tPA for Thrombosis in Cardiac Arrest

There are a limited number of medications which can be used to treat an acute thrombus.

Tissue Plasminogen Activators (tPA), such as alteplase and tenecteplase, are the mainstay of thrombolytic therapy.

Since the mid-1990s, numerous case reports and clinical trials have been published regarding the use of thrombolytic

therapy in cardiac arrest, however there is conflicting evidence regarding results about benefit and outcomes.

The 2015 AHA guidelines recommend considering thrombolytic therapy for cardiac arrest due to PE.

A more recent review article recommended a standard dose for this indication but this is anecdotal based on a

combination of studies. The clinical controversy includes route of administration, dose, and patient selection.

Dose

Various dosing strategies utilized in cardiac arrest- up to 100 mg max

o 50 mg or 100 mg bolus over 1-15 min x 1 dose

o 50 mg bolus followed by second 50 mg bolus 10-20 minutes later

Administration

IV as bolus dose or infusion

Mechanism of

Action

Initiates fibrinolysis by binding to fibrin in a thrombus and converts entrapped plasminogen to plasmin

PK/PD

Duration: 80% cleared within 10min; some fibrinolytic activity persists for 1 hr

t1/2 = 5 min

Adverse Effects

Hemorrhage (Intracranial, GI, GU)

Ecchymosis

Drug Interactions

and warnings

Contraindications

o Active bleeding

o h/o recent stroke, spinal surgery, head trauma

o Uncontrolled HTN

Interactions

o Antiplatelets (increased bleeding)

o Anticoagulants (increased bleeding)

o Nitroglycerin (decreased concentration of alteplase)

Compatibility

NOT compatible with

o Dobutamine

o Dopamine

o Heparin

o Nitroglycerin

Author,

year

Design/

sample size

Population

Intervention &

Comparison*

Outcome

Comments

Bottiger,

2001

Prospective,

observational

n = 40

• Out of hospital

arrest

• Any rhythm
• No ROSC after

15min

50mg alteplase +

5000units heparin

• Repeat dose after

30min of CPR

Bleeding: 5% (not associated with tPA)

ROSC: 68% tPA vs 44% no-tPA

Discharge: 15% tPA vs 8% no-tPA

tPA is safe & effective

for treatment of CA

due to PE

Abu-

Laban,

2002

Randomized,

double blind,

placebo

controlled

n = 117

• Out of hospital

arrest

• PEA rhythm
• No ROSC after

3min

tPA for PE-induced cardiac arrest has been studied for over 20 years but there is still no clear answer on how to

dose tPA.

AHA Guidelines state that thrombolysis may be considered when cardiac arrest is suspected to be caused by a

PE, but provides no recommendation on inclusion criteria, thrombolytic timing, drug or dose.

Studies support rapid utilization of a thrombolytic in patients with confirmed or highly suspicious for a PE is

beneficial.

Alteplase. [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from

http://www.micromedexsolutions.com/

Link MS. Circulation. 2015; 132[suppl 2]:S444-S464.

Bottiger BW. Lancet. 2001; 357:1583-5.

Abu-Laban RB. N Engl J Med. 2002; 346:1522-1528.

Janata K. Resuscitation. 2003; 57:49-55.

Fatovich DM. Resuscitation. 2004; 61:309-313.

Bottiger BW. N Engl J Med. 2008; 359:2651-2662.

Er, PLoS One. 2009; 4:e8323-8.

Sharifi M. Amer J Emerg Med. 2016; 34:1963-1967.

• Peppard SR. Am J Health-Syst Pharm. 2018; 75:870-875.
• Logan JK. Amer J Emerg Med 2014; 32:789-796.

Pharmacy Friday

evidence-based medicine

Other pearls found at:

PharmacyFriday.com

[email protected], [email protected], [email protected]

Overview of Evidence

Author,

year

Design/

sample size

Population

Intervention &

Comparison*

Outcome

Comments

Bottiger,

2001

Prospective,

observational

n = 40

• Out of hospital

arrest

• Any rhythm
• No ROSC after

15min

50mg alteplase +

5000units heparin

• Repeat dose after