Stroke Thrombolysis Dr Peter Anderton (Stroke Consultant DBTH)
Thrombolysis for ischaemic stroke Rationale Restoration of blood flow Salvage of ischaemic penumbra
Schematic of the mismatch model for defining the ischemic penumbra. Kidwell C S et al. Stroke 2003;34:2729-2735 Copyright American Heart Association
MRI of an acute right middle cerebral artery (MCA) infarct at 4 h. Warren D J et al. Postgrad Med J 2010;86:409-418 2010 by The Fellowship of Postgraduate Medicine
Thrombolysis benefit is time-dependent
Thrombolysis for ischaemic stroke ECASS 3 Trial: thrombolysis window extended to 4.5 hours
Thrombolysis for ischaemic stroke Indications/contraindications Check BM Indications Age no longer a contraindication Able to scan and treat within 4.5h of onset Time of onset = when last seen well Not dependent
Pharmacology Emerging evidence for TNK (longer t1/2, single bolus) Need to start infusion of tpa within 15 mins of bolus to maintain plasma levels
RCP guidance CT head. Ideally the next available slot on the CT scanner if considering thrombolysis Regardless of age or stroke severity, where treatment can be started < 4.5 hrs (if there are no contraindications), all patients should be considered for treatment using t-pa as soon as possible
Door to Needle Time Time is Brain
Each minute delay in treatment causes: Loss of 1.9 million neurones Loss of 14 billion synapses Loss 12 km (7.5 miles) of myelinated fibres Brain cell no regeneration!
Key points Time is brain! Refine processes Parallel processing Avoid unnecessary steps Increasingly, consider thrombectomy (for proximal occlusions) if unsuitable for tpa or tpa unsuccessful
DTN Audit DRI Dr Katherine Francis (CT2) Dr Sarah Stephenson (FY1) Evaluate Door to Needle Time (DNT) of stroke thrombolysis at Doncaster Royal Infirmary Evaluate reasons for delay in DNT Suggest an appropriate action plan to improve DNT
Data Collection 32 patient cases randomly selected Stroke thrombolysis between February to July 2016 (6 months) Retrospective data collection from the ambulance sheets, emergency department and medical notes and time of CT head from synapse Comparison made to audit Jan 2014- April 2015 (59 patients)
Stroke Thrombolysis Team 24/7 A local Stroke Consultant from the DRI covers the thrombolysis service Monday to Friday 0800-1700 Saturday to Sunday 0900-1700 an Acute Medicine Consultant Out of hours (weekday 1700-0800 and weekend 1700-0900) via the South Yorkshire telemedicine service (regional rota); an audio-visual link to a specialist consultant with remote access to the CT brain images
Stroke Thrombolysis Pathway 1) Onset of stroke symptoms 2) Call to 999 3) Paramedic calls Stroke Thrombolysis Red Phone on Ward 16 to give ETA 4) Arrival to A&E (DOOR) 5) Initial assessment, bloods, IV access and NIHSS score 6) CT head performed 7) Patient transferred to Ward 16 8) CT head reviewed 9) Recheck BP, weight and check contra-indications 9) Consent for thrombolysis 10) Dose of t-pa calculated 11) Thrombolysis initiated (NEEDLE)
Thrombolysis Thrombolytic therapy with recombinant tissue plasminogen activator (t-pa) Total dose 0.9 mg/kg eg. 70kg = 63mg The first 10% given as a bolus Then the rest as an infusion over 60 minutes
Patient Demographics Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) Patient No. 59 32 Female Male Mean Age 29 18 30 14 72 76
Age of patients thrombolysed 30 25 20 15 10 Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) 5 0 < 40 41-60 61-80 81-90 > 91
In hours or out of hours? Local stroke Cons in hours (mon-fri 8-17) Acute medicine Cons (weekend 9-17) Telemedicine (local + regional OOH) Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) 35/59 (60%) 20/32 (62%) 4/59 (7%) 6/32 (19%) 20/59 (33%) 6/32 (19%)
NIHSS Recommended NIHSS score for thrombolysis = 3 to 25 Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) NIHSS scores calculated 59/59 (100%) 31/32 (97%) Mean NIHSS 13 15 Median NIHSS - 16 Max NIHSS 26 31 Min NIHSS 3 3
Door to CT time (mins) Door to CT (mins) Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) Feb July 2016 (6 months) Feb July 2016 (6 months) Feb July 2016 (6 months) Working Hours Mon- Fri 0800-1700 Mean Mean Median Max 35 15 15 42 2 Min Weekend 0900-1700 (AMU cons) 38 27.5 30.5 41 9 Out of hours 39 18.3 20.5 26 4
CT to Needle Time (mins) CT to needle (mins) Jan 2014- April 2015 (16 months) Mean Feb July 2016 (6 months) Mean Feb July 2016 (6 months) Median Feb July 2016 (6 months) Max Feb July 2016 (6 months) Min Working Hours 27 32 21 135 12 Mon- Fri 0800-1700 Weekend 0900-1700 (AMU cons) 51 33 28.5 55 15 Out of hours 60.5 72.5 58 168 36
Door to Needle Time (mins) DNT (mins) Jan 2014- April 2015 (16 months) Mean Feb July 2016 (6 months) Mean Feb July 2016 (6 months) Median Feb July 2016 (6 months) Max Feb July 2016 (6 months) Working Hours 62 48 36 137 16 Mon- Fri 0800-1700 Min Weekend 0900-1700 89 60.5 62.5 91 34 (AMU cons) Out of hours 100 91 71.5 190 56 All 77 59 40 190 16
Mean DTN (minutes) 100 90 80 70 60 50 Mean DTN (minutes) 40 30 20 10 0 Mon- Fri 8-17 Weekend 9-17 Telemedicine OOH
Door to Needle Time (mins) DNT (mins) Jan 2014- April 2015 (16 months) Feb July 2016 (6 months) < 20 0/59 (0%) 1/31 (3%) 21-40 7/59 (12%) 16/31 (52%) 41-60 19/59 (32%) 3/31 (10%) 61-80 12/59 (20%) 5/31 (16%) 81-120 14/59 (24%) 4/31 (13%) 121-180 5/59 (8%) 1/31 (3%) >181 2/59 (3%) 1/31 (3%)
Door To Needle Time 18 16 14 12 10 8 6 4 2 0 < 20 minutes 21-40 minutes 41-60 minutes 61-80 minutes 81-120 minutes 121-180 minutes >180 minutes
DTN >120 mins (2 patients) Case One (137 mins) Local Stroke Cons in working hours 2 mins Door to CT 135 mins CT to needle (as NIHSS initially 2 and then increased to 4 so thrombolysed) Case Two (190 mins) Telemedicine (STH consultant) 22 mins Door to CT 168 mins CT to needle (clinical decision - delayed due to hypertension)
DTN 81-120 mins ( 5 patients) Case One (105 mins) Local stroke cons in working hours 19 mins door to CT 86 mins CT to needle (family initially declined thrombolysis then changed their minds) Case Two (92 mins) Local stroke cons in working hours 17 mins door to CT 75 mins CT to needle (delayed due to hypertension) Case Three (91 mins) Weekend AMU Cons 37 mins door to CT 54 mins CT to needle (no clear cause of delay documented)
DTN 81-120 mins Case Four (89 mins) Local stroke cons but at the weekend 34 mins door to CT 55 mins CT to needle (no clear cause of delay documented) Case Five (93 mins) Telemedine OOH 26 mins door to CT 67 mins CT to needle ( no clear cause of delay identified)
DTN 61-80 mins ( 4 patients) Case One (69 mins) Local Stroke Cons in working hours 42 mins Door to CT (no clear reason given for delay here) 27 mins CT to needle (collateral history awaited for time of onset) Case Two (65 mins) Local stroke cons at the weekend 27 mins Door to CT 38 mins CT to needle (no clear delay identifiable in the notes) Case Three (69 mins) Telemedicine OOH 21 mins Door to CT 48 mins CT to needle (medical SpR at a cardiac arrest so telemedicine call done by SHO) Case Four (78 mins) Telemedicine OOH 17 mins Door to CT 61 mins CT to needle (Easter Monday bank holiday difficulty finding Cons oncall)
Telemedicine Delays are usually multifactorial Long DNTs usually had a clear clinical reason why: NIHSS score, hypertension requiring treatment, family initially declining thrombolysis, awaiting collateral history Difficult to identify the delay from door to CT in some patient cases Biggest delays are OOH Door to CT: Mean 18.3 (mins). Median 20.5 (mins) CT to needle: Mean 72.5 (mins). Median 58 (mins) CT to needle time: Computers turned on and ready Inform oncall consultant so they are aware of potential thrombolysis or call them when everything is ready? Education of medical SpR Experienced stroke nurse covering out of hours
Summary 65% of patients were thrombolysed in <60 mins Improved from 44% in < 60 mins from 2014-2015 audit Average DTN 59 minutes (compared to 77 mins from 2014-2015 audit) From the 35% (11 patients) that took >60 mins: 5/11 had a clear clinical reason to delay thrombolysis 4/11 had no clear identifiable reasons in the notes (likely multifactorial) 2/11. One due to the medical SpR being at a cardiac arrest and the other difficulty identifying an oncall consultant on a bank holiday
Where can we improve? Possible solutions: Straight to CT if the patient is stable piloted to become SOP Reduce variability: SOP, parallel processing Bloods, NIHSS, etc, while tpa being drawn up Free up consultants to assess at front door job planning Thrombolysis in CT / ED to reduce transfer delay explored, more useful if TNK becomes standard (pharmacokinetics) Stroke code Training thrombolysis simulation Encourage early screening and pre-alert of Stroke consultants OOH being piloted need to check compliance: target for further (regional) audit
Actions Plan Emergency Stroke Alert pilot and evaluate Stroke induction training for Med SpRs Stroke training video CT stroke bleep (to expedite stroke scans from all clinical areas) Stroke Thrombolysis SOP Re-audit (pan-regional)
Thank you Questions?