Last week, I put out an EMCrit Podcast on ANDROMEDA-SHOCK-2. On that episode, I promised a discussion with the investigators and here it is!

My Guests

Glenn Hernandez, MD

Eduardo Kattan, MD

Patients

• Big percentage of abdominal sepsis, does this matter for generalizability?

Interventions

• Time from inclusion criteria to randomization is 2 hours (which is incredibly impressive), but do you think the benefit would be even higher if we started at time zero?

CRT Testing

• How do you translate testing CRT to real life? Microscope slide? stopwatch?
• Eduardo mentions this Meta-Analysis on CRT Methods as a Predictor of Mortality [10.1186/s13054-023-04751-9]

DBP Push

• Rationale?
• Did it matter?
• Why restrict to PP > 40?, ostensibly if we increased pressors to push to DBP>40 we would also be stressing venous side and increasing preload, leading to better preload and fluid utilization.

Fluids

• Less fluids as the result of the intervention. What do you think caused this? Limiting fluids to 1000 mls in Tier 1? Forcing Fluid Responsiveness checks every 500 ml? Forced slow fluids?
• 30 minute, 500 ml boluses is slow fluid and took the place of other interventions potentially in a six hour block. What is the rationale?
• Is my list of recommended fluid responsiveness tests correct?
• Why IVC collapsibility?
• Listener, David,  found a study that CRT decrease of 25% after PLR actually predicted response to 500 ml bolus [10.1186/s13054-019-2560-0]
• Safety Parameters for Fluid Admin in Tier 2?

Cardiac Dysfunction

• Did I get the parameters right?

Inotropes

• Why just dobutamine rather than epinephrine?

MAP Push for Hypertensives

• With the results of OPTIPRESS, would you have left this intervention in the study?

Steroids

• Why left to provider discretion?

Rescue Therapies

• What were they?

Results

• Projected 6% mortality difference and actual difference was none, what is the theory on why?
• Stratified, hierarchical win ratio–I understand all the reasons why, but does this allow trials that would normally be negative to get spun as positive?
• Was the usual care group's effect contaminated by study training?
• These bundled care studies can be a kitchen sink. We are now stuck with all of the bundle–are more focused trials or these bundled studies the way forward?
• I think the main reason EGDT study was positive was the Eagle Eye effect where a fellow was at the bedside throughout the 6 hours in the intervention group. Did that play a role here?

Translation and Adoption

• What should we do with the study results?
• EGDT was a similar trial and resulted in horrible changes in US healthcare (in my opinion)–will the same thing happen with AS2?
• One listener states that this is too much work for a study with no mortality benefit?
• What's next?

Papers Recommended by Dr. Hernandez

• The intricate relationship between capillary refill time and systemic hemodynamics in septic shock
• A plea for personalization of the hemodynamic management of septic shock

More on EMCrit

EMCrit 411 – You Need to Understand the Andromeda-Shock-2 RCT for Septic Shock

Additional Resources

• Author
• Recent Posts

Scott Weingart, MD FCCM

Editor-in-Chief, at EMCrit.org

An ED Intensivist from NY.
Professor
Nassau University Medical Center
No conflicts of interest (coi).

Latest posts by Scott Weingart, MD FCCM (see all)

• EMCrit Wee – ANDROMEDA-SHOCK-2 Explosion – A Discussion with the Lead Investigators - November 4, 2025
• EMCrit 411 – You Need to Understand the Andromeda-Shock-2 RCT for Septic Shock - October 30, 2025
• EMCrit 1:1 Nursing 006 – Post-Cardiac Arrest (Post-Arrest) Care - October 23, 2025