Jump to content

Etomindate


VentMedic

Recommended Posts

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 Science

The administration of etomidate has been linked to subsequent adrenocortical insufficiency in non-trauma patients but has not been well studied in the trauma population. These researches enrolled 30 multiple-trauma patients and randomized them to either receive etomidate (18 E patients) and succinylcholine, or a combination of fentanyl and midazolam (12 FM patients) with succinylcholine for RSI. They then measured their serum cortisol levels four to six hours afterward and performed a cortisol stimulation test by administering ACTH.

The patients reportedly had similar degrees of trauma and were aggressively resuscitated. They followed their clinical course and found the following. The serum cortisol levels of the 18 E patients was significantly lower than the FM patients and failed to respond to ACTH as well as the FM patients. This would consistent with suppression of the adrenal cortex.

Clinically, the patients in the E group required longer ICU stays (6.3 days versus 1.5 days, p < 0.05), more ventilator days (28 versus 17, p < 0.01), and longer hospital stays (11.6 days versus 6.4, p < 0.01) compared to the FM group.

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."

The Street

Just when you thought you had a handle on the RSI issue, someone comes along and throws another wrench in the works. The concern for adrenal insufficiency is why we abandoned high-dose steroids for suspected spinal injuries. Although I don't contest the cortisol levels the authors obtained in this study, I do question their conclusions.

First, the treating physicians were not blinded to which patients were in which group. They knew who was adrenosuppressed. Did this affect their treatment? The E group received significantly more intravenous fluids, blood and blood products. The authors state the patients had similar brain and lung injury severity scores, but we should take notice that the overall injury severity scores were higher (26 versus 19). Although not statistically significant, this may be due to the relatively low overall sample size of only 30 patients and the fact that 60% of the patients were in the E group.

The authors attempt to theorize that the adrenocortical insufficiency may have somehow altered the physiology of the E group in some way as to require their need for a greater need for volume replacement, but they do not provide us any supporting evidence for this theory. I would feel more confident if I knew more about the specific injuries of both groups. The injury severity score is simply not specific enough for such a small study group to make such generalizations.

Although this article sparks my interest, I'm not prepared to eliminate etomidate from my protocols just yet. More study is warranted, and I would ask future authors to be prepared to provide more details about the patient injuries so that we can attempt to determine what if any impact adrenocortical insufficiency, as it relates to etomidate administration, plays in the trauma victim.

********************************************************************************

Abstract of the orginal article:

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

Original Articles

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

Abstract:

Background: The administration of etomidate for rapid sequence induction (RSI) has been linked to subsequent adrenocortical insufficiency in nontrauma patients. However, etomidate-related adrenocortical insufficiency has not been well studied in the trauma population.

Purpose: We performed a prospective, randomized, controlled study to assess the effect of one dose of etomidate for RSI on adrenal function and its clinical significance during and after resuscitation in trauma patients.

Methods: Adult trauma patients admitted to our Level I trauma center requiring RSI were randomized to receive etomidate 0.3 mg/kg and succinylcholine 1 mg/kg (E group) or fentanyl 100 [mu]g, midazolam 5 mg, and succinylcholine 1 mg/kg (FM group) for induction. A baseline serum cortisol level was drawn before RSI. Four to six hours after RSI, a postintubation serum cortisol level was drawn. An ACTH stimulation test was performed.

Results: Thirty patients were enrolled: 18 E group patients and 12 FM group patients. No statistical difference was detected between the two groups with respect to age, injury severity score, and baseline serum cortisol. Mean serum cortisol levels were significantly lower in E group patients than in FM group patients 4 to 6 hours after intubation (18.2 vs. 27.8 [mu]g/dL, p < 0.05). Change in serum cortisol between baseline and postintubation levels was different (-12.8 [mu]g/dL +/- 9.6 [mu]g/dL vs. 1.1 [mu]g/dL +/- 7.6 [mu]g/dL, p < 0.01). Patients in the E group had an average increase in cortisol after ACTH administration of 4.2 [mu]g/dL +/- 4.9 [mu]g/dL vs. 11.2 [mu]g/dL +/- 6.1 [mu]g/dL in the FM group, p < 0.001. Patients in the E group required longer ICU lengths of stay (mean, 6.3 days vs. 1.5 days, p < 0.05), more ventilator days (mean, 28 days vs. 17 days, p < 0.01), and longer hospital lengths of stay (mean, 11.6 days vs. 6.4 days, p < 0.01).

Conclusions: The use of etomidate for RSI in trauma patients led to chemical evidence of adrenocortical insufficiency and may have contributed to increased hospital and ICU lengths of stay and increased ventilator days. Further studies should be considered to evaluate the safety profile of this drug in trauma patients.

Link to comment
Share on other sites

  • Replies 72
  • Created
  • Last Reply

Top Posters In This Topic

p3, since you bring up the topic of power, a few questions for you. What n would you need to improve the power of the study? Do you think we can draw conclusions based on the p values all being <.05?

Link to comment
Share on other sites

This the outline of the study and how it was set up with inclusions and exclusions.

http://www.clinicaltrials.gov/ct2/show/NCT...ate"&rank=6

The original article came with a long list of references cited. The article in JEMS by Dr. Wesley was a review of just one study. But, you would have read the original article for all of the references cited and the reasoning of the researcher for conducting the study. One must be aware that the opinions for just one article may not be a blanket statement for Etomindate applications or studies.

REFERENCES

1. Bergen JM, Smith DC. A review of etomidate for rapid sequence

intubation in the emergency department. J Emerg Med. 1997;

15:221–230.

2. de Jong FH, Mallios C, Jansen C, Scheck PA, Lamberts SW.

Etomidate suppresses adrenocortical function by inhibition of 11

beta-hydroxylation. J Clin Endocrinol Metab. 1984;59:1143–1147.

3. Ledingham IM, Watt I. Influence of sedation on mortality in

critically ill multiple trauma patients. Lancet. 1983;1:1270.

4. Watt I, Ledingham IM. Mortality amongst multiple trauma patients

admitted to an intensive therapy unit. Anaesthesia. 1984;39:973–981.

5. Fellows IW, Bastow MD, Byrne AJ, Allison SP. Adrenocortical

suppression in multiply injured patients: a complication of etomidate

treatment. Br Med J (Clin Res Ed). 1983;287:1835–1837.

6. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D.

Inhibition of adrenal steroidogenesis by the anesthetic etomidate.

N Engl J Med. 1984;310:1415–1421.

7. Allolio B, Dorr H, Stuttmann R, Knorr D, Engelhardt D,

Winkelmann W. Effect of a single bolus of etomidate upon eight

major corticosteroid hormones and plasma ACTH. Clin Endocrinol

(Oxf). 1985;22:281–286.

8. Allolio B, Stuttmann R, Leonhard U, Fischer H, Winkelmann W.

Adrenocortical suppression by a single induction dose of etomidate.

Klin Wochenschr. 1984;62:1014 –1017.

9. Wagner RL, White PF. Etomidate inhibits adrenocortical function in

surgical patients. Anesthesiology. 1984;61:647– 651.

10. Fragen RJ, Shanks CA, Molteni A, Avram MJ. Effects of etomidate

on hormonal responses to surgical stress. Anesthesiology. 1984;

61:652– 656.

11. Duthie DJ, Fraser R, Nimmo WS. Effect of induction of anaesthesia

with etomidate on corticosteroid synthesis in man. Br J Anaesth.

1985;57:156 –159.

12. Fellows IW, Yeoman PM, Selby C, Byrne AJ. The effect of

anaesthetic induction with etomidate on the endocrine response to

surgical trauma. Eur J Anaesthesiol. 1985;2:285–290.

13. De Coster R, Helmers JH, Noorduin H. Effect of etomidate on

cortisol biosynthesis: site of action after induction of anaesthesia.

Acta Endocrinol (Copenh). 1985;110:526 –531.

14. Borner U, Gips H, Boldt J, Hoge R, von Bormann B, Hempelmann

G. [Effect of an introductory dose of etomidate, methohexital and

midazolam on adrenal cortex function before and after ACTHstimulation.]

Dtsch Med Wochenschr. 1985;110:750 –752.

15. Fragen RJ, Weiss HW, Molteni A. The effect of propofol on

adrenocortical steroidogenesis: a comparative study with etomidate

and thiopental. Anesthesiology. 1987;66:839–842.

16. Mallios C, Scheck PA, de Jong FH, Lamberts SW. [Transient inhibition

of adrenal cortex function following induction of anesthesia with

etomidate.] Ned Tijdschr Geneeskd. 1987;131:918–920.

17. Diago MC, Amado JA, Otero M, Lopez-Cordovilla JJ. Anti-adrenal

action of a subanaesthetic dose of etomidate. Anaesthesia. 1988;

43:644–645.

18. Sear JW, Edwards CR, Atherden SM. Dual effect of etomidate on

mineralocorticoid biosynthesis. Acta Anaesthesiol Belg. 1988;

39:87–94.

19. Jameson P, Desborough JP, Bryant AE, Hall GM. The effect of

cortisol suppression on interleukin-6 and white blood cell responses

to surgery. Acta Anaesthesiol Scand. 1997;41:304 –308.

20. Zhang Y, Luo A, An G, Huang Y. [Effect of propofol and

etomidate for anesthesia induction on plasma total cortisol

concentration.] Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2000;

22:284 –286.

21. Montalban C, Del Moral I, Garcia-Unzueta MT, Villanueva MA,

Amado JA. Perioperative response of leptin and the tumor necrosis

factor alpha system in morbidly obese patients. Influence of cortisol

inhibition by etomidate. Acta Anaesthesiol Scand. 2001;45:207–212.

22. Fillinger MP, Rassias AJ, Guyre PM, et al. Glucocorticoid effects

on the inflammatory and clinical responses to cardiac surgery.

J Cardiothorac Vasc Anesth. 2002;16:163–169.

23. Oglesby AJ. Should etomidate be the induction agent of choice for

rapid sequence intubation in the emergency department? Emerg Med

J. 2004;21:655– 659.

24. Schenarts CL, Burton JH, Riker RR. Adrenocortical dysfunction

following etomidate induction in emergency department patients.

Acad Emerg Med. 2001;8:1–7.

25. Absalom A, Pledger D, Kong A. Adrenocortical function in critically

ill patients 24 h after a single dose of etomidate. Anaesthesia. 1999;

54:861– 867.

26. Malerba G, Romano-Girard F, Cravoisy A, et al. Risk factors of

relative adrenocortical deficiency in intensive care patients needing

mechanical ventilation. Intensive Care Med. 2005;31:388 –392.

27. Mohammad Z, Afessa B, Finkielman JD. The incidence of relative

adrenal insufficiency in patients with septic shock after the

administration of etomidate. Crit Care. 2006;10:R105.

28. Cohan P, Wang C, McArthur DL, et al. Acute secondary adrenal

insufficiency after traumatic brain injury: a prospective study. Crit

Care Med. 2005;33:2358 –2366.

29. Schulz-Stubner S. Sedation in traumatic brain injury: avoid

etomidate. Crit Care Med. 2005;33:2723; author reply 2723.

30. Cotton BA, Guillamondegui OD, Carpenter RO, Morris JA, Patel

SH, Fleming S. Etomidate use in the critically injured patient is

associated with an increased risk of adrenal insufficiency. Crit Care

Med. 2005;33:A46.

31. Cunitz G, Soerensen N. Control of intracranial pressure during

pediatric neurosurgery anesthesia. Childs Brain. 1978;4:205–215.

32. Nicholson G, Bryant AE, Macdonald IA, Hall GM. Osteocalcin and

the hormonal, inflammatory and metabolic response to major

orthopaedic surgery. Anaesthesia. 2002;57:319 –325.

33. Ho JT, Al-Musalhi H, Chapman MJ, et al. Septic shock and sepsis: a

comparison of total and free plasma cortisol levels. J Clin Endocrinol

Metab. 2006;91:105–114.

34. Arafah BM. Hypothalamic pituitary adrenal function during critical

illness: limitations of current assessment methods. J Clin Endocrinol

Metab. 2006;91:3725–3745.

35. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum

free cortisol in critically ill patients. N Engl J Med. 2004;

350:1629 –1638.

Link to comment
Share on other sites

I've heard of Etomidate being used in double dosage (0.6 mg/kg) when Succinylcholine is not available. I don't know if this practice is current or dated, but wouldn't their be even greater concern with patients who received this treatment? Is this something that has been added to a similar study?

Link to comment
Share on other sites

I've heard of Etomidate being used in double dosage (0.6 mg/kg) when Succinylcholine is not available. I don't know if this practice is current or dated, but wouldn't their be even greater concern with patients who received this treatment? Is this something that has been added to a similar study?

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.

Link to comment
Share on other sites

This study seems a little odd to me. They're trying to isolate the effect of etomidate, and yet they are comparing treatment regimens that differ on more than on level. Group "E" got etomidate and suxx. Group "FM" got fentanyl, versed, and suxx. Aren't those two completely different paths of treatment? How can they say that the endpoint differences between the groups can be attributed to only the etomidate? Why cant they say it's because of the versed? Or the fentanyl? The groups differed in those drugs, as well. Seems to me there are a lot of confounding factors here, and statistical trickery can only go so far to eliminate them.

p3, since you bring up the topic of power, a few questions for you. What n would you need to improve the power of the study? Do you think we can draw conclusions based on the p values all being <.05?

I'm no stats whiz, but...

Increasing the sample size (n) would of course increase the power of the study, but calculating the exact size necessary is a bit esoteric, and requires distribution knowledge about the population that I don't believe we have. What I also don't know is how sensitive this study really needs to be, as I'm not sure how fine the measurements of cortisol truly are. Are these lab levels normally highly variable or are they steady? The former would require a higher power (bigger sample) study, the latter could probably do with a smaller one.

The p value is the percentage chance that the null hypothesis was rejected in error (a type I error). Basically, it is the percentage chance that the difference between the two groups is due to chance rather than the treatment. The smaller the sample size, the more likely these types of errors are to occur. Therefore, we must set our alpha level (the "cutoff" point for the p value) lower for smaller sample sizes. <0.01 would probably be more appropriate here.

Link to comment
Share on other sites

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.

My guess is that it was used to circumvent the absence of RSI protocols, but I don't know for sure. :dontknow: It didn't sound like it's a common practice, but then again, common and EMS don't seem to go together well.

Link to comment
Share on other sites

fiznat, the selected drugs are appropriate for the purposes of this study. The reason for the study was to assess the effect of etomidate on adrenal function and its clinical significance during and after resuscitation in trauma patients. They wanted to see if there was a clinically significant change in cortisol levels when pts are given etomidate. You would want to use something on your control group that did not cause adrenal suppression, which is why fentanyl and versed were used. A p-value of <.05 is the accepted value to determine if something is clinically significant or not. What it tells you is that there is a less than 5% chance that the results you got from your study are due to chance and not due to a tue difference. There is no reason to change your p-value. Despite the fact that there was a small enrollment, you still have a study that has shown statistical significance.

Link to comment
Share on other sites

This thread is quite old. Please consider starting a new thread rather than reviving this one.

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.


×
×
  • Create New...