1. Complications following thrombolysis Phil Sanmuganathan Consultant Stroke Physician

2. Outline Pharmacological properties How to avoid or minimise complications Intracerebral haemorrhage and bleeding elsewhere Reperfusion cerebral excitability Cerebral oedema Anaphylaxis and angio-oedema Myocardial rupture

3. Pharmacology Alteplase is an enzyme Binds to fibrin in clots Converts plasminogen to plasmin Plasmin initiates local fibrinolysis Circulating fibrinogen drops by a third Half life distribution 5 min excretion 40 min

4. How to avoid complications Time of onset of symptoms Any seizure activity Severe strokes – NIHSS >20 BP <185/110 MI, Stroke 3/12 GI, urinary bleed 3/52 Major surgery 2/52

5. Bleeding complications Symptomatic ICH 6-9% stroke compared to 0.5-0.6% MI thrombolysis Usually massive Multifocal 30 day mortality 60%

6. Intracerebral bleeding Destroys and displaces brain tissue Increase ICP Haematoma growth Perihaematoma oedema + ischaemia Secondary intraventricular heamorrhage Hydrocephalus

7. Classification HI 1small petechiae infarct margins HI 2confluent petechiae within inf. No SOE PH 1clots exceeding 30% of infarct PH2clots exceeding 30% of infarct with SOE PHr1bleed away from the infarct mild SOE PHr2large bleed away from inf. Sig. SOE

8. Symptomatic ICH Parenchymal haemorrhage type 2 on post treatment scan neurological deterioration with 4 point increase in NIHSS

9. Parenchymal haematoma Plac.Rt-PA OTT (min) n bleed n bleeds 0-9015001615 91-180315330217 181-270-411739023 271-360508553837

10. ICH Analysis # of Risk Factors # of patients treated with t- PA (n=310) # of Symptomatic ICH’s (# of placebo patients with ICH) Percentage (%) 01142 (1)1.8 11447 (1)4.9 > 1521121.2 Baseline NIHSS > 20 Age > 70 years Ischemic changes present on initial CT Glucose > 300 mg/dl (16.7 mmol/L)

11. Treatment Stop alteplase infusion Airway, oxygenation, circulation Head 30 0 jugular venous drainage -  ICP BP <160/90 over 6hrs Platelet infusion 6-8 units Cryoprecipitate 6-10 bags Tranexemic acid 1 gm iv FFP 15-20 ml/kg

12. SBP management SBP >200 Labetalol 50 mg iv followed by 2-8mg/min (max. 200mg) SBP >180 Labetalol 50mg iv Aim to maintain SBP around 160 CPP >60 GTN 50mg in 50ml saline/dex. 0.6-12 ml/h

13. Reperfusion oedema Mannitol 1g/kg iv 8 hrly Epileptic fits lorazepam 4mg iv phenytoin 15mg/kg (50mg/min) INTENSIVE CARE

14. ITU Intravenous sedation – propofol Hyperventilation Manage cardiopulmonary instability associated with RICP DNAR

15. Angio-oedema Common in those on ACEI Usually self limitng Adrenaline 1:1000 nebulised if stridor Oxygen Alteplase infusion can be continued if ABC is not compromised

16. Anaphylaxis Laryngeal oedema, bronchospasm, hypotension Stop alteplase infusion Horizontal bed raise foot end Airway patent Adrenaline 1:10,000 five ml -1ml/min Chlorpheniramine 10mg slow iv Hydrocortisone 200 mg iv