Background/Objective: Sepsis is a leading cause of death in noncoronary intensive care units (ICUs). Fluids for intravascular resuscitation include crystalloids and colloids. There is extensive clinical evidence on colloid use, but large trials comparing gelatine with crystalloid regimens in ICU and septic patients are lacking. This study aimed to determine whether early, protocol-driven volume resuscitation using a gelatine-based regimen achieves hemodynamic stability (HDS) more rapidly than a crystalloid-based regimen in septic patients. Methods: This prospective, controlled, randomised, double-blind, multinational phase IV study compared two parallel groups of septic patients receiving a gelatine-based regimen (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG each, at a 1:1 ratio) or a crystalloid regimen (Sterofundin® ISO). Primary endpoint was time to first HDS within 48 h after randomisation. Secondary endpoints included fluid overload, fluid balance, and patient outcomes. Results: 167 patients were randomised. HDS was achieved after 4.7 h in the gelatine group and after 5.8 h in the crystalloid group (p = 0.3716). The gelatine group had a more favourable fluid balance at 24 h (medians: 3463.00 mL vs. 4164.00 mL; p = 0.0395) and less fluid overload (medians: 4296.05 vs. 5218.75%; p = 0.0217). No differences were observed in serious adverse events or mortality. Conclusions: The study provided clinical evidence of balanced gelatine solution for volume resuscitation in septic patients, although it was terminated prematurely. The early and protocol-based administration of gelatine was safe and effective in the enrolled patient population. Time to HDS was not different between groups but the gelatine-based regimen led to better fluid balance and less fluid overload.

Department of Anaesthesia and Critical Care Medicine Medical University Innsbruck Anichstraße 35 6020 Innsbruck Austria

Department of Anaesthesiology and Intensive Care Medicine Jena University Hospital Am Klinikum 1 07747 Jena Germany

Department of Anaesthesiology and Intensive Care Medicine University Hospital Tübingen Hoppe Seyler Straße 3 72076 Tübingen Germany

Department of Anaesthesiology and Intensive Care Medicine University Medical Center Rostock Schillingallee 35 18057 Rostock Germany

Department of Anaesthesiology Intensive Care Medicine and Pain Therapy University Hospital Frankfurt Goethe University Theodor Stern Kai 7 60590 Frankfurt am Main Germany

Department of Critical Care and Emergency Medicine Klinikum Bremen Mitte St Jürgen Straße 1 28177 Bremen Germany

Department of Intensive Care and Intermediate Care University Hospital RWTH Aachen Pauwelsstraße 30 52074 Aachen Germany

Faculty of Medicine in Hradec Kralove Charles University Prague University Hospital Hradec Kralove Department of Anaesthesiology Perioperative Medicine and Intensive Care Masaryk Hospital J E Purkinje University 400 96 Usti nad Labem Czech Republic

Hospital Universitario La Paz Instituto de investigación IdiPAZ Servicio de Medicina Intensiva Paseo de la Castellana 261 28046 Madrid Spain

Institute for Anaesthesiology Intensive Care and Emergency Medicine Johannes Wesling Hospital Minden Hans Nolte Str 1 32429 Minden Germany

Service d'Anesthésie Réanimation Nantes Université Centre Hospitalier Universitaire de Nantes Pôle Anaesthésie Réanimations Service d'Anesthésie Réanimation Chirurgicale 1 Place Alexis Ricordeau 44093 Nantes France

Service de Réanimation Polyvalente IRCAN Inserm U1081 CNRS UMR7284 et CHU de Nice Hôpital Pasteur 2 30 Voie Romaine CHU de Nice 06000 Nice France

Servicio de Medicina Intensiva Hospital Universitari Vall d'Hebron Passeig Vall d'Hebron 119 129 08035 Barcelona Spain

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