Sedatives for Emergency Intubation

(RSI Trial)

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)

2364 Participants Needed

Trial Summary

What is the purpose of this trial?

Among critically ill adults undergoing emergency tracheal intubation, one in five experience hypotension, cardiac arrest, or death. The sedatives used to rapidly induce anesthesia for emergency tracheal intubation have been hypothesized to effect cardiovascular complications and patient outcomes, but the optimal sedative medication for intubation of critically ill adults remains unknown. Ketamine and etomidate are the two most commonly used sedatives during intubation of critically ill adults. Data from a randomized clinical trial are urgently needed to determine the effect of ketamine versus etomidate on cardiovascular complications and clinical outcomes of emergency tracheal intubation.

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 data supports the effectiveness of the drug ketamine for emergency intubation?

Research shows that ketamine is a safe and effective sedative for emergency procedures, providing rapid sedation and pain relief with minimal side effects. It is often used successfully in emergency settings, including for intubation, and maintains stable heart and blood pressure conditions. ^{1 2 3 4 5}

Is ketamine generally safe for use in humans?

Ketamine is generally considered safe for sedation in humans, with minimal side effects, but there can be complications such as prolonged sedation and airway issues if overdosed. It has been used safely in children for sedation and pain management, with stable vital signs observed in studies. ^{3 6 7 8 9}

How does the drug ketamine differ from etomidate for emergency intubation?

Ketamine is unique because it may offer a survival benefit over etomidate for critically ill patients during emergency intubation, as suggested by hospital data. Additionally, ketamine can be administered through various routes, including intranasal and subcutaneous, which may provide flexibility in emergency settings. ^{1 2 6 10 11}

Research Team

Jonathan D Casey, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Matthew W Semler, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Todd W Rice, MD, MSc

Principal Investigator

Vanderbilt University Medical Center

Wesley H Self, MD, MPH

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. [2023]

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Prolonged sedation and airway complications after administration of an inadvertent ketamine overdose in emergency department. [2013]

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

Ketamine sedation for pediatric procedures: Part 1, A prospective series. [2019]

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

Low-dose ketamine: efficacy in pediatric sedation. [2016]

6. Germany pubmed.ncbi.nlm.nih.gov

A new route, jet-injection for anesthetic induction in children - II. ketamine dose-range finding studies. [2013]

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

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

8. England 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. [2013]

9. United States 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. [2023]

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

Management of Ketamine Extravasation in a Pediatric Patient During Procedural Sedation. [2022]

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

Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department. [2023]