Safety and Efficacy of 6% Hydroxyethyl Starch in Patients Undergoing Major Surgery: The Randomised Controlled PHONEICS Trial

Authors

• Wolfgang Buhre
• Óscar Díaz-Cambronero
• Simon Schaefer
• Martin Novacek
• Marina Soro Domingo
• Bjorn Stessel
• Aurelio Rodríguez-Pérez
• Torsten Richter
• Georg Rohe
• Bernard Cholley
• Matthias Gruenewald
• Gerhardus Kuiper
• Samir Jaber
• Dianne de Korte
• Javier Belda
• Marcelo Gama de Abreu
• Robert Baronica
• Thomas Scheeren
• Carlos Ferrando-Ortolá
• Wojciech Szczeklik
• Dana Tomescu
• Tomas Vyzamal
• Zejka Gavranovic
• María Pilar Argente-Navarro
• Guido Mazzinari
• Sarah Thaler
• Nuria García-Gregorio
• Jeroen Vandenbrande
• Diane Zlotnik
• Jakob Wittenstein
• Sonja Schmier
• Susanne Rohn
• Christoph Glasmacher
• Martin Holler
• Cornelius Jungheinrich
• Ulf Niess
• Daniel I Sessler
• Martin Westphal

Language

English

Publication Date

1-1-2026

Journal

European Journal of Anaesthesiology

DOI

10.1097/EJA.0000000000002307

PMID

41133731

PMCID

PMC12700675

PubMedCentral® Posted Date

10-24-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Abstract

Background: Hydroxyethyl starch (HES) is often used for maintaining vascular volume during major surgery. Long-term high-dose HES in septic patients promotes renal injury, whereas meta-analyses of current HES products in surgical patients do not show such effects.

Objective: We studied if the peri-operative use of HES is noninferior to crystalloids in terms of acute kidney injury. Secondary outcome was the noninferiority of HES on worsening of renal injury and/or the incidence of a composite endpoint of major complications and mortality until postoperative day 90.

Design: Randomised double-blind trial in patients undergoing elective abdominal surgery with expected blood loss at least 500 ml.

Setting: Multicentre trial at 53 study sites in 10 European countries.

Patients: One thousand nine hundred and eighty-five (HES 977, crystalloid-only 981) patients aged 40 to 85 years with ASA status II-III.

Intervention: Either 6% HES 130/0.4 or a crystalloid solution. Dosing was guided by mean arterial pressure and/or routine haemodynamic variables.

Main outcome measure: Change from pre-operative to lowest cystatin C-based eGFR during the first 3 postoperative days. Key secondary outcome was a composite endpoint of mortality and major postoperative complications after 90 days.

Results: Mean change in eGFR from baseline to minimum was -3.4 ± 17.7 ml min -1 1.73 m -2 in HES patients and -1.0 ± 17.1 ml min -1 1.73 m -2 in crystalloid-only patients ( P < 0.001 for noninferiority). The key secondary endpoint occurred in 35% of patients in each group. There were no clinically relevant differences in any safety endpoint including 90-day renal function. Any cause mortality-difference until the end of 1-year follow-up was not significantly different (8.6% in HES and 10.1% in crystalloid patients).

Conclusion: Peri-operative use of HES was noninferior to crystalloids in short-term renal function or a composite of mortality and major complications at 90 days. PHOENICS provides robust evidence that peri-operative in-label use of HES is well tolerated.

Keywords

Humans, Hydroxyethyl Starch Derivatives, Middle Aged, Male, Female, Aged, Double-Blind Method, Adult, Aged, 80 and over, Crystalloid Solutions, Plasma Substitutes, Acute Kidney Injury, Treatment Outcome, Postoperative Complications, Elective Surgical Procedures

Comments

Trial registration and funding: EudraCT no. 2016-002162-30, clinicaltrials.gov ID NCT03278548.

Published Open-Access

yes

Recommended Citation

Buhre, Wolfgang; Díaz-Cambronero, Óscar; Schaefer, Simon; et al., "Safety and Efficacy of 6% Hydroxyethyl Starch in Patients Undergoing Major Surgery: The Randomised Controlled PHONEICS Trial" (2026). Faculty, Staff and Student Publications. 1536.
https://digitalcommons.library.tmc.edu/uthsph_docs/1536