How a New Trial Exposes the Strange Gravity of Medical Fads
There’s a particular rhythm to the way medicine convinces itself of things. A drug becomes familiar through sheer repetition, a kind of clinical muscle memory. Etomidate held that place for years. A steady, unglamorous workhorse of emergency intubation, moving through ICUs and EDs with the quiet authority of something that simply worked well enough. Then the whispers began: adrenal suppression, theoretical danger, biochemical impurity. Suddenly, using etomidate was no longer merely a choice. It became a referendum on whether you were paying attention, whether you had evolved.
In that vacuum of certainty, ketamine rose not carefully, not with the sober confidence of evidence, but with the velocity of an idea that felt emotionally and aesthetically right. It was vivid, modern, and aligned with the cultural shift toward “physiology-first” thinking. And so it became the preferred induction agent long before it earned the right to be.
We now have another RSI Trial, just published in the New England Journal of Medicine. Sprawling, meticulously executed, and utterly uninterested in the narratives clinicians have spun around these drugs. Its message is clear, clarifying, and impossible to ignore.
Mortality: A Null Result That Speaks Loudly
Across fourteen sites, 2,365 critically ill adults entered a trial designed to settle a dispute that has hovered over airway care for years.
The outcome of in-hospital death by day 28 landed with a kind of anticlimax:
- Ketamine: 28.1%
- Etomidate: 29.1%
- Difference: statistically indistinguishable.
It turns out neither drug is the hero or the villain we made it out to be. The mortality landscape remains unchanged, unmoved by pharmacologic ideology. The belief that etomidate was dangerous, or that ketamine conferred some quiet survival advantage, dissolves under the weight of this data.
Hemodynamics: The Trial’s Most Uncomfortable Revelation
For years, ketamine’s reputation as the hemodynamically “safe” agent spread the way trends always do: through repetition, aesthetics, and the subtle peer pressure of consensus masquerading as fact.
But this trial reveals something more uneven beneath that self-assured assumption.
Cardiovascular collapse during intubation:
- Ketamine: 22.1%
- Etomidate: 17.0%
- Absolute difference: +5.1%
And the more fragile the patient, the sharper the discrepancy:
- Sepsis/septic shock: +9.7%
- High APACHE II: +10.7%
The results feel almost subversive. The drug marketed (socially, culturally, clinically) as protective turns out to be the destabilizer. The old standby, long maligned, holds the line with greater consistency.
It’s a plot twist that would be funny if the stakes weren’t so high.
Adrenal Suppression: The Ghost Story That Isn’t
Etomidate really does suppress cortisol synthesis. Entire academic arguments have been constructed on this biochemical detail. But the obsession with this mechanism eclipsed a simple question: Does it matter?
In this massive trial, including more than 1,100 septic patients, the answer is: apparently not. No mortality signal. No hidden subgroup harm. No narrative payoff.
The adrenal-suppression anxiety now looks like one of those medical ghost stories we tell ourselves because the plot is too good to check.
For those still arguing that the ghost of adrenal suppression may be lurking inside an “underpowered” study, the most important point is this: even in the worst-case scenario, any mortality effect is likely small.
Why? Because the investigators didn’t stop at in-hospital deaths. They also performed a sensitivity analysis that counted death in any location by day 28, and the result was essentially identical between groups (risk difference 0.0%, 95% CI –3.9 to +3.9).
That “risk difference 0.0%” means exactly what it sounds like.
The death rate was the same in both groups.
Not almost the same.
Not “trending.”
The same.
Could there still be a tiny mortality signal hiding in the noise? Possibly. But the data now exclude large, practice-changing effects in either direction. The idea that ketamine is quietly saving lives (or that etomidate is silently killing patients) no longer fits the evidence.
So take your pick: is ketamine the dangerous drug, or is etomidate? At this point, clinging to the belief that ketamine meaningfully improves survival over etomidate isn’t cautious. It’s irrational.
On the Level of Actual Practice: Almost Nothing Changes
- First-pass success? The same.
- Desaturation? The same.
- Ventilator-free, vasopressor-free, ICU-free days? Essentially the same.
All the things clinicians desperately hope their drug choice will influence remain serenely indifferent.
The Hard Truth: We Let a Trend Become a Doctrine
And here’s the part that should sting a little.
This trial is a case study in how medical culture is swept up in narratives that seem progressive, edgy, and intellectually correct, but aren’t grounded in anything more substantial than collective intuition.
Etomidate was the default until it wasn’t. Not because new evidence dethroned it, but because the vibe shifted. Early studies, adrenal folklore, and the rise of ketamine as an in-crowd cultural phenomenon all blended into a kind of atmospheric pressure that made people feel that using ketamine was being “current,” and using etomidate meant you hadn’t read enough.
But now we’re confronted with an uncomfortable reality: we may have worsened cardiovascular instability for thousands of critically ill patients by chasing a trend.
This isn’t an indictment of curiosity. It’s a warning about certainty, the premature kind, the confident kind, the kind that arrives before the evidence does.
When the next airway fad arrives (and it will), we should remember this moment. The rush to the social performance of being updated is seductive. But the ground truth doesn’t care about any of that.
What Actually Matters Going Forward
This trial reframes the conversation in a way that feels almost liberating:
• Mortality doesn’t care which drug you choose.
• Etomidate is more hemodynamically stable than ketamine—full stop.
• Ketamine’s reputation as a protective agent doesn’t survive contact with data.
• Both drugs still have their place, but neither deserves the fervor we attached to them.
Below the surface, this trial didn’t just answer a pharmacologic question. It revealed something about us and how we follow stories, how we mistake trends for truths, and how easily clinical culture can drift away from its evidence base.
As always, this study leaves us with more questions, because clarity never arrives without opening another door. But one truth is unmistakable: the induction drug was never the main character. It was only ever a supporting player. The real determinants of success live elsewhere: in the architecture of oxygenation, in the quiet labor of hemodynamic stability, in the choreography of resuscitation, and in the almost wordless way a team can move as a single organism when everything is on the line.
Undoubtedly, there will be some theatrical gnashing of teeth, a few elaborate attempts to insist that the sun really does revolve around the earth. Or, if we’re lucky, there will be a moment of genuine clarity, a widening of perspective that feels almost like relief.
For anyone who has lived entirely inside one RSI worldview, that world has now ended. What comes next is the work of integrating better evidence into better practice, and maybe even allowing ourselves the quiet astonishment that comes with finally seeing things as they are.
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Reference
Casey, J. D., Seitz, K. P., Driver, B. E., Gibbs, K. W., Ginde, A. A., Trent, S. A., Russell, D. W., Muhs, A. L., Prekker, M. E., Gaillard, J. P., Resnick-Ault, D., Stewart, L. J., Whitson, M. R., DeMasi, S. C., Robinson, A. E., Palakshappa, J. A., Aggarwal, N. R., Brainard, J. C., Douin, D. J., … Semler, M. W. (2025). Ketamine or etomidate for tracheal intubation of critically ill adults. The New England Journal of Medicine, 393, 1–13. https://doi.org/10.1056/NEJMoa2511420
Another Good Read:
PulmCrit: Hot take on RSI trial of ketamine vs etomidate. December 10, 2025 by Josh Farkas
