Thrombolysis in Acute Ischaemic Stroke
Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT)
Thrombolysis in acute ischaemic stroke – Assessment and eligibility for IV Alteplase Lead Author: Dr Chris Douglass; Consultant Neurologist Additional author(s) Dr Adrian Parry-Jones; Consultant Neurologist Dr Rekha Siripurapu; Consultant Neuroradiologists Professor Craig J Smith; Consultant Stroke Physician Division/ Department:: Stroke Services, Manchester Centre for Clinical Neurosciences Applies to: (Please delete) Salford Royal Care Organisation Approving Committee MNARC Date approved: 09/07/2019 Expiry date: July 2022 Contents Contents
Section Page 1 Overview 3 2 Scope & Associated Documents 3 3 Background 4 4 What is new in this version? 4 5 Policy 5 5.1 Initial urgent clinical assessment 5 5.2 Urgent brain imaging 7 5.3 Thrombolysis checklist 8 5.4 Information giving 11 6 Roles and responsibilities 12 7 Monitoring document effectiveness 12 8 Abbreviations and definitions 13 9 References 13 10 Appendices Patient information sheet 16 Thrombolysis in Children aged 16-18 18 Paediatric NIHSS 22 11 Document Control Information 29 12 Equality Impact Assessment (EqIA) screening tool 31
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Group arrangements: Salford Royal NHS Foundation Trust (SRFT) Pennine Acute Hospitals NHS Trust (PAT)
1. Overview (What is this policy about?)
Thrombolysis with intravenous (iv) tissue plasminogen activator (tPA; alteplase) is a cost- effective treatment for use in selected patients within 4.5 h of acute ischaemic stroke according to eligibility criteria derived from randomised-controlled trials (RCTs) and expert consensus.
The potential benefits from iv tPA are highly time-dependent (“time is brain”), meaning that focus on “door-to-needle” (DTN) and “onset-to-needle” (OTN) times is critical.
As iv thrombolysis is not without potentially serious side effects, appropriate selection of patients for treatment based on rapid assessment of the potential risks/benefits is of vital importance.
The purpose of this policy is to consolidate best evidence-based guidance to inform timely, safe and appropriate use of iv tPA in acute ischaemic stroke at SRFT.
This policy describes the processes involved in urgent assessment of eligibility for iv tPA and provides guidance on provision of standardised information about risks and benefits of thrombolysis to patients and their families.
There are currently no recommended decision tools for individualised prediction of risk-benefit when considering thrombolysis with iv tPA in clinical practice
2. Scope (Where will this document be used?)
SRFT is committed to high-quality care for patients with stroke. SRFT is the Comprehensive Stroke Centre (CSC) for the Greater Manchester Conurbation, providing a 24/7 iv thrombolysis service. This policy incorporates best evidence-based and consensus guidance and the local systems and processes relevant to delivering iv tPA safely and quickly. It describes the processes involved in urgent assessment of eligibility and provides guidance on provision of standardised information about risks and benefits of thrombolysis to patients and their families.
Associated Documents: http://guidance.nice.org.uk/TA264/Guidance/pdf/English http://www.rcplondon.ac.uk/sites/default/files/national-clinical-guidelines-for-stroke-fourth- edition.pdf https://www.rcpch.ac.uk/sites/default/files/2018-07/2017_stroke_in_childhood_- _guideline_final_3.6.pdf
Thrombolysis in acute ischaemic stroke – awareness and management of angioedema: TC 3 (09) – Issue No: 4 http://intranet.srht.nhs.uk/policies-resources/trust-policy-documents/trust-wide- clinical/gen/tc309/
Thrombolysis in acute ischaemic strokes; assessment and eligibility for iv Alteplase Reference Number TWCG6(12) Version 4 Issue Date: 05/09/2019 Page 2 of 31 It is your responsibility to check on the intranet that this printed copy is the latest version
Acute Stroke - Management of Hyperglycaemia: TWCG09(14) - Issue No 2 - Acute Stroke management of Hyperglycaemia http://intranet/policies-resources/trust-policy-documents/trust-wide-clinical/gen/twcg0914/ Thrombolysis in acute ischaemic stroke – management of acutely elevated blood pressure: TC 10 (10) – Issue No: 3 http://intranet.srht.nhs.uk/policies-resources/trust-policy-documents/trust-wide- clinical/gen/tc1010/
3. Background
Thrombolysis with iv tPA is an evidence-based and cost-effective therapy for ischaemic stroke in selected patients presenting within 4.5 hours of symptom onset.1,2,3 iv tPA is safe and effective when given up to 4.5 hours from symptom onset,4 and international thrombolysis audit registries confirm the safety and efficacy profile of iv tPA administered up to 4.5 hours in clinical practice, when patients are selected according to defined eligibility criteria.5
4. What is new in this version?
The eligibility criteria for iv tPA have been revised in line with recent consensus appraisal of the available literature,6 and consensus reached within the Greater Manchester Operational Delivery Network (ODN). The thrombolysis checklist (Table 3) has been amended accordingly.
The upper age limit of 80 y has been removed from the CTA protocol as there is no justification in excluding those >80 y from consideration of thrombectomy 7
The lower age limit of 18 has been reduced to 16 following the Royal College of Paediatrics and Child Health Guidelines of May 2017. 17
The patient and relative information has been updated in line with most recent data concerning risks and benefits of iv tPA
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5. Policy
5.1 Initial urgent clinical assessment
FAST 8 positive courtesy “red” call received via NWAS, activating acute stroke assessment team baton pagers
Patients self-presenting to A&E who are FAST positive and have an onset time within 4 hours will be reviewed by the Emergency Department (ED) consultant who will put a 2222 call to switchboard for immediate Stroke Team response via assessment team baton pagers
Acute stroke assessment nurse and duty registrar/ advanced nurse practitioner (ANP)/ senior Dr attend (ED) as soon as possible
Urgent observations in ED: o Airway integrity o Respiratory rate and oxygen saturations o Circulation (heart rate and blood pressure) o Glasgow Coma Scale (GCS) o BM stix; cannula o Urgent blood tests o 12-lead ECG
History & Examination to include: o drug history o pre-stroke mRS (modified Rankin Scale) score 9 (Table 1) o neurological examination o NIHSS (National Institutes of Health Stroke Scale) score 10 (Table 2)
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Table 1: Modified Rankin score (4 weeks before current stroke presentation)
0 No symptoms at all.
1 No significant disability despite symptoms. Able to carry out all usual duties and activities.
Slight disability: unable to carry out all previous activities, but able to look after own affairs without 2 assistance.
3 Moderate disability: requiring some help but able to walk without assistance.
Moderately severe disability: unable to walk without assistance and unable to attend to own bodily 4 needs without assistance.
5 Severe disability: bedridden, incontinent, and requiring constant nursing care and attention.
Table 2: NIHSS score Tested item Item Response and score 1A Level of consciousness 0-alert 1-drowsy 2-obtunded 3-coma/unresponsive 1B Orientation questions 0-answers both correctly 1-answers one correctly 2-answers neither correctly 1C Response to commands 0-performs both corerctly 1-perorms one correctly 2-performs neither correctly 2 Best gaze 0-normal horizontal movements 1-partial gaze palsy 2- complete gaze palsy 3 Visual fields 0-no visual field defect 1-partial hemianopia 2-complete hemianopia 3-bilateral hemianopia 4 Facial palsy 0-normal 1-minor facial weakness 2-partial facial weakness 3-complete unilateral palsy 5 Motor function arm 0-no drift a – left 1-drift before 5s b – right 2-falls before 10s 3-no effort against gravity 4-no movement 6 Motor function leg 0-no drift a – left 1-drift before 5s b – right 2-falls before 5s 3-no effort against gravity 4-no movement 7 Limb ataxia 0-no ataxia 1-ataxia in 1 limb 2-ataxia in 2 limbs 8 Sensory 0-normal 1-mild/moderate sensory loss 2-sever/total sensory loss 9 Best language 0-normal 1-mild/moderate aphasia 2-severe aphasia 3mute or global aphasia 10 Dysarthria 0-normal 1-mild/moderate dysarthria 2-severe dysarthria 11 Extinction/inattention 0-normal 1-mild loss (one modality) 2-severe loss (2 modalities)
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5.2 Urgent brain imaging
Plain CT brain scan next available slot, 24h/ day Proceed directly to CTA in selected patients (Category 1A) as per protocol (Figure 1) where appropriate without delaying IV treatment Before proceeding with thrombolysis, the imaging must be reviewed by an appropriately trained individual. This may be a consultant stroke physician/ neurologist or trainee. All imaging will be reviewed by the duty radiology SpR, or the teleradiology service overnight, and reported on EPR. Consider the need for intra-arterial intervention (see SRFT Emergency intra-arterial (IA) intervention in acute ischaemic stroke).11
Figure 1: Hyperacute Stroke CT/CTA Protocol
Patients being considered for iv tPA require an urgent plain CT (next available slot). In addition, consider CTA as follows:
Daily between 0800 and 1800; If the following criteria met and the patient is considered potentially eligible for IA intervention # • Within 4.5 hours of symptom onset • Aged ≥16 years of age • NIHSS ≥ 6 • Pre-stroke mRS 0-2 • Otherwise potential candidate for IA procedure
CATEGORY 1A: Direct access CT/CTA
Outside these hours: Non-contrast CT only If CTA required for suspected basilar thrombosis this requires consultant stroke physician
discussion with consultant neuroradiologist on a case-case basis
# If proven basilar artery occlusion (BAO), IA thrombectomy may be considered >4.5 h after symptom onset on an individual case basis (discuss with the available neurointerventionalist)
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5.3 Thrombolysis checklist
The SRFT eligibility criteria “checklist” (Table 3) for treatment with iv tPA is based on National/International guidelines, 1-3 and consensus within the Greater Manchester ODN. The checklist MUST be completed prior to administering iv tPA in all cases and counter-signed by two appropriate clinicians (usually the attending stroke assessment nurse and stroke physician/ neurologist) and a record of this process entered on EPR. The tPA doses MUST be prescribed and signed for on EPR. When the duty stroke consultant is off-site they must be satisfied (and document) that the imaging has been reviewed and the checklist has been completed (Figure 2).
Notes on eligibility criteria checklist:
The eligibility criteria for iv tPA have been revised and updated based on recent guidelines,6 regional consensus, European licensing, and consensus within the SRFT Stroke Consultant body:
Preceding mRS of >2: This has been removed from the absolute exclusion criteria. There is insufficient evidence to restrict thrombolysis to mRS 2, even though clinical trials excluded patients with pre-existing disability. Patients with mRS of >2 may be considered for thrombolysis on an individual case-case basis Age >80 years: Although alteplase is not licenced in Europe for use in individuals >80years of age, recent pooled analyses of RCT data suggest that favourable outcomes with iv tPA are similar in those >80years compared to those <80years, with no difference in symptomatic intracerebral haemorrhage (ICH).4 Whilst evidence supports thrombolysis with iv tPA in patients >80years of age, which is current practice at SRFT, its use is “off- licence” Age>18 years: Although Alteplase is not licensed in Europe for use in individuals <18 years of age recent guidelines from the Royal College of Paediatrics and Child Health have suggested that this age group may benefit from iv tPA or thrombectomy although the underlying mechanisms of the strokes may be different and so imaging with CT angiograms is necessary before thrombolysis in all cases. 17 Severe stroke: Severity of stroke does not modify the proportional treatment effect of iv tPA, although the absolute risk of symptomatic ICH is higher in more severe strokes. 4,12 Treatment of severe strokes (NIHSS > 25) should be with caution in view of the risk of ICH, particularly between 3-4.5 h, and considered on an individual case-case basis Minor or rapidly resolving symptoms: This has now been removed as an absolute exclusion criteria. Some patients with minor yet potentially disabling stroke (e.g. isolated homonymous hemianopia) are likely to benefit from iv alteplase. Likewise, patients with a moderate severity stroke may have rapidly improving stroke symptoms, but still to a level which is potentially disabling. Patients with minor or rapidly resolving symptoms should be considered for thrombolysis on an individual case-case basis Blood pressure: Blood pressure must be below 185/110 mmHg before, and for the first 24 hours after, initiation of thrombolysis. Refer to the Trust protocol for the approach to management of elevated BP in the setting of thrombolysis.13 Seizure at onset: This is not a contraindication to thrombolysis if there is otherwise evidence supporting an underlying acute ischaemic stroke Early signs of infarction on non-contrast CT: The significance of early signs of ischaemia when considering thrombolysis remains uncertain. Treatment should proceed with
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caution when there are signs of early infarction >one third of the territory of the middle cerebral artery Urgent INR: This is not required to complete the checklist unless existing warfarin treatment is definite or cannot confidently be excluded from the available information. Likewise, it is not necessary to wait for the platelet count to complete the checklist unless a high-level of clinical suspicion that significant thrombocytopenia is likely INR threshold of >1.7: This threshold is based on local consensus within the Greater Manchester ODN and FDA guidance Hyper- or hypoglycaemia: Thrombolysis may be considered after appropriate correction of hypoglycaemia (venous glucose <2.7mmol/l) or hyperglycaemia (>22.2mmol/l), followed by clinical re-assessment. Acute hyperglycaemia (BM>11 mmol/l) should be managed in line with local policy. 14 Newer Oral AntiCoagulants: Until further data/guidance become available, thrombolysis should be regarded as contraindicated in patients who have received treatment with one of the newer oral anticoagulant agents (NOAC e.g. direct thrombin inhibitors such as dabigatran; factor Xa inhibitors such as rivaroxaban) within the preceding 48h. Pregnancy: The risk-benefit profile of iv tPA in pregnancy and the early post-partum period (<14d) are uncertain. The AHA/ASA guidelines list pregnancy as a relative contra- indication, based on individual case-case evaluation and urgent consultation with an obstetrician/on call gynaecologist if out of hours. Recent lumbar puncture: Thrombolysis should be avoided within 7 days of a lumbar puncture. 6
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Table 3: Thrombolysis checklist Patient name Hospital number Date of birth
INCLUSION CRITERIA – MUST ANSWER YES TO ALL OF THE FOLLOWING Aged ≥16 years with symptoms of acute stroke Onset within last 4.5 hours* Measurable deficit on NIHSS Absence of haemorrhage or stroke mimic on baseline CT
ABSOLUTE EXCLUSION CRITERIA – MUST ANSWER NO TO ALL OF THE FOLLOWING Systolic BP>185 and/or diastolic BP >110 Symptoms and signs suggestive of a subarachnoid haemorrhage Any evidence of active bleeding History of any intracranial haemorrhage Arterial puncture at non-compressible site within 7 days Recent lumbar puncture within last 7 days Known or strongly suspected bacterial endocarditis Known or confirmed aortic dissection if suspected Major head trauma; brain or spinal surgery within last 3 months Platelet count <100 xퟏퟎퟗ/l if high-level of clinical suspicion Heparin or NOAC∞ within last 48 hours; or INR >1.7 on warfarin
RELATIVE EXCLUSION CRITERIA - CONSIDER ON CASE-CASE BASIS Pregnancy Stroke within last 3 months Major surgery or non-head trauma within last 2 weeks Brain tumour, cerebral aneurysm or AVM # Gastro-intestinal, urinary or gynaecological haemorrhage within last 21 days * proceed with caution between 3-4.5h window if age >80y, NIHSS>25 and/or early infarct change >one third of the MCA territory ∞ direct thrombin inhibitors (e.g. dabigatran) or factor Xa inhibitors (e.g. rivaroxaban) # may consider if underlying CNS lesions at low-risk of bleeding such as small unruptured aneurysms (<10mm) or benign tumours with low vascularity
CHECKLIST COMPLETED BY: Attending physician (print name) Signature
Acute assessment nurse (print name) Signature
Date and time
SRFT INFORMATION SHEET PROVIDED BY
ALTEPLASE PRESCRIBED ON EPR BY
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Figure 2: Assessment for IV tPA when duty/on-call consultant “off-site”
Potentially eligible patient for IV tPA
Assessment by on-site registrar/ ANP and ASU assessment nurse
CONTACT DUTY CONSULTANT URGENTLY FOR DISCUSSION
Duty consultant TELEMEDICINE/TELEPHONE review:
Review history, clinical findings # Ensure brain imaging has been reviewed Discuss each checklist item with registrar Confirm checklist completed and signed appropriately Consider CTA/IA procedure Document decision to proceed on EPR Consider attending for on-site review on individual patient basis
# Before proceeding with thrombolysis, the imaging must be reviewed by an appropriately trained individual. This may be a consultant stroke physician/ neurologist or trainee. All imaging will be reviewed by the duty radiology SpR and reported on EPR.
5.4 Information giving
Although written informed consent for IV thrombolysis is not required, a full explanation of the clinical scenario (including stroke severity and anticipated prognosis with usual care) proposed treatment (thrombolysis with alteplase; risks and benefits) is mandatory. 15 However, there are currently no sufficiently validated clinical prediction tools with sufficient precision for individualised risk/benefit assessment in thrombolysis. 15 The risk of angioedema should be assessed in line with existing Trust policy. 16 The patient information sheet (Appendix 1) has been approved by SRFT document control. It aims to provide standardised information on the risks and benefits of treatment with iv alteplase; based on published literature and local experience at SRFT. It is not intended to be proscriptive or replace clinical judgement, but should be used as a basis for discussions with patients and their families in conjunction with other clinical information used to inform risk/ benefit. The discussion and provision of the information sheet should be documented on EPR.
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6. Roles & responsibilities
ASU and HASU Ward Manager and Stroke Consultants: to ensure all medical and trained nursing staff are familiar with, and comply with this policy, in accordance with agreed competencies set-out for nursing and medical staff.
Stroke lead for neuroradiology: to ensure all Consultant and junior colleagues and CT radiographers are familiar with this policy, specifically the requirement for urgent, priority CT imaging including selection for CT/ CTA.
7. Monitoring document effectiveness
Key standards; Patients presenting with a suspected stroke within 4.5 hours of onset will be screened urgently by a trained ASU assessment nurse and senior stroke physician/ neurologist (specialist registrar (SpR)/ specialty trainee (ST) and/ or Consultant) according to this protocol.
In the absence of haemorrhage (or other stroke mimic) on urgent plain CT brain imaging, selected patients will proceed directly to CTA in line with the agreed algorithm (Category 1A).
Eligibility for iv tPA must be confirmed and counter-signed on the checklist by two appropriate clinicians (usually the attending stroke physician/ neurologist and assessment nurse), and documented on iSOFT.
All patients considered for iv tPA must be discussed with the duty Consultant stroke physician/ neurologist who must ensure the baseline brain imaging has been reviewed and the checklist has been completed before proceeding with treatment.
Thrombolysis should be administered as quickly as possible after appropriate assessment, and with a target DTN time of <50 mins iv tPA must be prescribed and signed-for on the EPR
The Trust patient information sheet will form the basis for providing patients and their families with the estimated risks and benefits of proceeding with iv tPA or not.
Methods;
All patients undergoing thrombolytic therapy are prospectively identified and entered both into the Sentinel Stroke Audit Programme (SSNAP) and onto a standardised proforma addressing the key assessment standards set out in this document. These form the basis for discussion of all patients receiving thrombolysis at monthly Stroke Mortality and Morbidity meetings and provides a resource for audit of care processes, locally-agreed standards and mortality.
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8. Abbreviations and definitions tPA tissue plasminogen activator ED Emergency Department DTN door to needle time (time from arrival in ED to thrombolysis) OTN onset to needle time (time from stroke onset to thrombolysis) CSC Comprehensive Stroke Centre (Salford Royal) FAST Face/Arm/Speech/Time test to screen for a stroke NIHSS National Institute of Health Stroke Scale; a score of stroke severity mRS modified Rankin score BAO basilar artery occlusion NOAC newer oral anticoagulants; drugs such as Apixaban or Dabigatran AVM arterio-venous malformation AIS acute ischaemic stroke
9. References
1. http://guidance.nice.org.uk/TA264/Guidance/pdf/English. Last accessed 05/07/2016
2. Jauch EC, Saver JL, Adams Jr HP, Connors AB, Demaerschalk BM, Khatri P, McMullan Jr PW, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H, on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, and Council on Clinical cardiology. Guidelines for the early management of adults with ischemic stroke. A Guideline for healthcare professionals from the American Heart Associations/American Stroke Association. Stroke 2013; 44: 870-947.
3. http://www.rcplondon.ac.uk/sites/default/files/national-clinical-guidelines-for-stroke-fourth- edition.pdf. Last accessed 01/08/2017
4. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W, for the Stroke Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929-1935
5. Ahmed N, Kellert L, Lees KR, Mikulik R, Tatlisumak T, Toni D, SITS Investigators. Results of intravenous thrombolysis within 4.5 to 6 hours and updated results within 3 to 4.5 hours of onset of acute ischemic stroke recorded in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register (SITS-ISTR): an observational study. JAMA Neurol 2013; 70: 837-844.
6. Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, Khalessi AA, Levy EI, Palesch YY, Prabhakaran S, Saposnik G, Saver JL, Smith EE, on behalf of the American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke. A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47: 581-641.
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7. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Dávalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy E, Berkhemer OA, Pereira VM, Rempel J, Millán M, Davis SM, Roy D, Thornton J, San Román L, RibóM, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG, for the HERMES collaborators. Endovascular thrombectomy after large-vessel iscahemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731.
8. Mohd Nor A, McAllister C, Louw SJ, Dyker AG, Davis M, Jenkinson D, Ford GA. Agreement between ambulance paramedic- and physician-reported neurological signs with face arm speech test (FAST) in acute stroke patients. Stroke 2004; 35: 1355-1359.
9. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19: 604-607.
10. Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine S, Haley EC, Grotta J, Marler J, and the NINDS TPA Stroke Study Group. Improved reliability of the NIH stroke scale using video training. Stroke 1994; 25: 2220-2226.
11. Urgent percutaneous reperfusion therapy in acute ischaemic stroke: TC 23 (09) – Issue No: 3. http://intranet.srht.nhs.uk/policies-resources/trust-policy-documents/trust-wide- clinical/gen/tc2309/ Last accessed 01/08/2017
12. Whiteley WN, Emberson J, Lees KR, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg MG, Lindley RI, Lyden P, Olivot JM, Parsons M, Toni D, Toyoda K, Wahlgren N, Wardlaw J, del Zoppo GJ, Sandercock P, Hacke W, Baigent C, for the Stroke Thrombolysis Trialists’ Collaboration. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient meta-analysis. Lancet Neurol 2016; Published Online June 8. http://dx.doi.org/10.1016/S1474-4422(16)30076-X
13. Thrombolysis in acute ischaemic stroke – management of acutely elevated blood pressure: TC 10 (10) – Issue No: 3 http://intranet/policies-resources/trust-policy-documents/trust-wide-clinical/gen/tc1010/ Last accessed 01/08/2017
14. Acute Stroke - Management of Hyperglycaemia: TWCG09(14) - Issue No: 2 http://intranet/policies-resources/trust-policy-documents/trust-wide-clinical/gen/twcg0914/ Last accessed 01/08/2017
15.https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/448997/Final_ conclusions_and_recommendations.pdf. Last accessed 01/87/2017
16. Thrombolysis in acute ischaemic stroke – awareness and management of angioedema: TC 3 (09) – Issue No: 4 http://intranet/policies-resources/trust-policy-documents/trust-wide-clinical/gen/tc309/ Last accessed 01/08/2017
17. Stroke in childhood; Clinical guideline for diagnosis, management and rehabilitation. May 2017. Royal College of Paediatrics and Child Health.
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”https://www.rcpch.ac.uk/sites/default/files/2018-07/2017_stroke_in_childhood_- _guideline_final_3.6.pdf
18. Ichord, R. N., Bastian, R., Abraham, L., Askalan, R., Benedict, S., Bernard, T. J., ... Jawad, A. F. (2011). Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke, 42(3), 613-617. DOI: 10.1161/STROKEAHA.110.607192
19 Thrombolysis in Pediatric Stroke Study. http://stroke.ahajournals.org/content/46/3/880/tab- figures-data.
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10. Appendices
Appendix 1 Patient information sheet
Salford Royal Foundation Trust Acute Stroke Unit and Comprehensive Stroke Centre
If you have any questions about the information in this leaflet please ask any of the nursing staff or doctors on the stroke units (ASU telephone: 0161 206 7209/4788; B3 telephone: 0161 206 1903)
Thrombolysis in Acute Stroke:
What is it?
Many strokes are caused by a clot in the blood stream suddenly blocking an artery to the brain. Thrombolysis is a “clot busting” treatment for acute stroke. The treatment aims to break down the blood clot in the artery, allowing blood to flow back to the brain.
What sort of strokes are treated with thrombolysis?
Strokes that are due to a blood clot in an artery in the brain which reduces the flow of blood to the part of the brain that gets its blood supply from that artery causing damage to that part of the brain. It is NOT suitable for people with a bleed in the brain (brain haemorrhage) or a history of brain haemorrhage in the past. Thrombolysis is not currently licenced for use in patients over the age of 80 years of age, although recently, the largest clinical trial of thrombolysis to date has confirmed that patients over 80 benefit the same as those under 80 years of age.
How soon after stroke can it be given?
The sooner the better. Thrombolysis must be given within 4 and a half hours of the first sign of the stroke (except in certain circumstances that would be discussed with you by the stroke consultant). A brain scan will be performed to rule-out any bleeding in the brain before the treatment is given.
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What are the potential benefits and risks?
The sooner treatment is started the better the chances of a good outcome. Research looking at clot busting treatment in stroke shows that:
Within 3 hours of stroke symptoms: Compared to not receiving treatment with thrombolysis, 1 in 10 patients treated will have an excellent outcome
Between 3 and 4 and a half hours of stroke symptoms: Compared to not receiving treatment with thrombolysis, 1 in 20 patients treated will have an excellent outcome
The likelihood of dying following a stroke is not changed by clot busting treatment
There are potential risks of treatment, which need to be considered. As thrombolysis temporarily stops the body forming clots, the main risk is bleeding during or shortly after the treatment.
Overall, compared with not receiving thrombolysis, around 1 in 30 patients treated will have significant bleeding in the brain after thrombolysis, which makes them worse or may be fatal
Around 1 in 14 will have some kind of allergic reaction to the thrombolysis, which is nearly always minor and resolves with medications. Very rarely, the allergic reaction can interfere with breathing, and breathing support on intensive care may be needed
The risks are highest in people with severe stroke. The stroke doctor will tell you what your or your relative’s stroke scale score is, which will tell you if it is mild, moderate or severe.
What happens now?
The doctor will guide the decision to treat with thrombolysis, and explain how the decision has been reached. If you agree to treatment, a safety checklist will be completed and the dose of thrombolysis will be based on a person’s weight. It will be started as soon as possible following the scan and a decision to proceed. The drug is given via a drip in the vein, and takes an hour to complete with close monitoring. Once the thrombolysis has finished , you or your relative will be moved to the hyper acute stroke unit and monitored carefully for any complications. A second brain scan (usually a CT scan) will be done at 24 hours following treatment, to check for any bleeding.
Salford Royal provides assessment and treatment for people with suspected stroke from all around Greater Manchester, 24 hours a day, seven days a week. If you or your relative is from another district other than Salford, we will arrange for a return to the local stroke unit following the second scan. This is because ongoing care, such as rehabilitation and follow-up, is best provided in your own locality.
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Appendix 2 Thrombolysis in children aged 16 to 18.
Adapted from “Stroke in childhood; Clinical guideline for diagnosis, management and rehabilitation. May 2017. Royal College of Paediatrics and Child Health.” 17
Stroke is an important childhood disorder and is at least as common as brain tumours, affecting several hundred children and young people in the UK each year. At least half of survivors have some long-term impairment
In arterial ischaemic stroke (AIS) the risk factors that predominate in children and young people are distinct from adults. These include arteriopathies such as moyamoya, cardiac disorders such as congenital heart disease, haemoglobinopathies such as sickle cell disease, chronic systemic conditions, infections, acute and chronic head and neck disorders (including trauma leading to extra-cranial arterial dissection), acute systemic conditions, and prothrombotic states. Of note, atheroma, the most common risk factor for adult AIS is not implicated in paediatric AIS, which reinforce the need to have different approaches between adults and children.
These guidelines will be contentious as they are not evidence-based; however, with the collapse of the multi-centre Thrombolysis in Paediatric Stroke study (TIPS); which was designed to assess the efficacy and safety of hyperacute thrombolysis in the paediatric population and had to be abandoned due to lack of patient recruitment, it seems unlikely that trial-based evidence for hyperacute paediatric AIS therapy will be forthcoming anytime soon. Given that hyperacute thrombolysis, and now thrombectomy, are the accepted standards of care in adults, the issue of how to manage children and young people with acute AIS is a challenge for paediatricians in day-to-day clinical practice. Clinical experience and audit suggests that each UK regional paediatric neuroscience centre would encounter fewer than five children annually who would meet the criteria stipulated in this guideline for hyperacute intravenous thrombolysis for AIS. Each DGH is therefore likely to see less than one eligible child per year, and management of these cases will be highly challenging, both to the generalist and to the stroke specialist/neurologist advising from a distance. Even more challenging will be the identification and transport of children and young people who might benefit from thrombectomy.
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Acute medical interventions for Acute Ischaemic Stroke; age <18.
• If a confirmed acute ischaemic stroke but not a candidate for thrombolysis or thrombectomy then prescribe and deliver 5mg/kg of aspirin up to a maximum of 300mg within 24 hours of diagnosis of AIS in the absence of contraindications (e.g. parenchymal haemorrhage). After 14 days reduce dose of aspirin to 1mg/kg to a max of 75mg.
• The off label use of tissue plasminogen activator (tPA) could be considered in children presenting with AIS who are more than eight years of age on a case-by-case basis when the following criteria have been met: - AIS has occurred as defined by: an acute focal neurological deficit consistent with arterial ischaemia AND
Paediatric National Institute of Health Stroke Scale (PedNIHSS) more than or equal to 4 and less than or equal to 24
AND treatment can be administered within 4.5 hours of known onset of symptoms
AND intracranial haemorrhage has been excluded:
CT and CTA demonstrates normal brain parenchyma or minimal early ischaemic change
AND CTA demonstrates partial or complete occlusion of the intracranial artery corresponding to clinical or radiological deficit
OR MRI and MRA showing evidence of acute ischaemia on diffusion weighted imaging plus partial or complete occlusion of the intracranial artery corresponding to clinical or radiological deficit
PROVIDING that there are no contraindications
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Contraindications to thrombolysis
Exclusion criteria for IV tPA (based on the Thrombolysis in Pediatric Stroke Study criteria 19 )
• Unknown time of symptoms onset • Pregnancy • Clinical presentation suggestive of subarachnoid haemorrhage (SAH), even if brain imaging is negative for blood • Patient who would decline blood transfusion if indicated • History of prior intracranial haemorrhage • Known cerebral arterial venous malformation, aneurysm or neoplasm • Persistent systolic blood pressure more than 15% above the 95th percentile for age while sitting or supine • Glucose less than 2.78mmol/L or more than 22.22mmol/L • Bleeding diathesis including platelets less than 100 000, prothrombin time (PT) more than15s (international normalised ratio (INR) more than 1.4), or elevated activated partial thromboplastin time (aPTT) more than upper limits of the normal range • Clinical presentation consistent with acute myocardial infarction (MI) or post-MI pericarditis that requires evaluation by cardiology before treatment • Prior stroke, major head trauma, or intracranial surgery within the past three months • Major surgery or parenchymal biopsy within 10 days (relative contraindication) • Gastrointestinal or urinary bleeding within 21 days (relative contraindication) • Arterial puncture at non-compressible site or LP within seven days (relative contraindication). Patients who have had a cardiac catheterization via a compressible artery are not excluded • Patient with malignancy or within one month of completion of treatment for cancer • Patients with an underlying significant bleeding disorder. Patients with a mild platelet dysfunction, mild von Willebrand disease, or other mild bleeding disorders are not excluded
• Stroke related exclusion criteria: - Mild deficit (Paediatric National Institute of Health Stroke Scale (PedNIHSS18 ) less than 4) at start of tPA infusion or at time of sedation for neuroimaging, if applicable - Severe deficit suggesting large territory stroke, with pre-tPA PedNIHSS more than 24, regardless of the infarct volume seen on neuroimaging - Stroke suspected to be because of subacute bacterial endocarditis, moyamoya, sickle cell disease, meningitis, bone marrow, air, or fat embolism - Previously diagnosed primary angiitis of the central nervous system (PACNS) or secondary central nervous system (CNS) vasculitis. Focal cerebral arteriopathy of childhood is not a contraindication
• Neuroimaging related exclusions: - Intracranial haemorrhage on pre-treatment head CT and MRI - Intracranial dissection (defined as at or distal to the ophthalmic artery or V4 segment of the vertebral artery) - Large infarct volume, defined by the finding of acute infarct on MRI involving one-third or more of the complete middle cerebral artery (MCA) territory involvement with an ASPECTS score of less than 6
• Drug-related exclusions: - Known allergy to recombinant tissue plasminogen activator - Patient who received heparin within four hours must have activated partial thromboplastin time (aPTT) in normal range
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- Low molecular-weight heparin (LMWH) within past 24 hours (aPTT and INR will not reflect LMWH effect)
Indications for referral to interventional neuroradiology
• Patients with acute AIS causing a disabling neurological deficit (NIHSS score of 6 or more) may be considered for intra-arterial clot extraction with prior intravenous thrombolysis, unless contraindicated, beyond an onset-to-arterial puncture time of five hours if a) PedNIHSS score is more than six, b) a favourable profile on salvageable brain tissue imaging has been proven, in which case treatment up to 12 hours after onset may be appropriate.
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Appendix 3
PedNIHSS Instructions; Administer stroke scale items in the order listed. Follow directions provided for each exam item. Scores should reflect what the patient does, not what the clinician thinks the patient can do. MODIFICATIONS FOR CHILDREN; Modifications to testing instructions from the adult version for use in children are shown in bold italic with each item where appropriate. Items with no modifications should be administered and scored with children in the same manner as for adults.
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11. Document Control Information
All sections must be completed by the author prior to submission for approval
Lead Author: Chris Douglass; Consultant Neurologist Lead author contact [email protected]; 0161 2064044 details: Consultation Name of person or group Role / Department / Committee (Care Org) Date List the persons or groups who have Prof Craig Smith Consultant stroke physician, SCO Jan 2019 contributed to this Dr Rekha Siripurapu Consultant neuroradiologist, SCO Jan 2019 policy. (please state Dr Adrian Parry-Jones Consultant neurologist, SCO Jan 2019 which Care Organisation)
Endorsement Name of person or group Role / Department / Committee (Care Org) Date List the persons or Chair, Medical Neurosciences Risk and Dr Martin Punter Jan 2019 groups who have Assurance Committee seen given their Divisional Clinical MCCN July 2019 support to this policy. Governance Committee (please state which Care Organisation)
Keywords / phrases: stroke; acute ischaemic stroke; ischaemic stroke; thrombolysis; alteplase; tPA; tissue plasminogen activator; CTA; computed tomography angiography
Communication The Stroke Unit Ward Manager and Clinical Stroke lead will hold the plan: implementation plan. Stroke service medical and nursing staff will be made aware of the protocol through local induction, mortality and morbidity/clinical governance, in-service training and stroke study days.
The Stroke Clinical Governance Group will review progress in implementation. Agreed competencies for assessment and delivery of IV thrombolysis will be assessed as follows: 1) Medical staff: All trainees require consultant supervision when assessing and delivering thrombolysis in all cases. This may be direct supervision or remote supervision (by telephone or telemedicine; Figure 2). Thrombolysis must not proceed without discussion with the duty consultant. 2) Nursing staff: All new starters will receive an induction to the ward including thrombolysis. All trained staff including Advanced Practitioners will complete a thrombolysis competency package and will be supported by senior nurses. Document review This document will be reviewed by the author, or a nominated person, at least once arrangements: every three years or earlier should a change in legislation, best practice or other change in circumstance dictate.
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This section will be completed following committee approval
Policy Approval: Name of Approving Committee: MCCN Divisional Clinical Governance Committee
Chairperson: Alison Dwyer
Approval date: 09/07/2019
Formal Committee decision (tick) x Chairperson’s approval (tick)
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12. Equality Impact Assessment (EqIA) screening tool Legislation requires that our documents consider the potential to affect groups differently, and eliminate or minimise this where possible. This process helps to reduce health inequalities by identifying where steps can be taken to ensure the same access, experience and outcomes are achieved across all groups of people. This may require you to do things differently for some groups to reduce any potential differences.
1a) Have you undertaken any consultation/ Yes, to inform development of the involvement with service users, staff or other information leaflet included within the previous version of this policy (2012) groups in relation to this document?
1b) Have any amendments been made as a Yes result? 2) Does this policy have the potential to affect any of the groups below differently or negatively? Some individuals with acute stroke will have visual, language or other impairments which may impair their capacity specific to decision-making in relation to urgent treatment with alteplase Protected Group Yes No Unsure Reasons for decision Age (e.g. are specific age groups excluded? Would the same X process affect age groups in different ways?) Sex (e.g. is gender neutral language used in the way the policy X or information leaflet is written?) Race (e.g. any specific needs identified for certain groups such X as dress, diet, individual care needs? Are interpretation and translation services required and do staff know how to book these?) Religion & Belief (e.g. Jehovah Witness stance on blood X transfusions; dietary needs that may conflict with medication offered.) Sexual orientation (e.g. is inclusive language used? Are X there different access/prevalence rates?) Pregnancy & Maternity (e.g. are procedures suitable for X Thrombolysis pregnant and/or breastfeeding women?) not licenced in pregnancy Marital status/civil partnership (e.g. would there be any X difference because the individual is/is not married/in a civil partnership?) Gender Reassignment (e.g. are there particular tests related X to gender? Is confidentiality of the patient or staff member maintained?) Human Rights (e.g. does it uphold the principles of Fairness, X Respect, Equality, Dignity and Autonomy?) Carers (e.g. is sufficient notice built in so can take time off work X to attend appointment?) Socio/economic (e.g. would there be any requirement or X expectation that may not be able to be met by those on low or limited income, such as costs incurred?) Disability (e.g. are information/questionnaires/consent forms X available in different formats upon request? Are waiting areas suitable?) Includes hearing and/or visual impairments, physical disability, neurodevelopmental impairments e.g. autism, mental health conditions, and long term conditions e.g. cancer. Thrombolysis in acute ischaemic strokes; assessment and eligibility for iv Alteplase Reference Number TWCG6(12) Version 4 Issue Date: 05/09/2019 Page 30 of 31 It is your responsibility to check on the intranet that this printed copy is the latest version
Are there any adjustments that need to be made to ensure that X people with disabilities have the same access to and outcomes from the service or employment activities as those without disabilities? (e.g. allow extra time for appointments, allow advocates to be present in the room, having access to visual aids, removing requirement to wait in unsuitable environments, etc.) 3) Where you have identified that there are potential differences, what steps have you taken to mitigate these? N/A
4) Where you have identified adjustments would need to be made for those with disabilities, what action has been taken? N/A 5) Where the policy, procedure, guidelines, patient information leaflet or project impacts on patients how have you ensured that you have met the Accessible Information Standard – please state below:
……………………………………………………………………………………………………………… EDI Team/Champion only: does the above ensure compliance with Accessible Information Standard o Yes o No If no what additional mitigation is required:
Will this policy require a full impact assessment? Yes / No
Please state your rationale for the decision:
(a full impact assessment will be required if you are unsure of the potential to affect a group differently, or if you believe there is a potential for it to affect a group differently and do not know how to mitigate against this - Please contact the Inclusion and Equality team for advice on [email protected])
Author: Chris Douglass Date: January 2019
Sign off from Equality Champion: Date:
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