title: Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study.
abstract: BACKGROUND
  Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest.
  
  
  METHODS
  Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients' temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn's multiple comparisons test was used for comparison of individual time points.
  
  
  RESULTS
  The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming.
  
  
  CONCLUSIONS
  Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.
authors.affiliation: Department of Intensive Care, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands. laurens.bisschops@radboudumc.nl.
authors.forename: Laurens L A
authors.initials: LL
authors.lastname: Bisschops
authors.affiliation: Department of Intensive Care, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands. hans.vanderhoeven@radboudumc.nl.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.affiliation: Institute of Immunology, Oslo University Hospital and University of Oslo, P.B. 4950, Nydalen, N-0424, Oslo, Norway. t.e.mollnes@medisin.uio.no.|Research Laboratory, Nordlandssykehuset, Bodø; and University of Tromsø, Prinsensgate 164, NO-8092, Bodø, Norway. t.e.mollnes@medisin.uio.no.
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Department of Intensive Care, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands. astrid.hoedemaekers@radboudumc.nl.
authors.forename: Cornelia W E
authors.initials: CW
authors.lastname: Hoedemaekers
mesh_terms: D000368:Aged; D005260:Female; D006323:Heart Arrest / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods / Q000639:trends*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017694:Rewarming / Q000379:methods / Q000639:trends*; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators