Dr. Devin R. Harris (biography and disclosures)
What I did before
The management of acute ischemic stroke in the emergency department has been a contentious issue since the publication of the NINDS trial showing that thrombolysis is beneficial in selected patients, if given under three hours from onset1. This trial has received considerable debate, largely due to the fact that it was a single randomized trial of 624 patients that significantly changed how acute ischemic strokes were treated – but the therapy potentially had significant, severe side effects.
Opinion leaders in emergency medicine were largely against this therapy, due to the fact it was a single trial with modest benefit, from specialized centers (not reproducible in most institutions), with significant baseline differences between the intervention and control groups, and that it excluded older patients.2-4 Arguably, hesitation in adopting the widespread application of thrombolysis for acute ischemic stroke as standard of care had legitimate grounds, prior to September 2008.
What changed my practice
In September 2008, the ECASS III trial was published, that confirmed and reinforced the effectiveness of thrombolysis (namely alteplase) in treating acute ischemic stroke.5 This was a study of 821 patients, randomized to receive alteplase or placebo, between 3 and 4.5 hours after the onset of a stroke. Set in Europe, the median time to administration of alteplase was 4 hours. 52.4% of patients given alteplase versus 45.2% given placebo had a ‘favorable outcome’ (defined as little or no disability) (95% confidence interval 1.02 to 1.76; p=0.04). Despite the fact that the incidence of any intracranial hemorrhage and symptomatic intracranial hemorrhage was significantly higher in the alteplase group than the control group; mortality did not differ between the two groups (7.7% mortality in alteplase versus 8.4% in control; p=0.68).
This trial was the first randomized trial since the NINDS trial to show benefit from the administration of a thrombolytic in acute ischemic stroke, and extended the time window of therapy up to 4.5 hours after the onset of stroke symptoms.
What I do now
As an emergency physician, the management of patients with acute ischemic stroke has changed significantly.
1. Public awareness and activation of emergency health services: The largest reason for ineligibility of administration of a thrombolytic in acute ischemic stroke is time delay; patients arrive too late and do not call 9-1-1. Education of the public, and targeted education of patients at high risk of stroke by their primary care physicians, could increase the number of stroke patients who arrive to emergency departments within the time window for assessment. Family physicians should emphasize that patients presenting with or calling in with features to suggest a stroke should be immediately triaged to the emergency department, rather than waiting to get into the family physician’s office.
2. “Code Stroke” Triage: Acute stroke in the emergency department is now treated with the highest urgency. Often, emergency department staff and stroke teams are notified by pre-hospital personnel, prior to patient arrival. Assessments are immediate upon arrival and stroke patients are rapidly taken to the CT scanner. In almost all institutions, the decision to thrombolyse patients is a shared decision between patients, caregivers, and treating physicians.
3. The British Columbia Stroke Strategy (BCSS) Telestroke Project:6 Certain emergency departments on Vancouver Island and in Fraser Valley are linked by videoconferencing capabilities to consulting stroke neurologists at the Victoria General Hospital and Vancouver Hospital, allowing for real-time examination of patients, review of imaging, and shared thrombolysis decision making.
Bottom Line: Thombolysis for acute ischemic stroke is a small component of comprehensive acute stroke therapy. However, there now should be no debate into its effectiveness and the widespread adoption of its use in carefully selected patients should be supported.
References: (Note: Article requests might require a login ID with the BC College of Physicians website or UBC)
1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581-8. (View article with CPSBC or UBC)
2. Hoffman JR. Should Physicians Give Tpa to Patients with Acute Ischemic Stroke? Against: And just what is the emperor of stroke wearing? West J Med 2000; 173(3): 149–150. (View article with CPSBC or UBC)
3. Hoffman JR, Schriger DL. A graphic reanalysis of the NINDS Trial. Ann Emerg Med 2009; 54(3): 329-36. (View article with UBC)
4. Hoffman JR. Tissue plasminogen activator (tPA) for acute ischaemic stroke: why so much has been made of so little. MJA 2003; 179 (7): 333-334. (View article with CPSBC or UBC)
5. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359: 1317-29. (View article with CPSBC or UBC)
6. The British Columbia Stroke Strategy: Telestroke Project. Online: http://www.bcstrokestrategy.ca/emergencyAcuteCare/telestroke/index.html (Accessed: October 22, 2010). (View article)
Loading ...
As rural MD I already am aware of needing to transport ASAP.
Compelling evidence exists for early triage and treatment. It would be reassuring to see once changes are implemented that completed stroke rates decline.
how would the treatment be of benefit for the victim who is already on maxmum asa therapy for a previous myocardial infarction?
I agree that is very important to educate the patients, in order to come to the emergency ASAP after they recognize the signs and symptoms of a stroke.
working in Nunavut in remote settlements without a CT scanner and other basic lab and an inevitable delay of many hours getting an air ambulance and flying the patient to Winnipeg in getting the patient to the right environment for throbolysis, the principle of earlty triage and treatment is impossible to execute. Universal healthcare remains a dream for many.
I agree that patient education of stroke signs and symptoms is a top priority here, with the message that they should present at the emergency as fast as possible if a stroke is likely.
Relying on this one and only acute intervention is rather impossible to defend. Where are the research trials checking out all these possibilities to reduce damage from the infarct during the acute phase?
anti-depressants, tumeric, stopping glutamate cell death, niacin, potassium,Irish coffee injection(caffeinol), xenon gas,Sigma-1 receptors,fish oil,marijuana, sensation stimulation, etanercept, caffeine, sleep, nicotine, alcohol, hypothermia, isomines and NEP1-40, SB623
And I know the clot still needs to be removed.
Thank you for the excellent comments and questions. Many of the comments relate to access, which, in rural and remote communities, is an ongoing issue. Current and future stroke planning within B.C. will keep rural and remote access issues as a priority. Initiatives such as Telestroke, thoughtful consideration of Regional and Provincial service structures, and ongoing quality improvement initiatives such as the B.C. Patient Safety and Quality Council Emergency Department Stroke and TIA Collaborative, will hopefully provide a network of care that allows rural and remote residents the same access to quality care.
Evidence from other jurisdictions (e.g. Ontario Stroke Strategy; Alberta Stroke Strategy) shows clear evidence that organized stroke systems of care reduces death and disability from stroke. Thombolytic administration is but a part of acute stroke care and now has good evidence for its benefit (Lees KR, Bluhmki E, von Kummer R, et al, for the ECASS, ATLANTIS, NINDS,and EPITHET rt-PA Study Group Investigators. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis ofECASS, ATLANTIS, NINDS and EPITHET trials. Lancet 2010; 375: 1695–703.) Best practice guidelines exist that are derived from good clinical evidence that show that organized inpatient care (stroke units), early home supported discharge, certain rehabilitation strategies, among others, have the largest impact in reducing disability (www.strokebestpractices.ca). And, for those patients who suffer a TIA, early investigation and management can reduce the risk of stroke after TIA by 80% within 90 days (Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JNE, et al on behalf of the Early use of Existing Preventive Strategies for Stroke (EXPRESS) study. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007; 370 (9596): 1432-1442.)
Regarding other therapies, being on aspirin is not a contraindication to acute thrombolytic therapy. Once administered a thrombolytic, anti-platelet medications are contraindicated for 24 hours after administration, however.
The administration of a thrombolytic medication for acute ischemic stroke should not be viewed as the only therapy. Judicious blood pressure management, prevention of hyperglycemia, anti-platelet therapy, DVT prophylaxis and excellent nursing care (avoidance of catherization, swallowing screens, early mobilization, for example) are just as important. Neuroprotective agents have been studied but, unfortunately, many have shown promise but none have been effective in clinical trials. Numerous trials are ongoing to find complimentary therapies for acute ischemic stroke.
Devin Harris
I too, am in a remote rural setting without a CT scanner or access to one in <4h, but wonder if now with teleradiology at our command if the health authorities could look at supplying hospitals such as ours, which are capable of thrombolysis for AMI's, with lower-cost small head-specific CT scanners, which I think cost out at <$400k (though there would also be technician/training costs). It seems to me it wouldn't take too many thrombolytic "saves" from long-term institutional care to offset these costs to the system.
I know about this very tight window of time for starting thrombolytic therapy. The real question is how to get these patient to the ER within the time frame, circumventing the delays in transportation, ambulance, ER overcrowding etc.
Good summary
I commpletely disagree with this article. I work at one of the telestroke centers, and you imply that the emergency physicians at that site all agree with the principles of this therapy. That is not the case.
You have not pointed out the relevant position of the Canadian Association of Emergency Physicians, which states, in part, “It is the position of the Canadian Association of Emergency Physicians that thrombolytic therapy for acute stroke should be restricted to use in the context of formal research protocols, or in closely monitored programs, until there is further evidence that the benefits of this therapy clearly outweigh the risks.” (CAEP website)
Who funded the studies you cite? Of the 8 large RCTs, 2 were positive, and you cite those. What about the SIX large RCTs which were negative studies? Since when does two minus six give a positive number?
The idea that we can offer something to stroke patients that might bring back the function they seem to have lost is very seductive. But the reality is that the treatment is far too dangerous, or at least far too debatable a benefit, to encourage ‘widespread’ use.
Your conclusions are wrong. There is ongoing and vigourous debate regarding the utility of stroke thrombolysis. You recommend “widespread adoption of its use.” Thereby, you imply that there is good, or any, evidence that this ‘therapy’ with the potential to kill or permanently disable patients who might otherwise recover, is effective in my setting. There is not. At my hospital we do not have a stroke unit, stroke neurologists, or stroke neuroradiologists, and we do not have ongoing trials that I am aware of. All of these were present in all of the relevent studies, and even then, most of those studies failed to show benefit.
I agree that a valuable use of resources is the implementation of some type of regional stroke care, and I hope this might happen. But as it stands, there is no health care center, from tertiary care, to regional, to rural and remote communities, that should ROUTINELY adopt the practice of thrombolytics for stroke.
I found it interesting that 3 of the articles that you listed at the end were from JR Hoffman who is pretty vehemently opposed to TPA for stroke. He disputes many of the studies and his graphing of the NINDS trial (number 3 above) suggested that time is not brain tissue (if I understood him correctly). Could you address his papers’ perspective in all of this?