Stroke Thrombolysis at UHB

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Stroke Thrombolysis at UHB

• Don Sims

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Stroke Thrombolysis

• The Development of Thrombolysis
• Eligibility for Treatment
• Assessment and Monitoring
• Practicalities of treatment
• Conclusions / Discussion

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Stroke incidence

• 110,000 people have their first stroke
• 7 per annum risk of further stroke
• 10,000 people affected under 55
• 1,000 people affected under 30
• Leading cause of disability in the U.K.
• 3rd leading cause of death (67,000 / year)

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Stroke burden

• Consumes 5 of the entire NHS yearly budget (2.8
  billion)
• Costs another 4.2 billion in lost productivity
  and informal care
• Stroke patients occupy over 20 of all hospital
  beds
• 300,000 people are living with moderate or severe
  disability as a result of stroke

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Thrombolysis

• Effective treatment is likely to have large
  mortality/morbidity and cost implications
• First trials begin to appear
• Mori E, in Japan 1993 (31 patients 6 hours)
• Haley E, in US 1993 (27 patients 90 mins)
• Little clarity on what agent to use or what time
  frame
• Already clearly a different entity to cardiac
  thrombolysis

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Stroke vs. Cardiac Thrombolysis

• Stroke is several different disease processes
• Small vessel disease (atherosclerosis)
• Large vessel disease (embolism of carotid
  atheroma)
• Cardio-embolic disease (AF, PFOs, LVF)
• Cerebral haemorrhage (aneurysmal / vessel wall)
• Cerebral haemorrhages
• Post MI are a rarely seen complication (lt1)
• Post stroke are common even if not always
  clinically significant

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Stroke vs. Cardiac Thrombolysis

• Decision to treat for MI
• is based on clear ECG criteria
• is a low-risk treatment
• And therefore mistakes have fewer consequences
• Decision to treat for stroke patients
• is based on clinical assessment and radiological
  assessment
• is comparatively high risk
• And therefore mistakes can be fatal

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National Institute of Neurological Disorders
(1995)

• Established the protocols still used
• Inclusion / Exclusion criteria
• Choice of agent
• Timing of administration
• Subsequent trials have shown
• Other agents less effective
• Over 6 hours post stroke is hazardous
• Deviation from the protocol often leads to more
  bleeds and a worse mortality

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Likelihood of Being Helpedvs. Harmed

• Number needed to treat NNT 3.1
• Number needed to harm NNH 30.1
• For every 100 patients treated with rt-PA
• 32 will have a better final outcome
• 3 have a worse final outcome and
• 65 have an unchanged final outcome
• Likelihood of helped verses being harmed (LHH)
• LHH (30/3) 10
• Intravenous alteplase is 10 times more likely to
  help than harm eligible patients with acute
  ischemic stroke

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Unchanged outcome for 65 of patients

• Overall stroke mortality remains 20
• Total anterior circulation strokes
• Mortality 39 (at 30 days, 60 at 1 year)
• Dependence 56
• Independence 4
• Lacunar strokes
• Mortality 2 (30 days)
• Dependence 36
• Independence 62

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Risk of cerebral haemorrhage

• 7 risk of haemorrhage visible on 24 hour scan
  with no improvement in NIHSS
• 4 risk of significant haemorrhage with a NIHSS
  change of 4
• 1.5 risk of large haemorrhage with significant
  space occupying effect
• Likely to prove fatal
• Not usually amenable to neurosurgical
  intervention
• Comparison with the risk of cerebral haemorrhage
  from MI thrombolysis

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Eligibility for Thrombolysis
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Eligibility Criteria

• Age gt 18 years
• Clinical diagnosis of ischaemic stroke
• Onset of symptoms within 2 hours
• To allow treatment within 3 hours
• Can be treated up to 6 hours (only in IST-3)
• Stroke symptoms present for at least 30 minutes
• A clearly measurable deficit (NIHSS gt 4)

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Contraindications

• Evidence of intracranial haemorrhage on CT scan
• Symptoms suggestive of subarachnoid haemorrhage
• Seizure at onset of stroke
• Systolic BP gt185 mmHg or diastolic BP gt110 mmHg
• Any history of other central nervous system
  damage
• Haemorrhagic retinopathy
• Bacterial endocarditis, pericarditis or
  pancreatitis
• Neoplasm with increased bleeding risk
• Any severe liver disease

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Contraindications

• Symptoms rapidly improving before thrombolysis
• Known history of or suspected intracranial
  haemorrhage
• Head injury within the last 3/12
• Ulcerative/bleeding GI disease during the last
  3/12
• Major surgery or significant trauma in last 3/12
• Recent puncture of a non-compressible blood
  vessel
• Recent (lt10 days) traumatic CPR or childbirth
• Anticoagulants (except warfarin if INRlt1.4)
• Platelet count of below 100,000/mm3
• Known haemorrhagic diathesis

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Contraindications (not IST-3)

• Age gt80 years
• Stroke (ischaemic) within the last 3 months
• Severe stroke as assessed clinically (e.g.
  NIHSSgt25)
• Severe stroke as assessed on CT scan
• gt1/3 MCA territory
• ASPECTS score lt7
• Previous functional status
• Rankin score 3 or more
• History of prior stroke and concomitant diabetes

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Aspects Score
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Assessment and Monitoring
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Thrombolysis in the ED

• Identify patients with symptoms of acute stroke
• Onset lt 2 hours immediately contact Stroke
  Physician
• Document observations every 15 minutes
• Rapid evaluation to rule out non-stroke pathology
• Check capillary blood sugar (BM)
• Administer oxygen at 2-10 l/min to O2 gt 95
• Place two 18 gauge cannulas in large veins,
  preferably in both antecubital fossa
• Take 20mls of blood for urgent analysis
• Acquire 12-lead ECG
• Organise IMMEDIATE CT SCAN

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Stroke Physician Assessment

• Examine patient and confirm diagnosis
• Discuss risks / benefits with the patient /
  relative and obtain consent
• Review and confirm all inclusion / exclusion
  criteria
• Complete NIHSS and Rankin scores
• Weigh patient or estimate if not able to weigh
• Age is lt 55 years, add thrombophilia screen to
  bloods
• Review all blood results if available
• Prepare to travel with patient to CT (alteplase,
  syringe, portable monitors, oxygen)

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Thrombolysis in CT

• Obtain CT scan and review images
• Final confirmation that inclusion / exclusion
  criteria are met
• Confirm consent obtained
• Review blood results
• Calculate dose of alteplase
• 0.9 mg/kg alteplase (max 90mg)
• 1 minute infusion of 10 of dose
• Remaining 90 over next 1 hour
• Admit patient to a continuous monitored bed on ASU

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Physiological Monitoring

• Continuous physiological monitoring
• Otherwise check observations
• Every 15 min for 2 hours
• Every 30 minutes for 6 hours
• Every 60 minutes for 16 hours
• NIHSS at 0, 2, 24 hours and 7 days (or discharge)
• Repeat CT head scan at 24-36 hours

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Post Thrombolysis

• Maintain oxygenation
• Treat pyrexia aggressively
• Manage blood glucose actively
• Prompt swallowing assessment
• IV fluids if needed
• Nurse at 30 degrees in bed

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Post Thrombolysis

• For the first 24 hours (where possible)
• No urinary catheters
• No NG tubes
• No aspirin / dipyridamole / clopidogrel
• No heparin (not even prophylatic doses)
• Avoid central venous and arterial lines

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24 Hours Post Treatment

• Likelihood of alteplase related complications
  recedes
• Usual stroke care resumes
• Aspirin 300 mg after repeat CT scan
• NG tube if required
• Investigations of stroke aetiology as indicated
• Secondary preventative therapy
• Begin normal rehabilitation protocols

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Problems arising post alteplase

• Neurological deterioration
• Repeat CT head scan
• Contact neurosurgery if haemorrhage
• Stop alteplase infusion!
• Check FBC and clotting studies
• Give FFP, cryoprecipitate, and platelets
• Most deterioration is not due to haemorrhage
• Treatment is usually conservative
• Surgical intervention usually futile though
  advice from neurosurgeons is recommended

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Problems arising post alteplase

• Significant hypertension post treatment
• Potentially hazardous due to haemorrhagic
  transformation
• Systolic gt180 mmHg or diastolic gt 105mmHg on two
  occasions over 5 minutes
• Labetalol 10-20 mg IV stat and consider labetalol
  infusion
• GTN infusion (as per cardiac dosing)
• Generally avoid IV calcium channel antagonists
• Sodium nitroprusside infusion (only on ITU)
• Repeated dose of labetalol can be used
• It is not advisable that labetalol is used
  pre-alteplase to allow thrombolysis to be
  undertaken

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Thrombolysis in practice at UHB

• Lessons learnt in the last 12 months

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Timing is everything

• Ambulance crew often pre-alert AE
• Sister in ED or triage nurse aware of stroke
  thrombolysis and contacts stroke team
• Take a colleague / junior doctor / nurse with you
  to assess patient / insert cannulas
• Need 30-40 minutes from time of call to delivery
  of alteplase
• Inform CT as soon as you are confidant you have a
  suitable candidate
• Inform ASU as soon as possible to allow bed
  clearing procedure to begin

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Collateral history

• You need a clear start time of symptoms
• Or a clear last known symptom-free time
• History from patient
• Collateral history from family member present at
  time of onset
• History from workmates
• The ambulance crew who can provide the number
  where the 999 call originated

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Practical steps

• Place a cannula in each antecubital fossa
• 1 for treatment and 1 for anything else needed
• pre-alteplase delivery
• Alteplase infusion tables are weight based and
  part of the protocol
• Travel with the patient to CT and get verbal
  report
• Strongly advised to develop a working knowledge
  of CT interpretation
• Likely return to ED resus bay to deliver
  treatment and arrange move to ASU between 15
  minute observations
• CT have never kept us waiting more than 10
  minutes and ASU never more than 30 minutes from
  first awareness of patient

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Monitoring and recording of data

• Clearly record all pertinent patient data
• Especially time of alteplase administration
• Much that follows depends on this time
• Clinician delivering the treatment has
  responsibility to ensure that nursing
  observations are undertaken as needed
• Out of hours the clinician will have to retain
  some clinical responsibility for the patient out
  of hours until the next working day

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Possible Outcomes

• Dramatic improvement
• Clot dissolved and almost total recovery within
  days (or even hours)
• Improvement faster than expected
• Slow steady improvement (as if untreated)
• Significant deterioration (as if untreated)
• Rapid deterioration
• As if untreated with oedema
• Or secondary to significant haemorrhage
• Dramatic improvement with total relapse and then
  steady improvement
• Alteplase has minor vasodilator action restoring
  blood flow but clot remains as after infusion
  stops patient resumes normal course

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Skills needed to deliver the service

• Making the diagnosis of acute stroke
• Stroke remains a clinical diagnosis
• Excluding stroke mimics
• Ability to assess severity of stroke
• Using the NIHSS
• Ability to assess the results of CT head scan in
  co-operation with radiology

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Cautious approach with new therapies

• If in doubt dont treat with alteplase
• Should have a clear diagnosis with lateralising
  signs
• Not solely an unexplained decreased conscious
  level
• Or other feature of stroke mimics (seizures /
  headache)
• If CT in doubt dont treat
• Limited subarachnoid bleeds easily missed
• Whole MCA territory infarctions have poor
  outcomes
• Patients will die as a result of treatment so
  care must be taken that treatment was warranted
• In practice though most litigation has been
  around why treatment was NOT given

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International Stroke Trial - 3

• Approximately halfway to recruiting 3100 patients
  by 2011 internationally (44 centres in the UK)
• Window widened to 6 hours
• No age or stroke severity limits
• Recruiting large numbers not present in other
  trials such as posterior circulation strokes and
  diabetics with prior stroke
• Already recruited over 500 patients over 80 years

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Unanswered Questions

• The role of perfusion scanning in detecting
  viable ischaemic penumbras
• Local intra-arterial thrombolysis
• Rescue angioplasty
• Other treatments have to be shown to be both more
  effective and delivered quick enough to reduce
  harm done by delaying intravenous lysis

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Conclusions

• Very beneficial treatment for a select number of
  stroke patients
• Careful assessment and monitoring of patients is
  essential
• Some responsibility for treated patients will
  likely have to stay with the clinician treating
  them for a short period of time

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Any Questions?