Levosimendan and Global Longitudinal Strain Assessment in Cardiogenic Shock Sepsis (GLASSES 1): a Study Protocol for an Observational Study

The present is an observational single centre no profit study. The duration is expected to be 12 months from September 2019.

The study will be conducted by enrolling patients aged 18 to 80 years in intensive care with diagnosis of septic shock according to the Third National Consensus Definitions for Sepsis and Septic Shock2, with the need for infusion of vasoactive drugs to maintain a PAM > 65 mmHg. The following will be subjected to echocardiographic examination with Sparq ultrasound machine (Philips Healthcare, Best, the Netherlands) and 3.6 MHz cardiology probe through which will be acquired the apical projections 2, 3 and 4 chambers necessary to calculate the global longitudinal strain (GLS) through AutoSTRAIN© (TOMTEC Imaging Systems GmbH, Unterschleissheim, Germany).

During the echocardiographic examination, the Ea/Ees ratio (ventricle-arterial coupling) will also be calculated using the method modified on a single beat of Chen (t0) 18 using the IElastance® application. Patients will be monitored with the PiCCO® system (Pulse index Continuous Cardiac Output, Pulsion Medical systems, Munich, Germany) which measures the cardiac index (CI) and the Stroke Volume Index (SVI). Those with Ea//Ees > 1, cardiac index values < 2.5 L/min/m2 and/or Stroke Volume Index < 30 mL/beat/m2 will be considered eligible to enroll in the study. In these patients, dobutamine infusion will be started from 5 mcg/kg/min following the bundles of the Surviving Sepsis Campaign at dosages that allow to obtain an CI >2.5 L/min/m2 and/or Stroke Volume Index >30 mL/beat/m2. With 24 hours to go before the dobutamine infusion starts, CI and SVI will be recalculated using PiCCO®, GLS and ventricle-arterial coupling index by ultrasound investigation and then levosimendan infusion will begin for 24 hours starting with an infusion of 0.1 mcg/kg/min in order to wean the patient from dobutamine infusion. Once the infusion cycle of the calcium-sensitizing drug has been carried out, if possible, the infusion of dobutamine will be reduced until it stops and CI, SVI, GLS and Ea/Ees will also be re-evaluated. The same echocardiographic evaluations and hemodynamic calculations using PiCCO® will be performed 72 and 96 hours after the start of the dobutamine infusion. All patients enrolled will be followed up by a Medical Outcomes Survey Short-Form 36 (SF-36) questionnaire 28 days and 90 days after discharge from intensive care.

It should be noted that all the procedures described (including echocardiographic monitoring) comply in quantity and frequency with the normal practice of care and management of patients admitted to intensive care with diagnosis of cardiogenic shock during sepsis in Azienda USL Toscana Centro.

In addition, the parameters measured during the echocardiographic examination are derived from the reprocessing of the images collected during the examination and therefore simply represent an in-depth examination for diagnostic purposes performed according to current practice at the Centre.