Download Dia 1 - Prehospital ICT Arena

Reperfusion in brain ischemia:
organizational aspects in view of the recent
randomized thrombectomy trials
Prehospital-IT-Stroke / METIS Forum
Lindholm Science Park
Gothenburg – Dec 8, 2015
Turgut Tatlisumak, MD, PhD
Inst. Neurosci & Physiol, Sahlgrenska Academy, Univ. Gothenburg
Dept. Neurol. Sahlgrenska Univ. Hospital, Gothenburg, Sweden
&
Dept. Neurol. Helsinki Univ. Central Hospital, Helsinki, Finland
Astrup J, Siesjö B, and Symon L.
Symon L, Lassen NA, Astrup J, Branston NM.
Thresholds of ischaemia in brain cortex.
Adv Exp Med Biol 1977 Jul 4-7;94:775-82.
Timely reperfusion is good for your health
•
The only approved recanalization drug for acute ischemic
stroke is IV TPA within 4.5 h of symptom onset
•
53 studies encompassing 3066 patients reported recanalization
rates as 24% spont., 46% IV, 63% IA, and 84% mechanical
•
Recanalization improved functional outcome (OR 4.4) and
reduced mortality (OR 0.24)
•
Hemorrhage rates  significantly
•
MCA and ACA recanalize more frequently than ICA
•
IA, mechanical, and combination approaches were better than
IV, but usually were implemented slower than i.v.
Rha and Saver, Stroke 2007
Efficacy of IV TPA in acute ischemic stroke –
Pooled Analysis 2010 (Lees KR et al. Lancet 2010)
NNT 4.5, CMH p=0.04
NNT 9.0, CMH p=0.05
NNT 14, CMH p=0.03
NNT 21, CMH 0=0.45
Thrombectomy trials: NNT for 1 additional independent patient is ~3-7
Results from the Last Pooled Analysis
(Emberson et al, Lancet 2014)
Individual patient data from 6756 patients in 9 randomized trials
All treated with iv TPA or placebo
Favorable outcome mRS 0-1
IV TPA benefit exists at all ages and stroke severities despite increased fatal ICH
Earlier treatment is better
REVASCAT
10-15% effect size
mortality
10-15% No
effect
size reduction
No mortality reduction
24-33% effect size
3-10% mortality
reduction
Courtesy of Prof A Demchuk
6
Time to Reperfusion and Outcome
Meretoja et al, Stroke 2014
Consensus statement on mechanical
thrombectomy in acute ischemic
stroke— ESO-Karolinska Stroke
Update 2014 in collaboration with
ESMINT and ESNR ESO-Karolinska
Stroke Update Conference 2014.
http://2014.strokeupdate.org/consens
us-statement-mechanicalthrombectomy-acute-ischemicstroke.
What is the portion of patients that
requires endovascular intervention?
• Patient flows change over time as they arrive earlier and earlier
• Current flows are according to “we have a treatment to offer
within 4.5 h (or 3h!) of onset”
• Karolinska/ESO consensus recommend a time window of 6 h
• During the REVASCAT trial (time window 8 h), 3.3% of all
ischemic stroke patients admitted to hospitals had endovascular
thrombectomy (Jovin TG et al, NEJM 2015)
• Much depends on age, stroke severity, time window, posterior
circulation, etc. indications
• Maybe ~10% of all ischemic strokes is a maximum guess
NIHSS changes at 2 h post-thrombolysis – the
Helsinki Stroke Thrombolysis Registry
•
•
•
•
•
•
•
•
n= 859
NIHSS  = 610 (71%)
NIHSS  = 124 (14%)
NIHSS  = 125 (14%)
NIHSS  ≥ 4 points or becomes 0 = 324 (38%)
NIHSS  ≥ 4 points = 38 (4%)
NIHSS is 0 or 1 = 100 (12%)
NIHSS ≥ 8 at 2 h = 370 (43%)
STROKE
NOTICE
CALL
TRANSFER
LAPSS (Los Angeles PrehospitaL Stroke Screen)
CPSS (Cinninnati Prehospital Stroke Scale)
MASS (Melbourne Ambulance Stroke Screen)
ROSIER (Recognition of stroke in the ER)
Kurashiki Prehospital Stroke Scale
Ontario Prehospital Stroke Screening Tool
CREATE THE NOTION OF:
THROMBOLYSIS/THROMBECTOMY CANDIDATE
How to recognize large-artery
occlusion in the field?
• Teaching NIHSS to EMS staff is feasible (Kesinger M et al, Stroke
2015)
• LAMS score ≥4 (Los Angeles Motor Scale – developed from LAPSS)
• Acute stroke patient with a NIHSS ≥ 9 within 3 h of onset or ≥ 7
within 3-6 h of onset carries ~85% chance (risk) of having a major
intracranial artery occlusion (Heldner M et al, Stroke 2013)
• Telecommunication (telestroke) connection to ambulances?
• There are rare patients with NIHSS 1 or 2, but having MCA occlusion
– how to deal with them?
Every hospital that admits stroke patients must have 24/7 access to acute
stroke care and a stroke unit where these patients should be treated…
But can we afford transferring and admitting all acute stroke patients to
Comprehensive stroke centers capable of offering endovascular treatment?
The biggest gains and losses occur in the
hyperacute phase…therefore invest to your
emergency room:
• Make the best experts available to the emergency room
• Develop the full emergency chain with no time losses
• Establish a diagnostic/therapeutic cluster within the ER
(CT, MRI; shock rooms, endovascular catheter lab)
• Critically ill neurological patient: all acute strokes,
unconscious patients, meningitis, encephalitis,
convulsing, resp insuff, etc.
• See: Tatlisumak T, Stroke 2015;46(6):1468-1473.
Patient transfer – Prehospital triage
How to organize regionally?
• All patients to the CSC or NIHSS-based selection?
• According to the distance? 1 h drive? 30 min?
• Almost all patients require CTA, immediate
teleradiology/telestroke evaluation
• If major artery occlusion, IV-TPA + transfer (drip and
ship)
• When endovascular treatment is indicated, expert to
site by helicopter?
• No system can guarantee 100% “best transfer”
NCCT and CTA head/neck
Primary Stroke Centres
Site of Occlusion
Good
collaterals
Occlusion site
Site of Occlusion
Good
collaterals
Phase 1
Intermediate
collaterals
“Collaterals”
NCCT/CTA nowIntermediate
standard of Poor
care and should be
collaterals
performed collaterals
sequentially while
on CT table
Phas
DTN <30 min/ DIDO <45 min
Door to CT scanner <10 min
Keep on the CT table for immediate CTA!
NCCT prep/scanning time <5 min
mCTA and CTP imaging are incongruent for treatment decision
NCCT
CTA prep/scanning time <5 min
mCTA and CTP imaging are incongruent for treatment decision
CTA reformatting time <5 min
CTA
Phase 1
Phase 2
Phase 3
Phase 2
Phase 3
1
All Phase
images
to decision
<10 min
mCTA and CTP imaging are incongruent for treatment decision
Tmax
CBF
Gray ma er
Keep on EMS stretcher!
White ma er
Phase 1
Phase 2
Phase 3
infarct
penumbra
CBF
Tmax
Tmax
NCCT to tPA decision via
telestroke <10 min mix/prep
for bolus <5 min
Door to needle <30 minutes
CBF
Gray ma er
Gray ma er
White ma er
Decision to
door out <10 min
White ma er
Door in door out <45 minutes
infarct
penumbra
infarct
penumbra
Reorganization of the ER: patientcentered NOT department-centered
• Critically ill neurological patient
• Shock room where stabilize, intubate, ABCD – team: anest,
neur, nurse
• Scanner next door (CT, MRI, X-ray, US). Radiologist on site
• Back to shock room for treatment (e.g. IV-TPA)
• Angiography suite in the ER (can serve neurosurgery,
vascular surgery, and others)
• All are within 30-40 m diameter
• Stroke unit & intensive care are preferably nearby the ER
50 consecutive patients with
angiographically-proven BAO
were treated with iv TPA+heparin.
At 1 year, 1/3 achieved mRS 0-2
and half died.
70-yo man
with BAO
Manpower is a bottleneck educational aspects
• Most stroke physicians are neurologists (here)
• EU abolished many medical specialties (2005/36/EC)
• Time to establish stroke medicine, interventional
radiology, neuroradiology
• 2-year training in stroke after neurology, geriatrics,
internal medicine, or alike training
• Standard training, maintenance, improvement
programs for interventionists (how many procedures
during training and afterwards annually per expert?)
• Can stroke physician do the trick?
Many questions remain….
1. Cost-effectiveness
2. General anesthesia vs conscious sedation
3. Drip and ship vs mothership vs interventionist to local hospital
by helicopter
4. Which patients directly to endovasc, which to IV-TPA first
5. How long should we wait during/after IV-TPA?
6. How to deal with posterior circulation occlusions
7. Time window vs tissue viability – up to 24 h
8. Should versatile imaging be used in all patients?
9. Ambulance-CSC telestroke connection for routing patients
10. Wake-up strokes?
The DRAGON Score for predicting
clinical response to iv thrombolysis
(Strbian et al, Neurology 2012)
The SEDAN Score for predicting
hemorrhage after iv thrombolysis
 n=974 (derivation) and n=828 (validation).
 All treated with iv TPA within 4.5h.
 AUC-ROC 0.77 for whole population.
(Strbian et al, Ann Neurol 2012)
Probable Future Directions
1. Bringing imaging and/or telestroke communication to (selected)
ambulances
2. Developing agents preserving penumbra that can be given in the
ambulance without brain imaging
3. Directing acute stroke patients to lesser number of well-equipped
hospitals (comprehensive stroke centers)
4. Rearrange ER to include shock room, scanner,
treatment/observation room, and angiography suite altogether
5. CT, CTA, and CTP or full-package MRI for (almost) all stroke
patients
6. Developing scores that predict accurately on an individual patient
level the benefits and harms of treatments
7. Changing practice from time-dependent to tissue viability dependent
treatment decisions
I frankly thank our stroke team...
and Prof. Andrew Demchuk (Calgary, CA)
for sharing his slides + views with me
”A rolling stone gathers no moss…..”