Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial

Trials. 2015 Apr 21:16:177. doi: 10.1186/s13063-015-0687-0.

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/design: 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.

Discussion: 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.

Trial registration: Clinicaltrials.gov: NCT02105415. 31 March 2014.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Anesthetics, Combined / administration & dosage*
  • Anesthetics, Combined / adverse effects
  • Anesthetics, Dissociative / administration & dosage*
  • Anesthetics, Dissociative / adverse effects
  • Anesthetics, Intravenous / administration & dosage*
  • Anesthetics, Intravenous / adverse effects
  • Clinical Protocols
  • Critical Illness
  • Etomidate / administration & dosage*
  • Etomidate / adverse effects
  • Hemodynamics / drug effects
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Intubation, Intratracheal*
  • Ketamine / administration & dosage*
  • Ketamine / adverse effects
  • Length of Stay
  • Minnesota
  • Propofol / administration & dosage*
  • Propofol / adverse effects
  • Research Design
  • Respiration, Artificial
  • Risk Factors
  • Sample Size
  • Time Factors
  • Treatment Outcome
  • Vasoconstrictor Agents / therapeutic use

Substances

  • Anesthetics, Combined
  • Anesthetics, Dissociative
  • Anesthetics, Intravenous
  • Vasoconstrictor Agents
  • Ketamine
  • Propofol
  • Etomidate

Associated data

  • ClinicalTrials.gov/NCT02105415