STROKE THROMBOLYSIS GUIDELINE (EMERGENCY DEPARTMENT RUN SERVICE)

STROKE THROMBOLYSIS GUIDELINE (EMERGENCY DEPARTMENT RUN SERVICE) 1. Aim/Purpose of this Guideline To deliver safe and effective thrombolysis for acute ischaemic stroke using robust evidence based clinical criteria. The service has been taken over by the Emergency Department in November 2013 and this updated guidance reflects this change in delivery. 2. The Guidance Contents Page Reason for change 2 Thrombolysis pathway 3 Clinical Exclusions from thrombolysis 5 Management of hypertension 7 r-tpa dose ready reckoner 8 Consent issues 9 Management of complications after thrombolysis 10 NIH Stroke Scale (full version) 11 ASPECTS score 19 Nursing protocol and care plan 20 References 22 Short NIHSS score sheet 23 Peninsula Heart & Stroke Network Clinical Reference Group statement on thrombolysis 24 Monitoring and Effectiveness and compliance 27 Governance information 28 Equality Impact Assessment 31 Page 1 of 30

Reason for change Referral of Patients with Acute Stroke and Proximal Artery Occlusion for Consideration of Intra-arterial Treatment at Derriford Hospital Publication of the MR CLEAN; EXTEND-IA; ESCAPE; and SWIFT PRIME thrombectomy trials. Taken together, these trials provide compelling evidence that quick, early thrombectomy with second-generation stent retriever devices is safe and effective for reducing disability when used to treat patients with stroke caused by proximal large artery occlusions in the anterior circulation [2-5]. The NNT for one additional person to achieve functional independence in these trials ranged from approximately 3 to 7.5. Referrals only accepted between the hours of 09:00 and 15:00 Monday to Friday. Please consider following patients for referral for intra-arterial treatment: Ischaemic stroke patient-if no improvement within 30 minutes of intravenous thrombolysis on NIHSS Demonstration of proximal vessel occlusion CT angiogram (terminal ICA, M1, proximal M2, basilar), considered responsible for the patient s presentation Possibility of clot extraction within 4.5 hours of stroke (time to groin puncture 4 hours). Exclusion criteria Any evidence of haemorrhagic transformation (or primary haemorrhage) Age greater than 80 Hypodensity involving more than 1/3 of middle cerebral artery territory Significant comorbidities that reduce the likelihood of a good clinical outcome Opinion of receiving clinician that clot extraction will be impossible in the required time How to proceed: ED consultant discusses patient with stroke consultant on Phoenix (ext 2120/via switch) ED consultant in charge of patients care requests urgent CT angiogram and contacts on call stroke neurology registrar at Derriford hospital. Ensure iv access (2 cannulas) Urgent transfer of patient by radiographers (main CT scanner) Patient accompanied to scanner by ED nurse Images are uploaded PACS as soon as obtained ED consultant contacts Derriford team once CTA images uploaded and arranges urgent transfer to Derriford hospital. Page 2 of 30

RCHT STROKE THROMBOLYSIS PATHWAY Derriford Hospital # 6171 request the stroke registrar (1908) to arrange bed and transfer PRE-HOSPITAL Stroke eligible for thrombolysis: Positive FAST (Face, Arm and Speech Test) Age 18 or older Symptoms noted on waking exclude thrombolysis Symptom onset to thrombolysis within 6h No seizure at onset Check BM, confirm time of onset, transport to ED RCHT, with NOK and list of pills if available. Pre-alert ED ensure name, DOB and AFFECTED SIDE included EMERGENCY DEPARTMENT Confirm stroke using ROSIER scale Book CT on MAXIMS ensure side affected is clear on request Ring 4444 to alert radiographer/stroke nurse/stroke ward Transport patient straight to CT on arrival for urgent CT head Brief medical history to confirm time of onset, inclusion and exclusion criteria Perform NIHSS examination (National Institute Health Stroke Scale) Brief general examination, estimate weight BP both arms, repeat higher arm BP after 15 minutes (manual cuff not dynamap) Manage high BP as per protocol iv access x2 Urgent bloods = FBC, U&E, clotting, G&S (INR if on warfarin), lipids, glucose ECG (and CXR if needed) CT SCANNER Radiographer performs scan and informs on call radiologist to report scan using ASPECTS score Page 3 of 30

DECISION TO THROMBOLYSE Repeat NIHSS to ensure not rapidly improving Do not delay while waiting for bloods (unless on warfarin or on chemo or known haematological disorder) Decision to thrombolyse taken by thrombolysing doctor Obtain verbal consent if possible Calculate dose using ready reckoner, give bolus in 10ml syringe over 1-2 minutes then infusion over 1 hour using 50ml syringe driver Start treatment in ED and organise bed on critical care via site coordinator (bleep 2634) If large vessel occlusion suspected (NIHSS >9) please consider referral for intraarterial treatment (see first page of guidance) MONITOR FOR COMPLICATIONS Watch for signs of neurological deterioration, bleeding, anaphylaxis Repeat NIHSS at 30 minutes Manual BP, pulse, GCS, respiratory rate, temperature, SaO2 every 15 min for 2h, then every 30 min for 6 h, then every hour for 18h Maintain BP Systolic <180 and Diastolic <105, Temperature < 37 C. Avoid urinary catheter, ng tube, im injections for first 24h Avoid antiplatelets / anticoagulants until repeat CT at 24h excludes bleeding Inform medical registrar of any concerns Manage complications as per protocol Prescribe Intermittent compression stockings for VTE prophylaxis AT 12 HOURS Arrange transfer to Phoenix via clinical site coordinator (bleep 2634) AT 24 HOURS Repeat routine CT scan and repeat NIHSS at 24h Start antiplatelet as per protocol if no bleeding on repeat CT Page 4 of 30

CLINICAL EXCLUSIONS FROM THROMBOLYSIS Do not give thrombolysis if you have ticked any YES boxes FROM THE HISTORY YES NO Time of onset unknown Awoke with symptoms Seizure at onset Known bleeding diathesis Arterial puncture at a non-compressible site, or lumbar puncture, within the last 7 days Major surgery within the last 14 days Gastrointestinal or urinary tract haemorrhage within 21 days Head injury, intracranial surgery or stroke within the last 3 months Any history of intracranial haemorrhage, brain tumour, intracranial AVM or aneurysm TIME OF ONSET Within 3h no upper age limit 3 to 4.5h can treat if 18-80y, patients over 80y do not benefit 4.5 to 6h patients 18-80 may benefit needs decision by thrombolysing doctor ANTICOAGULANTS Current warfarin treatment is not exclusion if the INR is 1.7 or less. Current heparin treatment is not an exclusion if the APTT ratio is less than 1.2 Full dose (but not low dose/prophylactic) LMWH is an exclusion Rivaroxaban/Dabigatran if a patient is on these treatments, 24h or 12h respectively should elapse before a parenteral anticoagulant is given. This excludes these patients from thrombolysis for stroke. PREGNANCY Pregnancy or women who are post-partum r-tpa is unlicensed for use in pregnancy. It should not be withheld in pregnant patients with ischaemic stroke, but because experience is limited, risks and benefits must be carefully weighed and should be discussed with on-call obstetrician CHEMOTHERAPY Some chemotherapy agents may be relative contra-indications to thrombolysis. Or patients may be cytopaenic. If patient on chemotherapy drugs please ensure bloods normal first and check with oncology or haematology before giving lysis CHILDREN Alteplase is not licensed for <18y. Studies are ongoing in children. Cases should be discussed by paediatric team with paediatric neurologists at Bristol. Page 5 of 30

ON INITIAL ASSESSMENT YES NO Coma (GCS <8; NIH-SS question 1a = 3) Minor stroke symptoms Sensory symptoms only Dysarthria only Ataxia only Minimal weakness not registering on NIHSS Partial visual field defect only Rapidly improving symptoms or signs Clinical presentation suggestive of subarachnoid haemorrhage (even if subsequent CT normal) DBP>140 or BP>180/105 having received more than 2 doses labetolol (see management of hypertension page 7) Capillary glucose <2.7 (Treat as per Trust protocol) ON LAB RESULTS Platelets <100 (only wait for FBC if known haematological disorder or on chemo) Current warfarin treatment with INR MORE THAN 1.7 Do not start treatment until INR available Current heparin treatment and APTT > 1.2 Do not start treatment until APTT available Current treatment with full dose LMWH Plasma glucose <2.7 (Treat as per Trust protocol) ON CT SCAN reported by radiologist YES NO Radiological signs of intracranial haemorrhage Diffuse swelling of a cerebral hemisphere ASPECTS score 7 or less is a relative contra-indication; in this instance consider carefully other factors that may influence the decision to treat or not to treat CONFIRM PATIENT ELIGIBLE FOR THROMBOLYSIS YES NO VERBAL CONSENT? YES NO SIGNATURE NAME DATE TIME Page 6 of 30

MANAGEMENT OF HYPERTENSION IN POTENTIAL THROMBOLYSIS PATIENTS Record BP in both arms using Manual cuff Use arm with highest BP reading thereafter Repeat after 15 minutes if hypertensive Blood Pressure < 180 Systolic <105 Diastolic Monitor BP, do not intervene, Thrombolyse if eligible Systolic > 220 mmhg And / Or Diastolic 121-140 mmhg *Give IV Labetalol 10 iv over 1-2 minutes Repeat same or double dose to bring BP down to 180/105 Or Labetalol Infusion 2-8mg/min Systolic >180 And/or Diastolic >105 mmhg *Give IV Labetalol 10 iv over 1-2 minutes Repeat same or double dose to bring BP down to 180/105 Or Labetalol Infusion 2-8mg/min If Diastolic above 140 mmhg patient NOT eligible for Thrombolysis *If more than 2 doses of labetolol needed Patient NOT eligible for Thrombolysis In asthma, cardiac failure or 1st Degree heart block use Isoket infusion (2-10mmHg /hr) Monitoring of BP after Thrombolysis Blood Pressure after Thrombolysis should be measured Every 15 minutes for 2 hours Every 30 minutes for 6 hours Hourly for 18 hours During Thrombolysis and afterwards BP should be managed to below 180/105 using the above instructions If Blood pressure rises sharply during or after Thrombolysis suspect Intracranial haemorrhage. Page 7 of 30

RtPA DOSE READY RECKONER Alteplase, Recombinant tissue plasminogen activator (Actilyse Boehringer Ingelheim) Unless the patient or companion knows their recent weight, estimate it to the nearest 5 kg The total dose of rt-pa is 0.9 mg/kg or 90 mg, whichever is the lesser (Column 3) Make up one or two vials of rt-pa using the 50 ml diluent in each drug pack, making a solution of 1 mg/ml rt-pa Draw up and give 10% as a bolus over 1-2 minutes (Column 4), using a 10 ml syringe Draw up the remaining 90% (the infusion dose, Column 5) into 1 or 2 50ml syringes and set up the 50ml syringe driver (IVAC) with the corresponding infusion rate in mls/hr. This infusion is given over 1h. Do not give the cardiac dose Do not give more than 90 mg 1 2 3 4 5 Estimate of patients weight (kg) Equivalent Imperial weight Bolus dose (mls) given over 1-2 minutes Infusion dose (mls) = infusion rate in mls/hr Total dose (mg at 1 mg/ml) One vial Two vials 45 7 st 1 lb 4 36 40 50 7 st 12 lb 5 40 45 55 8 st 9 lb 5 44 49 60 9 st 6 lb 5 49 54 65 10 st 3 lb 6 52 58 70 11 st 0 lb 6 57 63 75 11 st 11 lb 7 60 67 80 12 st 8 lb 7 65 72 85 13 st 5 lb 7 69 76 90 14 st 2 lb 8 73 81 95 14 st 13 lb 8 77 85 100 15 st 10 lb 9 81 90 Page 8 of 30

ISSUES AROUND CONSENT Information for patients / relatives before giving thrombolysis Thrombolysis with r-tpa is a licensed treatment for acute ischaemic stroke, so written consent is not required. If possible there should be agreement from the patient and / or relative. When the patient cannot agree because of their impairments and no relative is available, then treatment can still be given if it is judged to be in the best interests of the patient. Any explanation might include: There has been a significant stroke caused by a blocked artery preventing blood from getting to a part of the brain and causing permanent damage. With or without treatment there may be some recovery or things could get worse. Stroke is fatal in about a third of people. Only one treatment has been shown to prevent damage to the brain. This treatment dissolves the blood clot blocking the artery and allows blood to get back to the brain. It only works if given quickly after the stroke starting and the benefit is greater the sooner it is given There is a slight increased risk of death within the first week (8.9 vs 6.4%), mostly due to fatal intracranial bleeding (3.6 vs 0.6%). But after the first week there is a lower chance of death (11.5 vs 13.6%), so several months later there is no difference in chance of death overall. The chances of being alive and independent (Rankin score 0-2) several months later are higher, % chance of being alive and independent at 3 months if lysed % chance of being alive and independent at 3 months if not lysed Absolute benefit number of extra patients alive and independent at 3 months per 1000 patients treated if treated within 3h 40.7% 31.7% 90 If treated 3-6h 47.5% 45.7% 18 if treated within 6h 46.3% 42.1% 42 Page 9 of 30

MANAGEMENT OF COMPLICATIONS AFTER THROMBOLYSIS BP commonly drops after initiation of thrombolysis, not necessarily due to bleeding. If this happens give iv fluid bolus. Bleeding, by process of de-fibrination, is more common than with heparin (around 3%) Intracranial bleeding Should be suspected if there is neurological deterioration, new headache, fall in conscious level, acute hypertension, seizure, nausea or vomiting Initial action Stop infusion of r-tpa, repeat NIHSS, commence iv saline if needed Arrange urgent CT scan Check FBC, full coagulation screen, check blood sent for G&S If CT scan shows bleeding Is haemorrhage petechial? If so it is unlikely anything other than stopping r-tpa will be needed. Continue to observe patient closely Is haemorrhage parenchymal? Give 20% mannitol 200ml stat (dose may be repeated) Consider tranexamic acid 10 mg/kg IV and 10 units cryoprecipitate Further advice is available via the intranet anti-coagulation guidelines and Consultant Haematologist Consult neurosurgeon regarding possible transfer for haematoma evacuation If CT scan shows no bleeding Recheck patient for other causes of deterioration eg recurrent ischaemic stroke, sepsis, seizure, metabolic derangement, extracranial bleeding Extracranial bleeding Should be suspected if there is shock, drop in BP, evidence of blood loss although a high index of suspicion is needed as blood loss may not be obvious. Initial action Stop infusion of r-tpa Check FBC, full coagulation screen, check blood sent for G&S and/or arrange cross match depending on situation Commence iv saline or blood transfusion depending on situation If patient fails to respond to simple measures or there is severe haemorrhage, consider tranexamic acid 10 mg/kg IV and 10 units cryoprecipitate Further advice is available from intranet, on call geriatrician and haematologist as above. Anaphylaxis Anaphylactic reactions to r-tpa can occur but are rare. If an urticarial rash, peri-orbital swelling or tongue swelling occur, the r-tpa should be stopped and the patient reviewed by a doctor urgently. Page 10 of 30

NIH STROKE SCALE full version and master copy please record patient scores on quick version (see page 23) INSTRUCTION SCALE DEFINITION SCORE 1 1a. Level of Consciousness: The investigator must choose a response, even if a full evaluation is prevented by such obstacles as an endotracheal tube, language barrier, orotracheal trauma/ bandages. A 3 is scored only if the patient makes no movement (other than reflexive posturing) in response to noxious stimulation. 1b. LOC Questions: The patient is asked the month and his/her age. The answer must be correct - there is no partial credit for being close. Aphasic and stuporous patients who do not comprehend the questions will score 2. Patients unable to speak because of endotracheal intubation, orotracheal trauma, severe dysarthria from any cause, language barrier or any other problem not secondary to aphasia are scored 1. It is important that only the initial answer be graded and that the examiner not help the patient with verbal or non-verbal cues. 1c. LOC Commands: The patient is asked to open and close the eyes and then to grip and release the nonparetic hand. Substitute another one step command if the hands cannot be used. Credit is given if an unequivocal attempt is made but not completed due to weakness. If the patient does not respond to command, the task should be demonstrated to them (pantomime) and score the result (i.e., follows none, one, or two commands). Patients with trauma, amputation, or other physical impediments should be given suitable one-step commands. Only the first attempt is scored. 2. Best Gaze: Only horizontal eye movements will be tested. Voluntary or reflexive (oculocephalic) eye movements will be scored but caloric testing is not done. If the patient has a conjugate deviation of the eyes that can be overcome by voluntary or reflexive activity, the score will be 1. If a patient has an isolated peripheral nerve paresis (CN III, IV, OR VI) score a 1. Gaze is testable in all aphasic patients. Patients with ocular trauma, bandages, preexisting blindness or other disorder of visual acuity or fields should be tested with reflexive movements and a choice made by the Page 11 of 30 0 = Alert; keenly responsive. 1 = Not alert, but rousable by minor stimulation to obey, answer, or respond. 2 = Not alert, requires repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (not stereotyped). 3 = Coma; Responds only with reflex motor or autonomic effects, or totally unresponsive, flaccid, areflexic. 0 = Answers both questions correctly. 1 = Answers one question correctly. 2 = Answers neither question correctly. 0 = Performs both tasks correctly. 1 = Performs one task correctly. 2 = Performs neither task correctly. 0 = Normal 1 = Partial gaze palsy. This score is given when gaze is abnormal in one or both eyes, but where forced deviation or total gaze paresis are not present. 2 = Forced deviation, or total gaze paresis not overcome by the oculocephalic manoeuvre SCORE 2 ----------- ----------- ----------- ----------- ----------- ----------- ----------- -----------

investigator. Establishing eye contact and then moving about the patient from side to side will occasionally clarify the presence of a gaze palsy. 3. Visual: Visual fields (upper and lower quadrants) are tested by confrontation, using finger counting or visual threat as appropriate. Patient must be encouraged, but if they look at the side of the moving fingers appropriately, this can be scored as normal. If there is unilateral blindness or enucleation, visual fields in the remaining eye are scored. Score 1 only if a clear-cut asymmetry, including quadrantanopia is found. If patient is blind from any cause score 3. Double simultaneous stimulation is performed at this point. If there is extinction patient receives a 1 and the results are used to answer question 11. 4. Facial Palsy: Ask, or use pantomime to encourage the patient to show teeth or raise eyebrows or close eyes. Score symmetry of grimace in response to noxious stimuli in the poorly responsive or non-comprehending patient. If facial trauma/bandages, orotracheal tube, tape, or other physical barrier obscures the face, these should be removed to the extent possible. 5&6. Motor Arm and Leg: The limb is placed in the appropriate position: extend the arms 90 degrees (if sitting) or 45 degrees (if supine) and the leg 30 degrees (always tested supine). Drift is scored if the arm falls before 10 seconds or the leg before 5 seconds. The aphasic patient is encouraged using urgency in the voice and pantomime but not noxious stimulation. Each limb is tested in turn, beginning with the nonparetic arm. Only in the case of amputation or joint fusion at the shoulder or hip may the score be 9 and the examiner must clearly write the explanation for scoring as a 9. 0 = No visual loss. 1 = Partial hemianopia. 2 = Complete hemianopia. 3 = Bilateral hemianopia (blind including cortical blindness). ----------- ----------- 0 = Normal symmetrical movement. 1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling). 2 = Partial paralysis (total or near total paralysis of lower face). 3 = Complete paralysis (absence of facial movement in the upper and lower face). Arm 0 = No drift, arm holds 90 (or 45) degrees for full 10 seconds. 1 = Drift, arm holds 90 (45) degrees, but drifts down before full 10 seconds; does not hit bed or other support. 2 = Some effort against gravity, limb cannot get to or maintain (if cued) 90 (or 45) degrees, drifts down to bed, but has some effort against gravity. 3 = No effort against gravity, arm falls. 4 = No movement. 9 = Amputation, joint fusion -explain: 5a = Right Arm ----------- ----------- ----------- ----------- Page 12 of 30 5b = Left Arm Leg 0 = No drift, leg holds 30 degrees position for full 5 seconds. 1 = Drift, leg falls by the end of the 5 second period but does not hit bed. 2 = Some effort against gravity, leg falls to bed by 5 seconds, but has some effort against gravity. 3 = No effort against gravity, leg falls to bed immediately. 4 = No movement. 9 = Amputation, joint fusion -explain: ----------- -----------

6a = Right Leg 6b = Left Leg ----------- ----------- ----------- ----------- 7. Limb Ataxia: This item is aimed at finding evidence of a unilateral cerebellar lesion. Test with eyes open. In case of visual defect, ensure testing is done in intact visual field. The finger-nose-finger and heel-shin tests are performed on both sides, and ataxia is scored only if present out of proportion to weakness. Ataxia is absent in the patient who cannot understand or is hemiplegic. Only in the case of amputation or joint fusion may the item be scored 9, and the examiner must clearly write the explanation for not scoring. In case of blindness, test by touching nose from extended arm position. 8. Sensory: Sensation or grimace to pinprick when tested, or withdrawal from noxious stimulus in the obtunded or aphasic patient. Only sensory loss attributed to stroke is scored as abnormal and the examiner should test as many body areas [arms (not hands), legs, trunk, face] as needed to accurately check for hemisensory loss. A score of 2, severe or total, should only be given when a severe or total loss of sensation can be clearly demonstrated. Stuporous and aphasic patients will therefore probably score 1 or 0. The patient with brainstem stroke who has bilateral loss of sensation is scored 2. If the patient does not respond and is quadriplegic, score 2. Patients in coma (item 1a=3) are arbitrarily given a 2 on this item. 0 = Absent. 1 = Present in one limb. 2 = Present in two limbs. 0 = Normal; no sensory loss. 1 = Mild to moderate sensory loss; patient feels pinprick is less sharp or is dull on the affected side; or there is a loss of superficial pain with pinprick but patient is aware he/she is being touched. 2 = Severe to total sensory loss; patient is not aware of being touched. ----------- ----------- 9. Best Language: A great deal of information about comprehension will be obtained during the preceding sections of the examination. The patient is asked to describe what is happening in the attached picture, to name the items on the attached list of sentences. Comprehension is judged from responses here as well as to all of the commands in the preceding general neurological exam. If visual loss interferes with the tests, ask the patient to identify objects placed in the hand, repeat, and produce speech. The intubated patient should be asked to write. The patient in coma (question 1a = 3) will arbitrarily score 3 on this item. The Page 13 of 30 0 = No aphasia, normal. 1 = Mild to moderate aphasia; some obvious loss of fluency or facility of comprehension, without significant limitation on ideas expressed or form of expression. Reduction of speech and/or comprehension, however, makes conversation about provided material difficult or impossible. For example, in conversation about provided materials examiner can identify picture or naming card from patient s response. 2 = Severe aphasia; all communication is through fragmentary expression; great need for inference, questioning, and guessing by the listener. Range of ----------- -----------

examiner must choose a score in the patient with stupor or limited cooperation but a score of 3 should be used only if the patient is mute and follows no one step commands. 10. Dysarthria: If the patient is thought to be normal, an adequate sample of speech must be obtained by asking patient to read or repeat words from the attached list. If the patient has severe aphasia, the clarity of articulation of spontaneous speech can be rated. Only if the patient is intubated or has other physical barrier to producing speech may the item be scored 9", and the examiner must clearly write an explanation for not scoring. Do not tell the patient why he/she is being tested. 11. Extinction and Inattention (formerly Neglect) Sufficient information to identify neglect may be obtained during the prior testing. If the patient has severe visual loss preventing visual double simultaneous stimulation, and the cutaneous stimuli are normal, the score is normal. If the patient has aphasia but does appear to attend to both sides, the score is normal. The presence of visual spatial neglect or anosagnosia may also be taken as evidence of neglect. Since neglect is scored only if present, the item is never untestable. information that can be exchanged is limited; listener carries burden of communication. Examiner cannot identify materials provided from patient response. 3 = Mute, global aphasia; no usable speech or auditory comprehension. 0 = Normal. 1 = Mild to moderate; patient slurs at least some words and, at worst, can be understood with some difficulty. 2 = Severe; patient s speech is so slurred as to be unintelligible in the absence of or out of proportion to any dysphasia, or is mute/anarthric. 9 = Intubated or other physical barrier - explain: 0 = No abnormality. 1 = Visual, tactile, auditory, spatial, or personal inattention or extinction to bilateral simultaneous stimulation in one of the sensory modalities. 2 = Profound hemi-inattention or hemiinattention to more than one modality. Does not recognize own hand or orients to only one side of space. ----------- ----------- ----------- ----------- Total Max score 42 Total Max score 42 Page 14 of 30

Page 15 of 30

Page 16 of 30

Page 17 of 30

Page 18 of 30

ASPECTS score This is a topographic score for dividing middle cerebral artery territory into 10 regions. It is calculated from 2 standard axial CT cuts, one at the level of the basal ganglia and one at the corona radiate / centrum semiovale level. Subcortical structures are allotted 3 points and cortical structures 7 points. For each of these 10 areas a point is subtracted if there is evidence of ischemic damage there (eg reduced attenuation, loss of grey-white matter differentiation, focal swelling). A scan with no ischaemia in the MCA territory would score 10 and a scan with diffuse involvement of all MCA territory would score 0. An ASPECTS score 7 or less is a relative contra-indication to thrombolysis, with increased risk of haemorrhage; in this instance consider carefully other factors that may influence the decision to treat or not to treat M1 = anterior MCA cortex, M2 = MCA cortex lateral to insular ribbon M3 = posterior MCA cortex, M4, M5, M6 are anterior, lateral and posterior MCA territories immediately superior to M1, M2, M3 C = caudate, L = lentiform, IC = internal capsule, I = insular ribbon Page 19 of 30

Nursing Protocol Nursing Care Following Thrombolysis for Stroke 1. Patient to be nursed in identified bed space that allows for continuous observation. 2. Oxygen, Suction, Cardiac Monitor, Sphygmomanometer, O2 Saturation machine should be available at the bed side. Capillary blood glucose machine, Anaphylaxis box should be easily accessible. 3. Initiate post administration thrombolysis care plan on arrival 4. Perform patient observations as indicated and record a baseline ECG 5. If there are any concerns, medical review is essential. Report, review, document and increase frequency of observations accordingly. 6. Pyrexia > 37 C should be treated with PR or PO Paracetamol (1g 4-6 hourly. No more than 4g in 24 hours) 7. If haemorrhage is suspected, report immediately and arrange for urgent medical review. Send urgent FBC, clotting and group and save 8. If anaphylaxis is suspected (Tachypnoea, dyspnoea, tachycardia, swelling, rash) Stop infusion and employ anaphylaxis protocol. Arrange for urgent medical review or perform a crash call (2222)if required 9. Avoid catheterisation for 24 hours following thrombolysis infusion to minimise the risk of trauma and bleeding. If essential, consult with medical team. 10. Do not insert naso gastric tubes for 24 hours post thrombolysis infusion to minimise the risk of trauma and bleeding 11. IM injections should be avoided for 48 hours post thrombolysis infusion to minimise the risk of excessive bruising 12. Avoid giving heparin / warfarin. Refer to medical staff before commencing any anti coagulant or antiplatelet therapy (only given if CT at 24h shows no bleeding). Page 20 of 30

Observations following administration of thrombolysis for stroke Manual BP, Pulse, Temperature, Respirations, GCS and Oxygen Saturations (MEWS Score Refer to local Guidelines) Every 15 minutes for 2 hours Every 30 minutes for 6 hours Hourly for 18 hours Maintain BP < Systolic 180 / Diastolic 105 Temperature not to exceed 37 C. Observe for signs of raised intracranial pressure or intracranial bleeding Unequal pupils Sudden drop in GCS Onset of drowsiness Onset of nausea, vomiting (photophobia) Rising BP and falling pulse Page 21 of 30

Short NIHSS scoring sheet This is master copy patient packs include this sheet which should be filed in medical notes with completed inclusion/exclusion checklist National Institute for Health Stroke Scale (NIHSS) REFER TO LAMINATED FULL GUIDANCE FOR SCORING Date and Time 1a. LOC Score 0-3 1b. LOC Response to Questions Score 0-2 1c. LOC Response to Commands Score 0-2 2. Best gaze Score 0-2 3. Visual fields Score 0-3 4. Facial palsy Score 0-3 5. Right Arm motor Score 0-4 or X if untestable 6. Left Arm motor Score 0-4 or X if untestable 7. Right Leg motor Score 0-4 or X if untestable 8. Left leg motor Score 0-4 or X if untestable 9. Ataxia Score 0-2 or X if untestable 10. Sensory Score 0-2 11. Best language Score 0-3 12. Dysarthria Score 0-2 or X if untestable 13. Neglect/Inattention Score 0-2 Total Score (0-42) Score Score Score Score Page 22 of 30

Consensus statement on mechanical thrombectomy in acute ischemic stroke ESO-Karolinska Stroke Update 2014 in collaboration with ESMINT and ESNR. Treatment recommendations Mechanical thrombectomy, in addition to intravenous thrombolysis within 4.5 hours when eligible, is recommended to treat acute stroke patients with large artery occlusions in the anterior circulation up to 6 hours after symptom onset (Grade A, Level 1a, KSU Grade A). - new Mechanical thrombectomy should not prevent the initiation of intravenous thrombolysis where this is indicated, and intravenous thrombolysis should not delay mechanical thrombectomy (Grade A, Level 1a, KSU Grade A). - changed Mechanical thrombectomy should be performed as soon as possible after its indication (Grade A, Level 1a, KSU Grade A). For mechanical thrombectomy, stent retrievers approved by local health authorities should be considered (Grade A, Level 1a, KSU Grade A). - new Other thrombectomy or aspiration devices approved by local health authorities may be used upon the neurointerventionists discretion if rapid, complete and safe revascularisation of the target vessel can be achieved (Grade C, Level 2a, KSU Grade C) - new If intravenous thrombolysis is contraindicated (e.g. Warfarin-treated with therapeutic INR) mechanical thrombectomy is recommended as first-line treatment in large vessel occlusions (Grade A, Level 1a, KSU Grade A) changed and updated level of evidence. Patients with acute basilar artery occlusion should be evaluated in centres with multimodal imaging and treated with mechanical thrombectomy in addition to intravenous thrombolysis when indicated (Grade B, Level 2a, KSU Grade C); alternatively they may be treated within a randomized controlled trial for thrombectomy approved by the local ethical committee - new The decision to undertake mechanical thrombectomy should be made jointly by a multidisciplinary team comprising at least a stroke physician and a neurointerventionalist and performed in experienced centres providing comprehensive Page 23 of 30

stroke care and expertise in neuroanesthesiology (Grade C, Level 5, GCP, KSU Grade C). Mechanical thrombectomy should be performed by a trained and experienced neurointerventionalist who meets national and/or international requirements (Grade B, Level 2b, KSU Grade B) changed in level of evidence. The choice of anesthesia depends on the individual situation; independently of the method chosen, all efforts should be made to avoid thrombectomy delays (Grade C, Level 2b, KSU Grade C) changed. Patient selection Intracranial vessel occlusion must be diagnosed with non-invasive imaging whenever possible before considering treatment with mechanical thrombectomy (Grade A, Level 1a, KSU Grade A) - new. If vessel imaging is not available at baseline, a NIHSS score of 9 within three, and 7 points within six hours may indicate the presence of large vessel occlusion (Grade B, Level 2a, KSU Grade B) - new. Patients with radiological signs of large infarcts (for ex. using the ASPECTS score) may be unsuitable for thrombectomy (Grade B, Level 2a, KSU Grade B) - new Imaging techniques for determining infarct and penumbra sizes can be used for patient selection and correlate with functional outcome after mechanical thrombectomy (Grade B, Level 1b, KSU Grade B) - new. High age alone is not a reason to withhold mechanical thrombectomy as an adjunctive treatment (Grade A, Level 1a, KSU Grade A) new References 1. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke 2. NEJM 2008; 359: 3517-29 3. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial 4. Lancet 2012 ;379 :2352-63 Page 24 of 30

5. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis 6. Lancet 2012; 379: 2364-72 7. NICE Guidance TA 122 - Alteplase for the treatment of acute ischaemic stroke 8. National Stroke Strategy, Department of Health 2007 9. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy 10. Lancet 2000; 355:1670-1674 11. Use of the Alberta Stroke Program Early CT Score (ASPECTS) for Assessing CT Scans in Patients with Acute Stroke 12. Am J Neuroradiol 2001; 22:1534 42 13. Importance of Early Ischemic Computed Tomography Changes Using ASPECTS in NINDS rtpa Stroke Study Stroke 2005; 36:2110-15 14. Berkhemer OA et al. Mr CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11 15. Goyal M et al, ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019. 16. Saver JL et al. SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-pa vs. t-pa alone in stroke. N Engl J Med. 2015;372(24):2285 17. Campbell BC et al. Endovascular therapy for ischemic stroke with perfusionimaging selection. EXTEND-IA Investigators. N Engl J Med. 2015;372(11):1009. Page 25 of 30

3. Monitoring compliance and effectiveness Element to be Outcome of thrombolysis for individual patients monitored Lead Dr Katja Adie Tool Frequency Reporting arrangements Acting on recommendations and Lead(s) Change in practice and lessons to be shared Sentinel Stroke National Audit Programme (SSNAP) from the Royal College of Physicians Each thrombolysed patients details and outcomes are entered on to SSNAP Dr Adie reports outcome locally to the eldercare governance and Emergency Department meeting monthly SSNAP data is collected as part of the Trust Clinical Audit & Outcomes Programme on an ongoing basis SSNAP data is reported and published nationally and monitored by the Clinical Commissioning Group Dr Adie, Dr Harrington Required changes to practice will be identified and actioned within six months. Dr Adie and Dr Harrington as lead members of the team will take each change forward where appropriate. 4. Equality and Diversity 4.1 This document complies with the Royal Cornwall Hospitals NHS Trust service Equality and Diversity statement. 4.2 Equality Impact Assessment The Initial Equality Impact Assessment Screening Form is at Appendix 2. Page 26 of 30

Appendix 1. Governance Information Document Title Date Issued/Approved: 23/10/2015 Date Valid From: 23/10/2015 Date Valid To: 23/10/2018 Stroke Thrombolysis Guideline (Emergency Department run service) Directorate / Department responsible (author/owner): Dr Frances Harrington, Consultant Physician, Eldercare RCHT Contact details: 01872 252447 Brief summary of contents Guideline for the administration of thrombolysis for acute ischaemic stroke service taken over by ED Suggested Keywords: Target Audience Executive Director responsible for Policy: Stroke, Thrombolysis, Alteplase RCHT PCH CFT KCCG Rob Parry Date revised: 23/10/2015 This document replaces (exact title of previous version): Approval route (names of committees)/consultation: Divisional Manager confirming approval processes Name and Post Title of additional signatories Name and Signature of Divisional/Directorate Governance Lead confirming approval by specialty and divisional management meetings Publication Location (refer to Policy on Policies Approvals and Ratification): Document Library Folder/Sub Folder Links to key external standards Related Documents: Clinical guideline to deliver safe and effective thrombolysis for acute ischaemic stroke using robust evidence based clinical criteria Acute Stroke Group, SERCO, SWAST Mr A Virr Not Required Name: Page 27 of 30 Internet & Intranet Intranet Only Clinical / Neurology and Stroke NICE Guidance TA122 - Alteplase for the treatment of acute ischaemic stroke Advanced Stroke Management Pathway Acute Stroke Management

Training Need Identified? Stroke and TIA Multidisciplinary Care Pathway Secondary Prevention after Stroke or TIA Yes. Learning and Development department have been informed. Version Control Table Date Version No July 2008 V1.0 Initial Issue Summary of Changes Changes Made by (Name and Job Title) Dr F Harrington December 2010 V2.0 Amendment to 24/7 service Dr F Harrington 3/9/12 V3.0 Extended age and treatment window Dr F Harrington 21/1/14 V4.0 Change of service provision from Eldercare to Emergency Department team Dr F Harrington 2/10/2015 V5.0 Availability of intraarterial treatment Dr F Harrington Dr K Adie A James All or part of this document can be released under the Freedom of Information Act 2000 This document is to be retained for 10 years from the date of expiry. This document is only valid on the day of printing Controlled Document This document has been created following the Royal Cornwall Hospitals NHS Trust Policy on Document Production. It should not be altered in any way without the express permission of the author or their Line Manager. Page 28 of 30

Appendix 2. Initial Equality Impact Assessment Form Name of service, strategy, policy or project (hereafter referred to as policy) to be assessed: Directorate and service area: Is this a new or existing Procedure? existing Name of individual completing Telephone: 01872 253290 assessment: Dr F Harrington 1. Policy Aim* To safely administer thrombolytic agent to acute ischaemic stroke patients using updated, clearly defined criteria 2. Policy Objectives* Safe administration of emergency drug therapy Clear advice and guidance for staff involved in the administration of emergency treatment and aftercare of patients who have undergone thrombolysis for stroke 3. Policy intended As above Outcomes* 4. How will you measure Patient response to treatment the outcome? Audit ongoing local and RCP National Sentinel Stroke Audit Inclusion in international SITS-MOST register (Safe 5. Who is intended to benefit from the Policy? implementation of thrombolysis in stroke) Patients: through the promotion of safe, effective, evidence based practice 6a. Is consultation required with the workforce, equality groups, local interest groups etc. around this policy? b. If yes, have these groups been consulted? c. Please list any groups who have been consulted about this procedure. Yes Yes Acute Stroke Group, SERCO, SWAST 7. The Impact Please complete the following table. Are there concerns that the policy could have differential impact on: Equality Strands: Yes No Rationale for Assessment / Existing Evidence Age Removal of upper age limit for stroke thrombolysis based on recent randomised controlled trials Sex (male, female, transgender / gender reassignment) Race / Ethnic communities /groups Page 29 of 30

Disability - Learning disability, physical disability, sensory impairment and mental health problems Religion / other beliefs Marriage and civil partnership Pregnancy and maternity Sexual Orientation, Bisexual, Gay, heterosexual, Lesbian You will need to continue to a full Equality Impact Assessment if the following have been highlighted: You have ticked Yes in any column above and No consultation or evidence of there being consultation- this excludes any policies which have been identified as not requiring consultation. or Major service redesign or development 8. Please indicate if a full equality analysis is recommended. Yes No 9. If you are not recommending a Full Impact assessment please explain why. Signature of policy developer / lead manager / director Date of completion and submission Names and signatures of members carrying out the Screening Assessment 1. 2. Keep one copy and send a copy to the Human Rights, Equality and Inclusion Lead, c/o Royal Cornwall Hospitals NHS Trust, Human Resources Department, Knowledge Spa, Truro, Cornwall, TR1 3HD A summary of the results will be published on the Trust s web site. Signed Date Page 30 of 30