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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Postoperative Morbidity, Postoperative Mortality

Intervention / Treatment
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* Drug: Hydroxethyl starch


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: crystalloid group<br>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<br> <br> |
| Experimental: colloid group<br>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<br> <br> |

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| All-cause mortality |  | 28 days | 
| All-cause mortality |  | 3 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Goal-directed therapy, Fluid loading, Abdominal surgery, Postoperative morbidity, Postoperative mortality, Individualized goal-directed fluid therapy, Elective or emergency abdominal surgery, General Anesthesia, Moderate-to-high risk surgical patients