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VOLUME 28 , ISSUE 12 ( December, 2024 ) > List of Articles

Systematic Review/Meta-Analysis

The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis

Priyankar K Datta, Prachee Sathe, Avishek Roy, Tanima Baronia, Anirban Bhattacharjee, Riddhi Kundu

Keywords : Beta-blockers, Heart rate control, Ivabradine, Septic shock

Citation Information : Datta PK, Sathe P, Roy A, Baronia T, Bhattacharjee A, Kundu R. The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis. Indian J Crit Care Med 2024; 28 (12):1170-1179.

DOI: 10.5005/jp-journals-10071-24849

License: CC BY-NC 4.0

Published Online: 30-11-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Abstract

Objectives: Heart rate control using beta-blockers in sepsis has traditionally been avoided because of concerns with worsening cardiac index and organ perfusion. Recent studies has explored the possible beneficial effects of targeted heart rate control in patients with septic shock who have tachycardia despite initial resuscitation. We performed a systematic review and meta-analysis to explore the effects of heart rate control in septic shock patients. Methods: A systematic review and meta-analysis was conducted searching for studies from PubMed, Cochrane Central, and Embase registers for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with targeted rate control. The literature search was done to include studies from January 2013 to December 2023. Two independent researchers independently assessed the studies and included RCTS in which adult patients (>18 years of age) with septic shock were treated with targeted heart rate control vs placebo after initial resuscitation due to persistent tachycardia. The study data was extracted by two independent researchers. A random effects model was used to present the results. A trial sequential analysis (TSA) was performed for the primary outcome of 28-day mortality. Results: A total of 9 studies with a pooled sample size of 807 participants were included in the analysis. Eight of the included studies with a pooled sample size of 766 reported 28-day mortality. Targeted heart rate control was associated with a trend toward lower 28-day mortality [risk ratio (RR): 0.78; 95% CI: 0.62–0.99; p = 0.04; I2 = 48%]. Trial sequential analysis showed the cumulative effect lying within the zone of uncertainty, with diversity-adjusted required information size of 1,756 and pooled effect size of the pooled RR 0.78 (alpha-spending adjusted 95% CI: 0.53–1.15). There was a statistically significant lower heart rate associated with rate control (MD: –16.66; 95% CI: –23.89 to –9.42; p-value < 0.001) but no difference in mean arterial pressure. cardiac index, lactate levels, norepinephrine (NE) requirements, and ICU length of stay (LOS) in between the groups. Conclusion: Targeted heart rate control in patients with septic shock may be tolerated from a hemodynamic standpoint. However, the beneficial effect on mortality is less certain than was reported in the initial studies.

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  1. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study. Lancet 2020;395(10219):200–211. DOI: 10.1016/S0140-6736(19)32989-7.
  2. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;49(11):e1063–1143. DOI: 10.1007/s00134-021-06506-y.
  3. Ray S, Kumar P, Juneja D, Nasa P, Munjal M, Maharaj M, et al. The Indian Society of Critical Care Medicine position statement on the management of sepsis in resource-limited settings. Indian J Crit Care Med 2024;28(S2):S4–S19. DOI: 10.5005/jp-journals-10071-24682.
  4. Samavedam S. Sepsis and the heart: More to learn. Indian J Crit Care Med 2022;26(7):775–777. DOI: 10.5005/jp-journals-10071-24262.
  5. Lescroart M, Pequignot B, Kimmoun A, Klein T, Levy B. Beta-blockers in septic shock: What is new? J Intensive Med 2022;2(3):150–155. DOI: 10.1016/j.jointm.2022.01.004.
  6. Kimmoun A, Louis H, Al Kattani N, Delemazure J, Dessales N, Wei C, et al. β1-Adrenergic inhibition improves cardiac and vascular function in experimental septic shock. Crit Care Med 2015;43(9):e332– e340. DOI: 10.1097/CCM.0000000000001078.
  7. Suzuki T, Morisaki H, Serita R, Yamamoto M, Kotake Y, Ishizaka A, et al. Infusion of the β-adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med 2005;33(10):2294–2301. DOI: 10.1097/01.ccm.0000182796.11329.3b.
  8. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: A randomized clinical trial. JAMA 2013;310(16):1683. DOI: 10.1001/jama.2013.278477.
  9. Hasegawa D, Sato R, Prasitlumkum N, Nishida K, Takahashi K, Yatabe T, et al. Effect of ultrashort-acting β-blockers on mortality in patients with sepsis with persistent tachycardia despite initial resuscitation. Chest 2021;159(6):2289–2300. DOI: 10.1016/j.chest.2021.01.009.
  10. Zhang J, Chen C, Liu Y, Yang Y, Yang X, Yang J. Benefits of esmolol in adults with sepsis and septic shock: An updated meta-analysis of randomized controlled trials. Medicine 2022;101(27):e29820. DOI: 10.1097/MD.0000000000029820.
  11. Kakihana Y, Nishida O, Taniguchi T, Okajima M, Morimatsu H, Ogura H, et al. Efficacy and safety of landiolol, an ultra-short-acting β1-selective antagonist, for treatment of sepsis-related tachyarrhythmia (J-Land 3S): A multicentre, open-label, randomised controlled trial. Lancet Respir Med 2020;8(9):863–872. DOI: 10.1016/S2213-2600(20)30037-0.
  12. Whitehouse T, Hossain A, Perkins GD, Gordon AC, Bion J, Young D, et al. Landiolol and organ failure in patients with septic shock: The STRESS-L randomized clinical trial. JAMA 2023;330(17):1641. DOI: 10.1001/jama.2023.20134.
  13. Datta PK, Rewari V, Ramachandran R, Singh PM, Ray BR, Aravindan A, et al. Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial. Anaesth Intensive Care. 2021;49(5):366–378. DOI: 10.1177/0310057X211009913.
  14. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009;151(4):264–269, W64. DOI: 10.1371/journal.pmed.1000097.
  15. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343(oct18 2):d5928. DOI: 10.1136/bmj.d5928.
  16. Nuding S, Schröder J, Presek P, Wienke A, Müller-Werdan U, Ebelt H, et al. Reducing elevated heart rates in patients with multiple organ dysfunction syndrome with the If (Funny Channel Current) inhibitor ivabradine. Shock 2018;49(4):402–411. DOI: 10.1097/SHK.0000000000000992.
  17. Xinqiang L, Weiping H, Miaoyun W, Wenxin Z, Wenqiang J, Shenglong C, et al. Esmolol improves clinical outcome and tissue oxygen metabolism in patients with septic shock through controlling heart rate. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2015;27(9):759–763. PMID: 26955704.
  18. Wang S, Li M, Duan J, Yi L, Huang X, Chen D, et al. Effect of esmolol on hemodynamics and clinical outcomes in patients with septic shock. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017;29(5):390–395. DOI: 10.3760/cma.j.issn.2095-4352.2017.05.002.
  19. Liu H, Ding XF, Zhang SG, Wang HX, Luo YG, Duan XG, et al. Effect of esmolol in septic shock patients with tachycardia: A randomized clinical trial. Zhonghua Yi Xue Za Zhi 2019;99(17):1317–1322. DOI: 10.3760/cma.j.issn.0376-2491.2019.17.009.
  20. Cocchi MN, Dargin J, Chase M, Patel PV, Grossestreuer A, Balaji L, et al. Esmolol to treat the hemodynamic effects of septic shock: A randomized controlled trial. Shock 2022;57(4):508–517. DOI: 10.1097/SHK.0000000000001905.
  21. Yang S, Liu Z, Yang W, Zhang G, Hou B, Liu J, et al. Effects of the β-blockers on cardiac protection and hemodynamics in patients with septic shock: A prospective study. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014;26(10):714–717. DOI: 10.3760/cma.j.issn.2095-4352.2014.10.007.
  22. Schünemann HJ, Wiercioch W, Brozek J, Etxeandia-Ikobaltzeta I, Mustafa RA, Manja V, et al. GRADE Evidence to decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT. J Clin Epidemiol 2017;81:101–110. DOI: 10.1016/j.jclinepi.2016.09.009.
  23. Lanspa MJ, Shahul S, Hersh A, Wilson EL, Olsen TD, Hirshberg EL, et al. Associations among left ventricular systolic function, tachycardia, and cardiac preload in septic patients. Ann Intensive Care 2017;7(1):17. DOI: 10.1186/s13613-017-0240-2.
  24. Na SJ, Oh DK, Park S, Lee YJ, Hong SB, Park MH, et al. The association between tachycardia and mortality in septic shock patients according to serum lactate level: A nationwide multicenter cohort study. J Korean Med Sci 2023;38(40):e313. DOI: 10.3346/jkms.2023.38.e313.
  25. Geri G, Vignon P, Aubry A, Fedou AL, Charron C, Silva S, et al. Cardiovascular clusters in septic shock combining clinical and echocardiographic parameters: A post hoc analysis. Intensive Care Med 2019;45(5):657–667. DOI: 10.1007/s00134-019-05596-z.
  26. Vieillard-Baron A. Septic cardiomyopathy. Ann Intensive Care 2011;1(1):6. DOI: 10.1186/2110-5820-1-6.
  27. Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol 2021;18(6):424–434. DOI: 10.1038/s41569-020-00492-2.
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