OPTImized Restrictive Strategy Targeting Non-Resuscitative FLUIDs in Septic Shock: Pilot Study.
Condition: Septic Shock; Electrolyte and Fluid Balance Conditions
MeSH terms: Shock, Septic; Shock
Study type: Interventional

Summary: 
      Intravenous fluids are one of the keystones in the initial management of patients with septic
      shock, but they inevitably lead to a fluid overload, which is associated with poor outcome.

      So far no studies have evaluated the interest of a restrictive strategy for managing fluid
      intake targeting all non-resuscitative fluids (fluids for maintenance and drug dilution as
      well as nutrition) and especially the impact of this restrictive strategy on fluid overload.

      The hypothesis of this research is that an optimised restrictive strategy targeting all
      non-resuscitative fluids in patients hospitalised in the intensive care unit for septic
      shock, will have an impact on fluid balance in these patients.
    

Detailed description: 
      Sepsis and its most severe form, septic shock, are the cause of nearly 30% of admission in
      intensive care unit (ICU). The related mortality rate varies from 20 to 60% according to the
      studied population and the type of the study. With the concomitant and rapid treatment of the
      source of infection, hemodynamic optimization with fluid infusion (fluid resuscitation) is
      the cornerstone of management of patients in septic shock. Nevertheless, fluid overload has
      been shown to be associated with poor outcome. The negative effects of a positive fluid
      balance on ICU outcomes for septic patients has been well established.

      In patients with acute respiratory distress syndrome, a restrictive fluid therapy has been
      associated with shorter use of mechanical ventilation. In patients with acute renal failure,
      fluid overload is associated with longer need of renal replacement therapy. In patients with
      septic shock numerous non-randomised studies reported that a positive fluid balance at Day 3,
      Day 5 was associated with an increased risk of mortality.

      Actually, in patients with septic shock the part of resuscitation fluid is only the third of
      the total fluid input that can attain 25 liters at day 3. Some studies reported more
      specifically the role of the different types of fluid in the fluid balance at D3 and D5. In a
      retrospective single centre study including 14654 ICU patients over 10 years, the authors
      distinguished resuscitation, replacement and maintenance fluids, blood products, nutrition
      and fluid creep (to concentrate electrolytes, keep venous access and to infuse continuous
      medications). They reported that maintenance fluids and fluid creep represent more than 50%
      of fluid input during the first 5 ICU days with significant sodium and chloride loads. In a
      retrospective multi-centre study involving 400 patients mechanically ventilated > 24 h in 10
      ICUs, the authors reported that maintenance and fluid creep represented more than 50% of the
      fluids infused during the first 3 ICU days. In this study, fluid balance at Day3 was an
      independent risk factor for 30-day mortality.

      All these findings could lead to hypothesize that a restrictive strategy in fluid input for
      the maintenance of fluid and creep fluid could be associated with a better outcome without
      impairing the resuscitation phase.

      To our knowledge, to date, no study has focused on a restrictive strategy targeting
      non-resuscitative fluid input to optimize fluid balance in patients with septic shock.
      OPTIFLUID will be the first randomised controlled trial with the objective of reducing fluid
      balance through a fluid restriction targeted at all fluids other than resuscitative fluids.

      The only existing interventional studies on targeted restriction were limited to
      resuscitative intravenous fluids, and they failed showing a benefit.

      By optimizing fluid therapy, our approach is likely to improve patient-centred outcomes, but
      in this pilot study we focus only on the fluid balance and the safety.
    

Intervention name(s): Reduction of the patient's fluid intake during the first 7 days
Intervention type(s): Other
Intervention description(s): The volume of fluids infused to the patient will be reduced by the doctor in charge of the patient for the first 7 days of the patient's stay in the intensive care unit according to a protocol with instructions to reduce fluid intake as far as possible in terms of maintenance fluids, dilution of medication and artificial nutrition. This protocol will be begun immediately following the patient's inclusion on Day 1 and pursued for 7 days after inclusion (i.e. from Day 1 - to Day 7). The fluid restriction strategy does not involve the administration of any medication (i.e. diuretics). A clinical pharmacist will help the intensive care teams apply the fluid restriction protocol with a daily check. If the restrictive strategy leads to hypovolemia and / or a electrolyte anomaly (sodium, potassium, chloride, etc.), the physician in charge will be authorised to treat these anomalies in conformance with the protocol recommendations.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: Shock, Septic.; Fluid Balance