Original articleIntraoperative cerebral oxygenation, oxidative injury, and delirium following cardiac surgery
Graphical abstract
Introduction
Delirium is a manifestation of acute brain dysfunction and affects 20–30% of patients following cardiac surgery [1], [2]. Delirium is associated with increased mortality, pulmonary dysfunction, and duration of hospitalization following cardiac surgery, and is an independent predictor of long-term cognitive decline in other medical and surgical patient populations [3], [4], [5], [6].
During cardiac surgery impaired heart function, exposure to cardiopulmonary bypass, and rapid changes in temperature, intravascular pH, and arterial pressure lead to abrupt changes in cerebral perfusion, oxygen extraction, and oxygen consumption. These changes in brain oxygenation, along with exposure to anesthetics, systemic and cerebral inflammation, and microemboli may precipitate delirium following cardiac surgery, although precise mechanisms are poorly understood.
In preclinical studies tissue hypoxia, hyperoxia, ischemia, and hyperoxic reperfusion – all common in patients undergoing cardiac surgery – increase the production of reactive oxygen species and induce oxidative injury [7], [8], [9], [10]. Intraoperative oxidative injury may contribute to postoperative brain injury, as it has been demonstrated that intraoperative oxidative injury contributes to postoperative kidney injury, another organ susceptible to ischemia reperfusion injury [11]. Hyperoxia may contribute to this phenomenon. Indeed, in other clinical scenarios of cerebral ischemia and reperfusion injury, including cardiac arrest and stroke, hyperoxia during reperfusion is a strong predictor of neurologic damage [12], [13]. Hyperoxia during surgery remains standard clinical practice despite these potential deleterious effects.
We conducted this study to test the hypothesis that hyperoxic cerebral reperfusion is associated with the development of delirium following cardiac surgery and that increased oxidative injury may mediate this association.
Section snippets
Patients
We performed a cohort study using participants from the Statin AKI Cardiac Surgery RCT, a randomized clinical trial conducted to test the hypothesis that perioperative atorvastatin treatment compared to placebo reduces acute kidney injury, intensive care unit (ICU) delirium, and additional organ dysfunctions following cardiac surgery [14]. We used the Statin trial cohort because study participants were assessed for delirium by research personnel twice daily while in the ICU, had detailed
Results
The cohort included 310 patients. Demographic and intraoperative data are shown in Table 1. The median (10th percentile, 90th percentile) age of the cohort was 67 (47, 81) years, 30.6% of patients were diabetic, and 79.7% had surgery with the use of cardiopulmonary bypass. Ninety patients (29.0%) developed delirium after surgery for a median of 1.0 (1.0, 4.0) days. Treatment assignment of the parent trial (atorvastatin vs. placebo) did not affect oxygenation or delirium outcomes in this study.
Discussion
Reperfusion injury is frequently blamed for postoperative organ injury [22], [34], but clinicians do not limit hyper-oxygenation following intraoperative ischemia. In a well-phenotyped cohort of cardiac surgery patients intraoperative cerebral hyper-oxygenation following ischemia correlated strongly with an increased incidence of postoperative delirium, and we found some evidence that increased oxidative injury may partially mediate this association. Intraoperative cerebral hyper-oxygenation
Sources of funding
This work was supported by K23GM102676, R01GM112871, and UL1TR000445 from the National Institutes of Health, the Foundation for Anesthesia Education and Research, and the Vanderbilt University Medical Center Department of Anesthesiology.
Disclosures
None.
Acknowledgments
We acknowledge cardiopulmonary bypass perfusionists Matthew Warhoover, MS, MMHC, and Dane A. Fornero, BS, CCP, from the Vanderbilt Heart and Vascular Institute for assistance in obtaining cerebral oximetry data; Patty Hendricks, R.N., for nursing support; Will Hardeman, B.A., Cleo Carter, B.A., Kiersten Card, and Damon Michaels, B.S., of the Vanderbilt Department of Anesthesiology Perioperative Clinical Research Institute, for assisting us in data collection; Anthony DeMatteo, B.S., Stephanie
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