TOnicity of Perioperative Maintenance SoluTions

Overview

Prospective randomized double blind phase IV trial studying the efficacy and safety of the tonicity of two different perioperative maintenance solutions: an isotonic solution containing NaCl 0.9 in glucose 5% with an added 40 mmol/L of potassium or a commercially available premixed solution (Glucion 5%) containing a.o. 54 mmol/L of sodium and 26 mmol/L of potassium. Both solutions are administered at 27 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 and clinical parameters.

Full Title of Study: “TOnicity of Perioperative Maintenance SoluTions – Part 1: Thoracic Surgery”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Supportive Care
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: July 15, 2018

Interventions

• Drug: NaCl 0.9% in Glucose 5% + 40mmol/L Potassium
  • Study fluid used at maintenance rate of 27 mmol per kg of body weight per day from beginning of surgery until end of study.
• Drug: Glucion 5%
  • Study fluid used at maintenance rate of 27 mmol per kg of body weight per day from beginning of surgery until end of study.

Arms, Groups and Cohorts

• Active Comparator: NaCl 0.9% in Glucose 5% + 40mmol/L Potassium
• Active Comparator: Glucion 5%

Clinical Trial Outcome Measures

Primary Measures

• Fluid balance
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)
  • Difference between all fluid intake and output

Secondary Measures

• Resuscitation Fluids
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)
  • The cumulative amount of additional (resuscitation) fluids during the study period
• Vasopressor Use
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery)
  • The cumulative amount of vasopressors during the study period
• Physiological Mechanisms: Aldosterone level
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Change from baseline aldosterone level at start of surgery
• Physiological Mechanisms: Fractional Excretion of Sodium
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Change from baseline FeNa at start of surgery
• Electrolyte Homeostasis and Disorders: Sodium
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean sodium level and change from baseline. Occurrence of hypo and hypernatremia.
• Electrolyte Homeostasis and Disorders: Potassium
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean potassium level and change from baseline. Occurrence of hypo and hyperpotassemia.
• Electrolyte Homeostasis and Disorders: Chloride
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean chloride level and change from baseline. Occurrence of hypo and hyperchloremia.
• Electrolyte Homeostasis and Disorders: Strong Ion Difference
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean SID level and change from baseline.
• Electrolyte Homeostasis and Disorders: Phosphate
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean phosphate level and change from baseline. Occurrence of hypo and hyperphosphatemia.
• Electrolyte Homeostasis and Disorders: Calcium
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean calcium level and change from baseline. Occurrence of hypo and hypercalcemia.
• Clinical Endpoints: paO2/FiO2
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery) – Assessments at fixed time points.
  • Mean postoperative paO2/FiO2
• Clinical Endpoints: occurrence of de novo atrial fibrillation
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery). Continuous assessment.
  • occurrence of de novo atrial fibrillation (Y/N)
• Clinical Endpoints: occurrence of acute kidney injury (AKI)
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery). Continuous assessment.
  • AKI according to RIFLE-score creatinine and urine R-I-F)
• Sodium balance
  • Time Frame: From start of surgery until end of study, defined as one of the following (1) discharge from ICU (2) 8AM on third postoperative day (maximum: up to 72h after start of surgery).
  • Sodium balance (total in vs out) at end of study, assessed by urine collection.

Participating in This Clinical Trial

Inclusion Criteria

• Adult (at least 18 y.o.) – Undergoing elective lung resection (wedge resection, segmental resection, (bi)lobectomy, but not pneumonectomy) via thoracotomy or video- or robot assisted (VATS, RATS) – Normal renal function (eGFR >60 ml/min/1.73m² (CKD-EPI)) Exclusion Criteria:

• Under chronic treatment with diuretics or desmopressin – Heart failure (NYHA III-IV) – Liver Failure – Brittle diabetes mellitus – Neurological contra-indication for hypotonic fluids – SIADH or hyponatremia <130 or > 150 mmol/L at preoperative assessment – Hyperkalemia > 5 mmol/L at preoperative assessment – Under treatment with artificial nutrition (enteral or parenteral) – Pregnancy Additional pre-defined exclusion after initial inclusion – Massive perioperative transfusion or intraoperative resuscitation of +2.5L of crystalloids/colloids – Absence of admission to ICU

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Niels Van Regenmortel
• Provider of Information About this Clinical Study
  • Sponsor-Investigator: Niels Van Regenmortel, Dr. – University Hospital, Antwerp

References

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.