title: Intraoperative cerebral oxygenation, oxidative injury, and delirium following cardiac surgery.
abstract: Delirium affects 20-30% of patients after cardiac surgery and is associated with increased mortality and persistent cognitive decline. Hyperoxic reperfusion of ischemic tissues increases oxidative injury, but oxygen administration remains high during cardiac surgery. We tested the hypothesis that intraoperative hyperoxic cerebral reperfusion is associated with increased postoperative delirium and that oxidative injury mediates this association.
  
  
  
  We prospectively measured cerebral oxygenation with bilateral oximetry monitors in 310 cardiac surgery patients, quantified intraoperative hyperoxic cerebral reperfusion by measuring the magnitude of cerebral oxygenation above baseline after any ischemic event, and assessed patients for delirium twice daily in the ICU following surgery using the confusion assessment method for ICU (CAM-ICU). We examined the association between hyperoxic cerebral reperfusion and postoperative delirium, adjusted for the extent of cerebral hypoxia, the extent of cerebral hyperoxia prior to any ischemia, and additional potential confounders and risk factors for delirium. To assess oxidative injury mediation, we examined the association between hyperoxic cerebral reperfusion and delirium after further adjusting for plasma levels of F2-isoprostanes and isofurans at baseline and ICU admission, the association between hyperoxic cerebral reperfusion and these markers of oxidative injury, and the association between these markers and delirium.
  
  
  
  Ninety of the 310 patients developed delirium following surgery. Every 10%·hour of intraoperative hyperoxic cerebral reperfusion was independently associated with a 65% increase in the odds of delirium (OR, 1.65 [95% CI, 1.12-2.44]; P=0.01). Hyperoxia prior to ischemia was also independently associated with delirium (1.10 [1.01-1.19]; P=0.02), but hypoxia was not (1.12 [0.97-1.29]; P=0.11). Increased hyperoxic cerebral reperfusion was associated with increased concentrations of F2-isoprostanes and isofurans at ICU admission, increased concentrations of these markers were associated with increased delirium, and the association between hyperoxic cerebral reperfusion and delirium was weaker after adjusting for these markers of oxidative injury.
  
  
  
  Intraoperative hyperoxic cerebral reperfusion was associated with increased postoperative delirium, and increased oxidative injury following hyperoxic cerebral reperfusion may partially mediate this association. Further research is needed to assess the potential deleterious role of cerebral hyper-oxygenation during surgery.
authors.affiliation: Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Lopez
authors.affiliation: Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Pandharipande
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morse
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Shotwell
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Shaw
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: frederic.t.billings@vanderbilt.edu.
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002560:Cerebrovascular Circulation; D015331:Cohort Studies; D003693:Delirium / Q000097:blood / Q000209:etiology*; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000601:surgery*; D006801:Humans; D018496:Hyperoxia / Q000097:blood / Q000209:etiology*; D007432:Intraoperative Period; D028421:Isoprostanes / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016896:Treatment Outcome
chemical_list: D028421:Isoprostanes
keywords: Brain oxygenation; Delirium; F2-isoprostanes; Hyperoxia; Ischemia reperfusion; Isofurans; Oxidative injury; Oxidative stress; Oxygen; Surgery