I. Purpose of this chapter

This chapter is written for the physician who may encounter stroke patients at a non-stroke-center. It is not intended to be a comprehensive guide to managing a stroke patient, rather provide the critical points to get a patient with a suspected acute ischemic stroke the best possible care quickly, even if that means transferring them to a higher-level facility.

While hemorrhagic strokes are an important subset of stroke (15%), the majority of these patients should be managed emergently by a neuro-critical care or neurosurgical specialist and thus they are out of the scope of this chapter.

II. Recognition of Stroke and the Stroke Mimickers

A. NIH Stroke Scale (NIHSS)

  • There is no substitute for a neuro exam. One must familiarize themselves with the NIHSS and be well practiced (certificate available for free online) if there is any chance you will encounter acute stroke patients.

  • Scored from 0 to 42 points, the NIHSS is essentially an abridged neuro exam that can be done in under 5 min. The higher the score, the bigger the stroke.

  • Scores 8 or greater are more worrisome for large vessel occlusions and should be taken with vigilance for transfer to a higher-level stroke center that has neuro-interventional capabilities. See below.

B. Acute Focality: Sudden Onset, Unilateral Symptoms

  • In general, the key to recognition of a stroke is acute focality; Sudden onset unilateral symptoms:

    Facial droop

    Unilateral weakness (hemiparesis)

    Unilateral limb ataxia (dysmetria/dyscoordination)

    Speech difficulty (dysarthria or aphasia)

    Unilateral numbness

    Visual field cuts or forced eye deviation towards one side.

  • Any one or several of these symptoms should raise your suspicion for stroke. If you have a patient with generalized weakness, inattention or low level of consciousness without focality, it is rarely an acute ischemic stroke (though large, particularly midline intracranial hemorrhages can do this). If your CT scan is negative for bleed, look elsewhere.

  • Note: aphasia (inability to express and/or comprehend language) in an otherwise awake and attentive person is considered focal because something is impacting the language center while sparring many other areas of the brain. Someone with only slurred speech (dysarthria) and with lower level of consciousness without focality, likely has a process that is affecting the entire brain, which points away from stroke.

  • Note of caution: the NIHSS is weighted towards anterior circulation strokes, i.e. middle cerebral artery (MCA) strokes. Occasionally missed are the patients who present with posterior circulation signs/symptoms such as:

    Vertigo with unremitting or direction changing nystagmus

    Balance Problems (Gait Ataxia)

    Truncal or Limb Ataxia

    Nausea and Vomiting – (in combination with other focal signs)

    Be sure to be vigilant in these cases particularly if the aforementioned symptoms occurred suddenly.

C. Stroke Mimickers

  • While there are many stroke mimickers only the following are common and can be truly focal:

    Seizures (partial onset)

    Conversion Disorder

    Migraine (complex)

    Bell’s Palsy

  • Other mimickers like encephalopathy, sepsis, and hypoglycemia in general will not cause focal symptoms unless there is already an underlying brain or vascular lesion.

  • Rest assured however, because even if you do give IV tPA to a stroke mimicker who otherwise meets criteria for tPA, the risk of bleeding complications in those patients approaches 0%.

III. Acute Management – * Always Consult Neurology If Available*

  • Stabilize hemodynamically compromised patients

  • Rapidly correct hypoxia and hypoglycemia as these cloud the neurologic picture

  • Labs: CBC, CMP, PT/INR

  • Obtain EKG/ CXR (but do not delay potential treatment)

  • Stat head CT and if available, CT angiogram (CTA) of the head and neck vessels

    If head CT is positive for acute blood, mass, or new large stroke, get neurological/neurosurgical consultation.

    If the CTA is positive for large vessel occlusion, continue with tPA eligibility screening, and obtain emergent neurological consultation for transfer and possible mechanical thrombectomy. Do NOT delay tPA to patients who are eligible.

IV. Standard of Care Treatments: IV Tissue Plasminogen Activator (tPA) and Mechanical Thrombectomy

A. Speed Matters

  • Every minute of stroke, two million brain cells die on average. Thus, the key to effective stroke treatment is speed.

  • Despite much fear and dogma, IV tPa is a safe and efficacious treatment for acute ischemic stroke. The earlier it is given, the better the neurologic outcome and lower risk of bleeding complication. In total, if given < 4.5 hours, patients have 30-40% chance of having almost a full neurologic recovery vs a 6% chance of bleeding complication, 1% risk of death.

  • Further, if tPA is given in the first 90 min from stroke onset, a patient has a 2.6x likelihood of having said good outcome vs 1.3x likelihood, if it is given at 4.5 hours.

B. Size Matters

  • The larger the vessel that is occluded, the lower chance it will be opened by tPA alone.

    For M2 branch, tpa has a 44% recanalization rate,

    For M1 branch, tpa has a 30% recanalization rate,

    Terminal ICA, tPA has a 6% recanalization rate.

  • Mechanical thrombectomy with stent retriever devices have a 70-90% recanalization rate.

    Hence, eligible stroke patients with large vessel occlusions should have mechanical thrombectomy within 7 hours of onset of symptoms.

    Pts who receive this therapy have > 2x chance of having near complete neurologic recovery compared to those who do not.

    Approximately 30-55% of patients who get IV thrombectomy have a near full neurological recovery.

C. tPA Eligibility – Absolute Criteria Only

  • Age > 18 (No upper limit)

  • Suspected Ischemic Stroke

  • Neurologic Change from “Last Known Normal” <4.5 hours

    For tPA, stroke onset (last known normal time) must have occurred < 4.5 hours from administration per the American Heart Association. Note: the FDA only approved it for < 3 hours because they did not include European trial data when making this recommendation.

    “Last Known Normal” is the last time the patient was seen well. If the patient woke up at 7 am with symptoms- that is NOT their last known normal; usually, it is the time they went to bed.

  • CT Head- “The Cleaner, The Better”

    A normal CT implies there has not been enough ischemic damage done to be seen yet and the bleeding risk with tPA is lower. There is often radiologic delay of up to 6-12 hours before ischemic change can be detected on CT, so it is common (and reassuring) for a patient to have a high stroke scale with a normal CT.

    CT must be negative for:

    Blood of any age, in any space (i.e. epidural/subdural/subarachnoid/ intraparenchymal)

    Masses: tumor, metastasis, abscess, AV malformation

    Recent Stroke, or early ischemic change

    Early ischemic changes seen on CT indicate that the infarct is already far along and they are higher risk for bleeding complications with less benefit.

    If there is a stroke > 1/3 of cerebral hemisphere, you should get urgent neurological/surgical consultation as they are high risk for herniation when swelling and ICP peaks (usually at 72 hours).

  • Blood Pressure < 185/110 before administration, then < 180/105 for maintenance

  • No bleeding diathesis: Platelets > 100,000, INR <1.7

  • No Novel Anti-coagulant usage < 48 hours

  • No history of major head trauma, stroke or neurosurgery < 90 days

  • No Active internal bleeding

  • No Suspected endocarditis

D. Administration of IV tPA

1. Blood Pressure Management

It is critical to be aggressive with BP management, given much of the bleeding complications from tPA stem from failure in this step.

  • Target <185/110 for initiation and then <180/105 thereafter. *Avoid SBP falling < 140 for most patients

    PRN labetalol 10-20 mg IV or hydralazine 10-20 mg IV initially because they are usually readily available

    May repeat Labetalol Doses q 10 min until a maximum of 300 mg.

    Continuous titratable drips (labetalol or nicardipine) are actually preferable because they can offer tight control without blood pressure swings.

    Initiate Labetalol drip rate at 2-8 mg/min OR

    Initate Nicardapine drip rate at 5 mg/hr and titrated by 2.5 mg/hr to desired range

    Keep in mind, the brain’s auto-regulation vasculature is usually significantly impaired during stroke; meaning that big changes in blood pressure can often be more detrimental than an extreme high or low.

  • Monitoring: should be q15 minutes for 2 hours followed by q1 hour for the first 24 hours after tPA administration.

2. tPA Dose

  • 0.9 mg/kg not to exceed 90 mg, 10% as bolus over 1 minute

  • Remaining 90% as constant infusion over 1 hour (use infusion pump and discard volume not be used before infusing the tPA)

E. Mechanical Thrombectomy Eligibility

Since 2016, catheter-guided neuro thrombectomy using stent retriever devices such as the Trevo or Solitaire has become the standard of care for select patients with large vessel intracranial occlusion. Several randomized-multi-center-blinded-rater trials have shown that this technique dramatically reduces morbidity and even mortality in these patients.

1. Stroke Scales Scores of 8 should start to heighten suspicion for large vessel occlusion. Early neurologic consultation should always be obtained in these situations.

2. Both patients who have already received IV tPA AND patients that are out of window (or ruled out) for tPA are eligible for thrombectomy IF:

  • CTA confirms large vessel occlusion which corresponds with clinical data:

    MCA: M1 or M2 Branches

    ACA: A1 or A2

    Basilar

    Distal Internal Carotid

  • Timing: Groin puncture must be feasible <7 hours from stroke onset.

  • ASPECT score obtained from head CT should be 6 or greater

    ASPECT score approximates the early ischemic change that can be seen on CT by looking at 10 specific areas of the MCA territory. A normal CT starts at 10 points (10 normal regions), lower scores imply larger infarction core as more areas are impacted, and thus higher risk for intervention complications.

    Note: the ASPECT score is not an absolute criterion as it really only offers meaningful information for MCA territory strokes, which are in fact the majority of these cases.

3. BP should be tightly managed for patients being prepared for thrombectomy.

  • IV drips as described above are advisable in both tPA patients and non-tPa patients:

    Target range of 160-180 SBP.

4. Further Management of these patients are out of the scope of this chapter.

V. Post- tPA Management within 24 hours

A. Admit to an ICU bed, or minimally, telemetry bed with the following guidelines: keep the brain’s environment as nourishing and healthy as possible to optimize neurological recovery. Every minor parameter by itself may seem unimportant or impotent, but collectively, they make a powerful difference towards recovery.

1. Blood Pressure Management: every 15 min for 2 hrs, then every 30 min for 6 hrs, then every hour for 18 hrs, then q 4 hrs.

  • Target SBP 160-180- see drug options in prior section.

2. Vitals and Neurochecks: q 15 min × 2 hrs, then q 30 min × 6 hrs, then q 60 min × 24 hrs.

3. Neurological Changes

  • Any change in the neuro exam, worsening headache, lower level of consciousness, or increase of the NIHSS should raise suspicion of intracranial hemorrhage (ICH).

  • Particularly worrisome are NIHSS scores that increase 4 or more points.

  • If there is acute neurologic change:

    Immediately stop tPA if still running

    Obtain stat non contrast head CT

    Draw blood for PT, PTT, platelet count and fibrinogen

    If ICH is revealed by brain imaging:

    10 units of cryoprecipitate to increase the levels of fibrinogen and factor VIII

    Give 6-8 units of platelets

    Consult neurosurgery

4. Temperature Management:

  • It is important to keep neurologically injured patient’s temperature normal or slightly low.

  • Higher temperature is an independent marker for worse outcomes in stroke, including death in the first 30 days.

  • Higher temperature increases cerebral metabolic demand exponentially; in a stroke patient that inherently has supply problem (occluded blood vessels), this is quite detrimental.

  • For Temperatures > 37.5 (target 36-37 C)

    Use PRN Tylenol 500mg q 6 hours, then if need be,

    Cooling Blankets, I.e. arctic sun, blanketrol or comparable unit

5. Glucose Management:

  • Should be tightly controlled with weight based insulin regimens. Poor control is also associated with worse neurologic outcomes and longer hospital stays.

  • Recommend 0.4U/kg insulin, particularly for patients who present with glucose >200.

    50% long acting insulin at night,

    Then, divide the remaining 50% into three prandial short acting insulin doses.

    Always have correctional sliding scale insulin available

6. Evaluate for Angioedema q 20 min × 4 starting with tPA infusion. Patients on ACE inhibitors are at greatest risk. This can be quite dangerous and should be treated promptly and aggressively.

  • If angioedema is suspected immediately:

    Early discontinuation of tPA infusion (if still running)

    Benadryl 50 mg IV AND

    IV Ranitidine 50 mg Famotidine 20 mg

    If continues to enlarge, give Solumedrol 80-100 mg IV

    If any further increase in angioedema: Epinephrine 0.1% 0.3 mL SC or by nebulizer 0.5 mL and call ENT or Anesthesia for further airway management.

7. Head of bed does NOT have to be flat, this is now considered optional. May want to avoid flat beds in select patients, i.e. CHF, pneumonia or aspiration risk. If there is a high grade stenosis, one may prefer a flat bed, particularly if they are positionally symptomatic.

8. Avoid anticoagulants or antiplatelet agents for 24 hours. SCDs should be used instead.

9. Avoid inserting indwelling bladder catheter, NG tube or other invasive procedures for > 30 minutes after tPA administration, if possible. Ideally should be completed before starting.

10. Physical Therapy, Speech Therapy, Occupational therapy evaluations

  • NPO until cleared by speech or bedside swallow test. See below.

11. Avoid venipuncture of non-compressible sites for the first 24 hours if at possible. If you must do a central line, avoid subclavian. PICC would or Internal Jugular would be preferable.

12. Order a CT for 24 hours post tPA

B. After 24 hours in ICU

  • Obtain routine 24 hour non-contrast CT to evaluate for hemorrhage.

  • If CT negative:

    Start antiplatelet regimen if indicated (often dual anti platelet therapy ASA/clopidogrel for 90 days, then monotherapy thereafter – if they will not require anticoagulation).

    Start chemical DVT ppx: low dose heparin/ Enoxaparin.

    If patient was on anticoagulation previously or an indication for anticoagulation discovered already, initiate it.

  • Begin to gradually bring BP down by 10-20% per day until in acceptable range. Start PO BP medications early.

  • Start Statin medication if not already on.

  • Daily PT/OT/Speech evaluation and treatment as recommended.

  • May require long term feeding source (i.e. PEG tube) if they fail swallow studies – early cooperation with speech/nutrition always recommended.

  • Social work and case management teams should initiate evaluation for placement.

C. Establishing Diagnosis and Etiology of Stroke- What Tests Should Be Ordered?

By this stage in the admission, the acuity of the patient should be lower (hopefully) and you should be trying to elucidate the cause of the stroke. The diagnostic approach should include evaluation of the blood, brain, vessels, and heart. Stroke etiology is typically categorized by the:

  • TOAST criteria:

    Large Vessel (i.e. Carotid or MCA stenosis, typically from atherosclerosis or dissection)

    Small Vessel (i.e. lacunar infarcts and patients with multiple risk factors, i.e. smokers, HTN, DM, HLD— on MRI described as “chronic white matter changes”)

    Cardioembolic/Aortoembolic (i.e. Afib, CHF, or aortic plaques)

    Other (hypercoaguabilities, Sickle Cell, polycythemia, malignancy)

    Cryptogenic or more than one cause

  • Evaluation of the Blood

    Labs should be obtained for general management as well as to elucidate patients risk factors:

    CBC, CMP, PT/INR

    Fasting Lipid Panel

    A1c

    Trend Troponins PRN

    If the patient is young or otherwise healthy should consider hypercoaguable and rheumatologic panels.

    If there is concern for malignancy causing an hypercoagulability, consider CT chest abdomen pelvis with contrast

  • Evaluation of the Heart

    Tele-monitoring to evaluate for arrhythmias such as A-fib

    Transthoracic 2d echocardiogram to evaluate for thrombus and overall functionality of the heart i.e. low EF or wall motion abnormalities that increase risk for thrombus.

    Note: if high suspicion for cardioembolic source, get transesophogeal echocardiogram to better visualize left atrium and appendage.

  • Evaluation of the Blood Vessels: Aorta, Carotids, Vertbrals, and the Circle of Willis.

    If a CTA of head and neck was already obtained, you can skip this step. Otherwise head and neck vessel imaging recommended.

    MRA of head and neck if available (with contrast if possible).

    There are advantages to either CTA or MRA, depending on the facility and the patient. However, both modalities are acceptable and offer the advantage of being able to evaluate the aortic arch for disease (i.e. atheroma).

    Carotid Doppler’s are good additional or primary study, particularly if there is concern for carotid stenosis and you want corroborating study to calculate degree.

    Transcranial Doppler’s can be helpful for evaluating degree intracranial stenosis and for emboli detection if a bubble study is completed.

  • Evaluation of the Brain

    MRI brain, non-contrast – in addition to confirming diagnosis, giving clues to the etiology, it also allows the neurologist following the patient in the future to have a full baseline picture of the patient’s brain in case there are future changes.

  • What if the etiology cryptogenic?

    Consider long term cardiac monitoring such as an implantable loop recorder (Linq device), which can increase detection rate of A-fib from 3% to 30% over 3 years.

    Consider Paradoxical sources, i.e. Large PFO and DVT.

VI. Common Pitfalls

A. “Permissive Hypertension” Confusion

  • Unlike the “permissive hypertension” that is used in stroke patients who did not get an acute intervention, if the patient received tPA, they MUST have blood pressure aggressively controlled.

  • Permissive hypertension in a stroke patient who did not receive tPA should be done for 24 hours up to 220/110.

  • After 24 hours, BP should be gradually reduced by 10-20% per day until in an acceptable range.

B. There is NO UPPER AGE LIMIT for giving tPA- do not it delay if indicated.

C. “ Clear the Vessels”

  • In all patients, BP should be carefully managed. Only after obtaining vessel imaging that “clears” them from high grade stenosis, should your target SBP be normotensive.

  • i.e. if you have a high grade stenosis and drop pressures quickly you can cause worsening stroke symptoms, or new infarctions.

  • If the patient is getting tPA, the goal is to drop them to a target 160-180 SBP, not do to make them normotensive! In non-tPA patients, gradual lowering is recommended after 24 hours.

D. Restart Antiplatelets and chemical DVT ppx at 24 hours. This is commonly forgotten and can put stroke patients at high risk for thrombotic / embolic adverse events.

E. Early Physical Therapy, Occupational Therapy, Speech Therapy and Nutrition services are often overlooked but are critical to the patient’s recovery and important factors that impact length of stay.

VII. Management of Stroke with Medical Co-Morbidities.

A. Renal Insufficiency.

  • Take Consideration when ordering contrast studies and dosing of really cleared medications, i.e. levetiracetam (Keppra) or DOACs.

  • Beware of uremic encephalopathy worsening stroke symptoms; if the patient has an unexplained change in neuro exam, consider metabolic panel early.

B. Hepatic Insufficiency.

  • Take consideration when dosing medications, i.e. warfarin and valproic acid.

  • As with renal patients, beware of metabolic encephalopathy worsening stroke symptoms.

C. Systolic and Diastolic Heart Failure.

  • If having to use drips to control BP, then will need to watch for volume overload.

  • Make sure to keep head of bed elevated to avoid respiratory distress in such patients.

D. Coronary Artery Disease or Peripheral Vascular Disease.

  • No change in standard management but can often give clues as to the etiology.

E. Diabetes or other Endocrine issues.

  • No change in standard management.

F. Malignancy.

  • No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

  • Be careful with HAART medications interactions, particularly with warfarin and seizure medications.

H. Primary Lung Disease (COPD, Asthma, ILD).

  • No change in standard management.

I. Gastrointestinal or Nutrition Issues.

  • No change in standard management.

J. Hematologic or Coagulation Issues.

  • May have precluded patient receiving tPA in the first place.

K. Dementia or Psychiatric Illness/Treatment.

  • Should have higher vigilance for ICU delirium; these patients will be more susceptible to confusion from environmental changes. Make every effort to orient these patients, keep lights on in the day, lights off at night, and ensure patient can sleep through the night when possible (ie downgrade patient as soon as possible to avoid frequent nighttime awakenings). Use neuroleptics sparingly.

VIII. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Emphasizing that the received tPA is very important. The unusual care orders should be highlighted:

  • Yes, you really do want q 1 hour blood pressure and neuro checks for the first 24 hours.

  • Spell out the need to keep BP <180/105, using the protocol for prn’s and drips as described above.

  • Remind them no arterial sticks or venous sticks at non-compressible sites.

B. Anticipated Length of Stay.

Barring complication, receiving IV tPA should only add one day to the routine ischemic stroke admission. Additionally, if the tPA was effective, it may dramatically shorten the admission if the patient is able to avoid rehab or long-term facility placement.

C. When is the Patient Ready for Discharge?

  • After the first 24 hours, the patient can be returned to usual care for acute ischemic strokes, including diagnostic work up as described above.

D. Arranging for Clinic Follow-up

  • When should clinic follow up be arranged and with whom?

    Follow-up should be with neurology, preferably in a stroke clinic within 6-8 weeks.

    Warfarin/Coumadin clinic, if need be and if a DOAC is not chosen for anticoagulation.

    Cardiology, if implantable heart monitor being used.

  • What tests should be conducted prior to discharge to enable best clinic first visit.

    Nothing Specific

E. What tests should be ordered as an outpatient prior to the clinic visit?

  • Should be monitoring risk factors such as: A1c, Lipids, BP, INR if on warfarin.

  • Follow up head imaging may be necessary if there was bleed during admission and need to decide on whether to initiate AC.

F. Placement Considerations

Varies widely depending on neurologic outcome. Ranges from baseline/home, home with outpatient therapy, home with home therapy, inpatient rehab, SNF, nursing home, etc.

G. Prognosis and Patient Counseling for those who receive tPA.

Prognosis is good for post tPA stroke patients, if BP is controlled (per original NINDS trial, tPA gives 30% chance of little/no residual deficit at 3 months post-stroke but carries risk of 6% of major hemorrhage, 1% risk of death – remember that much of the risk hinges on BP control.

IX. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation with regards to tPA patients.

JCAHO indicators surround tPA being administered to appropriate candidates and to portions of their care relevant to general acute ischemic stroke care and not specific to post-tPA management.

B. Depending on the stroke designation of the Hospital (primary, comprehensive center etc.), there are different metrics used. Appropriate prophylaxis, secondary stroke prevention strategies (i.e. timely anti-platelet medications), early speech, PT, OT, and case management services are all among the most common quality measures used.

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