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

Abstract

BackgroundEndotracheal 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/designA 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.DiscussionThe 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 registrationClinicaltrials.gov: NCT02105415. 31 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0687-0) contains supplementary material, which is available to authorized users.

Proposals to Conduct Randomized Controlled Trials Without Informed Consent: a Narrative Review

“…9 A recent example compared two induction agents for emergent bronchial intubation. 16 Cluster randomized studies are the other common case of RWOC. Sim and Dawson offer a detailed discussion, in which they further divide the category into cluster-cluster and individual-cluster research.…”

Optimizing Outcomes for Mechanically Ventilated Patients in an Era of Endovascular Acute Ischemic Stroke Therapy

“…[42][43][44][45][46] Etomidate (0.3 mg/kg dose) has similar neutral hemodynamic effects but is associated with an increased incidence of adrenal insufficiency and mortality. 47 Ketofol and etomidate are being compared in an on-going clinical trial among critically ill patients. 47 Regardless of the choice of anesthesia, blood pressure should be monitored continuously and augmented as required until vessel recanalization is achieved.…”

“…47 Ketofol and etomidate are being compared in an on-going clinical trial among critically ill patients. 47 Regardless of the choice of anesthesia, blood pressure should be monitored continuously and augmented as required until vessel recanalization is achieved. Arterial line placement should be considered for the duration of the procedure including induction for intubation, provided this does not result in a significant delay to endovascular stroke treatment.…”

Shock Index as a Predictor of Post-Intubation Hypotension and Cardiac Arrest; A Review of the Current Evidence

“…A small retrospective cohort study assessed 240 intubated patients in the ED to quantify the relationship between SI with PIH and mortality [14]. The authors found that patients with a pre-intubation SI value of 0.8 or more were at higher risk of PIH (OR, 2.28; 95% CI, 1.18-4.43), but this value was not associated with a longer duration of intubation or higher in-hospital mortality.Kim et al conducted a retrospective study of 352 patients intubated in the ED to determine the risk factors for PIH [15]. The SI value was 0.68 for non-PIH patients and 0.79 for patients who developed PIH ( p <0.01).…”