Rationale for Thrombolysis

Thrombolysis following
Acute Stroke
Dr Niall Hughes
Stroke and Geriatrics Consultant
Campbell Chalmers
Stroke Nurse Consultant
NHS Lanarkshire

Rationale for Thrombolysis
• Thromboembolic occlusion (85% strokes) → drop in blood flow
in corresponding arterial territory
• Flow ~ 20 ml/100 g /minute (~40% of the normal) → sx
• 1 million neurons die each minute
• 10 - 20 ml/100g/min → may survive for a few hours, but likely
to die if blood flow is not re-established
• Spontaneous reperfusion may occur through endogenous
release of plasminogen activator (stimulates plasminogen →
plasmin)

Trial Evidence for Alteplase
• Surprisingly little (relatively)
• NINDS (1995) - alteplase 0.9mg/kg, treatment within 3 hours
- ≥ 30% more likely to have min/no disability 3 mths
- almost half treated

Pooled data analysis of NINDS, ATLANTIS and ECASS I and II trials (shaded gray) showing
odds ratios and 95% confidence intervals for favorable outcome in different time windows from
onset, adjusted for prognostic confounders, with ECASS III outcome [superimposed (shaded
black)]

Reasons Patients Not Thrombolysed
1) Failure to be assessed within 3 hours
2) Concerns of physicians
- Approval based on only one trial
- benefits in NINDS due to no treated

Alteplase conditionally licenced
by EMEA in Europe in 2002
• Reflected these concerns
• Two conditions
1) - observational safety study
- The Safe Implementation of Thrombolysis
in Stroke-Monitoring Study [SITS-MOST]
- patients treated within licence terms
(18-80, 25)
2) - randomised trial with time window
extended beyond 3 hours [ECASS 3]
- initially 3-4 hrs, later changed to 3-4.5 hrs

SITS-MOST (2007)
• Recruited from December 2002 – April 2006
• 6,483 patients, 285 centres, 14 countries
• Treated on average 140 mins (11%

Modified Rankin scores at 3 months
0 1 2 3 4 5 Dead
Pooled placebo
0–3 h (n=465)
14% 15% 11% 15% 20% 8% 17%
Pooled alteplase
0–3 h ( n=463)
19% 23% 7% 14% 12% 7% 18%
SITS-MOST
(n=6,136)
19% 20% 16% 15% 14% 5% 11%
Modified Rankin scores at 3 months in SITS-MOST and randomised
controlled trials for placebo and alteplase patients
Wahlgren N et al Lancet 2007; 369: 275−282.

Conclusions
• The results of SITS-MOST confirm that routine use of
alteplase within 3 hours of ischaemic stroke has a safety
profile at least as good as that seen in randomised
controlled trials
• Safety could be maintained across centres, regardless
of experience in acute stroke thrombolysis
• Thrombolysis should now be considered a part of routine
care of suitable stroke patients

ECASS 3 (2008)
• Initially 3-4 hours from onset (amended to 3-4.5 hours)
• Confirmed benefits of IV alteplase between 3 & 4.5hrs
• SICH 1.9% [SITS definition]

SIGN Guideline 108, 2008
Grade A evidence
• Patients admitted with stroke within four and a half
hours of definite onset of symptoms, who are
considered suitable, should be treated with 0.9mg/kg
(up to maximum 90mg) intravenous alteplase
• Onset to treatment time should be minimised.
Systems should be optimised to allow the earliest
possible delivery of treatment within the defined time
window

“TIME IS BRAIN”
Model estimating odds ratio for favourable outcome at 3 months in
tPA treated patients compared with controls by onset to treatment

What I expect A+E to do
1. Recognise this is a probable stroke ASAP (ROSIER)
2. CONFIRM TIME OF ONSET ASAP
3. Contact stroke team ASAP
4. Arrange CT brain ASAP
5. Do relevant urgent things ASAP:
-BP
- directed medical history ( contra-indications)
- bloods and blood sugar
- cannula

What I do
1. Let ward know
2. Get to A+E ASAP
3. CONFIRM TIME OF ONSET
4. Check for contra-indications
5. Complete NIHSS
6. Counsel patient/relatives (+/-consent), check weight
7. Wheel them to CT

If no contraindication….
• Dilute with sterile water
to 1mg/ml
• 10% of the total dose is
administered as an
initial intravenous bolus
over 2 minutes
• remaining 90% is
administered as an
infusion using syringe
pump over 1 hour

Nursing Monitoring & Observation
• Follow local protocols and guidelines
• Identified Register Nurse trained in
thrombolysis
• Close acute monitoring of vital signs,
GCS, NIHSS
• Observe for signs of bleeding, raised
intra-cranial pressure, anaphylaxis
• Prevention of deterioration and
complications
• Repeat CT scan at 24 hours

Nursing Observation
Observe for signs of bleeding:
• Minor or major bleeding
• Bruising
• Existing injuries, wounds and IV cannula
Observe for signs of raised intra-cranial pressure:
• Onset of drowsiness
• Irritability or agitation
• Onset of nausea, vomiting or photophobia
• New or increasing headache
• Unequal pupils
Observe for signs of anaphylaxis:
• Angio-oedema: swelling of the tongue and lips

Nursing Care
• Ensure safety and falls prevention
• Bed rest with safety sides in situ (as
appropriate) and a head position angle of
30 degrees or gentle mobilisation with direct
supervision
• Supervised toileting at bedside
• Oral care caution using toothbrushes and
suctioning
• Personal hygiene - avoid wet shaving
• Skin care and regular position changes for
pressure relief
• Care of IV cannula sites

Nursing Care
• Avoid urinary catheterisation, NG tube
insertion, central venous access, arterial
puncture or other invasive procedures
before treatment and for 24 hours after
• Consult with medical colleagues if any
invasive procedures are necessary
• Care should be taken when removing
urinary catheters
• Avoid anti-platelets, anti-coagulants, non
steroidal anti-inflammatories, sedatives or
narcotics for 24 hours
• Avoid giving IM injections for 48 hours

Methods of Organisational Delivery
• Medical Approach
• High Dependency Unit
• Specialist or Research
Nurse
• Acute Stroke Unit
(hyper-acute)
• Use of Tele-medicine

Medical Approach
Advantages
• Specialist in stroke:
skilled and
experienced medical
staff
Challenges
• Unpredictability
• Sustainability
• 24 hour service
• Lack of skilled and
experienced nurses in
thrombolysis
• Sufficient nursing
resource
• Bed availability

High Dependency Unit
Advantages
• Specialist in stroke:
skilled and
experienced medical
staff
• Skilled and
experienced nursing
staff in acutely ill
patient / thrombolysis
for MI
Challenges
• Unpredictability
• Bed availability
• Lack of early access to
Stroke Unit
• Lack of skilled and
experienced stroke
specialists
• Step down for patients
• Stroke nurses fail to
gain experience in
thrombolysis

Specialist or Research Nurse
Advantages
• Specialist in stroke:
skilled and
experienced
medical staff and
specialist or
research nurse
Challenges
• Unpredictability
• Sustainability
• 24 hour service
• Bed availability
• Stroke nurses fail
to gain experience
in thrombolysis

Acute Stroke Unit (hyper-acute)
Advantages
• Early access to
Stroke Unit
• Access to multidisciplinary
team
• Specialists in
stroke: skilled and
experienced
medical and
nursing staff
Challenges
• Unpredictability
• Identified register
nurse trained in
thrombolysis
• Sufficient nursing
resource
• Bed availability

Use of Telemedicine
• Tele-conferencing
kit: location
• Remote and rapid
access to a oncall
specialist stroke
physician
• Equity of access
• Local access
• Regional/national
network

Acute Stroke: Patient Pathway
• Early access to
Stroke Unit
• Acute assessment
and monitoring
• Access to multidisciplinary
team
• Specialists in
stroke
SIGN 108 (2008)
Grade A evidence

Stroke Nursing Care
• Acute assessment, observation and monitoring
• Swallow screening, hydration and nutrition
• Skin and oral care
• Continence management (bladder and bowel)
• Prevention of deterioration, complications and
HAI’s
• Access to multi-disciplinary team
• Early activation and therapeutic handling
• Goal setting and rehabilitation
• Coordinated planned discharges

Patient and Carers
• Verbal and written information
• Explains the benefits and risks
• Can support decision making
• Accessibility and formats
• Advice and support
• Carer’s support
and involvement

Case Study - John
• 69 year old male
• Lives in Lanarkshire
• Married with a Son
• PMH – Type II Diabetes, ex-smoker
• Cycled to Lidl, to do some shopping
• Collapsed and developed slurred
speech, and left-sided face, arm and
leg weakness
• Ambulance called

Patient Pathway
10.40am - Onset of symtpoms
10.45am - Ambulance called
11.40am - Arrived at A&E
1 hour
11.50am - Call to Stroke Consultant
NIHSS 9
1hr 10 mins
12.10pm - CT Scan – NAD 1hr 30 mins
No contraindications
12.20pm – IV Bolus
12.25pm - Infusion commenced
1hr 40 mins

Aftercare
• Rare anaphylactic reaction
• Developed unilateral tongue
swelling, breathlessness and
tachycardia
• Compromised airway – anaesthetist
called
• Treatment as per algorithm

Aftercare
• Good recovery and returned home
• Followed up by Stroke Liaison Nurse
• Experienced tiredness initially and a
weaker voice
• Has returned to cycling and bowling

Patient Experience of
Thrombolysis following Stroke
Insert screen shot of Node 29846

Challenges for Stroke Nursing
• Register Nurses trained in
thrombolysis treatment / NIHSS
• Sufficient nursing resource
• 24 hour service, 7days per week
• Unpredictability
• Bed availability

Benefits of Thrombolysis Treatment
• Improved outcome for patients – reduced death
and disability
• Early access to the acute stroke unit
• Improved acute management
• Improved development and retention of stroke
nursing staff

Thrombolysis following
Acute Stroke
Dr Niall Hughes
Stroke and Geriatrics Consultant
Campbell Chalmers
Stroke Nurse Consultant
NHS Lanarkshire