Hemodynamic Phenotype-Based,Capillary Refill Time-Targeted Resuscitation In Early Septic Shock:ANDROMEDA-SHOCK-2

Overview

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.

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.