Hemodynamic Phenotype-Based, Capillary Refill Time-Targeted Resuscitation In Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial (A2)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Intensive Care Unit Acquired Weakness
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Hemodynamic phenotyping may allow to individualize septic shock resuscitation. The ANDROMEDA-SHOCK trial found that a simple clinical and bedside CRT-targeted resuscitation reduces organ dysfunction and 28-day mortality in septic shock. The current study will examine the hypothesis that a CRT-targeted resuscitation based on hemodynamic phenotyping considering within an decision tree usual bedside clinical parameters such as pulse pressure, diastolic blood pressure, fluid responsiveness and cardiac performance can further decrease mortality in septic shock as compared to usual care.
Detailed Description
Septic shock is associated with a high mortality risk related to progressive tissue hypoperfusion.However, despite extensive research on the best monitoring and resuscitation strategies, many uncertainties remain. Over-resuscitation, particularly when inducing fluid overload, might contribute to a worse outcome. Fluid overload more likely occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued, or a "one-size-fit all" strategy is followed. From a hemodynamic point of view, several pathogenic mechanisms determine a progressive circulatory dysfunction While loss of vascular tone and relative hypovolemia predominate in early phases, more complex mechanisms such as endothelial and microcirculatory dysfunction, progressive vasoplegia, and myocardial dysfunction may be involved later. In effect, from a clinical point of view, many patients despite been fluid loaded in pre-intensive care unit settings, are still evidently hypovolemic and benefit from further administration of fluid boluses. Others, however, present very low diastolic arterial pressures reflecting profound vasoplegia, and recent data suggest that these patients may benefit from early norepinephrine instead of fluids\[; on the contrary, administering fluids may fail to correct vascular tone and increase the risk of fluid overload\[2\]. In addition, a recent echocardiography-based study confirms that a relevant myocardial dysfunction is present in a significant number of patients, and that several cardiovascular phenotypes with a potentially different therapeutic approach may be recognized\[8\]. Unfortunately, despite the availability of most of the parameters at the bedside and research efforts, no universally applicable clinical phenotyping method for septic shock patients has been translated to usual practice. This is particularly problematic since chocardiography is not immediately available in the majority of centers worldwide, and therefore initial decisions on fluid resuscitation are usually based on clinical grounds and tend to follow the one-size-fits-all principle, leading to the risk of fluid overload.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Consecutive adult patients (≥ 18 years)
- •Patients with septic shock according to Sepsis-3 consensus conference. In short, septic shock is defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000mL in 1h
- •Patient and/or relative informed and having signed the information and consent form for participation in the study
Exclusion Criteria
- •More than 4 hours since septic shock diagnosis,
- •Anticipated surgery or acute hemodialysis procedure to start during the 6h intervention period
- •Active bleeding,
- •Do not resuscitate status,
- •Child B-C Cirrhosis
- •Underlying disease process with a life expectancy \< 90 days and/or the attending clinician deems aggressive resuscitation unsuitable
- •Refractory shock (high risk of death within 24h)
- •Pregnancy
- •Concomitant severe acute respiratory distress syndrome
- •Patients in whom CRT cannot be accurately assessed
Outcomes
Primary Outcomes
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
Time Frame: 28 days
A hierarchical composite of all cause mortality within 28 days, time to cessation of vital support (truncated at 28 days) and length of hospital stay (truncated at 28 days).
Secondary Outcomes
- All-cause mortality within 28 days(28 days)
- Length of hospital stay(28 days)
- Vital support free days(28 days)