Stroke Thrombolysis Training Dr. Indira Natarajan Clinical Lead Acute Stroke and TIA Services

WHO DEFINITION “ rapidly developing clinical signs (at times global) of disturbance of cerebral function, lasting more than 24 hours with no apparent cause other than that of vascular origin” This definition includes signs and symptoms of suggestive of - ischaemic stroke - haemorrhages (intracerebral)

Diagnostic Dilemma “ Stroke Mimics ” or “ Stroke Syndrome ” 10% - 15% of patients referred with possible stroke have something else Some uncertainty is inevitable

Stop and Think! Drowsy and Delirious Patient with headache Drowsiness, confusion and headache

Drowsiness / Delirium SEIZURES METABOLIC / TOXIC SUBDURAL HAEMATOMA UNCONCONSCIOUS

ROSIER Scale Facial weakness +1 Arm weakness +1 Leg weakness +1 Speech disturbance +1 Visual disturbance +1 Loss of Consciousness - 1 Seizure episode - 1

Diagnostic Dilemma 68 year old Sudden onset Right facial arm and leg weakness with speech disturbance Vascular Risk factors: Hypertension Diabetes ....................... 32 year old Dubious onset Right facial arm and leg weakness Stuttering course No vascular risk factors ? Seizure ? Other causes

Treatments effective within first hours to days Aspirin Thrombolysis Acute Stroke Unit Hemicraniectomy

Effective treatment for 1 patient to benefit Numbers treated to benefit one patient Propotion of patients eligible Asprin 100 70 - 80% Stroke Unit 20 100% Thrombolysis 10 10% Hemicraniectomy 2 2%

Hyper-acute treatment of Stroke Re-Canalisation 10

Modified Rankin Scale 1 2 3 4 5 No Mild Moderately Severe Moderate Independent Dependent 11

TIME IS BRAIN 2 million neurons are lost every minute that treatment is delayed. Saver JL. Time is brain—quantified. Stroke 2006;37: 263–266. 12

rt-PA trials meta-analysis rt-PA trials meta-analysis. Benefit declines with increasing time to treatment, but scope for benefit up to 6h (Lancet 2004; 363: 768–74) Benefit Upper and lower 95% confidence limits Line of no effect Harm 3 hours 6 hours 13 13

Benefit of r-tpa at 90 days Time between event and treatment Odds ratio in favour of favourable outcome (95% CI) Estimated number needed to treat for favourable outcome 0-90 minutes 2.55 (1.44 to 4.52) 3.0 91-180 minutes 1.64 (1.12 to 2.40) 7.0 181-270 minutes 1.34 (1.06 to 1.68) 14.1 271-360 minutes 1.22 (0.92 to 1.61) 21.4

Acute Stroke Services... 1 hour 1 hour ESD 0 - 4.5 hours 999 A Patient's Journey..... 1 hour 1 hour ESD 0 - 4.5 hours

Exclude Hypo-glycaemia Check List Confirm diagnosis Exclude Hypo-glycaemia Confirm Onset Time NIHSS scale Eligibility Contra-indications Consent

NIHSS Scale International Scale Validated to be used across the world Mainly used to maintain consistency in all research studies Also to assess progress

Stroke Severity - NIHSS

Eligibility Age 80 or below Previously fit and independent Onset time known and less than 4.5 hours CT excludes haemorrhage

Exclusions Recent surgery, biopsies arterial cannaulation Increased bleeding risk Past history of intracranial haemorrhage Any CNS pathology other than current stroke Any past stroke plus diabetes Stroke within 3 months Systolic blood pressure >185 NIHSS < 4 or NIHSS > 25

Benefit of thrombolysis according to age group. Mishra. et Benefit of thrombolysis according to age group..... Mishra. et.al BMJ 2010; 341:c6046

Other ways of saving the Penumbra if beyond 3 - 6 hours Neuro-protection and Re-perfusion 22

Saving the Penumbra…….. Anitplatelets Aspirin and Dipyridamole Hydration use normal saline first 24 h Temperature keep below 37.5 Oxygenation treat if saturation <92% Blood glucose keep < 10 mmol/l Nutrition maintain Pain Control Analgesics Blood pressure Target 160-180/90-100 in normotensives Target 180/100-105 in hypertensives European Stroke Initiative 2003 (http://www.eusi-stroke.com/recommendations) unchanged in 200 23

Getting the right patient to the right place...... Admitting patient to the Acute Stroke Unit within 4 hours

Management of Complications

Figure 1 European Cooperative Acute Stroke Study (ECASS) classification of intracerebral haemorrhage (ICH) following thrombolysis (from Berger and colleagues38). (A) HI-1; (B) HI-2; (C) PH-1; (D) PH-2 Derex, L et al. J Neurol Neurosurg Psychiatry 2008;79:1093-1099 Copyright ©2008 BMJ Publishing Group Ltd. 26

Intracranial Haemorrhage Stop alteplase infusion Immediate non contrast CT head Immediate PT, APTT, fibrinogen FBC/Group and save Prepare 6 units platelets Prepare 6 units cryoprecipitate Haemorrhage on CT? NO YES Check lab results Give cryoprecipitate and platelets Notify Neurosurgeons Resume alteplase infusion Khaja, Lancet 2007; 396:319-330.

Intracranial haemorrhage within 36 h 7 % risk of Intracranial Haemorrhage (2 %of which were fatal) Asymptomatic 5%

Risk of haemorrhage depends on stroke severity NIHSS> 20 => haemorrhage risk 17% NIHSS <10 => Haemorrhage risk 3% Stroke 1997;28(11):2109-2118.

Extracranial bleeding Stop alteplase infusion Immediate PT, APTT, fibrinogen, FBC, group and save Use mechanical compression, if possible, to control bleeding form puncture sites Support circulation with fluids and blood transfusion, as appropriate For severe life threatening bleeding tranexamic acid 1 g i.v. over 15 min, repeated at 8 h if needed Consider transfusion of FFP and/or cryoprecipitate depending on the results of the coagulation screen

Reperfusion cerebral oedema Elevate the head to 30 degrees Correct hyperthermia, hypoxia, hyperglycaemia, hypotension Mannitol 0.25-0.5 mg/kg over 20 min i.v., repeat q 6-8 h, if necessary Dexamethasone 4 mg iv qds* Frusemide 20-40 mg iv* Avoid antihypertensives, especially vasodilators The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315–320 mOsm/L Steiner Neurol 2001 Consider decompressive hemicraniectomy (once clotting correct/corrected) If symptoms improve with mannitol reduce dose/frequency gradually AHA/ASA Stroke 2007;38:1655-1711. *as used by C. Roffe in Stoke, not in AHA/ASA guidance 31

Orololingual Angiooedema Stop alteplase infusion Antihistamines (clorpheniramine 10 mg i.v.) Hydrocortisone 200 mg i.v. Observe vital for signs of progression, dyspnoea, anaphylactic shock Usually starts early after the start of rx Resolves within 72 h Insula infarct=> contralateral tongue oedema Entgelter 2005 Most are on ACEI 1.9% after stroke thrombolysis 0.05% after MI thrombolysis Other rx ranitidine clemastin If sx are mild and non-progressive, alteplase can be restarted under close observation Khaja, Lancet 2007; 396:319-330. 32

Anaphylaxis Stop alteplase infusion Urgent medical assessment: Airway, Breathing, Circulation Adrenaline 0.5 -1 ml 1:1000 im or sc (not iv) Clorpheniramine 10 mg i.v. Hydrocortisone 200 mg i.v. Salbutamol nebulizer 5 mg If shocked i.v. saline and consider repeat doses of adrenaline

Thank you Any Questions ?