Bilateral Remote Ischemic Conditioning in Children: a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Objectives To determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for two common congenital heart defects, with or without cyanosis. Methods Prospective, double-blind, randomized controlled trial at two centers in the United Kingdom. Children aged 3-36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive either bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Trial registration: ISRCTN12923441. Results Between October 2016 and December 2020, 120 eligible children were randomized to receive either bilateral preconditioning (n=60) or sham intervention (n=60). The primary outcome, area under the curve for hs-troponin-T was higher in the preconditioning group (mean: 70.0±50.9μg/L/hr, n=56) than in controls (mean: 55.6±30.1μg/L/hr, n=58), mean difference 13.2μg/L/hr (95% CI: 0.5, 25.8; p=0.04). Sub-group analyses did not show a differential treatment effect by oxygen saturations (pinteraction=0.25) but evidence of a differential effect by underlying defect (pinteraction=0.04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning therefore cannot be recommended for myocardial protection during pediatric cardiac surgery.