Stroke thrombolysis guideline extended age and treatment window

CLINICAL GUIDELINE TO DELIVER SAFE AND EFFECTIVETHROMBOLYSIS FOR ACUTE ISCHAEMIC STROKE USINGROBUST EVIDENCE BASED CLINICAL CRITERIA1. Aim/Purpose of this GuidelineTo deliver safe and effective thrombolysis for acute ischaemic stroke usingrobust evidence based clinical criteria2. The GuidanceContentsPageReason for change 2Thrombolysis pathway 3Clinical Exclusions from thrombolysis 5Management of hypertension 7r-tPA dose ready reckoner 8Consent issues 9Management of complications after thrombolysis 10NIH Stroke Scale (full version) 12ASPECTS score 20Nursing protocol and care plan 21References 23Short NIHSS score sheet 24Peninsula Heart & Stroke Network Clinical Reference Groupstatement on thrombolysisMonitoring and Effectiveness and compliance 28Governance information 29Equality Impact Assessment 3125

Reason for changeECAS III AND IST-3 and an updated Cochrane review (available at www.ist3.com) haveled to a change in guidance across all hospitals in the SW peninsula (see Peninsula Heart& Stroke Network Clinical Reference Group statement on thrombolysis, appendix 2)The main changes are:1. NO UPPER AGE LIMIT FOR PATIENTS PRESENTING WITHIN 3 HOURS.2. PATIENTS 18-80y CAN BE TREATED UP TO 4.5 HOURS3. PATIENTS UNDER 80 PRESENTING WITHIN 4.5-6 HOURS ARE LIKELY TO HAVEA SMALLER BENEFIT BUT UNLIKELY TO HAVE GREATER RISK OFDEATH/BLEEDING– THESE DECISIONS SHOULD BE MADE ON CASE-BY-CASEBASIS BY THROMBOLYSING DOCTOR4. PATIENTS OVER 80 DO NOT BENEFIT IF TREATED AFTER 3 HOURS5. LARGER STROKES (ie HIGHER NIHSS AND EARLY ISCHAEMIC CHANGES) MAYALSO BENEFIT IF TREATED WITHIN 3 HOURSIn summary18-80y Over 80yWithin 3h YES YES3-4.5h YES NO4.5-6h MAY BENEFIT NOThe number needed to treat declines rapidly over time. Patients benefit the most if treatedwithin the first hour.DO NOT DELAY TREATMENT BECAUSE THE TIME WINDOW HAS BEENEXTENDED.6. PATIENTS ON WARFARIN CAN NOW BE LYSED IF INR ≤1.77. DIABETES MELLITUS AND OLD STROKE IS NO LONGER A CONTRA-INDICATIONStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 2 of 31

RCHT STROKE THROMBOLYSIS PATHWAYPRE-HOSPITALStroke 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 onsetCheck BM, confirm time of onset, transport to ED RCHT, with NOK and list of pills ifavailable. Pre-alert ED – ensure name, DOB and AFFECTED SIDE includedEMERGENCY DEPARTMENT• Confirm stroke using ROSIER scale• Book CT on MAXIMS – ensure side affected is clear on request• Page acute stroke doctor (In hours bleep 2866, out of hours Geriatrician on call)• Ring 4444 to alert radiographer/stroke nurse/stroke ward• Transport patient straight to CT on arrival for urgent CT head• Confirm time of onset• Brief medical history and examination, estimate weight• BP both arms, repeat higher arm BP after 15 minutes (manual cuff not dynamap)• iv access x2• Urgent bloods = FBC, U&E, clotting, G&S (INR if on warfarin), lipids, glucose• ECG (and CXR if needed)ACUTE STROKE DOCTOR (In hours bleep 2866,out of hours Geriatrician on call)• Confirm inclusion and exclusion criteria• Perform NIHSS examination (National Institute Health Stroke Scale)• Manage high BP as per protocol• Inform clinical site coordinator of need for critical care bed (bleep 2634)• Keep record of timesCT SCANNERRadiographer performs scan and informs on call radiologist to report scan usingASPECTS scoreStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 3 of 31

DECISION TO THROMBOLYSE• Repeat NIHSS to ensure not rapidly improving• Do not delay while waiting for bloods (unless on warfarin or on chemo or knownhaematological disorder)• Decision to thrombolyse taken by thrombolysing doctor• Obtain verbal consent if possible• Calculate dose using ready reckoner, give bolus in 10ml syringe over 1-2minutes then infusion over 1 hour using 50ml syringe driver• Start treatment in ED and organise bed on HDUMONITOR FOR COMPLICATIONS• Watch for signs of neurological deterioration, bleeding, anaphylaxis• Repeat NIHSS at 2h• Manual BP, pulse, GCS, respiratory rate, temperature, SaO2 every 15 min for2h, then every 30 min for 6 h, then every hour for 18h• Maintain BP Systolic

CLINICAL EXCLUSIONS FROM THROMBOLYSISDo not give thrombolysis if you have ticked any ‘YES’ boxesFROM THE HISTORYYESNOTime of onset unknownAwoke with symptomsSeizure at onsetKnown bleeding diathesisArterial puncture at a non-compressible site, or lumbarpuncture, within the last 7 daysMajor surgery within the last 14 daysGastrointestinal or urinary tract haemorrhage within 21 daysHead injury, intracranial surgery or stroke within the last 3monthsAny history of intracranial haemorrhage, brain tumour,intracranial AVM or aneurysmTIME OF ONSETWithin 3h – no upper age limit3 to 4.5h – can treat if 18-80, patients over 80y do not benefit4.5 to 6h – patients 18-80 may benefit – needs decision by thrombolysing doctorANTICOAGULANTSCurrent warfarin treatment is not an exclusion if the INR ≤1.7Current heparin treatment is not an exclusion if the APTT ratio is less than 1.2Full dose (but not low dose/prophylactic) LMWH is an exclusionRivaroxaban/Dabigatran – if a patient is on these treatments, 24h or 12h respectivelyshould elapse before a parenteral anticoagulant is given. This excludes these patientsfrom thrombolysis for stroke.PREGNANCYPregnancy 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 becauseexperience is limited, risks and benefits must be carefully weighed and should bediscussed with on-call obstetricianCHEMOTHERAPYSome chemotherapy agents may be relative contra-indications to thrombolysis. Orpatients may be cytopaenic. If patient on chemotherapy drugs please ensure bloodsnormal first and check with oncology or haematology before giving lysisCHILDRENAlteplase is not licensed for

ON INITIAL ASSESSMENT YES NOComa (GCS 140or BP>180/105 having received more than 2 doseslabetolol (see management of hypertension page 7)Capillary glucose

MANAGEMENT OF HYPERTENSION IN POTENTIAL THROMBOLYSIS PATIENTSBP should be recorded in both arms initially to exclude aortic dissection and CT thoraxconsidered. The arm with the highest reading should be used thereafter. Take anotherBP in this arm after 15 minutes.USE MANUAL CUFF NOT DYNAMAP1. If diastolic BP >140 on both readingsPatient is NOT eligible for thrombolysis even if other inclusion criteria met2. If systolic BP >220 and/or diastolic BP 121-140 on both readingsGive labetolol 10mg iv over 1-2 minutesRepeat as necessary at same or double dose at 10 minute intervals to bring BP below180/105 (maximum dose cumulative dose is 200mg, labetolol can be given 6 hourlythereafter as needed)Alternatively, after the bolus of labetolol an infusion of 2-8 mg/min can be initiated. If morethan 2 doses of labetolol required to control BP, patient is NOT eligible for thrombolysiseven if other inclusion criteria met.If asthma, cardiac failure or > 1 st degree heart block, use isoket infusion (2-10 mg/hr)3. If systolic BP 180-220 or diastolic BP 105-120 on both readingsIf patient is otherwise not eligible for thrombolysis monitor BP but do not interveneIf patient is otherwise eligible for thrombolysis, manage as per (2)4. If systolic BP

RtPA DOSE READY RECKONERAlteplase, Recombinant tissue plasminogen activator(Actilyse® Boehringer Ingelheim)• Unless the patient or companion knows their recent weight, estimate it to thenearest 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, makinga solution of 1 mg/ml rt-PA• Draw up and give 10% as a bolus over 1-2 minutes (Column 4), using a 10 mlsyringe• Draw up the remaining 90% (the ‘infusion dose’, Column 5) into 1 or 2 50mlsyringes and set up the 50ml syringe driver (IVAC) with the corresponding infusionrate in mls/hr.• Do not give the cardiac dose• Do not give more than 90 mg1 2 3 4 5Estimate ofpatientsweight (kg)EquivalentImperialweightBolus dose(mls)given over 1-2minutesInfusiondose (mls) =infusion ratein mls/hrTotal dose(mg at 1mg/ml)OnevialTwovials45 7 st 1 lb 4 36 4050 7 st 12 lb 5 40 4555 8 st 9 lb 5 44 4960 9 st 6 lb 5 49 5465 10 st 3 lb 6 52 5870 11 st 0 lb 6 57 6375 11 st 11 lb 7 60 6780 12 st 8 lb 7 65 7285 13 st 5 lb 7 69 7690 14 st 2 lb 8 73 8195 14 st 13 lb 8 77 85≥100 15 st 10 lb 9 81 90Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 8 of 31

ISSUES AROUND CONSENTInformation for patients / relatives before giving thrombolysisThrombolysis with r-tPA is a licensed treatment for acute ischaemic stroke, sowritten 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. Anyexplanation might include:• There has been a significant stroke caused by a blocked artery preventing bloodfrom getting to a part of the brain and causing permanent damage. With or withouttreatment there may be some recovery or things could get worse. Stroke is fatal inabout a third of people.• Only one treatment has been shown to prevent damage to the brain. This treatmentdissolves 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 thesooner it is given• There is a slight increased risk of death within the first week (8.9 vs 6.4%), mostlydue to fatal intracranial bleeding (3.6 vs 0.6%). But after the first week there is alower chance of death (11.5 vs 13.6%), so several months later there is nodifference in chance of death overall.• The chances of being alive and independent (Rankin score 0-2) several months laterare higher,% chance of thisoutcome if lysed% chance ofthis outcome ifnot lysedAbsolute benefit –number of extrapatients with thisgood outcome per1000 patientstreatedif treated within 6h 46.3% 42.1% 42if treated within 3h 40.7% 31.7% 90If treated 3-6h 47.5% 45.7% 18Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 9 of 31

MANAGEMENT OF COMPLICATIONS AFTER THROMBOLYSISBP commonly drops after initiation of thrombolysis, not necessarily due to bleeding. If thishappens give iv fluid bolus.Bleeding, by process of de-fibrination, is more common than with heparin (around 3%)Intracranial bleedingShould be suspected if there is neurological deterioration, new headache, fall in consciouslevel, acute hypertension, seizure, nausea or vomitingInitial actionStop infusion of r-tPA, repeat NIHSS, commence iv saline if neededArrange urgent CT scanCheck FBC, full coagulation screen, check blood sent for G&SIf CT scan shows bleeding• Is haemorrhage petechial? If so it is unlikely anything other than stopping r-tPA will beneeded. 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 cryoprecipitateFurther advice is available via the intranet anti-coagulation guidelines and from the on-callgeriatrician and Consultant HaematologistConsult neurosurgeon regarding possible transfer for haematoma evacuationIf CT scan shows no bleedingRecheck patient for other causes of deterioration eg recurrent ischaemic stroke, sepsis,seizure, metabolic derangement, extracranial bleedingExtracranial bleedingShould be suspected if there is shock, drop in BP, evidence of blood loss – although ahigh index of suspicion is needed as blood loss may not be obvious.Initial actionStop infusion of r-tPACheck FBC, full coagulation screen, check blood sent for G&S and/or arrange cross matchdepending on situationCommence iv saline or blood transfusion depending on situationIf patient fails to respond to simple measures or there is severe haemorrhage, considertranexamic acid 10 mg/kg IV and 10 units cryoprecipitateFurther advice is available from intranet, on call geriatrician and haematologist as above.AnaphylaxisAnaphylactic reactions to r-tPA can occur but are rare. If an urticarial rash, peri-orbitalswelling or tongue swelling occur, the r-tPA should be stopped and the patient reviewed bya doctor urgently.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 10 of 31

NIH STROKE SCALE – full version and master copy – please record patient scores on quick version(see page 23)INSTRUCTION SCALE DEFINITION SCORE11a. Level of Consciousness:The investigator must choose a response,even if a full evaluation is prevented bysuch obstacles as an endotracheal tube,language barrier, orotracheal trauma/bandages. A 3 is scored only if the patientmakes no movement (other than reflexiveposturing) in response to noxiousstimulation.1b. LOC Questions:The patient is asked the month and his/herage. The answer must be correct - there isno partial credit for being close. Aphasicand stuporous patients who do notcomprehend the questions will score 2.Patients unable to speak because ofendotracheal intubation, orotrachealtrauma, severe dysarthria from any cause,language barrier or any other problem notsecondary to aphasia are scored 1. It isimportant that only the initial answer begraded and that the examiner not “help” thepatient with verbal or non-verbal cues.1c. LOC Commands:The patient is asked to open and close theeyes and then to grip and release thenonparetic hand. Substitute another onestep command if the hands cannot be used.Credit is given if an unequivocal attempt ismade but not completed due to weakness.If the patient does not respond tocommand, the task should be demonstratedto them (pantomime) and score the result(i.e., follows none, one, or two commands).Patients with trauma, amputation, or otherphysical impediments should be givensuitable one-step commands. Only the firstattempt is scored.2. Best Gaze:Only horizontal eye movements will betested. Voluntary or reflexive(oculocephalic) eye movements will bescored but caloric testing is not done. If thepatient has a conjugate deviation of theeyes that can be overcome by voluntary orreflexive activity, the score will be 1. If apatient has an isolated peripheral nerveparesis (CN III, IV, OR VI) score a 1. Gazeis testable in all aphasic patients. Patientswith ocular trauma, bandages, preexistingblindness or other disorder of visual acuityor fields should be tested with reflexivemovements and a choice made by theStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 11 of 310 = Alert; keenly responsive.1 = Not alert, but rousable by minorstimulation to obey, answer, or respond.2 = Not alert, requires repeatedstimulation to attend, or is obtunded andrequires strong or painful stimulation tomake movements (not stereotyped).3 = Coma; Responds only with reflexmotor or autonomic effects, or totallyunresponsive, 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 = Normal1 = Partial gaze palsy. This score isgiven when gaze is abnormal in one orboth eyes, but where forced deviation ortotal gaze paresis are not present.2 = Forced deviation, or total gazeparesis not overcome by theoculocephalic manoeuvreSCORE2----------- ---------------------- ---------------------- ---------------------- -----------

investigator. Establishing eye contact andthen moving about the patient from side toside will occasionally clarify the presence ofa gaze palsy.3. Visual:Visual fields (upper and lower quadrants)are tested by confrontation, using fingercounting or visual threat as appropriate.Patient must be encouraged, but if theylook at the side of the moving fingersappropriately, this can be scored as normal.If there is unilateral blindness orenucleation, visual fields in the remainingeye are scored. Score 1 only if a clear-cutasymmetry, including quadrantanopia isfound. If patient is blind from any causescore 3. Double simultaneous stimulationis performed at this point. If there isextinction patient receives a 1 and theresults are used to answer question 11.4. Facial Palsy:Ask, or use pantomime to encourage thepatient to show teeth or raise eyebrows orclose eyes. Score symmetry of grimace inresponse to noxious stimuli in the poorlyresponsive or non-comprehending patient.If facial trauma/bandages, orotracheal tube,tape, or other physical barrier obscures theface, these should be removed to the extentpossible.5&6. Motor Arm and Leg:The limb is placed in the appropriateposition: extend the arms 90 degrees (ifsitting) or 45 degrees (if supine) and the leg30 degrees (always tested supine). Drift isscored if the arm falls before 10 seconds orthe leg before 5 seconds. The aphasicpatient is encouraged using urgency in thevoice and pantomime but not noxiousstimulation. Each limb is tested in turn,beginning with the nonparetic arm. Only inthe case of amputation or joint fusion at theshoulder or hip may the score be “9” andthe examiner must clearly write theexplanation for scoring as a “9”.0 = No visual loss.1 = Partial hemianopia.2 = Complete hemianopia.3 = Bilateral hemianopia (blind includingcortical blindness). ----------- -----------0 = Normal symmetrical movement.1 = Minor paralysis (flattened nasolabialfold, asymmetry on smiling).2 = Partial paralysis (total or near totalparalysis of lower face).3 = Complete paralysis (absence of facialmovement in the upper and lower face).Arm0 = No drift, arm holds 90 (or 45) degreesfor full 10 seconds.1 = Drift, arm holds 90 (45) degrees, butdrifts down before full 10 seconds; doesnot hit bed or other support.2 = Some effort against gravity, limbcannot get to or maintain (if cued) 90 (or45) degrees, drifts down to bed, but hassome effort against gravity.3 = No effort against gravity, arm falls.4 = No movement.9 = Amputation, joint fusion -explain:5a = Right Arm----------- ---------------------------------Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 12 of 315b = Left ArmLeg0 = No drift, leg holds 30 degrees positionfor full 5 seconds.1 = Drift, leg falls by the end of the 5second period but does not hit bed.2 = Some effort against gravity, leg fallsto bed by 5 seconds, but has some effortagainst gravity.3 = No effort against gravity, leg falls tobedimmediately.4 = No movement.9 = Amputation, joint fusion -explain:----------------------

6a = Right Leg6b = Left Leg--------------------------------------------7. Limb Ataxia:This item is aimed at finding evidence of aunilateral cerebellar lesion. Test with eyesopen. In case of visual defect, ensuretesting is done in intact visual field. Thefinger-nose-finger and heel-shin tests areperformed on both sides, and ataxia isscored only if present out of proportion toweakness. Ataxia is absent in the patientwho cannot understand or is hemiplegic.Only in the case of amputation or jointfusion may the item be scored “9”, and theexaminer must clearly write the explanationfor not scoring. In case of blindness, testby touching nose from extended armposition.8. Sensory:Sensation or grimace to pinprick whentested, or withdrawal from noxious stimulusin the obtunded or aphasic patient. Onlysensory loss attributed to stroke is scoredas abnormal and the examiner should testas many body areas [arms (not hands),legs, trunk, face] as needed to accuratelycheck for hemisensory loss. A score of 2,“severe or total”, should only be given whena severe or total loss of sensation can beclearly demonstrated. Stuporous andaphasic patients will therefore probablyscore 1 or 0. The patient with brainstemstroke who has bilateral loss of sensation isscored 2. If the patient does not respondand is quadriplegic, score 2. Patients incoma (item 1a=3) are arbitrarily given a 2on 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; patientfeels pinprick is less sharp or is dull onthe affected side; or there is a loss ofsuperficial pain with pinprick but patient isaware he/she is being touched.2 = Severe to total sensory loss; patient isnot aware of being touched.----------- -----------9. Best Language:A great deal of information aboutcomprehension will be obtained during thepreceding sections of the examination. Thepatient is asked to describe what ishappening in the attached picture, to namethe items on the attached list of sentences.Comprehension is judged from responseshere as well as to all of the commands inthe preceding general neurological exam. Ifvisual loss interferes with the tests, ask thepatient to identify objects placed in thehand, repeat, and produce speech. Theintubated patient should be asked to write.The patient in coma (question 1a = 3) willarbitrarily score 3 on this item. TheStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 13 of 310 = No aphasia, normal.1 = Mild to moderate aphasia; someobvious loss of fluency or facility ofcomprehension, without significantlimitation on ideas expressed or form ofexpression. Reduction of speech and/orcomprehension, however, makesconversation about provided materialdifficult or impossible. For example, inconversation about provided materialsexaminer can identify picture or namingcard from patient’s response.2 = Severe aphasia; all communication isthrough fragmentary expression; greatneed for inference, questioning, andguessing by the listener. Range of----------- -----------

examiner must choose a score in thepatient with stupor or limited cooperationbut a score of 3 should be used only if thepatient is mute and follows no one stepcommands.10. Dysarthria:If the patient is thought to be normal, anadequate sample of speech must beobtained by asking patient to read or repeatwords from the attached list. If the patienthas severe aphasia, the clarity ofarticulation of spontaneous speech can berated. Only if the patient is intubated or hasother physical barrier to producing speechmay the item be scored “9", and theexaminer must clearly write an explanationfor not scoring. Do not tell the patient whyhe/she is being tested.11. Extinction and Inattention(formerly Neglect)Sufficient information to identify neglectmay be obtained during the prior testing. Ifthe patient has severe visual losspreventing visual double simultaneousstimulation, and the cutaneous stimuli arenormal, the score is normal. If the patienthas aphasia but does appear to attend toboth sides, the score is normal. Thepresence of visual spatial neglect oranosagnosia may also be taken asevidence of neglect. Since neglect isscored only if present, the item is neveruntestable.information that can be exchanged islimited; listener carries burden ofcommunication. Examiner cannot identifymaterials provided from patient response.3 = Mute, global aphasia; no usablespeech or auditory comprehension.0 = Normal.1 = Mild to moderate; patient slurs at leastsome words and, at worst, can beunderstood with some difficulty.2 = Severe; patient’s speech is so slurredas to be unintelligible in the absence of orout of proportion to any dysphasia, or ismute/anarthric.9 = Intubated or other physical barrier -explain:0 = No abnormality.1 = Visual, tactile, auditory, spatial, orpersonal inattention or extinction tobilateralsimultaneous stimulation in one of thesensory modalities.2 = Profound hemi-inattention or hemiinattentionto more than one modality.Does not recognize own hand or orientsto only one side of space.----------- ---------------------- -----------TotalMaxscore 42TotalMaxscore 42Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 14 of 31

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ASPECTS scoreThis is a topographic score for dividing middle cerebral artery territory into 10 regions. It iscalculated from 2 standard axial CT cuts, one at the level of the basal ganglia and one atthe corona radiate / centrum semiovale level. Subcortical structures are allotted 3 pointsand cortical structures 7 points.For each of these 10 areas a point is subtracted if there is evidence of ischemic damagethere (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 diffuseinvolvement of all MCA territory would score 0.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 18 of 31

An ASPECTS score 7 or less is a relative contra-indication to thrombolysis, with increasedrisk of haemorrhage; in this instance consider carefully other factors that may influence thedecision to treat or not to treatM1 = anterior MCA cortex, M2 = MCA cortex lateral to insular ribbonM3 = posterior MCA cortex, M4, M5, M6 are anterior, lateral and posterior MCA territoriesimmediately superior to M1, M2, M3C = caudate, L = lentiform, IC = internal capsule, I = insular ribbonStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 19 of 31

Nursing ProtocolNursing Care Following Thrombolysis for Stroke1. Patient to be nursed in identified bed space that allows for continuous observation.2. Oxygen, Suction, Cardiac Monitor, Sphygmomanometer, O2 Saturation machine should beavailable at the bed side. Capillary blood glucose machine, Anaphylaxis box should beeasily accessible.3. Initiate post administration thrombolysis care plan on arrival4. Perform patient observations as indicated and record a baseline ECG5. If there are any concerns, medical review is essential. Report, review, document andincrease frequency of observations accordingly.6. Pyrexia > 37°C should be treated with PR or PO Paracetamol (1g 4-6 hourly. No morethan 4g in 24 hours)7. If haemorrhage is suspected, report immediately and arrange for urgent medicalreview. Send urgent FBC, clotting and group and save8. If anaphylaxis is suspected (Tachypnoea, dyspnoea, tachycardia, swelling, rash) Stopinfusion and employ anaphylaxis protocol. Arrange for urgent medical review orperform a crash call (2222)if required9. Avoid catheterisation for 24 hours following thrombolysis infusion to minimise the risk oftrauma and bleeding. If essential, consult with medical team.10. Do not insert naso gastric tubes for 24 hours post thrombolysis infusion to minimise therisk of trauma and bleeding11. IM injections should be avoided for 48 hours post thrombolysis infusion to minimise therisk of excessive bruising12. Avoid giving heparin / warfarin. Refer to medical staff before commencing any anticoagulant or antiplatelet therapy (only given if CT at 24h shows no bleeding).Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 20 of 31

Observations following administration ofthrombolysis for strokeManual BP, Pulse, Temperature, Respirations,GCS and Oxygen Saturations (MEWS Score – Refer to localGuidelines)Every 15 minutes for 2 hoursEvery 30 minutes for 6 hoursHourly for 18 hoursMaintain BP < Systolic 180 / Diastolic 105Temperature not to exceed 37°C.Observe for signs of raised intracranial pressure or intracranialbleeding• Unequal pupils• Sudden drop in GCS• Onset of drowsiness• Onset of nausea, vomiting (photophobia)• Rising BP and falling pulseStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 21 of 31

ReferencesThrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic StrokeNEJM 2008; 359: 3517-29The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogenactivator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): arandomised controlled trialLancet 2012 ;379 :2352-63Recombinant tissue plasminogen activator for acute ischaemic stroke: an updatedsystematic review and meta-analysisLancet 2012; 379: 2364-72NICE Guidance TA 122 - Alteplase for the treatment of acute ischaemic strokeNational Stroke Strategy, Department of Health 2007Validity and reliability of a quantitative computed tomography score in predicting outcomeof hyperacute stroke before thrombolytic therapyLancet 2000; 355:1670-1674Use of the Alberta Stroke Program Early CT Score (ASPECTS) for Assessing CT Scans inPatients with Acute StrokeAm J Neuroradiol 2001; 22:1534–42Importance of Early Ischemic Computed Tomography Changes Using ASPECTS inNINDS rtPA Stroke StudyStroke 2005; 36:2110-15Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 22 of 31

Short NIHSS scoring sheetThis is master copy – patient packsinclude this sheet which should be filedin medical notes with completedinclusion/exclusion checklistNational Institute for Health Stroke Scale (NIHSS)REFER TO LAMINATED FULL GUIDANCE FOR SCORINGDate and Time1a. LOCScore 0-31b. LOC – Response to QuestionsScore 0-21c. LOC – Response to CommandsScore 0-22. Best gazeScore 0-23. Visual fieldsScore 0-34. Facial palsyScore 0-35. Right Arm motorScore 0-4 or X if untestable6. Left Arm motorScore 0-4 or X if untestable7. Right Leg motorScore 0-4 or X if untestable8. Left leg motorScore 0-4 or X if untestable9. AtaxiaScore 0-2 or X if untestable10. SensoryScore 0-211. Best languageScore 0-312. DysarthriaScore 0-2 or X if untestable13. Neglect/InattentionScore 0-2Total Score (0-42)Score Score Score ScoreStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 23 of 31

Peninsula Heart & Stroke Network Clinical Reference GroupAugust 2012Statement on Thrombolysis for Acute Ischaemic Stroke1. Intravenous AlteplaseWith the publication of IST3 in May 2012, linked to an updated Cochrane Review (both available atwww.ist3.com) the indications for rtPA (alteplase) treatment for acute ischaemic stroke within 6hours of known onset were considered at the June PH&SN Clinical Reference Group (CRG)meeting. The updated 4 th Edition of the RCP’s National Clinical Guidelines for Stroke will bepublished in September 2012 also taking account of the new evidence and systematic review.Summary of main IST3 findings3035 patients were randomised between rtPA or control at up to 6 hours after onset. 95% ofpatients were outside the prevailing EU licence at the time, and 53% were above the age of 80.Within 3 hours, the large majority of patients were over 80, whereas beyond 4.5 hours the majoritywere younger than 80. 30% of patients had atrial fibrillation, 43% had a TACI syndrome.Safety: the overall incidence of symptomatic intracranial haemorrhage (ICH) in IST3 was 7%, verysimilar to the reported incidence in the SITS-MOST audit dataset. The risk of intracerebralhaemorrhage did not increase with time from onset, or with age. The excess of ICH wasresponsible for an excess early mortality with rtPA (within 7 days) of 11% versus 7% with control.Between 7 days and 6 months there was an excess of deaths in the control group such that by 6months, mortality between the two groups was entirely equivalent at 27%.Efficacy: the trial’s primary endpoint was the proportion of patients ‘alive and independent’ at 6months (an Oxford Handicap Scale score [OHS; roughly equivalent to the modified Rankin Scale]of 0-2). This proportion was higher with rtPA, but not statistically significant – 37% with rtPAversus 35% with control. Shift analysis of the probability of a better outcome as determined by thefinal category of the OHS indicated a 27% higher chance of a better outcome with rtPA, and thiswas statistically significant (95% CI 1.10-1.47; p=0.001).Subgroups: the benefit from rtPA was at least as great for patients over the age of 80 as foryounger patients. Patients with severe stroke benefitted at least as much as those with lesssevere stroke. The benefit was greatest in patients treated within 3 hours of onset, bearing in mindthat these patients tended to be older and more severe. The presence of acute ischaemicchanges on baseline CT scan did not appear to prejudice the benefit from treatment.Updated Cochrane ReviewThe data from IST3 were added to the 11 existing trials of rtPA, with the numbers of patientstreated up to 6 hours from onset almost doubling to over 7000. Almost all the data in patients overthe age of 80 comes from IST3. The review confirms an excess risk of fatal ICH (four-foldincreased risk) and a 44% relative increase in risk of death within 7 days to 8.9%. At six months,total mortality was the same with or without rtPA treatment, with an overall absolute increase inpatients with reduced or absent disability of 5.5% with treatment. Early treatment (within 3 hours)was definitely beneficial, increasing the relative odds of a good outcome by 53%. The magnitudeof the benefit of treatment within 3 hours was very similar for patients above or below the age of 80(a 9.5% absolute increase in the chance of a good outcome), but beyond 3 hours there was nobenefit for patients over 80, and a lesser benefit for younger patients.Clinical ImplicationsThe European licence for rtPA in acute ischaemic stroke has recently been amended to licencetreatment in patients aged 80 or younger up to 4.5 hours after known onset, based on the results ofStroke Thrombolysis Guideline Extended Age and Treatment WindowPage 24 of 31

the ECASS III trial and the updated individual patient meta-analysis of Lees et al (2010). The moststraightforward conclusion the CRG drew from the additional IST3 data was that the benefits ofthrombolysis can be immediately extended to those patients previously excluded by age, by strokeseverity or by the presence of early ischaemic changes on CT scan. The relation to time totreatment is more complex, although IST3 adds further emphasis to the importance of treating allpatients as early as possible to maximise the chances of benefit. Subdividing the Cochrane reviewby age (above or below 80 years) and time to treatment (before 3 hours or between 3-6 hours)indicates clear benefit below 3 hours regardless of age, but no clear evidence of benefit forpatients over 80 beyond 3 hours. Thus the extension to include older patients within 3 hours isstraightforward, but beyond 3 hours probably requires the results of other current or planned trialsfor a clearer answer. The Cochrane review provides reassurance regarding the risks of ICH, whichare not higher than previously reported even among patients with severe stroke or those treated upto 6 hours, and so may provide justification for patients below the age of 80 with severe stroke anda lot to lose being treated up to 6 hours after symptom onset.The Stroke CRG thus concluded that:1. Any patient, regardless of age or stroke severity, where treatment can be started within 3 hoursof known symptom onset and who has been shown not to have an intracerebral haemorrhageor other contraindications should be considered for treatment using alteplase.2. Between 3 and 4.5 hours of known symptom onset, patients under 80 who have been shownnot to have an intracerebral haemorrhage or other contraindication should be considered fortreatment with alteplase.3. Between 3 hours and 6 hours of known symptom onset patients should be considered fortreatment with alteplase on an individual basis recognising that the benefits of treatment arelikely to be smaller than those treated earlier, but that the risks of a worse outcome, includingdeath, will on average not be increased.4. To permit these decisions to be considered in every case in a timely fashion, the South WesternAmbulance Service should deliver every patient with suspected stroke within 6 hours of onset tothe nearest ED as fast as possible with a pre-alert (according to local arrangements) and a ‘bluelight’ transfer, without further pre-selection.2. Intra-arterial interventions for acute ischaemic strokeThe other main development in acute stroke thrombolysis is the suspension of the IMS III trial bythe National Institutes of Health in May 2012. IMS III was planned to compare outcomes in 900patients randomised to intravenous rtPA or to an IV/IA regimen, using mechanical clot retrieval orintra-arterial rtPA within 7 hours of known onset. The trial was suspended after 656 patients wererandomised on the grounds of futility, given that the trial had a very low likelihood of demonstratinga clinically significant difference in benefit between the treatment arms of the study. Othertreatment regimens are being studied in the US and elsewhere (including with tenectaplase ordesmoteplase), but at present the data supporting an IV/IA rescue strategy are not sufficient toadvocate a major change in management approach. This is in keeping with the upcoming NationalClinical Guidelines recommendation that intra-arterial interventions should only be used in thecontext of a clinical trial.The approach to intra-arterial interventions within the Peninsula Heart & Stroke Network willtherefore be based on the consensus statements from the Stroke Improvement Programmemeeting of October 2011, as follows:1. The widespread adoption of intra-arterial interventions in acute stroke could not berecommended at the present time, on the grounds that the available randomised controlled trialevidence was insufficient.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 25 of 31

2. A number of trials are in progress that may help clarify the appropriate role of such therapiesand devices and it is strongly recommended that further research is conducted.3. Intra-arterial interventions in acute stroke should only be undertaken within the context of a trialor national/international registry and at specialist stroke centres that fulfil agreed standards ofcare.4. Further work at a national level should be undertaken to agree and describe the requiredstandards of care for both staff and processes at such centres: standards that would includedemonstrable research capability and activity in trials of interventional treatments.Implications for the Peninsula Heart & Stroke NetworkFollowing the results of IST3 and the updated Cochrane Review, the Clinical Reference Groupaimed for a consistent approach to eligibility for intravenous alteplase treatment across thePeninsula. This will include the need for thrombolysis protocols to be amended, and to liaise withthe South Western Ambulance Services Trust to achieve a consistent approach to pre-hospitalcare. At the same time, SINAP data for the first full year (2011-12) continue to show very low ratesof thrombolysis across the Peninsula (from less than 2% to 6%) when the comparative nationalSINAP average for the first quarter of 2012-13 is now 11%. Removing the upper age limit fortreatment will have an immediate effect on the proportion of patients eligible for treatment, butfurther efforts are needed to increase the disability benefit for patients through the eradication ofdelays to treatment in all centres.3. Monitoring compliance and effectivenessElement to be Outcome of thrombolysis for individual patientsmonitoredLeadDr Katja AdieToolFrequencyReportingarrangementsActing onrecommendationsand Lead(s)Change inpractice andlessons to besharedSITS(MOST) -Safe implementation of Thrombolysis in StrokeMonitoring Study – an international monitoring studySentinel Stroke National Audit Programme (SSNAP) from the RoyalCollege of PhysiciansEach thrombolysed patients details and outcomes are entered onto the SITS MOST database and the SSNAP Audit ProgrammeDr Adie reports outcome locally to the eldercare governancemeeting six monthlySSNAP data is collected as part of the Trust Clinical Audit &Outcomes Programme on an ongoing basisSSNAP data is reported and published nationally and monitored bythe Strategic Health AuthorityDr Adie, Dr HarringtonRequired changes to practice will be identified and actioned withinsix months. Dr Adie and Dr Harrington as lead members of theteam will take each change forward where appropriate.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 26 of 31

4. Equality and Diversity4.1 This document complies with the Royal Cornwall Hospitals NHS Trust serviceEquality and Diversity statement.4.2 Equality Impact AssessmentThe Initial Equality Impact Assessment Screening Form is at Appendix 2.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 27 of 31

Appendix 1. Governance InformationDocument TitleDate Issued/Approved: 3/9/12Date Valid From: 3/9/12Date Valid To: 1/9/15Stroke Thrombolysis Guideline Version 3Extended Age and Treatment WindowDirectorate / Department responsible(author/owner):Dr Frances Harrington, ConsultantPhysician, Eldercare RCHTContact details: 01872 253290Brief summary of contentsGuideline for the administration ofthrombolysis for acute ischaemic stroke –upper age limit removed, time windowextended for some patients from 3h to 6hSuggested Keywords:Target AudienceExecutive Director responsible forPolicy:Date revised: 22/8/12This document replaces (exact title ofprevious version):Approval route (names ofcommittees)/consultation:Divisional Manager confirmingapproval processesName and Post Title of additionalsignatoriesSignature of Executive Director givingapprovalPublication Location (refer to Policyon Policies – Approvals andRatification):Document Library Folder/Sub FolderLinks to key external standardsRelated Documents:Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 28 of 31Stroke, Thrombolysis, AlteplaseRCHT PCT CFTMedical DirectorStroke Thrombolysis 24/7 ProtocolAcute Stroke Group, SERCO, SWASTDr Duncan BrowneNot RequiredInternet & Intranet Intranet OnlyClinical / Neurology and StrokeNICE Guidance TA122 - Alteplase for thetreatment of acute ischaemic strokeAdvanced Stroke Management PathwayAcute Stroke ManagementStroke and TIA Multidisciplinary CarePathwaySecondary Prevention after Stroke or TIA

Training Need Identified?Yes. Learning and Developmentdepartment have been informed.Version Control TableDateVersionNoJuly 2008 V1.0Initial IssueSummary of ChangesChanges Made by(Name and Job Title)Dr F HarringtonDecember2010V2.0 Amendment to 24/7 service Dr F Harrington3/9/12 V3.0 Extended age and treatment window Dr F HarringtonAll or part of this document can be released under the Freedom of InformationAct 2000This document is to be retained for 10 years from the date of expiry.This document is only valid on the day of printingControlled DocumentThis document has been created following the Royal Cornwall Hospitals NHS TrustPolicy on Document Production. It should not be altered in any way without theexpress permission of the author or their Line Manager.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 29 of 31

Appendix 2. Initial Equality Impact Assessment ScreeningFormName of service, strategy, policy or project (hereafter referred to as policy) to beassessed: Stroke Thrombolysis Guideline Extended Age and Treatment WindowDirectorate and service area:Is this a new or existing Procedure? existingName of individual completingTelephone:assessment: Dr F Harrington01872 2532901. Policy Aim* To safely administer thrombolytic agent to acute ischaemicstroke patients using updated, clearly defined criteria2. Policy Objectives* Safe administration of emergency drug therapyClear advice and guidance for staff involved in theadministration of emergency treatment and aftercare ofpatients who have undergone thrombolysis for stroke3. Policy – intended As aboveOutcomes*4. How will you measurethe outcome?5. Who is intended tobenefit from the Policy?6a. Is consultationrequired with theworkforce, equalitygroups, local interestgroups etc. around thispolicy?b. If yes, have thesegroups been consulted?c. Please list any groupswho have been consultedabout this procedure.Patient response to treatmentAudit – ongoing local and RCP National Sentinel StrokeAuditInclusion in international SITS-MOST register (Safeimplementation of thrombolysis in stroke)Patients: through the promotion of safe, effective, evidencebased practiceYesYesAcute Stroke Group, SERCO, SWAST*Please see Glossary7. The ImpactPlease complete the following table using ticks. You should refer to the EA guidance notesfor areas of possible impact and also the Glossary if needed.• Where you think that the policy could have a positive impact on any of the equalitygroup(s) like promoting equality and equal opportunities or improving relationswithin equality groups, tick the ‘Positive impact’ box.Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 30 of 31

• Where you think that the policy could have a negative impact on any of the equalitygroup(s) i.e. it could disadvantage them, tick the ‘Negative impact’ box.• Where you think that the policy has no impact on any of the equality group(s) listedbelow i.e. it has no effect currently on equality groups, tick the ‘No impact’ box.Equality Positive Negative No Reasons for decisionGroup Impact Impact ImpactAge X Removal of upper age limit forstroke thrombolysis based onrecent randomised controlled trialsDisabilityXReligion orbeliefGenderTransgenderPregnancy/MaternityRaceSexualOrientationMarriage / CivilPartnershipXXXXXXXYou will need to continue to a full Equality Impact Assessment if the following havebeen highlighted:• A negative impact and• No consultation (this excludes any policies which have been identified as notrequiring consultation).8. If there is no evidence that the policypromotes equality, equal opportunitiesor improved relations - could it beadapted so that it does? How?Full statement of commitment to policy ofequal opportunities is included in the policyPlease sign and date this form.Keep one copy and send a copy to Matron, Equality, Diversity and Human Rights,c/o Royal Cornwall Hospitals NHS Trust, Human Resources Department, ChyveanHouse, Penventinnie Lane, Truro, Cornwall, TR1 3LJA summary of the results will be published on the Trust’s web site.Signed ________________________________________Date _________________________________________Stroke Thrombolysis Guideline Extended Age and Treatment WindowPage 31 of 31