Rewriting the Resuscitation End Points: Lessons From TARTARE-2S

For decades, septic shock resuscitation has revolved around numbers we can measure—such as lactate levels and mean arterial pressure (MAP)—as the scaffolding for our hemodynamic decision-making. Often, because they are reproducible and easy to follow, they have been embedded into bundles and guidelines as surrogates for tissue perfusion.^1,2 In 2019, the ANDROMEDA-SHOCK trial challenged lactate-guided resuscitation and demonstrated how targeting capillary refill time rather than lactate clearance resulted in less fluid administration and lower organ dysfunction at 72 hours.³ The trial did not eliminate lactate from practice, but it exposed an important truth: hyperlactatemia is not synonymous with tissue hypoxia. In this Concise Critical Appraisal, we review another pillar of resuscitation care that has been recently challenged. 

The universal MAP goal of 65 mm Hg was largely based on consensus and observational associations rather than definitive physiologic evidence.^4,5 The recently published TARTARE-2S trial revisited this cornerstone of septic shock resuscitation and examined the physiologic and clinical consequences of individualized, alternative MAP strategies.⁶ Patients were randomized to differing pressure targets with protocolized vasopressor adjustments to achieve those goals.

A total of 194 patients were analyzed for the primary outcome, with 97 assigned to targeted tissue perfusion (TTP) and 97 to standard care (SC). The primary end point (days alive within 30 days with normal lactate and free of vasopressor or inotropic support) was similar between groups. The median was 23 days in the TTP group versus 22 days in the SC group. Thirty-day mortality was also comparable: 24 patients (24.7%) in the TTP group versus 27 patients (27.8%) in the standard care group. The absolute difference was small and not statistically significant. Secondary outcomes, including days alive without organ support and serious adverse events, were not significantly different. Notably, MAP levels were lower in the TTP group, yet this did not translate into worse outcomes. This suggests that lower norepinephrine exposure did not result in worsened downstream organ function.

For clinicians at the bedside, this finding is uncomfortable because blood pressure feels actionable. Blood pressure is something we can see, trend, and correct. The findings force us to reconsider how reflexively we pursue numeric targets in septic shock. The trial does not advocate for MAP target abandonment—it tells us to contextualize it. As ANDROMEDA suggested, a simple bedside capillary refill time may be as meaningful a marker of perfusion as biochemical trends. Now, TARTARE-2S reinforces how pushing vasopressors to reach arbitrary pressure targets may increase treatment intensity without changing outcomes. When we escalate vasopressors to reach higher MAP targets, we may increase the risk of arrhythmias, ischemia, and catecholamine toxicity without necessarily restoring cellular perfusion. In practice, this means more central lines, more vasopressor titration, more telemetry alarms—and more exposure to the physiologic cost of catecholamines—without clear survival benefit.

Septic shock resuscitation may require less rigid target-chasing and more clinical judgment—integrating perfusion markers, trajectory, organ response, and context. A MAP of 65 mm Hg may be sufficient for some patients and inadequate for others. The goal is not to hit a number, it is to restore effective perfusion with the least harm possible. The lesson from TARTARE-2S is not that pressure does not matter. It is that pressure alone is not perfusion. More vasopressor does not always mean better outcomes. The art of resuscitation remains knowing when enough is enough.


References

1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552.
2. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Crit Care Med. 2018 Jun;46(6):997-1000. 
3. Hernández G, Ospina-Tascón GA, Petri Damiani L, et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: the ANDROMEDA-SHOCK randomized clinical trial. JAMA. 2019 Feb 19;321(7):654-664. 
4. Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-1815. 
5. Asfar P, Meziani F, Hamel JF, et al; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-1593.
6. Pettilä V, Pfortmüller CA, Perner A, et al. Targeted tissue perfusion versus macrocirculatory-guided standard care in patients with septic shock: a randomized clinical trial—the TARTARE-2S trial. Crit Care Med. 2026 Jan 1;54(1):24-34.