Esmolol Effects on Heart and Inflammation in Septic Shock (ESMOSEPSIS)

Beta adrenergic system, over-activated in septic shock patients, is a key modulator of the inflammatory response. Experimental works demonstrated that Esmolol, an highly selective beta-1 blocker, reduces heart rate and regulates the inflammatory response. A recent mono centric, double blind, randomized clinical work in septic shock patients has shown that Esmolol administration is safe and reduces effectively heart rate. However there are only sparse data on 1) regional and micro-circulation, 2) inflammation modulation in human resuscitated septic shock patients treated by esmolol.

Resuscitated, hyperkinetic septic shock patients are treated with esmolol in order to reduce heart rate of 20% during 6 hours. During the intervention period, multimodal macro and micro hemodynamic data are recorded.

After, at least six hours of hemodynamic optimization, patients with an hyper dynamic shock received a conventional management with a continuous infusion of Esmolol titrated to gain a 20% reduction in heart rate. This infusion is maintained for six hours.

Compare, in septic shock patients, the mean cardiac index before and after administration of Esmolol.

Before administration (H0) and each hour (H1-H2-H3-H4-H5-H6) during the whole administration period and one hour after Esmolol cessation (H7)

Effects on vasopressor requirement (amount of norepinephrine infused in microgram/kg) during Esmolol administration

Record of each change in vasopressor dosage to maintain a mean arterial pressure at 70 mmHg during the whole Esmolol administration period (H0 to H6) and one hour after esmolol cessation (H7)

NIRS (near-infrared spectroscopy) SDF (Sidestream Dark Field imaging) / Limon (non-invasive measurement of liver function and splanchnic perfusion monitoring) are used to asses microcirculatory and regional circulation effects

Changes in the Cytokine pattern(pro and anti inflammatory cytokines assay) induced by Esmolol administration in septic shock patients

Before administration (H0), at 4 hours, 6 hours after introduction and 1 hours after esmolol cessation

Inclusion Criteria: septic shock patients following the definition of the Surviving Sepsis Campaign femoral and central venous catheters for thermodilution monitoring fluid optimization with a cardiac index > 3 l/min/m2 Heart Rate >100 /min Exclusion Criteria: Cardiogenic shock Bradycardia History of Severe Asthma Indications against esmolol

Levy B, Fritz C, Piona C, Duarte K, Morelli A, Guerci P, Kimmoun A, Girerd N. Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study. Crit Care. 2021 Jan 7;25(1):21. doi: 10.1186/s13054-020-03445-w.