LAUSR

BACKGROUND Peri-intubation 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 post-drug administration. METHODS Emergent-use, stratified (shock status and unit type), multi-unit, 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 and 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 post-drug administration [treatment difference (ketamine/propofol admixture - etomidate): -2.1 mmHg 95% C.I. (-6.9 mmHg, +2.7 mmHg); P=0.385]. In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 and 15 minutes post-drug 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 [13/16 (81%) vs. 5/13 (38%), 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). CONCLUSIONS 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 Level 1, TherapeuticClinicalTrials.gov, # NCT02105415, Ketamine / Propofol Admixture 'Ketofol' at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB# 13-000506, Trial Registration: 03/31/2014.