Fluid Loading in Abdominal Surgery: Saline Versus Hydroxyethyl Starch (FLASH Study) (FLASH)

Fluid Loading in Abdominal Surgery: Saline Versus Hydroxyethyl Starch: A Double-blinded Multicenter Prospective Randomized Trial (FLASH Study)

The primary purpose of the study is to evaluate whether the type of fluid (0.9% saline or 6% Hydroxyethyl starch 130/0.4) in the context of an individualized goal-directed fluid therapy is associated with a difference in morbidity and mortality within the first 14 days in patients at moderate-to-high risk of postoperative complications after abdominal surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Mortality; Postoperative Morbidity
• Intervention / Treatment: Drug: Hydroxethyl starch

Detailed Description

Fluid administration is the mainstay treatment for suspected hypovolemia during surgery, but the effects of different crystalloid and colloid solutions on outcome remain poorly explored in surgical patients.

Two recent international multicenter studies (6S and CHEST studies) have shown that, compared to crystalloid solutions, the use of hydroxyethyl starch (HES) could be responsible for higher morbidity, especially renal failure, and mortality in ICU patients, thus leading to a recent restriction of their range of indications.

In contrast, in surgical patients, recent meta-analyses have concluded on the absence of difference in terms of mortality and postoperative renal failure between crystalloids and latest generation HES. Excessive fluid administration during surgery is associated with increased risk of postoperative morbidity, including renal dysfunction and mortality. It has been suggested that, compared with the volume-restoring effects of colloids, crystalloid use may require the administration of higher fluid volumes, which may contribute to poorer outcomes. In the surgical context, clinical trials and meta-analyses have shown that individualized goal-direct fluid administration can reduce postoperative morbidity. Although most GDT studies have used colloid solutions for fluid loading, the effects of the type of fluids are currently unknown and crystalloids are proposed for first-line therapy.

The proposed Flash multicenter study will be conducted to assess if the use of HES or crystalloid solutions during an individualized GDT contribute to outcome differences in patients at moderate-to-high risk of postoperative complications after abdominal surgery. As these fluids are widely used during surgery and because of current concerns about the risks related to the use of HES-based products in ICU patients, the trial will provide important data to clinicians involved in perioperative care.

• Study Type: Interventional
• Enrollment (Actual): 826
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All adult patients who

• Undergo elective or emergency abdominal surgery under general anesthesia
• With an estimated surgical duration greater than or equal to 2 hours
• With moderate-to-high risk of postoperative complications defined by an AKI risk index≥ class 3, as defined by the presence of at least 4 of the following factors: age> 56 years, male gender, intraperitoneal surgery, active congestive heart failure, ascites, hypertension, emergency surgery, mild or moderate renal insufficiency, diabetes mellitus treated by oral or insulin therapy

Exclusion Criteria:

The following patients will not be evaluated for inclusion:

• Age <18 years
• Preoperative acute heart failure
• Preoperative acute coronary insufficiency
• Preoperative severe renal failure (defined by creatinine clearance <30 ml/min or requiring renal replacement therapy)
• Preoperative shock defined by the need for vasoactive amines
• History of allergy with the use of 6% Hydroxethyl starch 130/0.4
• Contraindication to the use of HES: sepsis, burnt patient, renal insufficiency or dialysis, cerebral hemorrhage, ICU patient , hypervolemia, lung edema, dehydration, severe hypernatremia or severe hyperchloremia, severe hepatic insufficiency, congestive heart failure, severe coagulopathy, organ transplant
• Patient's or relative's refusal to participate
• Parturient or breastfeeding woman
• Protected major (guardianship)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: crystalloid group; The proposed Flash multicenter study will be conducted to assess if the use of HES or crystalloid solutions during an individualized GDT contribute to outcome differences in patients at moderate-to-high risk of postoperative complications after abdominal surgery	Drug: Hydroxethyl starch
Experimental: colloid group; The proposed Flash multicenter study will be conducted to assess if the use of HES or crystalloid solutions during an individualized GDT contribute to outcome differences in patients at moderate-to-high risk of postoperative complications after abdominal surgery	Drug: Hydroxethyl starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal dysfunction	Renal dysfunction (defined by KDIGO stage 1 or higher)	during the first 14 postoperative days
Pulmonary complication	Pulmonary complication (defined by the need for noninvasive or invasive ventilatory assistance for postoperative acute respiratory failure)	during the first 14 postoperative days
Cardiovascular complication	Cardiovascular complication (defined by the development of acute heart failure)	during the first 14 postoperative days
Infectious complication	Infectious complication (defined by the development of sepsis, severe sepsis or septic shock)	during the first 14 postoperative days
Surgical complication	Surgical complication (defined as the need for surgical reoperation)	during the first 14 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		3 months
All-cause mortality		28 days
Total fluid volume	Total fluid volume (0.9% saline and HES 130/0.4)	during the surgical period and the first 24 postoperative hours
Volume of blood loss		during the surgical period and the first 24 postoperative hours
Renal complications : oliguria	Postoperative complications	within 14 days
Cardiovascular complications	Postoperative complications	within 14 days
Respiratory complications	Postoperative complications	within 14 days
SIRS score	Postoperative complications	within 14 days
Infectious complications	Postoperative complications	within 14 days
Surgical complications	Postoperative complications	within 14 days
Severity organ failure assessment score from postoperative		Day-1 to Day-7
Unexpected ICU admission (or readmission) following surgery		within 28 days
Serum lactate		from Day-1 to Day-7
C-reactive protein		from Day-1 to Day-7
Plasma chloride		from Day-1 to Day-7
number of units of packed red blood cells		during the surgical period and the first 24 postoperative hours

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Agence Nationale de sécurité du Médicament; Programme Hospitalier de Recherche Clinique (AOI N° 2013 _ Futier); Société Française Anesthesie-Réanimation (SFAR)
• Investigators: Principal Investigator: Samir JABER, University Hospital, Montpellier; Principal Investigator: Julien POTTECHER, CHRU Strasbourg; Principal Investigator: Alexandre OUATTARA, CHU Bordeaux; Principal Investigator: Thomas LESCOT, Hôpital Saint-Antoine (APHP); Principal Investigator: Hélène BELOEIL, CHU Rennes; Principal Investigator: Gilles LEBUFFE, CHRU Lille; Principal Investigator: Julien BUREY, Hôpital Tenon (APHP); Principal Investigator: Willy-Serge MFAM, CH Orleans; Principal Investigator: Vincent PIRIOU, CHU Lyon; Principal Investigator: Sébastien BERTRAN, Chu Nimes; Principal Investigator: Marion FAUCHER, Institut Paoli-Calmettes; Principal Investigator: Catherine PAUGAM-BURTZ, Hopital Beaujon; Principal Investigator: Lionel VELLY, AP-HM; Principal Investigator: Olivier HUET, CHU Brest; Principal Investigator: Pierre SAINT-LEGER, CH Valenciennes

Publications and helpful links

General Publications

• Futier E, Garot M, Godet T, Biais M, Verzilli D, Ouattara A, Huet O, Lescot T, Lebuffe G, Dewitte A, Cadic A, Restoux A, Asehnoune K, Paugam-Burtz C, Cuvillon P, Faucher M, Vaisse C, El Amine Y, Beloeil H, Leone M, Noll E, Piriou V, Lasocki S, Bazin JE, Pereira B, Jaber S; FLASH Trial Group; Lasocki S, Huet O, Cadic A, Jacob C, Paugam-Burtz C, Restoux A, Ouattara A, Feitita I, Deloge E, Defaye M, Joannes-Boyau O, Carles P, Napolitano G, Monziols S, Futier E, Vignaud M, Paul S, Gahbiche K, Fayon J, Laroche E, Bazin JE, Brandely A, Le Moal C, Lebuffe G, Garot M, Piriou V, Jaber S, Chanques G, Verzilli D, De Jong A, Millot A, Castagnoli A, Leone M, Pastene B, Castelli C, Medam S, Velly L, Vaisse C, Faucher M, Asehnoune K, Samba E, Roquilly A, Le Penndu M, Cuvillon P, Yves Lefrant J, Wira O, Dubout E, Mfam WS, Lescot T, Begneu E, Burey J, Cirilovic T, Beloeil H, Allo G, Pottecher J, Lebas B, Venot C, Rameau JP, Dimache F, Leger PS, El Amine Y. Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial. JAMA. 2020 Jan 21;323(3):225-236. doi: 10.1001/jama.2019.20833.
• Futier E, Biais M, Godet T, Bernard L, Rolhion C, Bourdier J, Morand D, Pereira B, Jaber S; FLASH trial management committee. Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial. Trials. 2015 Dec 21;16:582. doi: 10.1186/s13063-015-1085-3.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): July 22, 2018
• Study Completion (Actual): October 22, 2018

Study Registration Dates

• First Submitted: July 13, 2015
• First Submitted That Met QC Criteria: July 16, 2015
• First Posted (Estimate): July 20, 2015

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 20, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Abdominal surgery; General Anesthesia; Postoperative mortality; Postoperative morbidity; Goal-directed therapy; Fluid loading; Individualized goal-directed fluid therapy; Elective or emergency abdominal surgery; Moderate-to-high risk surgical patients
• Other Study ID Numbers: CHU-0242; 2014-005575-84 (EudraCT Number)