Last month, Mark Sutherland posted an overview of a new article investigating the use of personalized MAP targets in resuscitation for septic shock (1). Now, the authors of ANDROMEDA-SHOCK-2 (2) suggest a new multimodal approach to personalize resuscitation in septic shock that largely operates outside of the traditional focus on MAP and lactate.

In 2019, the ANDROMEDA-SHOCK Trial (3) suggested that capillary refill time (CRT) may be a better resuscitation in septic shock than lactate. Now, the same group is suggesting that a stepwise algorithm to guide resuscitation may provide more optimal and “personalized” results when compared to usual care for patients with abnormal CRT:

Tier 1: If CRT is abnormal, assess pulse pressure (PP) and DBP: 

• PP (<40mmHg) OR DBP (>50mmHg)?  Assess for fluid responsiveness and challenge with up to 1L IVF if fluid responsive.
• PP (>40mmHg) AND DBP (<50mmHg)? Increase norepinephrine (NE) for DBP >50mmHg, followed by assessment for fluid responsiveness and possible fluid challenge if CRT remains abnormal.

Tier 2: If CRT remains abnormal despite the above, use POCUS to assess for cardiac dysfunction.

• LV dysfunction? Trial dobutamine @ 5-75 mcg/kg/min (stop for HR > 120 or tachyarrhythmia, or if it doesnt help CRT)
• RV dysfunction? The authors recommend avoiding fluids, increasing pressors if needed, as well as decreasing PEEP, limiting plateau pressures, and/or proning the patient if they have ARDS
• If there is no cardiac dysfunction, assess for fluid responsiveness and fluid challenge if fluid responsive. Continue this cycle until CRT normalizes or there is evidence of harm (evidence of pulmonary edema, worsening oxygenation/ventilation, or high central venous pressure).
  • If the patient is not fluid responsive, investigate for a history of HTN
    • If they have a history of HTN, push MAP to 80-85 for 1h and see if it improves CRT (if not, revert back)
    • If they do not, trial dobutamine @ 5 for 1h and see if it improves CRT (if not, DC dobutamine)
• If CRT remains abnormal after all of this, move on to “rescue therapies” (high dose steroids, hemofiltration, ECMO).

The authors found that at 6 hours, following the protocol resulted in increased use of dobutamine, lower fluid balance, and similar CVP and MAP with lower lactate levels and CRT. They reported an improvement in their composite hierarchical outcome at 28 days, primarily driven by a shorter duration of organ support (vasoactives, mechanical ventilation, renal replacement therapy) and among sicker patients. No difference in mortality was observed between groups.

Food for Thought:

• CRT is a subjective assessment, and all participating clinicians in this study underwent mandatory training. Other, more objective measures that can be used to assess organ perfusion (lactate clearance, urine output, MAP) were excluded from this protocol.
• Fluid responsiveness was assessed using the “preferred technique by each center.” Suggested techniques included pulse pressure/stroke volume variation, change in VTI with passive leg raise, IVC variability, or change in CO with end expiratory pause.
• There was no standardization regarding the integration of vasopressin, and steroids were reserved as “rescue therapies” and considered at the same point as mechanical hemodynamic support. 
• The effect of other inotropic agents (like low dose epinephrine) was not discussed.

Study Details:

• Setting: multicenter randomized control trial conducted in 86 ICUs across 19 countries
• Patients:
  • >1450 adults from the ED, ICU, OR, or floor with septic shock based on Sepsis-3 criteria - suspected/confirmed infection + lactate >2 + pressor requirement to maintain MAP> 65 despite 1L+ IVF bolus.
  • Patients with Child B or C cirrhosis, acute hematologic malignancy, severe ARDS, or anticipated surgery or HD within 8h of being diagnosed with septic shock, or who could not be enrolled within 4h of diagnosis were excluded. Pregnant patients were also excluded.
  • Almost half had an abdominal source of infection, followed by respiratory and urinary.
  • The median time to enrollment was 2h from meeting sepsis criteria
• Outcome: a hierarchical composite outcome using all-cause mortality, duration of vital support (vasoactives, invasive mechanical ventilation, or renal replacement therapy), and hospital LOS at 28d.
  • The primary outcome was assessed in a hierarchical fashion using “wins” and “losses.” The intervention group “won” in 48.9% of cases, while the usual care group “won” in 42.1%, for a Stratified Win Ration of 1.16 (95% CI 1.02-1.33).

References

(1) ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network, Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), and Latin American Intensive Care Network (LIVEN). Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA. 2025 Dec 9;334(22):1988-1999. doi: 10.1001/jama.2025.20402. PMID: 41159835; PMCID: PMC12573117.

(2) Hernández G, Ospina-Tascón GA, Damiani LP 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. doi: 10.1001/jama.2019.0071. PMID: 30772908; PMCID: PMC6439620.