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Ketamine/propofol admixture vs etomidate for intubation in the critically ill

KEEP PACE Randomized clinical trial

Smischney, Nathan Jerome MD, MSc; Nicholson, Wayne T. MD, PharmD; Brown, Daniel R. MD, PhD; Gallo De Moraes, Alice MD; Hoskote, Sumedh S. MBBS; Pickering, Brian MB, BCh; Oeckler, Richard A. MD, PhD; Iyer, Vivek N. MD, MPH; Gajic, Ognjen MD; Schroeder, Darrell R. MS; Bauer, Philippe R. MD, PhD

Journal of Trauma and Acute Care Surgery: October 2019 - Volume 87 - Issue 4 - p 883–891
doi: 10.1097/TA.0000000000002448

BACKGROUND Periintubation hypotension is associated with poor outcomes in the critically ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes postdrug administration.

METHODS Emergent-use, stratified (shock status and unit type), multiunit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture (0.5 mg/kg of ketamine and propofol each) or reduced dose etomidate (0.15 mg/kg) for emergent intubation.

RESULTS One hundred sixty participants were randomized, and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes postdrug administration (treatment difference [ketamine/propofol admixture—etomidate]: −2.1 mm Hg; 95% confidence interval, −6.9 mm Hg to +2.7 mm Hg; p = 0.385). In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 minutes and 15 minutes postdrug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non–red blood cell transfusions (16 [22%] vs. 8 [10%], p = 0.046). For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027). Serious adverse events were rare, 2 (3%) (cardiac arrest, hypotension) in ketamine/propofol admixture and 4 (5%) (hypertension, hypotension) in etomidate (p = 0.430).

CONCLUSION In a heterogeneous critically ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically ill.

LEVEL OF EVIDENCE Therapeutic/Care Management, level II.

TRIAL REGISTRY, NCT02105415, Ketamine/Propofol Admixture “Ketofol” at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB 13-000506, Trial Registration: March 31, 2014

From the Department of Anesthesiology and Perioperative Medicine (N.J.S., W.T.N., D.R.B., B.P.), Division of Pulmonary and Critical Care Medicine (A.G.D.M., S.S.H., R.A.O., V.N.I., O.G., P.R.B.), Department of Biostatistics (D.R.S.), and Hemodynamic and Airway Management Group (HEMAIR) (N.J.S., D.R.B., O.G.), Mayo Clinic, Rochester, Minnesota.

Submitted: April 4, 2019, Revised: June 6, 2019, Accepted: June 28, 2019, Published online: July 16, 2019.

2018 Military Health System Research Symposium, August 20-23, 2018, in Kissimmee, Florida; 2018 Georgia Society of Anesthesiologists Summer Meeting, July 13–15, 2018 in Lake Oconee, Greensboro, Georgia.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Address for reprints: Nathan J. Smischney, MD, Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; email:

Online date: July 22, 2019

© 2019 Lippincott Williams & Wilkins, Inc.