title: Microvascular effects of heart rate control with esmolol in patients with septic shock: a pilot study.
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.
  
  
  METHODS
  Prospective, observational clinical study.
  
  
  METHODS
  Multidisciplinary ICU at a university hospital.
  
  
  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.
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, University of Rome, La Sapienza, Italy. andrea.morelli@uniroma1
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Abele
authors.initials: A
authors.lastname: Donati
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rehberg
authors.forename: Tim
authors.initials: T
authors.lastname: Kampmeier
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orecchioni
authors.forename: Annalia
authors.initials: A
authors.lastname: D'Egidio
authors.forename: Valeria
authors.initials: V
authors.lastname: Cecchini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Pietropaoli
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Mario
authors.initials: M
authors.lastname: Venditti
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
mesh_terms: D000293:Adolescent; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D015897:Comorbidity; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D010865:Pilot Projects; D011412:Propanolamines / Q000494:pharmacology*; D011446:Prospective Studies; D012772:Shock, Septic / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects; D055815:Young Adult
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D011412:Propanolamines; C036604:esmolol