Clinical trial NCT03420261: Hemostasis Evolution During Fluid Loading in Abdominal Surgery. Effects of Fluid Choice: Saline Versus Hydroxyethyl Starch (HAEMO Study)
Official title: Hemostasis Evolution During Fluid Loading in Abdominal Surgery. Effects of Fluid Choice: Saline Versus Hydroxyethyl Starch (HAEMO Study, an Ancillary Study of FLASH Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Morbidity
Postoperative Mortality
Hemostasis Change
Keywords: 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
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Prothombin Time
timeFrame: at day 1
measure: Activated Cephalin TimeF
timeFrame: at day 1
measure: Fibrinogen level and activity
timeFrame: at day 1
measure: Von Willebrand factor
timeFrame: at day 1
measure: Coagulation cascade
timeFrame: at day 1
measure: Thrombin Generation test
timeFrame: at day 1
measure: Fibrin Clot Permeability Test
timeFrame: at day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Chu Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Thomas GODET
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.