Safety and Efficacy of 6% Hydroxyethyl Starch (HES) Solution Versus an Electrolyte Solution in Patients Undergoing Elective Abdominal Surgery

• Volulyte 6% (Drug), also known as Hydroxyethyl starch 130/0.4: Solution for infusion
• Ionolyte (Drug), also known as Electrolyte solution: Solution for infusion

Primary outcomes

• Difference in mean estimated glomerular filtration rate (eGFR) (calculated from highest cystatin-C levels measured during post-operative days 1-3 (POD 1-3)) between the two treatment groups [post-operative days 1-3]

Secondary outcomes

• Renal function [until 1 year after surgery]
• Calculated red blood cell (RBC) loss [on post-operative day 3]
• Estimated intra-operative blood loss [end of surgery]
• Coagulation [until post-operative day 1]
• Inflammation [until post-operative day 1]
• Adverse events [until post-operative day 90]
• Major post-operative complications [until post-operative day 90]
• Mortality [1 year]
• Composite of mortality and major post-operative complications (including renal) [until post-operative day 90]
• Total volume of administered investigational product [until 24 hours after investigational product treatment start]
• Fluid balance [Sum of volume of all intravenous medication (including investigational product and blood products) minus sum of volume of urine output (if available), drainage and estimated intra-operative blood loss] [until post-operative day 3]
• Heart Rate [until post-operative day 3]
• Body temperature [until post-operative day 3]
• Mean arterial pressure [until post-operative day 3, if available]
• Systolic arterial blood pressure [until end of surgery]
• Diastolic arterial blood pressure [until end of surgery]
• Central venous pressure (if available) [until end of surgery]
• Haemodynamics readings as required to determine volume responsiveness [at least one parameter (stroke volume, stroke volume variation, stroke volume index, pulse pressure variation, mean arterial pressure) has to be used to guide volume administration] [until 24 hours after investigational product treatment start]
• Partial pressure of carbon dioxide [until end of surgery]
• Partial pressure of oxygen [until end of surgery]
• Bicarbonate [until end of surgery]
• Arterial oxygen saturation [until end of surgery]
• Haemoglobin [until post-operative day 3]
• Haematocrit [until post-operative day 3]
• pH [until end of surgery]
• Base Excess [until end of surgery]
• Lactate [until post-operative day 3]
• Central venous oxygen saturation (if available) [until post-operative day 1]
• Serum sodium [until post-operative day 1]
• Serum potassium [until post-operative day 1]
• Serum calcium [until post-operative day 1]
• Serum chloride [until post-operative day 1]
• Length of stay in the hospital/intensive care unit [until post-operative day 90]
• Hours on mechanical ventilation [until post-operative day 7]

Sex: All, ages: 41 Years to 85 Years

Inclusion:

* Male or female adult patients > 40 and ≤ 85 years of age. Women of child bearing potential must test negative on standard pregnancy test (urine or serum)
* Patients undergoing elective abdominal surgery with an expected blood loss of ≥ 500 ml
* ASA Physical Status II - III
* Signed written informed consent form

Exclusion:

* Hypersensitivity to the active substances or to any of the other excipients of the investigational medicinal products
* Body weight ≥ 140 kg
* Sepsis
* Burns
* Renal impairment (AKIN stage ≥ 1 or chronic) or acute and/or chronic renal replacement therapy
* Intracranial or cerebral haemorrhage
* Critically ill patients (typically admitted to the intensive care unit)
* Hyperhydration
* Pulmonary oedema
* Dehydration
* Hyperkalaemia
* Severe hypernatraemia
* Severe hyperchloraemia
* Severely impaired hepatic function
* Congestive heart failure
* Severe coagulopathy
* Organ transplant patients
* Metabolic alkalosis
* Simultaneous participation in another interventional clinical trial (drugs or medical devices studies)

• Results publication: Buhre W, Diaz-Cambronero O, Schaefer S, Novacek M, Domingo MS, Stessel B, Rodriguez-Perez A, Richter T, Rohe G, Cholley B, Gruenewald M, Kuiper G, Jaber S, de Korte D, Belda J, de Abreu MG, Baronica R, Scheeren T, Ferrando-Ortola C, Szczeklik W, Tomescu D, Vyzamal T, Gavranovic Z, Argente-Navarro MP, Mazzinari G, Thaler S, Garcia-Gregorio N, Vandenbrande J, Zlotnik D, Wittenstein J, Schmier S, Rohn S, Glasmacher C, Holler M, Jungheinrich C, Niess U, Sessler DI, Westphal M; New Collective Author. Safety and efficacy of 6% hydroxyethyl starch in patients undergoing major surgery: The randomised controlled PHOENICS trial. Eur J Anaesthesiol. 2026 Jan 1;43(1):1-10. doi: 10.1097/EJA.0000000000002307. Epub 2025 Oct 24. PMID 41133731
• Results publication: Buhre W, de Korte-de Boer D, de Abreu MG, Scheeren T, Gruenewald M, Hoeft A, Spahn DR, Zarbock A, Daamen S, Westphal M, Brauer U, Dehnhardt T, Schmier S, Baron JF, De Hert S, Gavranovic Z, Cholley B, Vymazal T, Szczeklik W, Bornemann-Cimenti H, Soro Domingo MB, Grintescu I, Jankovic R, Belda J. Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study. Trials. 2022 Feb 22;23(1):168. doi: 10.1186/s13063-022-06058-6. PMID 35193648
• Results publication: Chappell D, Jacob M. Should hydroxyethyl starch be banned? Lancet. 2018 Jul 14;392(10142):118. doi: 10.1016/S0140-6736(18)31174-7. No abstract available. PMID 30017128

• Wolfgang F. Buhre, Prof. Dr. med., Study chair, Department of Anesthesiology and Pain Management, Maastricht University, The Netherlands