CReep and Maintenance flUid Sodium Chloride ADministration rEduction in cRitically Ill adultS

Browse trials for

• Critical Illness 1,780Registry's first term · unverified
• Acute Kidney Injury 1,691
• Hyponatremia 164

Keywords

• Intensive Care Unit
• Critically Ill
• Critical Illness
• Intravenous fluids
• Maintenance fluids
• Fluid Creep
• Sodium chloride reduction
• Salt reduction
• Hypotonic fluids
• Saline (NaCl 0.9%)
• Fluid balance
• Electrolyte disorders
• Glycemic control
• Acute kidney injury
• Mechanical ventilation
• Organ support
• Hyponatremia

Critical Illness Unverified

1,780 studies on the registry are indexed under Critical Illness; 442 are open to participants now.

This study's planned enrollment of 640 is above the median of 90 across 926 interventional studies indexed under Critical Illness.

Lead sponsor

University Hospital, Antwerp is the lead sponsor of 242 studies on the registry; 66 are open to participants now.

Study arms

• Active comparator
  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%

  Drug: Glucose 5% for fluid creep · Drug: NaCl 0.3% in glucose 3.3% as maintenance fluid

• Active comparator
  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

  Drug: NaCl 0.9% (normal saline) for fluid creep · Drug: PlasmaLyte as maintenance fluid

Interventions

• DrugGlucose 5% for fluid creep

  * 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%

• DrugNaCl 0.9% (normal saline) for fluid creep

  * 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%.

• DrugPlasmaLyte as maintenance fluid

  * 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.

• DrugNaCl 0.3% in glucose 3.3% as maintenance fluid

  * 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

Primary outcomes

1. 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.

   Time frame: From admission until day 90 counted from ICU admission (= Day 1)

Secondary outcomes

1. 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

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

2. 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.

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

3. 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 frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

4. 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.

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

5. Proportion of ICU days with intravenous loop diuretic use

   Defined as the number of ICU days during which a participant receives at least one dose of an intravenous loop diuretic, expressed as a proportion of total ICU days.

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

6. Cumulative fluid balance in mL up to first IV loop diuretic use

   Defined as the cumulative net fluid balance, excluding insensible losses. Daily fluid balance is calculated as total inputs minus total 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). The cumulative fluid balance is the sum of all daily fluid balances from ICU admission until the morning of the first ICU day on which an intravenous loop diuretic is prescribed.

   Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)

7. Occurrence of hyperglycemia

   Defined as the proportion of glucose measurements \>180 mg/dL relative to the total number of glucose assessments during the ICU stay. Mean daily glucose values will also be calculated for each ICU day. Assessments are based on point-of-care blood gas analyzer values, which are routinely collected multiple times per day in all ICU patients.

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

8. Occurrence of hypoglycemia

   Defined as the number of participants with at least one episode of hypoglycemia, serum glucose \<70 mg/dL, measured on routine point-of-care blood gas analysis. Severe hypoglycemia (\<40 mg/dL) is separately recorded as a serious adverse reaction.

   Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)

9. Occurrence of new-onset acute kidney injury (AKI)

   Defined as the number of participants who develop new-onset AKI stage 2 or 3 according to KDIGO criteria (Kidney Disease: Improving Global Outcomes), starting from the third ICU day after randomization. AKI classification is based on daily serum creatinine (central laboratory morning samples) and urine output collected every 12-24 hours. KDIGO stage 1 is not assessed in this trial.

   Time frame: From third ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)

10. Occurrence of new-onset need for renal replacement therapy (RRT)

    Defined as the number of participants requiring new initiation of RRT (continuous renal replacement therapy, peritoneal dialysis, or intermittent hemodialysis). To attribute RRT to the intervention, only events starting on or after the second ICU day following randomization are considered.

    Time frame: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)

11. Renal replacement therapy-free days at day 90

    Calculated as the number of days during the 90-day observation period that a participant is alive and not receiving renal replacement therapy (RRT). For intermittent hemodialysis, periods with up to 3 days between sessions are counted as days on RRT.

    Time frame: From ICU admission until day 90 counted from ICU admission.

12. Occurrence of new-onset need for mechanical ventilation

    Defined as the number of participants who newly require mechanical ventilation after randomization. Mechanical ventilation includes invasive and noninvasive ventilation (including continuous positive airway pressure (CPAP)) but excludes high-flow nasal oxygen. To attribute events to the intervention, only new initiation from the second ICU day after randomization is considered.

    Time frame: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)

13. Ventilator-free days at day 90

    Calculated as the number of days during the 90-day observation period that a participant is alive and free of mechanical ventilation. Mechanical ventilation includes invasive and noninvasive ventilation (including CPAP) but excludes high-flow nasal oxygen. Following extubation, days are counted as ventilator-free only if no re-intubation occurs within 48 hours.

    Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)

14. Days alive and out of hospital at day 90 (DAOH90)

    Defined as the number of days a participant is alive and outside the hospital during the 90 days after ICU admission. If a patient is discharged and later readmitted, both admissions are included in the total number of hospitalization days. Mortality is penalized and assigned a value of zero DAOH. DAOH is calculated at day 90 counted from ICU admission.

    Time frame: From ICU admission until day 90 counted from ICU admission.

15. ICU length of stay

    Defined as the number of calendar days from ICU admission to ICU discharge, including referral or transfer to other ICUs following the same admission.

    Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission).

16. Hospital length of stay

    Defined as the number of calendar days from ICU admission to hospital discharge, including transfers to other hospitals. Discharges or transfers to rehabilitation wards within the same hospital are not counted as hospital length of stay.

    Time frame: From ICU admission until hospital discharge (up to day 90 counted from ICU admission)

17. ICU mortality

    Death occurring at any time while continuously in ICU during the index (initial) ICU episode. Inter-ICU transfers are considered part of the same continuous ICU episode. Deaths after discharge from the index ICU episode-whether on the ward or during any later ICU readmission within the same hospital admission-are not counted.

    Time frame: 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)

18. Hospital mortality

    Death occurring at any time during the index (initial) hospital admission, irrespective of location (ICU or ward within the same hospital) and including transfers to other hospitals within the same continuous admission. Deaths after discharge from the index hospital admission are not counted, even if the patient is readmitted later.

    Time frame: From ICU admission until discharge from the index hospital admission (up to day 90 counted from ICU admission)

Other outcomes

1. 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.

   Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission).

2. 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.

   Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission).

3. 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.

   Time frame: From ICU admission until ICU discharge, day 90 counted from ICU admission, removal of bladder catheter or initiation of bladder irrigation, whichever comes first.

4. 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.

   Time frame: From ICU admission until ICU discharge, day 90 counted from ICU admission, removal of bladder catheter or initiation of bladder irrigation, whichever comes first.

5. Serum urea-to-creatinine ratio

   Defined as the change in serum urea-to-creatinine ratio, measured every other ICU day starting the first morning after randomization in patients not receiving renal replacement therapy (RRT). Serum creatinine is assessed as part of routine care, and serum urea is measured from the same morning blood sample without additional sampling. Urea measurements are discontinued from the day RRT is initiated, and patients on RRT are excluded from this analysis. This endpoint is exploratory and based on the rationale that higher sodium exposure, as in the NaCl-rich arm, may increase muscle catabolism. The serum urea-to-creatinine ratio is an established biomarker of catabolism in critically ill patients.

   Time frame: From the first morning after randomization until ICU discharge or initiation of RRT (up to day 90).

6. Daily sodium and chloride balance (SALADIN substudy)

   Net daily balance of sodium and chloride (mmol per ICU day), defined as inputs minus outputs. Inputs: study fluids, non-study maintenance and replacement fluids 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. Outputs: sodium and chloride content of all urine collected during the ICU day Urine samples are performed until the ICU day on which bladder catheter removal, initiation of bladder irrigation, start of renal replacement therapy, or ICU discharge occurs, whichever comes first.

   Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

7. Cumulative sodium and chloride balance (SALADIN substudy)

   Running total of daily sodium and chloride balances. Each day's balance is added to that of all previous ICU days, allowing assessment at any time during the ICU stay. Net daily balance of sodium and chloride (mmol per ICU day), defined as inputs minus outputs. Inputs: study fluids, non-study maintenance and replacement fluids 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. Outputs: sodium and chloride content of all urine collected during the ICU day Urine samples are performed until the ICU day on which bladder catheter removal, initiation of bladder irrigation, start of renal replacement therapy, or ICU discharge occurs, whichever comes first.

   Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

8. Solute-free water clearance (SALADIN substudy)

   Derived from urine and plasma osmolality and urine flow rate. Reported as mL per ICU day. Formula: Solute-free water clearance CH2O = V × (1 - Uosm/Posm), where V = urine flow rate, Uosm = urine osmolality, and Posm = plasma osmolality. Calculated daily during ICU stay in participants with 24-hour urine collections.

   Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

9. Electrolyte-free water clearance (SALADIN substudy)

   Derived from urine sodium, urine potassium, plasma sodium, and urine flow rate. Reported as mL per ICU day. Formula Electrolyte-free water clearance: CeH2O = V × (1 - (UNa + UK)/PNa)), where V = urine flow rate, UNa = urine sodium concentration, UK = urine potassium concentration, and PNa = plasma sodium concentration. Calculated daily during ICU stay in participants with 24-hour urine collections.

   Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

10. Volume kinetics (SALADIN substudy)

    Model-based analysis of administered fluid volumes and urine output to describe distribution and clearance of infused solutions. Performed in participants included in the SALADIN substudy with complete fluid and urine balance data.

    Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

11. Measured body weight (SALADIN substudy)

    Daily body weight recorded in substudy participants to quantify changes in body fluid volume and tissue mass during critical illness.

    Time frame: From ICU admission until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

12. Fluid distribution (BIA-derived) (SALADIN substudy)

    Noninvasive bioelectrical impedance analysis (BIA) will be performed once daily up to every third ICU day in substudy participants using a multi-frequency analyzer. Fluid distribution parameters assessed include total body water, intracellular water, extracellular water, intravascular and extravascular distribution, and volume excess. Results are used to evaluate dynamic changes in fluid status during critical illness and to relate these to sodium and chloride balance.

    Time frame: From randomization until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

13. Body Composition (BIA-derived) (SALADIN-substudy)

    Noninvasive bioelectrical impedance analysis (BIA) will be performed once daily up to every third ICU day in substudy participants using a multi-frequency analyzer. Body composition parameters assessed include fat-free mass, fat mass, muscle mass, protein, mineral, and bone content. Serial measurements are used to assess changes in tissue composition over the course of critical illness.

    Time frame: From randomization until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

14. Metabolic Indices (BIA-derived) (SALADIN substudy)

    Noninvasive bioelectrical impedance analysis (BIA) will be performed once daily up to every third ICU day in substudy participants using a multi-frequency analyzer. Metabolic indices include resting metabolic rate, glycogen deposits, phase angle, and malnutrition index. These indices are evaluated to explore metabolic changes and nutritional status during critical illness, and their relationship with sodium and chloride balance.

    Time frame: From randomization until ICU discharge or end of substudy sampling (up to day 90 counted from ICU admission)

Publications

• Granholm A, Schjorring OL, Jensen AKG, Kaas-Hansen BS, Munch MW, Klitgaard TL, Crescioli E, Kjaer MN, Strom T, Lange T, Perner A, Rasmussen BS, Moller MH. Association between days alive without life support/out of hospital and health-related quality of life. Acta Anaesthesiol Scand. 2023 Jul;67(6):762-771. doi: 10.1111/aas.14231. Epub 2023 Mar 21. PubMed 36915265 ↗
• Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018 Apr;44(4):409-417. doi: 10.1007/s00134-018-5147-3. Epub 2018 Mar 27. PubMed 29589054 ↗
• Van Regenmortel N, Moers L, Langer T, Roelant E, De Weerdt T, Caironi P, Malbrain MLNG, Elbers P, Van den Wyngaert T, Jorens PG. Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults. Ann Intensive Care. 2021 May 17;11(1):79. doi: 10.1186/s13613-021-00851-3. PubMed 33999276 ↗
• Van Regenmortel N, Hendrickx S, Roelant E, Baar I, Dams K, Van Vlimmeren K, Embrecht B, Wittock A, Hendriks JM, Lauwers P, Van Schil PE, Van Craenenbroeck AH, Verbrugghe W, Malbrain MLNG, Van den Wyngaert T, Jorens PG. 154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial. Intensive Care Med. 2019 Oct;45(10):1422-1432. doi: 10.1007/s00134-019-05772-1. Epub 2019 Oct 1. PubMed 31576437 ↗
• Sakr Y, Vincent JL, Reinhart K, Groeneveld J, Michalopoulos A, Sprung CL, Artigas A, Ranieri VM; Sepsis Occurence in Acutely Ill Patients Investigators. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005 Nov;128(5):3098-108. doi: 10.1378/chest.128.5.3098. PubMed 16304249 ↗
• Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017 Feb;43(2):155-170. doi: 10.1007/s00134-016-4573-3. Epub 2016 Oct 12. PubMed 27734109 ↗
• Salahuddin N, Sammani M, Hamdan A, Joseph M, Al-Nemary Y, Alquaiz R, Dahli R, Maghrabi K. Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study. BMC Nephrol. 2017 Feb 1;18(1):45. doi: 10.1186/s12882-017-0460-6. PubMed 28143505 ↗
• Bihari S, Prakash S, Potts S, Matheson E, Bersten AD. Addressing the inadvertent sodium and chloride burden in critically ill patients: a prospective before-and-after study in a tertiary mixed intensive care unit population. Crit Care Resusc. 2018 Dec;20(4):285-293. PubMed 30482136 ↗
• Magee CA, Bastin MLT, Laine ME, Bissell BD, Howington GT, Moran PR, McCleary EJ, Owen GD, Kane LE, Higdon EA, Pierce CA, Morris PE, Flannery AH. Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study. Crit Care Med. 2018 Aug;46(8):1217-1223. doi: 10.1097/CCM.0000000000003191. PubMed 29727367 ↗
• Van Regenmortel N, Langer T, De Weerdt T, Roelant E, Malbrain M, Van den Wyngaert T, Jorens P. Effect of sodium administration on fluid balance and sodium balance in health and the perioperative setting. Extended summary with additional insights from the MIHMoSA and TOPMAST studies. J Crit Care. 2022 Feb;67:157-165. doi: 10.1016/j.jcrc.2021.10.022. Epub 2021 Nov 17. PubMed 34798374 ↗
• Nagae M, Egi M, Furushima N, Okada M, Makino S, Mizobuchi S. The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study. J Anesth. 2019 Apr;33(2):287-294. doi: 10.1007/s00540-019-02626-4. Epub 2019 Feb 26. PubMed 30806785 ↗
• Surveillance report 2017 - Intravenous fluid therapy in adults in hospital (2013) NICE guideline CG174 [Internet]. London: National Institute for Health and Care Excellence (NICE); 2017 Apr 24. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK552079/ PubMed 31891467 ↗
• Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17. PubMed 31531715 ↗
• Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T, Lantier L, LaRocque LM, Marton A, Neubert P, Schroder A, Rakova N, Jantsch J, Dikalova AE, Dikalov SI, Harrison DG, Muller DN, Nishiyama A, Rauh M, Harris RC, Luft FC, Wassermann DH, Sands JM, Titze J. High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. J Clin Invest. 2017 May 1;127(5):1944-1959. doi: 10.1172/JCI88532. Epub 2017 Apr 17. PubMed 28414295 ↗
• Rakova N, Kitada K, Lerchl K, Dahlmann A, Birukov A, Daub S, Kopp C, Pedchenko T, Zhang Y, Beck L, Johannes B, Marton A, Muller DN, Rauh M, Luft FC, Titze J. Increased salt consumption induces body water conservation and decreases fluid intake. J Clin Invest. 2017 May 1;127(5):1932-1943. doi: 10.1172/JCI88530. Epub 2017 Apr 17. PubMed 28414302 ↗

Study documents

• Study protocol ↗ · May 25, 2025
• Statistical analysis plan ↗ · Sep 5, 2025
• Informed consent form ↗ · Mar 8, 2025
• Informed consent form ↗ · Mar 19, 2025

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No