What are the findings of the Andromeda Shock-2 trial on early goal-directed therapy for shock?

The ANDROMEDA-SHOCK-2 Trial: Latest Findings and Implications

The ANDROMEDA-SHOCK-2 trial demonstrates that hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock is superior to standard care, resulting in improved patient outcomes including reduced mortality and organ dysfunction.

Background and Context

• The ANDROMEDA-SHOCK-2 trial builds upon the evolution of septic shock management, moving away from the original Early Goal-Directed Therapy (EGDT) protocol toward more individualized approaches based on continuous assessment of patient response 1
• Previous landmark trials (ProCESS, ARISE, ProMISe) had shown that strict adherence to EGDT protocols did not reduce mortality compared to well-executed usual care 2, 3
• The original EGDT approach, described by Rivers in 2001, showed significant mortality reduction (30.5% vs 46.5%) but has been difficult to replicate in multicenter trials 4, 2

ANDROMEDA-SHOCK-2 Trial Design

• ANDROMEDA-SHOCK-2 is an international, multicenter randomized controlled trial comparing a novel approach to standard care in early septic shock (diagnosed within 4 hours) 5, 6
• The trial enrolled 1,500 patients to provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy 6
• The primary outcome is a hierarchical composite of mortality, time to organ support cessation, and hospital length of stay 5
• The statistical analysis uses the stratified win ratio method to analyze this hierarchical primary outcome 5

Intervention Strategy

• The intervention focuses on peripheral perfusion assessment using capillary refill time (CRT) measured hourly for 6 hours 6
• If CRT is abnormal, patients enter an algorithm starting with pulse pressure assessment 6:
  • Pulse pressure <40mmHg: Test for fluid responsiveness and administer fluids accordingly 6
  • Pulse pressure >40mmHg: Titrate norepinephrine to maintain diastolic arterial pressure >50mmHg 6
• If CRT remains abnormal after these steps, critical care echocardiography is performed to evaluate cardiac dysfunction 6
• Final steps include vasopressor and inodilator tests to further optimize perfusion 6

Key Findings

• The hemodynamic phenotype-based, CRT-targeted resuscitation strategy demonstrated superiority over standard care in the composite outcome 5
• This approach allows for more targeted fluid administration based on individual patient needs, potentially avoiding unnecessary fluid overload 6
• The strategy aligns with current recommendations for individualized assessment and treatment rather than protocol-driven approaches 1

Clinical Implications

• The findings support a shift from static parameters (like central venous pressure) to dynamic variables for predicting fluid responsiveness 1
• This approach may be particularly beneficial in resource-limited settings as it relies on clinical assessment (capillary refill time) rather than advanced monitoring 6
• The trial reinforces the importance of early identification and treatment of tissue hypoperfusion in septic shock 6
• The strategy aligns with current recommendations for maintaining mean arterial pressure ≥65 mmHg and normalizing lactate as markers of adequate tissue perfusion 1

Comparison to Previous Evidence

• Unlike the original Rivers EGDT study which showed a 16% absolute mortality reduction 4, ANDROMEDA-SHOCK-2 focuses on a composite outcome that includes mortality but also organ dysfunction and resource utilization 5
• Previous multicenter trials like ProMISe showed no mortality benefit with strict EGDT protocols (29.5% vs 29.2%, relative risk 1.01) 3, suggesting that more tailored approaches like in ANDROMEDA-SHOCK-2 may be more effective
• The ANDROMEDA-SHOCK-2 approach addresses limitations of previous protocols by avoiding unnecessary interventions based on fixed targets 1, 6

Practical Application

• Clinicians should consider implementing CRT assessment as part of routine monitoring in septic shock patients 6
• The phenotype-based approach allows for more precise interventions based on the underlying hemodynamic abnormality 6
• This strategy can be implemented with bedside tools without requiring advanced monitoring in all cases 6
• Regular reassessment of perfusion markers is essential to guide ongoing therapy 1

Limitations and Considerations

• Implementation requires education and training of clinical staff to accurately assess capillary refill time 6
• The approach requires more frequent clinical assessments than standard protocols 6
• Single-center positive trials have historically shown larger treatment effects than subsequent multicenter trials, so these results should be interpreted with appropriate caution 2

The ANDROMEDA-SHOCK-2 trial represents an important advancement in septic shock management, moving toward more personalized resuscitation strategies based on clinical assessment of tissue perfusion and hemodynamic phenotypes.