Sedatives for Emergency Intubation

(RSI Trial)

No longer recruiting at 5 trial locations

Overseen By Jonathan D Casey, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Under 18, Pregnant, Prisoner, Trauma, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Immediate (procedure duration)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two sedatives, ketamine and etomidate, to determine which better reduces heart-related problems during emergency intubation (when a tube is placed down the throat to assist with breathing). This is crucial because one in five patients currently experiences serious issues like low blood pressure or cardiac arrest during the procedure. Critically ill individuals needing emergency intubation with a laryngoscope (a tool to view the throat) might be suitable for this trial. The research aims to enhance patient safety and outcomes during these urgent medical situations. As a Phase 4 trial, it involves treatments already FDA-approved and proven effective, seeking to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on the use of sedatives during emergency intubation, so it's best to discuss your current medications with the trial team.

What is the safety track record for ketamine and etomidate?

Research shows that etomidate is often used when placing a breathing tube, but it may carry some risks. Some studies indicate that etomidate helps maintain steady heart rate and blood pressure during the procedure. However, other reports suggest it might increase the risk of in-hospital mortality. One analysis found that people who received etomidate had a higher death rate compared to those who received other drugs.

In contrast, studies show that ketamine does not seem to increase the risk of dying shortly after the breathing tube is placed. Research also indicates that ketamine does not affect the success of placing the tube on the first try. Ketamine appears to be a safe option without the added risk of serious complications.

Both drugs have their pros and cons, so patients should discuss with their doctors which might be the best choice for their specific situation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for emergency intubation, which often involves medications like propofol or midazolam, this trial is exploring two drugs: etomidate and ketamine. Etomidate is known for providing stable cardiovascular conditions during induction, which can be crucial for patients with heart issues. Ketamine, on the other hand, offers the unique ability to provide both anesthesia and pain relief, while also maintaining respiratory drive, which is especially beneficial in emergency settings. Researchers are excited about these treatments because they offer potential alternatives that could improve patient outcomes in critical situations.

What evidence suggests that this trial's treatments could be effective for emergency intubation?

Research shows that both ketamine and etomidate are commonly used to sedate patients during emergency intubation. In this trial, participants will receive either ketamine or etomidate. A review of several studies has found that etomidate is linked to a lower risk of low blood pressure after intubation compared to ketamine. However, another study found that etomidate might be associated with a higher risk of death in the hospital compared to ketamine. Conversely, ketamine might reduce the risk of death, but some studies suggest no clear difference in survival rates between the two drugs. Overall, neither drug has proven consistently better for very sick patients, and more research is needed to understand their effects on survival and complications. ^{2 4 6 7 8}

Who Is on the Research Team?

Jonathan D Casey, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Todd W Rice, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Matthew W Semler, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Wesley H Self, MD, MPH

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for critically ill adults needing emergency tracheal intubation with sedation. Participants must be undergoing the procedure in a participating unit and not be prisoners, pregnant, allergic to the study drugs, under 18 years old, or have trauma as a primary diagnosis.

Inclusion Criteria

My procedure will be done by a clinician skilled in tracheal intubation.

I am scheduled for a procedure to have a tube placed in my windpipe using a throat scope.

I am critically ill and need an emergency procedure to help me breathe.

Exclusion Criteria

I do not require immediate breathing support through a tube.

I am under 18 years old.

I chose not to participate in the RSI trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ketamine or etomidate for induction of anesthesia during tracheal intubation

Immediate (procedure duration)

1 visit (in-person)

Follow-up

Participants are monitored for cardiovascular complications and clinical outcomes after intubation

4 weeks

Long-term follow-up

Participants are monitored for long-term survival and outcomes

28 days

What Are the Treatments Tested in This Trial?

Interventions

• Etomidate
• Ketamine

Trial Overview The trial is testing whether Ketamine or Etomidate is better for sedating critically ill adults during emergency tracheal intubation. It aims to see which drug leads to fewer cardiovascular complications and improves patient outcomes.

How Is the Trial Designed?

Group I: Ketamine Group Active Control 1 Intervention

Patients in the ketamine group will be assigned to receive intravenous ketamine for induction of anesthesia during tracheal intubation. A dose of 2 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). In this pragmatic trial, treating clinicians will be able elect to give a lesser or greater dose of ketamine than recommended if felt to be required for optimal patient care.

Group II: Etomidate Group Active Control 1 Intervention

Patients in the etomidate group will be assigned to receive intravenous etomidate for induction of anesthesia during tracheal intubation. A dose of 0.3 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). In this pragmatic trial, treating clinicians will be able elect to give a lesser or greater dose of etomidate than recommended if felt to be required for optimal patient care.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 801 critically ill patients undergoing emergency intubation, those who received ketamine had a significantly higher Day 7 survival rate (85.1%) compared to those who received etomidate (77.3%), suggesting ketamine may be a safer option for sedation in these situations.

However, by Day 28, there was no significant difference in survival rates between the two groups, indicating that while ketamine may provide an early survival benefit, the long-term outcomes are similar for both medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Matchett, G., Gasanova, I., Riccio, CA., et al.[2023]

Jet-injection of ketamine (K) for anesthetic induction in 30 children aged 1-6 years was found to be effective and pain-free, eliminating the need for physical restraint during the procedure.

The study indicated that a lower dose of 3.5 mg/kg of ketamine is sufficient for routine use, as the higher dose of 6.0 mg/kg increased the risk of laryngospasm without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new route, jet-injection for anesthetic induction in children - II. ketamine dose-range finding studies. Zsigmond, EK., Kovacs, V., Fekete, G.[2013]

Intranasal (IN) ketamine is a safe and effective alternative for providing analgesia and anxiolysis in pediatric emergency department patients, with 100% provider comfort and high satisfaction scores (90 out of 100).

The use of IN ketamine resulted in a significantly shorter emergency department length of stay (mean 237.9 minutes) compared to traditional intravenous sedation methods (mean 332.4 minutes), while maintaining a low rate of minor adverse events (6%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department. Guthrie, AM., Baum, RA., Carter, C., et al.[2023]

Preanesthetic inhaled ketamine provided significantly better sedation in children compared to both oral ketamine and apple juice, indicating its effectiveness for preoperative anxiety management.

Both inhaled and oral ketamine were found to be safe, but inhaled ketamine resulted in lower postoperative pain management needs and fewer gastrointestinal side effects compared to oral ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preanesthetic nebulized ketamine vs preanesthetic oral ketamine for sedation and postoperative pain management in children for elective surgery: A retrospective analysis for effectiveness and safety. Chen, C., Cheng, X., Lin, L., et al.[2023]

In a study of 108 children aged 14 months to 13 years, ketamine sedation (4 mg/kg IM) was highly effective, achieving acceptable sedation conditions in 97% of cases, with full sedation occurring within five minutes for 83% of patients.

While there was one case of transient laryngospasm, all other patients maintained airway patency and independent respiration, indicating that ketamine can be safely used for procedural sedation in children, though emergency physicians should be prepared for potential airway management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine sedation for pediatric procedures: Part 1, A prospective series. Green, SM., Nakamura, R., Johnson, NE.[2019]

In a study of 72 pediatric patients, 97% achieved adequate sedation with intravenous (IV) ketamine, suggesting that lower doses (0.5 to 1.0 mg/kg) can be effective for procedural sedation.

The results indicate that 88% of patients were successfully sedated with initial doses of 1 mg/kg or less, highlighting the potential for using lower doses of ketamine in pediatric emergency settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose ketamine: efficacy in pediatric sedation. Bleiberg, AH., Salvaggio, CA., Roy, LC., et al.[2016]

A case report describes a 12-year-old boy who received subcutaneous ketamine (1 mg/kg) after an intravenous line extravasation, leading to effective procedural sedation without complications.

This case highlights the potential for subcutaneous absorption of ketamine to provide satisfactory sedation, despite limited data on its pharmacokinetics in this route of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Ketamine Extravasation in a Pediatric Patient During Procedural Sedation. Smith, SA., Fitzpatrick, CT., Olesky, CL., et al.[2022]

In a study of 620 trauma patients, those sedated with ketamine experienced greater hemodynamic instability, showing a faster heart rate and more hypotension compared to those sedated with etomidate.

Despite the differences in hemodynamic effects, there were no significant differences in clinical outcomes such as first-pass intubation success, mortality rates, or length of hospital stay between the two sedation agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea. Kim, J., Jung, K., Moon, J., et al.[2023]

Ketamine is recognized as a safe and effective sedative for pediatric patients undergoing painful procedures in the Emergency Department, providing rapid sedation and potent pain relief.

However, there is a risk of complications, such as prolonged sedation and airway issues, particularly in cases of inadvertent overdose, highlighting the importance of careful dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged sedation and airway complications after administration of an inadvertent ketamine overdose in emergency department. Capapé, S., Mora, E., Mintegui, S., et al.[2013]

Oral administration of 200 mg/kg of ketamine hydrochloride to six domestic turkeys did not produce any noticeable anesthetic effect, indicating that this dose may be ineffective for anesthesia in this species.

When the same turkeys were given a higher dose of 500 mg/kg one week later, they exhibited ataxia within 10 minutes, but only mild sedation was observed, as they were still able to escape when challenged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inefficacy of oral ketamine for chemical restraint in turkeys. Clutton, RE.[2013]

The study found that a specific batch of ketamine did not produce adverse effects that would complicate intubation in sheep, as all drug combinations allowed for successful intubation by veterinary students.

The combination of medetomidine and alphaxalone resulted in faster recovery times compared to the ketamine groups, indicating it may be a preferable option for anesthesia in sheep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of two different ketamine and diazepam combinations with an alphaxalone and medetomidine combination for induction of anaesthesia in sheep. Walsh, VP., Gieseg, M., Singh, PM., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8783236/

Etomidate Compared to Ketamine for Induction during ... The meta-analysis showed that etomidate was associated with decreased risk of post-induction hypotension compared to ketamine (OR: 0.53; 95% CI: 0.31– ...

2. nature.com nature.com/articles/s41598-023-33679-x

Clinical outcomes after a single induction dose of ... We found no significant differences in survival at 24 h, 7 days, and 28 days in sepsis patients intubated with etomidate or ketamine.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2949788425000504

Protocol and Statistical Analysis Plan for a Multicenter ... The trial compares ketamine vs etomidate for induction of anesthesia among 2,364 critically ill adults undergoing emergency tracheal intubation. The primary ...

4. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202404-0813OC

Evaluation of Etomidate Use and Association with Mortality ... Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality than use of ketamine.

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-024-04831-4

Ketamine versus etomidate as an induction agent for tracheal ... This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11568430/

An Expiration Date for Etomidate? - PMC Overall, pooled data in several meta-analyses point to the potential for increased mortality when etomidate is used to facilitate endotracheal ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024143058

Comparison of efficacy and safety of etomidate with other ... Patients receiving etomidate demonstrated a more stable hemodynamic profile after induction and intubation compared to those receiving comparator drugs. The ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8343213/

A retrospective data analysis on the induction medications ... The most common induction agents were etomidate (68%), propofol (17%), and ketamine (11%). In-hospital mortality was highest in the etomidate group (25.5%), ...