What’s the Code Dose of tPA?

What’s the Code Dose of tPA?

2016-12-16T10:23:50+00:00

Suppose you have a patient in whom you highly suspect a pulmonary embolism (PE) that devolves into PEA arrest while awaiting a CT angiogram. Or, what about a patient with an ECG showing clear STEMI that loses pulses?

Clinical Question: In the rare situation where fibrinolytics may be indicated in cardiac arrest from PE or Acute Myocardial Infarction (AMI), what’s the dose?

 

Citation Study Design Condition Drug Dose
Kurkciyan et al. 1 Retrospective cohort PE Alteplase 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min)
Ruiz-Bailen et al. 2 Case series (6 pts) PE Alteplase 50 mg bolus, repeat 50 mg in 30 min
Janata et al. 3 Retrospective cohort PE Alteplase 0.6-1.0 mg/kg bolus (up to 100 mg)
Sharifi et al. 4 Case series (23 pts) PE Alteplase 50 mg bolus
Lederer et al. 5 Retrospective cohort AMI Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
Ruiz-Bailen et al. 6 Retrospective cohort AMI Alteplase 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min)
Schreiber et al. 7 Retrospective cohort AMI Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
Kurkciyan et al. 8 Retrospective cohort AMI Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
Bottiger et al. 9 Prospective observational Nontraumatic cardiac arrest Alteplase 50 mg bolus, repeat 50 mg in 30 minutes
Abu-Laban et al. 10 RCT Cardiac arrest from any cause Alteplase 100 mg over 15 min
Fatovich et al. 11 RCT Cardiac arrest from any cause Tenecteplase 50 mg bolus
Bozeman et al. 12 Prospective cohort Nontraumatic cardiac arrest Tenecteplase 0.5 mg/kg bolus
Bottiger et al. 13 RCT Cardiac arrest from any cause Tenecteplase 0.5 mg/kg bolus
* Table includes only studies which fibrinolytic dose/administration is clearly specified.

Take Home Points

  • The dose of tPA in cardiac arrest is somewhere between 50-100 mg given as a bolus +/- infusion.
  • According to the 2010 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, “Ongoing CPR is not an absolute contraindication for fibrinolysis.”
  • Some studies suggest allowing 15 minutes of CPR for drug to work.
  • Evidence is ‘best’ for PE; data does not support for undifferentiated cardiac arrest.
  • Anticoagulants, such as heparin, were used in most studies along with the fibrinolytic.

Last updated: Aug 14, 2016

1.
Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529-1535. [PubMed]
2.
Ruiz-Bailén M, Aguayo-de-Hoyos E, Serrano-Córcoles M, et al. Thrombolysis with recombinant tissue plasminogen activator during cardiopulmonary resuscitation in fulminant pulmonary embolism. A case series. Resuscitation. 2001;51(1):97-101. [PubMed]
3.
Janata K, Holzer M, Kürkciyan I, et al. Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Resuscitation. 2003;57(1):49-55. [PubMed]
4.
Sharifi M, Berger J, Beeston P, et al. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the “PEAPETT” study). Am J Emerg Med. 2016;34(10):1963-1967. [PubMed]
5.
Lederer W, Lichtenberger C, Pechlaner C, Kroesen G, Baubin M. Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out-of-hospital cardiac arrest. Resuscitation. 2001;50(1):71-76. [PubMed]
6.
Ruiz-Bailén M, Aguayo de, Serrano-Córcoles M, Diáz-Castellanos M, Ramos-Cuadra J, Reina-Toral A. Efficacy of thrombolysis in patients with acute myocardial infarction requiring cardiopulmonary resuscitation. Intensive Care Med. 2001;27(6):1050-1057. [PubMed]
7.
Schreiber W, Gabriel D, Sterz F, et al. Thrombolytic therapy after cardiac arrest and its effect on neurological outcome. Resuscitation. 2002;52(1):63-69. [PubMed]
8.
Kurkciyan I, Meron G, Sterz F, et al. Major bleeding complications after cardiopulmonary resuscitation: impact of thrombolytic treatment. J Intern Med. 2003;253(2):128-135. [PubMed]
9.
Böttiger B, Bode C, Kern S, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet. 2001;357(9268):1583-1585. [PubMed]
10.
Abu-Laban R, Christenson J, Innes G, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med. 2002;346(20):1522-1528. [PubMed]
11.
Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313. [PubMed]
12.
Bozeman W, Kleiner D, Ferguson K. Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation. 2006;69(3):399-406. [PubMed]
13.
Böttiger B, Arntz H, Chamberlain D, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359(25):2651-2662. [PubMed]

Bryan D. Hayes, PharmD, FAACT, FASHP

Bryan D. Hayes, PharmD, FAACT, FASHP

Chief Science Officer, ALiEM
Creator and Lead Editor, Capsules series, ALiEMU
Attending Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
  • Excellent review of the literature. I think the key here is, if you clinically suspect PE as the culprit, it is really the only diagnosis that seems to benefit from lytics peri-arrest. That being said physicians need to remember that MI/ACS is the number one killer, followed by PE is the number two killer for out of hospital arrest. Great post, great topic for discussion.

  • The data for PE is definitely there in the peri-arrest patient. The arresting STEMI patient should also be receiving this therapy. After all, the current AHA guidelines do consider thrombolytic therapy for STEMI to be appropriate if primary PCI is not readily available. I am not sending a coding patient to the cath lab. Yes, they need the intervention, but after they have been resuscitated. I personally use the 50 mg dose for PE and 100 mg for STEMI, both doses given over approximately 15 minutes. This is not the therapy for the undifferentiated arrest patient.

  • Josh Farkas

    Great post, thanks.

    I have a slightly different question. I’ve had two cardiac arrests due to PE where I used TPA during CPR. In both cases I pushed the entire bag (100mg) of TPA as a bolus. Both patients improved hemodynamically and got ROSC rapidly.

    The question then arose: should we follow the 100-mg TPA bolus with a prolonged infusion? Both of these patients were near death, and we were concerned that simply a bolus wouldn’t be sufficient to keep them out of trouble, perhaps they needed some prolonged TPA activity as well. In both cases we ended up waiting for a fair amount of time (perhaps 45 minutes) and then adding an infusion of TPA for about 90 minutes. It’s been a while since I had these cases but the more recent patient did wind up getting a very high total doe of TPA (probably around 140 mg total over a 2.5 hour period).

    Both of these patients did great, but that could certainly relate to luck rather than pharmacology. Any thoughts?

    Thanks,
    Josh

    • Bryan D. Hayes

      Josh,

      Thanks for your question. I haven’t seen any data to support an infusion after the initial bolus. Some of the studies used an infusion as part of the cardiac arrest treatment course, but still equaling a total tPA dose of no more than 100 mg. Heparin infusion would certainly be indicated, but probably not tPA.

      • emcrit

        Josh,
        think it is appropriate to reassess clot burden and hemodynamic function after the completion of tPA’s fibrinolytic activity (1-2 hrs??) Then decide. If they need prolonged infusion, catheter based makes a lot more sense as these pt’s would already have disrupted coagulopathy from the 1st dose.

  • Hassan Almaateeq

    great information Dr.Bryan.. thanks
    from where we got the idea of alteplase in AMI (35mg bolus then 50mg infusion, then 15mg infusion !! )

  • Julian Owen

    Great discussion in an area with little guidance. PEITHO and TOPCOAT looked at TNK and the bolus dose, weight-based protocol takes some of the mental work out of mg/kg dosing. Important as mentioned to continue good mechanical clot disruption (CPR) for a prolonged time after either agent is given.