This study is enrolling adult patients who require a prolonged stay in the intensive care unit (ICU). These patients often receive large amounts of intravenous fluids, which can contain more salt (sodium and chloride) than the body normally needs. Extra salt and water can build up in the body and may delay recovery.
The study will test two strategies:
Fluid creep: These are fluids used to dilute medications or keep intravenous lines open. Usually, the choice is based on habit. In the intervention group, a salt-free glucose 5% solution will be used (if the responsible pharmacist confirms it is compatible with the medication).
Maintenance fluids: These fluids cover daily needs for water and electrolytes. In the intervention group, a lower-salt solution (NaCl 0.3% in glucose 3.3%) will be given, with volume decided by the treating physician.
The comparison group will receive usual care: NaCl 0.9% (commonly called "normal saline") for fluid creep, and an isotonic solution (PlasmaLyte) for maintenance fluids.
The main outcome is the number of days patients are alive and free of life support (such as ventilator or dialysis) during the first 90 days. Other outcomes include abnormal sodium, chloride, or glucose levels, fluid balance and need for diuretics, kidney injury, use of dialysis, time on the ventilator, survival, and length of ICU and hospital stay.
A smaller substudy (SALADIN) will measure in detail how the body handles sodium, chloride, and water using additional calculation on blood tests, urine collections, body weight, and bioimpedance analysis
At least 18 years of age
Patients who are admitted to the ICU for medical or surgical emergencies, including complications of elective surgery
The treating physician expects the patient will still require ICU care in two days, indicating a severe or complex condition at enrollment
The patient is expected to receive at least 300 mL of fluid creep or at least 1 liter of maintenance fluid according to study-arm during the first 24h after inclusion
A contraindication to hypotonic fluids due to risk of brain edema (including traumatic brain injury, major stroke, intracranial/subarachnoid hemorrhage, meningoencephalitis, intracranial malignancies…), with the timing and clinical judgment left at the discretion of the treating physician.
Hyponatremia below 131 mmol/L at admission
Admission solely for treatment of fluid accumulation due to cardiac decompensation, without other acute medical conditions requiring ICU-level care. Note: Patients with heart failure as a comorbidity, those on chronic diuretic therapy, or presenting with edema/bilateral lung infiltrates due to other conditions (e.g., sepsis, pneumonia) are not excluded.
Patient's death is deemed imminent and inevitable, admission for palliative care or admission solely for organ donation
Parallel
Glucose 5% for fluid creep
Drug* Medications, including concentrated electrolytes, are dissolved in glucose 5% except when another solvent is mandatory according to the responsible pharmacist. * Infusions to keep intravenous lines open are glucose 5%
NaCl 0.9% (normal saline) for fluid creep
Drug* Medications, including concentrated electrolytes, are dissolved in NaCl 0.9% except when another solvent is mandatory according to the responsible pharmacist. * All infusions to keep intravenous lines open are NaCl 0.9%.
PlasmaLyte as maintenance fluid
Drug* Type: Maintenance fluid is PlasmaLyte. Potassium chloride or potassium phosphate can be added (or administered separately) whenever deemed necessary. * Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate.
NaCl 0.3% in glucose 3.3% as maintenance fluid
Drug* Type: maintenance fluid is NaCl 0.3% in glucose 3.3%. Potassium chloride or potassium phosphate can be added (or administered separately) at the discretion of the treating physician whenever necessary. * Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate
Days alive and without life support at day 90 (DAWOLS90)
The composite endpoint DAWOLS90 is defined as the number of days alive and without the use of life support within 90 days counted from ICU admission. Unit of measure: days. Patients who die before D90 are assigned zero days. The following life-support therapies are considered 1/ Mechanical ventilation: includes invasive and noninvasive ventilation, including continuous positive airway pressure (CPAP) but excluding high-flow nasal oxygen. Each ICU day counts as a ventilator day if support is in place. Post-extubation days are counted as ventilator-free only if no re-intubation occurs within 48 hours. 2/ Renal replacement therapy (RRT): includes continuous RRT, peritoneal dialysis, or intermittent hemodialysis (IHD). If IHD is given, periods with up to 3 days between sessions are counted as days with RRT.
Occurrence of moderate and severe hyponatremia
Defined as the number of participants with at least one episode of: Moderate hyponatremia: serum sodium 125-129 mmol/L Severe hyponatremia: serum sodium \<125 mmol/L To be counted as an event, the sodium level must decrease by at least 3 mmol/L from baseline to reduce misclassification due to pre-existing mild hyponatremia or analytical variation. Assessments are based on daily routine morning serum sodium values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care sodium values (measured within 2 hours) will be recorded to allow cross-checks and sensitivity analyses
Occurrence of moderate and severe hypernatremia
Defined as the number of participants with at least one episode of: Moderate hypernatremia: serum sodium 151-155 mmol/L Severe hypernatremia: serum sodium \>155 mmol/L To be counted as an event, the sodium level must increase by at least 3 mmol/L from baseline to account for pre-existing mild hypernatremia and analytical variation. Assessments are based on daily routine morning serum sodium values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care sodium values (measured within 2 hours of the central measurement) will be recorded to allow cross-checks and sensitivity analyses.
Occurrence of moderate and severe hyperchloremia
Defined as the number of participants with at least one episode of: Moderate hyperchloremia: serum chloride 111-115 mmol/L Severe hyperchloremia: serum chloride \>115 mmol/L To be counted as an event, the chloride level must increase by at least 2 mmol/L from baseline to account for pre-existing mild hyperchloremia and analytical variation. Assessments are based on daily routine morning serum chloride values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care chloride values (measured within 2 hours of the central measurement) will be recorded to allow cross-checks and sensitivity analyses
Time to first administration of intravenous loop diuretic
Defined as the time (in hours) from randomization until the first administration of an intravenous loop diuretic (e.g., furosemide or bumetanide). The exact timestamp of first administration is recorded.
Daily sodium, chloride and glucose administration
Total daily amount of sodium, chloride, and glucose (mmol or g per ICU day) from study fluids, non-study maintenance, replacement and resuscitation fluids, enteral and parenteral nutrition, and blood products (sodium/chloride content estimated from reference values). Excludes non-study fluid creep and oral intake.
Cumulative sodium, chloride and glucose administration
Running total of sodium, chloride, and glucose (mmol or g) from ICU admission onward. Each day's administered amount is added to all previous ICU days. Same sources and exclusions as for daily administration.
Daily fluid balance (mL)
Daily fluid balance is calculated as inputs minus outputs (mL per ICU Day). Inputs: study fluids, non-study fluid creep, non-study maintenance and replacement fluids, non-study resuscitation fluids, enteral and parenteral nutrition, blood products, and oral intake. Outputs: urine output, net ultrafiltration by renal replacement therapy, gastric aspirates, drain outputs, and diarrhea (if precisely measured). From the time renal replacement therapy or intravenous loop diuretics are initiated, fluid balance will be analyzed separately from patients who do not receive these interventions.
Cumulative fluid balance (mL)
Cumulative fluid balance is defined as the running total of daily net fluid balances (inputs minus outputs), excluding insensible losses. Each day's balance is added to that of all previous ICU days, allowing assessment at any time during the ICU stay. Daily fluid balance is calculated as inputs minus outputs (mL per ICU Day). Inputs: study fluids, non-study fluid creep, non-study maintenance and replacement fluids, non-study resuscitation fluids, enteral and parenteral nutrition, blood products, and oral intake. Outputs: urine output, net ultrafiltration by renal replacement therapy, gastric aspirates, drain outputs, and diarrhea (if precisely measured). From the time renal replacement therapy or intravenous loop diuretics are initiated, fluid balance will be analyzed separately from patients who do not receive these interventions.
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University Hospital, Antwerp
Lead sponsor
Ziekenhuis aan de Stroom
Collaborator
Research Foundation Flanders
Collaborator
