title: Evolution of insulin sensitivity and its variability in out-of-hospital cardiac arrest (OHCA) patients treated with hypothermia.
abstract: BACKGROUND
  Therapeutic hypothermia (TH) is often used to treat out-of-hospital cardiac arrest (OHCA) patients who also often simultaneously receive insulin for stress-induced hyperglycaemia. However, the impact of TH on systemic metabolism and insulin resistance in critical illness is unknown. This study analyses the impact of TH on metabolism, including the evolution of insulin sensitivity (SI) and its variability, in patients with coma after OHCA.
  
  
  METHODS
  This study uses a clinically validated, model-based measure of SI. Insulin sensitivity was identified hourly using retrospective data from 200 post-cardiac arrest patients (8,522 hours) treated with TH, shortly after admission to the intensive care unit (ICU). Blood glucose and body temperature readings were taken every one to two hours. Data were divided into three periods: 1) cool (T <35°C); 2) an idle period of two hours as normothermia was re-established; and 3) warm (T >37°C). A maximum of 24 hours each for the cool and warm periods was considered. The impact of each condition on SI is analysed per cohort and per patient for both level and hour-to-hour variability, between periods and in six-hour blocks.
  
  
  RESULTS
  Cohort and per-patient median SI levels increase consistently by 35% to 70% and 26% to 59% (P <0.001) respectively from cool to warm. Conversely, cohort and per-patient SI variability decreased by 11.1% to 33.6% (P <0.001) for the first 12 hours of treatment. However, SI variability increases between the 18th and 30th hours over the cool to warm transition, before continuing to decrease afterward.
  
  
  CONCLUSIONS
  OCHA patients treated with TH have significantly lower and more variable SI during the cool period, compared to the later warm period. As treatment continues, SI level rises, and variability decreases consistently except for a large, significant increase during the cool to warm transition. These results demonstrate increased resistance to insulin during mild induced hypothermia. Our study might have important implications for glycaemic control during targeted temperature management.
authors.affiliation: Centre for Bio-Engineering, Department of Mechanical Engineering, University of Canterbury, 20 Kirkwood Avenue, Christchurch, 8140, New Zealand. azurashisham.sahpri@pg.canterbury.ac.nz.
authors.forename: Azurahisham
authors.initials: A
authors.lastname: Sah Pri
authors.affiliation: Centre for Bio-Engineering, Department of Mechanical Engineering, University of Canterbury, 20 Kirkwood Avenue, Christchurch, 8140, New Zealand. geoff.chase@canterbury.ac.nz.
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Chase
authors.affiliation: Centre for Bio-Engineering, Department of Mechanical Engineering, University of Canterbury, 20 Kirkwood Avenue, Christchurch, 8140, New Zealand. chris.pretty@canterbury.ac.nz.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Pretty
authors.affiliation: Department of Intensive Care, Christchurch Hospital, Riccarton Avenue, Christchurch, 8140, New Zealand. geoff.shaw@cdhb.govt.nz.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Department of Intensive Care, Erasme University Hospital (CUB), University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium. jean-charles.preiser@erasme.ulb.ac.be.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Preiser
authors.affiliation: Department of Intensive Care, Erasme University Hospital (CUB), University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium. jlvincen@ulb.ac.be.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Department of Intensive Care, Lausanne University Hospital (CHUV), Rue du Bugnon 46, 1011, Lausanne, Switzerland. Mauro.Oddo@chuv.ch.
authors.forename: Mauro
authors.initials: M
authors.lastname: Oddo
authors.affiliation: Department of Intensive Care, Erasme University Hospital (CUB), University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium. ftaccone@ulb.ac.be.
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Taccone
authors.affiliation: Cardiovascular Research Center, Universite de Liege, Allée du 6 Août 17, B4000, Liege, Belgium. Sophie.Penning@ulg.ac.be.
authors.forename: Sophie
authors.initials: S
authors.lastname: Penning
authors.affiliation: Cardiovascular Research Center, Universite de Liege, Allée du 6 Août 17, B4000, Liege, Belgium. tdesaive@ulg.ac.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: Desaive
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods / Q000639:trends*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin