Updates in the Treatment of Acute Stroke Sarah Keir Western General Hospital

Acute Stroke Update Stroke: the scale of the problem Pathophysiology of stroke Rationale for thrombolysis Identification of stroke suitable for thrombolysis Delivery of thrombolysis

Scale of the Problem UK 120,000 strokes annually Scotland 10,000 strokes annually Incidence 3/1,000 Prevalence 10/1,000

Mortality In The UK Stroke is the second commonest cause of death Death within 30 days 8-12% ischaemic strokes 37-38% intracerebral haemorrhages Death within a year of first stroke 22% men 25% women Men Women IHD 20% 16% Stroke 7.9% 12.9% Lung cancer 6.9% 4.5% Breast cancer

The Cost of Stroke Commonest cause of disability 50% survivors disabled at 6 months Over 300,000 living with moderate to severe disability from stroke 28% strokes occur under 65 years of age 14% will have another stroke or tia within a year Of 1 million people … 2000 have a new stroke 10,000 are living with stroke …

The Cost of Stroke 20% of all acute hospital beds 25% long-term beds Cost of stroke to NHS £2.8 billion 3-4% of total healthcare costs in western Europe Informal care cost £2.4 billion

Pathophysiology Of Acute Stroke

Time is Brain

Restore Cerebral Blood Flow: Dissolve the Clot (thrombolysis) Before After

Any Problems with Trying to Remove Clot?… …The brain is not the heart It is much more fragile and more likely to bleed

NNT 0-90 4.5 91 – 180 9 180 – 270 14 270-180 21 (ns) MI 30

Effectiveness of treating 2,000 new ischaemic stroke patients each year each year Strategy Target Pop ARR Number of dead or dependent prevented Aspirin 1,900 (95%) 1.2% 23 Thrombolysis 200 (10%) 5.9% 12 Stroke unit 1,600 (80%) 4.3% 69

To Summarise so far… Stroke is common Stroke is deadly and disabling Thrombolysis works… …but increases intracerebral haemorrhage which may lead to death The time window is tiny

Identification of Suitable Stroke Patients Get the patient into hospital quickly Or else it’s pointless Is it really a stroke? Exclude stroke mimics What part of the brain is affected? Informs prognosis How bad is it? Helps assess risk of thrombolysis

FAST Stroke Assessment Face Arm Speech Test Facial Palsy affected side Arm Weakness Speech Impairment 100% sensitivity / 92% specificity

Is it Really a Stroke? Stroke Mimics Syncope Seizure Sepsis Migraine Metabolic Tumour Functional Old Stroke 20 – 40% case series Definition “Rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than vascular origin.” Hatano, WHO, 1976 ACCURATE HISTORY IS ESSENTIAL

What Part of the Brain is Involved? * HCD – higher cortical dysfunction

How Bad is it? National Institute of Health Stroke scale 0 = no stroke 1-4 = minor stroke 5-15 = moderate stroke 15-20 = moderate/severe stroke 21-42 = severe stroke

Thrombolysis: Getting Ready to Give it Does the patient fulfil licencing criteria? Check for contraindications Getting patient consent (relative assent) What if they’re outside criteria/ have a contraindication?

Thrombolysis: Licence Criteria Age 18 – 80 Within 3 hours of onset of symptoms No haemorrhage on CT

Suitability For Thrombolysis Contraindications (stroke-specific) Unknown time of onset Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l Rapidly resolving symptoms Minor stroke (NIHSS <5) Severe stroke (NIHSS >25) or by imaging Seizure at onset Evidence of ICH on CT scan Symptoms suggestive of SAH even if CT negative Received heparin within 48 hrs & APTT > upper limit of normal Any history of prior stroke and diabetes Prior stroke within 3 months PT > 15 sec (INR > 1.7) Platelets below 100 Contraindications (general) Known bleeding diathesis Receiving warfarin History of ICH Suspected or previous aneurysmal SAH History of CNS damage (tumour, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy (<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel Severe hypertension Bacterial endocarditis, pericarditis Acute pancreatitis Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis Major surgery or significant trauma (<3/12)

Suitability For Thrombolysis Contraindications (stroke-specific) Unknown time of onset Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l Rapidly resolving symptoms Minor stroke (NIHSS <5) Severe stroke (NIHSS >25) or by imaging Seizure at onset Evidence of ICH on CT scan Symptoms suggestive of SAH even if CT –ve Received heparin within 48 hrs & APTT > upper limit of normal Any history of prior stroke and diabetes Prior stroke within 3 months PT< 15 sec (INR < 1.7) Platelets below 100 Contraindications (general) Known bleeding diathesis Receiving warfarin History of ICH Suspected or previous aneurysmal SAH History of CNS damage (tumour, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy (<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel Severe hypertension Bacterial endocarditis, pericarditis Acute pancreatitis Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis Major surgery or significant trauma (<3/12)

Suitability For Thrombolysis Contraindications (stroke-specific) Unknown time of onset Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l Rapidly resolving symptoms Minor stroke (NIHSS <5) Severe stroke (NIHSS >25) or by imaging Seizure at onset Evidence of ICH on CT scan Symptoms suggestive of SAH even if CT –ve Received heparin within 48 hrs & aptt > upper limit of normal Any history of prior stroke and diabetes Prior stroke within 3 months Pt < 15 sec (inr < 1.7) Platelets below 100 Contraindications (general) Known bleeding diathesis Receiving warfarin History of ICH Suspected or previous aneurysmal SAH History of CNS damage (tumour, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy (<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel Severe hypertension Bacterial endocarditis, pericarditis Acute pancreatitis Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis Major surgery or significant trauma (<3/12)

Suitability For Thrombolysis Contraindications (stroke-specific) Unknown time of onset Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l Rapidly resolving symptoms Minor stroke (NIHSS <5) Severe stroke (NIHSS >25) or by imaging Seizure at onset Evidence of ICH on CT scan Symptoms suggestive of SAH even if ct –ve Received heparin within 48 hrs & APTT > upper limit of normal Any history of prior stroke and diabetes Prior stroke within 3 months PT < 15 sec (INR < 1.7) Platelets below 100 Contraindications (general) Known bleeding diathesis Receiving warfarin History of ICH Suspected or previous aneurysmal SAH History of CNS damage (tumour, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy (<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel Severe hypertension Bacterial endocarditis, pericarditis Acute pancreatitis Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis Major surgery or significant trauma (<3/12)

Suitability For Thrombolysis Contraindications (stroke-specific) Unknown time of onset Systolic BP >185 mmHg or diastolic BP >110mmHg or aggressive treatment needed to reduce BP to these limits Blood glucose > 22.2 mmol/l OR < 2.8 mmol/l Rapidly resolving symptoms Minor stroke (NIHSS <5) Severe stroke (NIHSS >25) or by imaging Seizure at onset Evidence of ICH on CT scan Symptoms suggestive of SAH even if CT –ve Received heparin within 48 hrs & APTT > upper limit of normal Any history of prior stroke and diabetes Prior stroke within 3 months PT < 15 sec (INR < 1.7) Platelets below 100 Contraindications (general) Known bleeding diathesis Receiving warfarin History of ICH Suspected or previous aneurysmal SAH History of CNS damage (tumour, aneurysm, intracranial or spinal surgery) Haemorrhagic retinopathy (<10 days) traumatic CPR, childbirth, puncture of non-compressible vessel Severe hypertension Bacterial endocarditis, pericarditis Acute pancreatitis Ulcerative gi disease <3/12, oesophageal varices, arterial aneurysms, a-v malformations Severe liver disease, liver failure, cirrhosis, portal hypertension, active hepatitis Major surgery or significant trauma (<3/12)

IV tPA - Patient Information Outcome at 90 days: Usual Treatment Clot-Busting Treatment (Aspirin & supportive care) (Thrombolysis) 1 in 10 greater chance of independence (being able to carry out all previous activities or with only a slight disability) 1 in 10 reduced risk of being dependent (requiring help to walk or needing help with most bodily needs) 1 in 30 chance of symptomatic haemorrhage (commonly leading to death)

What if they’re ‘Not Suitable’? Just give it any way Cleveland SICH 15.7% Just out of time? ECASS 3 Up to 4.5 hours mean NIHSS 9 (smaller) benefit Cleveland treated 50% outside guidelines

Randomise into IST3 No upper age limit No BP criteria Clinical equipoise Recruiting to 2011, reporting 2012 Aiming 3100 Currently 2800 – on target

Other Ways to Reperfuse Intra-arterial thrombolysis Clot retrieval …jury is still out…

Delivering Thrombolysis: Drug Delivery Must be initiated by a physician specialised in neurological care Dose is different to that for myocardial infarction 0.9 mg / kg (Max. 90mg) 10% as initial IV bolus Infuse rest over 60 mins. Avoid Aspirin & Heparin for 24 hours

Monitoring Cardiac monitor Oxygen saturation Monitor BP & GCS 15 mins during infusion 30 mins for next 6 hours Hourly for 6 hours 4 hourly for 36 hours NIHSS at 2 hours Avoid NG tube, catheter, central lines, arterial puncture for 24 hrs

Physiological Stabilisation IV saline Avoid hypotonic solutions Keep temperature below 37 oC Paracetamol, cooling Maintain O2 saturation > 95% Avoid hyperglycaemia Worsens outcome Watch BP closely Increased risk at extremes Use short-acting drugs if necessary

Complications Symptomatic haemorrhage ~ 7.3% If bleeding: Reduced GCS, headache, nausea, vomiting, hypertension, worsening symptoms If bleeding: Urgent FBC, fibrinogen, INR, APTT Platelet infusion 6-8 units Cryoprecipitate 6-8 units (or FFP) Factor VIII Discuss with neurosurgery (SAH or subdural) Mortality 11.3% SITS-MOST 17.1% in trials 30% natural history of stroke Essential to adhere to protocols

Complications Angio-oedema and anaphylaxis Stop infusion of rt-PA Urgent medical assessment – ‘ABC’ Hydrocortisone 200mg IV Chlorpheniramine 10mg IV Salbutamol nebuliser – 5mg if severe reaction: Adrenaline 0.5-1ml of 1 in1000 IM Fluid resuscitation if shocked and consider repeat doses of adrenaline as required

Requirements for Delivering Thrombolysis Place to deliver it Acute stroke unit CCU HDU Fast access to neuroimaging Within hours Out of hours Patients Front door staff Nurses, doctors Radiographers Radiologists Minimum door-to- needle time at WGH is 30 minutes

Delivering Thrombolysis Regionally:Telemedicine

Thrombolysis: the Challenges Getting the patients to attend quickly Getting hospital staff to attend the patient quickly Get the neuroimaging quickly Getting enough staff for a 24/7 service Getting enough staff with expertise in every hospital Making it as safe as possible – tailoring treatment to the patient