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A Comparison of the Effects of Etomidate and Midazolam on the Duration of Vasopressor Use in Patients with Suspected Sepsis

David A. Barounis, MD; Erik Kulstad, MD, MS; Karis Tekwani, MDAdvocate Christ Medical Center, Department of Emergency Medicine

INTRODUCTION

METHODS AND MATERIALS

CONCLUSIONSRESULTS

REFERENCES

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ABSTRACT

CONTACTDavid A. Barounis Advocate Christ Medical CenterEmail: david.barounis@gmail.comPhone: 630-202-0145Website: christem.com

STUDY OBJECTIVE: Etomidate is known to cause adrenal suppression after a single bolus dose, which has been suggested to cause increased vasopressor requirements. We analyzed an existing data set to determine if a single bolus dose of etomidate increased the duration of vasopressor requirements in patients with sepsis.

METHODS: This was a secondary analysis of data obtained from patients enrolled in a double-blind, randomized study at our hospital. This study compared length of stay between patients with suspected sepsis who were intubated with either etomidate or midazolam in our emergency department over an 18-month period. For the current analysis, data on vasopressor duration were collected from medical records.

RESULTS: A total of 122 patients were enrolled in the study; after randomization 59 received midazolam and 63 received etomidate. Of this 96 (80%) patients met sepsis criteria, and 59 (48%) patients required vasopressors. There was no statistically significant difference in mean hours on vasopressors for all patients 33.4 (95% CI 17 – 49) versus; 33.2 (95% CI 16 - 50 hours) or in the subset of patients with confirmed sepsis 39 (95% CI 19 - 58 hours) versus; 36 (95% CI 18- 55 hours) between patients who received etomidate and patients who received midazolam, respectively.

CONCLUSIONS: We found no significant difference in duration of vasopressor use between patients who were given etomidate and patients given midazolam in our study sample. These results do not support the contention that etomidate causes significant increases in vasopressor requirements.

A total of 122 patients were enrolled in the study; after randomization 59 received midazolam and 63 received etomidate. Of this 96 (80%) patients met sepsis criteria, and 59 (48%) patients required vasopressors.

The mean duration of vasopressor use in all patients included in the study was 33.4 (95% CI 17-49) hours and 33.2 (95% CI 16-50 ) hours in patients receiving etomidate and midazolam respectively.

Patients with confirmed sepsis had a mean duration of vasopressor use of 39 (95% CI 19-58) hours versus; 36 (95% CI 18-55) hours for patients who received etomidate and midazolam respectively.

In the subset of patients who received immediate vasopressors, meaning within 48 hours of intubation, the mean duration of vasopressors for etomidate was 46 (95% CI 5- 196) hours versus 30 ( 95% CI 11-118) hours in patients who received midazolam.

The initial study was a prospective, randomized, double-blinded clinical trial, comparing hospital length of stay in patients who were randomized to etomidate (0.3mg/kg dose) with the length of stay with patients randomized to midazolam (0.1mg/kg dose) intravenously for sedation prior to rapid sequence intubation over an 18-month period.

After randomization, patients were confirmed as having sepsis by the original study authors using the following approach. If patients fulfilled 2 of the 4 systemic inflammatory response syndrome criteria and a documented infection was confirmed, the patient was considered to be septic.

Patients charts were then retrospectively reviewed to identify the type, duration and number of concurrent vasopressors used. Patients who had vasopressor therapy that was started after the initial 48-hour period in which they received etomidate or versed were eliminated from the study, assuming that any hypotension at this point was unrelated to adrenal-axis suppression.

We found no significant difference in mean duration of vasopressor therapy in patients randomized to receive etomidate or versed. In the subset of patients who were placed immediately on vasopressors and met sepsis criteria there was a non-statistically significant trend towards prolonged vasopressor use in patients randomized to etomidate.

Larger randomized controlled trials are necessary to further evaluate the trends toward longer vasopressor use in patients recieveing bolus-dose etomidate for RSI.

Etomidate remains one of the most common choices for rapid sequence intubation (RSI) in most emergency department settings. Despite its frequency the safety in patients with suspected sepsis has been questioned.

Several papers have been able to demonstrate a significant increase in mortality in ICU patients who were sedated with etomidate. (1,2). It is now recognized that etomidate when used for prolonged sedation results in significant adrenal suppression, and is no longer recommended for prolonged use.

Evidence has arisen suggesting that even a single bolus dose of etomidate (0.3mg/kg), may result in adrenal suppression for up to 48 hours 3,4 .This assertion has been investigated in several non-randomized controlled trials.

We sought to determine the effects of single bolus-dose etomidate on the duration of vasopressor use in patients with suspected sepsis .

1. Annane et al. ICU physicians should abandon the use of etomidate. Int Care Med (2005) 31: 325-326.

2. Malbera et al. Risk Factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Int Care Med (2005) 31:388-392.

3. Annane et al. The effect of treatment with low doses of Hydrocortisone and Fludrocortisone on Mortality in Patients with Septic Shock. JAMA (2002) 288; 862-871.

4. Jabre et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised trial.. The Lancet (2009)

Figure 1. Total Pressor Duration.

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Total Pressor Duration (Hours)4003002001000

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Medication

Etomidate

Midazolam

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12.5

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Total Pressor Duration (Hours)4003002001000

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12.5

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7.5

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Midazolam

Etomidate

Immediate Pressors (within 48 hours)