Metabolism of Isotonic Versus Hypotonic Maintenance Solutions in Fasting Healthy Adults (MIHMoSA)

Metabolism of Isotonic Versus Hypotonic Maintenance Solutions in Fasting Healthy Adults, a Single-Blind Randomized Crossover Trial

The prescription of intravenous maintenance solutions - although widespread - lacks important data on the optimal sodium and potassium content, which has given rise to an important debate in the scientific literature. Our study compares two different infusion fluids in 12 healthy adult volunteers without renal failure in a single-blind randomized crossover design over two 48 hour periods during which subjects are not allowed to eat or drink. Fluid 1 is a premixed solution containing 54 mmol/L of sodium and 26 mmol/L of potassium; fluid 2 is sodium chloride 0.9% in glucose 5% with 40 mmol/L of potassium. Both solutions are administered at 25 mL/kg of ideal body weight, as recommended by current guidelines (NICE 174) and both solutions are widely used in daily clinical practice. The primary hypothesis is that isotonic maintenance solutions lead to more fluid retention than hypotonic fluids. Metabolism of both solutions is assessed by sequential analysis of urine and serum, clinical parameters and bioelectrical impedance analysis.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Volunteers
• Intervention / Treatment: Drug: NaCl 0.9% in Glucose 5% with 40mEq Potassium; Drug: Glucion 5%

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • University Hospital, Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults, 18-70 years of age
• BMI 17-45 kg/m².
• Creatinine clearance >60 ml/min (according to eGFR CKD-EPI formula).

Exclusion Criteria:

• Acute medical illness within 3 weeks of first study period
• Chronic medication: under diuretic therapy or other chronic medication that interfere with urine output or induce urine retention. All chronic medication should be declared before being enrolled in the study.

• Medical history:

  • cardiac failure,
  • malnourishment,
  • diabetes mellitus,
  • urological disease preventing spontaneous or complete emptying of the bladder,
• any medical or non-medical issue preventing complaint-free fasting for 48 hours (e.g. active peptic ulcer, psychosis, substance abuse…)
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Isotonic Maintenance Fluid	Drug: NaCl 0.9% in Glucose 5% with 40mEq Potassium; NaCl 0.9% in Glucose 5% with 40mEq Potassium, administered at 25 mL/kg IBW/h for 48h
ACTIVE_COMPARATOR: Hypotonic Maintenance Fluid	Drug: Glucion 5%; Glucion 5% (premixed solution containing 54 mmol/L sodium and 26 mmol/L potassium amongst others), administered at 25 mL/kg IBW/h for 48h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Output	Urinary output over study period (as AUC).	48h
Body weight	Body weight over study period (as AUC), used as a back up parameter for urinary output.	48h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of sodium retention / excretion (excreted sodium / administered sodium)	Sodium retention / excretion over study period (mean at 24 and 48h)	48h
Number of episodes of hypokalemia (<3.5 mmol/L), hyponatremia (<135 mmol/L), hypernatremia (>145 mmol/L)		48h
Change of sodium level from its baseline value.	Area under the electrolyte concentration curve (baseline level is reference line)	48h
Change of sodium and potassium level from its baseline value.	Area under the electrolyte concentration curve (baseline level is reference line)	48h

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Osmoregulatory Profile 1: urinary volume (mL)	Sequential changes in mean urinary volume (per fluid type) at T0-T12-T24-T36-T48.	48h
Osmoregulatory Profile 2: urinary osmolality (mOsm/kg)	Sequential changes in mean urinary osmolality (per fluid type). Urinary osmolality is determined on a sample of every individual diuresis. Subjects urinate as the urge rises.	48h
Osmoregulatory Profile 3: serum antidiuretic hormone (ADH) (pg/mL)	Sequential changes in mean serum ADH (per fluid type) at T0-T24-T48.	48h
Osmoregulatory Profile 4: thirst score (scale 0-5)	Sequential changes in mean thirst score (per fluid type) at T0-T12-T24-T36-T48. The thirst score is a subjective score on a scale of 0-5.	48h
Volume Regulatory Profile 1: urinary sodium (mmol/L)	Sequential changes in mean urinary sodium (per fluid type). Urinary sodium is determined on a sample of every individual diuresis. Subjects urinate as the urge rises. Urinary sodium is used to calculate the fractional excretion of sodium.	48h
Volume Regulatory Profile 2: serum aldosterone (ng/dL)	Sequential changes in mean serum aldosterone (per fluid type) at T0-T24-T48.	48h
Volume Regulatory Profile 3: urinary potassium (mmol/L)	Sequential changes in mean urinary potassium (per fluid type). Urinary potassium is determined on a sample of every individual diuresis. Subjects urinate as the urge rises.	48h
Acid-Base Profile 1: serum chloride (mmol/L)	Sequential changes in mean serum chloride (per fluid type) at T0-T12-T24-T36-T48.	48h
Acid-Base Profile 2: serum apparent strong ion difference (mEq/L)	Sequential changes in mean serum apparent strong ion difference (per fluid type) at T0-T12-T24-T36-T48.	48h
Acid-Base Profile 3: urinary anion gap (mmol/L)	Sequential changes in mean urinary anion gap (per fluid type). Urinary potassium is determined on a sample of every individual diuresis. Subjects urinate as the urge rises.	48h
Other Electrolytes Profile 1: Serum phosphate (mmol/L)	Sequential changes in mean serum phosphate (per fluid type) at T0-T24-T48.	48h
Other Electrolytes Profile 2: Red blood cell magnesium (mmol/L)	Sequential changes in mean red blood cell magnesium (per fluid type) at T0-T24-T48.	48h
Cortisol (µg/dL)	Serum cortisol as a measure of stress due to fasting.	48h
Bioelectrical impedance analysis 1: Total body water	Sequential changes in mean total body water (per fluid type) at T0-T24-T48.	48h
Bioelectrical impedance analysis : Extracellular volume	Sequential changes in mean extracellular volume (per fluid type) at T0-T24-T48.	48h

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Niels Van Regenmortel, M.D., University Hospital, Antwerp

Publications and helpful links

General Publications

• Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet. 2002 May 25;359(9320):1812-8. doi: 10.1016/S0140-6736(02)08711-1.
• Moritz ML, Ayus JC. Maintenance Intravenous Fluids in Acutely Ill Patients. N Engl J Med. 2015 Oct;373(14):1350-60. doi: 10.1056/NEJMra1412877. No abstract available.
• Van Regenmortel N, De Weerdt T, Van Craenenbroeck AH, Roelant E, Verbrugghe W, Dams K, Malbrain MLNG, Van den Wyngaert T, Jorens PG. Effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers. Br J Anaesth. 2017 Jun 1;118(6):892-900. doi: 10.1093/bja/aex118.

Helpful Links

• NICE guideline on Intravenous Fluid Therapy in Adults in Hospital
• GIFTASUP guidelines

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (ESTIMATE): July 6, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): August 9, 2016
• Last Update Submitted That Met QC Criteria: August 7, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Maintenance; Sodium; Potassium; Intravenous fluids; Intravenous solutions; Tonicity; Fluid retention
• Other Study ID Numbers: 16/15/175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED