Skip to main content
SpringerLink
Log in

The Effect of Vasopressin and Methylprednisolone on Return of Spontaneous Circulation in Patients with In-Hospital Cardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials

  • Systematic Review
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Introduction

Cardiac arrest is often fatal if not treated immediately by cardiopulmonary resuscitation to restore a normal heart rhythm and spontaneous circulation. We aim to evaluate the clinical benefits of vasopressin and methylprednisolone versus placebo for patients with in-hospital cardiac arrest.

Data Sources

We searched PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar from inception to October 17, 2021, by using search terms included "Vasopressin" AND "Methylprednisolone" AND "Cardiac arrest".

Study Selection and Data Extraction

We included randomized controlled trials (RCTs) that compared vasopressin and methylprednisolone to placebo. The main outcomes were the return of spontaneous circulation (ROSC) and survival to hospital discharge.

Data Synthesis

A total of three RCTs, with a total of 869 patients, were included. The pooled risk ratios (RRs) were calculated along with their 95% confidence intervals (CIs). Our result showed an increase in ROSC in patients who received vasopressin and methylprednisolone (RR = 1.32; 95% CI = [1.18, 1.47], p < 0.00001) when compared with the placebo group. However, there was no difference between both groups regarding survival to hospital discharge (RR = 1.76; 95% CI = [0.68, 4.56], p= 0.25).

Relevance to Patient Care and Clinical Practice

The current guidelines recommend epinephrine for patients with in-hospital cardiac arrest. Our meta-analysis updates clinicians about using vasopressin and methylprednisolone besides epinephrine, providing them with the best available evidence in managing patients with in-hospital cardiac arrest.

Conclusion

Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone besides epinephrine is associated with increased ROSC compared with placebo and epinephrine. However, high-quality RCTs are necessary before drawing a firm conclusion regarding the efficacy of vasopressin and methylprednisolone for patients with in-hospital cardiac arrest.

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
Fig. 2
Figure 3

Similar content being viewed by others

References

  1. Sandroni C, Nolan J, Cavallaro F, Antonelli M. In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival. Intensive Care Med. 2006;33(2):237–45.

    Article  Google Scholar 

  2. Andersen LW, Holmberg MJ, Berg KM, Donnino MW, Granfeldt A. In-hospital cardiac arrest: a review. JAMA. 2019;321(12):1200–10.

    Article  Google Scholar 

  3. Girotra S, Nallamothu BK, Spertus JA, Li Y, Krumholz HM, Chan PS, et al. Trends in survival after in-hospital cardiac arrest. N Engl J Med. 2012;367(20):1912–20.

    Article  CAS  Google Scholar 

  4. Olasveengen TM, Semeraro F, Ristagno G, Castren M, Handley A, Kuzovlev A, et al. European resuscitation council guidelines 2021: basic life support. Resuscitation. 2021;161:98–114.

    Article  Google Scholar 

  5. Neumar RW, Otto CW, Link MS, Kronick SL, Shuster M, Callaway CW, et al. Part 8: adult advanced cardiovascular life support. Circulation. 2010;122(18_suppl_3):S729–67

    Article  Google Scholar 

  6. Krismer AC, Dnser MW, Lindner KH, Stadlbauer KH, Mayr VD, Lienhart HG, et al. Vasopressin during cardiopulmonary resuscitation and different shock states. Am J Cardiovasc Drugs. 2006;6(1):51–68.

    Article  CAS  Google Scholar 

  7. Hékimian G, Baugnon T, Thuong M, Monchi M, Dabbane H, Jaby DL, et al. Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation. Shock. 2004;22(2):116–9.

    Article  Google Scholar 

  8. Ito T, Saitoh D, Takasu A, Kiyozumi T, Sakamoto T, Okada Y. Serum cortisol as a predictive marker of the outcome in patients resuscitated after cardiopulmonary arrest. Resuscitation. 2004;62(1):55–60.

    Article  CAS  Google Scholar 

  9. Sahebnasagh A, Nejad PS, Salehi-Abargouei A, Dehghani MH, Saghafi F. A characterization of cortisol level and adrenal reservation in human cardiopulmonary arrest: systematic review and meta-analysis. Syst Rev. 2021;10(1):266.

    Article  Google Scholar 

  10. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10(1):89.

    Article  Google Scholar 

  11. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160.

    Article  Google Scholar 

  12. Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. http://www.covidence.org. Accessed 03 Jan 2022.

  13. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Article  Google Scholar 

  14. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

  15. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  Google Scholar 

  16. Axtell AL, Funamoto M, Legassey AG, Moonsamy P, Shelton K, D’Alessandro DA, et al. Predictors of neurologic recovery in patients who undergo extracorporeal membrane oxygenation for refractory cardiac arrest. J Cardiothorac Vasc Anesth. 2020;34(2):356–62.

    Article  Google Scholar 

  17. Mentzelopoulos SD, Koliantzaki I, Karvouniaris M, Vrettou C, Mongardon N, Karlis G, et al. Publisher correction: exposure to stress-dose steroids and lethal septic shock after in-hospital cardiac arrest: individual patient data reanalysis of two prior randomized clinical trials that evaluated the vasopressin-steroids-epinephrine combination versus epinephrine alone. Cardiovasc Drugs Ther. 2018;32(6):639–41.

    Article  Google Scholar 

  18. Papastylianou AMS, Zakynthinos S, Zakynthinos E, Makris D, Sourlas S, Aloizos S, Mentzelopoulos S. Predictors of neurological recovery in refractory in hospital cardiac arrest. ESICM 2010 MONDAY SESSIONS 11 October 2010. Intensive Care Med. 2010;36:86–204.

    Article  Google Scholar 

  19. Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310(3):270–9.

    Article  Google Scholar 

  20. Ballew KA, ACP Journal Club. Combined vasopressin, steroids, and epinephrine improved survival in in-hospital cardiac arrest. Ann Intern Med. 2013;159(10):JC4.

    Article  Google Scholar 

  21. Haukoos J, Douglas IS, Sasson C. Vasopressin and steroids as adjunctive treatment for in-hospital cardiac arrest. JAMA. 2021;326(16):1583–5.

    Article  Google Scholar 

  22. Rehnberg JV, Patrick N. Vasopressin, steroids and epinephrine and neurologically favourable survival after in-hospital cardiac arrest. J Intensive Care Soc. 2015;16(1):77–9.

    Article  Google Scholar 

  23. Berg RA, Meaney PA, Nadkarni VM. Does a resuscitation pharmacologic bundle of epinephrine, terlipressin, and corticosteroids improve outcome from asphyxial cardiac arrest? Pediatr Crit Care Med. 2014;15(6):573–4.

    Article  Google Scholar 

  24. Andersen LW, Sindberg B, Holmberg M, Isbye D, Kjaergaard J, Zwisler ST, et al. Vasopressin and methylprednisolone for in-hospital cardiac arrest—protocol for a randomized, double-blind, placebo-controlled trial. Resusc Plus. 2021;5:100081.

    Article  Google Scholar 

  25. Andersen LW, Isbye D, Kjaergaard J, Kristensen CM, Darling S, Zwisler ST, et al. Effect of vasopressin and methylprednisolone vs placebo on return of spontaneous circulation in patients with in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2021;326:1586–94.

    Article  CAS  Google Scholar 

  26. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169(1):15–24.

    Article  CAS  Google Scholar 

  27. Reynolds JC, Salcido DD, Menegazzi JJ. Coronary perfusion pressure and return of spontaneous circulation after prolonged cardiac arrest. Prehosp Emerg Care. 2010;14(1):78–84.

    Article  Google Scholar 

  28. Paradis NA. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. J Am Med Assoc. 1990;263(8):1106.

    Article  CAS  Google Scholar 

  29. Leopold V, Gayat E, Pirracchio R, Spinar J, Parenica J, Tarvasmaki T, et al. Epinephrine and short-term survival in cardiogenic shock: an individual data meta-analysis of 2583 patients. Intensive Care Med. 2018;44(6):847–56.

    Article  CAS  Google Scholar 

  30. Angelos MG, Butke RL, Panchal AR, Torres CAA, Blumberg A, Schneider JE, et al. Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest. Resuscitation. 2008;77(1):101–10.

    Article  CAS  Google Scholar 

  31. Stroumpoulis K, Xanthos T, Rokas G, Kitsou V, Papadimitriou D, Serpetinis I, et al. Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study. Crit Care. 2008;12(2):R40.

    Article  Google Scholar 

  32. Gk Mutlu, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med. 2004;30(7):1276–91.

    Google Scholar 

  33. Schummer C, Wirsing M, Schummer W. The pivotal role of vasopressin in refractory anaphylactic shock. Anesth Analg. 2008;107(2):620–4.

    Article  CAS  Google Scholar 

  34. Sreevastava DK, Roy PK, Dass SK, Bhargava A, Chakrabarty A, Rai V, et al. Cardio-pulmonary resuscitation: an overview of recent advances in concepts and practices. Med J Armed Forces India. 2004;60(1):52–8.

    Article  CAS  Google Scholar 

  35. Stiell IG, Hébert PC, Wells GA, Vandemheen KL, Tang ASL, Higginson LAJ, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001;358(9276):105–9.

    Article  CAS  Google Scholar 

  36. Tsai M-S, Huang C-H, Chang W-T, Chen W-J, Hsu C-Y, Hsieh C-C, et al. The effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest patients: a pilot study. Am J Emerg Med. 2007;25(3):318–25.

    Article  Google Scholar 

  37. Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350(2):105–13.

    Article  CAS  Google Scholar 

  38. Soar J, Bottiger BW, Carli P, Couper K, Deakin CD, Djarv T, et al. European Resuscitation Council Guidelines 2021: adult advanced life support. Resuscitation. 2021;161:115–51.

    Article  Google Scholar 

  39. Belletti A, Benedetto U, Putzu A, Martino EA, Biondi-Zoccai G, Angelini GD, et al. Vasopressors during cardiopulmonary resuscitation. A network meta-analysis of randomized trials. Crit Care Med. 2018;46(5):e443–51.

    Article  CAS  Google Scholar 

  40. Shah K, Mitra AR. Use of corticosteroids in cardiac arrest-a systematic review and meta-analysis. Crit Care Med. 2021;49(6):e642–50.

    Article  CAS  Google Scholar 

  41. Shah K, Mitra AR. The authors reply. Crit Care Med. 2021;49(12):e1259–60.

    Article  Google Scholar 

  42. Hoybye M, Stankovic N, Holmberg M, Christensen HC, Granfeldt A, Andersen LW. In-hospital vs. out-of-hospital cardiac arrest: patient characteristics and survival. Resuscitation. 2021;158:157–65.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. McLaren Health Care, Flint, MI, USA

    Basel Abdelazeem

  2. Michigan State University, East Lansing, MI, USA

    Basel Abdelazeem & Arvind Kunadi

  3. Faculty of Medicine, Ain-Shams University, Cairo, Egypt

    Ahmed K. Awad & Merihan A. Elbadawy

  4. Detroit Medical Center/Sinai Grace Hospital, Detroit, MI, USA

    Nouraldeen Manasrah

  5. Wayne State University, Detroit, MI, USA

    Nouraldeen Manasrah

  6. East Carolina University, Greenville, NC, USA

    Soban Ahmad

  7. Ochsner Louisiana State University Health, Monroe, LA, USA

    Pramod Savarapu

  8. Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Kirellos Said Abbas

  9. Department of Internal Medicine, 401 S Ballenger Hwy, Flint, MI, 48532, USA

    Basel Abdelazeem

Authors
  1. Basel Abdelazeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed K. Awad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nouraldeen Manasrah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Merihan A. Elbadawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soban Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pramod Savarapu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kirellos Said Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arvind Kunadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Basel Abdelazeem.

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Basel Abdelazeem, Ahmed K. Awad, Nouraldeen Manasrah, Merihan A. Elbadawy, Soban Ahmad, Pramod Savarapu, Kirellos Said Abbas, and Arvind Kunadi declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

The data that support the findings of this study are available from the corresponding author, Basel Abdelazeem, upon reasonable request.

Code availability

Not applicable.

Author contributions

BA conceived and designed the work. AKA, MAE, BA collected the data. AKA, MAE, BA performed the analysis. NM, SA, PS, AK gave substantial contributions to data acquisition and interpretation for the work; NM and BA drafted the work. AKA, MA, SA, PS, AK revised it critically for important intellectual content. All the authors gave the final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript.

Ethics approval

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 25 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdelazeem, B., Awad, A.K., Manasrah, N. et al. The Effect of Vasopressin and Methylprednisolone on Return of Spontaneous Circulation in Patients with In-Hospital Cardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Cardiovasc Drugs 22, 523–533 (2022). https://doi.org/10.1007/s40256-022-00522-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-022-00522-z

Search

Navigation