Psychiatric–Medical ComorbidityThe role of oxidative stress in postoperative delirium
Introduction
Postoperative delirium is a frequent complication of cardiopulmonary bypass (CPB) surgery. According to DSM-IV-TR [1], delirium is defined as a transient mental syndrome of acute onset, characterized by global impairment of cognitive functions, a reduced level of consciousness, attention abnormalities, increased or decreased psychomotor activity and a disordered sleep–wake cycle.
Although the cause of delirium after cardiac surgery is unclear, some mechanisms have been proposed. The brain may be injured by microembolism [2], [3], [4], [5], [6], [7], reduced cerebral perfusion/oxygenation [8], [9] and imbalance of the noradrenergic/cholinergic neurotransmission [10]. Another potential mechanism for delirium in this condition is the fact that an alteration in the tryptophan-to-phenylalanine ratio may result in serotonin excess or deficiency. High levels of phenylalanine (common in postoperative catabolic states) and low tryptophan-to-phenylalanine ratios have been associated with delirium [11]. The other possible causes for delirium after CPB may be preoperative deficits in neuropsychological function and low antioxidant levels.
CPB surgery has been shown to induce systemic inflammatory response [12] such as complement activation, endotoxin release, leukocyte activation, the expression of adhesion molecules and the release of many inflammatory mediators including oxygen free radicals [13], arachidonic acid metabolites, cytokines [14], [15], platelet-activating factor, nitric oxide and endothelins. This inflammatory cascade may contribute to the end-organ damage seen after cardiovascular operations [16]. Increased free-radical-induced oxidative stress together with a gradual appearance of antioxidative defense system during and after CPB by measuring F(2)-isoprostanes and alpha- and gamma-tocopherol has been shown [17]. The brain is a target for free radical damage because it has a large lipid content of myelin sheaths, a high rate of brain oxidative metabolism and a low antioxidant capacity. The cerebral tissue is therefore threatened by the increased formation of free radicals and their metabolites such as hydrogen peroxide and superoxide radicals [18], [19]. To help protect against these destructive effects of free radicals, the organism produces protective antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Whereas SOD catalyzes the reaction of the superoxide anion to hydrogen peroxide, CAT and GSH-Px catalyze the breakdown of peroxides [20]. Particularly in erythrocytes, this appears to be the main and preferred mechanism over catalysis. It has been known that malondialdehyde (MDA), the last oxidative product of unsaturated fatty acids [21], [22], and SOD values increase during reperfusion [21], [23].
The antioxidant enzyme status of the tissue is important for the primary endogenous defense against free-radical-induced injury [24]. The weak antioxidant defense mechanisms may be preoperatively leading to inadequate compensation of stress appearing in various mechanisms in patients during CPB or to the inappropriate activation of antioxidants. The fact that neurons are very sensitive to oxidative stress and such conditions can lead to their death or apoptosis.
Active oxygen species are highly reactive and very short lived and are therefore difficult to measure directly [25]. For this reason, most methodologies involve indirect determinations of antioxidants and the extent of oxidative stress that an organ has been submitted. The use of peripheral markers of oxidative stress could provide a tool that may be useful to define the role of oxidative stress in several pathological conditions of the brain [26]. Kramer et al. [27] investigated whether biochemical changes that occur in rat brain tissue are also reflected in the erythrocytes. They found partial parallelism between changes in cerebral cortex homogenate and erythrocytes after complete brain ischemia.
It is proposed that even after the abolishment of dementia, cognitive sequelae and predisposition to dementia may be noted [28]. From this point of view, it is important to verify the predisposing variables and preventive means for delirium. In this study, we aimed to verify an indicator related to oxidative process that could predict delirium preoperatively. Peripheral blood samples have been used to obtain information on the altered balance between the production of free radicals and the antioxidant capacity [21].
Section snippets
Patient selection
The study was carried out on patients admitted for CPB surgery to our Cardiovascular Surgery Clinic between February 2003 and December 2003. The approval of the Ethics Committee was obtained. A total of 50 consecutive patients (13 females; 37 males) who did not have dementia, who did not suffer from any systemic disease except hypertension or coronary artery disease and who had not smoked for at least 7 days before surgery were included into the study. All subjects were informed about the aims
Results
Twelve of the 50 study subjects met the DSM-IV-TR diagnostic criteria for delirium during postoperative follow-up. Patients diagnosed with delirium had a mean score of 15.7±4.3 points (range, 12–26) on the DRS. The delirium was mild in 7 patients and moderate in 5 patients according to the scores obtained from the DRS. The MMSE values showed a statistically significant postoperative decrease compared with the preoperative period in both groups.
The average age, bypass duration, cross-clamp
Discussion
It has been known for a long time that the risk of delirium and neuropsychological deficit development is high after CPB [34], [35], [36]. We found a significant decline in the MMSE score in the postacute stage after surgery in both the delirium and nondelirium groups. Berr et al. [37], [38] have shown with a series of studies that “oxidative stress and/or antioxidant deficiencies” increase damage to cerebral tissue and lead to cognitive decline with irreversible degeneration. Jackson et al.
Acknowledgment
This research has been supported by a research fund from Inonu University.
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