Fluid Challenge in Intensive Care The FENICE II Study (FENICE II)

Fluid Challenge in Intensive Care: a Worldwide Global Inception Cohort Study: The FENICE II Study

Fluids are considered the primary treatment for critically ill patients admitted to the intensive care unit (ICU), aiming to replace losses and or to enhance venous return, stroke volume, and consequently, cardiac output and tissue oxygen delivery. The modalities, volumes, and targets employed to titrate fluid therapy vary significantly in current clinical practice, as shown by the original FENICE study 10 years ago. FENICE studied how fluid challenges are given at the bedside. Very little is known about how this practice has changed since, how fluid administration (maintenance) is performed in general, and how the modality may impact outcomes. FENICE II is designed to explore these issues.

Objectives:

To provide a comprehensive global description of fluid administration modalities during the initial days of ICU admission and to explore any association between fluid administration characteristics and clinical outcomes.

To describe the fluid challenge administration modality and appraise the use of variables and functional hemodynamic tests to guide bolus infusion.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Septic Shock
• Intervention / Treatment: Other: Fluid administration (any type)

Detailed Description

Primary aim: The primary aim is to describe the modality of fluid administration during the first 5 days of ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration.

Secondary aims:

• To explore any association between fluid administration characteristics and clinical outcomes (see further)
• To evaluate factors potentially associated with the respective proportion of the different modalities of fluid administration
• To characterize FC administration modality in a large cohort of ICU patients.

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.

Volume of fluid and fluid balance (primary outcome) will be reported as median [IQR] from day 1 to day 5. This volume, fluid balance and respective volume of bolus and continuous fluid administration will be reported as distinct alluvial plots reporting median of fluid at day 1 to 5 per quartile along with outcome.

In way to assess relationship between volume of fluid received, characteristics and outcome (secondary outcome), longitudinal cluster modelling will be used to identify clusters of patients with similar patterns of fluid administration profile. Longitudinal k-mean will be used to assess change in fluid received each day from day 1 to day 3. In way to avoid misinterpretation of findings due to time dependent competing events such death or ICU discharge, this analysis will be performed on patients alive and still in the ICU at day 3. A sensitivity analysis will be performed during first 5 days on the subgroup of patients alive and not discharged during first 5 ICU-days.

In way to assess impact of fluid administration modality/strategy on outcome (secondary endpoint), factors associated with in-hospital mortality, including identified cluster of fluid administration, will be assessed using mixed logistic regression where in-hospital mortality will be event of interest. Center effect will be included as a random effect against the intercept.

For secondary outcomes, and in particular for day-30 mortality, number of days alive without vasopressors, mechanical ventilation or renal replacement therapy, will be assessed using survival analysis.

All tests will be two-sided, and P-value less than 0.05 will be considered statistically significant.

• Study Type: Observational
• Enrollment (Actual): 4734

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Humanitas Research Hospital
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Humanitas Clinical and Research center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All consecutive adult (≥18 years old) patients admitted to the intensive care unit and expected to stay at least 48h.

Description

Inclusion Criteria:

• All consecutive adult (≥18 years old) patients admitted to ICU and expected to stay at least 48h.

Exclusion Criteria:

• Planned admission after surgery for overnight ICU stay.
• Refusal of consent
• Moribund patients (i.e. expected survival < 24h)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of various aspects of fluid therapy	Modality of fluid administration during ICU stay considering 1) the overall fluid balance; 2) the characteristics of the fluids given; 3) the modality of fluid administration	FIve days from ICU admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality	Mortality during ICU stay	Up to 30 days from ICU admission
Alive without any organ support	Number of calendar days between inclusion and 28 days that the patient is alive and with no requirement of cardiovascular, respiratory and renal support.	between inclusion and 30 days later
Organ Dysfunction - Heart	Time to cessation of vasopressor support during ICU stay (The number of hours between enrollment and complete stopping of vasopressor support (defined as its complete interruption for at least 24 consecutive hours).	between inclusion and 30 days later
Organ Dysfunction - Renal	Time to cessation of Renal Replacement during ICU stay [The number of calendar days between start of renal replacement therapy and complete liberation from renal replacement therapy (at least 48 hours for continuous replacement modalities and 5 days for intermittent ones).	between inclusion and 30 days later
In-hospital Mortality	Mortality during hospital stay after ICU discharge	Up to 30 days from ICU admission
Organ Dysfunction - Lung	Time to cessation of mechanical ventilation during ICU stay [The number of calendar days between intubation / start of mechanical ventilation and extubation / liberation from mechanical ventilation] (maintained for at least 48 hours)].	between inclusion and 30 days later
Organ Dysfunction - Renal	Variation of creatinine-based KDIGO stage. Renal function assessed according to KDIGO staging system.	between inclusion and 5 days later
Organ Dysfunction	Variation of daily SOFA score.	between inclusion and 5 days later

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All aforementioned outcomes	Pre-defined subgroup analysis in patients admitted with septic shock	30 days from ICU admission
All aforementioned outcomes	Pre-defined subgroup analysis in patients admitted with neutropenia	30 days from ICU admission

Collaborators and Investigators

• Sponsor: Humanitas Clinical and Research Center
• Collaborators: European Society of Intensive Care Medicine

Publications and helpful links

General Publications

• Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Actual): November 30, 2025
• Study Completion (Actual): November 30, 2025

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: April 28, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Intensive Care; Fluid Therapy; Fluid Challenge; Hemodynamic Monitoring; Fluid Bolus
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Critical Illness; Shock, Septic; Physiological Phenomena; Biochemical Phenomena; Chemical Phenomena; Metabolism; Homeostasis; Osmoregulation; Water-Electrolyte Balance
• Other Study ID Numbers: FENICE II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No