Microvascular effects of heart rate control with esmolol in patients with septic shock: A pilot study

Andrea Morelli, Abele Donati, Christian Ertmer, Sebastian Rehberg, Tim Kampmeier, Alessandra Orecchioni, Annalia D'Egidio, Valeria Cecchini, Giovanni Landoni, Paolo Pietropaoli, Martin Westphal, Mario Venditti, Alexandre Mebazaa, Mervyn Singer

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Objective:: β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation. Design:: Prospective, observational clinical study. Setting:: Multidisciplinary ICU at a university hospital. Measurements and Main Results:: After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p <0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p = 0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p = 0.002). PaO2 and pH increased while PaCO2 decreased (all p <0.05). Of note, norepinephrine requirements were significantly reduced by selective β-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] μg/kg/min; p = 0.03). Conclusions:: This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.

Original languageEnglish
Pages (from-to)2162-2168
Number of pages7
JournalCritical Care Medicine
Volume41
Issue number9
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Septic Shock
Heart Rate
Norepinephrine
Stroke Volume
Hemodynamics
Low Cardiac Output
Microcirculation
Cardiac Catheterization
Adrenergic Receptors
Catecholamines
Observational Studies
esmolol
Arterial Pressure
Maintenance
Therapeutics

Keywords

  • β-blockers
  • esmolol
  • septic shock
  • tachycardia

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Morelli, A., Donati, A., Ertmer, C., Rehberg, S., Kampmeier, T., Orecchioni, A., ... Singer, M. (2013). Microvascular effects of heart rate control with esmolol in patients with septic shock: A pilot study. Critical Care Medicine, 41(9), 2162-2168. https://doi.org/10.1097/CCM.0b013e31828a678d

Microvascular effects of heart rate control with esmolol in patients with septic shock : A pilot study. / Morelli, Andrea; Donati, Abele; Ertmer, Christian; Rehberg, Sebastian; Kampmeier, Tim; Orecchioni, Alessandra; D'Egidio, Annalia; Cecchini, Valeria; Landoni, Giovanni; Pietropaoli, Paolo; Westphal, Martin; Venditti, Mario; Mebazaa, Alexandre; Singer, Mervyn.

In: Critical Care Medicine, Vol. 41, No. 9, 09.2013, p. 2162-2168.

Research output: Contribution to journalArticle

Morelli, A, Donati, A, Ertmer, C, Rehberg, S, Kampmeier, T, Orecchioni, A, D'Egidio, A, Cecchini, V, Landoni, G, Pietropaoli, P, Westphal, M, Venditti, M, Mebazaa, A & Singer, M 2013, 'Microvascular effects of heart rate control with esmolol in patients with septic shock: A pilot study', Critical Care Medicine, vol. 41, no. 9, pp. 2162-2168. https://doi.org/10.1097/CCM.0b013e31828a678d
Morelli, Andrea ; Donati, Abele ; Ertmer, Christian ; Rehberg, Sebastian ; Kampmeier, Tim ; Orecchioni, Alessandra ; D'Egidio, Annalia ; Cecchini, Valeria ; Landoni, Giovanni ; Pietropaoli, Paolo ; Westphal, Martin ; Venditti, Mario ; Mebazaa, Alexandre ; Singer, Mervyn. / Microvascular effects of heart rate control with esmolol in patients with septic shock : A pilot study. In: Critical Care Medicine. 2013 ; Vol. 41, No. 9. pp. 2162-2168.
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AU - Morelli, Andrea

AU - Donati, Abele

AU - Ertmer, Christian

AU - Rehberg, Sebastian

AU - Kampmeier, Tim

AU - Orecchioni, Alessandra

AU - D'Egidio, Annalia

AU - Cecchini, Valeria

AU - Landoni, Giovanni

AU - Pietropaoli, Paolo

AU - Westphal, Martin

AU - Venditti, Mario

AU - Mebazaa, Alexandre

AU - Singer, Mervyn

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N2 - Objective:: β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation. Design:: Prospective, observational clinical study. Setting:: Multidisciplinary ICU at a university hospital. Measurements and Main Results:: After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p <0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p = 0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p = 0.002). PaO2 and pH increased while PaCO2 decreased (all p <0.05). Of note, norepinephrine requirements were significantly reduced by selective β-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] μg/kg/min; p = 0.03). Conclusions:: This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.

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KW - β-blockers

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