Timing and Dose of Fluid Deresuscitation in Critically Ill Patients (TIDE)

Timing and Dose of Fluid Deresuscitation in Critically Ill Patients: a Prospective Observational Multicenter Study

Fluid deresuscitation is an important intervention in the Intensive Care Unit (ICU). This study aims to find (1) determinants of successful deresuscitation, (2) the optimal rate (dose) of deresuscitation based on these determinants, and (3) differences in metabolic profiles for a more personalized approach of deresuscitation.

This study is a multicenter, prospective, observational cohort study in critically ill patients. This study will include ICU patients who have a clinical indication for deresuscitation as set by the treating physician. Clinical, ultrasound and laboratory values will be collected and used for analysis.

Study Overview

• Status: Recruiting
• Conditions: Fluid Overload; Deresuscitation; Critical Care, Intensive Care

Detailed Description

Primary objective:

The aim of this study is to identify determinants of successful deresuscitation in ICU patients, defined as achieving a negative fluid balance within 24 hours without hemodynamic consequences.

Secondary objectives:

• Timing of deresuscitation:

  • Identify determinants of successful deresuscitation in ICU patients, defined as achieving a negative fluid balance within 24 hours;
  • Compare these determinants with determinants for the clinical decision of deresuscitation by the treating physician;
  • Identify differences in these determinants within subgroups of sepsis, ARDS and cardiac patients, provided the numbers are sufficient;

• Rate (dose) of deresuscitation:

  • Identify parameters associated with diuretic or natriuretic response during deresuscitation;
  • Find individualized optimal rates of deresuscitation based on these determinants;

• Possible complications of deresuscitation:

  • Determine whether there is an association between electrolyte or acid-base disturbances during deresuscitation (e.g. the Strong Ion Difference) and clinical outcomes;
  • Determine whether there is an association between the rate of deresuscitation and hemodynamic consequences;
  • Determine whether there is an association between the timing and rate of deresuscitation and atrial fibrillation (AF);
  • Determine whether there is an association between deresuscitation and the occurrence of delirium;
  • Determine whether there is an association between timing and rate of deresuscitation and acute kidney injury (AKI).

Study design:

The TIDE study is a multicenter, prospective, observational cohort study in the ICUs of the Amsterdam UMC and OLVG in Amsterdam, the Netherlands.

Study population:

Adult patients admitted to the ICU, who have a clinical indication for deresuscitation as set by the treating physician, using diuretics or ultrafiltration; first deresuscitation attempt during the ICU stay.

Sample size calculation:

For finding associations with logistic regression with a moderate (odds ratio >1.5) to strong (odds ratio >2.5) effect an alpha set at 0.05, power set at 0.8 and an estimated failure of 50% or more, we would need a sample size of around 150-210 patients.

Methods:

Patients in the participating ICUs are screened for eligibility when the treating physician sets a clinical indication for deresuscitation. Eligible patients will be included in the study. At that time, defined as baseline, clinical, ultrasound and laboratory measures will be collected. Clinical measures among others include: heart rate, mean arterial pressure, dose of vasopressors, and capillary refill time. Ultrasound measurements include: lung ultrasound scores (LUS), venous excess ultrasound (VExUS), and cardiac ultrasound, including VTI during a passive leg raise (PLR). Laboratory measurements include arterial blood gas analysis and urinalysis. Furthermore, baseline characteristics such as demographics, reason for ICU admission, severity of illness scores, and medical history are collected.

Deresuscitation will be performed according to standard care according to the treating physician's insights. Primary follow up is 24 hours in which granular data of deresuscitation tactics, deresuscitation output, electrolyte and acid-base disturbances, and hemodynamic consequences are collected. Secondary follow up is at 7 days for complications such as acute kidney injury and at 28 days for mortality, ICU length of stay (LOS) and ventilator free days (VFD), where available.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Krijna Opschoor, MD; Phone Number: +31 (0)20 566 9111; Email: k.opschoor@amsterdamumc.nl
• Study Contact Backup: Name: Santje A.S. Slot, MD; Email: s.a.s.slot@olvg.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Recruiting
    • Amsterdam UMC
    • Contact: Krijna Opschoor, MD; Phone Number: +31 (0)20 566 9111; Email: k.opschoor@amsterdamumc.nl
  • Amsterdam, Netherlands, 1091AC
    • Recruiting
    • OLVG
    • Contact: Santje A.S. Slot, MD; Phone Number: +31 (0)20 599 9111; Email: s.a.s.slot@olvg.nl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients admitted to the Intensive Care Unit

Description

Inclusion Criteria:

• Admission to one of the participating ICUs;
• Clinical indication for deresuscitation using diuretics or ultrafiltration as set by the treating physician; first attempt during the ICU stay.

Exclusion Criteria:

• Age below 18 years old;
• Major cardiac shunts;
• Moderate to severe aortic regurgitation;
• Morbid Obesisty (BMI >40);
• POCUS impossible or unreliable (i.e. pre-existing interstitial lung disease);
• PLR or modified form of PLR impossible (i.e. ECMO);
• Transfer from another ICU;
• Previous inclusion in this study;
• Patients who are moribund or facing the end of life;
• Opt out.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful deresuscitation without hemodynamic consequences	Reach negative fluid balance in first 24 hours without hemodynamic consequences (yes/no), defined as either hypotension or hypoperfusion: HypotensionInterventions required to maintain blood pressure MAP > 65mmHgDeresuscitation is stoppedFluid bolus needs to be givenNoradrenaline (or other vasopressor) needs to be initiated, increased to > 0.2 microg/kg/min, or increased by 50%Dose reduction or interruption of RRT; Hypoperfusion (one of the following):Arterial lactate level >3 and/or increased 25% or moreNew development of mottled skinCapillary refill time > 3 secondsNew oliguria (urine output < 0.3-0.5ml/kg/hour for the previous 6 hours)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful deresuscitation	Reach negative fluid balance in the first 24 hours	24 hours
Rate of deresuscitation	Urine output or ultrafiltration rate in mL/kg/h	24 hours
Dose of deresuscitation	Fluid balance in mL/kg	24 hours
Natriuresis	Urinary sodium output in mmol/L/24h	24 hours
Delta Strong Ion Difference	ΔSID in mmol/L	24 hours
Delta serum sodium	Serum ΔNa in mmol/L	24 hours
Delta serum chloride	Serum ΔCl in mmol/L	24 hours
Atrial fibrillation	Occurrence of ≥1 hour AF or AF for which treatment is needed during the deresuscitation window if not present at baseline	24 hours
Acute Kidney Injury (AKI)	AKI as diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria: Stage 1: sCreat 1.5-1.9 times baseline OR ≥0.3 mg/dl (≥26.5 mmol/l) increase OR urine output <0.5 ml/kg/h for 6-12 hours Stage 2: sCreat 2.0-2.9 times baseline OR urine output <0.5 ml/kg/h for ≥12 hours Stage 3: sCreat 3.0 times baseline OR Increase in serum creatinine to ≥4.0 mg/dl (X353.6 mmol/l) OR Initiation of renal replacement therapy OR urine output <0.3 ml/kg/h for ≥24 hours OR anuria for ≥ 12 hours	7 days
Persistent AKI	Prolonged AKI for ≥48 hours if not present before start deresuscitation	7 days
Renal Replacement Therapy (RRT)	Need for RRT after start deresuscitation if not used at baseline and primary deresuscitation	7 days
Delirium	Need 1 or more types of medication to treat delirium after start deresuscitation	7 days
ICU-mortality	Mortality within ICU stay	28 days
28-day mortality	Mortality after 28 days	28 days
Ventilator free days (VFD)	Patient is alive and breathes without assistance of the mechanical ventilator, if the period of unassisted breathing lasted at least 24 consecutive hours: VFD-28 = 0 if subject dies within 28 days of mechanical ventilation; VFD-28 = 28 - x if successfully liberated from ventilation x days after initiation successful liberation: extubation (planned or unplanned) without death or reintubation within the next 72 hours; VFD-28 = 0 if the subject is mechanically ventilated for ≥ 28 days	28 days
ICU length of stay (LOS)	Length of stay in the intensive care unit	28 days

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: OLVG

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: ultrasound, RRT, furosemide
• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Edema
• Other Study ID Numbers: 2025.0391

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No