Acute Stroke
Clinical Snapshot
Acute ischemic stroke is a sudden focal neurologic deficit caused by occlusion of a cerebral artery, accounting for the large majority of all strokes; the remainder are hemorrhagic (intracerebral or subarachnoid hemorrhage). Once a vessel occludes, tissue in the ischemic core dies quickly, while a surrounding rim of at-risk but still-salvageable tissue — the ischemic penumbra — survives only until blood flow is restored. The guiding principle of hyperacute stroke care is therefore time is brain: every minute of delay to reperfusion narrows the chance of a good functional outcome. This chapter covers the hyperacute, emergency-department phase of ischemic stroke — thrombolysis, mechanical thrombectomy, and the acute-phase supportive-care decisions (blood pressure, glucose, temperature, and antithrombotic timing) that follow reperfusion therapy — and is distinct from long-term secondary-prevention pharmacotherapy. Hemorrhagic stroke is addressed only briefly toward the end of this chapter, since its pharmacotherapy is largely reversal-agent-focused rather than a parallel reperfusion pathway.[1]
Recognize the Condition
F.A.S.T. — the public and first-responder warning-sign check
| Sign | What to check |
|---|---|
| Face | Ask the person to smile — look for one side drooping. |
| Arms | Ask the person to raise both arms — look for one arm drifting down. |
| Speech | Ask the person to repeat a simple sentence — listen for slurred or jumbled speech. |
| Time | If any sign is present, note the time and call 911 immediately — do not wait to see whether symptoms resolve. |
Presentation by vascular territory
Anterior circulation (carotid, MCA, ACA)
Contralateral hemiparesis and/or hemisensory loss (face and arm more than leg with MCA involvement, leg more than arm with ACA involvement), aphasia (dominant hemisphere) or neglect/anosognosia (non-dominant hemisphere), and homonymous hemianopia. This is the territory responsible for the large-vessel occlusions most amenable to endovascular thrombectomy.
Posterior circulation (vertebrobasilar, including basilar artery occlusion)
Vertigo, diplopia, dysarthria, ataxia, crossed sensorimotor signs (cranial nerve findings on one side with limb findings on the other), and — with basilar artery occlusion specifically — a declining level of consciousness or a locked-in state. Posterior circulation stroke is more easily missed than anterior circulation stroke because the presentation is less classically focal; keep a high index of suspicion for sudden vertigo accompanied by any other neurologic symptom.
Lacunar (small-vessel)
A limited set of recognizable pure syndromes — pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, and dysarthria-clumsy hand syndrome — without cortical signs (no aphasia, neglect, or visual field cut). Caused by occlusion of a single small penetrating artery, classically in the setting of chronic hypertension or diabetes.
Transient ischemic attack (TIA)
A TIA produces stroke-like symptoms that fully resolve without infarction on imaging. A TIA is not a benign event — it substantially raises the risk of a disabling stroke in the near term, most steeply in the first days afterward. Manage a suspected TIA with the same urgency as an evolving stroke: same-day assessment, same-day imaging, and same-day initiation of secondary prevention, since the window to prevent a disabling stroke is narrow.[1]
Risk Factors
- Hypertension — the single most important modifiable risk factor for stroke.
- Atrial fibrillation or another cardioembolic source (recent MI with LV thrombus, valvular disease, cardiomyopathy).
- Diabetes mellitus.
- Dyslipidemia.
- Current smoking.
- Excessive alcohol intake.
- High body mass index and low physical activity.
- Known vascular disease — coronary artery disease, peripheral arterial disease, prior MI, heart failure, renal vascular disease.
- Prior stroke or TIA.
- Carotid, vertebral, or basilar artery stenosis.
- Migraine with aura.
- Obstructive sleep apnea.
- Family history of premature vascular disease or a known hemostatic/thrombophilic disorder.
- Illicit stimulant use (cocaine, amphetamines) — can precipitate stroke through vasospasm, hypertension, or cardioembolism, including in young patients without traditional risk factors.
Red Flags & Refer
Any suspected acute stroke is itself the red flag — activate the institution's stroke protocol immediately (STAT non-contrast CT, STAT stroke-team page) rather than waiting for a full history; the following need additional, specific escalation on top of standard hyperacute management.
- Suspected large-vessel occlusion (severe hemiparesis, gaze deviation, aphasia, or neglect) — route directly to, or immediately transfer to, a centre capable of endovascular thrombectomy; do not delay transfer to wait for a full thrombolysis eligibility work-up to finish first.
- Suspected basilar artery occlusion (rapidly declining level of consciousness, crossed signs, quadriparesis) — this carries very high mortality if missed and needs emergency imaging and reperfusion consideration regardless of the usual anterior-circulation time cutoffs.
- Neurologic deterioration, new severe headache, or new nausea/vomiting during or after thrombolytic infusion — stop the infusion immediately, obtain an emergency CT head, and treat as hemorrhagic transformation until proven otherwise.
- Signs of orolingual angioedema after thrombolysis (tongue or lip swelling, stridor) in a patient taking an ACE inhibitor — this can obstruct the airway rapidly and needs immediate airway assessment plus IV corticosteroid and antihistamine treatment.
- Declining consciousness, a new fixed and dilated pupil, or worsening exam roughly 1 to 4 days after a large middle cerebral artery territory infarct — suggests malignant cerebral edema with mass effect and needs emergent imaging, osmotic therapy, and neurosurgical consultation.
- Sudden, severe (thunderclap) headache with or without a decreased level of consciousness — treat as suspected subarachnoid hemorrhage and refer immediately to a neurosurgical centre.
- Any acute hemorrhage identified on the initial CT — this changes the entire management pathway; ischemic-stroke reperfusion therapy is absolutely contraindicated.
Assessment & Diagnosis
Stroke mimics — screen for these before committing to a stroke work-up
| Mimic | Distinguishing feature |
|---|---|
| Hypoglycemia | Check point-of-care glucose immediately in every patient with a focal deficit — symptoms resolve promptly once glucose is corrected. |
| Todd paralysis (post-ictal) | A preceding witnessed or suspected seizure; focal weakness resolves gradually over hours; look for tongue biting or incontinence. |
| Subdural hematoma | History of trauma, even minor or weeks prior, especially in an older or anticoagulated patient; onset is often more gradual than a stroke. |
| Brain abscess or other CNS infection | Fever, subacute progression, immunocompromise, or a recent dental, sinus, or ear infection. |
| Herpes simplex encephalitis | Fever, behavior or personality change, seizures, subacute progression over days. |
| Brain tumor (primary or metastatic) | Gradual or progressive course, headache worse in the morning or with Valsalva, papilledema. |
| Multiple sclerosis | A younger patient, prior neurologic episodes separated in time and CNS location, subacute onset over days. |
| Migraine with aura | Prior similar episodes; the aura typically spreads or evolves over minutes and then resolves, with headache following the neurologic symptoms. |
| Conversion (functional neurologic symptom) disorder | Inconsistent findings on exam (give-way weakness, non-anatomic sensory loss); a genuine diagnosis of exclusion — never delay the stroke work-up to make it. |
History
- Time last known well, time of symptom onset, and whether symptoms were first noted on waking from sleep.
- Symptoms at onset and whether they have worsened or improved since.
- Medications — especially the time of the last dose of any anticoagulant or antiplatelet drug, and any anticonvulsant, diabetes medication, chemotherapy agent, or steroid that might point to an alternative diagnosis.
- Antecedent trauma, illness, or a previous neurovascular event.
- Vascular comorbidity (angina, MI, heart failure, peripheral or renal vascular disease) or atrial fibrillation.
- Vascular risk factors (see Risk Factors).
- Pre-stroke cognitive and functional status, place of residence, occupation, and social supports — these shape both treatment decisions and disposition planning.
Physical examination
- Rapid evaluation of airway, breathing, and circulation; obtain vital signs including blood pressure.
- Localize the lesion and grade stroke severity using the NIH Stroke Scale (NIHSS — see below).
- Assess for comorbid conditions and a possible underlying cause.
Emergency laboratory and imaging
- CBC, INR, PTT, albumin, electrolytes, glucose (to exclude hypoglycemia as a mimic), HbA1c, urea, creatinine, troponin, liver function tests, lipid profile, and TSH.
- Immediate neurovascular imaging to confirm the diagnosis and plan treatment — noncontrast CT head plus CT angiography (CTA) of the head and neck is the preferred hyperacute imaging strategy. Noncontrast CT head demonstrates changes of ischemic stroke, hemorrhagic stroke, or a mimic such as tumor. CTA head shows intracranial occlusions or stenosis; multiphase CTA provides information about collateral circulation and helps guide acute management. CTA neck can show occlusion, stenosis, dissection, or fibromuscular dysplasia of the carotid, vertebral, or basilar arteries.
- CT perfusion is sometimes used to improve diagnostic yield for small infarcts, exclude mimics, and inform extended-window treatment decisions. MRI brain is occasionally used for extended-window thrombolysis decisions, though emergency MRI access in Canada is limited. Carotid dopplers remain a useful screening tool for carotid stenosis when CTA is unavailable.
- ECG to look for atrial fibrillation, MI, or left ventricular hypertrophy.
Additional investigations if indicated
- Chest x-ray.
- Prolonged cardiac monitoring (minimum 24-hour Holter, though 2 weeks is preferred) and echocardiography (transthoracic, with a bubble study if under 60 years old, plus transesophageal if needed) to search for atrial fibrillation or another cardiac embolic source.
- Brain MRI with diffusion-weighted imaging if the cause of stroke is uncertain, particularly in a young patient.
- Antiphospholipid antibodies, factor V Leiden, and prothrombin gene mutation if an arterial hypercoagulable state is suspected; protein C, protein S, and antithrombin III if venous embolism is suspected together with a patent foramen ovale in a younger patient.
- Inflammatory markers (ESR, CRP, ANA) as a screen for vasculitis.
- Blood cultures and an urgent echocardiogram if infectious endocarditis is suspected.
- MRA with vessel wall imaging, with or without catheter cerebral angiography, if vasculitis or a vascular anomaly is suspected.
- Lumbar puncture if vasculitis, syphilis, or another CNS infection is suspected, or if the CT is negative for blood but subarachnoid hemorrhage is still suspected.
- Malignancy work-up (CT chest, abdomen, pelvis), pregnancy test, and syphilis/HIV serology as indicated.
NIH Stroke Scale (NIHSS) — quantifying severity
The NIHSS is the standard tool for quantifying stroke severity, localizing the lesion, and tracking neurologic change, and it directly drives thrombolysis and thrombectomy eligibility decisions.
| Item | Score range | What it assesses |
|---|---|---|
| 1a. Level of consciousness | 0-3 | Alertness |
| 1b. LOC questions | 0-2 | Orientation (month, age) |
| 1c. LOC commands | 0-2 | Ability to follow simple commands |
| 2. Best gaze | 0-2 | Horizontal eye movement |
| 3. Visual fields | 0-3 | Visual field cuts |
| 4. Facial palsy | 0-3 | Facial symmetry |
| 5a/5b. Motor arm (left/right) | 0-4 each | Arm drift or weakness |
| 6a/6b. Motor leg (left/right) | 0-4 each | Leg drift or weakness |
| 7. Limb ataxia | 0-2 | Cerebellar findings |
| 8. Sensory | 0-2 | Pinprick sensation |
| 9. Best language | 0-3 | Aphasia |
| 10. Dysarthria | 0-2 | Speech clarity |
| 11. Extinction and inattention | 0-2 | Neglect |
The total score ranges from 0 (no deficit) to a maximum of 42. As a rough severity guide: 0 equals no stroke symptoms, 1-4 is a minor stroke, 5-15 is a moderate stroke, 16-20 is a moderate-to-severe stroke, and 21-42 is a severe stroke — these bands inform, but do not alone determine, reperfusion-therapy eligibility (see Choose Initial Treatment).
Unlike the point-sum risk scores used elsewhere in this reference library (for example, the TIMI score in Acute Coronary Syndromes, where every criterion contributes exactly one point), the NIHSS is not a simple binary checklist: each of its 15 items is independently graded across its own point range (0-2, 0-3, or 0-4) based on the severity found on a structured bedside neurologic exam, and several items require the examiner to actually observe a specific finding (visual fields, limb drift, articulation, extinction) rather than tick a present-or-absent box. This graded, exam-driven structure does not fit a simple interactive checkbox calculator the way a uniform one-point-per-criterion score does, and a miscoded severity grade could silently produce a wrong total in a tool meant for real clinical use. This chapter therefore provides the teaching table above rather than a live calculator — score the NIHSS using a validated bedside instrument or certified training module, not by estimation.
Treatment Targets
- Reperfuse the occluded vessel as fast as possible — target a door-to-needle time of 30 minutes or less for thrombolysis, and the fastest achievable door-to-groin-puncture time for thrombectomy.
- Limit infarct growth by keeping blood pressure, glucose, temperature, and oxygenation within their acute-phase targets.
- Prevent early complications — aspiration pneumonia, venous thromboembolism, hemorrhagic transformation, and malignant cerebral edema.
- Prevent early recurrent stroke through appropriately timed antiplatelet or anticoagulant therapy once it is safe to start.
- Preserve the option of endovascular thrombectomy — do not let thrombolysis, or the work-up for it, delay transfer to a thrombectomy-capable centre.
- Begin the transition to secondary-prevention pharmacotherapy and rehabilitation before transfer or discharge.
Choose Initial Treatment
The three hyperacute treatment tracks
Track A — thrombolysis-eligible
Meets time-window and safety criteria for IV alteplase or tenecteplase. Give the thrombolytic regardless of whether thrombectomy is also planned — do not withhold or delay thrombolysis in an otherwise-eligible patient simply because thrombectomy is being arranged at the same time.
Track B — thrombolysis-ineligible but thrombectomy-eligible
An absolute thrombolysis exclusion (for example, an anticoagulated patient outside the reversal window, or presentation beyond every thrombolysis window) but a confirmed large-vessel occlusion within the thrombectomy window with a small-to-moderate infarct core. Proceed directly to thrombectomy.
Track C — neither reperfusion therapy indicated
No large-vessel occlusion, and outside or ineligible for the thrombolysis window, or a nondisabling deficit where trial evidence does not support thrombolysis. Manage with antiplatelet therapy (single-agent or short-course dual, see below) and standard supportive care.
Step 1 — screen every candidate for thrombolysis eligibility
Any patient with a measurable neurologic deficit and a clear or reliably estimated time last known well within a treatment window is a potential thrombolysis candidate. Standard window give alteplase or tenecteplase within 4.5 hours of onset or last known well, regardless of NIHSS score and without requiring advanced imaging, once the exclusion criteria below have been checked.[2]
| Category | Criteria |
|---|---|
| Treatment criteria (must be met) | Ischemic stroke causing a measurable neurologic deficit, in a patient 18 years or older, within 4.5 hours of onset or last known well — or meeting the extended/late-window imaging criteria below. |
| Absolute exclusions | Active hemorrhage, or any condition that would materially increase major-bleeding risk after a thrombolytic; any acute hemorrhage on intracranial imaging. |
| Relative exclusions — historical | History of intracranial hemorrhage; stroke or serious head/spinal trauma within the preceding 3 months; major surgery within the preceding 14 days; arterial puncture at a noncompressible site within the preceding 7 days; any other condition that could meaningfully raise post-thrombolysis hemorrhage risk. |
| Relative exclusions — clinical | Symptoms suggestive of subarachnoid hemorrhage; stroke symptoms explained by another nonischemic acute neurologic condition (seizure with postictal Todd paralysis, severe hypo- or hyperglycemia); hypertension refractory to therapy such that a blood pressure below 185/110 mmHg cannot be reached; anticoagulated with a direct oral anticoagulant, unless a reversal pathway brings the patient back into range (see Special Populations). |
| Relative exclusions — laboratory | Blood glucose below 2.7 or above 22.2 mmol/L; elevated activated partial thromboplastin time; INR above 1.7; platelet count below 100 × 10⁹/L. |
| Relative exclusions — imaging | CT or MRI showing signs of extensive established infarction, given both treatment futility and a higher hemorrhagic-transformation rate. |
Extended window, 4.5-9 hours in a patient who wakes with stroke symptoms (within 9 hours of the midpoint of sleep) or presents 4.5 to 9 hours after last known well, thrombolysis is reasonable if advanced imaging (CT perfusion or MRI) shows a salvageable ischemic penumbra with only a small established core.[2]
Late window, 4.5-24 hours, large-vessel occlusion only for a patient with a confirmed large-vessel occlusion and salvageable tissue on advanced imaging who cannot receive thrombectomy, thrombolysis is reasonable up to 24 hours from last known well.[2]
Do not give thrombolysis for a mild, nondisabling deficit within the standard window — trial evidence does not show a benefit of thrombolysis over dual antiplatelet therapy in this specific group, and the added bleeding risk of thrombolysis is not offset by a demonstrated gain; use the dual-antiplatelet pathway below instead.[2]
Step 2 — choose and dose the thrombolytic agent
Tenecteplase 0.25 mg/kg IV as a single bolus (maximum 25 mg) — now co-equally preferred to alteplase, with practical advantages (one bolus instead of a bolus-plus-infusion, fewer dosing-related errors) and no increase in symptomatic intracranial hemorrhage in head-to-head trial data.[3][2]
Alteplase 0.9 mg/kg IV (maximum 90 mg) — give 10% of the total dose as an initial bolus over 1 minute, then infuse the remaining 90% over 60 minutes. An equally acceptable choice to tenecteplase, and still the more familiar agent at many sites.[2]
Use whichever agent your institution has adopted as its default — most Canadian centres have moved to tenecteplase given single-bolus administration, but both are guideline-endorsed first-line options with no preference between them based on efficacy or safety.[1]
Step 3 — manage blood pressure before and after thrombolysis
Before thrombolysis treat blood pressure to below 185/110 mmHg before giving the thrombolytic — if this target cannot be reached with a reasonable dose of an IV antihypertensive, thrombolysis is contraindicated.
After thrombolysis, first 24 hours maintain blood pressure below 180/105 mmHg; treat with IV labetalol or hydralazine if it rises above this threshold on 2 or more readings 5 to 10 minutes apart.
Do not intensively lower blood pressure to a systolic target below 140 mmHg after thrombolysis in a patient with a mild-to-moderate stroke — trial evidence shows this does not improve functional outcome despite a lower rate of intracranial hemorrhage, and the current guideline explicitly recommends against it.[2]
For a patient who is not a thrombolysis candidate and has no other acute indication for blood pressure lowering (for example, concurrent MI, aortic dissection, or hypertensive encephalopathy), permissive hypertension is standard — do not routinely treat blood pressure below roughly 220/120 mmHg in the first 24 to 48 hours, since a sudden drop in perfusion pressure can extend the infarct.[1]
Step 4 — time antiplatelet and anticoagulant therapy around thrombolysis (the 24-hour rule)
Withhold all antiplatelet and anticoagulant drugs for 24 hours after thrombolysis, and until a repeat CT at 24 hours has excluded hemorrhagic transformation.
If thrombolysis was not given and intracranial hemorrhage has been excluded on the initial CT, give ASA 160 mg immediately, then 80 to 325 mg daily indefinitely.
If thrombolysis was given wait until the 24-hour CT has excluded hemorrhage, then give ASA 160 mg once, followed by 80 to 325 mg daily indefinitely.
After thrombectomy the timing of ASA is less standardized; many centres wait until follow-up imaging has excluded hemorrhage before starting ASA 80 to 325 mg daily indefinitely.
Give ASA as a suppository or via nasogastric tube in a dysphagic patient — confirm the swallowing screen result before giving any oral medication.
Mechanical (endovascular) thrombectomy
Offer thrombectomy to every patient meeting all 4 eligibility domains: patient criteria (age over 18, baseline functional independence), symptom criteria (a disabling deficit — generally NIHSS greater than 5 — with last known well within 24 hours), occlusion criteria (a technically accessible large-vessel occlusion of the anterior circulation — intracranial ICA or MCA-M1 — or of the basilar artery), and brain-parenchyma criteria (a small infarct core, generally an ASPECTS score of 6 or more, or a moderate core with an ASPECTS score of 3 to 5).[4]
Give thrombolysis first if the patient is also eligible — do not withhold or delay thrombolysis while arranging thrombectomy, and do not delay thrombectomy to see whether thrombolysis works first; bridging therapy is standard where both are indicated.
Medium-vessel occlusions (M2, A2, or P2) are not yet routinely supported by randomized trial evidence — consider on a case-by-case basis after discussion between the treating stroke physician and the neurointerventionalist rather than treating this as a default indication.[4]
Basilar artery occlusion should also be considered for thrombectomy up to 24 hours from last known well, given the very high mortality of untreated basilar occlusion, even though the anterior-circulation evidence base is more extensive.[4]
Minor stroke or high-risk TIA not receiving thrombolysis
Preferred regimen for a nondisabling ischemic stroke or high-risk TIA (NIHSS 0 to 5) who did not receive thrombolysis and is not at high bleeding risk, start dual antiplatelet therapy — ASA plus clopidogrel — within 24 to 72 hours of symptom onset and continue for 21 days, then transition to single-agent antiplatelet therapy for long-term secondary prevention.[5][2]
Alternative combination ASA plus ticagrelor for 30 days is a reasonable alternative, and is preferred specifically when a CYP2C19 loss-of-function allele (clopidogrel poor-metabolizer status) is known or strongly suspected — pharmacogenomic testing to confirm this is not yet widely available in Canadian practice.[6]
Use single-agent ASA instead of dual therapy in a patient at high bleeding risk (for example, a significant prior gastrointestinal or genitourinary bleed) — the recurrence-reduction benefit of dual therapy does not clearly outweigh the added bleeding risk in this group.
Anticoagulation for a cardioembolic source (atrial fibrillation)
Do not start systemic anticoagulation immediately after an acute ischemic stroke, even with known atrial fibrillation — early anticoagulation reduces early recurrent ischemic stroke, but this is offset by an increase in major intracranial and extracranial bleeding.[1]
Use ASA as a bridge until anticoagulation is started, unless thrombolysis was given, in which case follow the 24-hour rule above first.
Base the timing of anticoagulation initiation on stroke severity, most often by NIHSS: a widely used consensus approach re-institutes anticoagulation at 1 day after a TIA, and at 3, 6, or 12 days after a mild, moderate, or severe stroke respectively — though more recent trial evidence supports safely starting earlier, typically within 5 days, in appropriately selected patients. In practice, many centres repeat brain imaging before starting anticoagulation to exclude an asymptomatic hemorrhagic transformation first.[1]
Preferred long-term agent a direct oral anticoagulant (apixaban, dabigatran, edoxaban, or rivaroxaban) over warfarin, given the lower intracranial hemorrhage risk, no INR monitoring requirement, and fewer drug interactions; select the specific agent based on renal function, adherence likelihood, drug interactions, and patient preference.
Non-Pharmacologic Treatment
- Admit to a dedicated stroke unit with a coordinated interdisciplinary team — this alone improves outcomes independent of drug therapy.
- Continuous cardiac and neurologic monitoring per the post-thrombolysis protocol (see Monitoring and Follow-up) even when thrombolysis was not given.
- Give supplemental oxygen only to correct documented hypoxemia (target SpO2 above 90%) — routine oxygen in a normoxic patient is not beneficial.
- Perform a bedside dysphagia screen before any oral intake, ideally by a trained team; keep the patient nil by mouth if there is reduced consciousness, suspected brainstem stroke, severe dysarthria, a wet voice, a weak cough, impaired palatal sensation, inability to sit upright, or suspected aspiration.
- Use a videofluoroscopic (modified barium swallow) study when the bedside screen is ambiguous and significant aspiration needs to be excluded.
- Start a texture-modified diet for a dysphagic patient at lower aspiration risk, with additional IV fluids as needed; place a nasogastric tube if significant aspiration is demonstrated or suspected and this fits the patient's goals of care. Do not initiate early percutaneous endoscopic gastrostomy (PEG) feeding — delay the PEG discussion until swallowing has had adequate time to recover.
- Mobilize as early as possible once medically stable, and maintain adequate hydration.
- Apply intermittent pneumatic compression stockings within the first 24 hours for venous thromboembolism prevention — they do not cause bleeding and can be used even after intracerebral hemorrhage. Do not rely on graduated compression stockings alone; they lack efficacy for this indication.
- Delay placement of nasogastric tubes, indwelling urinary catheters, and intra-arterial pressure catheters during and shortly after thrombolytic infusion to minimize bleeding risk at puncture or insertion sites.
- Involve family or next of kin as early as possible to provide collateral history (especially time last known well) and consent, since the patient is often unable to communicate.
- Begin rehabilitation as soon as the patient is medically stable, and engage family and community supports early for social reintegration planning.
Special Populations
Pregnancy
Manage suspected stroke in pregnancy or within 6 weeks postpartum with the same urgency and the same initial investigations as a non-pregnant patient, using a combined obstetric, maternal-fetal-medicine, and stroke team. A noncontrast CT head exposes the fetus to a negligible radiation dose; CT contrast has no known harm but limited evidence; MRI is not associated with fetal risk, but avoid gadolinium enhancement.[1]
Alteplase and tenecteplase do not cross the placenta and are considered a reasonable treatment option in pregnancy despite the absence of trial data (pregnant patients were excluded from the founding trials) — the main patient-specific consideration is an increased risk of postpartum hemorrhage and of bleeding after epidural/spinal anesthesia or cesarean delivery, which should be discussed with obstetrics before treatment where time allows.[1]
Offer thrombectomy to a pregnant patient with a confirmed large-vessel occlusion using the same criteria as a non-pregnant patient; depending on the clinical scenario, it may be reasonable to forgo thrombolysis and proceed directly to thrombectomy.
ASA at usual doses is safe in pregnancy. Clopidogrel is the preferred P2Y12 inhibitor if dual antiplatelet therapy is needed (ticagrelor is not well studied in pregnancy). UFH and LMWH can be used for anticoagulation, with awareness of increased maternal bleeding risk; warfarin is potentially teratogenic (especially at 6 to 12 weeks' gestation) and should be avoided, and direct oral anticoagulants have insufficient safety data in pregnancy.
Breastfeeding
Continuation of breastfeeding after CT contrast exposure poses no known risk to the infant. Any thrombolytic drug is expected to be destroyed in the infant's gastrointestinal tract, and no hazard has been identified from thrombolysis during breastfeeding, though thrombolysis itself may still raise maternal postpartum or procedural bleeding risk as above. Low-dose ASA is considered compatible with breastfeeding. If anticoagulation is required, LMWH and warfarin are both considered safe during breastfeeding; direct oral anticoagulant safety in breastfeeding has not been established.
Older adults
Age alone should not exclude a patient from thrombolysis or thrombectomy — both remain guideline-endorsed at advanced age, though the eligibility criteria above already account for the higher hemorrhage and futility risk that comes with a large established infarct core, which becomes more common with age. Review comorbidities and pre-stroke functional status carefully, since these — not chronological age by itself — drive the realistic benefit of reperfusion therapy.
Renal impairment
Enoxaparin requires dose reduction, or a switch to unfractionated heparin, at a creatinine clearance of 30 mL/min or less. Consider contrast-induced nephropathy risk before CT angiography, and ensure adequate hydration where feasible without delaying emergency imaging.
A patient taking a direct oral anticoagulant
DOAC use is a relative thrombolysis exclusion requiring clinical judgment, not an automatic one. For a patient on dabigatran, idarucizumab can reverse the anticoagulant effect and may bring the patient back into an eligible window for thrombolysis where the clinical urgency supports it. Reversal of a factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) with andexanet alfa specifically to enable thrombolysis is far less established, and andexanet alfa has limited availability in Canada — in a DOAC-anticoagulated patient with a large-vessel occlusion, proceeding directly to thrombectomy, which does not carry the same systemic bleeding profile, is often the more practical pathway than pursuing thrombolysis-enabling reversal.[7]
Monitoring & Follow-Up
Post-thrombolysis monitoring protocol
| Parameter | Frequency and action |
|---|---|
| Blood pressure and neurologic exam | Baseline, then every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after starting the thrombolytic. Call the physician if systolic BP exceeds 180 mmHg or diastolic exceeds 110 mmHg on 2 or more readings 5-10 minutes apart. |
| Bleeding assessment | Visual check for bleeding every 30 minutes during the infusion and hourly for 6 hours, then every 4 hours until 24 hours post-thrombolytic. |
| Neurologic deterioration | Stop the infusion, obtain an emergency CT scan, and notify the physician immediately for any new neurologic deterioration, severe headache, or new nausea/vomiting. |
| Blood glucose | Call the physician if glucose exceeds 12 mmol/L. |
| Lines and tubes | Delay placement of nasogastric tubes, indwelling urinary catheters, and intra-arterial pressure catheters during this window. |
| Repeat imaging | Noncontrast CT head at 24 hours to confirm the absence of hemorrhagic transformation before starting antiplatelet or anticoagulant therapy. |
For every ischemic stroke patient, regardless of reperfusion therapy: reassess swallowing status at each shift change until it has stabilized; monitor temperature and treat fever promptly; monitor and correct both hyperglycemia and hypoglycemia; and reassess functional status daily to guide rehabilitation and disposition planning. Before transfer or discharge, confirm secondary-prevention pharmacotherapy has been initiated (antiplatelet or anticoagulant therapy, a high-intensity statin, and blood-pressure management as appropriate), and arrange follow-up with a stroke prevention clinic.[1]
Common Errors to Avoid
- Delaying CT imaging or the thrombolysis decision to wait for coagulation results in a patient with no history suggesting a bleeding diathesis and no anticoagulant use — this wastes time a low-risk patient did not need to spend.
- Giving ASA or any other antiplatelet/anticoagulant within 24 hours of thrombolysis, or before the 24-hour CT has excluded hemorrhagic transformation.
- Withholding or delaying thrombectomy because thrombolysis was given first, or withholding thrombolysis because thrombectomy is also planned — give both when both are indicated (bridging therapy), without either one delaying the other.
- Intensively lowering blood pressure to a systolic target below 140 mmHg after thrombolysis — no demonstrated functional benefit, and the current guideline recommends against it.
- Missing a history of direct oral anticoagulant use before giving thrombolysis — always ask specifically about the timing of the last dose of any anticoagulant or antiplatelet drug.
- Starting an oral medication, including ASA, before a bedside dysphagia screen has been completed.
- Using an aggressive IV insulin regimen to tightly control glucose — targets in the 4.4 to 7.2 mmol/L range increase hypoglycemia without improving outcomes; use a subcutaneous regimen targeting 7.8 to 10 mmol/L instead.
- Giving routine supplemental oxygen to a patient with a normal oxygen saturation.
- Using prophylactic osmotic therapy before any sign of mass effect has appeared, or continuing osmotic therapy indefinitely once started — both risk rebound cerebral edema; reserve it for actual signs of mass effect and treat it as a bridge to definitive management.
- Missing the window for malignant cerebral edema by not watching closely enough for declining consciousness in the first several days after a large middle cerebral artery infarct.
- Treating asymptomatic, mild-to-moderate hypertension aggressively in a non-thrombolysis-candidate ischemic stroke patient — permissive hypertension is standard in this group.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.
Thrombolytics
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Tenecteplase | Adults: 0.25 mg/kg IV single bolus, maximum 25 mg, given as a rapid IV push Pediatric: Not established for routine pediatric use — pediatric acute ischemic stroke is managed at a specialized pediatric stroke centre. | Bleeding (superficial and internal — GI, GU, respiratory tract, retroperitoneal), intracranial hemorrhage, cerebral edema/herniation, seizures, hypersensitivity including orolingual angioedema | Additive bleeding risk with any antiplatelet or anticoagulant given within 24 hours | Confirm the full eligibility checklist immediately beforehand. Withhold antiplatelet/anticoagulant drugs for 24 hours and until repeat CT excludes hemorrhage. |
| Alteplase | Adults: 0.9 mg/kg IV, maximum 90 mg: 10% of the total dose as an initial bolus over 1 minute, remaining 90% infused over 60 minutes Pediatric: Not established for routine pediatric use — pediatric acute ischemic stroke is managed at a specialized pediatric stroke centre. | Bleeding (superficial and internal — GI, GU, respiratory tract, retroperitoneal), intracranial hemorrhage, cerebral edema/herniation, seizures, hypersensitivity including orolingual angioedema | Additive bleeding risk with any antiplatelet or anticoagulant given within 24 hours | Requires an infusion pump for the 60-minute component. Do not exceed the 90 mg maximum total dose regardless of the calculated weight-based dose. |
Antiplatelet agents
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| ASA | Adults, loading: 160 mg PO once, once ICH is excluded (immediately, or 24h after thrombolysis plus a clear repeat CT) Adults, maintenance: 80-325 mg PO daily, indefinitely Pediatric: Ischemic stroke is rare in children and is managed by a pediatric stroke specialist — routine adult dosing does not apply. | Nausea, vomiting, hemorrhage, rare hypersensitivity/bronchospasm | Additive bleeding with heparin, enoxaparin, warfarin, DOACs, and other antiplatelet drugs | Give via NG tube or as a suppository to a dysphagic patient. Use an enteric-coated formulation for a patient who can swallow. |
| Clopidogrel | Adults, DAPT loading: 300 mg PO once Adults, DAPT maintenance: 75 mg PO daily with ASA for 21 days, then reassess Pediatric: Not established. | Hemorrhage, skin rash, diarrhea | Reduced efficacy with strong CYP2C19 inhibitors (e.g., omeprazole); additive bleeding with other antiplatelet/anticoagulant drugs | Preferred DAPT partner for minor stroke/high-risk TIA. Consider ticagrelor instead if CYP2C19 loss-of-function is known or suspected. |
| Ticagrelor | Adults, DAPT loading: 180 mg PO once Adults, DAPT maintenance: 90 mg PO BID with ASA for 30 days Pediatric: Not established. | Hemorrhage, rash, dizziness, diarrhea, dyspnea, bradyarrhythmia | Avoid strong CYP3A4 inhibitors/inducers | Preferred over clopidogrel-based DAPT specifically when CYP2C19 poor-metabolizer status is known or suspected. |
Anticoagulants — cardioembolic (AF-associated) stroke
Timing of the first dose follows the stroke-severity-based initiation guidance in Choose Initial Treatment.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Apixaban | Adults: Per current stroke-prevention dosing guidance, renal/age/weight-adjusted | Bleeding | Strong dual CYP3A4/P-glycoprotein inhibitors or inducers | Preferred over warfarin for long-term stroke prevention in atrial fibrillation. |
| Dabigatran | Adults: Per current stroke-prevention dosing guidance, renal-adjusted | Bleeding, dyspepsia | P-glycoprotein inhibitors/inducers | Idarucizumab is available as a specific reversal agent if urgent reversal is needed. |
| Edoxaban | Adults: Per current stroke-prevention dosing guidance, renal/weight-adjusted | Bleeding | P-glycoprotein inhibitors | |
| Rivaroxaban | Adults: Per current stroke-prevention dosing guidance, renal-adjusted | Bleeding | Strong dual CYP3A4/P-glycoprotein inhibitors or inducers | |
| Warfarin | Adults: Dose to maintain INR 2-3 | Bleeding | Numerous — CYP2C9/VKORC1-mediated and diet (vitamin K intake) | Reserve for a patient who cannot use a DOAC. Vitamin K1 and prothrombin complex concentrate are used for warfarin-associated intracranial hemorrhage. |
VTE prophylaxis
For a patient who cannot mobilize one or both lower limbs independently and has no contraindication; stop once therapeutic anticoagulation starts.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Enoxaparin | Adults: Prophylactic dose per institutional VTE-prevention protocol | Bleeding, injection-site hematoma, rare heparin-induced thrombocytopenia | Additive bleeding with other antiplatelet/anticoagulant drugs | Dose-reduce, or switch to unfractionated heparin, at ClCr ≤30 mL/min. |
| Unfractionated heparin | Adults: Prophylactic dose per institutional VTE-prevention protocol | Bleeding, heparin-induced thrombocytopenia | Additive bleeding with other antiplatelet/anticoagulant drugs | Preferred over enoxaparin in significant renal impairment. |
Acute blood-pressure-lowering agents
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Labetalol | Adults: 10-20 mg IV over 1-2 minutes; may repeat or double every 10 minutes to a maximum cumulative dose of 300 mg, or start a continuous infusion per institutional protocol | Bradycardia, hypotension, bronchospasm | Additive bradycardia with other AV-nodal-blocking drugs | 1st-line IV agent to reach the below-185/110 mmHg pre-thrombolysis target. Avoid in significant bronchospasm or bradycardia. |
| Hydralazine | Adults: 10-20 mg IV over 1-2 minutes, may repeat every 20-30 minutes as needed | Reflex tachycardia, headache, hypotension | Additive hypotension with other antihypertensives | Alternative when beta-blockade is undesirable; reflex tachycardia may need concurrent beta-blockade if not contraindicated. |
Glucose management
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Insulin (regular) | Adults: Subcutaneous sliding-scale or basal-bolus regimen per institutional protocol, target 7.8-10 mmol/L | Hypoglycemia | None specific to this indication | Correct hypoglycemia (below 3.3 mmol/L) immediately. Do not use an aggressive IV insulin regimen targeting near-normal glucose. |
Antipyretic/analgesic
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Acetaminophen | Adults: 650 mg PO or PR Q4H PRN for temperature 38°C or higher, or for analgesia Pediatric: Weight-based dosing per standard pediatric antipyretic guidance; not specific to stroke. | Hepatotoxicity at high cumulative dose | None significant at standard dose | Treat fever promptly and investigate its cause — elevated temperature is associated with worse outcome. |
Cerebral edema
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Mannitol | Adults: 1 g/kg IV, may repeat every 4-6 hours | Rebound cerebral edema with prolonged use, electrolyte disturbance, acute kidney injury, hypotension if over-diuresed | Additive nephrotoxicity with other nephrotoxic drugs | Reserve for a patient with actual signs of mass effect (declining consciousness, pupillary change) — do not use prophylactically. A bridge to definitive neurosurgical management, not a standalone long-term therapy. |
Anticoagulant reversal (hemorrhagic transformation / anticoagulant-associated ICH)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Vitamin K1 | Adults: Per current warfarin-reversal dosing guidance for major bleeding | Rare anaphylactoid reaction with rapid IV administration | Reverses warfarin's mechanism of action specifically | Give together with prothrombin complex concentrate for rapid warfarin reversal in intracranial hemorrhage — vitamin K alone acts too slowly for emergency reversal. |
| Prothrombin complex concentrate (human) | Adults: Weight- and INR-based dosing per current reversal guidance | Thromboembolism, hypersensitivity | None specific | Preferred rapid-reversal agent for warfarin-associated intracranial hemorrhage; give together with vitamin K1 for sustained reversal. |
| Idarucizumab | Adults: 5 g IV, given as two 2.5 g doses | Headache, hypokalemia | None specific — reverses dabigatran only, not other anticoagulants | Specific reversal agent for dabigatran-associated bleeding, including to enable emergency thrombolysis where appropriate. |
| Andexanet alfa | Adults: Weight- and dose-based bolus-plus-infusion regimen per current reversal guidance | Thromboembolism, infusion reactions | Reduces the anticoagulant effect of heparin given afterward | Reverses apixaban, edoxaban, and rivaroxaban specifically. Limited availability in Canada — confirm local access before relying on it as a treatment pathway. |
| Tranexamic acid | Adults: Per current reversal-adjunct dosing guidance | Thromboembolism (theoretical concern with any antifibrinolytic), rare seizures at high doses | Avoid combining with factor VIIa or other strong procoagulants outside specialist direction | Emerging adjunct for post-thrombolysis symptomatic intracranial hemorrhage alongside cryoprecipitate; evidence in this specific setting is still limited. |
References
- Canadian Stroke Best Practice Recommendations: Acute Stroke Management, 7th Edition Practice Guidelines Update, 2022 — Canadian Journal of Neurological Sciences (Heran M, Lindsay P, Gubitz G, et al.). Can J Neurol Sci 2024;51(1):1-31
- 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association — Stroke (Prabhakaran S, Gonzalez NR, Zachrison KS, et al.). Stroke 2026 (published online January 26, 2026)
- Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial — The Lancet (Menon BK, Buck BH, Singh N, et al., AcT Trial Investigators). Lancet 2022;400(10347):161-169
- Canadian Stroke Best Practice Recommendations: Endovascular Thrombectomy for Acute Ischemic Stroke, Interim Update 2025 — Canadian Journal of Neurological Sciences, Canadian Stroke Best Practice Recommendations Writing Group. Can J Neurol Sci 2025 (published ahead of print):1-6
- Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of the CHANCE and POINT Trials — JAMA Neurology (Pan Y, Elm JJ, Li H, et al.). JAMA Neurol 2019;76(12):1466-1473
- Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA — New England Journal of Medicine (Johnston SC, Amarenco P, Denison H, et al., THALES Investigators). N Engl J Med 2020;383(3):207-217
- Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association — Stroke (Yaghi S, Willey JZ, Cucchiara B, et al.). Stroke 2017;48(12):e343-e361
- Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials — Lancet Neurology (Vahedi K, Hofmeijer J, Juettler E, et al.). Lancet Neurol 2007;6(3):215-222
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.