Difference between revisions of "Thrombolytics for acute ischemic stroke"

(Created page with "==Inclusion Criteria== 1) Clinical diagnosis of stroke 2) Clear onset (last witnessed well) <3 hours 3) Age >18 yrs ==Exclusion Criteria== (ABSOLUTE) 1) BP Systolic...")
 
 
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==Inclusion Criteria==
+
==Background==
 +
''[[EBQ:Studies_List_of_Thrombolytics_for_Acute_Stroke|see list of all thrombolytic trials in CVA for more details]]''
 +
===NINDS Trial (treated within 3hrs)===
 +
Benefits:
 +
*12% absolute risk reduction benefit (NNT = 8-9) at 3 months
 +
*Lower percentage of patients who left hospital severely disabled
 +
*Comparable 3-month mortality rate (even with increased rate of ICH)
 +
Risks:
 +
*1% increase in mortality
 +
*5% increase in nonfatal intracranial hemorrhage
 +
===ECASS Trial (treated within 4.5hrs)===
 +
*Confirmed NINDS findings even when therapeutic window extended to 4.5hr
 +
*As a result AHA/ASA now recommends tPA for patients presenting up to 4.5hr after symptom onset
  
 +
==Studies Required==
 +
*Physical exam: [[NIH Stroke Scale]]
 +
*[[Head CT]]
 +
*CBC (hemoglobin, plt)
 +
*PT/PTT/INR
 +
**Only need to wait for result if suspicion of abnormal value, patient has received heparin or warfarin, or use of anticoagulants is unknown
 +
*Glucose
 +
*[[ECG]]
 +
*Urine pregnancy (pregnancy is relative contraindication)
  
1) Clinical diagnosis of stroke
+
==tPA <3hr==
 +
===Inclusion Criteria===
 +
*Diagnosis of ischemic stroke causing measurable neuro deficit
 +
*Clear onset (last witnessed well) <3hr (see below for extension to <4.5hr)
 +
*Age >18yr
  
2) Clear onset (last witnessed well) <3 hours
+
===Exclusion Criteria===
 +
*Historical
 +
**[[Stroke]] or [[head trauma]] in previous 3 months
 +
**Any history of [[intracranial hemorrhage]]
 +
**Major surgery in the previous 14 days
 +
**[[GI bleed|GI]] or [[hematuria|urinary tract]] bleeding in previous 21 days
 +
**[[Myocardial infarction]] in previous 3 months
 +
**Arterial puncture at noncompressible site in previous 7 days
 +
*Clinical
 +
**Spontaneously clearing stroke symptoms
 +
**Only minor and isolated neurologic signs
 +
**[[Seizure]] at stroke onset
 +
*Persistent [[hypertension|SBP >185]] or DBP >110 despite treatment
 +
*Use of direct thrombin inhibitors (e.g. [[dabigatran]], [[argatroban]]) or direct factor Xa inhibitors (e.g. [[rivaroxaban]], [[apixaban]]) with elevated aPTT, INR, or factor Xa assay
 +
*Active bleeding or acute [[trauma]] ([[fracture]]) on exam
 +
*Labs
 +
**Platelets <100K
 +
**Serum glucose <50, >400
 +
**INR >1.7 or PT >15 sec if on warfarin
 +
**Elevated PTT if on heparin
 +
*[[Head CT]]
 +
**Evidence of [[ICH|hemorrhage]]
 +
**Evidence of multilobar infarction with hypodensity involving >33% of cerebral hemisphere
 +
**Intracranial neoplasm, [[AVM]], or aneurysm
 +
*Use of dabigatran within 48hrs is relative contraindication
  
3) Age >18 yrs
+
===Relative Exclusion Criteria===
 +
*Minor or rapidly improving stroke symptoms
 +
*[[Pregnancy]]
 +
*[[Seizure]] at onset with postictal residual neuro impairments
  
+
==tPA between 3-4.5hrs==
 +
===Inclusion Criteria===
 +
*Same as for <3hr
  
==Exclusion Criteria==
+
===Exclusion Criteria===
 +
*All of the above plus:
 +
**Age >80yr
 +
**Combination of both previous stroke and DM
 +
**NIHSS score >25
 +
**Oral [[anticoagulant]] use regardless of INR
  
 +
==Administration==
 +
{{TPA Stroke}}
  
+
==tPA Complications==
 
+
*[[Post-tPA Hemorrhage]]
(ABSOLUTE)
+
*[[Angioedema]]
 
 
1) BP Systolic >185, diastolic >110 (can receive 1-3 doses anti-hypertensive)
 
 
 
2) PTT >34, PT >15, or INR >1.7
 
 
 
3) Platelet count <100,000
 
 
 
4) Blood Glucose <50 or >400 mg/dl
 
 
 
5) Minor stroke or rapidly resolving stroke
 
 
 
6) Hemorrhage or edema on non-con head CT
 
 
 
7) Suspected SAH
 
 
 
6) Seizure at onset of stroke
 
 
 
7) Heparin treatment during the past 48 hours with an elevated PTT
 
 
 
8) Evidence of acute myocardial infarction
 
 
 
 
 
 
(RELATIVE)
 
 
 
5) History of prior intracranial hemorrhage, neoplasm, AVM or aneurysm
 
 
 
6) Major surgery/trauma within <14 days
 
 
 
7) Stroke or serious head injury within 3 months
 
 
 
8) GI/GU bleeding within <21 days
 
 
 
9) Lactation or pregnancy within <30 days
 
 
 
(ADDITONAL PER HARBOR NEURO)
 
 
 
10) AMI or pericarditis (ECG)
 
 
 
11) Aggressive treatment needed to control BP
 
 
 
12) Lumbar puncture within <7 days
 
 
 
13) Occult blood in urine or stool (UA + Guiac)
 
 
 
 
 
 
ECASS III Exclusion Criteria (if giving tPA between 3-4.5 hours)
 
 
 
Age > 80
 
 
 
Baseline NIHSS > 25
 
 
 
Any oral anticoagulant use
 
 
 
History of prior stroke and DM
 
 
 
 
 
 
==Studies Needed==
 
 
 
 
 
1) Head CT
 
 
 
2) CBC
 
 
 
3) PT/PTT
 
 
 
4) Glu check
 
 
 
5) ECG
 
 
 
6) Icon
 
 
 
 
 
 
==Giving tPA==
 
 
 
 
 
1) Alteplase (Activase/tPA): 0.9mg/kg (max 90mg total) IV; Give 10% as bolus over 1 min, remainder by continous infusion over 60min
 
 
 
2) Neuo check Q15min x 2hrs, Q30min x6hrs, Q1hr x 16hrs
 
 
 
3) Keep BP <185/95 (labetalol/nipride gtt if nec)
 
 
 
4) NO anticoatulation/antiplatelet agents x24hrs
 
 
 
5) Stop tPA if worsening neuro exam --> STAT head-CT
 
 
 
 
  
 
==See Also==
 
==See Also==
 +
*[[CVA (Main)]]
 +
*[[Post-tPA Hemorrhage in CVA]]
 +
*[[NIH Stroke Scale]]
 +
*[[EBQ:Studies List of Thrombolytics for Acute Stroke|List of studies: Thrombolytics in CVA]]
 +
*[[Thrombolytics]]
  
 +
==References==
 +
*Hacke W, Kaste M, Bluhmi E, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13): 1317, 2008
 +
*ACEP/AAN Guidelines
 +
*AHA/ASA Guidelines
  
Neuro: post-tPA Hemmorhage
+
[[Category:Neurology]]
 
+
[[Category:Procedures]]
 
 
 
==Source==
 
 
 
 
 
1/26/06 DONALDSON (adapted from Lampe, Tintinali)
 
 
 
2/20/10 PANI (ACEP/AAN Guidelines--class B recommendations)
 
 
 
 
 
 
 
 
 
[[Category:Neuro]]
 

Latest revision as of 22:44, 1 October 2019

Background

see list of all thrombolytic trials in CVA for more details

NINDS Trial (treated within 3hrs)

Benefits:

  • 12% absolute risk reduction benefit (NNT = 8-9) at 3 months
  • Lower percentage of patients who left hospital severely disabled
  • Comparable 3-month mortality rate (even with increased rate of ICH)

Risks:

  • 1% increase in mortality
  • 5% increase in nonfatal intracranial hemorrhage

ECASS Trial (treated within 4.5hrs)

  • Confirmed NINDS findings even when therapeutic window extended to 4.5hr
  • As a result AHA/ASA now recommends tPA for patients presenting up to 4.5hr after symptom onset

Studies Required

  • Physical exam: NIH Stroke Scale
  • Head CT
  • CBC (hemoglobin, plt)
  • PT/PTT/INR
    • Only need to wait for result if suspicion of abnormal value, patient has received heparin or warfarin, or use of anticoagulants is unknown
  • Glucose
  • ECG
  • Urine pregnancy (pregnancy is relative contraindication)

tPA <3hr

Inclusion Criteria

  • Diagnosis of ischemic stroke causing measurable neuro deficit
  • Clear onset (last witnessed well) <3hr (see below for extension to <4.5hr)
  • Age >18yr

Exclusion Criteria

  • Historical
  • Clinical
    • Spontaneously clearing stroke symptoms
    • Only minor and isolated neurologic signs
    • Seizure at stroke onset
  • Persistent SBP >185 or DBP >110 despite treatment
  • Use of direct thrombin inhibitors (e.g. dabigatran, argatroban) or direct factor Xa inhibitors (e.g. rivaroxaban, apixaban) with elevated aPTT, INR, or factor Xa assay
  • Active bleeding or acute trauma (fracture) on exam
  • Labs
    • Platelets <100K
    • Serum glucose <50, >400
    • INR >1.7 or PT >15 sec if on warfarin
    • Elevated PTT if on heparin
  • Head CT
    • Evidence of hemorrhage
    • Evidence of multilobar infarction with hypodensity involving >33% of cerebral hemisphere
    • Intracranial neoplasm, AVM, or aneurysm
  • Use of dabigatran within 48hrs is relative contraindication

Relative Exclusion Criteria

  • Minor or rapidly improving stroke symptoms
  • Pregnancy
  • Seizure at onset with postictal residual neuro impairments

tPA between 3-4.5hrs

Inclusion Criteria

  • Same as for <3hr

Exclusion Criteria

  • All of the above plus:
    • Age >80yr
    • Combination of both previous stroke and DM
    • NIHSS score >25
    • Oral anticoagulant use regardless of INR

Administration

Alteplase

  • NOTE - in stroke, do not give aspirin until 24 hours after giving tPA, as ASA with tPA does not improve outcomes and increases bleed risk[1]
  • Do not give acutely heparin (or any anticoagulation) if giving tPA[2]

Dosing:

  • 0.9mg/kg IV (max 90mg total)
    • 10% of dose is administered as bolus; rest is given over 60min
  • Neuro check Q15min x 2hr
  • No anticoagulation/antiplatelets x 24hr
  • Blood pressure (keep SBP <180, DBP <105)

If SBP is >180-230 or DBP is >120:

  • Nicardipine 5 mg/hr by slow infusion (50 mL/hr) initially; may be increased by 2.5 mg/hr every 15 minutes; not to exceed 15 mg/hr OR
  • Labetalol 10mg IV over 1–2 min; repeat dose q10–20min up to 300mg max OR
  • Labetalol 10mg IV followed by infusion at 2–8 mg/min

If BP not controlled by above measures:

  • Nitroprusside 0.5–10mcg/kg/min
  • Continuous arterial monitoring advised
  • Use with caution in patients with hepatic or renal insufficiency

tPA Complications

See Also

References

  • Hacke W, Kaste M, Bluhmi E, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13): 1317, 2008
  • ACEP/AAN Guidelines
  • AHA/ASA Guidelines
  • Zinkstok SM, Roos YB, ARTIS Investigators . Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet (2012) 380(9843):731–7.10.1016/S0140-6736(12)60949-0.
  • Periprocedural Antithrombotic Treatment During Acute Mechanical Thrombectomy for Ischemic Stroke: A Systematic Review. Rob A. van de Graaf, Vicky Chalos, Gregory J. del Zoppo, Aad van der Lugt, Diederik W. J. Dippel, Bob Roozenbeek. Front Neurol. 2018; 9: 238.