Septic Shock: The Balance Between Fluid and
Vasopressor Administration on Mortality


  • Increasing doses of vasopressors within the first 6 hours are associated with increased mortality unless paired with at least 2,000 mL of fluid administration.
  • Increasing vasopressor doses are associated with increasing mortality over the first 24 hours of septic shock.
  • Additional evaluations optimal balance between fluid and vasopressor administration.


  • Vasopressors are recommended to be initiated within 6 hours of sepsis in hemodynamically unstable patients after fluid resuscitation.
  • The ideal balance between fluid and vasopressor administration in patients with septic shock is not known.
  • Current guidelines outline WHAT to do (fluid resuscitation followed by vasopressors in hemodynamically unstable septic shock patients), but there is a lack of guidance on HOW to achieve this desired hemodynamic endpoint within the bundle.
  • The association between administration of fluids and/or vasopressors to achieve the desired hemodynamic endpoint and impact on mortality is unknown.


A recent review of 616 patients with septic shock from 33 hospitals retrospectively evaluated vasopressor administration following fluid resuscitation.

  • Data from September 1, 2017 – February 1, 2018, consecutive septic shock patients
  • The goals were to:

o Determine if vasopressor response varies depending on fluid administration volume.

o Determine the association between vasopressor dosing and 30-day in-hospital mortality.

  • Data from 12 hours before to 24 hours following shock onset.
  • Fluid administration was the total volume of all fluids and blood products administered from 0-24 hours.
  • Vasopressors:

o Dopamine; epinephrine; norepinephrine; phenylephrine; vasopressin

o All doses converted to “Norepinephrine Equivalents” (NEE).

o NEE determined for 0-6 hours and 0-24 hours with time-weighted rules.

  • Vasopressor Dosing Intensity (VDI) across the 2 time periods were categorized as:
  • 0-6 hour: Increased 30-Day mortality with increasing VDI with less than 2000 mL fluid administration
  • 0-24 hour: Increased VDI also associated with increased 30-Day mortality, but did not vary with fluid administration

o Every 10 mcg/min increase in VDI increased odds of 30-Day mortality by 33%.

  • Patients who were in the Early High/Late Low VDI dosing group were associated with lower mortality rates compared the Early Low/Late High VDI group.
  • Common Fluid and Vasopressor strategies to achieve desired mean arterial pressure (MAP).

    o Start vasopressors at a moderate dose with gradual increase.

    o Administer incremental fluid boluses while gradually increasing the vasopressor dose.

    o Start higher dose of vasopressor and reduce the dose after MAP achieved.

    o Restrictive fluid strategies early on, combined with earlier aggressive vasopressor support.


  • The optimal balance between fluid and vasopressor administration is unknown and needs to be evaluated.

  • The minimum threshold of fluid administration prior to vasopressor initiation is unknown.
  • Volume administration of less than 2000 ml combined with vasopressor administration was associated with higher trends in mortality.
  • Individualized therapy balancing fluid and vasopressor dosing in terms of amount and timing are necessary.

Erkan Hassan is the Co-Founder & Chief Clinical Officer of Sepsis Program Optimization where he designs & oversees the implementation of solutions to optimize sepsis programs.

To discuss your organization’s Barriers of Effective Sepsis Care, contact Erkan by phone (844) 4SEPSIS (844-473-7747), email (, or video chat.