Targeted Tissue Perfusion Versus Macrocirculatory-Guided Standard Care in Patients With Septic Shock: A Randomized Clinical Trial-The TARTARE-2S Trial.

Objectives To determine whether treatment targeting improving tissue perfusion while allowing lower than recommended blood pressure (targeted tissue perfusion [TTP]) improves outcome compared with mean arterial pressure (MAP)-guided standard care (SC). Design A randomized, parallel-group, open-label clinical trial with 30-day follow-up. Allocation was stratified according to trial site and presence of chronic arterial hypertension. Setting Three European university hospital ICUs with enrollment from 2016 to 2022. Patients Two hundred nineteen patients with septic shock and blood lactate greater than 3 mmol/L allocated to TTP (n = 111) vs. SC (n = 108). Interventions The TTP protocol comprised capillary refill time, peripheral skin temperature, arterial lactate concentrations, and MAP 50-65 mm Hg. The SC protocol comprised the hemodynamic targets of 2012 Surviving Sepsis Campaign. Measurements And Main Results Ninety-seven (87.4%) in TTP and 97 (89.8%) in SC group (total n = 194) were analyzed for the primary outcome. The median (interquartile range) of days alive in 30 days with normal lactate and without vasopressor/inotropic drugs (primary outcome) was 23 (10-27) in TTP group and 22 (1-27) in SC group (difference in medians, 0.59; 95% CI, -3 to 4). Secondary outcomes (single components of the primary outcome, days alive without organ support and mortality, all at 30 d) and serious adverse reactions were not significantly different between intervention groups. At day 30, 24 patients (24.7%) in TTP group vs. 27 patients (27.8%) in SC group had died. MAP levels were lower in the TTP group vs. the SC group. Conclusions In ICU patients with septic shock and lactate greater than 3 mmol/L, targeting tissue perfusion and allowing lower than recommended MAP did not increase the number of days alive with normal lactate and without vasopressor/inotropic drugs at 30 days. No additional safety concerns with the TTP strategy were detected compared with SC.