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

Luca Cioccari*, Nora Luethi, Michael Bailey, Yahya Shehabi, Belinda Howe, Anna S. Messmer, Helena K. Proimos, Leah Peck, Helen Young, Glenn M. Eastwood, Tobias M. Merz, Jukka Takala, Stephan M. Jakob, Rinaldo Bellomo, ANZICS Clinical Trials Group and the SPICE III Investigators

*Corresponding author for this work

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    Abstract

    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 ClinicalTrials.gov (NCT01728558).

    Original languageEnglish
    Article number441
    Pages (from-to)1-13
    Number of pages13
    JournalCritical Care
    Volume24
    Issue number1
    DOIs
    Publication statusPublished - 16 Jul 2020

    Bibliographical note

    Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Dexmedetomidine
    • Hemodynamics
    • Noradrenaline
    • Sedation
    • Sepsis
    • Septic shock

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