Etomindate

[p3medic]

I'm not sure what I would consider an adequate sample size, however I know 18 is way too few. Any given trauma center could generate 100 times those numbers of patients, which to me would hold a lot more water. There are too many variables with human physiology to accept this small a population when deciding to remove a drug from the RSI toolbox. We all know adrenal suppression happens, how clinically significant that is can't be derived from this small study. (I haven't read the study in its entirety, only the abstract.)

[ERDoc]

I'm not sure what I would consider an adequate sample size, however I know 18 is way too few. Any given trauma center could generate 100 times those numbers of patients, which to me would hold a lot more water. There are too many variables with human physiology to accept this small a population when deciding to remove a drug from the RSI toolbox. We all know adrenal suppression happens, how clinically significant that is can't be derived from this small study. (I haven't read the study in its entirety, only the abstract.)

I think, based on the statistics, it was a fairly good study. I don't think anyone is advocating getting rid of etomidate. The next step would be to give solumedrol, solucortef, etc with the etomidate and repeat the study.

[p3medic]

The research thread by fiznat gives me an opportunity to present this topic in hopefully a scientific perspective.

The review on JEMS.com

Etomidate and Adrenocortical Insufficiency in the Trauma Patient

Keith Wesley, MD, FACEP

Street Science

2009 Jan 5

Review of: Hildreth AN, Mejia VA, Maxwell RA, et al: "Adrenal suppression following a single dose of etomidate for rapid sequence induction: A prospective randomized study." Journal of Trauma. 65(3):573–579, 2008.

The authors conclude that the use of etomidate for RSI in trauma patients let to chemical evidence of adrenocortical insufficiency and may have contributed to the clinical findings listed above. In the text of the article, the authors make this statement: "In light of our study, we recommend that other drugs should be used as first-line agents for RSI in trauma patients."

It seems they are suggesting that etomidate should be replaced by another, or combination of agents for induction of the trauma patient. I can't see changing clinical practice based on this one study, which in my opinion is very light on number of patients. Etomidate has the least effect on hemodynamics, much less than versed, and certainly less than a versed/fenanyl combination. You have seen in your own practice the variability of response to these agents. Does morbidity/mortality worsen in trauma patients that have a precipitous drop in blood pressure secondary to opiate/benzo induction? Do patients recieve adequate sedation with opiate/benzo v.s. etomidate? (For the procedure) Does a single dose of etomidate supress adrenal function enough to worsen outcomes?

[ERDoc]

I must appologize p3, I did not read the JEMS article. I skipped to the original study and pulled it up on pubmed. I was not able to access the full original article. The abstract does not say that the authors of the original study said, "In light of our study, we recommend that other drugs should be used as first-line agents for RSI in trauma patients," as the JEMS article reports. Maybe in the full paper it does, but their conclusions in the abstract say that more research is needed.

To answer a few of your questions, I prefer etomidate over fentanyl/versed. I my experience (which obviously is not even close to a reasonable study) they do not provide adequate sedation. Fentanyl will not cause a significant hemodynamic affect (which is why it is ideal for pain control in the early management of trauma). Versed on the other hand, well, you know how that goes. I think this study shows that there is a significant difference in clinical measures between the two groups. I do agree that a larger scale study needs to be done but this is how research works. We get a small study to see if there is a difference and then perform larger studies that confirm the original findings. This study was also done on a trauma population. I would like to see the same study done on medical pts that receive etomidate for RSI. It definitely makes me consider changing my practice to give a stress dose of steroids.

[VentMedic]

[

Etomidate and Adrenocortical Insufficiency in the Trauma Patient

Keith Wesley, MD, FACEP

Street Science

2009 Jan 5

Review of: Hildreth AN, Mejia VA, Maxwell RA, et al: "Adrenal suppression following a single dose of etomidate for rapid sequence induction: A prospective randomized study." Journal of Trauma. 65(3):573–579, 2008.

The authors conclude that the use of etomidate for RSI in trauma patients let to chemical evidence of adrenocortical insufficiency and may have contributed to the clinical findings listed above. In the text of the article, the authors make this statement: "In light of our study, we recommend that other drugs should be used as first-line agents for RSI in trauma patients."

It seems they are suggesting that etomidate should be replaced by another, or combination of agents for induction of the trauma patient. I can't see changing clinical practice based on this one study, which in my opinion is very light on number of patients.

That is why I prefer to pull up the original article to see exactly what was said and not just one sentence that may be surrounded by other pertinent information. JEMS authors have a tendency to over simplify and insert their own opinions. Unfortunately some do take JEMS as "the absolute truth" and look no further.

Adrenal Suppression Following a Single Dose of Etomidate For Rapid Sequence Induction: A Prospective Randomized Study.

Original Articles

more from the article

Journal of Trauma-Injury Infection & Critical Care. 65(3):573-579, September 2008.

Hildreth, Amy N. MD; Mejia, Vicente A. MD; Maxwell, Robert A. MD; Smith, Philip W. MD; Dart, Benjamin W. MD; Barker, Donald E. MD

DISCUSSION

Etomidate has been used for many years as an induction agent for RSI in trauma patients. Advantages of etomidate in this population include easy dosing and administration, minimal cardiovascular effects during induction and a short duration of sedation. There has also been a reported reduction in intracranial pressure which may have obvious advantages in head injury patients.31 Numerous studies have demonstrated that etomidate produces chemical evidence of adrenocortical suppression when given as a single dose.6–20,25–28,30 However, a difference in clinical outcomes related to chemical adrenocortical suppression has not been prospectively evaluated in the trauma patient population. However, the possibility that etomidate causes chemical adrenocortical suppression after a single dose raises concern for its safety in the trauma population who may have minimal physiologic reserve.

This study prospectively evaluates the effect of etomidate on total serum cortisol and outcomes in trauma patients. Physiologic data and resuscitation values were recorded for the 24 hours immediately after dosing because previous studies have shown that the effects of etomidate as a single dose usually resolve within 12 to 24 hours after administration.7–10,12–20,22,32 Although patients in both E and

FM Groups had equivalent baseline physiologic characteristics, after induction, the two groups developed noteworthy differences. Consistent with the findings of previous studies, the E Group patients had significantly lower postintubation and post-CST serum cortisol levels. E Group patients required

more packed cells, FFP, and intravenous fluid than FM Group patients in the first 24 hours after RSI. Urine

output was similar between groups indicating similar adequacy of resuscitation.

We theorize that the E group patients received more blood products and intravenous fluids because of physiologic alterations. E group patients had significantly longer ICU and hospital lengths of stay and more ventilator days, although these patients had similar lung and brain injuries as analyzed by AIS. The only patients who required vasopressors, decompression for abdominal compartment syndrome, or expired

were in the E Group. Together these findings suggest that the suppression of adrenocortical function caused by etomidate leads to subtle hemodynamic instability and greater resuscitation requirements, which ultimately may result in more ventilator days, increased hospital and ICU length of stay, and possibly mortality.

In our study, we measured total serum cortisol concentrations. Critical illness has been shown to variably depress concentrations of circulating cortisol-binding proteins. Concurrently, marked elevations in free serum cortisol occur independent of total serum cortisol level.33–35 It is difficult, if not impossible, to analyze free serum cortisol status based on total serum cortisol levels. In fact, different values may be

obtained with different total serum cortisol assays. In the present setting, it is likely that the E Group patients had lower free serum cortisol concentrations as well as lower total serum cortisol concentrations, as evidenced by outcome differences between the groups. We were not able to test directly whether depression of total serum cortisol concentration after etomidate also represented depression of free serum cortisol concentration, a measurement better representing adrenocortical

function, because an assay of free serum cortisol with validated reference ranges in trauma is not yet available.

Our study had other limitations. It was a small trial at a single institution. We were unable to blind the study because of constraints imposed by our facility’s Institutional Review Board. Therefore, this inability to blind the study may have led to bias. In addition, all patients were resuscitated at the discretion of each attending trauma surgeon. There were no standardized resuscitation guidelines, and we depended on

the clinical judgment of the attending trauma surgeon to analyze adequacy of resuscitation. We did not designate a transfusion threshold hematocrit, and this could have led to bias concerning amount of packed red blood cells transfused. We had some difficulty with patient recruitment, in large part because of protocol violations that occurred as hospital and prehospital air medical personnel were becoming acquainted with the study protocol. In addition, the clinical data in this study were only accumulated over a 24-hour time period after RSI. Clinical data accrual over a longer time period may have led to a better understanding of the differences between the two groups in outcome variables.

In conclusion, we assert that single-dose etomidate for RSI suppresses serum total cortisol in trauma patients. Our patient outcomes suggest that this suppression is indicative of decreased adrenocortical function in these patients. In light of the results of our study, we recommend that other drugs should be used as first-line agents for RSI in trauma patients. Any report suggesting suppression of adrenal function in critical illness should include data pertaining to the use of etomidate. Further study should be undertaken to evaluate the safety of etomidate use for RSI in trauma patients.

ERdoc

I would like to see the same study done on medical pts that receive etomidate for RSI. It definitely makes me consider changing my practice to give a stress dose of steroids.

Look at the long list of references I posted from this trauma article. They appear to have the thought, "it this occurs in sepsis patients, what about trauma".

It was the sepsis articles that changed our thinking somewhat where I work. I just happened on this article from "reading JEMS". But, if the article interest me, I pull up the orgiinal or the abstract if I am not on the University or hospital computer to see how they derived at their conclusions.

The article is 7 pages but I will try to post more excerts that may be relevant.

[ambodriver]

Wow, why do that? You are not going to have the same action as sux by doubling your etomidate dose. From what I understand, a single "normal" dose of etomidate has been shown to cause adrenal suppression. At one time, etomidate was used for ongoing sedation in ICU's; however, the practice was stopped and now etomidate is not to be given in follow up doses or for ongoing sedation.

I do not think anybody can argue the fact that adrenal suppression can occur with etomidate. However, I am not ready to convert to some other agent. I am curious to see what other studies find; however, when compared to the alternatives, I still like the advantages etomidate brings to the table. In addition, with the push to "stress dose" people with steroids, I will be curious to see how the whole etomidate concept pans out.

I have also been in at least two discussions about etomidate on flightweb.

Take care,

chbare.

In our system, if we RSI with Etomidate and there is a head injury we automatically goto .6mg/kg as opposed to the normal .3 mg/kg

[Niftymedi911]

Ambo,

Is the double dose an effort to decrease the ICP in head injury patient's??

[ERDoc]

I have to agree. The 0.6mg/kg doesn't make sense. Why give more than you need to? I have never seen a pt that couldn't be brought down with 0.3mg/kg.

[chbare]

Some providers may use 06. mg/kg; however, to give a double dose of etomidate to compensate for the lack of sux is a dangerous precedent to set and defeats the purpose of RSI. Regardless of the 0.3 mg/kg or 0.6 mg/kg dose, etomidate is not a replacement for paralysis.

Take care,

chbare.

[ERDoc]

Some providers may use 06. mg/kg; however, to give a double dose of etomidate to compensate for the lack of sux is a dangerous precedent to set and defeats the purpose of RSI. Regardless of the 0.3 mg/kg or 0.6 mg/kg dose, etomidate is not a replacement for paralysis.

Take care,

chbare.

You are correct. Etomidate should not be a substitiute. I assumed that when ambo said that the higher dose etomidate was used during RSI, that they were still paralysing the person (otherwise it would not be RSI).