The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial

Crit Care. 2020 Jul 16;24(1):441. doi: 10.1186/s13054-020-03115-x.


Background: Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting.

Methods: In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4).

Results: Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio.

Conclusions: In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP.

Trial registration: The SPICE III trial was registered at ( NCT01728558 ).

Keywords: Dexmedetomidine; Hemodynamics; Noradrenaline; Sedation; Sepsis; Septic shock.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Deep Sedation / methods
  • Dexmedetomidine / adverse effects*
  • Dexmedetomidine / pharmacology
  • Dexmedetomidine / therapeutic use
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / pharmacology
  • Hypnotics and Sedatives / therapeutic use
  • Intensive Care Units / organization & administration
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Respiration, Artificial
  • Retrospective Studies
  • Shock, Septic / drug therapy*
  • Shock, Septic / physiopathology
  • Switzerland
  • Vasoconstrictor Agents / administration & dosage*
  • Vasoconstrictor Agents / therapeutic use
  • Victoria


  • Hypnotics and Sedatives
  • Vasoconstrictor Agents
  • Dexmedetomidine

Associated data