Perioperative Fluid Management: Goal-directed Versus Restrictive Strategy

Study Overview
=================
Brief Summary
-----------------
There is no ideal cookbook recipe for fluid prescription that would fit every surgical patient. In this study, the investigators working hypothesis is that the adoption of an integrative algorithm for perioperative fluid and haemodynamic management would improve clinical outcome and reduce hospital resource utilization in noncardiac surgical procedures (major-to-intermediate level of stress. Two intraoperative fluid strategies will be compared: Restrictive vs. goal-directed therapy (GDT). In the GDT group, haemodynamic information will be obtained by a flow monitoring device coupled with standard heart rate and blood pressure monitoring.

Detailed Description
-----------------
The rationale of minimizing body weight gain and avoiding unnecessary fluid compensation of the third compartment is now well justified and achievement of supra-normal oxygen delivery values is likely not necessary in most surgical patients. Therefore,it would be tempting to adopt fluid restriction protocols given the potentials of better wound healing, faster return of bowel function and shorter hospital stay after major surgical procedures. Although dynamic flow indices of volume responsiveness have been validated in critically-ill patients, concerns have been raised regarding the risk of overzealous fluid administration in non-critically-ill patients undergoing elective surgery. To date, RCTs comparing fluid regimen (liberal versus restrictive or liberal versus GDT) have yielded controversial results with no consensus regarding appropriate fluid administration in the perioperative period. Interestingly, restrictive protocols have been associated with more frequent adverse events (e.g., nausea, vomiting) following minor surgical procedures and concerns have been raised regarding the possibility of tissue hypoperfusion leading to end-organ dysfunction.

Official Title
-----------------
Perioperative Fluid Management: Goal-Directed Therapy vs. Restrictive Approach, a Randomized Controlled Trial

Conditions
-----------------
Complication, Postoperative

Intervention / Treatment
-----------------
* Procedure: Goal-directed therapy
* Procedure: Restrictive fluid therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patient elective noncardiac surgery (moderate-high-risk) lasting > 2h hours (, gastrectomy, pancreatectomy, nephrectomy, radical cystectomy, hepatic resection, open colonic or rectal surgery) Exclusion Criteria: end-stage organ failure (hemofiltration/dialysis; Child-Pugh class C or MELD score >22; predicted forced expiratory volume < 30%, severe heart failure) life expectancy < 24h psychiatric disorders or unability to give independent consent to the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Goal-Directed-Therapy (GDT)<br>Besides the basal infusion of crystalloids at 3-6 ml/kg/h, colloids (200 ml) or crystalloids (200 ml) are given over 10 min in the presence of signs of absolute/relative hypovolemia as detected by a fall in cardiac output/stroke volume (CO/SV) or if Pressure Pulse Variation (PVV) or Stroke Volume Variation (SVV) exceeds 10-12%, particularly in the presence. Fluid filling is interrupted when SV fail to increase > 10% (or PVV/SVV =< 10%) Otherwise, vasopressors can be used to achieve appropriate mean arterial pressure (MAP>70 mmHg, within ±20% of baseline). Blood losses are replaced with colloids (1:1) or crystalloids (2:1). | Procedure: Goal-directed therapy<br>* Optimize CO with additional fluid according to dynamic indices (PPV, SVV, Stroke volume)<br>* Other names: GDT;|
| Active Comparator: Restrictive strategy<br>Crystalloids are given at a fixed rate of 3-6 ml/kg/h. Otherwise, vasopressors can be used to achieve appropriate MAP (>70 mmHg, within ±20% of baseline). Blood losses are replaced with colloids (1:1) or crystalloids (2:1). Clinicians in charge of the patients are free to use hemodynamic parameters such as PVV or SVV, always attempting to limit the amount of fluid infusion and to maintain normovolemia | Procedure: Restrictive fluid therapy<br>* Keep normovolemia with basal crystalloids infusion (3-6 ml/kg/h) and compensate additional fluid losses with colloids or crystalloids.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite index of serious postoperative adverse events | early postoperative major outcomes: mortality, cardiovascular, respiratory, renal and infectious complications | from date of surgery till hospital discharge or 30-day postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body weight changes (kg, postoperative value - preoperative value) | comparison of body weight (preop versus postop value, kg) | from date of surgery till hospital discharge, or 30-day postoperative | 
| fluid balance | amount of fluids (ml) infused, amount of fluid losses change in body weight | intra-operative and first 24hours after surgery | 
| Acute Kidney Injury based on RIFLE | measurements of creatinine (preoperative, postoperative day 1, 2, 3 after surgery) and assessing the changes in glomerular filtration rate (%) | from the day before to 3 days after surgery | 
| Sequential Organ Failure Assessment (SOFA) | scoring the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems | from date of surgery till hospital discharge, up to 15 weeks after date of surgery | 
| tissue oximetry (%) | Monitoring of oxygen delivery/utilization in the brain area with near-infra-red spectroscopy (NIRS) | intraoperative period, day of surgery | 
| survival | patients (family, next of kin, doctor) are contacted by phone or mail | survival 1-3 years after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
operative mortality, myocardial infarct, arrhythmia, heart failure, stroke, pneumonia, atelectasis, acute lung injury, surgical site infection, acute kidney injury, body weight