Air Care Series: Acute Ischemic Stroke Updates

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CASES

AirCare 2 is dispatched to an outside hospital for transport of a 60-year-old-male with a history of atrial fibrillation, diabetes, and hypertension who presented with aphasia and right sided upper and lower extremity weakness and numbness 10 hours prior to arrival concerning for a left MCA occlusion. He is being transferred to UCMC for further CT perfusion and evaluation for thrombectomy…

INTRODUCTION

The term stroke has evolved over the past 400 years. In 1689 the term stroke was introduced by William Cole, replacing the term “apoplexy” to describe acute non-traumatic brain injuries. In the 1970s the World Health Organization defined stroke as "rapidly developing clinical signs of focal or global disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin". Annually, strokes kills over 140,000 Americans while more than 800,000 people in the United States have a stroke. 610,000 annual strokes are first time strokes costing the United States an estimated $34 billion each year. (1).

“Time is Brain”

Time to blood flow restoration is of the highest priority in patients suffering strokes, as we attempt to salvage viable cells, preventing an irreversible infarction. The disruption of blood flow can be secondary to an obstruction of a vessel (ischemic stroke) or damage to the blood vessel causing bleeding within the brain itself (hemorrhagic stroke). The majority of strokes are ischemic strokes with hemorrhagic strokes accounting for a smaller percentage of strokes. The scope of this paper will focus on acute ischemic strokes.

In 2019, Critical Care Transport Medicine (CCTM) providers are frequently dispatched for an encounter with a patient who has sustained a stroke. The hemodynamic stability of stroke patients can be profoundly different for each encounter as the pathophysiology of strokes varies vastly. CCTM teams may act in the same capacity of ground EMS crews, who screen patients for stroke like symptoms prior to arriving at a medical facility, when dispatched to a scene stroke. However, CCTM crews often have more information about the status of the patient’s stroke such as modern imaging and lab results. Among these advances are the intravenous administration of tissue plasminogen activator (tPA) for thrombolysis as well as endovascular approaches such as mechanical thrombectomy. While tPA should be available at most facilities, IR is a limited resource only available at comprehensive stroke centers. The optimization of pre-hospital care, a key aspect of the American Heart Association’s Stroke Survival Chain guidelines, has led to improved patient treatment and outcomes (2).

 INDICATIONS FOR TRANSPORT in Acute Ischemic Strokes

 In regard to stroke transport, research increased following the approval of tPA with original studies dating back to 1985 (3). Stroke patients require CCTM for transport to a tPA capable center, ICU level management and further neurointerventional therapies. Primary stroke centers were established in 2000 by the American Stroke Association and The Joint Commission designating centers with acute stroke teams, stroke units and integrated emergency response systems. However, a study by Albright et al., discovered that only 22.3% and 55.4% of Americans have access within 30 and 50 minutes, respectfully, of a primary stroke center. Populations such as the elderly patients and those in non-urban areas were also noted to have longer times between 9-1-1 activation and arrival to definitive therapy. The utilization of CCTM provides access to 26% and 79.3% of the population within 30 and 60 minutes, respectfully. (4).

 In evaluating the ability to get a patient to their destination where they can receive IV alteplase, helicopter transport was shown to be 3-4 times more likely to get their patients there faster compared to ambulance transport in a study of 32 stroke centers within Austria. This study showed that 70% of patients transported by helicopter arrived within 2 hours of stroke onset, well within the tPA window. (5). This falls in line with the most recent 2018 AHA Guidelines for ischemic stroke management that give quick transport of a patient with a stroke their highest recommendation level stating:

“On 9-1-1 activation, EMS dispatch and clinical personnel should prioritize the potential stroke case, minimize on-scene times, and transport the patient as quickly as possible to the most appropriate hospital. A recent US-based analysis of EMS response times found that median EMS response time (9-1-1 call to ED arrival) in 184 179 cases in which EMS provider impression was stroke was 36 minutes (interquartile range, 28.7–48.0 minutes). (20) On-scene time (median, 15 minutes) was the largest component of this time, and longer times were noted for patients 65 to 74 years of age, whites, and women and in nonurban areas. Dispatch designation of stroke was associated with minimally faster response times (36.0 versus 36.7 minutes; P<0.01). Notably, only 52% of cases were identified by dispatch as stroke. < 0.01). (6)”
— Powers et al. Stroke 2018

While rapid transport is of utmost importance, key important data points that need to be collected prior to transport include:

  • Last known normal (LKN)

  • Anti-coagulation status of the patient

  • Blood glucose level

  • Neurological deficits on exam

  • Transport the CT scan images (or ensure they are viewable remotely)

  • Medical Interventions started/completed

  • Consider bringing along witness or obtaining reliable contact information

 The 2018 AHA Guidelines for management of acute ischemic stroke (AIS) patients dedicated a portion of their recommendations to EMS and prehospital management. The treatment and management of ischemic strokes can be simplified to IV alteplase (tPA) administration, need for thrombectomy and management of blood pressure both before and after administration of IV alteplase.

CCTM plays an important part in the level I recommendation pertaining to rapid transport of patients who have sustained a stroke to the nearest facility with IV alteplase capabilities. Additionally, some patients have already received IV alteplase after a diagnosis of ischemic stroke but need a facility with neuroinvasive or neurosurgical capabilities. A goal of achieving door-to-needle (DTN) times within 60 minutes in ≥ 50% of patients with AIS is a Level I recommendation. However, a new recommendation is now a DTN times within 45 minutes for patients suffering from AIS. (6)

General en route Management of Acute Ischemic Strokes:

CCTM interventions for both scene stroke patients and the interhospital transfer of a stroke patient:

  • Manage the ABCs.

  • Support the airway and provide ventilation to those patients who have a decreased LOC or who have bulbar dysfunction compromising the airway.

  • Supplemental O2 (if needed) to maintain an oxygen saturation of at least 94%

  • Hypotension and hypovolemia should be addressed to maintain perfusion to organs (MAP >65)

  • Hypoglycemia (BG < 60 mg/dL) should be treated

  • Temperature >38 degrees Celcius should be identified and treated.

CCTM interventions specific for scene stroke patient:

Scene strokes are logistically challenging because you are acting as the primarily EMS crew and the info you gather will be critical to determining the initial course – you’ll beat family there and we must make crucial decisions in the first 10-15 minutes of ED arrival. 

  • Bring a witness with you if possible. If unable to bring a witness, determine the last known normal (LKN) time and obtain contact information for the witness.

  • Establish right-sided intravenous access.

  • Elevated BP in those who are eligible for IV alteplase should be carefully lowered so the systolic BP is <185 mmHg and the diastolic BP is <110 mmHg before the thrombolytic is administered.

    • Labetalol 10-20 mg IV over 1-2 min. (May repeat one time)

    • Nicardipine 5mg/h IV; can titrate up 2.5mg/h every 5-15min (max 15mg/h)

  • Give report to receiving facility and determine destination (CT scan vs. Emergency Department vs ICU)

CCTM interventions specific for the interhospital transfer of a stroke patient:

  • Confirm final destination (Emergency Department, CT Scanner, Interventional Radiology suite, or ICU)

  • For AIS patients status post tPA, BP should be maintained <180/105 mmHg for at least 24 hours after treatment

Upon arrival to a comprehensive stroke center most stable patients will be directed to the CT scanner for further vascular imaging followed by evaluation by the emergency provider. Prior to a patient receiving tPA, a blood glucose measurement and an EKG are recommended (6). If the patient is a candidate for mechanical thrombectomy this requires the patient to be at a comprehensive stroke center with rapid access to cerebral angiography, qualified neurointerventionalists and a periprocedural care team.

IV Alteplase:

IV Alteplase has been evaluated through many randomized trials showing clear benefit in acute ischemic stroke. When given within three hours 40% of alteplase-treated patients will be functionally independent compared with 32% of those allocated to the control group ( P < 0.0001) at final follow-up. (7)  Rapidity of treatment with IV alteplase remains of ultimate importance as 90-day outcomes are largely dependent on time from onset to treatment with the odds ratio of a favorable outcome decreasing from 2.81 (1.75–4.50) when treated within 90 minutes to 1.55 (1.12–2.15) for those treated from 91–180 minutes. (8) Recent trials show potential for the use of advanced imaging [diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR)] to select patients for alteplase treatment when exact time of onset is unknown. While typically not administered en route, with the exception of mobile stoke units, last known normal must be established and absolute contraindications reviewed prior to administration of IV alteplase.

Adverse Effects of IV Alteplase:

Intracranial Bleeding

Following administration of tPA, if the patient starts to develop a severe headache, acute hypertension, deteriorating neurological examination, nausea or vomiting a repeat emergent head CT scan prior to transporting that patient is indicated. The tPA infusion should be immediately discontinued prior to getting the CT scan if it is still infusing. An observational study using data from the AHA Get With The Guidelines-Stroke Registry observed 23,347 patients receiving tPA with a 4.6% rate of spontaneous intracranial hemorrhage leading to a 75% mortality in patients suffering this complication. (9)

If the patient is having intracranial hemorrhage following tPA administration

  • Measure BP and perform neurological assessments every 15 minutes within a 2-hour window of tPA administration.

  • Administer antihypertensive medications to maintain BP at or below 180/105 mmHg.

  • Tranexamic acid 1000 mg IV infused over 10 min can be given.

  • Continue supportive therapy including BP management, temperature and glucose control. (6)

Angioedema

While even rarer than spontaneous intracranial hemorrhage, angioedema can lead to potential life-threatening complications. A prospective cohort study with 1135 patients reported an incidence of 1.3%. (10) Endotracheal intubation may not be necessary if edema is limited to anterior tongue and lips. If the edema involves the larynx or oropharynx with rapid progression (within 30 minutes) then this will require airway protection via intubation.

Interventions:

  • Protect the airway

  • Awake fiberoptic intubation is optimal.

    • Nasal-tracheal intubation may be required but there is increased risk of epistaxis after tPA

    • Cricothyroidotomy is rarely needed and also problematic after IV alteplase.

  • Discontinue tPA infusion

  • Give IV methylprednisolone 125 mg

  • Give IV diphenhydramine 50 mg

  • For continuing worsening angioedema, give 0.3 mL subcutaneously of (1:1000 epinephrine) or by nebulizer 0.5 mL

Endovascular Thrombectomy:

IV alteplase alone has lower recanalization and poorer functional outcomes in cases of LVO compared with medium and small vessel occlusions. (11,12) Given these poor outcomes, multiple alternative treatments for LVOs have been explored. The MERCI trial, a prospective nonrandomized, multicenter trial, evaluated the first-generation endovascular thrombectomy device in patients who were not candidates for IV alteplase achieving recanalization in 46% of patients, a significant improvement compared to historical controls. (13) More recent studies evaluating the Solitaire Flow Restoration System showed reduced mortality (17 vs 38; P =0·02) and improved 90-day functional outcomes (58% vs 33%; P =0·02) when compared with MERCI. (14)

Between 2014 and 2018, 11 positive randomized controlled trials of new-generation endovascular thrombectomy devices were published consistently demonstrating improved functional outcomes at 90 days with a number needed to treat of 2.6. (15-25) In nine of these trials, treatment occurred within six hours of LKN. However, beyond six hours salvageable brain tissue may be present in a subset of patients, requiring DWI or CTP imaging to determine eligibility. In DAWN, endovascular thrombectomy was completed six to 24 hours from LKN in patients whose clinical exam were disproportionately severe in relation to the infarct volume on advanced imaging. (21) 49 percent in the endovascular thrombectomy arm of DAWN achieved functional independence compared to 13% in the control group (95% CI, 24 to 44; posterior probability of superiority, > 0.999), with no difference in ICH. (21) The DEFUSE-3 trial, patients with salvageable ischemic brain tissue on advanced imaging six to 16 hours from LKN underwent endovascular thrombectomy or best medical treatment. (20) 45 percent in the endovascular thrombectomy group achieved functional independence compared to 17% in the control group (P < 0.001) with decreased 90-day mortality (14% vs. 26%; P=0.05). (20) These studies indicate that patients with symptoms of LVO should be considered for potential thrombectomy up to 24 hours out from their LKN and transported to a comprehensive stroke center by CCTM when outside the tPA window.

For ground transport, there are decisions rules, such as C-STAT, to help determine the final destination. According to the Southwest Ohio Protocols ground transport should go directly to closest Joint Commission Certified Comprehensive (CSC) or Thrombectomy Capable Stroke Center (TSC) if: (1) C-STAT/LVO tool is positive, (2) Last known normal is less than 24 hours and (3) The CSC or TSC is no more than 15 minutes further away than the closest Primary Stroke Center/Acute Stroke Ready Hospital. (26)

Summary

  • The diagnosis of a stroke is time dependent

  • Safe, rapid transport is important to getting the patient to definitive care

  • The majority of strokes are ischemic strokes

  • IV alteplase is given for ischemic strokes within a window within 4.5 hours for select patients

  • Do a primary assessment and intervene to optimize patients’ ABCs

  • Maintain BP <180/105 and O2 above 94% status post IV alteplase

  • tPa administration can lead to intracranial hemorrhage and angioedema

 AUTHORED BY Edmond Irankunda, MD and ADAM GOTTULA, MD

Dr. Irankunda is a second-year Emergency Medicine resident at the University of Cincinnati with an interest in EMS

Dr. Gottula is a third-year Emergency Medicine resident at the University of Cincinnati with an interest in critical care and HEMS

FACULTY EDITOR Charles Kircher, MD

Charles Kircher, MD is an attending in the Department of Emergency Medicine, Neuroscience ICU and Stroke Team Member at the University of Cincinnati

References:

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  4. Albright K, Branas C, Meyer B, et al. Acute Cerebrovascular Care in Emergency Stroke Systems. Arch Neurol. 2010;67(10):1210–1218. 

  5. Reiner-Deitemyer V, Teuschl Y, Matz K, et al. Helicopter transport of stroke patients and its influence on thrombolysis rates: Data from the Austrian stroke unit registry. Stroke. 2011;42:1295–1300.

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  17. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. The New England journal of medicine. 2015;372(11):1019-1030.

  18. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. The New England journal of medicine. 2015;372(24):2296-2306.

  19. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. The New England journal of medicine. 2015;372(24):2285-2295.

  20. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378(8):708-718.

  21. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378(1):11-21.

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  23. Mocco J, Zaidat OO, von Kummer R, et al. Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone. Stroke. 2016;47(9):2331-2338.

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  25. Khoury NN, Darsaut TE, Ghostine J, et al. Erratum to &quot;Endovascular thrombectomy and medical therapy versus medical therapy alone in acute stroke: A randomized care trial&quot;[J. Neuroradiol. 44 (2017) 198-202]. J Neuroradiol. 2017;44(5):351.

  26. Curry, Bently W. ACADEMY OF MEDICINE OF CINCINNATI PROTOCOLS FOR SOUTHWEST. http://www.hamiltoncountyfirechiefs.com/uploads/2/9/3/3/29330831/2018_ems_protocols_final_v3.1.pdf.