Intraoperative cerebral oxygenation, oxidative injury, and delirium following cardiac surgery

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Brain oxygenation; Delirium; F2-isoprostanes; Hyperoxia; Ischemia reperfusion; Isofurans; Oxidative injury; Oxidative stress; Oxygen; Surgery.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1. Illustration of cerebral oxygenation metrics

Four different patients’ peripheral arterial hemoglobin oxygen saturations (SpO2) and cerebral hemoglobin oxygen saturations plotted during surgery were chosen to illustrate oxygenation metrics and observed patterns. Hyperoxic cerebral reperfusion was defined as any cerebral oxygenation greater than baseline that followed a period of cerebral ischemia. Cerebral ischemia was defined as cerebral oxygenation 80% of baseline for five or more minutes or the equivalent AUC for desaturations to less than 80% of baseline (e.g., 60% for 2.5 minutes). Cerebral hypoxia was quantified by calculating the AUC below 80% of baseline throughout surgery, and cerebral hyperoxia by calculating the AUC above baseline throughout surgery prior to any ischemia or the AUC above baseline throughout surgery in patients that never experienced ischemia.

Figure 2. Associations between intraoperative cerebral hyperoxic reperfusion, cerebral hyperoxia, and cerebral hypoxia and postoperative delirium

Odds ratios (OR) represent the odds of postoperative delirium for every 10%·hour (e.g., 20% above baseline for 30 minutes equals one 10%·hour hyperoxia) intraoperative oxygenation metric, adjusted for potential confounders, risk factors, and the other oxygenation metrics. For example, a patient with two 10%·hours of hyperoxic reperfusion had a 65% increase in the odds of delirium compared to the patient with one 10%·hours of hyperoxic reperfusion independent of the effects of hyperoxia prior to reperfusion, hypoxia, confounders, and risk factors on delirium. Cerebral oxygenation parameters (x-axis) were truncated at the 90th percentile to simplify exposition.

Figure 3. Associations between baseline and ICU admission concentrations of F2-isoprostanes and isofurans and postoperative delirium

Odds ratios (OR) represent the odds of postoperative delirium for every 20 pg/ml increase in plasma concentrations of F2-isoprostanes and isofurans measured at baseline or at ICU admission, adjusted for potential confounders, risk factors, and ICU admission or baseline oxidative injury biomarkers, respectively. For example, a patient with an ICU admission plasma concentration of 120 pg/ml F2-isoprostanes and isofurans had a 30% increase in the odds of delirium compared to a patient with a concentration of 80 pg/ml, independent of the effects of baseline oxidative injury concentrations, potential confounders, and risk factors on delirium.