Emergency Echocardiography in Sepsis (GENESIS)

University of Limoges (UL)

Status: Completed

Conditions: Emergencies; Organ Dysfunction Syndrome Sepsis; Echocardiography; Sepsis

Treatments: Procedure: standards of care; Procedure: early transthoracic echocardiography

Study type: Interventional

Funder types: Other

Identifiers

NCT04580888

87RI19_0038 (GENESIS)

Details and patient eligibility

About

Acute circulatory failure that combines hypovolemia, vasoplegia and cardiac dysfunction plays a major role in the development of sepsis-related organ dysfunction. Pathophysiological mechanisms are multiple and complex. The objective of the GENESIS study is to determine the impact of early haemodynamic assessment using echocardiography in association with a therapeutic algorithm (intervention arm), when compared with standard of care based on the current Surviving Sepsis Campaign (SSC) recommendations (control arm), on the development of organ dysfunctions in patients admitted to the Emergency Department for sepsis or septic shock.

Full description

Sepsis is currently defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection (Sepsis-3). Septic shock is a subgroup of patients who also have sustained arterial hypotension requiring vasopressors and tissue dysoxia. The mortality varies from 10 to 40% depending on the severity. The latest "bundles" of the SSC request to perform within the first hour of sepsis identification a fluid loading of 30 mL/kg of crystalloids in the presence of hypotension, and to initiate a vasopressor support in case of persistent hypotension to maintain a mean arterial pressure ≥ 65 mmHg. However, early fluid resuscitation is not necessarily associated with an improvement of sepsis prognosis and may even be deleterious when leading to excessive positive fluid balance. Accordingly, the SSC recommends investigating a personalized approach to define for each patient the appropriate volume of fluids to be administered according to the initial mechanism of sepsis-induced cardiovascular failure. Echocardiography is currently recommended as a first-line modality to identify the origin of acute circulatory failure, sepsis remaining the leading cause. It has been shown to alter ongoing treatment based on the sole SSC recommendations in the intensive care unit. In contrast, the impact of hemodynamic assessment using echocardiography at the early stage of sepsis in patients admitted to the Emergency Department (ED) is unknown.

In this randomized trial, patients will be either assessed hemodynamically using transthoracic echocardiography to guide early therapeutic management (intervention arm) or managed according to standards of care based on current SSC recommendations (control arm). Early echocardiography will be performed after 500 mL of fluid loading initiated upon identification of septic patients based on the qSOFA score (hemodynamic criterion required: systolic blood pressure ≤ 100 mmHg). This will allow identifying the hemodynamic profile at the origin of sepsis-induced circulatory failure and to monitor both the efficacy and tolerance of fluid resuscitation, or of any other therapeutic intervention (e.g., inotropic support) according to a predefined therapeutic algorithm. Patients allocated to the control arm will be managed conventionally according to current SSC recommendations, including a standardized fluid loading of 30 mL/kg.

Organ dysfunctions will be assessed in the two study arms by the SOFA score 24 hours after randomization and patient will be followed up until hospital discharge to determine outcome.

Enrollment: 312 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients admitted to the ED
• Age ≥ 18 years and affiliation to Social Security
• With sepsis (Sepsis-3 definition):

Clinically suspected or documented acute infection

AND a quick score Sequential Organ Failure Assessment (qSOFA) ≥ 2 points with:

• Systolic blood pressure ≤ 100 mmHg (1 point) requiring fluid loading
• AND encephalopathy (1 point) OR respiratory rate ≥ 22 cpm (1 point) AND a systolic blood pressure ≤ 100 mmHg after 500 mL of crystalloid vascular filling - Informed consent

Exclusion criteria

• Decision to limit care or moribund status
• Pregnancy or breast feeding
• Subject under juridical protection.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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312 participants in 2 patient groups

Intervention arm

Experimental group

Description:

Assessment using an early transthoracic echocardiography (after 500 mL of fluids) to identify the hemodynamic profile responsible for the acute circulatory failure associated with sepsis / septic shock and to guide ongoing treatment (therapeutic algorithm) and monitor its efficacy and tolerance.

Treatment:

Procedure: early transthoracic echocardiography

Control arm

Other group

Description:

Conventional management according to current standards of care based on SSC recommendations, including a standardized fluid resuscitation of 30 mL/kg.

Treatment:

Procedure: standards of care