis

Recent GI bleed

Hx stroke, intracranial tumour/aneurysm, spinal surgery

Pancreatitis

Bacterial endocarditis

Documented GI neoplasm, varices

Recent surgery

Thrombolysis - Technique Contralateral access via common femoral artery Guidewire traversal test / Catheter tip into thrombus. Single vs multi side holeLow-Dose Infusion: 0.5-1mg tPA per hourHeparin – pericatheter thrombosisSequential angiogramsAdvance catheter tip / co-axial system? Treatable critical stenosisAccelerated InfusionPulse Spray, Hi-dose bolus

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

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

Baseline obs & Dopplers

Check 1/2 hourly obs:

• T°, HR, BP• Inspect access

site of thrombolysis catheter

• Dopplers

CALL SURGICAL TEAM

Causes for concern:• Bleeding from site• Persistant tachycardia post thrombolysis

initiation• Increasing groin pain• Hypotension• Headache• Altered motor function(?TIA/CVA)• Altered mental state

Check tPA and Heparin are correctly connected and running

MANAGEMENT OF PATIENTS ON TPA

Infusion running

No Change

Infusion NOT running

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

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 yrSurgery: 74.8% (6/12), 69.9%

- Major Haemorrhage 12.5% Vs 5.5%- Open procedures 315 Vs 551 at 6 months

To summarise

Rochester – Mortality Surgery > Thrombolysis, similar outcome limbSTILE – acute cases better with lysisTOPAS – Similar outcome with decreased need for open surgeryAll showed higher risk bleeding with thrombolysis

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

Cochrane review

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).

Results

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

NATALI

Adverse Predictors of Amputation free survival

Age, DM, Duration + Severity of Ischemia, Neurosensory deficit

Poor Predictors of Patient SurvivalFemale, Age, IHD, Native vessel occlusion and

embolic etiology