Thrombolytics for acute ischemic stroke: Difference between revisions
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== Background ==
==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


#Pros:
==Studies Required==
##30% greater chance of good neurologic outcome at 3 months
*Physical exam: [[NIH Stroke Scale]]
##Comparable 3-month mortality rate
*[[Head CT]]
#Cons
*CBC (hemoglobin, plt)
##Intracranial hemorrhage occurs in ~5% of pts
*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
**[[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


*Coag results prior to tx is only required for pts on anticoagulants
===Relative Exclusion Criteria===
*...but if history unable to be obtained must wait for coag results prior to starting tx
*Minor or rapidly improving stroke symptoms
*[[Pregnancy]]
*[[Seizure]] at onset with postictal residual neuro impairments


== Inclusion Criteria ==
==tPA between 3-4.5hrs==
===Inclusion Criteria===
*Same as for <3hr


#Diagnosis of ischemic stroke causing measurable neuro deficit
===Exclusion Criteria===
#Clear onset (last witnessed well) <3 hours (see below for extension to <4.5 hours)
*All of the above plus:
#Age >18 yrs
**Age >80yr
**Combination of both previous stroke and DM
**NIHSS score >25
**Oral [[anticoagulant]] use regardless of INR


== Exclusion Criteria ==
==Administration==
{{TPA Stroke}}


=== Absolute ===
==tPA Complications==
*[[Post-tPA Hemorrhage]]
*[[Angioedema]]


#Head trauma or prior stroke in previous 3 months
==See Also==
#Symptoms suggestive of SAH
*[[CVA (Main)]]
#Arterial puncture at noncompressible site in previous 7 days
*[[Post-tPA Hemorrhage in CVA]]
#History of previous ICH
*[[NIH Stroke Scale]]
#Elevated BP (sys > 185 or dia > 110
*[[EBQ:Studies List of Thrombolytics for Acute Stroke|List of studies: Thrombolytics in CVA]]
#Active bleeding on exam
*[[Thrombolytics]]
#Acute bleeding diathesis:
##Plt count < 100K
##PTT > upper limit of normal
##INR >1.7
#Blood Glucose <50
#CT demonstrates multilobar infarction (hypodensity > 1/3 cerebral hemisphere)


=== Relative ===
==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


#Minor stroke or rapidly improving stroke symptoms
[[Category:Neurology]]  
#Seizure at onset with postictal residual neuro impairments
#Major surgery or serious trauma within previous 14 days
#Acute GI or GU hemorrhage (within previous 21 days)
#Acute MI (within previous 3 months)
 
=== 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 ==
 
#Head CT
#CBC
#PT/PTT
#Glu check
#ECG
#Icon
 
== tPA Administration ==
 
#Alteplase 0.9mg/kg IV (max 90mg total)
##Load with .09mg/kg (10% of dose) as IV bolus over 1min, followed by 0.81mg/kg (90% of dose) as cont. infusion over 60min
#Neuo check Q15min x 2hrs, Q30min x6hrs, Q1hr x 16hrs
#Keep BP <180/105
##Labetalol 10mg IV followed by continous IV infusion 2-8mg/min OR
##Nicardipine IV 5mg/h, titrate up to desired effect by 2.5mg/hr q 5-15min, maximum 15mg/h
##If BP not controlled or dia > 140 consider nitroprusside
#No anticoatulation/antiplatelets x 24hrs
#Stop tPA and consider head CT if pt develops:
##Neuro changes
##Acute hypertension
##Nausea/vomiting
 
== See Also ==
 
[[Post-tPA Hemorrhage]]
 
== Source ==
1/26/06 DONALDSON (adapted from Lampe, Tintinali)
 
2/20/10 PANI (ACEP/AAN Guidelines--class B recommendations)
 
AHA/ASA Guidelines
 
[[Category:Neuro]]  
[[Category:Procedures]]
[[Category:Procedures]]

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
  1. ↑ 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.
  2. ↑ 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.
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