title: Influence of core body temperature on Tryptophan metabolism, kynurenines, and estimated IDO activity in critically ill patients receiving target temperature management following cardiac arrest.
abstract: Temperature control improves neurological prognosis in comatose cardiac arrest (CA) survivors. Previous reports demonstrate that most affected patients show signs of significant systemic inflammation. In an effort to better characterize potential temperature-related effects on key inflammatory pathways, we investigate the course of Tryptophan (Trp) levels, Tryptophan catabolites (including kynurenines) and indoleamine-2,3-dioxygenase (IDO)-activity in post CA patients.
  
  
  
  In an observational blinded endpoint analysis, a total of n=270 serial samples from 20 post CA patients (63.1±16.6 yrs., 45% shockable rhythm, mean time to return of spontaneous circulation (ROSC) 26.6±16.0min) treated with target temperature management (TTM) were analyzed. Core body temperatures, course of Trp, Trp catabolites (incl. kynurenines), and estimated IDO-activity were followed up for a maximum of 7 days after ROSC. Patients were followed up until hospital discharge or death and functional outcome was recorded.
  
  
  
  Over the 7-day observational interval, marked changes in Trp serum levels and IDO-activity were noted. In general, Trp serum levels but not IDO-activity seemed to parallel with the course of core body temperature. In explorative analyses, a correlation of Trp (rho=0.271 (95%-CI: 0.16-0.38, p<0.0001) and IDO-activity (rho=-0.155, 95%-CI: -0.27 to -0.037, p=0.01) with core body temperature was observed. Linear mixed effect models revealed a positive significant association of core body temperature with Trp serum levels (Likelihood ratio test χ(2)=6.35, p=0.012). In patients with good (vs. unfavorable) outcome, a tendency toward higher Trp serum levels, lower IDO-activity, and lower Kynurenic acid levels was noted.
  
  
  
  We observed significant changes in Trp catabolism and IDO-activity that appeared temperature associated in post CA patients. Under hypothermia, decreased serum levels of Trp and increased IDO-activity were noted. We speculate from our data that IDO-induction during hypothermia contributes to the previously described increased susceptibility to infection or sepsis under reduced temperatures.
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital, Bern, Switzerland; Department of Nephrology and Intensive Care Medicine, Charite University Medicine, Berlin, Germany.
authors: Joerg C
authors: JC
authors: Schefold
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
authors: Nora
authors: N
authors: Fritschi
authors: Department of Pediatrics, McMaster University, Hamilton, Canada.
authors: Gerhard
authors: G
authors: Fusch
authors: Department of Pediatrics, McMaster University, Hamilton, Canada.
authors: Aldin
authors: A
authors: Bahonjic
authors: Centre for Stroke Research Berlin, Charité Medical School, Berlin, Germany.
authors: Wolfram
authors: W
authors: Doehner
authors: University of Göttingen Medical School, Department of Cardiology and Pneumology, Göttingen, Germany.
authors: Stephan
authors: S
authors: von Haehling
authors: Department of Nephrology and Intensive Care Medicine, Charite University Medicine, Berlin, Germany; Department of Gastroenterology, Charite University Medicine, Berlin, Germany.
authors: Rene
authors: R
authors: Pschowski
authors: Department of Nephrology and Intensive Care Medicine, Charite University Medicine, Berlin, Germany.
authors: Christian
authors: C
authors: Storm
authors: Department of Nephrology and Intensive Care Medicine, Charite University Medicine, Berlin, Germany.
authors: Tim
authors: T
authors: Schroeder
mesh_terms: D000368:Aged; D001831:Body Temperature; D003128:Coma / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D005260:Female; D005858:Germany; D006323:Heart Arrest / Q000150:complications / Q000628:therapy; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000379:methods; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D020127:Recovery of Function; D013223:Statistics as Topic; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan
keywords: Cell-mediated immune system; Indoleamine 2,3 dioxygenase; Inflammation; Intensive care unit patients; Sepsis; Target temperature management