Table 2.

Detailed description of the SQUEEZE study arms

Intervention tier	Usual Care arm	Fluid Sparing arm
Tier 1	Usual Care	Early initiation of vasoactive medications to spare fluid
Bolus fluid therapya,b	• Following randomization, further isotonic fluid bolus therapy [crystalloid (0.9% normal saline or Ringer’s lactate) or colloid (5% albumin)] may be administered in any volume and as requested by the caring physician	• Following randomization, further isotonic fluid bolus therapy [crystalloid (0.9% normal saline or Ringer’s lactate) or colloid (5% albumin)] should be avoided and provided only if required due to: 1. delay in the ability to immediately initiate vasoactive medication(s) and/or 2. to treat intravascular hypovolemia. The reason/indication for administration of further fluid bolus therapy prior to the initiation of vasoactive medications must be documented
Vasoactive medicationc	• The decision to initiate vasoactive medication(s) is at the discretion of the treating physician. Vasoactive support should not be started until the participant has received a minimum of 60 mL/kg (3 L for participants ≥50 kg) of isotonic fluid as boluses (includes fluid boluses received in the 6 h prior to randomization) • The choice of initial vasoactive medication and the initial dose is to be at the discretion of the caring physician	• Vasoactive medication(s) should be initiated immediately following randomization • The choice of initial vasoactive medication and the initial dose is to be at the discretion of the caring physician
Tier 2	Usual Care	Preferential escalation of vasoactive medications
Bolus fluid therapya,b	• Further isotonic fluid bolus therapy may be administered at the discretion of the caring physician • The type and dose of any further isotonic fluid bolus therapy is at the discretion of the caring physician	• Further isotonic fluid bolus therapy may be administered by the caring physician to treat documented inadequate intravascular filling/preload • If further isotonic fluid bolus therapy is provided, the dose provided should be in 5–10-mL/kg aliquots (250-500 mL for participants ≥50 kg) with the lowest acceptable volume preferred and the indication for administration documented • Aliquots of isotonic fluid bolus therapy may be administered “back-to-back” if required to address inadequate intravascular volume status • The type of isotonic fluid bolus therapy provided is at the discretion of the caring physician
Vasoactive medicationc	• If initiated, vasoactive medication(s) may be titrated (increased, decreased, or discontinued) at the discretion of the caring physician • Additional vasoactive medication(s) may be initiated at the discretion of the caring physician	• Escalation of vasoactive medications should be the first line to achieve hemodynamic goals (provided intravascular volume status is judged to be adequate) • The initiated vasoactive medication(s) may be titrated (increased, decreased, or discontinued) at the discretion of the caring physician • Additional vasoactive medication(s) may be initiated at the discretion of the caring physician
Intervention end	• When the patient is free from vasoactive medication support and shock is reversed or the patient is placed on mechanical circulatory support,e.g., extracorporeal membrane oxygenation (ECMO) or death occurs	• When the patient is free from vasoactive medication support and shock is reversed or the patient is placed on mechanical circulatory support, e.g., ECMO or death occurs

^aBolus: a (fluid) bolus is a discrete volume of fluid prescribed to be administered intravascularly (intravenous (IV) or intraosseous (IO)) over a defined period of time (ranging from stat, i.e., as fast as possible to typically no greater than 60 min). A fluid bolus typically ranges in size from usually not less than 5 mL/kg (250 mL for participants ≥50 kg) to 20 mL/kg (1 L for participants ≥50 kg, although some clinicians may use per kilogram dosing in larger patients). A documented medical order is required for a fluid bolus. Routine fluid replacement is not considered to be bolus(es)

^bFluid therapy: isotonic crystalloid or colloid solutions which include 0.9% normal saline, Ringer’s lactate, and 5% albumin

^cVasoactive medications are administered by intravascular (IV or IO) infusion and include: dobutamine, dopamine, epinephrine, norepinephrine, vasopressin, phenylephrine, milrinone