ANDROMEDA Trial: Key Findings on Septic Shock Management
The ANDROMEDA trial demonstrated that systematic assessment of fluid responsiveness during early septic shock resuscitation allows clinicians to safely withhold fluid boluses in non-fluid responsive patients without negatively impacting mortality or organ dysfunction, challenging the traditional approach of aggressive fluid administration. 1
Core Findings from ANDROMEDA Trial
Fluid Responsiveness Assessment
- 70% of early septic shock patients were fluid responsive at baseline, while 30% were non-fluid responders who did not benefit from additional fluid boluses 1
- Fluid responsiveness could be determined in over 80% of patients using systematic per-protocol assessment 1
- Only 13 patients remained fluid responsive throughout the entire intervention period, indicating that fluid responsiveness is a dynamic state requiring repeated assessment 1
Clinical Outcomes Based on Fluid Responsiveness Status
Non-fluid responsive patients received significantly less resuscitation fluid (0 mL vs. 1500 mL median) but achieved comparable resuscitation targets and identical clinical outcomes compared to fluid responders 1
Key outcome comparisons between fluid responders (FR+) and non-responders (FR-):
- 28-day mortality: 40% vs. 36% (p=0.5) - no significant difference 1
- 24-hour SOFA score: 9 vs. 8 (p=0.4) - equivalent organ dysfunction 1
- Need for mechanical ventilation: 78% vs. 72% (p=0.16) 1
- Need for renal replacement therapy: 18% vs. 21% (p=0.7) 1
- ICU length of stay: 6 vs. 6 days (p=0.2) 1
Fluid Balance and Vasopressor Use
- Non-fluid responders exhibited less positive fluid balances, avoiding potentially harmful fluid overload 1
- Non-fluid responders required more vasopressor support, which appropriately addressed their hemodynamic needs without fluid administration 1
Integration with Current Guidelines
Fluid Resuscitation Strategy
The ANDROMEDA findings align with the 2016 Surviving Sepsis Campaign shift away from rigid protocols:
- Initial fluid resuscitation should begin with 30 mL/kg crystalloid within 3 hours 2
- After initial resuscitation, further fluid administration should be guided by dynamic assessment of fluid responsiveness rather than static targets like CVP 2
- Dynamic variables (pulse pressure variation, passive leg raise, stroke volume changes) should be used over static measurements 2
Vasopressor Management
When patients are non-fluid responsive:
- Norepinephrine remains the first-choice vasopressor to maintain MAP ≥65 mmHg 2, 3
- Vasopressin (up to 0.03 U/min) can be added to norepinephrine if hypotension persists 2, 3
- Epinephrine should be considered as third-line therapy 2, 4, 3
Clinical Implications and Algorithm
For early septic shock resuscitation:
Administer initial 30 mL/kg crystalloid bolus 2
Assess fluid responsiveness before each subsequent fluid bolus using:
If fluid responsive: Continue fluid boluses with repeated reassessment 1
If non-fluid responsive:
Critical Pitfalls to Avoid
- Do not continue fluid boluses without assessing fluid responsiveness - this leads to unnecessary fluid overload in 30% of patients who will not benefit 1
- Do not rely on CVP alone to guide fluid therapy - it has poor predictive value for fluid responsiveness 2
- Do not delay vasopressor initiation in non-fluid responsive patients - early vasopressor use is safe and appropriate 3, 1
- Do not assume fluid responsiveness persists throughout resuscitation - only 13 patients remained fluid responsive throughout the study period, requiring repeated assessment 1
Ongoing Research
The ANDROMEDA-SHOCK-2 trial is currently investigating whether a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment improves outcomes compared to standard care 5