1	100	100	100	100	–	–	–	–	–	–
2	52	57	85	85	–	1	–	–	–	–
3	47	76	80	95	–	–	–	–	–	–
4	85	80	95	100	3	3	–	–	–	–
5	NA	50	NA	71	4	5	–	–	1	1
6	66	80	100	100	3	3	–	–	–	–
7	76	76	84	90	3	2	2	2	–	–
8	42	57	78	95	4	4	2	2	–	–
9	NA	14	NA	61	6	5	–	–	1	2
10	47	61	90	85	1	–	–	–	3	–
11	100	100	100	100	–	–	–	–	–	–
12	42	38	90	85	1	1	–	–	–	–
13	100	100	100	100	–	–	–	–	–	–
14	85	76	90	80	–	–	2	2	2	2
Average a	70.2	75.1	91.0	92.9
Note: The rate of correct response indicates correct response at both occasions (6-10 days in between) for the 2 groups of respondents. Raw Agreement Measure indicates the agreement in the response irrespective of right or wrong response. Don’t know means that the respondents chose the response alternative “Don’t know”. The response alternative “Don’t know” was not available in the first version of the questionnaire. 1:1 indicates first version, first response; 1:2, first version, second response; 2:1, second version, first response; 2:2, second version, second response; NA, not available. a Not including questions 5 and 9.

[11] Masters JC, Hulsmeyer BS, Pike ME, Leichty K, Miller MT, Verst AL. Assessment of multiple-choice questions in selected test banks accompanying text books used in nursing education. J Nurs Educ 2001;40:25-32.

Table 3 The rate of correct response and the Raw Agreement Measure on each question when presented to 2 different groups of 21 respondents before and after corrections of single questions in a questionnaire concerning knowledge in heart-lung resuscitation

Question Rate of Rate of Raw correct correct Agreement response, response, Measure, first second first

group (%) group (%) group (%)

Raw Agreement Measure, second group (%)

No. of respondents answering “Don’t know”

No. of respondents who didn’t give any response

2:1

2:2

1:1

1:2

2:1

2:2

Should etomidate be used for Rapid-sequence intubation induction in critically ill septic patients? Probably not

To the Editor,

Etomidate as an Induction agent for critically ill patients was widely debated in the European intensive care and anesthesia literature in 2005 [1,2]. As Fengler describes, etomidate is well recognized to cause Adrenal suppression in both elective surgical patients [3,4] and more profoundly in the critically ill. Adrenal suppression in this patient group is associated with increased mortality [5]. The use of steroid supplementation in severe sepsis and septic shock is still undecided, and CORTICUS has shown no benefit from the use of steroids in patients with or without evidence of adrenal axis suppression [6]. Etomidate use continues to be associated with a worse outcome and adrenal suppression [7-12]. Surely there can be no justification for using a drug

that is known to cause adrenal suppression, where this is associated with increased mortality and where other options exist.

In sepsis, the volume of distribution of many drugs including induction agents is altered. Furthermore, in states of septic shock, blood is preferentially distributed to the vital organs, ultimately the brain and the heart. This will result in a greater concentration, than would be anticipated, of induc- tion agent at its site of action. A reduced drug dose can therefore be administered. In severe sepsis and septic shock, cardiac output is also altered (increased or decreased), resulting in an altered circulation time. These factors in combination imply that a traditional approach to rapid sequence induction cannot be undertaken. In critically ill patients with sepsis, conventional induction agents result in significantly less cardiovascular instability if they are titrated slowly to effect rather than given on a dose per kilogram basis. When used in this way, significantly less drug is required. Cricoid pressure can still be applied throughout this process to prevent passive regurgitation of gastric contents. Both propofol (2,6-diisopropylphenol) and thiopentone sodium (sodium thiopental) can be used in this way. The concomitant use of liberal fluid resuscitation and, where necessary, vasopressors can prevent profound hypotension.

If concern remains with regard to hypotension on induction, as Fengler eludes, ketamine provides a solution in septic patients, where with the possible exception of meningiococcal sepsis, the likelihood of concurrent intra- cranial hypertension is extremely low.

There is no role for an agent known to cause adrenal suppression in the induction of critically ill patients. A randomized controlled trials, as suggested by Fengler, would surely be unethical in the face of substantial evidence to show its detrimental effects. A careful rethink on the way in which rapid sequence induction is performed on critically ill patients with septic shock can prevent the profound Hemodynamic collapse feared from traditional induction agents.

Etomidate no longer has a role as the induction agent of choice in patients with septic shock in the anesthetic room or intensive care unit. Its use in the emergency department should similarly be abandoned.

Paul Dean MB ChB FRCA

Salford Royal Hospitals NHS Foundation Trust

Intesive Care Hope Hospital Salford, Greater Manchester, M6 8HD, UK E-mail address: [email protected]

doi:10.1016/j.ajem.2008.04.010

References

1. Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med 2005;31:325-6.
2. Morris C. Etomidate for emergency anaesthesia; mad, bad, and dangerous to know? Anaesthesia 2005;60:737-40.
3. Fragen RJ, Shanks CA, Molteni A. Effect on plasma cortisol concentrations of a single induction dose of etomidate or thiopentone. Lancet 2005;2:625.
4. Duthie DJR, Fraser R, Nimmo WS. Effect of induction of anaesthesia with etomidate on corticosteroid synthesis in man. Br J Anaesth 1985;57:156-9.
5. De Jong M, Beishuizen A, Spijkstra J, Groeneveld J. Relative Adrenal insufficiency as a predictor of disease severity, mortality, and beneficial effects of corticoSteroid treatment in septic shock. Crit Care Med 2007;35(8).
6. Sprung CL, Annane D, Keh D, Moreno R, for the CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. NEJM 2008;358:111-24.
7. Lipiner-Friedman D, Sprung CL, Laterre PF, Weiss Y, et al, for the Corticus Study Group. adrenal function in sepsis: the retrospective CORTICUS cohort study. Crit Care Med 2007;35(4):1012-8.
8. 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: 388-92.
9. Mohammad Z, Afessa B, Finkielman JD. The incidence of Relative adrenal insufficiency in patients with septic shock after the adminis- tration of etomidate. Crit Care 2006;10:R105.
10. Bloomfield R, Noble DW. Etomidate, pharmacological adrenalectomy and the critically ill: a matter of vital importance. Crit Care 2006;10 (4):161.
11. Cotton BA, Guillamondegui OD, Fleming SB, Carpenter RO, Patel SH, Morris Jr JA, et al. Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients. Arch Surg 2008;143(1):62-7 [discussion 67].
12. Lundy JB, Slane ML, Frizzi JD. Acute adrenal insufficiency after a single dose of etomidate. J Intensive Care Med 2007;22(2): 111-7.

    The author responds to: Should etomidate be used for rapid-sequence intubation induction in critically ill septic patients? Probably not

    I would like to thank Dr Dean for his thoughtful response to my article, “Should etomidate be used for rapid-sequence intubation induction in critically ill septic patients?” [1]. I agree with the assessment expressed that the use of etomidate for the induction of critically ill septic patients should be highly reconsidered by emergency medicine physicians.

    Since my original article was written, there have been several additional studies that have associated etomidate exposure with sustained adrenal insufficiency and death. As part of the retrospective CORTICUS cohort study, etomidate use was associated with an increased risk of mortality (odds ratio, 1.53; 95% confidence interval, 1.06-2.26) [2]. In another study, etomidate use was associated with adrenal insufficiency in 71% of patients as compared with 52% of those who had not received etomidate (P = .03) [3]. When added to the studies previously discussed in my original article, the accumulat- ing evidence of an association between etomidate use with sustained adrenal insufficiency and death cannot be ignored (although all of these studies looked at the use of etomidate retrospectively).

    This debate has become even more important with the recent CORTICUS findings that steroid supplementation with hydrocortisone in critically ill patients (with or without adrenal insufficiency) may not improve mortal- ity [4]. The efficacy of steroid supplementation in patients with adrenal insufficiency is likely to be hotly debated in the intensive care unit literature. Never- theless, if steroid supplementation may offer no benefit to patients with adrenal insufficiency, then we as emergency medicine physicians need to be even more careful that we are not causing untreatable adrenal sup- pression in these patients.

    Every patient that is intubated in the emergency department should have their induction regimen tailored to their specific condition. In many patients, etomidate is the ideal agent due to its rapid onset of action, reliable pharmacokinetics, and cardiovascular stability. However, in critically ill septic patients, Alternative agents should be highly considered. Some may simply require small, titrated doses of a benzodiazepine agent, propofol, or thiopentone for sedation (most critically