Abstract
BackgroundSeptic 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.MethodsIn 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).ResultsBetween 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.ConclusionsIn 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 registrationThe SPICE III trial was registered at ClinicalTrials.gov (NCT01728558).
Highlights
Septic shock is associated with decreased vasopressor responsiveness
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
Dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target Noradrenaline equivalents to MAP ratio (MAP)
Summary
The SPICE III trial was a randomized, open-label trial conducted at 74 sites in eight countries [11]. Inclusion and exclusion criteria In addition to the abovementioned inclusion criteria of the SPICE III trial, patients had to meet all the following criteria to be eligible for this subgroup analysis: documented (or strong suspicion of) infection with at least 2 clinical signs of inflammation (temperature > 38 °C or < 36 °C, heart rate > 90/min, respiratory rate > 20/min, or PaCO2 < 32 mmHg, white cell count > 12 × 109/l or < 4 × 109/l or > 10% immature neutrophils), and administration of vasopressors or inotropes prior to randomization and for a cumulative duration of ≥ 4 h to maintain blood pressure targets set by the treating clinician. Group comparisons were performed using chi-square tests for equal proportion, Student’s t tests for normally distributed data, and Wilcoxon rank-sum tests otherwise, with results presented as numbers (%), means (standard deviations), or medians (interquartile range), respectively. Across the range of the data, a difference of this magnitude approximately equates to a 20% difference, which is perceived to be of clinical importance
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