Esmolol for the treatment of refractory ventricular fibrillation: a systematic review and meta-analysis

Richard Armour, Leon Baranowski

DOI: http://dx.doi.org/10.32378/ijp.v4i2.177

Abstract

Introduction: In light of recent research the efficacy of current advanced life support treatments has been questioned. Ventricular fibrillation refractory to standard therapy is a presentation which may benefit from an updated approach to management, with the b1-adrenoreceptor antagonist esmolol considered a therapy which may confer benefit. This systematic review and meta-analysis aimed to summarise the available evidence for esmolol in refractory ventricular fibrillation and identify if it may have any role in ACLS guidelines.

Methods:  The Cochrane Library, MEDLINE, CINAHL and EMBASE were systematically reviewed, along with trial registries and the grey literature. Studies were included in the review and subsequent meta-analysis if they examined adult patients in cardiopulmonary arrest with ventricular fibrillation refractory to at least three attempts at defibrillation and one dose of adrenaline or anti-arrhythmic therapy, who subsequently received intravenous esmolol.

Results:  2,617 results were obtained with 12 full-text articles reviewed for inclusion. Ultimately, two unique results fulfilled the inclusion criteria. A total of 66 patients were included in the meta-analysis, of whom 22 received esmolol. Esmolol appears to improve to survival to hospital admission (RR 2.63, 95% CI 1.37-5.07, p=0.004), temporary (RR 2.34, 95% CI 1.09-5.02, p=0.03) and sustained ROSC (RR 2.63, 95% CI 1.37-5.07, p=0.004) and favourable neurological status at hospital discharge (RR 3.44, 95% CI 1.11-10.67, p=0.03). The use of esmolol also appeared to likely confer a benefit in survival to hospital discharge (RR 2.82, 95% CI 1.01-7.93, p=0.05). However, significant bias was observed across all outcomes and overall these results were considered to be of low to very low certainty.

Conclusion: The use of esmolol in refractory ventricular fibrillation appears to improve survival to hospital admission, temporary and sustained ROSC and neurological status at hospital discharge, but not survival to hospital discharge. However, these results should be interpreted with caution in light of the limitations of included studies and the subsequent impact of these limitations on the outcomes included in the meta-analysis. Further high-quality, prospective research is required prior to recommending esmolol for use in refractory ventricular fibrillation.


Keywords

Cardiac Arrest; Ventricular Fibrillation; Out-of-Hospital Cardiac Arrest; Esmolol

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References

Myerburg, R. Sudden Cardiac Death: Interface Between Pathophysiology and Epidemiology. Cardiac Electrophysiology Clinics (Online). 2017;9(4):515-524 DOI: 10.1016/j.ccep.2017.07.003

Hayashi, M. Shimzu, W. & Albert, C. The Spectrum of Epidemiology Underlying Sudden Cardiac Death. Circulation Research (Online). 2015;116(12):1887-1906 DOI: 10.1161/CIRCRESAHA.116.304521

van Diepen, S. Girotra, S. Abella, B. Becker, L. Bobrow, B. Chan, P. Fahrenbruch, C. Granger, C. Jollis, K. McNally, B. White, L. Yannopoulos, D. & Rea, T. Multistate 5-Year Initiative to Improve Care for Out-of-Hospital Cardiac Arrest: Primary Results from the HeartRescure Project. Journal of the American Heart Association (Online). 2017;6(9):e005716 DOI: 10.1161/JAHA.117.005716

Perkins, G. & Brace-McDonnel, S. The UK Out-of-Hospital Cardiac Arrest Outcome (OHCAO) Project. BMJ Open (Online). 2015;5(10) DOI: 10.1136/bmjopen-2015-008736

Gardner, M. Leather, R. & Teo, K. Chapter 1: Epidemiology. Prevention of Sudden Cardiac Death from Ventricular Arrhythmia. Canadian Cardiovascular Society (Online). 1999. Available from: http://ccs.ca/Guidelines_library/1999_Prevention_ventricular_arrhythmia-1.pdf

Beck, B. Bray, J. Smith, K. Walker, T. Grantham, H. Hein, C. Thorrowgood, M. Smith, A. Inoue, M. Smith, T. Dicker, B. Swain, A. Bosley, E. Pemberton, K. McKay, M. Johnston-Leek, M. Cameron, P. Perkins, G. Nichol, G. & Finn, J. Epidemiology of Out-of-Hospital Cardiac Arrest (OHCA) in Australia and New Zealand: Results from the Aus-ROC OHCA Epistry. Resuscitation (Online). 2017;118(Supplement 1):e23 DOI: 10.1016/j.resuscitation.2017.08.065

Benjamin, E. Virani, S. Callaway, C. Chamberlain, A. Chang, A. Cheng, S. Chiuve, S. Cushman, M. Delling, F. Deo, R. de Ferranti, S. Ferguson, J. Fornage, M. Gillespie, C. Isasi, C. Jimenez, M. Jordan, L. Judd, S. Lackland, D. Lichtman, J. Lisabeth, L. Liu, S. Longenecker, C. Lutsey, P. Mackey, J. Machar, D. Matsushita, K. Mussolino, M. Nasr, K. O’Flaherty, M. Palaniappan, L. Pandey, A. Pandey, D. Reeves, M. Ritchey, M. Rodriquez, C. Roth, G. Rosamond, W. Sampson, U. Satou, G. Shah, S. Spartano, N. Tirschwell, D. Tsao, C. Voeks, J. Willey, J. Wilkins, J. Wu, H. Alger, H. Wong, S. & Muntner, P. Heart Disease and Stroke Statistics – 2018 Update: A Report from the American Heart Association. Circulation (Online). 2018;137(12):e67-e492

Park, G. Song, K. Shin, S. Lee, K. Ahn, K. Lee, E. Hong, K. & Ro, Y. Timely Bystander CPR Improves Outcomes Despite Longer EMS Times. American Journal of Emergency Medicine (Online). 2017;35(8):1049-1055 DOI: 10.1016/j.ajem.2017.02.033

Riddersholm, S. Kragholm, K. Mortensen, R. Pape, M. Hansen, C. Lippert, F. Torp-Pedersen, S. Christiansen, C. & Rasmussen, B. Association of Bystander Interventions and Hospital Length of Stay and Admission to Intensive Care Unit in Out-of-Hospital Cardiac Arrest Survivors. Resuscitation (Online). 2017;119:99-106 DOI: 10.1016/j.resuscitation.2017.07.014

Rajan, S. Wissenberg, M. Folke, F. Hansen, S. Gerds, T. Kragholm, K. Hansen, C. Karlsson, L. Lippert, F. Kober, L. Gislason, G. & Torp-Pedersen, C. Association of Bystander Cardiopulmonary Resuscitation and Survival According to Ambulance Response Times After Out-of-Hospital Cardiac Arrest. Circulation (Online). 2016;134(25):2095-2104 DOI: 10.1161/CIRCULATIONAHA.116.024400

Benger, J. Kirby, K. Black, S. Brett, S. Clout, M. Lazaroo, M. Nolan, J. Reeves, B. Robinson, M. Scott, L. Smartt, H. South, A. Stokes, E. Taylor, J. Thomas, M. Voss, S. Wordsworth, S. & Rogers, C. Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome. Journal of the American Medical Association (Online). 2018;320(8):779-791 DOI: 10.1001/jama.2018.11597

Perkins, G. Ji, C. Deakin, C. Quinn, T. Nolan, J. Scomparin, C. Regan, S. Long, J. Slowther, A. Pocock, H. Black, J. Moore, F. Fothergill, R. Rees, N. O’Shea, L. Docherty, M. Gunson, I. Han, K. Charlton, K. Finn, J. Petrou, S. Stallard, N. Gates, S. & Lall, R. A Randomised Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. New England Journal of Medicine (Online). 2018;379:711-721 DOI: 10.1056/NEJMoal806842

Kudenchuk, P. Brown, S. Daya, M. Rea, T. Nichol, G. Morrison, L. Leroux, B. Vaillancourt, C. Wittwer, L. Callaway, C. Christenson, J. Egan, D. Ornato, J. Weisfeldt, M. Stiell, I. Idris, A. Aufderheide, T. Dunford, J. Colella, R. Vilke, G. Brienza, A. Desvigne-Nickens, P. Gray, P. Gray, R. Seals, N. Straight, R. & Dorian, P. Amiodarone, Lidocaine or Placebo in Out-of-Hospital Cardiac Arrest. New England Journal of Medicine (Online). 2016;374:1711-1722 DOI: 10.1056/NEJMoal1514204

Jabre, P. Penaloza, A. Pinero, D. Duchateau, F. Borron, S. Javaudin, F. Richard, O. de Longueville, D. Bouilleau, G. Devaud, M. Heidet, M. Lejeune, C. Fauroux, S. Greingor, J. Manara, A. Hubert, J. Guihard, B. Vermylen, O. Lievens, P. Auffret, Y. Maisondieu, C. Huet, S. Claessens, B. Lapostolle, F. Javaud, N. Reuter, P. Baker, E. Vicaut, E. & Adnet, F. Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest. Journal of the American Medical Association (Online). 2018;319(8):779-787 DOI: 10.1001/jama.2018.0156

Jacobs, I. Finn, J. Jelinek, G. Oxer, H. & Thompson, P. Effect of Adrenaline on Survival in Out-of-Hospital Cardiac Arrest: A Randomised Double-Blind Placebo-Controlled Trial. Resuscitation (Online). 2011;82(9):1138-1143 DOI: 10.1016/j.resuscitation.2011.06.029

Holmberg, M. Holmberg, S. & Herlitz, J. Incidence, Duration and Survival of Ventricular Fibrillation in Out-of-Hospital Cardiac Arrest Patients in Sweden. Resuscitation (Online). 2000;44(1):7-17 DOI: 10.1016/S0300-9572(99)00155-0

Keller, S. & Halperin, H. Cardiac Arrest: the Changing Incidence of Ventricular Fibrillation. Current Treatment Options in Cardiovascular Medicine (Online). 2015;17(7):392 DOI: 10.1007/s11936-015-0392-z

Dorian, P. Cass, D. Schwartz, B. Cooper, R. Gelaznikas, R. & Barr, A. Amiodarone as Compated with Lidocaine for Shock-Resistant Ventricular Fibrillation. New England Journal of Medicine (Online). 2002;346:884-890 DOI: 10.1056/NEJMoa013029

Bourque, D. Daoust, R. Huard, V. & Charneux, M. -Blockers for the Treatment of Cardiac Arrest from Ventricular Fibrillation? Resuscitation (Online). 2007;75(3):434-444 DOI: 10.1016/j.resuscitation.2007.05.013

Yannopoulos, D. Bartos, J. Martin, C. Raveendran, G. Missov, E. Conterato, M. Frascone, R. Trembley, A. Sipprell, K. John, R. George, S. Carlson, K. Brunsvold, M. Garcia, S. & Aufderheide, T. Minnesota Resuscitation Consortium’s Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation. Journal of the American Heart Association (Online). 2016;5:e003732 DOI: 10.1161/JAHA.116.003732

Siao, F. Chiu, C. Chiu, C. Chen, Y. Chen, Y. Hsieh, Y. Lee, C. Wu, C. Chou, C. & Yen, H. Managing Cardiac Arrest with Refractory Ventricular Fibrillation in the Emergency Department: Conventional Cardiopulmonary Resuscitation versus Extracorporeal Cardiopulmonary Resuscitation. Resuscitation (Online). 2015;92:70-76 DOI: 10.1016/j.resuscitation.2015.04.016

Hira, R. & Nichol, G. Management of Refractory Ventricular Fibrillation: Extracorporeal Membrane Oxygenation or Epinephrine? Journal of the American College of Cardiology (Online). 2017;2(3) DOI: 10.1016/j.jacbts.2017.04.001

Surawicz, B. Ventricular Fibrillation. Journal of the American College of Cardiology (Online). 1985;5(6):43B-54B DOI: 10.1016/S0735-1097(85)80526-X

Luqman, N. Sung, R. Wang, C. & Kuo, C. Myocardial Ischemia and Ventricular Fibrillation: Pathophysiology and Clinical Implications. International Journal of Cardiology (Online). 2007;119(3):283-290 DOI: 10.1016/j.ijcard.2006.09.016

Tang, W. Weil, M. Gazmuri, R. Duggal, C. & Bisera, J. Pulmonary Ventilation/Perfusion Defects Induced by Epinephrine During Cardiopulmonary Resuscitation. Circulation (Online). 1991;84(5):2101-2107 DOI: 10.1161.01.CIR.84.5.2101

Hilwig, R. Kern, K. Berg, R. Sanders, A. Otto, C. & Ewy, G. Catecholamines in Cardiac Arrest: Role of Alpha Agonists, Beta-Adrenergic Blockers and High-Dose Epinephrine. Resuscitation (Online). 2000;47(2):203-208 DOI: 10.1016/S0300-9572(00)00261-6

Eschenhagen, T. Is Ryanodine Receptor Phosphorylation Key to the Fight or Flight Response and Heart Failure? The Journal of Clinical Investigation (Online). 2010;120(12):4197-4203 DOI: 10.1172/JCI45251

Zaugg, C. Current Concepts on Ventricular Fibrillation: A vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance and Termination of Ventricular Fibrillation. Indian Pacing and Electrophysiology Journal (Online). 2004;4(2):85-92

Ross, E. Redman, T. Harper, S. Mapp, J. Wampler, D. & Miramontes, D. Dual Defibrillation in Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis. Resuscitation (Online). 2016;106:14-17 DOI: 10.1016/j.resuscitation.2016.06.011

Hajjar, K. Berbari, I. El Tawil, C. Bou Chebl, R. & Abou Dagher, G. Dual Defibrillation in Patients with Refractory Ventricular Fibrillation. American Journal of Emergency Medicine (Online). 2018;36(8):1474-1479 DOI: 10.1016/j.ajem.2018.04.060

Pourmand, A. Galvis, J. & Yamane, D. The Controversial Role of Dual Sequential Defibrillation in Shockable Cardiac Arrest. American Journal of Emergency Medicine (Online). 2018;36(9):1674-1679 DOI: 10.1016/j.ajem.2018.05.078

Boehm, K. Keyes, D. Mader, L. & Moccia, J. First Report of Survival in Refractory Ventricular Fibrillation after Dual-Axis Defibrillation and Esmolol Administration. Western Journal of Emergency Medicine (Online). 2016;17(6):762-765 DOI: 10.5811/westjem.2016.8.30351

de Oliveira, F. Feitosa-Filho, G. & Ritt, L. Use of Beta-Blockers for the Treatment of Cardiac Arrest Due to Ventricular Fibrillation/Pulseless Ventricular Tachycardia: A Systematic Review. Resuscitation (Online). 2012;83(6):674-683 DOI: 10.1016/j.resuscitation.2012.01.025

Delorenzo, A. Nehme, Z. Yates, J. Bernard, S. & Smith, K. Double Sequential External Defibrillation for Refractory Ventricular Fibrillation Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis. Resuscitation (Online). 2018:Article in Press. DOI: 10.1016/j.resuscitation.2018.10.025

Wiest, D. & Haney, J. Clinical Pharmacokinetics and Therapeutic Efficacy of Esmolol. Clinical Pharmacokinetics (Online). 2012;51(6):347-356 DOI: 10.2165/11631590-000000000-00000

Tang, W. Weil, M. Sun, S. Noc, M. Yang, L. & Gazmuri, R. Epinephrine Increases the Severity of Post-Resuscitation Myocardial Dysfunction. Circulation (Online). 1995;92:3089-3093 DOI: 10.1161/01.CIR.92.10.3089

Theochari, E. Xanthos, T. Papdimitriou, D. Demestiha, T. Condilis, N. Nikolaos, N. Tsiftsi, K. & Papadimitriou, L. Selective Beta Blockade Improves the Outcome of Cardiopulmonary Resuscitation in a Swine Model of Cardiac Arrest. Annali Italiani di Chirurgia (Online). 2008;79(6):409-414

Killingsworth, C. Wei, C. Dell’Italia, L. Ardell, J. Kingsley, M. Smith, W. Ideker, R. & Walcott, G. Short-Acting Beta-Adrenergic Antagonist Esmolol Given at Reperfusion Improves Survival After Prolonged Ventricular Fibrillation. Circulation (Online). 2004;109:2469-2474 DOI: 10.1161/01.CIR.0000128040.43933.D3

Reynolds, E. How are cerebral performance category scores measured for audit and research purposes? Resuscitation (Online). 2014;85(5):e73-e74. DOI: 10.1016/j.resuscitation.2014.01.011

Critical Appraisal Skills Program. CASP Systematic Review Checklist (Online). 2018. Available from: https://casp-uk.net/wp-content/uploads/2018/03/CASP-Systematic-Review-Checklist-2018_fillable-form.pdf

Critical Appraisal Skills Program. CASP Cohort Studies Checklist (Online). 2018. Available from: https://casp-uk.net/wp-content/uploads/2018/03/CASP-Cohort-Study-Checklist-2018_fillable_form.pdf

Moola, S. Munn, Z. Tufanaru, C. Aromataris, E. Sears, K. Sfetcu, R. Currie, M. Qureshi, R. Mattis, P. Lisy, K. & Mu, P. Chapter 7: Systematic Reviews of Aetiology and Risk. Joanna Briggs Institute Reviewer’s Manual (Online). The Joanna Briggs Institute. 2017. Available from: https://joannabriggs.org/sites/default/files/2019-05/JBI_Critical_Appraisal-Checklist_for_Case_Control_Studies2017_0.pdf

Daya, M. Schmicker, R. Zive, D. Rea, T. Nichol, G. Buick, J. Brooks, S. Christenson, J. MacPhee, R. Craig, A. Rittenberger, J. Davis, D. May, S. Wigginton, J. & Wang, H. Out-of-Hospital Cardiac Arrest Survival Improving Over Time: Results from the Resuscitation Outcomes Consortium (ROC). Resuscitation (Online). 2015;91:108-115 DOI: 10.1016/j.resuscitation.2015.02.003

Viera, A. Odds Ratios and Risk Ratios: What’s the Difference and Why Does it Matter? Southern Medical Journal (Online). 2008;101(7):730-734 DOI: 10.1097/SMJ.0b013e31817a7ee4

Driver, B. Debaty, G. Plummer, D. & Smith, S. Use of Esmolol after Failure of Standard Cardiopulmonary Resuscitation to Treat Patients with Refractory Ventricular Fibrillation. Resuscitation (Online). 2014;85(10):1337-1341 DOI: 10.1016/j.resuscitation.2014.06.032

Lee, Y. Lee, K. Min, Y. Ahn, H. Sohn, Y. Lee, W. Oh, Y. Cho, G. Seo, J. Shin, D. Park, S. & Park, S. Refractory Ventricular Fibrillation Treated with Esmolol. Resuscitation (Online). 2016;107:150-155 DOI: 10.1016/j.resuscitation.2016.07.243

Benjamin, E. Virani, S. Callaway, C. Chamberlain, A. Chang, A. Cheng, S. Chiuve, S. Cushman, M. Delling, F. Deo, R. de Ferranti, S. Ferguson, J. Fornage, M. Gillespie, C. Isasi, C. Jimenez, M. Jordan, L. Judd, S. Lackland, D. Lichtman, J. Lisabeth, L. Liu, S. Longenecker, C. Lutsey, P. Mackey, J. Matchar, D. Matsushita, K. Mussolino, M. Nasir, K. O’Flaherty, M. Palaniappan, L. Pandey, A. Pandey, D. Reeves, M. Ritchey, M. Rodriguez, C. Roth, G. Rosamond, W. Sampson, U. Satou, G. Shah, S. Spartano, N. Tirschwell, D. Tsao, C. Voeks, J. Willey, J. Wilkins, J. Wu, J. Alger, H. Wong, S. & Munter, P. Heart and Stroke Statistics – 2018 Update: A Report from the American Heart Association. Circulation (Online). 2018;137:e67-e492 DOI: 10.1161/CIR.00000000000000558

Andrew, E. Nehme, Z. Bernard, S. & Smith, K. The Influence of Comorbidity on Survival and Long-Term Outcomes after Out-of-Hospital Cardiac Arrest. Resuscitation (Online). 2017;110:42-47 DOI: 10.1016/j.resuscitation.2016.10.018

Peberdy, M. Callaway, C. Neumar, R. Geocadin, R. Zimmerman, J. Donnino, M. Gabrielli, A. Silvers, S. Zaritsky, A. Merchant, R. Vanden Hoek, T. & Kronick, S. Post-Cardiac Arrest Care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation (Online). 2010;122:S768-S786 DOI: 10.1161/CIRCULATIONAHA.110.971002

Guyatt, G. Oxman, A. Vist, G. Kunz, R. Falck-Ytter, Y. Alonso-Coello, P. & Schunemann, H. GRADE: An Emerging Consensus on Rating Quality of Evidence and Strength of Recommendations. British Medical Journal (Online). 2008;336:924 DOI: 10.1136/bmj.39489.470347.AD



DOI: http://dx.doi.org/10.32378/ijp.v4i2.177

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