Pilot Study for the SQUEEZE Trial
Condition: Septic Shock
MeSH terms: Shock, Septic; Shock
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the SQUEEZE Trial is to determine which fluid resuscitation strategy results
      in the best outcomes for children treated for suspected or confirmed septic shock. In this
      study, eligible children will be randomized to either the 'Usual Care Arm' or the 'Fluid
      Sparing Arm'. Children will receive treatment according to current ACCM Septic Shock
      Resuscitation Guidelines, with the assigned resuscitation strategy used to guide
      administration of further fluid boluses as well as the timing of initiation and escalation of
      vasoactive medications to achieve ACCM recommended hemodynamic targets.
    

Detailed description: 
      Current pediatric surviving sepsis guidelines from the American College of Critical Care
      Medicine (ACCM) emphasize an early and goal-directed approach to resuscitation. These
      guidelines suggest that fluid resuscitation should be aggressive with repeated intravenous
      (IV) fluid boluses of 20 mL/kg, such that some children may require as much as 200 mL/kg of
      fluid to achieve therapeutic endpoints. The guidelines also recommend the initiation of
      vasoactive agents at the stage of "fluid refractory shock", i.e. when there is persistent
      hypoperfusion despite at least 60 ml/kg IV fluid. Improvements in pediatric septic shock
      survival have been attributed to adherence to the first iteration of the ACCM septic shock
      guidelines, and the use of goal directed targets. However, the largest and most publicized
      pediatric trial of fluid resuscitation in children with suspected septic shock (FEAST Trial),
      published in NEJM in 2011, demonstrated an increased mortality among children treated with
      aggressive fluid resuscitation in comparison to the conservative fluid resuscitation arm. As
      a result, the pediatric critical care community clearly acknowledges that these results,
      while important, are not necessarily generalizable to developed countries such as Canada.

      Emerging publications in the ICU literature suggest that excessive compared to conservative
      fluid administration in adults with septic shock worsens outcomes such as duration of
      mechanical ventilation, complications related to the third-spacing of fluids, length of ICU
      stay, and mortality. A systematic review published in August 2012 reveals a paucity of
      randomized controlled trial (RCT) evidence apart from the FEAST trial examining the impact of
      fluid resuscitation on mortality in children with septic shock. This raises the important
      question of whether children in developed countries would also benefit from a fluid sparing
      resuscitation strategy to achieve the ACCM goal-directed targets. Use of such a fluid sparing
      strategy would, by default, require earlier initiation and preferential escalation of
      vasoactive medications to meet ACCM hemodynamic goals. The optimal degree of fluid
      resuscitation and the timing of initiation of vasoactive support in order to achieve
      therapeutic targets in children with septic shock remains unanswered.

      This Pilot Randomized Controlled Trial constitutes the first step in answering our research
      question of whether, in pediatric patients with septic shock, use of a fluid sparing strategy
      to achieve ACCM therapeutic goals, results in improved clinical outcomes without an increased
      risk of adverse events, compared to the usual care of aggressive fluid resuscitation as
      currently recommended by the ACCM guidelines. The purpose of the pilot study is to determine
      feasibility and inform the appropriate methodological design of the larger multi-centre RCT
      to fully answer our research question. The hypothesis of the pilot study is that the SQUEEZE
      Trial is feasible to conduct.
    

Intervention name(s): Fluid Sparing Resuscitation Strategy
Intervention type(s): Other
Intervention description(s): Tier 1: Initiate IV/IO vasoactive medication infusion support immediately. Further IV/IO isotonic fluid bolus therapy [crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)] should be avoided; small volume isotonic fluid boluses [5-10 mL/kg (250-500 mL for participants ≥ 50 kg)] may be provided if required due to A. Clinically unacceptable delay in ability to initiate vasoactive medication infusion(s) and/or 2. Documented intravascular hypovolemia.
Tier 2: Vasoactive medication(s) should be preferentially titrated/escalated to achieve recommended ACCM hemodynamic goals. Further IV/IO isotonic fluid bolus therapy [crystalloid (0.9% Normal Saline or Ringers Lactate) or colloid (5% Albumin)] should be avoided; small volume isotonic fluid boluses [5-10 mL/kg (250-500 mL for participants ≥ 50 kg)] may be provided if required due to A. Documented intravascular hypovolemia.
Intervention end: Patient is free from vasoactive medication support and shock is reversed.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Sepsis; Septic Shock; Fluid Therapy; Pediatrics; Resuscitation; Emergency Medicine; Critical Care