Article

Time to change course: comment on the section regarding automated external defibrillator use in the 2013 American Heart Association consensus statement on in-hospital resuscitation

Correspondence / American Journal of Emergency Medicine 32 (2014) 14131432 1431

venous thromboembolism disease, there are important differences in severity and mortality risk. However, the treatment is almost identical for most patients [4].

There is a suggestion to adjust the intensity of anticoagulant therapy in PTE by continuing stronger type of anticoagulation (eg, low- molecular-weight heparin or fondaparinoux) until the disease gets under control (eg, until satisfactory improvement in symptoms and results of D-dimer, oxygen saturation, electrocardiogram, echocardio- gram, Computed tomography pulmonary angiography, etc) [5]. In addition to the lack of supporting studies, the obvious limitation of this approach is prolonged administration of low-molecular-weight hepa- rin/fondaparinoux, which represents significant discomfort for patients. Recent advance in VTE therapy is the anticoagulant rivaroxaban, the first oral anticoagulant for VTE, recommended in the 9th American College of Chest Physicians Guidelines in 2012 [6]. EINSTEIN PE and DVT trials served as the evidence for this recommendation as well as approval from Food and Drug Administration and The European Committee for Medicinal Products for Human Use [7-10]. Rivaroxaban was used in the EINSTEIN program in doses 30 mg/d for 3 weeks, followed by 20 mg for 3, 6, or 12 months. Therefore, the practical way toindividualize therapy in PTE is to administer 30 mg of rivaroxaban per day for 3 weeks (if this drug was chosen) but not to decrease the dose to 20 mg daily until

substantial improvement in the aforementioned categories is achieved.

Indeed, the higher dose of rivaroxaban is more effective, as shown in the article by Kubitza et al [11]. Assessment of hemorrhagic risk would be needed in individual patients, using published criteria [12]. The individualized approach to PTE initial anticoagulant treatment needs confirmation in a randomized controlled clinical trial. The risk of heparin- induced thrombocytopenia, related to rivaroxaban, is very low, as no such case report has been published in available medical literature. Search of PubMed with key words “Heparin-induced thrombocytopenia” (HIT) and “rivaroxaban” was performed on August 18, 2014, resulting in no case reports on this topic. To the contrary, rivaroxaban has not been shown to have an effect on the interaction of platelet factor 4 or anti-platelet factor 4/heparin antibodies with platelets. Moreover, a prospective study has been planed to investigate if rivaroxaban might be good therapeutic option for HIT [13]. Meanwhile, the first case reports are published showing good response to rivaroxaban in HIT [14].

Conclusion

A simple way to adjust the intensity of anticoagulant therapy for PTE is suggested, using doses of rivaroxaban, recommended in relevant contemporary guidelines. This drug might be administered in higher of 2 doses for longer period, if substantial improvement is not reached within 3 weeks. Randomized Controlled clinical trials are needed to evaluate potential benefits of such approach.

Acknowledgment

This work has been supported by the Serbian Ministry of Education and Science, grant number 175092.

The author would like to thank Associate Professor Vera Ignjatovic PhD, BSc (Hons), Co-Group Leader, Haematology Research, Murdoch Childrens Research Institute; Principal Fellow, Department of Paediatrics, The University of Melbourne, Australia, for the scientific edit of the manuscript.

Goran P. Koracevic, MD, PhD Department of Cardiology, Clinical Center and Medical Faculty, University of Nis, Nis, Serbia

9.brig. 53/50 18000 Nis, Serbia Tel.: +381 18533644; fax: +381 18238770

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.09.003

References

  1. Kaczynska A, Kostrubiec M, Pacho R, Kunikowska J, Pruszczyk P. Elevated D-dimer concentration identifies patients with incomplete recanalization of pulmonary artery thromboemboli despite 6 months anticoagulation after the first episode of acute pulmonary embolism. Thromb Res 2008;122:21-5.
  2. Morris TA. Why acute pulmonary embolism becomes chronic thromboembolic pulmonary hypertension: clinical and genetic insights. Curr Opin Pulm Med 2013; 19:422-9.
  3. Koracevic GP. Current protocol for initial anticoagulants in pulmonary embolism: one size fits all? Am J Emerg Med 2011;29:460-2.
  4. Koracevic GP. Treatment for deep vein thrombosis and pulmonary thromboem- bolism is almost the same-it does not seem quite logical. J Emerg Med 2013;45: e49-51.
  5. Koracevic GP. Time to individualize duration of parenteral anticoagulation in pulmonary thromboembolism? Am J Emerg Med 2012;30:1004-6.
  6. Kearon C, Akl EA, Comerota AJ, American College of Chest Physicians, Prandoni P, Bounameaux H, et al. antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 141(2 Suppl). Chest, 9th ed.; 2012.

    p. e419S-94S.

    EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363:2499-510.

  7. EINSTEIN-PE Investigators, Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97.
  8. FDA expands use of Xarelto to treat, reduce recurrence of Blood clots. downloaded from http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm326654. htm. [downloaded 8/18/2014].
  9. European Approval for Rivaroxaban for PE/DVT. downloaded from http://www. medscape.com/viewarticle/774885. [downloaded 8/18/2014].
  10. Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005;78:412-21.
  11. Nieto JA, Solano R, Ruiz-Ribo MD, Riete Investigators, Ruiz-Gimenez N, Prandoni P, et al. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry. J Thromb Haemost 2010;8: 1216-22.
  12. Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, et al. Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Throm- bolysis 2014 [Epub ahead of print].
  13. Ng HJ, Than H, Teo EC. First experiences with the use of rivaroxaban in the treatment of heparin-induced thrombocytopenia. Thromb Res 2014 [Epub ahead of print].

    Time to change course: comment on the section regarding automated external defibrillator

    use in the 2013 American Heart Association consensus statement on in-hospital resuscitation?

    To the Editor,

    As one who helped bring the problem of delayed in-hospital defibrillation to the attention of the American Heart Association (AHA) in the mid-1980s, I have long been interested in how the issue is addressed by the AHA. I find the approach to delayed in-hospital defibrillation in their recent statement [1] troubling–specifically the continued promotion of automated external defibrillators (AEDs) as the best way to address the problem.

    The use of AEDs in hospitals was officially endorsed in the 2000 AHA/International Liaison Committee on Resuscitation Emergency Cardiac Care Guidelines, but it had by then been advocated for several years in AHA instructional materials and statements, before any supporting studies were available. The AHA continues its support of the AED approach in the current statement.

    The references cited in support of the AED approach were all published after 2003. Three of the citations were small single-center studies lacking a control group, as the statement acknowledges. The single cited study with a historical control [2] has serious problems–

    ? No industry relationships or sources of support.

    1432 Correspondence / American Journal of Emergency Medicine 32 (2014) 14131432

    Table

    Survival to hospital discharge (AED vs manual defibrillator)

    Study

    Survival VF/VT

    Survival asystole and PEA

    Survival overall

    Chan et al [3]

    38.4% (n = 947) vs 39.8% (n = 1132), P = .99

    10.4% (n = 3568) vs 15.4%, (n = 6048), P b .001

    16.3% (n = 4515) vs 19.3% (n = 7180), P b .001

    Forcina et al [4]

    31% (n = 45) vs 29% (n = 42), P = .8

    15% (n = 239) vs 23% (n = 235), P = .04

    18% (n = 284) vs 23% (n = 277), P = .09

    Smith et al [5]

    54% (n = 20) vs 38% (n = 18), P = .43

    16% (n = 71) vs 15% (n = 67), P = 1.0

    22% (n = 82) vs 19% (n = 84), P = .56

    VF indicates ventricular fibrillation; VT, ventricular tachycardia; and PEA, pulseless electrical activity.

    principally, the conflation of the addition of AEDs and dual-mode (AED or manual) defibrillators with an intensive hospital-wide early- defibrillation education program implemented at the same time, together with lack of data regarding when (or if) AEDs were used. It is therefore impossible to separate out the factors of the intensive education program, the Hawthorne effect, and the addition of AED technology. These limitations are not mentioned in the statement.

    In contrast, the consensus statement does speculate about possible limitations of the single cited study that showed no Survival benefit from in-hospital AED use. This large multicenter study by Chan et al. [3], using the AHA’s own data (from the Get With the Guidelines- Resuscitation registry), showed no survival improvement from AED use for tachyarrhythmic arrests and a decrease in survival from nonshockable initial rhythms. The consensus statement says that “it is likely that AEDs were placed in areas less well served by the cardiac arrest team, representing a selection bias,” but that hypothesis seems incompatible with the reported finding that “these relationships between AED use and survival were consistent in monitored and nonmonitored hospital units for each rhythm type.”

    Two studies that the AHA statement fails to cite largely support the findings of the study of Chan et al. [3]. In 2007, before that study, an article was published about survival rates at a large Michigan hospital before and after the hospital-wide change from manual defibrillators to devices with an AED mode, at a cost of 2 million dollars [4]. Survival rates from the year before implementation were compared with rates for the year after. The results were remarkably similar to the study of Chan et al [3]: no survival benefit for arrests with Shockable rhythms and a decrease in survival for nonshockable rhythms. A similar before- and-after study conducted at an Australian hospital was reported in 2011 [5]. That smaller study looked at the 3 years before and 3 years after AED deployment, and it also showed no overall improvement in survival to discharge (Table).

    Despite this evidence, the AHA statement calls for controlled trials to further evaluate AED use in hospitals. Although randomized controlled trials are always desirable, they are very difficult to conduct in the area of resuscitation research. This obstacle results in a built-in resistance to change in the guidelines process that has been described by other authors [6,7]. Parts of the guidelines that may have been introduced

    because they seemed to make sense or were marketed well are continued for decades despite little or no supporting evidence. The AHA/ ILCOR statement’s insistence on a probably unachievable Level of evidence before changing the guidelines will ensure that years, if not decades, will pass before things change.

    The problem of delayed in-hospital defibrillation will not go away. Current science is good enough to show that relying on AED technology alone to fix the problem is a dead end–but rapid defibrillation remains the only intervention known to bring patients in cardiac arrest back to life. The AHA/ILCOR should actively encourage investigators and hospitals to explore other approaches to shortening defibrillation delays.

    John A. Stewart, RN, MA

    Seattle, WA

    Corresponding author. 9407-A Linden Ave N, Seattle

    WA 98103. Tel.: +1 206 683 9736

    E-mail address: [email protected]

    http://dx.doi.org/10.1016/j.ajem.2014.09.012

    References

    Morrison LJ, Neumar RW, Zimmerman JL, Link MS, Newby LK, McMullan Jr PW, et al. Strategies for improving survival after in-hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation 2013;127(14):1538-63.

  14. Zafari AM, Zarter SK, Heggen V. A program encouraging Early defibrillation results in improved in-hospital resuscitation efficacy. J Am Coll Cardiol 2004;44(4): 846-52.
  15. Chan PS, Krumholz HM, Spertus JA, Jones PG, Cram P, Berg RA, et al. Automated external defibrillators and survival after in-hospital cardiac arrest. JAMA 2010;304(19):2129-36.
  16. Forcina MS, Farhat AY, O’Neil WW, Haines DE. Cardiac arrest survival after implementation of automated external defibrillator technology in the in-hospital setting. Crit Care Med 2009;37(4):1229-36.
  17. Smith RJ, Hickey BB, Santamaria JD. Automated external defibrillators and in- hospital cardiac arrest: patient survival and device performance at an Australian teaching hospital. Resuscitation 2011;82(12):1537-42.
  18. Kern KB, Valenzuela TD, Clark LL, Berg RA, Hilwig RW, Berg MD, et al. An alternative approach to advancing resuscitation science. Resuscitation 2005;64(3):261-8.
  19. Sanders AB, Ewy GA. Cardiopulmonary resuscitation in the real world: when will the guidelines get the message? JAMA 2005;293(3):363-5.

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