The New Era of Acute Stroke Management

Emerg Med 39(12):13, 2007

By Frank Rasler, MD, MPH

Timing is the key to stroke care. Having an efficient stroke protocol ready to go in your emergency department could mean the difference between a patient regaining function and losing it forever.

NOTE: This online article contains graphic elements and text boxes that did not appear in the print journal.

Discussing the emergency medicine aspects of ischemic stroke has become much more interesting in the past decade. Following the first successful thrombolytic trials, emergency physicians began to look at stroke care in a different way. In the past, our function had been to make the diagnosis, look for other problems, and then call a consultant. The rest we left to our colleagues in rehab to treat. Now the emergency department has become the focus for stroke care and research.

Although thrombolysis is used in only a small minority of stroke patients and is clearly not yet considered the standard of care for emergency medicine, its success has led to the formation of rapid treatment protocols and stroke centers. Early data on hospitals with stroke centers are beginning to show improved patient outcomes with reduced complications, length of stay, and cost of care for all types of strokes. The true benefit of a stroke center, however, may result from its focused multidisciplinary care rather than improved technology (see box below).

Hierarchy of Stroke Care A number of initiatives have established a hierarchy of care for stroke that resembles the system for trauma center designation. In its simplest form, written protocols for rapid stroke identification and treatment by an emergency department stroke team are essential. But many other factors, including administrative support, must be considered in deciding whether your hospital should pursue certification as a Joint Commission-designated primary or comprehensive stroke center. Even without an official designation, all emergency departments should offer patients an efficient process for early stroke identification and treatment. Those departments without 24-hour CT or lab capability should still employ specific stroke guidelines or protocols with triage, updated at least once a year. Current technology allowing for accurate diagnosis via the Internet offers the opportunity for larger stroke centers to assist small or rural emergency departments. Components for a primary stroke center include 24-hour availability for rapid neurologic consultation, CT interpretation, and lab testing, plus written stroke and thrombolytic protocols with complications management. Neurosurgical care should be available on-call or within two hours if hospital transfer is required. Primary stroke centers that admit patients will have a defined stroke unit with trained staff and monitoring equipment. Leadership by a neurologist or emergency physician is needed to unite the many hospital departments involved. A stroke log is needed to maintain performance data for quality improvement. Strong integration and training of emergency medical services (EMS) personnel are also key. Approximately one-half of all stroke patients arrive by ambulance. Stroke assessment screening by EMS is reasonably accurate, and their early notification of emergency departments of the need for potential thrombolysis promotes efficiency. They may also provide precise information on the time of symptom onset obtained from family or bystanders. Trained EMS providers can make it possible for the patient to get an earlier CT exam by drawing labs, inserting an intravenous line, and performing an ECG and a glucose check during transit. Education for EMS and staff, as well as public education on prevention and early recognition, should be provided at least twice a year, and eight hours of CME is required for physicians.

This article will detail the planning of an emergency department stroke team and its function as the key component of a hospital’s stroke center. Public education must also be emphasized in this new era of stroke care. Stroke is preventable by reducing risk factors, and immediate recognition of symptoms is the only hope of reducing morbidity.

DRAMATIC DETERIORATION

The following case is an example of dramatic deterioration during an evolving stroke. It also demonstrates the difficulty in treating a stroke within the three-hour thrombolytic window when the patient denies or ignores the earliest symptoms.

Mr. L, a previously healthy 60-year-old, was playing in a local chess competition. When he came to the emergency department, he brought his handwritten record of the chess match, in which you write down each move that you and your opponent make. At the beginning of a game each move may take only a few seconds, but as the game progresses more thought is required and each move may take a few minutes. As seen by the change in his handwriting (see image below), Mr. L’s stroke began at perhaps the twentieth move and progressed with time. He said he had no difficulty in formulating chess strategy and thought his handwriting deteriorated simply because he was getting tired. He may have been so involved in the game that he didn’t recognize a problem, and it is also possible that he was subconsciously ignoring the symptoms. When he eventually realized something was wrong and got up from his chair to leave for the emergency department, he noticed his leg wasn’t moving normally.

Documented loss of function. Mr. L's notations of the moves in a chess match illustrate how quickly function can become impaired with the onset of acute stroke.

At the stage of the chess game where Mr. L’s handwriting began to deteriorate, each move was probably taking two to three minutes. Multiplying this by two opponents over 15 moves each gives us the first hour of Mr. L’s stroke. In this rare opportunity to see handwriting samples, we can imagine an increasing number of neurons progressing through reversible ischemic injury to death. This shows why thrombolysis can work—if the patient gets to a stroke center immediately and the necessary interventions take place without wasting precious minutes. The earliest-affected neurons will die, but others in the surrounding ischemic zone may be saved.

This is why strict adherence to a rapid stroke protocol and regular practice of the protocol is essential. It can make the difference between a mild and a debilitating stroke. Until circulation is restored, every minute wasted results in more lost function. After prevention, this narrow therapeutic window is our next best opportunity to help stroke victims. For emergency physicians, this is the future of ischemic stroke care.

STROKE PROTOCOL: FOUNDATION OF TREATMENT

Thrombolysis changed the way we treat myocardial infarction (MI). It’s been the cardiac standard of care for so long that it’s easy to forget that emergency physicians were initially reluctant to use it. The main differences between MI and stroke thrombolysis are that the time window is shorter with stroke, the complications more frequent, and the diagnosis often harder to make compared with seeing an MI on an ECG. The other point to keep in mind is how many different hospital departments and people must coordinate effectively to make stroke thrombolysis work.

There is a lot of controversy about stroke thrombolysis, and only time will tell how beneficial it really is. The current belief is that for patients meeting strict criteria, it can result in a major improvement if given very quickly—that is, within two hours of symptom onset. Intravenous stroke thrombolysis must begin within three hours of symptom onset at the latest, but earlier administration clearly produces better results and probably reduces the risk of hemorrhagic complications. It is critical to note that waking up with stroke symptoms present is not considered the time of onset. Rather, it is the time when function was last known to be intactour Acute Stroke/TIA Order Set

Stroke protocols are the foundation of rapid treatment in suspected stroke. (Sample protocols developed at our institution and by other voluntary organizations are available to download and adapt to your own emergency department. Click here for a PDF file of our Acute Stroke/TIA Order Set.) Protocols can also help prevent complications that may have an impact on stroke outcome. For example, the simple act of leaving a stroke patient lying flat on his back or allowing him to drink water or take an oral medication can result in fatal aspiration pneumonia. All patients experiencing acute stroke should have their head elevated and must be NPO until their swallowing ability has been assessed. If they have any difficulty or if there is cranial nerve involvement, a formal swallowing evaluation is needed. Bedside evaluation with a sip of water or an ice chip is often used in the emergency department. However, it is probably wise to keep the patient NPO because the stroke may evolve.

Success with stroke teams and protocols has also intensified this new era of exciting research. Some clinicians are experimenting with catheters to remove the blood clot and with ultrasound or laser therapy to break it up; others administer a thrombolytic directly into the clotted artery up to six hours after symptom onset. Recent research with computed tomography (CT) angiography has helped predict which types of stroke may respond best to thrombolysis.

Induced cerebral hypothermia has recently shown promise in minimizing ischemic injury. There is also intense research into a diverse class of neuroprotective agents, including progesterone, which may someday prolong the current three-hour window for intravenous thrombolysis. In the future, paramedics may administer neuroprotective agents to help injured cells recover or to slow cell death long enough to get to an emergency department with a stroke center, where blood flow can be restored either by thrombolysis or by actual clot removal.

THROMBOLYSIS: MAKING THE MOST OF 60 MINUTES

The “time lost is brain lost” mantra is not trendy jargon. What happens in the prehospital phase and in the emergency department is the most important factor in outcome for all stroke patients. Emergency department guidelines need to incorporate speed and efficiency in their design and also must be applicable to patients who are not candidates for thrombolysis, including the 15% of patients with hemorrhagic strokes.

A thrombolytic door-to-needle time of less than 60 minutes is achievable (see table below), but it requires cooperation between your stroke team and multiple hospital departments, supported by regular practice drills. Extensive preparation is required for a procedure you don’t use very often, but just one or two minutes saved at each step will reduce the extent of the final ischemic injury.

Desired Time Goals for IV Stroke Thrombolysis   Acceptable goal (min) Achievable ideal (min) door to doctor <15 <10 door to CT completion <25 <20 door to CT interpretation <45 <30 door to lab test results <45 <30 door to needle <60 ?

The process begins when either the paramedics or emergency department triage call to say they have a recent stroke (less than six hours): We designate this patient “code red.” We use six hours as a time frame to allow for uncertainty about the time of symptom onset and the potential for deterioration in the early phase of a stroke. A stroke page is placed to alert the CT scan technician, the lab, and the on-call neurologist.

The patient is immediately brought to a room for the usual evaluation of ABCs, placement of a single intravenous line, oxygen administration, glucose check, and cardiac rhythm and blood pressure monitoring. It is absolutely essential that labs are drawn before the patient goes for the CT scan, so that results are available soon after the scan is complete. An “acute stroke box” (see below) containing the items for use prior to CT scanning can help save critical minutes. Nonessential tests, such as an ECG or chest x-ray, should be done after the head CT unless there is concern for coronary ischemia, an arrhythmia, or impaired oxygenation. Quick patient registration is also done at this time.

Acute Stroke Box Contents 1 promethazine 25 mg 1 labetolol 100 mg 1 nitroglycerin paste and paper 3 IV start kits 3 saline IV flush 1 nasal O2 tubing Hemoccult slide and developer 1 set of lab blood tubes, needles, and syringes for IV meds stroke guidelines, consent form, NIH scale and exclusions

Within 10 minutes of the patient’s arrival, the emergency department physician begins a rapid history and physical, establishes a time of symptom onset, and goes through the long list of thrombolytic exclusions (see table below). At this point, the physician decides if this appears to be a true stroke that can potentially be thrombolysed within three hours and notifies the neurologist. Computed tomography scanning begins within 20 minutes of arrival, then the radiologist is immediately called to get the results and determine whether the patient is a candidate for thrombolysis.

Potential Exclusions for IV t-PA For patients >18 years showing a measurable deficit with clear onset <3 hours (all must be considered before treatment with t-PA): hemorrhage on CT or suspicion of subarachnoid aggressive treatment to maintain SBP <185, DBP <110 <3 months post MI, CVA, neurosurgery, significant head trauma <7 days post lumbar puncture or noncompressible arterial puncture history of intracranial bleed, aneurysm, AVM, significant CNS tumor anticoagulation INR >1.7, platelets <100,000 heparin administration <48 hours with elevated PTT known bleeding disorder <14 days from major surgery or trauma minor or rapidly improving symptoms <21 days from GI or GU hemorrhage <6 weeks since pericarditis, endocarditis seizure with residual neurologic impairment pregnancy glucose <50 mg/dl diabetic hemorrhagic retinopathy

Meanwhile, the lab is rapidly doing a complete blood count, chemistries, and clotting times. The American Stroke Association (ASA) goal is to have results within 45 minutes, but a 30-minute goal is achievable by partnering with your lab. Next, the patient returns to the emergency department for a detailed history and re-examination. This includes an initial discussion with the patient or family regarding potential thrombolysis and its risks, making certain the time of symptom onset is as accurate as possible, obtaining a chest x-ray and ECG, placing extra intravenous lines, monitoring blood pressure, and possibly preparing tissue plasminogen activator (t-PA). By now the neurologist has arrived or, in some cases, has reviewed details of the case with the emergency physician by phone en route to the hospital.

The final elements should include a formal stroke assessment (for example, using the National Institute of Health’s stroke scale), a risk/benefit discussion, patient or family consent, and a review of stat labs and exclusion criteria. Assuming everything is in order and the patient is still within the three-hour window, t-PA can then be administered.

WATCHING AND WAITING

Next, we would closely monitor for potential bleeding and blood pressure complications. The risk of significant intracranial hemorrhage (ICH) is minimized by adherence to written guidelines and to the potential exclusion criteria. The radiologist also follows exclusion criteria for the CT scan that relate to the size and etiology of the acute stroke. The low risk of ICH from inadvertent administration of t-PA to stroke mimics such as migraine, transient ischemic attack (TIA), or psychiatric conversion deficits appears to be the same as that for MI thrombolysis.

Why is there such a high risk of ICH in ischemic stroke? Recent studies suggest that subclinical petechial hemorrhage may be very common. Thrombolysis then promotes bleeding where ischemia has weakened vascular cells. Interestingly, however, about 20% of these bleeds occur at a site distant from the acute stroke, suggesting prior damage from causes such as hypertensive and amyloid angiopathy.

Before, during, and after thrombolysis, blood pressure must be closely monitored, with checks at least every 15 minutes for the first two hours post-thrombolysis. Written treatment guidelines need to be followed for any elevation above 185 systolic or 110 diastolic. High blood pressure is common during acute stroke, but most patients will have a spontaneous reduction in their pressure within 90 minutes. In patients who are not thrombolysis candidates, pressures as high as 220 systolic and 120 diastolic can be closely observed unless there is suspicion of an additional risk of damage from hypertension (such as coronary ischemia, congestive heart failure, acute renal failure, dissection, or encephalopathy). In the past, we treated hypertensive patients with ischemic stroke aggressively. Now we find that leaving blood pressure relatively high may improve cerebral perfusion, although the recommendations here are based on limited data.

HEMORRHAGIC COMPLICATIONS

Despite the known risks, many physicians are not prepared to treat hemorrhagic complications with the urgency they require. Although specific reversal agents are available, when a critical hemorrhage occurs, you don’t have time to begin thinking about treatment options or to call a hematologist for advice. Every hospital using thrombolytics—for stroke, MI, or pulmonary embolism—would benefit from having written guidelines immediately available in the emergency department and in the intensive care and coronary care units to treat hemorrhagic complications. This may actually help reduce the reluctance among physicians to administer stroke thrombolysis because of the fear of hemorrhagic complications and possible litigation.

We developed our own specific guidelines for hemorrhagic complications of thrombolysis (see box below), which we keep with our acute stroke box and acute MI boxes, rather than just attaching them to a manual with other hospital protocols. The guidelines apply to initial management of thrombolytic- associated bleeding at any body site.

Guidelines for Hemorrhagic Complications of Thrombolysis Indicated Stop thrombolytic infusion. Draw CBC, INR, PTT, thrombin time, fibrinogen (before and after treatment). Rapidly administer 10 units of cryoprecipitate IV. Give 1 platelet pheresis unit IV (equivalent to six units of platelets). For recent heparin and low-molecular-weight heparin, give up to 50 mg protamine IV. Consult immediately with hematologist (and neurosurgeon for CNS bleed). For CNS bleed, consider seizure prophylaxis (especially for lobar hemorrhage). Maintain systolic BP <180 and mean arterial pressure <130 (or much lower acutely?). Minimize ICP elevation with gentle intubation techniques. Possibly indicated (depending on bleed severity and volume status) Give FFP 2 units (or prohtrombin complex concentrate) if potential for coagulopathy exists. Administer RBC transfusion if anemia is present. (Hemostasis improves with higher hematocrit.) Give 1 unit for Hg 10-11 g; or two units for Hg <10 g, over 1 hour each. Source: Rasler F: Emergency treatment of hemorrhagic complications of thrombolysis. Ann Emerg Med 50:485, 2007.

Physicians and nurses must be diligent in watching for early signs of ICH and other bleeding complications and be ready to initiate the guidelines. Based on clinical signs alone, it may be necessary to stop the thrombolytic infusion and begin thawing cryoprecipitate even before an immediate CT scan is done. Time is the critical issue when you decide to give a thrombolytic, and this same sense of urgency may help limit damage if hemorrhage occurs.

Cryoprecipitate is urgently needed to replace fibrinogen, which is depleted by thrombolysis. Platelets are indicated because patients at risk for stroke or MI commonly use platelet-inhibiting medications. It may eventually be recognized that platelets should be considered in all types of truly life-threatening hemorrhage, medical and traumatic, due to the common use of prescribed and over-the-counter platelet-inhibiting medications. No recommendation at this time can be made for activated factor VII, although theoretically it may offer an option for treating thrombolytic-associated bleeding.

Seizure prophylaxis should be considered for ICH because there is a 10% risk of that complication, usually with an early onset, and especially with lobar (subcortical) bleeds. Although it is not clearly recommended in the 2007 American Heart Association/ASA guidelines, I would favor immediate seizure prophylaxis, especially for lobar bleeding. Consider the low risk of a phenytoin load versus the risk of further bleeding during a grand mal seizure (from the shaking of the head in an anticoagulated patient who is already bleeding). Elevated blood pressure following ICH must also be addressed to potentially limit hematoma expansion. Avoid rapid blood pressure reduction, however, and elevate the head of the bed 30° and keep the patient’s head in a midline position. Consider sedation and simple analgesic measures such as relieving a headache or distended bladder to minimize fluctuations in blood pressure and intracranial pressure. If intubation is performed, the usual measures to minimize its acute effect on intracranial pressure should be used.

Acute treatment goals for hypertension in thrombolytic-associated ICH have not been established; each patient should be treated individually. Recommendations for treating spontaneous ICH (bleeding not caused by thrombolysis) suggest maintaining a systolic blood pressure below 180 and a mean arterial pressure below 130. For thrombolytic-associated ICH (and warfarin- or heparin-associated ICH), much lower pressures may be appropriate in the acute phase, although no recommendations currently exist. It would seem reasonable to want a lower pressure at least until anticoagulant reversal has begun, and titration with short-acting agents may be preferable. The theory is to maintain a reduced blood pressure to limit further bleeding (while maintaining a tamponade effect from cerebral pressure) and at the same time prevent ischemic levels of cerebral perfusion.

PREVENTION: BETTER THAN INTERVENTION

Stroke is the third leading cause of death in the United States, and many deaths occur before the ambulance even arrives. So prevention of stroke is at least as important as its treatment.

For a variety of reasons, patients may not get to the hospital in time to meet the very narrow three-hour window for thrombolytic therapy. Therefore, despite its efficacy, thrombolysis is at present only potentially useful in about 5% to 10% of ischemic strokes. For the vast majority of strokes, there is little we can prescribe except prevention.

Our impressive new therapies should not detract from basic prevention. Modifiable risk factors for stroke include the usual suspects: blood pressure, smoking and drugs, diabetes, cholesterol, weight, exercise, and diet. Success with smoking cessation or blood pressure control is clearly more important than thrombolysis. Another consideration is the need to anticoagulate for atrial fibrillation.

Furthermore, having a stroke or TIA implies a high risk for subsequent stroke. In past decades, having a TIA was almost considered no more than a minor inconvenience that needed follow-up. Now we know that after a TIA you have a 10% chance of a full stroke in the next three months—and half of these occur within just a few days. Platelet inhibitors have proven beneficial in many patients at risk. However, once again, it’s public education that is needed to teach people how to recognize that a TIA has happened and to understand its serious implications. Likewise, we could offer thrombolysis to potentially 10 times as many patients if they came as soon as symptoms appear.

TEACHABLE MOMENTS

A growing elderly population ensures that stroke care will continue to be a national priority. Our expertise continues to improve, but it will always be limited by the patient’s or family’s ability to recognize stroke symptoms and call for help. Even with an MI, denial of symptoms can be impressive. And unlike an MI, an ischemic stroke is typically painless. The patient may find the symptoms easy to ignore or may simply hope they go away, as did Mr. L, the chess player.

The emergency department remains unused and relatively unstudied as a site for behavioral intervention. A number of barriers may interfere with an emergency physician’s ability to provide counseling, such as time constraints, patient volume, and reimbursement issues. Add to those factors some physicians’ perception of patient disinterest and the belief that the emergency department is not an appropriate setting for counseling.

The challenge is to quickly convey key information without causing excess anxiety, depression, or guilt in our patients. Using positive concepts can help: “Now is your opportunity to change,” rather than, “All your years of smoking and obesity have caused your disease.” We need to engage their fear that things will only get worse if they don’t change and explain why that is the case.

In fact, emergency department patients are in a unique situation. Unlike with an office visit, the fear and stress induced by simply being in an emergency department could actually motivate some patients to change high-risk behaviors. It may be the perfect time to give them the information they need on risk factor reduction—and to encourage a genuine decision to change.

Studies on brief periods of counseling in the emergency department have, in fact, shown that these sessions can be successful and that providing written information and follow-up advice increases the likelihood of change. Moreover, patient surveys demonstrate a very high level of interest in obtaining health information while waiting in an emergency department. At least for the few hours they’re with us, they are an interested and captive audience. And let’s not forget that for many patients the emergency department is their only source of medical care and advice regarding disease prevention. We ignore these “teachable moments” at their peril.

Medicolegal Issues Related to Stroke Thrombolysis No discussion of stroke thrombolysis would be complete without considering its potential for litigation. The major concern is symptomatic intracranial hemorrhage (ICH), which occurs in 6% of stroke patients who receive thrombolysis and carries a 3% risk of death. Higher rates have been found when the exclusion criteria are not strictly followed. These are frightening statistics that the patient and family must consider. With MI thrombolysis, in contrast, reperfusion arrhythmias are a greater concern and the ICH risk is only about 0.5%. The fear of ICH also causes some hesitation in physicians when it comes to initiating thrombolysis. Although the thrombolytic risk of ICH is higher with stroke thrombolysis, it actually occurs more often with MI thrombolysis, but only because it is used much more frequently for MI. Since it is the standard of care for MI, a consent form is not used. However, for stroke, a specific thrombolysis consent form that details the unique risks is advisable. Litigation can also occur when thrombolytic therapy is not administered to a stroke patient who met the criteria for treatment and arrived within the three- hour window.  Therefore, the reason for deciding not to thrombolyse should be documented. For example, significantly improving stroke symptoms are among the exclusion criteria. Emergency department “protocols” are expected to work efficiently, but perhaps “guidelines” is a better term to use on your documents because each patient is unique and any deviation from strict protocols may increase the chance of litigation. The best way to prevent litigation is through careful documentation of informed consent and of your re-examination of the patient before thrombolysis. An honest explanation of the real risk of ICH and death and acknowledgement that the science is still unclear must be conveyed despite the brief period of time available in the three-hour window.  The decision to accept the risk then becomes that of the patient and family. Finally, guidelines for rapidly treating hemorrhagic complications resulting from thrombolysis should be immediately available.

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Suggested Reading Adams HP Jr, et al.: Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 38(5):1655, 2007. Broderick J, et al.: Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 38(6):2001, 2007. Brown DL, et al.: Survey of emergency physicians about recombinant tissue plasminogen activator for acute ischemic stroke. Ann Emerg Med 46(1):56, 2005. Irvin CB: Public health preventive services, surveillance, and screening: the emergency Department’s potential. Acad Emerg Med 7(12):1421, 2000. Magid D, et al.: Stroking the data: re-analysis of the NINDS trial. Ann Emerg Med 45(4):385, 2005. Schwamm LH, et al.: Recommendations for the establishment of stroke systems of care: recommendations from the American Stroke Association’s Task Force on the Development of Stroke Systems. Stroke 36(3):690, 2005. Stead LG et al.: The concept of permissive hypertension for acute ischemic stroke. Ann Emerg Med 46(3 Suppl):1, 2005. Additional information is available at www.stroke-site.org.

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