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Microvascular Effects of Heart Rate Control With Esmolol in Patients With Septic Shock: A Pilot Study*

Morelli, Andrea MD1; Donati, Abele MD2; Ertmer, Christian MD3; Rehberg, Sebastian MD3; Kampmeier, Tim MD3; Orecchioni, Alessandra MD1; D’Egidio, Annalia MD1; Cecchini, Valeria MD1; Landoni, Giovanni MD4; Pietropaoli, Paolo MD1; Westphal, Martin MD3; Venditti, Mario MD5; Mebazaa, Alexandre MD6; Singer, Mervyn MD, FRCP7

doi: 10.1097/CCM.0b013e31828a678d
Clinical Investigations

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/m2; p < 0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m2; 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.

1Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, University of Rome, “La Sapienza”, Italy.

2Department of Neuroscience-Anesthesia and Intensive Care Unit, Università Politecnica delle Marche, Italy.

3Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital of Muenster, Germany.

4Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano, Italy.

5Department of Public Health and Infectious Diseases, University of Rome, “La Sapienza”, Italy.

6Department of Anesthesiology and Critical Care Medicine, Lariboisière Hospital, University Paris Diderot, Paris, France.

7Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.

* See also p. 2237.

Supported, in part, by an independent research grant from the Department of Anesthesiology and Intensive Care of the University of Rome “La Sapienza”.

Dr. Morelli received honorarium from Baxter for speaking at one symposium. Dr. Singer has received honoraria from Baxter for chairing or speaking at satellite symposia. The remaining authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: andrea.morelli@uniroma1

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins