Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial

Ketamine

Brief Summary

The hypothesis of this study is that a Ketamine / Propofol mixture will produce more stable hemodynamics as compared to Etomidate during emergent intubations in the intensive care unit. Patients that require a breathing tube to be placed in the ICU will be randomized to receIve either a Ketamine / Propofol mixture or Etomidate for sedation in order to place the breathing tube.

Intervention / Treatment

  • Ketamine / Propofol Admixture (DRUG)
    N/A
  • Etomidate (DRUG)
    N/A

Condition or Disease

  • Critical Illness

Phase

  • Phase 2
  • Phase 3

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 99 Years
    Enrollment: 160 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    TRIPLE:
    • Participant
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Apr 01, 2014
    Primary Completion: Nov 28, 2017 ACTUAL
    Completion Date: Aug 01, 2018 ACTUAL
    Study First Posted: Apr 07, 2014 ESTIMATED
    Results First Posted: Jan 11, 2019 ACTUAL
    Last Updated: May 28, 2020

    Sponsors / Collaborators

    Lead Sponsor: Mayo Clinic
    Responsible Party: N/A

    Location

    Rochester, Minnesota, USA

    Endotracheal intubation is a procedure that may cause significant hemodynamic perturbations and can severely impact the outcome of the critically ill. To ensure a safe outcome during this particular procedure, there are many factors that the clinician is faced with. One decision that confronts the critical care physician involves the correct combination of medications with which to facilitate such a safe outcome. Given the reported hemodynamic stability, etomidate is a medication that is chosen by many providers in this particular situation. However, its association with a possible increase in mortality makes it less than ideal for a number of critical care physicians. In recent years, an admixture of propofol and ketamine has been studied that demonstrates hemodynamic stability based on the balancing of the hemodynamic effects of these two individual agents alone. This novel medication combination, sometimes referred to as "ketofol", may offer a valuable alternative to the critical care physician. Therefore, a randomized parallel-group clinical trial of adult critically ill patients admitted to a medical and/or surgical intensive care unit at Mayo Clinic Rochester who meet the criteria designated below for which urgent and/or emergent intubation is needed will receive one of two interventions based on stratified randomization. The "active" intervention arm will receive ketamine/propofol (ketofol) to facilitate endotracheal intubation. The comparison arm will receive etomidate. The primary outcome will focus on hemodynamic data recorded during the first 5 minutes post-administration with secondary outcomes looking at hemodynamic data at 10 and 15 minutes and addressing intensive care unit length of stay, mortality, adrenal function, and vasoactive medication use, among others.

    Participant Groups

    • weight based dose of 0.15mg/kg

    • weight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 99
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * 18 years of age or older
    * Surgical or medical intensive care unity patients requiring endotracheal intubation
    * Consulting physician agrees to study plan and will follow drug randomization

    Exclusion Criteria:

    * Known intracranial pathology
    * Known chronic opiate-dependence
    * Received continuous sedative infusion in the last 24 hours
    * Known severe psychiatric illness
    * Known egg allergies
    * Known contraindication to fentanyl, midazolam, ketamine, propofol or etomidate
    * Intubation in which standard practice is not to use sedation
    * No known documented weight or weight greater than 140 kg or less than 30 kg
    * Prior participation in the study
    * Of childbearing age (18-50) with no known negative pregnancy test on this admission.

    Primary Outcomes

    • Mean arterial pressure for the ketamine/propofol group at a 1:1 dose ratio compared to the etomidate group within the first 15 minutes post-administration in patients in need of urgent and/or emergent endotracheal intubation, as defined by any intubation within the intensive care unit excluding intubations for elective procedural events and codes.

    Secondary Outcomes

    • In-hospital/28 day mortality among patients in ketamine/propofol combination compared to in-hospital/28-day mortality in etomidate.

    • The use of vasoactive medications to restore the blood pressure post-administration in the ketamine/propofol combination as compared to the etomidate group.

    • Incidence of adrenal insufficiency between ketamine/propofol admixture and etomidate. Adrenal insuffiency was evaluated with co-syntropin stimulation test.

    • comparison of mechanical ventilation free days between the two groups

    • blood product transfusions \[Red Blood Cells vs. non-Red Blood Cells\] between the two groups

    • comparison of intensive care unit free days between the two groups

    • Comparison of number of participants who were positive for delirium using CAM-ICU between groups

    More Details

    NCT Number: NCT02105415
    Acronym: KEEP PACE
    Other IDs: 13-000506
    Study URL: https://clinicaltrials.gov/study/NCT02105415
    Last updated: Sep 29, 2023