THROMBOLYTIC T ACUTE ISCHEMIC STROKE - Thrombosis Canada

[Pages:3]THROMBOLYTIC THERAPY IN ACUTE ISCHEMIC STROKE

TARGET AUDIENCE: All Canadian health care professionals, emergency health care providers,

radiologists, neurologists and primary care practitioners involved in acute stroke care.

OBJECTIVE:

To outline the evidence, indications and cautionary guidance relating to the use thrombolytic therapy in the form recombinant tissue plasminogen activator (rt-PA) for the early management of acute ischemic stroke (AIS).

ABBREVIATIONS:

AIS CT INR IV PT rt-PA

acute ischemic stroke computed tomography international normalized ratio intravenous prothrombin time recombinant tissue plasminogen activator

BACKGROUND:

Thrombolytic therapy in AIS is one of most controversial and high-risk areas of emergency medical care. The most well-studied agent used in this setting has demonstrated efficacy since 1993, but its widespread uptake in emergency settings remains limited. The primary concern lies in the narrow margin between achieving long-term functional benefits and the real risk of iatrogenic mortality mediated via fatal intracranial bleeding. The treatment is extraordinarily time-sensitive, with rapid decay in benefit if therapy is not initiated early after witnessed onset. An effective stroke protocol demands highly coordinated and multi-stakeholder input from a primed prehospital and emergency department team (including full collaboration from radiology to ensure emergent computed tomography [CT] scans to confirm eligibility) and from stroke neurologists. Current evidence is robust and includes over 7000 patients from 12 randomized trials. Evidencebased guidelines support its use. Thrombolytic therapy with rt-PA improves the likelihood of being alive and independent after AIS. This is particularly true if administered within the first three hours after symptom onset. This benefit comes at the cost of an increase in the risk of early (within 7 days or less) mortality mediated primarily through fatal intracranial bleeding precipitated by rt-PA.

? 2013 Thrombosis Canada.

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AGENTS AND DOSING:

The recommended dose of rt-PA for AIS is 0.9 mg/kg (maximum 90 mg) infused over 60 minutes, with 10% of the total dose administered as an initial IV bolus over 1 minute.

Absolute contraindications for rt-PA therapy for AIS include the following:

a) History or evidence of intracranial hemorrhage b) Clinical presentation suggestive of subarachnoid hemorrhage c) Known arteriovenous malformation d) Systolic blood pressure exceeding 185 mmHg or diastolic blood pressure exceeding 110 mmHg

despite repeated measurements and treatment e) Seizure with post-ictal residual neurologic impairment f) Platelet count below 100,000/?L g) Prothrombin time (PT) above 15 or international normalized ratio (INR) above 1.7 h) Active internal bleeding or acute trauma (fracture) i) Head trauma or stroke in the previous 3 months j) Arterial puncture at a non-compressible site within 1 week

Relative contraindications for rt-PA therapy for AIS include the following:

a) Suspected acute pericarditis b) Rapidly improving stroke symptoms c) Myocardial infarction in the previous 3 months d) Glucose level lower than 3.0 mmol/L or higher than 22 mmol/L

MONITORING:

The patient should be observed in a critical care area so that frequent neurologic assessments as well as blood pressure and cardiovascular monitoring can be performed. The clinician must be ready to recognize and manage possible complications. The effectiveness of thrombolytic therapy in stroke is strongly correlated with strict patient selection according to the inclusion and exclusion criteria. No adjunctive therapies should be given with rt-PA for the management of AIS. Anticoagulants and antiplatelet agents may increase the risk of bleeding complications and are not recommended within 24 hours of rt-PA administration.

SPECIAL CONSIDERATIONS:

The most controversial issues in rt-PA administration for AIS relate to the timing of administration and the age eligibility of patients. Administration of rt-PA within three hours of symptom onset clearly carries the greatest benefit in terms of both efficacy and safety, and is supported by the most robust evidence. Treatment beyond the 3-hour window is modestly beneficial if provided within 4.5 hours of symptom onset and is even more marginal within 6 hours. Fortunately, there are validated and easy-to-use tools that can identify patients at increased risk of symptomatic

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intracranial bleeding, which is the most dreaded adverse event associated with treatment. Although less than 25% of patients enrolled in thrombolytic trials were older than 80 years of age, the subgroup analyses suggest that rt-PA carries overall benefits in this age group similar to those of their younger counterparts, especially if treated within 3 hours.

PEDIATRICS:

There are currently no safety and efficacy data in children; however, there is an ongoing clinical trial. Pediatricians with expertise in pediatric stroke should manage, where possible, pediatric patients with stroke. When this is not possible, a combination of a neonatologist/pediatrician and an adult neurologist, supported by consultation with an experienced pediatric specialist in stroke, is recommended.

REFERENCES:

Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e601S-36S. Menon BK, Saver JL, Prabhakaran S, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke 2012;43(9):2293-2299. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e737S-801S. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012;379:2364-2372.

Please note that the information contained herein is not to be interpreted as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter, you should consult your doctor or other professional healthcare providers, and as such you should never delay seeking medical advice, disregard medical advice or discontinue medical treatment because of the information contained herein.

? 2013 Thrombosis Canada.

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