Protocol-based Fluid Management for Critical Illness

(Probe-Fluid Trial)

Not currently recruiting at 1 trial location

Overseen By Caroline Vallière

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Severe burns, Abnormal sodium, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing fluids in critically ill patients receiving kidney replacement therapy. The goal is to determine if a specific fluid management plan (protocol-based fluid management) is more effective than usual care. This plan aims to prevent and treat fluid buildup, maintaining a stable or reduced fluid level daily. The trial is suitable for ICU patients with acute kidney injury (a sudden decrease in kidney function) who are about to start or have just started kidney therapy. Participants should not have severe burns or major fluid loss issues requiring ongoing IV fluids. As an unphased trial, this study allows patients to contribute to innovative research that could enhance fluid management in critical care settings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this protocol-based fluid management is safe for critically ill patients?

Research shows that carefully managing fluids in very sick patients can be safe. Studies have examined patient outcomes with a fluid plan that avoids extra fluid buildup. In one study, patients following this plan did not experience more serious problems than those receiving regular care.

Some worry that fluid management might cause issues, but research suggests this method is generally well-tolerated. Studies with very sick patients have not linked it to higher death rates or severe side effects. This suggests the treatment is reasonably safe, though individual experiences may differ.

For those considering a trial with this fluid management approach, this evidence can help reassure about its safety. However, discussing any concerns with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about protocol-based fluid management for critical illness because it offers a structured approach to managing fluid levels in critically ill patients, which can be more precise than the usual care. Unlike the standard practice that often relies on physician judgment, this protocol provides a standardized method, potentially reducing variability in patient outcomes. By streamlining fluid removal, it aims to prevent complications from fluid overload, a common issue in critical care. This method could lead to more consistent and improved recovery rates, offering a promising advancement in treating critically ill patients.

What evidence suggests that this protocol-based fluid management is effective for critical illness?

This trial will compare protocolized fluid removal with usual care for managing fluids in critically ill patients. Research has shown that a planned approach to fluid management can help very sick patients by maintaining proper fluid levels. Studies have found that reducing fluid intake and removing excess fluid can prevent fluid buildup. Specifically, one study showed that patients following a specific fluid removal plan had less fluid in their bodies by the fifth day in the ICU. This reduction in unnecessary fluid can aid recovery. The goal is to maintain balanced or slightly reduced fluid levels to avoid complications from fluid overload. ^{4 6 7 8 9}

Who Is on the Research Team?

William Beaubien-Souligny, MD PhD

Principal Investigator

CHUM

Ron Wald, MDCM MPH

Principal Investigator

Unity Health Toronto

Sean Bagshaw, MD MSc

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults over 18 in the ICU with acute kidney injury (AKI) who meet specific criteria related to changes in serum creatinine or urine output. They must be starting kidney replacement therapy soon or have started it within the last 48 hours. People can't join if they're not expected to receive full support, might leave ICU soon, have severe burns, extreme sodium levels, ongoing fluid loss, or if their care team thinks the trial isn't right for them.

Inclusion Criteria

I am currently in the Intensive Care Unit.

You have experienced kidney injury during your current hospital stay, as defined by specific levels of creatinine in your blood or low urine output.

I am starting kidney replacement therapy soon or have started it within the last 2 days.

Exclusion Criteria

Probable discharge from the ICU within the next 48 hours according to treating physician

The clinical care team believes that the proposed intervention is inappropriate.

Lack of commitment to maintain kidney, pharmacologic or respiratory support at the time of screening, or probable transition to comfort care within 48 hours according to the treating physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a protocol-based fluid management strategy or usual care for fluid balance management

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Extension

Participants may continue to be monitored for long-term outcomes and resource utilization

Up to 90 days

What Are the Treatments Tested in This Trial?

Interventions

• Protocol-based fluid management
• Usual care

Trial Overview The study tests a protocol-based fluid management strategy against usual care in critically ill patients on kidney replacement therapy. The goal is to manage fluids more actively to prevent and treat fluid buildup by aiming for neutral or negative daily fluid balance.

How Is the Trial Designed?

Group I: Protocolized fluid removal Experimental Treatment 1 Intervention

Group II: Usual care Active Control 1 Intervention

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Published Research Related to This Trial

In adults, well-constructed mechanical ventilation protocols can significantly improve outcomes such as reducing the duration of ventilation and length of hospital stay, but their effectiveness is inconsistent.

In pediatrics, while routine use of ventilator management protocols is not recommended due to shorter weaning durations, careful titration of sedation and daily assessments of spontaneous breathing trials (SBTs) are beneficial and should be more widely implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventilator management protocols in pediatrics. Graham, AS., Kirby, AL.[2007]

A new systematic resuscitation algorithm was developed to quickly identify and correct hypovolemia, which is crucial for improving patient outcomes and reducing complications.

Preliminary results from ongoing clinical trials indicate that using this algorithm leads to shorter resuscitation times and fewer hospital stays, ICU days, and instances of mechanical ventilation, ultimately reducing mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resuscitation algorithm for management of acute emergencies. Shoemaker, WC., Hopkins, JA., Greenfield, S., et al.[2019]

In a study of 612 mechanically ventilated patients with shock, protocol-based fluid management was associated with a significant reduction in ICU mortality, suggesting that structured fluid management can improve survival outcomes in critically ill patients.

Approximately 39.5% of patients received the fluid management protocol within the first 24 hours, and about 53.6% of these patients showed a positive response, indicating that close monitoring and adherence to fluid protocols can effectively guide treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shock in the first 24 h of intensive care unit stay: observational study of protocol-based fluid management. See, KC., Mukhopadhyay, A., Lau, SC., et al.[2015]

In a study of 888 pediatric patients in a PICU, using a restrictive fluid protocol showed that cumulative fluid balance did not significantly affect 28-day mortality rates, with similar outcomes in both positive and negative fluid balance groups.

Despite differences in fluid balance, there were no significant variations in organ dysfunction or acute kidney injury, although patients with positive fluid balance had longer stays in the PICU and hospital.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Cohort Study on Cumulative Fluid Balance and Outcome in Critically Ill Children Using a Restrictive Fluid Protocol. Rameshkumar, R., Chidambaram, M., Bhanudeep, S., et al.[2022]

In a review of over 5000 surgical and septic patients, goal-directed fluid therapy did not lead to less fluid accumulation or a decrease in acute kidney injury (AKI) or the need for renal replacement therapy.

While albumin solutions and balanced crystalloids are better tolerated than synthetic colloids in terms of kidney health, their clinical benefits compared to standard saline (0.9% sodium chloride) have not yet been established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does fluid management affect the occurrence of acute kidney injury? Mårtensson, J., Bellomo, R.[2018]

In a study analyzing 160 newborn records in an ICU, 21.3% of infants experienced hospital infections identified as adverse medical events, highlighting a significant safety concern in neonatal care.

The use of trigger tools effectively identified various adverse events, such as low glucose levels and electrolyte imbalances, suggesting that these tools could be crucial for developing a national system to monitor and improve patient safety in neonatal intensive care units.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Incidence of adverse medical events in the neonatal intensive care unit with the help of a global trigger tool]. Фастовец, МН., Белорус, АИ., Лысак, ВП., et al.[2017]

A protocol-driven (PRD) electrolyte replacement strategy in the ICU significantly reduced the time from identifying low electrolyte levels to starting replacement therapy compared to a physician-driven (PHD) approach, with times of 19-26 minutes for PRD versus 161-189 minutes for PHD.

The PRD strategy also resulted in fewer missed replacements, indicating improved efficiency, while maintaining safety, as no patients experienced high post-replacement serum concentrations of potassium, magnesium, or phosphate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol-driven vs. physician-driven electrolyte replacement in adult critically ill patients. Hijazi, M., Al-Ansari, M.[2019]

In a study of 88 critically ill patients, 52.3% experienced adverse events, which were linked to increased care needs, greater severity of illness, and longer hospital stays.

The average Nursing Activities Score indicated that patients required about 12 hours and 24 minutes of care, highlighting a significant nursing staff shortage of 20% to 30%, which may contribute to the high prevalence of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in critically ill patients: a cross-sectional study. Assis, SF., Vieira, DFVB., Sousa, FREG., et al.[2023]

In a study of 950 adult patients with severe sepsis or septic shock over 10 years, protocol-based therapy significantly reduced hospital mortality (28.4% vs 44.7%) and ICU mortality (24.2% vs 31.6%) compared to non-protocolized care.

The survival advantage from protocol-based management was established after one year and maintained throughout the study, indicating that structured clinical pathways can effectively improve outcomes in sepsis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 10-Year Longitudinal Analysis of Protocol-Based Sepsis Management in a Philippine Tertiary ICU. Bumanglag, NM., San Juan, MDJ., Palo, JEM.[2022]

Aggressive volume expansion during the early resuscitation phase for critically ill children, particularly those in septic shock, significantly improves outcomes by enhancing tissue oxygen delivery.

After initial resuscitation, managing fluid balance to avoid positive fluid retention is crucial, as it is linked to shorter hospital stays and fewer complications, highlighting the need for more research on fluid management specifically in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluid management in the critically ill child. Raman, S., Peters, MJ.[2021]

In a study of 167 patients recently discharged from an Australian ICU, 10% experienced adverse events within 72 hours, with over half (52%) deemed probably preventable, highlighting significant opportunities for improving patient safety during transitions from ICU to the ward.

The most common adverse events were related to fluid management, and the outcomes included ICU readmissions and even deaths, indicating that better monitoring and support systems are needed to prevent these incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining the occurrence of adverse events within 72 hours of discharge from the intensive care unit. McLaughlin, N., Leslie, GD., Williams, TA., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10581269/

Current management of fluid balance in critically ill patients ... Of the 13,767 studies reviewed, 22 met the inclusion criteria. Two studies examined manipulation of fluid input, 18 studies assessed enhancing fluid removal, ...

2. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-025-05624-z

Restrictive fluid management with early de-escalation versus ... A restrictive fluid strategy with early de-escalation and de-resuscitation is feasible and may reduce fluid accumulation and showed a signal for ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883944122002787

Fluid de-resuscitation in critical illness – A journey into ... The primary endpoint, the cumulative fluid balance was significantly lower in the early dry group at intensive care unit (ICU) day 5, death or discharge (median ...

4. ctv.veeva.com ctv.veeva.com/study/proactive-prescription-based-fluid-management-vs-usual-care-in-critically-ill-patients-on-kidney-rep

Proactive Prescription-based Fluid Management vs Usual ... The study is a pilot randomized clinical trial comparing a protocol-based fluid management strategy with usual care in critically ill patients receiving KRT.

5. researchgate.net researchgate.net/publication/372854323_Restrictive_fluid_management_and_early_fluid_de-escalation_versus_usual_care_in_critically_ill_patients_A_feasibility_trial_protocol_for_the_REDUCE_randomized_clinical_trial

A feasibility trial protocol for the REDUCE randomized ... Objectives: To compare the efficacy of protocol-based fluid-restrictive management versus standard care in critically ill patients with circulatory shock.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31023358/

study protocol for a multi-centre randomized controlled trial Discussion: If study results will show that LUS guided fluid management protocol improves outcome in ICU patients, it will be the base for other ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12465594/

Restrictive fluid management with early de-escalation versus ... This pilot study assessed the efficacy of a restrictive fluid strategy aimed at achieving a neutral to negative fluid balance within the first ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1441277223000236

Current management of fluid balance in critically ill patients ... An association between fluid balance (FB) and adverse patient-centred outcomes in critically ill patients with AKI regardless of severity has been demonstrated.

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202707

Restriction of Intravenous Fluid in ICU Patients with Septic ... Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid ...