title: Normothermic versus hypothermic cardiopulmonary bypass in children undergoing open heart surgery (thermic-2): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  During open heart surgery, patients are connected to a heart-lung bypass machine that pumps blood around the body ("perfusion") while the heart is stopped. Typically the blood is cooled during this procedure ("hypothermia") and warmed to normal body temperature once the operation has been completed. The main rationale for "whole body cooling" is to protect organs such as the brain, kidneys, lungs, and heart from injury during bypass by reducing the body's metabolic rate and decreasing oxygen consumption. However, hypothermic perfusion also has disadvantages that can contribute toward an extended postoperative hospital stay. Research in adults and small randomized controlled trials in children suggest some benefits to keeping the blood at normal body temperature throughout surgery ("normothermia"). However, the two techniques have not been extensively compared in children.
  
  
  OBJECTIVE
  The Thermic-2 study will test the hypothesis that the whole body inflammatory response to the nonphysiological bypass and its detrimental effects on different organ functions may be attenuated by maintaining the body at 35°C-37°C (normothermic) rather than 28°C (hypothermic) during pediatric complex open heart surgery.
  
  
  METHODS
  This is a single-center, randomized controlled trial comparing the effectiveness and acceptability of normothermic versus hypothermic bypass in 141 children with congenital heart disease undergoing open heart surgery. Children having scheduled surgery to repair a heart defect not requiring deep hypothermic circulatory arrest represent the target study population. The co-primary clinical outcomes are duration of inotropic support, intubation time, and postoperative hospital stay. Secondary outcomes are in-hospital mortality and morbidity, blood loss and transfusion requirements, pre- and post-operative echocardiographic findings, routine blood gas and blood test results, renal function, cerebral function, regional oxygen saturation of blood in the cerebral cortex, assessment of genomic expression changes in cardiac tissue biopsies, and neuropsychological development.
  
  
  RESULTS
  A total of 141 patients have been successfully randomized over 2 years and 10 months and are now being followed-up for 1 year. Results will be published in 2015.
  
  
  CONCLUSIONS
  We believe this to be the first large pragmatic study comparing clinical outcomes during normothermic versus hypothermic bypass in complex open heart surgery in children. It is expected that this work will provide important information to improve strategies of cardiopulmonary bypass perfusion and therefore decrease the inevitable organ damage that occurs during nonphysiological body perfusion.
  
  
  BACKGROUND
  ISRCTN Registry: ISRCTN93129502, http://www.isrctn.com/ISRCTN93129502 (Archived by WebCitation at http://www.webcitation.org/6Yf5VSyyG).
authors.affiliation: Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors.forename: Sarah
authors.identifier: http://orcid.org/0000-0003-2039-8768
authors.initials: S
authors.lastname: Baos
authors.forename: Karen
authors.identifier: http://orcid.org/0000-0003-1606-8184
authors.initials: K
authors.lastname: Sheehan
authors.forename: Lucy
authors.identifier: http://orcid.org/0000-0002-9255-6617
authors.initials: L
authors.lastname: Culliford
authors.forename: Katie
authors.identifier: http://orcid.org/0000-0002-9565-8993
authors.initials: K
authors.lastname: Pike
authors.forename: Lucy
authors.identifier: http://orcid.org/0000-0001-8179-5172
authors.initials: L
authors.lastname: Ellis
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-4322-7884
authors.initials: AJ
authors.lastname: Parry
authors.forename: Serban
authors.identifier: http://orcid.org/0000-0002-0456-1249
authors.initials: S
authors.lastname: Stoica
authors.forename: Mohamed T
authors.identifier: http://orcid.org/0000-0002-4945-0390
authors.initials: MT
authors.lastname: Ghorbel
authors.forename: Massimo
authors.identifier: http://orcid.org/0000-0001-7508-0891
authors.initials: M
authors.lastname: Caputo
authors.forename: Chris A
authors.identifier: http://orcid.org/0000-0002-9624-2615
authors.initials: CA
authors.lastname: Rogers
keywords: cardiac surgery; cardiopulmonary bypass; clinical trials; hypothermia; normothermia; pediatrics; randomized; temperature