Dr. Walter Himmel, “the walking encyclopedia of Emergency Medicine” & Dr. Dan Selchen, the head of the stroke program at St. Micheal’s Hospital in Toronto with 30+ years of experience as a stroke neurologist, update us on the literature regarding Emergency Stroke Controversies including the ABCD2 Score to predict Stroke after TIA, as well as the current thinking around the best carotid imaging for patients who have had a TIA. They then review the important findings of the key thrombolysis stroke trials & how we could incorporate these findings into our daily practice. Dr. Selchen reviews the key CT findings we should look for in stroke, & Dr. Himmel takes us through how to manage the dreaded complication of ICH post thrombolysis. This episode is super controversial – so please ‘speak your mind’ at the bottom of the page.
Dr. Himmel and Dr. Selchen answer questions such as: Should we be ordering CT angiograms of the neck in the ED for our patients with TIA or stroke? Should elderly patients be excluded from lytic protocols? Should community hospitals be using lytic for stroke or only stroke centres? Is there a role for intra-arterial thrombolysis? Are rapidly resolving or fluctuating symptoms a contra-indication to lysis for stroke? What are the key early signs of stroke on CT that ED docs should know about and why? What CT findings are contraindications to lytic? What are the most important supportive measures that we can do to improve our patients’ outcomes?
Lower risk (0-3pts), moderate risk (4-5pts), high risk (6-7pts)
Recent criticism of ABCD2 score:
Ann Emerg Med. 2011;57:46-51. In population that was treated very aggressively with early carotid + brain imaging and treatment, the rate of stroke was independent of the ABCD2 stratification.
CMAJ. July 12th, 2011;183(10). Sensitivity & specificity for predicting stroke 7 and 90 days after ED visit for TIA. Found that ABCD2 score is inaccurate at any cut-point as a predictor of stroke.
Dr. Himmel’s conclusion: Patients in these trials were investigated and treated more aggressively compared to when the ABCD2 score was initially developed. If you investigate patients with TIA within 24-48hrs and treat aggressively, the risk of stroke drops dramatically and the ABCD2 score is less important.
ABCD2 should not be used as rigid rule, but still helpful as a rough guide in determining which patients need urgent follow- up and aggressive investigation. Some argue that every patient with a probable TIA should be worked up urgently. A low ABCD2 score does not necessarily mean that the patient is at low risk for stroke, especially if posterior circulation TIA.
Update on Carotid Imaging for TIA
Consider Carotid Doppler Ultrasound or CT Angiogram of the neck in the ED for high risk TIA patients, to determine those with carotid artery stenosis who would benefit from time-sensitive early surgical intervention with carotid endarterectomy.
Important Thrombolysis Trials for Ischemic Emergency Stroke Controversies
Prior to NINDS, thrombolytic trials showed negative results because of either higher dose of lytic or concomitant treatment with anticoagulants resulting in an unacceptable rate of ICH.
NINDS trial 1995: 2 trials of 624 patients at 0-90min and 90-180min; NNT of 8 for post-hoc ‘favorable’ outcome functional measure.
ATLANTIS trial 1999: Favorable functional outcome at 3 months; increased ICH (7% vs. 1%) and nonsignificant increase in mortality (11% vs. 7%)
ECASS-3 trial 2008: trial of 3-4.5hr, where patients did better than no thrombolytics, but not as good as patients treated earlier. Different exclusion criteria compared to NINDS (eg: excluded diabetics). This trial showed benefit compared to ATLANTIS because they paid more attention to excluding patients based on imaging results and because the bulk of patients were treated earlier (<4hrs).
Dr. Himmel & Selchen’s Conclusions: There is a linear relationship between time to treatment and improved functional outcome in carefully selected patients in a systematized protocol, but no mortality benefit.
For a more detailed analysis of all systemic lytic studies for stroke up to 2013 visit The NNT
Should Elderly be excluded from thrombolysis protocols?
Dr. Himmel & Selchen believe that although there have been few elderly patients in lytic trials, being elderly should not be an absolute contra-indication to thrombolytics, as registry data show improved outcomes and the notion of increased risk of ICH in the elderly with lytics has been overstated in their opinions
Should community hospitals be using thrombolysis for stroke?
If systematized protocol in place, then yes. CASES study – Thrombolysis for acute ischemic stroke: Results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005, 172(10):1307-12. Prospective cohort study to assess effectiveness of lytic in actual practice in 60 centres. Improved clinical outcome in 37% with symptomatic ICH in 4.6%.
Volume of Infarct and Ischemic Penumbra as a factor in deciding lytic treatment: A small volume of infarct with a large surrounding ischemic penumbra is more likely to benefit from lytic compared to a large infarct with small penumbra. CT perfusion scanning or diffusion MR is used in some centres to determine size of infarct and penumbra which helps neurologists make lytic decisions in the later time window even beyond 4.5hrs, although data is not strong enough currently to make any definitive recommendations.
Intra-arterial (IA) thrombolytics: for ‘late presenters’ and for certain stroke types (eg: in large upper internal carotid or very proximal MCA clots seen on CT angiogram), patients do not derive benefit from IV thrombolytics, so IA t-PA is either added to IV lytic or used alone in the cath lab up to 6hrs after symptom onset for anterior circulation, and up to 12hrs for basilar occlusion. The ED doc needs to make the call to interventionist within 4hrs of symptom onset in anterior circulation strokes and within 10hrs in posterior circulation stroke for consideration of IA lytics to allow time for transfer and cath lab activation.
Some Issues around Contraindications to thrombolytics:
Rapidly resolving or fluctuating deficits may mean collateral circulation is temporarily perfusing brain tissue, and therefore is NOT an absolute contraindication. If a patient improves to a point where there is still a significant functional deficit they may still benefit from thrombolytic.
INR should be below 1.5-1.7 – Do you need to wait for INR result before giving lytic? If answer is “no” to the 3 following questions, one study showed 100% sensitivity for normal INR: use of warfarin? use of heparin? and hemodialysis? (also consider bleeding diathesis and liver disease)
Blood work Contra-indications: platelet count <100,000, serum glucose >22.2mmol/L (increased ICH risk). Some experts would correct a low glucose, and if stroke symptoms persists, will give thrombolytic.
Update 2015: Position statement on the use of thrombolytic therapy for acute ischemic stroke from CAEP here.
Update 2015: NEJM publishes three trials with promising results on endovascular therapies for ischemic stroke: MR-CLEAN, ESCAPE, EXTEND-IA.
An analysis of the MR-CLEAN, ESCAPE and EXTEND-IA trials on EM Lit of Note.
Imaging for Emergency Stroke
Early signs of stroke on plain CT head (not contraindications to lytic): blurring in basal ganglia, internal capsule or insula; loss of the grey-white junction clarity, sulcal effacement (gyri edema), hyperdense MCA sign has a large differential so exercise caution in ruling in stroke based solely on hyperdense MCA sign (see image)
CT contraindications to lytic: hemorrhage (differentiate from bilateral basal ganglia calcifications), and clear evidence of large area of ischema (>1/3rd MCA territory or large part of 2 lobes)
Dr. Selchen’s Tips on Informed Consent for Lytic: the patient is often not able to provide informed consent because of ‘stunned brain’ from the stroke, so next of kin should be contacted. Explain that t-PA is not a ‘miracle drug’ (i.e. doesn’t work in every patient) with benefit of 13-25% that outweighs the hemorrhage risk of 6% (in the brain and the gut most likely) – if no family member available, argument for treatment with t-PA as the standard of care is possible (i.e. treat as a surgical emergency – “treat now and discuss later”)
Thrombolytic Adverse Events
Consider symptomatic intracranial hemorrhage if patient develops severe headache (especially if associated with vomiting) or new neurologic symptoms – stop t-PA and obtain plain CT head, and consider giving 10u of cryoprecipitate (to replace the fibrinogen) and a pool of platelets – Recombinant Factor VIIa and Prothrombin Complex Concentrates are not indicated; neurosurgery does not need to be involved immediately given that an operation would be contraindicated right after giving a thrombolytic
Other ED supportive measures (as per AHA guidelines): intubation as necessary, oxygen to maintain O2 >92%, IV fluids: normal saline to maintain euvolemia, avoid hyperglycemia (<10mmol/L) – note that there is no benefit to ‘tight’ glucose control (4-7mmol/l) and keep patient normothermic (tylenol PRN), Foley catheter if retention to avoid excessive hypertension, and resist urge to decrease blood pressure dramatically: goal of <220/120mmHg (or MAP <150) if not thrombolysed, and <185/110mmHg (or MAP <130) if thrombolyzed – decrease by 10-15% with IV labetalol or nicardipine
=>3 numbers to remember for BP goal in stroke: MAP for ischemic stroke not thrombolysed, MAP <130 if thrombolyzed, MAP <110 for ICH
Antiplatelets and Heparin for Ischemic Stroke
Antiplatelets: Similar to TIA; as soon as CT scan shows NO hemorrhage: ASA 160-325mg chew or crushed down NG tube or rectally, or for ASA allergy or failure, Clopidogrel (Plavix) 300mg load then 75mg daily (if allergy to or failed ASA), or Aggrenox BID (but often causes headaches)
Heparin: very unusual to give to stroke patient (except in the setting of of extra-cranial carotid/vertebral dissection, crescendo stroke), and should be discussed with neurologist
Posterior circulation stroke
NIH Stroke Score quite insensitive to posterior circulation stroke due to overreliance on motor weakness findings; CT scan also insensitive, so MRI is required
Suspect cerebellar edema and increased ICP with decreasing LOC, headache, vomiting, loss of sensation or weakness, or upgoing toes; look for decreased 4th ventricle size on CT scan – consider neurosurgery consult
Anticoagulation for Acute Stroke Patients with Atrial Fibrillation
Delay starting Warfarin for a few days after massive stroke because of high risk of hemorrhagic transformation and lower risk of repeat stroke in the first few days, but start Warfarin 5mg right away after small strokes given low risk of hemorrhagic transformation
Dr. Himmel, Dr. Helman and Dr. Selchen have no conflicts of interest to declare.
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Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.