Fluid challenge in Intensive Care: a worldwide global inception cohort study. The FENICE II study.

Introduction:

Fluids are the first line treatment of critically ill patients with shock aiming to increase venous return, stroke volume (SV) and, consequently, cardiac output (CO) and tissue oxygen delivery (DO2) [1-5]. Fluid administration is also one of the most disputed interventions in the treatment of critically ill patients [6, 7]. Even more debated is how to appraise and manage the response to fluid administration [1-6]. The optimal volume of fluids to be given in hypotensive patients with sepsis or in septic shock is still debated. The 2016 Surviving Sepsis Campaign (SSC) guidelines (SCC) strongly recommended giving at least 30 ml/kg of crystalloids for initial resuscitation of patients with sepsis-induced hypoperfusion [8]. This was downgraded to a weak recommendation in the 2021 update of the SSG due to a lack of prospective intervention studies comparing different volumes for initial resuscitation in sepsis or septic shock [9]. A recent randomized-controlled trial in patients with sepsis-induced hypoperfusion (averaged mortality of 14%) [10] and another in patients with septic shock (averaged mortality of 42%) [11], showed that a “restrictive” fluid strategy was non inferior to a “liberal” one.

From a physiological point of view, the goal of fluids is to increase SV and then CO and should only be given if the plateau of cardiac function is not reached in the individual patient (fluid responsiveness state). Fluid challenge (FC) is a diagnostic test consisting in the administration of a fixed volume of fluids with the purpose of identifying patients who will increase CO in response to fluid infusion [3, 12, 13]. Since several bedside clinical signs, systemic arterial pressure and static volumetric variables are poorly predictive of the effect of FC, the response to FC may be predicted at the bedside by using a functional hemodynamic test. This consists of a manoeuvre that affects cardiac function and/or heart-lung interactions, with a subsequent hemodynamic response, the extent of which varies between fluid responders and non-responders [14-16]. The combination of a functional hemodynamic test to assess fluid responsiveness and FCs to customize fluid infusion may be used to reduce the risk of fluid overload. Of note, at least 30% of the overall amount of fluid administered in septic patients may be related to the hidden and unintentional creep volume [17] (i.e. fluid administration not driven by a functional assessment of hemodynamics). In fact, a recent retrospective study on 14,654 patients during the cumulative 103,098 days showed that maintenance and replacement fluids accounted for 24.7% of the mean daily total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were the most important sources of sodium and chloride. Fluid creep represented a striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308-1039 mL)]

Unfortunately, neither the FC nor the use of functional hemodynamic test are standardised in current clinical practice [18-21]. This was confirmed by the FENICE study, a large observational study on 2,213 patients conducted by the European Society of Intensive Medicine (ESICM) [19]. Since the first FENICE study publication, many activities have been by provided by the ESICM in an effort to improve education and implementation of evidence-based haemodynamic management in intensive care unit (ICU) patients. These programs have focused on physiology, haemodynamic monitoring and interpretation, and fluid therapy. These efforts may have improved the use of functional hemodynamic tests and FC at bedside, with an impact on haemodynamic management and fluid administration policy in the ICU

Aims & Objectives:

The primary aim of the FENICE II study is to describe the modality of fluid administration in the acute phase of resuscitation from hemodynamic instability in ICU patients.

As secondary aims, we’ll appraise in-hospital, ICU and 30-day mortality and major organ dysfunction. Finally, we’ll assess the use of variables (including clinical signs of hypovolemia, and indexes/images obtained from hemodynamic monitoring or echography) and functional hemodynamic tests to guide FC infusion in ICU patients, and the modality of FC administration (i.e. volume, rate, type of fluid), of evaluation of fluid responsiveness at the bedside.

Statistical analysis:

Data will be described as median and interquartile range (IQR) or number and percentage. Categorical variables were compared using Fisher’s exact test and continuous variables using the nonparametric Wilcoxon test, Mann-Whitney test, or Kruskal-Wallis test.