title: Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability.
  
  
  METHODS
  A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients.
  
  
  CONCLUSIONS
  The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT02105415. 31 March 2014.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Smischney.nathan@mayo.edu.|Department of Respiratory Care, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Smischney.nathan@mayo.edu.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Smischney
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Hoskote.sumedh@mayo.edu.
authors.forename: Sumedh S
authors.initials: SS
authors.lastname: Hoskote
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. gallodemoraes.alice@mayo.edu.
authors.forename: Alice
authors.initials: A
authors.lastname: Gallo de Moraes
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. racedoafricano.carlos@mayo.edu.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Racedo Africano
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Carrera.perliveh@mayo.edu.
authors.forename: Perliveh M
authors.initials: PM
authors.lastname: Carrera
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Tedja.rudy@mayo.edu.
authors.forename: Rudy
authors.initials: R
authors.lastname: Tedja
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. pannu.jasleen@mayo.edu.
authors.forename: Jasleen K
authors.initials: JK
authors.lastname: Pannu
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Hassebroek.elizabeth@mayo.edu.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Hassebroek
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. reddy.dereddiraja@mayo.edu.
authors.forename: Dereddi Raja S
authors.initials: DR
authors.lastname: Reddy
authors.affiliation: Department of Anesthesiology, Division of Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. hinds.richard@mayo.edu.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hinds
authors.affiliation: Department of Critical Care Medicine, Geisinger Medical Center, 100 North Academy Avenue, Danville, PA, 17822, USA. lokendrat2001@gmail.com.
authors.forename: Lokendra
authors.initials: L
authors.lastname: Thakur
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D019162:Anesthetics, Combined / Q000008:administration & dosage* / Q000009:adverse effects; D000778:Anesthetics, Dissociative / Q000008:administration & dosage* / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D016638:Critical Illness; D005045:Etomidate / Q000008:administration & dosage* / Q000009:adverse effects; D006439:Hemodynamics / Q000187:drug effects; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007442:Intubation, Intratracheal; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D007902:Length of Stay; D008910:Minnesota; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D012121:Respiration, Artificial; D012307:Risk Factors; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D019162:Anesthetics, Combined; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D014662:Vasoconstrictor Agents; D007649:Ketamine; D015742:Propofol; D005045:Etomidate