Etomidate vs Propofol for Anesthesia in Major Surgery

Overseen By Fabio Rodriquez Patarroyo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The Cleveland Clinic

Must be taking: Antihypertensives

Disqualifiers: Carotid, Intracranial, Nephrectomy, Liver, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: During surgery

6254 Participants Needed

Trial Summary

What is the purpose of this trial?

Some patients participating in the underlying GUARDIAN trial (NCT04884802) will be additionally randomized to etomidate vs propofol for anesthetic induction.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be taking at least one anti-hypertensive medication to participate.

What data supports the effectiveness of the drugs Etomidate and Propofol for anesthesia in major surgery?

Research suggests that Etomidate may have a more favorable effect on heart function during anesthesia compared to Propofol, which can be important for patients undergoing major surgery. Additionally, both drugs have been studied for their use in anesthesia, with considerations for their safety and side effects. ^{1 2 3 4 5}

Is it safe to use Etomidate and Propofol for anesthesia in major surgery?

Both Etomidate and Propofol are used for anesthesia, but they have different safety profiles. Propofol can cause heart and breathing problems, while Etomidate is generally stable for the heart and lungs but may affect hormone levels temporarily. More research is needed to fully understand their safety in different situations. ^{4 5 6 7 8}

How do the drugs Etomidate and Propofol differ for anesthesia in major surgery?

Etomidate is often chosen over Propofol for anesthesia in major surgery because it tends to have a more stable effect on blood pressure and heart function, making it safer for patients with heart issues. However, Etomidate may increase the risk of infections after surgery, which is a consideration when choosing between these drugs. ^{1 4 5 9 10}

Research Team

Daniel Sessler, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults over 45 who need major noncardiac surgery lasting at least 2 hours and will stay in the hospital overnight. They must have certain risk factors like being over 65, having a history of heart or artery disease, diabetes, smoking history, high body mass index (BMI), or specific blood markers indicating heart stress.

Inclusion Criteria

I expect to stay in the hospital overnight or longer.

I am over 65, have had vascular surgery, or have certain health conditions.

I will have my blood pressure monitored directly during surgery.

Exclusion Criteria

I cannot take norepinephrine or phenylephrine due to my doctor's advice.

I am scheduled for a liver transplant.

I am scheduled for surgery on my carotid artery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either etomidate or propofol for induction of anesthesia, along with routine or tight intraoperative blood pressure management

During surgery

Postoperative Monitoring

Participants are monitored for postoperative delirium and other complications during the initial four postoperative days

4 days

Follow-up

Participants are monitored for serious perfusion-related complications and other outcomes

30 days

Long-term Follow-up

Participants are assessed for cognition and major adverse cardiac events

1 year

Treatment Details

Interventions

• Etomidate
• Propofol

Trial Overview The study tests two anesthetic drugs—Etomidate and Propofol—used during surgery to see which one better maintains blood pressure when combined with either routine or tight blood pressure control methods in patients undergoing major surgeries.

Participant Groups

Group I: Routine Pressure Management with etomidate induction Active Control 2 Interventions

Etomidate will be used as an induction agent.

Group II: Routine Pressure Management with propofol induction Active Control 2 Interventions

Propofol will be used as an induction agent.

Group III: Tight Pressure Management with etomidate induction Active Control 2 Interventions

Etomidate will be used as an induction agent.

Group IV: Tight Pressure Management with propofol induction Active Control 2 Interventions

Propofol will be used as an induction agent.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

Etomidate demonstrated a superior haemodynamic profile compared to propofol, causing a 34% lesser reduction in mean arterial blood pressure (MAP) after induction of anaesthesia in patients undergoing cardiac surgery, based on a study of 150 participants.

Despite propofol being associated with a greater reduction in MAP, the use of vasopressors was not significantly different between the two groups, indicating that etomidate may be a safer option for maintaining blood pressure during anaesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery. Hannam, JA., Mitchell, SJ., Cumin, D., et al.[2019]

In a study of 1018 patients undergoing radical gastric cancer surgery, those who received propofol had significantly longer survival times compared to those who received etomidate, particularly in TNM stage IIIA and IIIC patients.

Specifically, patients in TNM stage IIIA had survival times of 41.79 months with propofol versus 36.10 months with etomidate, and in stage IIIC, survival times were 35.20 months with propofol compared to 26.57 months with etomidate, indicating that propofol may enhance postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Propofol or Etomidate as General Anaesthesia Induction on Gastric Cancer: A Retrospective Cohort Study with 10 Years' Follow-Up. Lu, X., Yu, Y., Wang, Y., et al.[2022]

In a study of 214 patients undergoing procedural sedation in the emergency department, both etomidate and propofol were found to be equally safe, with no clinically significant complications reported.

However, etomidate was associated with a lower procedural success rate (88.6%) compared to propofol (97.2%) and caused myoclonus in 20% of patients, indicating potential drawbacks despite its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. Miner, JR., Danahy, M., Moch, A., et al.[2022]

In a study of 100 patients undergoing elective surgery, etomidate demonstrated better hemodynamic stability compared to propofol, with minimal changes in mean arterial pressure and heart rate during induction.

While propofol was associated with more pain on injection, etomidate resulted in higher instances of myoclonus, suggesting that etomidate may be a safer choice for hemodynamically unstable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparative study between propofol and etomidate in patients under general anesthesia]. Aggarwal, S., Goyal, VK., Chaturvedi, SK., et al.[2016]

In a study of 100 patients undergoing elective surgery, etomidate demonstrated better hemodynamic stability compared to propofol, with minimal changes in mean arterial pressure and heart rate during induction.

While propofol caused more pain upon injection, etomidate was associated with higher instances of myoclonus, suggesting that etomidate may be a safer choice for hemodynamically unstable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study between propofol and etomidate in patients under general anesthesia. Aggarwal, S., Goyal, VK., Chaturvedi, SK., et al.[2022]

In a study of 128 patients undergoing endoscopic procedures, etomidate was associated with significantly fewer cases of oxygen desaturation (6.25% vs 31.25%) and respiratory depression (7.81% vs 32.81%) compared to propofol, indicating better respiratory safety.

While etomidate showed improved respiratory outcomes and higher physician satisfaction, it was linked to a higher incidence of myoclonus (34.37% vs 12.50%) and increased systolic blood pressure, suggesting a trade-off in its use for sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etomidate versus propofol sedation for complex upper endoscopic procedures: a prospective double-blinded randomized controlled trial. Kim, MG., Park, SW., Kim, JH., et al.[2018]

In a study of 12,526 critical care patients, those administered etomidate had a 1.84 times higher risk of in-hospital mortality compared to those given propofol, indicating significant safety concerns.

Etomidate was associated with a 57% lower chance of survival within the first 48 hours and a 1.77 times higher risk of infectious complications, suggesting it is not an effective choice for patients on mechanical ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of etomidate use in ICU patients on ventilator therapy: a study of 12,526 patients in an open database from a single center. Park, HY., Lee, Y., Lim, CY., et al.[2022]

Etomidate is an intravenous anesthetic that is considered safe for use in patients at high risk of hemodynamic instability, but it can cause temporary suppression of adrenal function, which may increase mortality in septic patients.

Current literature does not provide strong evidence against using a single-bolus dose of etomidate for induction in surgical patients, indicating that more large-scale randomized controlled trials are needed to fully assess its safety compared to other anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etomidate--a review of robust evidence for its use in various clinical scenarios. Erdoes, G., Basciani, RM., Eberle, B.[2022]

In a study of 1,462 cardiac surgery patients, etomidate did not significantly increase the risk of postoperative sepsis compared to propofol, with rates of 11.5% for etomidate versus 8.2% for propofol (p = 0.052).

However, patients receiving etomidate were more likely to develop hospital-acquired pneumonia (18.6% vs. 14.0% for propofol, p = 0.031), indicating a potential safety concern with etomidate use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious Complications after Etomidate vs. Propofol for Induction of General Anesthesia in Cardiac Surgery-Results of a Retrospective, before-after Study. Weiss, B., Schiefenhövel, F., Grunow, JJ., et al.[2021]

In a study of 25 patients undergoing elective orthopedic surgeries, Etomidate demonstrated more stable hemodynamic responses compared to Propofol, with significantly lower changes in blood pressure and a lower incidence of hypotension (8% vs. 26.1%).

The findings suggest that Etomidate may be a safer choice for patients with limited hemodynamic reserve, as it maintains cardiovascular stability better than Propofol during anesthesia induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cardiovascular response to laryngoscopy and tracheal intubation after induction of anesthesia by Propofol and Etomidate. Masoudifar, M., Beheshtian, E.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of Propofol or Etomidate as General Anaesthesia Induction on Gastric Cancer: A Retrospective Cohort Study with 10 Years' Follow-Up. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. [2022]

4. Brazil pubmed.ncbi.nlm.nih.gov

[A comparative study between propofol and etomidate in patients under general anesthesia]. [2016]

5. Brazil pubmed.ncbi.nlm.nih.gov

A comparative study between propofol and etomidate in patients under general anesthesia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Etomidate versus propofol sedation for complex upper endoscopic procedures: a prospective double-blinded randomized controlled trial. [2018]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Effects of etomidate use in ICU patients on ventilator therapy: a study of 12,526 patients in an open database from a single center. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Etomidate--a review of robust evidence for its use in various clinical scenarios. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Infectious Complications after Etomidate vs. Propofol for Induction of General Anesthesia in Cardiac Surgery-Results of a Retrospective, before-after Study. [2021]

10. India pubmed.ncbi.nlm.nih.gov

Comparison of cardiovascular response to laryngoscopy and tracheal intubation after induction of anesthesia by Propofol and Etomidate. [2021]