Current drug therapy for an acute ischemic stroke is a thrombolytic agent that dissolves clots in the blood vessels of the brain. Although clinical trials have evaluated such medications for brain attack since the 1960s, complications included such a high rate of intracranial bleeding that the agents were temporarily abandoned for use in this patient population. As recently as 1994, the American Heart Association (AHA) Stroke Council cautioned against the use of thrombolytic drugs in patients following acute ischemic stroke. However, favorable results from a recent large clinical trial encouraged the Food and Drug Administration (FDA) in June of 1996 to approve the first thrombolytic drug to be used specifically for brain attack — t-PA.¹

Opening occluded vessels in the brain permits reperfusion of ischemic neurons and promotes recovery of function.² Thrombolytic agents work on the occlusion by activating the conversion of plasminogen to plasmin, the enzyme that breaks down clots.¹ When the clot is lysed, byproducts that act as potent inhibitors of further clot formation are also released into the blood stream.

Nurses’ role in screening

Rapid diagnosis and intervention for brain attack are essential because the current evidence-based recommendation calls for thrombolytic therapy to begin on carefully selected patients within three hours of the onset of symptoms.³ Nurses can play an important role in determining patients’ eligibility for t-PA. A rapid screening process can identify the appropriate candidates within this tight time frame. Primary eligibility requirements are —

• Symptoms clearly indicate an ischemic stroke.
• Treatment can be started within three hours of symptom onset.
• CT scan is negative for blood in the brain.
• No seizure occurred with the onset of symptoms.³

Advanced practice nurses are often an integral part of brain attack teams and the early evaluation of patients with potential stroke. Stroke nurse practitioners, in some centers, meet the ambulance in the ED, provide the initial evaluation, initiate the stroke response, and provide leadership.⁴

A number of pathways are available from the Brain Attack Coalition website http://www.stroke-site.org/pathways/pathways.html.

The National Institutes of Health Stroke Scale (NIHSS) is a valuable tool for obtaining serial measures of neurological deficits. This 42-point instrument, which quantifies neurological deficits in 11 categories, differentiates between ischemic strokes and transient ischemic attacks (TIAs).² For example, in tracking the progression of Stella’s speech difficulty, rapidly improved NIHSS scores could have suggested the presence of a TIA. Administration of t-PA is not recommended for patients with TIAs or isolated, mild neurological deficits, such as ataxia alone. The AHA Stroke Council also urges caution before administering t-PA to patients with severe stroke, defined as a score greater than 22 on the NIHSS.³

The time of symptom onset is a critical factor. Patients who wake from sleep with symptoms may not be eligible, since it would be impossible to tell when they began. Stella is eligible for t-PA because she came to the ED within half an hour of experiencing her symptoms. She also has right-sided weakness and speech difficulty — clear symptoms of a brain attack involving the left hemisphere. Finally, the CT scan did not show signs of a hemorrhagic stroke. Additional information regarding Stella makes her eligible for t-PA. She is not currently taking an oral anticoagulant, such as warfarin sodium (Coumadin) and has not received heparin in the past 48 hours. It is not the drugs themselves, but their effects that are important. Patients need to have a prothrombin time of less than 15 seconds, an international normalized ratio (INR) less than 1.7, a platelet count of greater than 100,000 per cubic millimeter, and a normal partial thromboplastin time (35 to 40 seconds).^2,3

Nurses should be alert for patients who may be ineligible for thrombolytic therapy. Patients cannot receive t-PA if they had —

• A major stroke or head trauma within the last three months
• Major surgery within the past two weeks
• Gastrointestinal (GI) or urinary tract hemorrhage within the last 21 days³
• Seizure at onset of stroke
• Uncontrolled hpertension at time of treatment (e.g., systolic >185 mmHg ir duastikuc >110 mmHg
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Recent MI

Nurses can also ensure informed consent. Patients and their families need to understand that, although t-PA is a relatively new treatment that could help them, it is not without risks. Bleeding in the brain or in other organs of the body, especially those in the abdomen, can occur.

Additional interventions in the ED

Nurses and other healthcare professionals in the emergency department (ED) should take the opportunity, as time permits while treating the initial event of a brain attack, to assess risk factors and initiate evidence-based secondary prevention measures. Three important categories of interventions include pharmacotherapy, behavior modification, and surgical intervention.

Pharmacotherapy

• Appropriate antithrombotic therapy needs to be initiated and maintained.⁵
• Statins should be considered to treat dyslipidemia and for additional protective benefits.⁵
• Antihypertensive therapy should be considered, including an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker plus a thiazide diuretic.⁵

Behavior modification

• Education about smoking cessation,6 exercise, diet, and the warning signs of another brain attack should be provided as often as possible.⁵

Surgical Intervention

• Patients need to be evaluated and referred, as appropriate to their condition, for 1) angioplasty and stenting or 2) carotid endarterectomy.⁵

Care during drug administration

The AHA Stroke Council recommends that patients who are to receive t-PA should be quickly transferred to an acute stroke unit or a critical care area. Treatment with t-PA, which must be administered IV, must be initiated within three hours of symptom onset. Cleared by the liver, the pharmacological half-life of t-PA is five to seven minutes. The recommended dose is 0.9 mg/kg - 10% administered as an initial bolus over one minute; infuse the remaining 90% over one hour with a maximum dosage of 90 mg.1 t-PA has a lower risk of triggering a systemic lytic state than other thrombolytic agents that are now used in patients with myocardial infarction. Although this agent is clot-specific, this complication can still occur when doses greater than 100 mg are given.

Nursing care includes frequent neurological assessment, as well as careful monitoring for potential complications during and following administration of the drug. Complications can be cardiovascular in nature, such as high or low blood pressure (BP) and hemorrhage. They most often include myocardial ischemia and dysrhythmias. Rapid detection and treatment of cardiac problems enhance patients’ chances of making a good recovery. A baseline 12-lead ECG is usually completed in the ED, followed by continuous cardiac monitoring for at least the first 24 hours of the hospital stay.^3,7

Careful monitoring and management of BP is another essential component of care during the first 24 hours after administration.^2,4 Elevated BP can cause bleeding in the brain, while low BP may worsen the ischemia and enlarge the area of infarcted brain tissue. One schedule for monitoring BP is —

• Every 15 minutes for the first two hours after starting the t-PA infusion, then
• Every 30 minutes for the next six hours, followed by
• Hourly assessment until 24 hours have lapsed from initiation of treatment.^3,7

The potential for hemorrhage is a major concern in the patient receiving t-PA. Major sites for bleeding are the brain and the genitourinary and GI tracts. Frequent neurological checks, performed hourly for the first 24 hours, can detect signs of bleeding in the brain. Nurses should check the size of the pupils, assess cranial nerves, and use the Glasgow Coma Scale (GCS) to monitor level of consciousness, along with the NIHSS to evaluate the extent of neurological deficits.²

Another potential complication to observe for is orolingual angioedema that affects about 5% of patients who receive t-PA. While typically mild and transient, anaphylaxis and airway compromise can occur. Patients on angoitensin-converting-enzyme (ACE) inhibitors appear to be at highest risk. Most centers treat with immediate administration of IV antihistamines and steroids.²

During the first 24 hours of t-PA therapy, nurses can minimize the risk of bleeding in organs by avoiding central venous access placement, arterial punctures, and the insertion of nasogastric tubes. The placement of an indwelling urinary catheter is also not recommended during the infusion of the medication and during the first 30 minutes following the administration.⁸

Management of bleeding complications

Patients need to receive care in a facility that is equipped to handle bleeding complications, if they occur. Any sign of intracranial bleeding, such as a significant change in pupil size GCS or NIHSS scores should prompt another CT on an emergent basis. For a life-threatening complication of intracranial, GI, or retroperitoneal bleeding —

• Stop the t-PA infusion.
• Draw blood specimens for coagulation tests.
• Request a surgical consultation if indicated
• Consider administering whole blood, cryoprecipitate, and/or platelets as in accordance with coagulation study results.

If bleeding is suspected, blood specimens for hematocrit, hemoglobin, partial thromboplastin and prothrombin time, INR, platelet count, and fibrinogen should be obtained.²

Current recommendations address t-PA administration and the critical first 24 hours. Following this period, patients are usually transferred to a general nursing unit. During the remainder of the hospital stay, nurses need to continue to be vigilant for potential bleeding. Neurological checks of pupil size, cranial nerves, level of consciousness with the GCS, and the motor strength of extremities should be done at least once a shift to detect delayed intracranial bleeding. Assess the abdomen at least every shift, and check bowel movements, urine, and emesis for occult blood.

Educate the patient

Patients and their families need to know that although t-PA is the most current treatment for ischemic stroke, it is not a miracle drug. A large clinical trial randomized 624 patients to receive a placebo or t-PA.¹ Patients were assessed at 24 hours and three months after receiving the drug. At 24 hours, patients had improved an average of four points on the NIHSS. At three months, the 312 patients who had received t-PA were at least 30% more likely to have minimal or no disability, compared to patients who received a placebo. Several assessment scales, including the NIHSS, were used at this time, and this treatment appears to improve long-term versus short-term outcomes.(See bibliography)

Patients and their families may ask about the ongoing controversy that surrounds t-PA: Is the high cost of the drug justified? The minimum wholesale cost of a course of treatment is about $2,000. With the addition of hospital and physician charges, actual costs to the patient can be much higher. Most health professionals who treated brain attack in the early days following t-PA approval felt that the expenditure was justified in that the initial cost was at least partially offset by the shorter hospital length of stay due to the greater likelihood of improved function. In August 2005, the thinking about costs changed when a new ruling by the U.S. Centers for Medicare and Medicaid Services was announced. Since October 1, 2005, the discrepancy between cost and reimbursement has been remedied and U.S. hospitals are receiving approximately $6000 more per patient with stroke when thrombolysis treatment is administered.⁹

Because patients who have had one brain attack are at risk of suffering another, prevention, started in the ED, is an important continuing goal during the subacute and chronic phases of care. Risk assessment and early intervention begun in the ED needs to be communicated and continue during the admission and medical work-up for a patient who has had a brain attack. Nurses need to make sure the following evidence-based interventions are addressed:

• Hypertension needs to be controlled.^10,11
• Blood pressure and lipids should be controlled in patients with diabetes.¹¹
• Elevated cholesterol levels need to be treated with lifestyle modifications, dietary guidelines, and medication with a focus on maintaining low-density lipoproteins (LDL), 100 mg/dl.^10,11
• Heavy drinkers (>5 drinks/day) should eliminate or reduce their intake of alcohol.¹¹
• Patients who are capable should engage in 30 minutes a day of moderate-intensity physical exercise.¹¹
• Weight reduction may be considered for all overweight ischemic stroke and TIA patients to maintain the goal of a BMI of between 18.5 to 24.9 kg/m2 and a waist circumference of 35 inches for women and 40 inches for men.¹¹
• Carotid endarterectomy (CEA) for severe (70%-99%) carotid artery stenosis.^10,11
• Anticoagulation for AF.^11,12
• Smoking cessation must be addressed.⁶
• Make sure the patient is discharged on appropriate antithrombotic therapy.¹³

Most patients receive some combination of antithrombolytic or antiplatelet-aggregating medications to prevent further clots from forming. Antithrombotic drugs interfere with clotting, and the antiplatelet drugs prevent platelets from adhering to damaged arteries and forming clots. Researchers are still trying to determine the best combination and dosage of these drugs.

Nurses need to initiate patient teaching aimed at reducing risks and preventing another brain attack. The mechanism of brain attack and the importance of early treatment for symptoms must be stressed with patients and their family members. A number of patient resources that may be of use in patient teaching are available at the Brain Attack coalition’s website< www.stroke-site.org/patnt_resources/patnt_resources.html>.

Other therapies

The FDA has approved four thrombolytic agents for general use in the U.S. — streptokinase (Streptase), urokinase (Abbokinase), anisoylated plasminogen streptokinase activator (APSAC), and t-PA.⁴ All four have approval for patient use following myocardial infarction, but only one, t-PA, currently has approval specifically for use in patients with brain attack. Several ongoing international clinical trials are investigating the use of these thrombolytic agents for stroke patients.

A new therapy, still in the experimental stage, involves delivering a thrombolytic agent directly through the intraarterial (IA) route. This has several advantages over IV administration, which include the ability to deliver the agent directly to the clot in the brain, reducing systemic exposure, gentle mechanical disruption of the clot with the catheter and wire, and visualization of the recanalization of the vessel. The major advantage is the longer time frame (six hours) for intervention compared to the three hour time frame allowed by the FDA for IV t-PA. Drugs used for IA thrombolysis or which are under investigation include t-PA, urokinase, and recombinant prourokinase (rpro-UK). Similar to IV t-PA administration, one disadvantage is the possibility of bleeding into the brain.¹⁴

Another new therapy is known as neuroprotective agents. The term neuroprotection is quite broad and refers to pharmacological and nonpharmacological treatments used to halt the sequence of events that are known to occur in ischemic brain injury. Neuroprotective drugs and treatments are mostly still in the clinical trial phase of development.¹⁴

The latest development in the care of patients with ischemic stroke is the clearance by the FDA of a device that can remove a clot from the brain. This device has approval for use in patients who fail or are not eligible for IV t-PA. The device is the MERCI Retriever made by Concentric Medical. The MERCI Retriever is a flexible microcatheter used to access and revascularize occluded vessels. Ongoing study of this device is needed because, in many of the patients studied so far, the clot was removed but the mortality rate was very high www.fda.gov/fdac/features/2005/205_ stroke.html.

Stay informed

The current challenge in brain attack is to deliver thrombolytic therapy to the patient within the window of opportunity of only three hours of symptom onset. To accomplish this, nurses must be informed about eligibility criteria, the method of administration, and care of the patient during and after administration of the drug. Current recommendations address the first 24 hours of care. As more is learned about using t-PA for brain attack, protocols are sure to expand to cover a longer timeframe.

This is an exciting time to be involved in the care of patients like Stella, who made a full recovery from her brain attack and was discharged with a plan for prevention of another stroke. As new developments rapidly occur and nurses are challenged to keep abreast, many ways are available for nurses to stay informed. One way is to read the list of ongoing clinical trials, which are published every February, June, and October in the American Heart Association’s publication, Stroke: A Journal of Cerebral Circulation <http://stroke.ahajournals.org/>. Nurse coordinators at stroke centers are also very involved in education, so watch for their informative programs. The American Association of Neuroscience Nursing’s publication: The Journal of Neuroscience Nursing <www.aann.org/journal/index.htm>, and the Stroke Council <www.americanheart.org/presenter.jhtml?identifier=1197> of the American Heart Association are other valuable resources.