Background

The optimal approach to haemodynamic resuscitation in patients with septic shock is uncertain. Conventional practice, supported by international consensus guidelines, is initial administration of 30 ml/kg of intravenous (IV) fluids for newly diagnosed septic shock. Emerging evidence of harm associated with excessive IV fluids has led to more recent variation in practice with some clinicians favouring smaller fluid volumes combined with early vasopressor administration to restore systemic blood pressure. The impact on clinical outcomes among patients with septic shock presenting to emergency departments in Australia and New Zealand is unknown.

Aim

To compare the effect of a strategy of restricted fluids and early introduction of vasopressors to a strategy which involves a larger initial volume of IV fluid and later vasopressor administration if required, for haemodynamic resuscitation of patients with early septic shock.

Objectives

To provide robust evidence for clinicians regarding the optimal approach to early haemodynamic resuscitation in septic shock to improve patient-centred clinical outcomes.

Methods

This multicentre, randomised controlled trial will enrol 1000 patients presenting with septic shock to the emergency department (ED) of participating hospitals in Australia and New Zealand. Participants will receive haemodynamic resuscitation with either a restricted fluids and early vasopressor regimen or a larger initial IV fluid volume with later introduction of vasopressors if required. Clinical care including the type of resuscitation fluid and vasopressor agent, will otherwise be in accordance with accepted standard care and according to clinician discretion. The study intervention will be delivered for at least 6 hours and up to 24 hours post-randomisation. Participants will be followed for up to 12 months and outcomes analysed on an intention-to-treat basis.

Study population

Adult patients admitted to the ED of a participating institution with septic shock. Eligible patients must meet the inclusion criteria within the first 6 hours of ED presentation and must be randomised within 2 hours of meeting the last inclusion criterion.

Inclusion criteria

Patients will be eligible if ALL of the following criteria are met while in the ED:

  1. Clinically suspected infection
  2. Systolic blood pressure (SBP) < 90 mm Hg or mean arterial pressure (MAP) <65 mm Hg, despite a >= 1000ml cumulative total bolus of IV fluid administered over a maximum of 60 minutes; including pre-hospital boluses
  3. Arterial or venous blood lactate >2.0 mmol/L
  4. At least one dose of an IV antimicrobial has been commenced.

Exclusion criteria

Patients will be excluded if ANY of the following apply:

  1. Age < 18 years
  2. Confirmed or suspected pregnancy
  3. Transferred from another acute care facility
  4. Hypotension suspected to be due to a non-sepsis cause
  5. >2L total IV fluid administered (including prehospital fluids but excluding drugs and flushes)
  6. More than 6 hours has elapsed since presentation to the ED or more than 2 hours has elapsed since last inclusion criterion has been met
  7. Treating clinician considers that one or both of the treatment regimens are not suitable for the patient or the study protocol cannot be delivered e.g. limitation of care, requirement for immediate surgery
  8. Death is considered imminent or inevitable
  9. Underlying disease that makes survival to 90 days unlikely
  10. Inability to follow patient up to day 90 e.g. unstable accommodation, overseas visitor
  11. Previously enrolled in this study