title: Pilot randomized controlled trial on early and late remote ischemic preconditioning prior to complex cardiac surgery in young infants.
abstract: BACKGROUND
  Remote ischemic preconditioning involves providing a brief ischemia-reperfusion event to a tissue to create subsequent protection from a more severe ischemia-reperfusion event to a different tissue/organ. The few pediatric remote ischemic preconditioning studies in the literature show conflicting results.
  
  
  OBJECTIVE
  We conducted a pilot randomized controlled trial to determine the feasibility of conducting a larger trial and to gather provisional data on the effect of early and late remote ischemic preconditioning on outcomes of infants after surgery for congenital heart disease.
  
  
  METHODS
  This single-center, double-blind randomized controlled trial of remote ischemic preconditioning vs control (sham-remote ischemic preconditioning) in young infants going for surgery for congenital heart disease at the Stollery Children's Hospital. Remote ischemic preconditioning was performed at 24-48 h preoperatively and immediately prior to cardiopulmonary bypass. Remote ischemic preconditioning stimulus was performed with blood pressure cuffs around the thighs. Primary outcomes were feasibility and peak blood lactate level on day 1 postoperatively.
  
  
  RESULTS
  Fifty-two patients were randomized but seven patients became ineligible after randomization leaving 45 patients included in the study. In the included patients, 7 (15%) had protocol deviations (five infants did not have the preoperative intervention and two did not receive the intervention in the operating room). From a comfort point of view, only one subject in the control group and two in the Remote ischemic preconditioning group received sedation during the preoperative intervention. There were no study-related adverse events and no complications to the limbs subjected to preconditioning. There were no significant differences between the Remote ischemic preconditioning group and the control group in the highest blood lactate level on day 1 postoperatively (mean difference, 1.28; 95%CI, -0.22, 2.78; P-value = 0.093).
  
  
  CONCLUSIONS
  In infants who underwent surgery for congenital heart disease, our pilot randomized controlled trial on early and late remote ischemic preconditioning proved to be feasible but did not find any significant difference in acute outcomes. A larger trial may be necessary.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Gonzalo Garcia
authors.identifier: http://orcid.org/0000-0001-6407-0823
authors.initials: GG
authors.lastname: Guerra
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Ari R
authors.initials: AR
authors.lastname: Joffe
authors.affiliation: Department of Anesthesia and Pain Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Rob
authors.initials: R
authors.lastname: Seal
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Phillipos
authors.affiliation: Stollery Children's Hospital, Edmonton, Canada.
authors.forename: Maggie
authors.initials: M
authors.lastname: Wong
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Canada.
authors.forename: Elham Khodayari
authors.initials: EK
authors.lastname: Moez
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Canada.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Dinu
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Duff
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rebeyka
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Charlene M T
authors.initials: CM
authors.lastname: Robertson
mesh_terms: D006348:Cardiac Surgical Procedures; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007231:Infant, Newborn; D019194:Ischemic Preconditioning / Q000379:methods*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control*
keywords: cardiovascular surgery; congenital heart disease; critical care; pediatrics; remote ischemic preconditioning; reperfusion injury