Clinical trial NCT05355961: Effect of Norepinephrine Administration on Ventricular Systolic Function in Septic Shock
Official title: Effect of NorEpinephrine Administration on Ventricular Systolic Function in Septic Shock Patients: the ENESySS Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Septic Shock
Keywords: NorEpinephrine
Septic Shock
Beta-1adrenergic effect
Ventricular Systolic Function
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2022-05-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preload non-responder patients admitted to the ICU with a diagnosis of septic shock.

Brief summary: This observational, pharmacological, prospective study aims to assess the improvement of ventricular systolic function mediated by norepinephrine (NE) administration in preload non-responders septic shock patients. Left ventricular outflow tract velocity time integral (LVOT-VTI) is an echocardiographic index of ventricular systolic function and it will be measured at different NE dosages.

Detailed description: Norepinephrine (NE) is recommended as first line vasopressor in septic shock. Besides increasing arterial tone and thus arterial pressure, NE improves cardiac output (CO) as a result of two main mechanisms: (i) the increase in venous return due to venoconstriction, in case of preload responsiveness, (ii) the improvement of coronary perfusion through augmentation of diastolic arterial pressure. Experimental data show that NE may incrase cardiac output by exerting also a direct β1-adrenergic stimulation on ventricular myocardial fibers. However, there are few clinical data dealing with the direct effect of NE administration on ventricular systolic function in human septic shock.

Our study aims to demonstrate that norepinephrine administration in early septic shock preload non-responder patients may improve left ventricular outflow tract velocity time integral (LVOT-VTI), measured by trans-thoracic echocardiography (TTE). We will include patients requiring an increase of NE dose for clinical need according to treating physician's decision. For each enrolled patient we will record standard hemodynamic data and perform TTE before NE dosage change (T0). After the increase of NE infusion rate targeting clinical need, a second set (T1) of hemodynamic and TTE data will be obtained.

All TTE examinations will be performed by two experienced and certified clinicians according to current guidelines. After being acquired, all TTE data will be independently analyzed by both clinicians and averaged. LVOT-VTI will be measured in the left ventricular outflow tract on the apical five-chamber (A5C) view. Referring to available literature data, we expect a mean LVOT-VTI of about 18 cm in our patients and we will consider clinically relevant an increase of 15% in LVOT-VTI from T 0 to T 1. We calculated that at least 30 patients need to be enrolled considering an alpha of 0.05 and a power of 80%. The benefits deriving from this study lay in the possibility of improving the clinical understanding of septic shock derived hemodynamic derangements and of widening therapeutic perspectives. Such an information meets the increasing topical need to customize medical interventions, especially in the context of critically ill patients.

Eligibility criteria: Inclusion Criteria:

* less than 6 hours from the diagnosis of septic shock
* ongoing vasopressor therapy by continuous intravenous infusion of norepinephrine
* treating physician's decision to increase norepinephrine dose

Exclusion Criteria:

* preload responsiveness assessed through dynamic indices
* pregnancy
* myocardial disfunction due to active cardiac disease
* inadequate acoustic window for transthoracic echocardiography
* need for emergency treatment

Primary outcomes:
measure: Variation of LVOT-VTI
timeFrame: 1 hour
Secondary outcomes:
measure: Variation of left ventricle end-systolic elastance
timeFrame: 1 hour
measure: Variation of tricuspid annulus plane systolic excursion
timeFrame: 1 hour
measure: Variation of LVOT-VTI, left ventricle end-systolic elastance and tricuspid annulus plane systolic excursion in patients with pre-existing depressed left ventricular systolic function.
timeFrame: 1 hour
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: RM
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Simone Carelli, MD
role: PRINCIPAL_INVESTIGATOR
References: