Crystalloids or Colloids for Goal-directed Fluid Therapy With Closed-loop Assistance in Major Surgery

Study Overview
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Brief Summary
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Study goal: This study will examine whether there is a significant difference in postoperative outcomes between GDFT using a colloid solution versus a crystalloid solution. Hypothesis: Perioperative fluid optimization through the use of a closed-loop assistance with a balanced starch solution (volulyte®) will be associated with a decrease in postoperative complications compared to the same approach using a balanced crystalloid solution (Plasmalyte®). Objective: To establish which kind of intravenous fluid used for goal directed therapy with closed-loop assistance will reduce the number of postoperative complications (evaluation made by the POMS score).

Detailed Description
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Controversy still persists regarding the type of fluid to use in the operating room to avoid hypovolemia and any circulatory insufficiency. While crystalloids and colloid solutions are frequently used to optimize intravascular volume during surgery, crystalloid solutions require more volume for hemodynamic optimization which may result in higher volumes of fluid administration and potentially side effects. Compared with crystalloids, colloids have the advantages of remaining in the intravascular space longer, achieving faster circulatory stabilization, maintaining colloid osmotic pressure and increasing micro perfusion. However, colloids are more expensive and may have various side effects. In addition to the effect of crystalloids and colloids on the patient, the amount of each fluid administered is also under debate. Goal-directed fluid therapy (GDFT) strategies based on cardiac output (CO) optimization have been shown to benefit moderate- to high-risk surgery patients and have recently been recommended by professional societies in the UK, in France, and in Europe. However, despite the growing evidence, these strategies are often not implemented in current practice. One of the reasons for this lack of implementation is that GDFT strategies, like any other complex clinical protocol, require significant provider attention and vigilance for consistent implementation and it is well known that even under study conditions protocol compliance rates are often not greater than 50% In another hand, one of the chief complicating factors in fluid administration studies is variation in provider administration practices, even when attempting to follow a protocol. Previous studies have used closed-loop (automated) systems to deliver fluid by a standardized protocol, removing variation between providers as one of the confounders of the study. Dr. Cannesson and Rinehart (UC Irvine, California, USA) have recently developed and used a closed-loop system for the provision of GDFT in clinical studies at UC Irvine and La Pitie hospital in France. The closed-loop system is beneficial because it involves the standardization of fluid management and all patients are treated equivalently. This system will thus provide consistent GDFT for all cases in the protocol and remove inter-provider variability as a confounder between groups. Study goal: This study will examine whether there is a significant difference in postoperative outcomes between GDFT using a colloid solution versus a crystalloid solution. Hypothesis: Perioperative fluid optimization through the use of a closed-loop assistance with a balanced starch solution (volulyte®) will be associated with a decrease in postoperative complications compared to the same approach using a balanced crystalloid solution (Plasmalyte®). Objective: To establish which kind of intravenous fluid used for goal directed therapy with closed-loop assistance will reduce the number of postoperative complications (evaluation made by the POMS score).

Official Title
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Phase IV, Multicentric, Prospective, Controlled, Randomized, Double Blind Study Comparing a Crystalloid to a Colloid Used in the Perioperatory Hemodynamic Optimisation With a 'Closed Loop' Automatic Filling System, on the Post-surgery Morbidity in Major Abdominal Surgery.

Conditions
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Surgery

Intervention / Treatment
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* Drug: Plasmalyte
* Drug: Volulyte


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (over the age of 18) undergoing elective major abdominal surgery that is expected to take longer than 3 hours and requiring a general anesthesia and a minimally invasive cardiac output monitoring (Vigileo/Flotrac) Patients who provide written informed consent Exclusion Criteria: Patients under 18 years of age Patients not undergoing surgery, requiring anesthesia, or cardiac output monitoring Patients with arrhythmia and/or atrial fibrillation Patients who are allergic to HES Patients with renal insufficiency (serum creatinine of >2 mg/ml) or hepatic dysfunction (liver enzymes >1.5) Patients who has coagulation disorders (please define: values higher than 1.5x normal values Patients without the capacity to give written informed consent or refusal of consent Patients included in another protocol within a period of 3 months or Participating in another randomised trial Pregnancy at time of enrolment.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volulyte<br>A baseline crystalloid infusion (plasmalyte®) will be set by the attending physician at 3 cc/kg/hr (standard patient care) for each of the randomized groups. The patient will receive fluid management via a closed loop (automated) system that will use an infusion pump (Q-Core) and a controller (a computer run index and algorithm developed by Sironis) to standardize the way fluids are administered intra-operatively and eliminate variation between clinical providers. The liquid perfused will be bolus amounts of volulyte. | Drug: Volulyte<br> <br> |
| Active Comparator: Plasma-Lyte<br>A baseline crystalloid infusion (plasmalyte®) will be set by the attending physician at 3 cc/kg/hr (standard patient care) for each of the randomized groups. The patient will receive fluid management via a closed loop (automated) system that will use an infusion pump (Q-Core) and a controller (a computer run index and algorithm developed by Sironis) to standardize the way fluids are administered intra-operatively and eliminate variation between clinical providers. The liquid perfused will be bolus amounts of plasma-lyte. | Drug: Plasmalyte<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POMS score | Difference between the 2 groups in postoperative morbidity identified with the Post-Operative Morbidity Survey (POMS score) on postoperative days 2. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | Difference in 30-day post-operative mortality between the 2 groups | 30 days | 
| Length of hospitalisation | Difference in duration of hospital length of stay as well as ICU length of stay. | every day up to 90 days after hospitalisation | 
| Quantity of fluid administered during surgery | Fluid balance during surgery | 24 hours | 
| Transfusion rate | Differences of transfusion rate between the two groups, in ml | 8 days | 
| Hypotension incidence | Incidence of hypotension (defined as total case time spent with 20% drop from baseline preoperative blood pressure). | 8 days | 
| Need of vasopressors | Difference in the need and quantity of vasopressors between the two groups | 24 hours | 
| Mean case cardiac index (L /BSA) | Mean case cardiac index (L /BSA), Mean case cardiac stroke volume index (mL/ BSA). | 24 hours | 
| Whodas scale | Enrolled patients will be contacted by phone and their quality of life assessed by the Whodas scale | 6 months after surgery | 
| Whodas scale | Enrolled patients will be contacted by phone and their quality of life assessed by the Whodas scale | 1 year after surgery | 
| Pruritus apparition | Enrolled patients will be contacted by phone 6 months after surgery and any pruritus apparition will be recorded | 6 months after surgery | 
| Pruritus apparition | Enrolled patients will be contacted by phone 1 year after surgery and any pruritus apparition will be recorded | 1 year after surgery | 
| Renal function - urea level | Urea levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 6 months after surgery | 
| Renal function - urea level | Urea levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 1 year after surgery | 
| Renal function - creatinine level | Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 6 months after surgery | 
| Renal function - creatinine level | Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 1 year after surgery | 
| Renal function - Estimated glomerular filtration rate (eGFR) | Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 6 months after surgery | 
| Renal function - Estimated glomerular filtration rate (eGFR) | Creatinine levels. Measured in a blood sample taken according to the standard of care outpatient post-operative follow appointments. | 1 year after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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laparotomy, plasma-Lyte, volulyte, close loop, abdominal surgery