Sedation and pain management/original research
Randomized Clinical Trial of Etomidate Versus Propofol for Procedural Sedation in the Emergency Department

https://doi.org/10.1016/j.annemergmed.2006.06.042Get rights and content

Study objective

We compare the efficacy, adverse events, and recovery duration of etomidate and propofol for use in procedural sedation in the emergency department (ED).

Methods

This was a randomized nonblinded prospective trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients received either propofol or etomidate. Doses, vital signs, nasal end-tidal CO2 (etco2), pulse oximetry, and bispectral electroencephalogram analysis scores were recorded. Subclinical respiratory depression was defined as a change in etco2 greater than 10 mm Hg, an oxygen saturation of less than 92% at any time, or an absent etco2 waveform at any time. Clinical events related to respiratory depression, including an increase in supplemental oxygen, the use of a bag-valve-mask apparatus, airway repositioning, or stimulation to induce breathing, were noted during the procedure. After the procedure, patients completed visual analog scales about perceived pain during the procedure and recall of the procedure.

Results

Two hundred twenty patients were enrolled; 214 underwent sedation and were analyzed. One hundred five patients received etomidate and 109 received propofol. No clinically significant complications were noted. Subclinical respiratory depression was observed in 36 of 105 (34.3%) patients in the etomidate group and 46 of 109 (42.2%) in the propofol group (difference –7.9%; 95% confidence interval [CI] –20.9% to 5.1%). Myoclonus was noted in 21 of 105 (20.0%) patients in the etomidate group and 2 of 109 (1.8%) in the propofol group (difference 18.2%; 95% CI 10.1% to 26.2%). The mean difference between baseline systolic blood pressure and the nadir was 3.8% (95% CI 2.3% to 5.3%) for etomidate and 7.9% (95% CI 6.1% to 9.7%) for propofol. Clinical events related to respiratory depression included an increase in supplemental oxygen in 6.7% of etomidate patients and 5.5% of propofol patients (difference 1.2%; 95% CI –5.2% to 7.6%), the use of bag-valve-mask apparatus in 3.8% of patients in the etomidate groups and 4.6% in the propofol group (difference –0.8%; 95% CI –6.1% to 4.6%), airway repositioning in 13.3% of etomidate patients and 11.0% of propofol patients (effect size 2.3%; 95% CI –6.4% to 11.1%), and stimulation to induce breathing in 11.4% of etomidate patients and 11.9% of propofol patients (difference –0.5%; 95% CI –9.1% to 8.1%). The procedures were successful in 93 of 105 (88.6%) for etomidate and 106 of 109 (97.2%) for propofol (difference –7.4%; 95% CI –14.3% to –1.1%).

Conclusion

Etomidate and propofol appear equally safe for ED procedural sedation; however, etomidate had a lower rate of procedural success and induced myoclonus in 20% of patients.

Introduction

Patients undergoing painful procedures in the emergency department (ED), such as orthopedic manipulations or abscess drainage, often require moderate or deep procedural sedation for successful performance of the procedure. This sedation is achieved with the use of a sedative agent administered at a dose that allows patients to maintain airway reflexes and have some response to verbal stimuli (moderate sedation) or to pain (deep sedation). The ideal sedative agent for this purpose would provide adequate sedation to perform the procedure successfully, with a minimum of cardiorespiratory adverse effects, and have a short duration of action. Etomidate and propofol are 2 ultrashort-acting sedative agents thought to provide these characteristics.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Despite their common use in procedural sedation, the performance and safety of these 2 agents have not been compared in a randomized controlled fashion.18

Propofol has an onset of action of approximately 45 seconds and begins to redistribute from the blood to fat and muscle in 3 to 5 minutes, with a rapidly resolving clinical effect. Propofol provides reliable amnesia and rapid recovery when used for procedural sedation.11 Etomidate has an onset of action of approximately 1 minute and duration of action of 5 to 15 minutes. It is considered to have the least homodynamic effect of any of the agents available for procedural sedation. A number of studies have found that etomidate provides effective, reliable sedation with minimal adverse effects.2, 5, 10, 15, 17

Both of these agents are frequently used for procedural sedation in the ED, but it is not yet known whether one of these agents is more effective or safe than the other. Determining differences in the effectiveness and safety of these agents will allow the development of more specific guidelines about their use.

This study prospectively compared procedural sedation with etomidate or propofol in terms of the level of sedation achieved, the rate of subclinical respiratory depression, the rate of clinical signs of respiratory depression, the time required for patients to return to baseline mental status, the success of the procedure, and patient-derived outcome factors of perceived pain, recall of the procedure, and satisfaction with the care they received.

Section snippets

Study Design

This was a prospective, randomized, nonblinded, clinical trial of propofol versus etomidate for ED procedural sedation of patients undergoing painful procedures between June 1, 2004, and September 1, 2005. The institutional review board of Hennepin County Medical Center approved the study. Patients provided prospective informed consent before enrollment.

Setting

This study was performed at an urban county medical center with approximately 97,000 ED patient visits per year. In our ED, procedural sedation

Characteristics of Study Subjects

Two hundred ninety-six patients met the inclusion and exclusion criteria for the study during the enrollment dates. Patient enrollment is shown in the Figure. The characteristics of the study subjects and the procedures for which patients were sedated are described are presented in Table 1.

Main Results

The main results are described in Table 2. Clinical events related to respiratory depression are described in Table 3. There was no difference in the need for increased supplemental oxygen or airway

Limitations

There are 2 principal limitations to our trial. The first is that we were unable to blind patients, physicians, or data collectors to the agent used in each procedural sedation. Propofol is white and opaque, and etomidate is clear, and because of the specific nature of the dosing, we did not think blinding could be safely achieved. All of the physicians who enrolled patients in this study are familiar with both of these agents and likely had preconceived notions about the 2 agents, resulting in

Discussion

This comparison of etomidate and propofol found that both agents have similar rates of sedation, subclinical respiratory depression, hypoxia, apnea, and clinical events related to respiratory depression. Propofol had a higher rate of procedural success than etomidate, myoclonus was observed much more frequently with etomidate, and hypotension was observed more frequently with propofol. None of these differences resulted in clinically significant adverse events, and it appears that both of these

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    Supervising editor: Steven M. Green, MD

    Author contributions: JRM and MD conceived and designed the trial. JRM, MD, AM, and MB supervised the conduct of the trial and data collection. JRM provided statistical advice and analyzed the data. JRM drafted the manuscript, and MD, AM, and MB contributed substantially to its revision. JRM takes responsibility for the paper as a whole.

    Funding and support: This work was funded by a grant from the Emergency Medicine Foundation. None of the authors have financial or other interests in the medications used in this study.

    Reprints not available from the authors.

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