Etomidate & adrenal suppress. - OK to use-may add steroids

[IVAN HRONEK]

Markus,
 
it's hard to know what they are talking about in the papers you listed, MDconsult lists only citations. Can you mail the actual articles or abstracts so we'd know what we are talking about  ?
I do believe in many situations there is no replacement for Etomidate and we use it like water - and here's my reasons:
 
 




Adrenocortical dysfunction following etomidate induction in emergency department patients. - Schenarts CL - Acad Emerg Med - 01-JAN-2001; 8(1): 1-7 (From NIH/NLM MEDLINE) 

OBJECTIVE: To assess adrenocortical function following intravenous etomidate use in emergency department (ED) patients requiring intubation. METHODS: This was a prospective, randomized, controlled trial of consecutive patients presenting to the ED requiring intubation. Patients were randomized to receive a single bolus induction dose of either 0.05-0.1 mg/kg midazolam (control group) or 0.3 mg/kg etomidate (etomidate group) during a standardized rapid-sequence intubation (RSI) with succinylcholine. The primary outcome variable was adrenocortical function at 4, 12, and 24 hours post-induction as assessed by measured serum cortisol response to exogenous cosyntropin (cosyntropin stimulation test, CST). Fisher's exact test was used to compare CST results between groups. RESULTS: Thirty-one patients were enrolled: 8 control, 10 etomidate, and 13 excluded from analysis for either incomplete data or steroid use during the study period. The 4-hour CST results were significantly different between study groups, with a normal response in 100% of control patients vs 30% of etomidate patients (p = 0.004). The 12- and 24-hour CSTs did not differ significantly between groups: normal CST in 100% of control patients at 12 and 24 hours vs 100% and 90% among etomidate patients at 12 and 24 hours, respectively (p = 1.0 at 12 and 24 hours). Measured cortisol levels of patients with abnormal CSTs remained within normal laboratory reference ranges. CONCLUSION: Use of etomidate in ED patients requiring RSI results in adrenocortical dysfunction. However, cortisol levels remain within normal laboratory levels during this period of dysfunction. Adrenocortical dysfunction appears to resolve within 12 hours of a single bolus dose of 0.3 mg/kg 
etomidate.
 
Should etomidate be the induction agent of choice for rapid sequence intubation in the emergency department?Oglesby AJ - Emerg Med J - 01-NOV-2004; 21(6): 655-9
 
The ideal induction agent for emergency airway management should be rapidly acting, permit optimum intubating conditions, and be devoid of significant side effects. This review was performed to ascertain whether etomidate should be the induction agent of choice for rapid sequence intubation (RSI) in the emergency department, specifically examining its pharmacology, haemodynamic profile, and adrenocortical effects. A search of Medline (1966-2002), Embase (1980-2002), the Cochrane controlled trials register, and CINAHL was performed. In addition, the major emergency medicine and anaesthesia journals were hand searched for relevant material. Altogether 144 papers were identified of which 16 were relevant. Most studies were observational studies or retrospective reviews with only one double blind randomised controlled trial and one un-blinded randomised controlled trial. Appraisal of the available evidence suggests that etomidate is an effective induction agent for emergency department RSI; it has a rapid onset of anaesthesia and results in haemodynamic stability, even in hypovolaemic patients or those with limited cardiac reserve. Important questions regarding the medium to long term effects on adrenocortical function (even after a single dose) remain unanswered.

 





Etomidate for Endotracheal Intubation in Sepsis
Chest - Volume 127, Issue 3 (March 2005)  -  Copyright © 2005 The American College of Chest Physicians  -  About This Journal 



Editorials


Etomidate for Endotracheal Intubation in Sepsis
Acknowledging the Good While Accepting the Bad
We would like to commend Dr. Jackson (see page 1031) on both his historical review and critical appraisal of the use of etomidate as an anesthetic induction agent. This appraisal is a good summary of the debate that has occurred over the past quarter century in regard to the safety of etomidate as an anesthetic induction agent. The observations of Led ingham and Watt[1] in the early 1980s indicated that etomidate should not be used for long-term sedation in the ICU due to the mortality cost incurred from long-term adrenal suppression. The effect of etomidate on adrenal function is both dose-dependent and cumulative. A single dose of etomidate will blunt the adrenocortical axis for up to 24 h. The effect of short-term suppression of adrenal synthesis on patient outcome is, however, less clear. This clinical question, although seemingly simple, is quite complex. The net effect of etomidate as an anesthetic induction agent is the sum of several factors. Etomidate has several properties, which makes it, at least in theory, a good first-line anesthetic induction agent. The dose required to achieve unconsciousness is relatively predictable. This hypnotic effect is much more predictable than that with benzodiazepines. The onset of action is fast, essentially in one arm to brain circulation. In addition, etomidate has a short duration of action. Etomidate does not cause histamine release, which is a factor contributing to its relative hemodynamic stability (the reader is referred to an in-depth clinical review of the pharmacology of etomidate[2] ). One would expect that these factors would result in a mortality benefit; however, the magnitude of this benefit is unknown. The major concern regarding the use of etomidate is transient adrenal suppression. The unpublished subgroup analysis data presented in the study by Annane et al[3] may provide us with a glimpse of the cost resulting from the adrenal suppression by etomidate. The fact that 68 of the 72 patients (94%) who received etomidate for the induction of anesthesia did not respond to a high-dose cosyntropin stimulation test, is consistent with other published reports of adrenal insufficiency 12 to 24 h after the administration of etomidate. The data from the study by Annane et al[3] seems to indicate a significant mortality cost for etomidate anesthetic induction in septic patients. The mortality rate in the placebo-treated group was 75.7% vs 54.8% for the corticosteroid-treated group. These data indicate that the adrenal insufficiency of sepsis should be treated with the administration of stress doses of corticosteroids. The continued use of etomidate for anesthesia induction would be a clinical conundrum if this mortality effect persisted despite corticosteroid administration. From the available data, we have a presumed, but have not yet measured, mortality benefit incurred from the beneficial effects of etomidate as an anesthetic induction agent. The mortality cost of adrenal suppression by etomidate anesthesia induction seems to be completely offset by corticosteroid administration in those patients who show evidence of adrenal insufficiency. As a result, we feel that the net effect still favors the use of etomidate as an anesthesia induction agent.
The choice of induction agent in hemodynamically labile septic patients is inherently complex, as no perfect anesthesia induction agent exists. Midazolam is typically underdosed when used as the sole anesthetic induction agent, and the time to peak effect is unpredictable.[4] Propofol and barbiturate induction delivers rapid, predictable unconsciousness, with equally predictable hypotension. Ketamine is perhaps the only available agent that provides equally favorable sedation and hemodynamic qualities as those of etomidate, but with its own set of adverse reactions. Dr. Jackson suggests that the induction of unconsciousness and adequate muscular relaxation are measures of the utility of an anesthetic induction agent. We would like to reinforce the notion that these are different issues. Firstly, look at intubation success, and the optimal laryngeal view is best facilitated by muscular relaxation in the form of paralysis. Achieving this level of relaxation with most anesthetic induction agents will only further worsen hypotension during intubation. Furthermore, many of these patients should be considered to have full stomachs, and a rapid-sequence intubation with both an anesthetic induction agent and a paralytic agent should limit the risk of aspiration.
Sepsis continues to be a high-mortality illness. Optimal treatment requires attention to detail and the implementation of many time-dependent therapies starting at the recognition of occult sepsis. We should strive for early empiric antibiotic administration. Early goal-directed resuscitation, as proposed by Rivers et al,[5] has been shown to reduce mortality in this patient population. The treatment of sepsis-induced adrenal insufficiency and tight glycemic control play a significant role in reducing mortality. High-risk patients benefit from the administration of activated protein C. The treatment of sepsis at this time is akin to our current understanding of acute myocardial infarction. There is no magic bullet; rather, several therapies must be quickly brought to bear on this complex pathologic state to maximize the benefit of each intervention while limiting the incurred risk. In our minds, the same holds true for the intubation of a septic patient. This is a high-stakes intervention with a large potential cost if it is not performed well. Significant aspiration or a prolonged period of hypotension may well abolish any benefit from all of the above therapies. We think that etomidate is still a very good agent for the induction of unconsciousness, and when combined with muscle relaxation provides the best scenario for rapid, smooth, hemodynamically stable intubation. The ba sics of care, the "ABCs," should not be forgotten. Immediate correction of respiratory failure should be performed in a manner that impacts the circulatory system the least. In a Dutch study, Arbous et al[6] demonstrated that about two thirds of the mortality during the induction phase of anesthesia was due to cardiovascular events. This underscores the need for hemodynamic stability during anesthesia induction. Etomidate provides the stability and predictability needed to be a first-line agent. From a practical standpoint, a better anesthetic induction agent is simply not available. As Jackson states it, it is sometimes necessary to stabilize the immediate situation while accepting a future cost. In this case, the future cost is adrenal suppression. Fortunately, the limited available data indicate that this effect is completely reversed with the administration of corticosteroids. For this reason, we think that all hypotensive septic patients should be treated with stress doses of corticosteroids, particularly if the random (stress) cortisol level is < 25 μg/dL.[7] We recommend initiating therapy with hydrocortisone, 100 mg IV every 8 h, until the results of the stress cortisol level measurements are available. The "cost" of such an approach is likely to be very low, and the potential benefit to be quite high. The cost of such an approach is likely to be very low, and the potential benefit to be quite high.
Dr. Murray is Chief Fellow, Department of Critical Care Medicine, University of Pittsburgh Medical Center. Dr. Marik is Chief of Pulmonary and Critical Care Medicine, Thomas Jefferson University.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions at chestnet.org).
Correspondence to: Paul E. Marik, MD, FCCP, Chief of Pulmonary and Critical Care Medicine, Thomas Jefferson University, 1015 Chestnut Street, Suite M100, Philadelphia, PA 19107; e-mail: paul.marik at jefferson.eduIvan Hronek MDChief, Critical Care & Trauma AnesthesiaSFMC Gas, Inc.Lynwood, CA 90262 Cell: 310 487-3288Pager: 310 636-6020



> Date: Thu, 2 Aug 2007 11:47:10 +0200> From: markus.weis at med.lu.se> To: trauma-list at trauma.org> Subject: Re: Etomidate> > An editorial in Anaesthesia in 2005 (1) stated that etomidate had been> withdrawn in the United States, Australia, Canada and the Republic of> Ireland. Apparently this was based on information from a pharmaceutical> company and in correspondence (2) to the article it showed to be incorrect,> at least regarding it being withdrawn in the United States.> > The editorial was published two years ago, but sometimes rumours don't stop> circulating...> > BFM: What do you use instead of etomidate?> > Markus> > > (1) Morris C, McAllister C. Etomidate for emergency anaesthesia: mad, bad> and dangerous to know? Anaesthesia 2005; 60: 737-40.> (2) Jackson MT, Ramos AS. Etomidate - misused or misunderstood? Anaesthesia> 2006; 61: 191.> > On Thu, 02 Aug 2007 09:15 +0100 (BST), Blueflightmedic <> trauma at emergencyunit.com> wrote:> >> > Firstly congratulations to all those who responded so magnificently in> > Minneapolis. Condolences to the bereaved. The news broke here in the UK> > at 1 AM just as I was returning home from dealing with a very nasty> > head-on RTC; three serious, 1 died in my hands on scene from massive> > haemorrhage - probably ruptured liver.> >> > Etomidate is rapidly becoming a drug to avoid because of its prolonged> > suppressant effect on the adrenal response. We though initially that it> > was only infusions that caused the problem but there is now good evidence> > that a single induction dose of etomidate causes problems for some days,> > and patients with multiple trauma or severe sepsis do not need adrenal> > suppression. We scarcely ever use it now.> >> >> > > *From:* "Hardcastle, Tim, Dr < tch at sun.ac.za>" <tch at sun.ac.za>> > > *To:* "Trauma-List (E-mail)" <trauma-list at trauma.org >> > > *Date:* Thu, 2 Aug 2007 07:11:01 +0200> > >> > > Hi all> > >> > > A query regarding Etomidate: there is a rumour spreading around> > > South Africa that Etomidate has been "black-boxed" by the FDA and> > > this includes a warning to not use it for RSI. I have been unable> > > to confirm this on their website, but maybe I don't have adequate> > > access. Any list member out tere form the USA who can confirm /> > > deny / give the correct details, so we can give clear guidelines -> > > we still use Etomidate for our RSI in NON-SEPTIC patients (i.e.> > > acute trauma).> > >> > > My reading of the literature does not support avoiding of Etomidate> > > in trauma, with only one study in head trauma suggesting a possible> > > link.> > >> >> > BFM> > --> > trauma-list : TRAUMA.ORG> > To change your settings or unsubscribe visit:> > http://www.trauma.org/index.php?/community/> >> --> trauma-list : TRAUMA.ORG> To change your settings or unsubscribe visit:> http://www.trauma.org/index.php?/community/