Persistent tissue hypoperfusion improves risk stratification beyond vasopressor dose in refractory septic shock: a secondary analysis of the ANDROMEDA-SHOCK-2 trial.
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Kattan Eduardo, Ospina-Tascón Gustavo A, Orozco Nicolas, Teboul Jean-Louis, Melo Paulo, Wendel-Garcia Pedro D, Morales Sebastian, Amthauer Macarena, Hunsicker Oliver, Ibarra-Estrada Miguel, Leone Marc, Khanna Ashish K, Hamzaoui Olfa, Messina Antonio, Myatra Sheila Nainan, Ramasco Fernando, Vieillard-Baron Antoine, Putowski Zbigniew, Ferri Giorgio, Castro Ricardo, Biasi-Cavalcanti Alexandre, De Backer Daniel, Bakker Jan, Hernandez Glenn, ANDROMEDA-SHOCK-2 investigators, ANDROMEDA-Research Network
Аннотация
METHODS: We performed an exploratory secondary analysis of the ANDROMEDA-SHOCK-2 trial. After 6 h of hemodynamic resuscitation, refractoriness was operationalized as a norepinephrine equivalent dose (NEE) > 0.5 µg/kg/min plus an abnormal capillary refill time (> 3 s) and non-decreasing lactate (two-hypoperfusion criteria). A complementary analysis included NEE > 0.5 µg/kg/min combined with either of the tissue perfusion criteria. The primary outcome was 28-day mortality.
RESULTS: Among 1363 patients with complete data, 188 (13.8%) had NEE > 0.5 µg/kg/min at 6-h, with 47.9% mortality. Fifty-three patients (3.9%) were classified as refractory septic shock under the two-hypoperfusion criteria and 124 (9.1%) under the ≥ 1-hypoperfusion criterion. Mortality was 73.6% (39/53) among patients meeting two-hypoperfusion criteria, compared with 23.7% (310/1310) among those classified as non-refractory according to these criteria. (aHR, 4.68; 95% CI 3.31-6.64;p < 0.001). Under ≥ 1-hypoperfusion criterion, mortality was 55.0% (68/124), compared with 22.7% (281/1239) among those classified as non-refractory under this approach (aHR, 2.62; 95% CI 1.90-3.46;p < 0.001). Refractory patients under either approach required had fewer life-support free days. Compared with NEE > 0.5 µg/kg/min alone, the two-hypoperfusion construct yielded superior prognostic enrichment for 28-day mortality (LR + , 8.12; 95% CI 4.70-14.03 vs. 2.71; 95% CI 2.10-3.50;p < 0.001).
CONCLUSION: In early septic shock, combining persistent tissue hypoperfusion with vasopressor dose improves risk stratification beyond vasopressor dose alone and identifies a subgroup with markedly increased mortality. These hypothesis-generating findings require validation in future studies.