Hemostasis Evolution During Fluid Loading in Abdominal Surgery. Effects of Fluid Choice: Saline Versus Hydroxyethyl Starch (HAEMO Study) (HAEMO)

Hemostasis Evolution During Fluid Loading in Abdominal Surgery. Effects of Fluid Choice: Saline Versus Hydroxyethyl Starch (HAEMO Study, an Ancillary Study of FLASH Trial)

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.

Further investigation include the analysis of hemostasis modifications according to the fluid group during the first 7 days after abdominal surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Mortality; Postoperative Morbidity; Hemostasis Change
• Intervention / Treatment: Biological: 0.9% saline; Biological: HES 130/0.4

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.

Moreover conflicting results on hemostatic effects of HES have been reported. HES have been associated with increased bleeding volume and transfusion requirements, especially in the ICU setting in septic patients. Perioperative use of HES was not associated with such findings. Biological effects of HES on hemostasis has barely been investigated and only by diluting plasma of healthy donors with HES.

The proposed Haemo multicenter study will be conducted to assess if the use of HES or crystalloid solutions during an individualized GDT contribute to biological hemostatic 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 and hemostasis.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

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:

• • - 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
  • Included in Clermont-Ferrand and Montpellier centers

Exclusion Criteria:

• • - 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% hydroxyethyl 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 Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Crystalloid group; individualized goal-directed fluid optimization (cardiac preload) by 250 ml boluses of 0.9% saline (up to a maximum of 30 ml/kg)	Biological: 0.9% saline; Fluid administration
Experimental: Colloid group; individualized goal-directed fluid optimization (cardiac preload) by 250 ml boluses of HES 130/0.4 (up to a maximum of 30 ml/kg, VOLUVEN ®, Fresenius Kabi)	Biological: HES 130/0.4; Fluid administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prothombin Time	Evaluation of hemostasis parameters	at day 1
Activated Cephalin TimeF	Evaluation of hemostasis parameters	at day 1
Fibrinogen level and activity	Evaluation of hemostasis parameters	at day 1
Von Willebrand factor	Evaluation of hemostasis parameters	at day 1
Coagulation cascade	Evaluation of hemostasis parameters	at day 1
Thrombin Generation test	Evaluation of hemostasis parameters	at day 1
Fibrin Clot Permeability Test	Evaluation of hemostasis parameters	at day 1

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Puechal X, DeBandt M, Berthelot JM, Breban M, Dubost JJ, Fain O, Kahn JE, Lequen L, Longy-Boursier M, Perdriger A, Schaeverbeke T, Toussirot E, Sibilia J; Club Rhumatismes Et Inflammation. Tocilizumab in refractory adult Still's disease. Arthritis Care Res (Hoboken). 2011 Jan;63(1):155-9. doi: 10.1002/acr.20319.
• Tournadre A, Dubost JJ, Soubrier M. Treatment of inflammatory muscle disease in adults. Joint Bone Spine. 2010 Oct;77(5):390-4. doi: 10.1016/j.jbspin.2010.04.007. Epub 2010 Jun 2.
• Soubrier M, Mathieu S, Payet S, Dubost JJ, Ristori JM. Elderly-onset rheumatoid arthritis. Joint Bone Spine. 2010 Jul;77(4):290-6. doi: 10.1016/j.jbspin.2010.04.004. Epub 2010 May 31.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): July 22, 2018
• Study Completion (Actual): July 30, 2018

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 5, 2018

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-346; 2014-005578-84 (Other Identifier: 2014-005578-84)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No