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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Ketamine / Propofol Admixture
* Drug: Etomidate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Etomidate<br>weight based dose of 0.15mg/kg | Drug: Etomidate<br> <br> |
| Experimental: Ketamine / Propofol Admixture<br>weight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol | Drug: Ketamine / Propofol Admixture<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Arterial Pressure | 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. | baseline and every 5 minutes up to 15 minutes minutes post study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | In-hospital/28 day mortality among patients in ketamine/propofol combination compared to in-hospital/28-day mortality in etomidate. | Hospital Discharge or Day 28, whichever comes first | 
| Vasopressor Use | The use of vasoactive medications to restore the blood pressure post-administration in the ketamine/propofol combination as compared to the etomidate group. | up to 24 hours post study drug administration | 
| Number of Participants With Adrenal Insufficiency | Incidence of adrenal insufficiency between ketamine/propofol admixture and etomidate. Adrenal insuffiency was evaluated with co-syntropin stimulation test. | up to 24 hours post study drug administration | 
| Mechanical Ventilation Free Days | comparison of mechanical ventilation free days between the two groups | hospital discharge or day 28, whichever comes first | 
| Blood Product Transfusions | blood product transfusions [Red Blood Cells vs. non-Red Blood Cells] between the two groups | hospital discharge or day 28, whichever comes first | 
| Intensive Care Unit Free Days | comparison of intensive care unit free days between the two groups | hospital discharge or day 28, whichever comes first | 
| Number of Participants Experiencing Delirium Using Confusion Assessment Method in ICU | Comparison of number of participants who were positive for delirium using CAM-ICU between groups | up to 24 hours post study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critical care, Emergent, Etomidate, Hemodynamics, Intensive care unit, Intubation, Ketamine-Propofol admixture