Effect of Reduced Sodium Chloride in Fluid Creep and Maintenance Fluids in Critically Ill Adults: A Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 640
- 试验地点
- 4
- 主要终点
- Days alive and without life support at day 90 (DAWOLS90)
研究概览
简要总结
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
详细描述
Critically ill patients admitted to the intensive care unit (ICU) often receive large volumes of intravenous fluids. Beyond resuscitation fluids, which have been extensively studied, two other sources contribute substantially to fluid, sodium, and chloride exposure:
Fluid creep, the use of diluents and small-volume infusions to dissolve medications or maintain line patency.
Maintenance fluids, prescribed to cover daily fluid and electrolyte needs when oral intake is insufficient.
Together, fluid creep and maintenance fluids account for more than half of all intravenous fluids given in ICU patients. These fluids frequently contain supraphysiologic amounts of sodium and chloride. Because the kidneys of critically ill patients are unable to excrete these excesses efficiently, sodium and chloride accumulate, leading to positive fluid balances, electrolyte disturbances, pulmonary edema, renal dysfunction, and prolonged organ support. Observational data have linked both fluid overload and hyperchloremia to higher morbidity and mortality.
Prior research has focused mainly on resuscitation fluids. Large randomized trials comparing chloride-rich saline to balanced crystalloids demonstrated only small differences in outcomes, in part because resuscitation fluids make up a limited fraction of overall fluid exposure. In contrast, fluid creep and maintenance solutions offer a larger and modifiable source of sodium and chloride. Small studies and volunteer experiments have shown that sodium-poor maintenance fluids and sodium-free diluents reduce fluid retention and hyperchloremia, but their effect on patient-centered outcomes has never been tested in a large randomized trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinding is ensured by the use of opaque blinding labels applied by unblinded hospital pharmacists. These labels conceal the identity of the solution while leaving mandatory information such as fluid volume, batch number, and expiry date visible, in line with regulatory requirements. The fluids are otherwise indistinguishable and are labeled only with a randomization code letter. Randomization letters are changed monthly to prevent recognition of fluid composition. Only the pharmacists are unblinded; they handle labeling, storage, and distribution but are not involved in patient care or outcome assessment. In the ICU, nurses and physicians administer fluids documented simply as "study fluid," without access to the underlying composition.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Patient receiving chronic renal replacement therapy
- •Patients referred after a stay of more than 24 hours in another ICU
- •Patients randomized in CRUSADERS before
- •Patient is co-enrolled in an unapproved concomitant ICU-trial or in any trial with an intervention that affects fluid administration or fluid balance
- •Additional exclusion criteria for the SALADIN nested substudy
- •Patients expected to require renal replacement therapy within 24 hours
- •Increased insensible fluid losses: burns, extensive wounds or skin defects or massive diarrhea,…
- •Patients without a urine catheter
- •Patients expected to require bladder irrigation within 24 hours
- •Patients on chronic treatment with loop or thiazide diuretics (including combination preparations)
研究组 & 干预措施
Sodium chloride reduction strategy, the NaCl-poor arm
Participants receive a sodium-chloride reduction strategy during their ICU stay. Medications are diluted in glucose 5% (unless another solvent is mandatory), and intravenous line patency fluids are glucose 5%. Daily maintenance fluids are NaCl 0.3% in glucose 3.3%, with the volume determined by the treating physician. The goal is to reduce sodium and chloride exposure while maintaining fluid and electrolyte support.
Interventions:
Drug: Glucose 5% Drug: NaCl 0.3% in Glucose 3.3%
干预措施: Glucose 5% for fluid creep (Drug)
Sodium chloride reduction strategy, the NaCl-poor arm
Participants receive a sodium-chloride reduction strategy during their ICU stay. Medications are diluted in glucose 5% (unless another solvent is mandatory), and intravenous line patency fluids are glucose 5%. Daily maintenance fluids are NaCl 0.3% in glucose 3.3%, with the volume determined by the treating physician. The goal is to reduce sodium and chloride exposure while maintaining fluid and electrolyte support.
Interventions:
Drug: Glucose 5% Drug: NaCl 0.3% in Glucose 3.3%
干预措施: NaCl 0.3% in glucose 3.3% as maintenance fluid (Drug)
Isotonic fluid strategy, the NaCl-rich arm
Participants receive a standard isotonic fluid strategy during their ICU stay. Medications are diluted in NaCl 0.9% (unless another solvent is mandatory), and intravenous line patency fluids are NaCl 0.9%. Daily maintenance fluids are PlasmaLyte, with the volume determined by the treating physician. This reflects the common standard of care in many ICUs.
Interventions:
Drug: NaCl 0.9% Drug: PlasmaLyte
干预措施: NaCl 0.9% (normal saline) for fluid creep (Drug)
Isotonic fluid strategy, the NaCl-rich arm
Participants receive a standard isotonic fluid strategy during their ICU stay. Medications are diluted in NaCl 0.9% (unless another solvent is mandatory), and intravenous line patency fluids are NaCl 0.9%. Daily maintenance fluids are PlasmaLyte, with the volume determined by the treating physician. This reflects the common standard of care in many ICUs.
Interventions:
Drug: NaCl 0.9% Drug: PlasmaLyte
干预措施: PlasmaLyte as maintenance fluid (Drug)
结局指标
主要结局
Days alive and without life support at day 90 (DAWOLS90)
时间窗: From admission until day 90 counted from ICU admission (= Day 1)
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.
次要结局
- Occurrence of moderate and severe hyponatremia(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of moderate and severe hypernatremia(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of moderate and severe hyperchloremia(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Time to first administration of intravenous loop diuretic(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Proportion of ICU days with intravenous loop diuretic use(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Cumulative fluid balance in mL up to first IV loop diuretic use(From ICU admission until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of hyperglycemia(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of hypoglycemia(From randomization until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of new-onset acute kidney injury (AKI)(From third ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission))
- Occurrence of new-onset need for renal replacement therapy (RRT)(From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission))
- Renal replacement therapy-free days at day 90(From ICU admission until day 90 counted from ICU admission.)
- Occurrence of new-onset need for mechanical ventilation(From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission))
- Ventilator-free days at day 90(From ICU admission until ICU discharge (up to day 90 counted from ICU admission))
- Days alive and out of hospital at day 90 (DAOH90)(From ICU admission until day 90 counted from ICU admission.)
- ICU length of stay(From ICU admission until ICU discharge (up to day 90 counted from ICU admission).)
- Hospital length of stay(From ICU admission until hospital discharge (up to day 90 counted from ICU admission))
- ICU mortality(From ICU admission until discharge from the index ICU episode, including any continuous referrals/transfers to other ICUs (up to day 90 counted from ICU admission))
- Hospital mortality(From ICU admission until discharge from the index hospital admission (up to day 90 counted from ICU admission))