Skip to main content

Advertisement

SpringerLink
Log in

Effect of prehospital epinephrine on out-of-hospital cardiac arrest: a report from the national out-of-hospital cardiac arrest data registry in Japan, 2011–2012

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The effect of prehospital epinephrine on neurological outcome in out-of-hospital cardiac arrest (OHCA) is still controversial. We sought to determine whether prehospital epinephrine administration was associated with improved outcomes in adult OHCA.

Methods

A nationwide, population-based, propensity score-matched study of OHCA patients from January 1, 2011, to December 31, 2012, in Japan was conducted. We included adult OHCA patients treated by emergency medical service personnel without an excessive delay. The primary outcome was neurologically favorable survival 1 month after OHCA.

Results

A total of 237,068 patients (16,616 with a shockable rhythm and 220,452 with a non-shockable rhythm) were included in the final cohort. A total of 4024 out of the 16,616 shockable OHCAs and 29,393 out of the 220,452 non-shockable OHCAs received prehospital epinephrine. In the propensity score-matched cohort, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival (shockable OHCA 7.6 vs. 17.9 %, OR 0.38 [95%CI 0.33–0.43]; non-shockable OHCA 0.6 vs. 1.2 %, OR 0.47 [95%CI 0.39–0.56]). In the subgroup analyses, prehospital epinephrine was significantly associated with poor neurological outcome in all subgroups. In the ancillary analyses, although the neurological outcome was worse as the number of epinephrine doses increased or the time to epinephrine increased, patients had a greater chance of a favorable neurological outcome only when a single dose of epinephrine was administered within 15 min of the emergency call in shockable OHCA.

Conclusions

Among adult OHCA patients, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival. Situations in which prehospital epinephrine is effective may be extremely limited.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW (2015) Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 132(18 Suppl 2):S444–S464

    Article  PubMed  Google Scholar 

  2. Soar J, Nolan JP, Böttiger BW, Perkins GD, Lott C, Carli P, Pellis T, Sandroni C, Skrifvars MB, Smith GB, Sunde K, Deakin CD, Adult advanced life support section Collaborators (2015) European Resuscitation Council guidelines for resuscitation 2015: section 3 adult advanced life support. Resuscitation 95:100–147

    Article  PubMed  Google Scholar 

  3. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L (2009) Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA 302:2222–2229

    Article  PubMed  Google Scholar 

  4. Jacobs IG, Finn JC, Jelinek GA, Oxer HF, Thompson PL (2011) Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 82:1138–1143

    Article  CAS  PubMed  Google Scholar 

  5. Olasveengen TM, Wik L, Sunde K, Steen PA (2012) Outcome when adrenaline (epinephrine) was actually given vs. not given—post hoc analysis of a randomized clinical trial. Resuscitation 83:327–332

    Article  PubMed  Google Scholar 

  6. Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S (2012) Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA 307:1161–1168

    Article  CAS  PubMed  Google Scholar 

  7. Nakahara S, Tomio J, Takahashi H, Ichikawa M, Nishida M, Morimura N, Sakamoto T (2013) Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ 347:f6829

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dumas F, Bougouin W, Geri G, Lamhaut L, Bougle A, Daviaud F, Morichau-Beauchant T, Rosencher J, Marijon E, Carli P, Jouven X, Rea TD, Cariou A (2014) Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients? J Am Coll Cardiol 64:2360–2367

    Article  CAS  PubMed  Google Scholar 

  9. Koscik C, Pinawin A, McGovern H, Allen D, Media DE, Ferguson T, Hopkins W, Sawyer KN, Boura J, Swor R (2013) Rapid epinephrine administration improves early outcomes in out-of-hospital cardiac arrest. Resuscitation 84:915–920

    Article  CAS  PubMed  Google Scholar 

  10. Arrich J, Sterz F, Herkner H, Testori C, Behringer W (2012) Total epinephrine dose during asystole and pulseless electrical activity cardiac arrests is associated with unfavourable functional outcome and increased in-hospital mortality. Resuscitation 83:333–337

    Article  CAS  PubMed  Google Scholar 

  11. Fukuda T, Yasunaga H, Horiguchi H, Ohe K, Fushimi K, Matsubara T, Yahagi N (2013) Health care costs related to out-of-hospital cardiopulmonary arrest in Japan. Resuscitation 84:964–969

    Article  PubMed  Google Scholar 

  12. Fukuda T, Matsubara T, Doi K, Fukuda-Ohashi N, Yahagi N (2014) Predictors of favorable and poor prognosis in unwitnessed out-of-hospital cardiac arrest with a non-shockable initial rhythm. Int J Cardiol 176:910–915

    Article  PubMed  Google Scholar 

  13. Fukuda T, Ohashi-Fukuda N, Matsubara T, Doi K, Kitsuta Y, Nakajima S, Yahagi N (2015) Trends in outcomes for out-of-hospital cardiac arrest by age in Japan: an observational study. Medicine (Baltimore) 94:e2049

    Article  Google Scholar 

  14. Cummins RO, Chamberlain D, Hazinski MF, Nadkarni V, Kloeck W, Kramer E, Becker L, Robertson C, Koster R, Zaritsky A, Bossaert L, Ornato JP, Callanan V, Allen M, Steen P, Connolly B, Sanders A, Idris A, Cobbe S (1997) Recommended guidelines for reviewing, reporting, and conducting research on in-hospital resuscitation: the in-hospital ‘Utstein style’. Am Heart Assoc Circ 95:2213–2239

    CAS  Google Scholar 

  15. Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, Cassan P, Coovadia A, D'Este K, Finn J, Halperin H, Handley A, Herlitz J, Hickey R, Idris A, Kloeck W, Larkin GL, Mancini ME, Mason P, Mears G, Monsieurs K, Montgomery W, Morley P, Nichol G, Nolan J, Okada K, Perlman J, Shuster M, Steen PA, Sterz F, Tibballs J, Timerman S, Truitt T, Zideman D, International Liaison Committee on Resuscitation, American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation; Resuscitation Councils of Southern Africa, ILCOR Task Force on Cardiac Arrest and Cardiopulmonary Resuscitation Outcomes (2004) Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa). Circulation 110:3385–3397

    Article  PubMed  Google Scholar 

  16. Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1:480–484

    Article  CAS  PubMed  Google Scholar 

  17. Rosenbaum PR, Donald BR (1985) Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat 39:33–38

    Google Scholar 

  18. Tang W, Weil MH, Sun S, Gazmuri RJ, Bisera J (1993) Progressive myocardial dysfunction after cardiac resuscitation. Crit Care Med 21:1046–1050

    Article  CAS  PubMed  Google Scholar 

  19. Angelos MG, Butke RL, Panchal AR, Torres CA, Blumberg A, Schneider JE, Aune SE (2008) Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest. Resuscitation 77:101–110

    Article  CAS  PubMed  Google Scholar 

  20. Ristagno G, Tang W, Huang L, Fymat A, Chang YT, Sun S, Castillo C, Weil MH (2009) Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit Care Med 37:1408–1415

    Article  CAS  PubMed  Google Scholar 

  21. Fries M, Tang W, Chang YT, Wang J, Castillo C, Weil MH (2006) Microvascular blood flow during cardiopulmonary resuscitation is predictive of outcome. Resuscitation 71:248–253

    Article  PubMed  Google Scholar 

  22. Goto Y, Maeda T, Goto Y (2013) Effects of prehospital epinephrine during out-of-hospital cardiac arrest with initial non-shockable rhythm: an observational cohort study. Crit Care 17:R188

    Article  PubMed  PubMed Central  Google Scholar 

  23. Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C, American Heart Association’s Get With The Guidelines-Resuscitation Investigators (2014) Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ 348:g3028

    Article  PubMed  PubMed Central  Google Scholar 

  24. Andersen LW, Berg KM, Saindon BZ, Massaro JM, Raymond TT, Berg RA, Nadkarni VM, Donnino MW, American Heart Association Get With the Guidelines–Resuscitation Investigators (2015) Time to epinephrine and survival after pediatric in-hospital cardiac arrest. JAMA 314:802–810

    Article  CAS  PubMed  Google Scholar 

  25. Iwami T, Kitamura T, Kiyohara K, Kawamura T (2015) Dissemination of chest compression-only cardiopulmonary resuscitation and survival after out-of-hospital cardiac arrest. Circulation 132:415–422

    Article  PubMed  Google Scholar 

  26. Blom MT, Beesems SG, Homma PC, Zijlstra JA, Hulleman M, van Hoeijen DA, Bardai A, Tijssen JG, Tan HL, Koster RW (2014) Improved survival after out-of-hospital cardiac arrest and use of automated external defibrillators. Circulation 130:1868–1875

    Article  PubMed  Google Scholar 

  27. SOS-KANTO 2012 Study Group (2015) Changes in treatments and outcomes among elderly patients with out-of-hospital cardiac arrest between 2002 and 2012: a post hoc analysis of the SOS-KANTO 2002 and 2012. Resuscitation 97:76–82

    Article  Google Scholar 

  28. Tagami T, Matsui H, Fushimi K, Yasunaga H (2016) Changes in therapeutic hypothermia and coronary intervention provision and in-hospital mortality of patients with out-of-hospital cardiac arrest: a Nationwide database study. Crit Care Med 44:488–495

    Article  CAS  PubMed  Google Scholar 

  29. Anderson ML, Nichol G, Dai D, Chan PS, Thomas L, Al-Khatib SM, Berg RA, Bradley SM, Peterson ED, American Heart Association’s Get With the Guidelines-Resuscitation Investigators (2016) Association between hospital process composite performance and patient outcomes after In-hospital cardiac arrest care. JAMA Cardiol 1:37–45

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the University of Tokyo. We thank all of the EMS personnel and participating physicians in Japan as well as the FDMA for their generous cooperation in establishing and maintaining the All-Japan Utstein Registry. The FDMA oversees/approves data queries and manuscript submissions. However, the author group is responsible for the conception of the project, all data analyses, and manuscript writing. TF, as the principal investigator, participated in the study concept and design; acquisition, analysis, or interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content. O-F N, MT, GM, KY, and YN participated in acquisition, analysis, or interpretation of data and critical revision of the manuscript for important intellectual content. TF performed statistical analysis. All authors approved the final version. TF had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Author information

Authors and Affiliations

  1. Department of Emergency and Critical Care Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Tatsuma Fukuda, Naoko Ohashi-Fukuda, Takehiro Matsubara & Naoki Yahagi

  2. Department of Disaster Medical Management, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masataka Gunshin

  3. The Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    Masataka Gunshin

  4. Department of Emergency Medicine, Graduate School of Medicine, University of Ryukyus, 207, Uehara, Nishihara-cho, Okinawa, 903-0215, Japan

    Yutaka Kondo

  5. Division of Acute Care Surgery, Trauma, and Surgical Critical Care, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA

    Yutaka Kondo

Authors
  1. Tatsuma Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoko Ohashi-Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takehiro Matsubara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masataka Gunshin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yutaka Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naoki Yahagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatsuma Fukuda.

Ethics declarations

This study was conducted in accordance with the amended Declaration of Helsinki. The institutional review board of the University of Tokyo approved the study with a waiver of informed consent because of the anonymous nature of the data (no. 10096).

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 58.3 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fukuda, T., Ohashi-Fukuda, N., Matsubara, T. et al. Effect of prehospital epinephrine on out-of-hospital cardiac arrest: a report from the national out-of-hospital cardiac arrest data registry in Japan, 2011–2012. Eur J Clin Pharmacol 72, 1255–1264 (2016). https://doi.org/10.1007/s00228-016-2093-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-016-2093-2

Keywords

Search

Navigation