The TARTARE-2S trial investigated whether a haemodynamic strategy focused on improving tissue perfusion while permitting lower-than-recommended mean arterial pressure (MAP) could improve outcomes in patients with septic shock compared with conventional MAP-guided standard care. Current sepsis guidelines prioritise maintaining MAP targets, typically ≥65 mm Hg, yet these recommendations are supported by only moderate or low-quality evidence. Moreover, increasing vasopressor use to reach higher MAP targets may worsen microcirculatory flow and tissue perfusion. The investigators hypothesised that directly targeting markers of tissue perfusion, rather than macrocirculatory blood pressure alone, might hasten shock resolution and reduce organ support requirements.
The clinical trial was conducted in three European university hospital ICUs. Adults aged 18–80 years with septic shock were eligible if they required vasopressors after adequate fluid resuscitation and had arterial lactate ≥3 mmol/L. A total of 219 patients were randomised: 111 to targeted tissue perfusion (TTP) and 108 to standard care (SC). After withdrawals and exclusions, 194 patients (97 in each group) were analysed for the primary outcome.
The TTP strategy focused on clinical and biochemical markers of peripheral and organ perfusion. Targets included capillary refill time <3 seconds, warm extremities, absence of mottling, urine output ≥0.5 mL/kg/hour, arterial lactate <2 mmol/L, and MAP between 50–65 mm Hg (65–70 mm Hg for patients with chronic hypertension). Temporary increases in MAP were allowed if oliguria persisted. In contrast, SC followed Surviving Sepsis Campaign haemodynamic goals, targeting MAP 65–75 mm Hg (higher if hypertensive) and using central venous pressure as a safety parameter. Both groups received clinician-directed interventions such as fluids, vasopressors, inotropes, and advanced monitoring as required.
The primary outcome was the number of days alive within 30 days with both normal lactate (<2 mmol/L) and no requirement for vasopressor or inotropic support. Secondary outcomes included time to lactate normalisation, days free from organ support (vasopressors, mechanical ventilation, renal replacement therapy), acute kidney injury, vasopressor dose, adverse events, and mortality at 30 and 90 days.
Achieved MAP values differed significantly between groups. Patients in the TTP arm had lower average MAPs during the first 72 hours (mean 68.5 mm Hg) compared with the SC group (74.8 mm Hg), confirming separation of treatment strategies. Despite this, lactate trajectories, cumulative fluid balance, and many haemodynamic interventions were similar between groups.
The primary outcome showed no statistically significant difference. Median days alive with normal lactate and without vasoactive drugs were 23 in the TTP group and 22 in the SC group. Thus, the TTP strategy did not hasten shock resolution or reduce vasopressor dependence.
Secondary outcomes likewise revealed no meaningful differences. Time to lactate normalisation, days alive without vasopressors or inotropes, ventilator-free days, renal replacement therapy-free days, and days alive without any organ support were comparable. Mortality at day 30 was 24.7% in TTP and 27.8% in SC, and no differences were observed at day 90. Rates of acute kidney injury, renal replacement therapy, and cumulative norepinephrine exposure were also similar.
Safety outcomes did not indicate harm from the lower MAP strategy. Serious adverse reactions were infrequent and distributed similarly between groups. The authors concluded that targeting tissue perfusion while allowing lower MAP appears feasible and safe but confers no clear clinical advantage over standard MAP-guided care.
In conclusion, among ICU patients with septic shock and elevated lactate, a treatment strategy targeting tissue perfusion and permitting lower MAP did not increase days alive free from vasopressors or improve other clinical outcomes compared with standard MAP-guided management. The absence of safety concerns supports further investigation of lower MAP targets combined with careful perfusion monitoring in larger trials.
Source: Critical Care Medicine
Image Credit: iStock
