Etomidate meta-analysis: increased mortality

[Tipsy McStagger]

Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials

I was a big fan of Methohexital in the past, but my go-to lately has been etomidate now that I'm at a hospital where it's not available. Never been a huge fan of ketamine for induction, same with propofol though I've certainly used both. For any delayed sequence I'm not using etomidate anyway. This is a bummer, etomidate (aside from Brevital) was my favorite induction agent.


(PIC FROM META-ANALYSIS ABOVE)

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[chessknt]

Idk man meta-analysis is highly dependent on input quality and complex statistical wizardry. We can't prove mortality benefit with all kinds of **** in CC studies yet they want us to believe that a non-etomidate RSI agent gets a mortality benefit? I can't see the full article but how do they account for different levels of severity of illness? I imagine etomidate is used more often in medical populations than surgical ICU populations, how do we account for that effect?

I'll wait for the more math-savvy members to weigh in but I wouldn't stop using etomidate because of this.

 

[SurfingDoctor]

I don't use a lot of etomidate, but if there's hemodynamic concerns, it's far more gentle compared to the other things they looked at like Versed, Propofol and Thiopental. Hell, even Ketamine can drop your BP. And mortality from what?

Also, relative adrenal insufficiency is a meaningless outcome and that term should probably be killed with fire or napalm.

 

[Tipsy McStagger]

This meta-analysis is not built on the strongest of evidence, not sure if it's a game changes or not. Will have to read back through some of these studies. I still like etomidate, there are so many confounding variables with critically ill patient's it's sometimes hard to see the forest for the trees.

 

[lymphocyte]

This meta-analysis is consistent with what has been published before and is not new. I think there are enough signals of harm around Etomidate to be concerned. We worry much more about things with way less evidence.

The excess mortality seems to correlate with increasing severity of underlying illness as measured by APACHE or SOFA and only seems to make a difference in the sickest of patients, so it probably doesn't matter most of the time.

I have no experience with Etomidate since it's not available in Australia. I use ketamine almost exclusively.

Etomidate, Adrenal Insufficiency and Mortality Associated With Severity of Illness: A Meta-Analysis - PubMed

Whereas etomidate causes adrenal insufficiency, it was not shown to increase mortality in many analyzed here in ICU settings. However, etomidate associated relative mortality rates increased progressively and correlated with the severity of critical illness scores. Intensivists should anticipate...

pubmed.ncbi.nlm.nih.gov

 

[SpacemanSpifff]

The study out of Parkland a couple years ago did make me think harder about etomidate, in the critically ill especially. I use a lot of ketamine already, usually with some combination of midazolam and/or fentanyl, so it didn’t change my practice per se. Usually I reserve etomidate for cardioversion.

Although it’s a pretty well done study the findings are curious - the ketamine group had significantly more hemodynamic compromise than etomidate, yet one week later more of them were alive? And that difference disappeared at one month? Possibly some effect of increased attentiveness to those who crashed peri-intubation?

 

[SurfingDoctor]

This meta-analysis is consistent with what has been published before and is not new. I think there are enough signals of harm around Etomidate to be concerned. We worry much more about things with way less evidence.

The excess mortality seems to correlate with increasing severity of underlying illness as measured by APACHE or SOFA and only seems to make a difference in the sickest of patients, so it probably doesn't matter most of the time.

I have no experience with Etomidate since it's not available in Australia. I use ketamine almost exclusively.

Etomidate, Adrenal Insufficiency and Mortality Associated With Severity of Illness: A Meta-Analysis - PubMed

Whereas etomidate causes adrenal insufficiency, it was not shown to increase mortality in many analyzed here in ICU settings. However, etomidate associated relative mortality rates increased progressively and correlated with the severity of critical illness scores. Intensivists should anticipate...

pubmed.ncbi.nlm.nih.gov

From the abstract:

Conclusions: Whereas etomidate causes adrenal insufficiency, it was not shown to increase mortality in many analyzed here in ICU settings. However, etomidate associated relative mortality rates increased progressively and correlated with the severity of critical illness scores. Intensivists should anticipate the need for glucocorticoid supplementation after etomidate in those with severe critical illness and in those with acute deterioration of vital signs.

This statement is utterly confusing, so it causes adrenal insufficiency, but that doesn't cause mortality so be sure to give hydrocortisone?
Interestingly, in this meta-analysis, the data and analysis is heavily weighted by the Annane hydrocortisone trial for sepsis from 2 decades ago. They didn't intend to study the type of sedation used in that trial, but since it wasn't randomized nor blinded, and knowing that Etomidate has a better hemodynamic profile compared to many other sedatives, one could easily imagine the sickest patients getting Etomidate and then invariably having worse outcomes not because of the Etomidate but because they were sicker.

Either way, I suppose someone should do a RTC to find the real answer (which, based on most critical care trials, would be a negative study... but sometime the field needs that to cut down the noise)

 

[SurfingDoctor]

The study out of Parkland a couple years ago did make me think harder about etomidate, in the critically ill especially. I use a lot of ketamine already, usually with some combination of midazolam and/or fentanyl, so it didn’t change my practice per se. Usually I reserve etomidate for cardioversion.

Although it’s a pretty well done study the findings are curious - the ketamine group had significantly more hemodynamic compromise than etomidate, yet one week later more of them were alive? And that difference disappeared at one month? Possibly some effect of increased attentiveness to those who crashed peri-intubation?

That's a good study as far as groups and randomization, though its a little problematic that there were significantly more SICU patients in the Etomidate group when I ran the data.

Table Analyzed​	Data 1​	​	​
​	​	​	​
P value and statistical significance​	​	​	​
Test​	Fisher's exact test​	​	​
P value​	0.0271​	​	​
P value summary​	*​	​	​
One- or two-sided​	Two-sided​	​	​
Statistically significant (P < 0.05)?​	Yes​	​	​
​	​	​	​
Effect size​	Value​	95% CI​	​
Attributable risk (P1 - P2)​	0.1080​	0.01470 to 0.2059​	​
NNT (reciprocal of attrib. risk)​	9.256​	4.856 to 68.04​	​
​	​	​	​
Methods used to compute CIs​	​	​	​
Attributable risk (P1 - P2)​	Newcombe/Wilson with CC​	​	​
​	​	​	​
Data analyzed​	Etomidate​	Ketamine​	Total​
MICU​	261​	286​	547​
SICU​	79​	56​	135​
Total​	340​	342​	682​

When they don't have a reason for why the Etomidate group had an early mortality difference, this seems like a potential confounder.