Efficacy and Safety of Esmolol in Treatment of Patients with Septic Shock

Wei Du, Xiao-Ting Wang, Yun Long, Da-Wei Liu, Wei Du, Xiao-Ting Wang, Yun Long, Da-Wei Liu

Abstract

Background: Previous studies have suggested that β1-receptor blockers benefit septic shock patients. This study aimed to determine whether β1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis.

Methods: Consecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) ≥100 beats/min. Esmolol therapy achieved the target HR of 10-15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR.

Results: Sixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 ± 22.7 vs. 49.9 ± 23.7 ml, t = -2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 ± 0.8 vs. 1.1 ± 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 ± 3.3 vs. 4.3 ± 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 ± 0.3 vs. 1.1 ± 0.2 cm, t = 2.4, P = 0.034).

Conclusions: SV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use.

Trial registration: ClinicalTrials.gov, NCT01920776; https://ichgcp.net/clinical-trials-registry/NCT01920776?term=NCT01920776&rank=1.

Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
ROC curve comparing an increase in MAPSElat with an increase in SV before esmolol therapy in septic shock patients. The area under the curve was 0.911 ± 0.05 (P = 0.001). The cutoff value of MAPSElat before esmolol use for predicting an increase in SV in septic shock patients was 1.32, resulting in a sensitivity of 66.7% and a specificity of 99.9%. ROC: Receiver operating characteristic; MAPSElat: Mitral lateral annular plane systolic excursion; SV: Stroke volume.

References

    1. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. 2007;35:1599–608. doi: 10.1097/01.CCM.0000266683.64081.02.
    1. Surbatovic M, Veljovic M, Jevdjic J, Popovic N, Djordjevic D, Radakovic S. Immunoinflammatory response in critically ill patients: Severe sepsis and/or trauma. Mediators Inflamm 2013. 2013 362793. doi: 10.1155/2013/362793.
    1. Schmittinger CA, Torgersen C, Luckner G, Schröder DC, Lorenz I, Dünser MW. Adverse cardiac events during catecholamine vasopressor therapy: A prospective observational study. Intensive Care Med. 2012;38:950–8. doi: 10.1007/s00134-012-2531-2.
    1. Rudiger A. Beta-block the septic heart. Crit Care Med. 2010;38(10 Suppl):S608–12. doi: 10.1097/CCM.0b013e3181f204ca.
    1. 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;310:1683–91. doi: 10.1001/jama.2013.278477.
    1. Friese RS, Barber R, McBride D, Bender J, Gentilello LM. Could beta blockade improve outcome after injury by modulating inflammatory profiles? J Trauma. 2008;64:1061–8. doi: 10.1097/TA.0b013e3181684cf0.
    1. Salim A, Hadjizacharia P, Brown C, Inaba K, Teixeira PG, Chan L, et al. Significance of troponin elevation after severe traumatic brain injury. J Trauma. 2008;64:46–52. doi: 10.1097/TA.0b013e31815eb15a.
    1. Schroeppel TJ, Fischer PE, Zarzaur BL, Magnotti LJ, Clement LP, Fabian TC, et al. Beta-adrenergic blockade and traumatic brain injury: Protective? J Trauma. 2010;69:776–82. doi: 10.1097/TA.0b013e3181e981b8.
    1. Arbabi S, Ahrns KS, Wahl WL, Hemmila MR, Wang SC, Brandt MM, et al. Beta-blocker use is associated with improved outcomes in adult burn patients. J Trauma. 2004;56:265–9. doi: 10.1097/01.TA.0000109859.91202.C8.
    1. Rudiger A, Singer M. The heart in sepsis: From basic mechanisms to clinical management. Curr Vasc Pharmacol. 2013;11:187–95. doi: 10.2174/1570161111311020008.
    1. Sanfilippo F, Santonocito C, Morelli A, Foex P. Beta-blocker use in severe sepsis and septic shock: A systematic review. Curr Med Res Opin. 2015;31:1817–25. doi: 10.1185/03007995.2015.1062357.
    1. Ince C. To beta block or not to beta block; that is the question. Crit Care. 2015;19:339. doi: 10.1186/s13054-015-1059-6.
    1. Mayo PH, Beaulieu Y, Doelken P, Feller-Kopman D, Harrod C, Kaplan A, et al. American College of Chest Physicians/La Sociétéde Réanimation de Langue Française statement on competence in critical care ultrasonography. Chest. 2009;135:1050–60. doi: 10.1378/chest.08-2305.
    1. Expert Round Table on Ultrasound in ICU. International expert statement on training standards for critical care ultrasonography. Intensive Care Med. 2011;37:1077–83. doi: 10.1007/s00134-011-2246-9.
    1. He H, Long Y, Liu D, Wang X, Zhou X. Clinical classification of tissue perfusion based on the central venous oxygen saturation and the peripheral perfusion index. Crit Care. 2015;19:330. doi: 10.1186/s13054-015-1057-8.
    1. Vallée F, Vallet B, Mathe O, Parraguette J, Mari A, Silva S, et al. Central venous-to-arterial carbon dioxide difference: An additional target for goal-directed therapy in septic shock? Intensive Care Med. 2008;34:2218–25. doi: 10.1007/s00134-008-1199-0.
    1. Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330:1717–22. doi: 10.1056/NEJM199406163302404.
    1. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107–33. doi: 10.1016/j.echo.2008.11.023.
    1. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quiñones MA. Doppler tissue imaging: A noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527–33. doi: 10.2174/1570161111311020008.
    1. Khankirawatana B, Khankirawatana S, Peterson B, Mahrous H, Porter TR. Peak atrial systolic mitral annular velocity by Doppler tissue reliably predicts left atrial systolic function. J Am Soc Echocardiogr. 2004;17:353–60. doi: 10.1016/j.echo.2003.12.023.

Source: PubMed

3
Se inscrever