Ross Prager Profile picture
Oct 29 10 tweets 5 min read Read on X
(1/x) Andromeda-Shock 2 was just published in JAMA and is the most important septic shock trial in the past DECADE.

They found that phenotyped resuscitation improves the composite outcome of mortality, vital support, and hospital LOS.

Here's how you can apply this protocol to your practice 👇Image
(2/x) At the core of AS2 is the concept of ‘microcirculation’ or that hemodynamic interventions we perform should improve tissue level perfusion.

To assess this, we can use the validated surrogate capillary refill time that helps approximate what is happening in the microcirculation.

Full article is here: jamanetwork.com/journals/jama/…
(3/x) Andromeda-Shock 2 RCT used a tiered approach to guide resuscitation, all centered around cap refill time.

Tier 1:
Check Cap Refill - if normal, periodic monitoring (you can't be better than normal!!)

If abnormal, first check pulse pressure (PP), a surrogate for stroke volume.

If narrow PP, check for fluid responsive.

If wide PP, check diastolic blood pressure and if <50mmHg, augment with norepinephrine.

Repeat cap refill serially.Image
(4/x) If after Tier 1 the Cap Refill Time is still abnormal move on to Tier 2 which is echo driven:

1. Cardiac dysfunction on echo? Inotropes.

2. Fluid responsive? Consider fluid bolus.

3. Still hypoperfused despite this? Consider MAP augmentation challenge.

The key here is that interventions are performed and then their impact on microcirculation assessed through cap refill time.

NO empiric 30ml/kg boluses.Image
(5/x) So what did the primary outcome show?

A reduction in composite of mortality, vital support, and hospital LOS (driven primarily by vital support)

Directly from the abstract: “There were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95%CI, 1.02-1.33; P = .04).”Image
(6/x) What about secondary outcomes and other key takehomes?

CRT guided resus patients received less fluid (595 mL vs 847 mL;)

CRT guided resus patients received more dobutamine (84/684 [12.3%] vs 37/694 [5.3%])

CRT guided patients had lower CVP and lactate

CRT guided patients had less FR assessments and received less resuscitative IV fluids

CRT guided patients had greater improvement in SOFA score over 7 days

Across subgroups with greater acuity (high SOFA & lactate) seems to be more of an effectImage
(7/x) What does this mean for both the management and research of septic shock?

Despite decades of negative trials, we don’t have to be nihilistic. We CAN improve outcomes, but the key is in phenotyping our interventions to the patient in front of us.

We need to STOP performing ‘one-size-fits-all’ trials for a syndrome like sepsis that is so heterogenous.
(8/x) How do the results of AS-2 change my practice?

1. Assess cap refill time - if normal, monitor periodically.

2. If abnormal, think about SV (e.g. narrow pulse pressure is a low SV surrogate) and if low, consider fluids if fluids responsive. If high pulse pressure and a low diastolic, augment the MAP.

REPEAT THE CRT SERIALLY.

3. If this isn’t working and still abnormal CRT, we need to echo the patient as cardiac dysfunction (and congestion) prevalent. This is a echo (+ VeXUS - our Andromeda-VEXUS paper will help color this in a bit more) and then treat the underlying cardiac dysfunction.

Empiric fluid loading (30ml/kg), one-size fits all resuscitation is not the answer in 2025.Image
(9/x) A huge shoutout is needed for all the AS2 investigators, particularly @AndromedaShock @edu_kattan Jan Bakker, Nico Orozco but so many more.

They started this study without funding, and with sheer passion managed to get hundreds of centers worldwide to recruit 1500 patients with phenotyped resuscitation. With this passion, funding, support, and collaborators came to support this vision.

For my friends and colleagues here on X, please read this study and share broadly as I think it has the potential to change how we resuscitate septic shock!!

Full article: (the supplement has a ton of incredible stuff too!) jamanetwork.com/journals/jama/…

Super excited to start analyzing our Andromeda-VEXUS data not that the embargo is lifted, stay tuned!

@NephroP @ArgaizR @ThinkingCC @katiewiskar @KiranRikhraj @nickmmark @TheSGEM @emcrit @PulmCrit @john_basmaji @MaratSlessarev @HoosierPocus @Bram_Rochwerg
@AndromedaShock @edu_kattan Pinging a few more to join in the discussion here!!
@icmteaching @DrAkhilX @cardiacACCP @cliffreid @CharlesLutzMD @FH_Verbrugge @jeffgadsden @CriticalCareNow

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More from @ross_prager

Oct 30
(1/x) With the publication of Andromeda-Shock 2 in JAMA there has been a lot of excitement, and rightly so, a lot of questions and skepticism.

The main criticism I've heard is: "there is mainly a reduction in organ support, not mortality, is that even patient important?"

I think it is! 👇Image
(2/x) For context, AS-2 was a 1500 patient RCT of a 6 hour resuscitation window compared to standard care in septic shock.

Full Article: jamanetwork.com/journals/jama/…

The intervention used Cap Refill Time as a surrogate of end-organ perfusion, and if abnormal, did physiology informed maneuvers (fluids, vasopressors, inotropes) to improve perfusion.

They found "there were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04)."

Most of this was driven by lower organ support in the phenotyped (intervention) arm.

Patients in the intervention arm received 1) less fluids 2) more inotropes 3) had improved SOFA/lactates 4) and less organ support (vasopressors primarily).

So is this patient important?Image
(3/x) It is important to contextualize this in the broader sepsis research landscape.

EGDT in 2001 --> 46.5 vs. 30.5% mortality
ARISE in 2014 --> ~19%
PROCESS in 2014 --> ~21%
PROMISE in 2015 --> ~29%

ANDROMEDA-SHOCK in 2019 ~43% vs 35% (intervention)

Why a higher mortality for Andromeda-Shock than the older ARISE/PROCESS/PROMISE?

It may be related to patient demographics, particularly recruiting patients from more low-middle income countries where sepsis mortalities are higher.

In Andromeda-Shock 2, mortality was only 26%, 10-15% lower than the previous study (and lower than expected) likely reflecting improved sepsis care globally.

The truth is, for any septic shock study, an outcome like mortality is only modifiable for a subset of patients.

Some are too sick and will die regardless of resuscitation.

Some are well enough that they will live despite what we do.

There is a window of patients in the middle whose mortality is modifiable... but as baseline mortality decreases and overall sepsis care improves, this mortality modifiable group becomes smaller.Image
Read 5 tweets
Aug 26
(1/9) Here’s how to become the best doctor you can in 2025…

Some advice (e.g. learn from your pts) is timeless but some thing are different than when Osler trained.

🧵 Image
(2/9) Learn from your patients

Learning ~= cases seen × learning extracted per case

Maximizing both is key.

Volume exposes you to varied presentations, and reflection deepens your understanding.

There’s no substitute for either. Perhaps in the coming years AI simulated presentations may assist in pattern recognition (e.g. high exposure to simulated pathology) but not quite there yet.
(3/9) Develop skills beyond knowledge

Knowledge matters, but communication, listening, problem-solving, studying, and teamwork matter more in practice.

When trainees struggle, it’s often these skills, not medical knowledge, that hold them back.
Read 10 tweets
Aug 10
(1/x) In fellowship, I managed a peri-arrest patient in the middle of the night who changed my understanding and appreciation for hemodynamics, ultrasound, and TEE.

I've seen similar cases dozens of times now, yet this commonly gets missed, even at top institutions worldwide.

A 🧵
(2/x) When I met this pt. they had a HR of 170 and a blood pressure on arterial line of 50/30. They were mottled head to toe, ashen, and looked like they were seconds away from arresting.

They had a recent NSTEMI and my first thought was cardiogenic shock or a mechanical complication of their MI --> VSD, tamponade, free wall rupture etc.

No transthoracic views on echo.
(3/x) I started the usually therapy, phenylephrine pushes, levophed, vaso pushes, and epi infusion.

No response.

I started bolusing aliquots of 20-50mcg of epinephrine ... no response. We intubated while this was going on.
Read 8 tweets
Jul 29
(0/x) How do I approach the first 2 minutes of meeting a new critically ill pt?

My approach has been forged from my learnings as a paramedic.

Here's my approach as an ICU doc 🧵 Image
(1/x) I start with a scene survey.

I want to understand who's in the room and what are their roles. Is someone currently leading the resuscitation? What monitors are on the patient? What drugs are hooked up to the patient?

In EMS, one of the first things we are taught is to not rush to the patient.

This is for your own safety in case there's a hazard, but also because you can learn so much about what's going on by observing your environment as you approach the patient.

This gets missed in the hospitals.

Take some time and even by understanding what pumps they're on, you can often learn a lot about what might be going on in this very moment. You can also learn what help you might have if 💩🪭Image
(2/x) Next, I start perform a very quick (<15 seconds) scan of the patient

Essentially quickly checking the ABCs

This involves:
Reviewing the monitor for current vitals
Looking at the patient's skin colour
Looking for mottling
Looking at the Work of Breathing
Looking for LOC
Approaching the patient and briefly feeling their feet or hands for temperature and pulse characteristics

My goal here is to determine whether we need to go straight into resuscitation within seconds (cardiac arrest) or peri-arrest, or whether I can take a bit more detailed handover from the team that's already caring for the patient.Image
Read 6 tweets
Jul 28
(0/x) For the past 2 years I have worked in our chronic ICU helping wean difficult to wean patients with neurological weakness.

Here are some of the things I’ve learned from my vastly expert multi-disciplinary team 🧵

Really these are just great practices for weaning ALL ICU pts. off ventilators...Image
(1/x) Deeming a patient impossible to wean should only be done by groups of clinicians with extensive experience in this.

In fact, evidence suggests that physicians are often poor at predicting weaning failure.

We've had patients with neuromuscular weakness who have been ventilated for close to a year or longer who have successfully weaned entirely from mechanical ventilation with thoughtful, deliberate weaning strategies.
(2/x) Optimizing volume status is crucial to weaning patients.

For neuromuscular weakness patients, even having 500 mL of pleural effusion adds a pound of weight onto each diaphragm.

When multiplied over the thousands of breaths per day, this significantly contributes to weaning failure.

Optimize your patient's volume status to help them wean!
Read 8 tweets
Jul 23
(1/9) Its July and medical trainees are starting their medical school residency or fellowship.

Here is my advice for any ICU fellows starting out to avoid making some of the same mistakes that I've made in the past.

A 🧵 Image
Tip 1: Just go see the patient.

When somebody is calling the intensive care unit in the hospital, they are calling for help. We are the 911 for hospitalized patients.

Even if there may not be a clear ICU indication based on your initial phone call with the referring physician or nurse, just go see the patient.

Often I find that we can still improve patient care for those patients even if they don't need vasopressors, ventilator, or inotropes. Often they are quite sick, and our expertise managing sick patients can be very useful.

In 2025, we need to move away from the restricted notion that the intensive care unit expertise only pertains to ventilators, vasopressors, and inotropes.

We are experts in managing acutely unwell patients even before they require ICU, so we should lend our expertise to help patients anywhere in the hospital.
Tip 2: When you first meet a patient or family, listen more than you speak.

Ask the patient and family lots of questions about their values, functions, and what's important to them in their life.

Try to get to know them as a person before they became into the ICU.

Taking time to ask the patient and family these questions up front will actually answer a lot of questions for you down the road and save time in conversations.

It also builds rapport, shows that you are committed to their loved one, and will often get you useful clinical information that helps solve any diagnostic puzzles you have

Avoid launching into a medical update within the first 5 minutes of meeting a family.

Often they are not yet primed to hear this information, and spending a bit of time building rapport ahead of time is invaluable.Image
Read 11 tweets

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