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. 2023 Aug 23;12:1–9. doi: 10.31661/gmj.v12i.3045

Postoperative Delirium and Dementia in Patients Undergoing Cardiac Surgery: A Review of Randomized Controlled Trials

Venus Shahabi Raberi 1, Morteza Solati Kooshk Qazi 2, Ali Zolfi gol 3, Rahil GhorbaniNia 4, Ozra Kahourian 1, Reza Faramarz Zadeh 1,*
PMCID: PMC11108672  PMID: 38774845

Abstract

Delirium and dementia are considered to be the most significant postoperative neurocognitive complications in patients undergoing cardiac surgery, particularly those aged 60 years and older, which reduces the post-surgery quality of life, prolongs hospitalization, increases costs, and elevated the rates of mortality. Nevertheless, the etiology, risk factors, and predictive biomarkers, have not been well elucidated particularly, in patients with unmanifested underline cognitive impairments. The present study aimed to review the findings on the etiology, factors increasing the risk of incidence, and predictive biomarkers of postoperative delirium and dementia after cardiac surgery, and to describe the suggested pharmacological and non-pharmacological interventions.

Keywords: Dementia, Postoperative Complications, Cardiac Surgery

Introduction

Postoperative cognitive decline (POCD) is a common sub-clinical condition following cardiac and non-cardiac surgery [1][2]. POCD is widely considered to be the most prominent in people over the age of 65 [3], and as the population all over the world is aging at an unprecedented rate, POCD has become more common [4]. Patients with POCD will generally experience a variety of neurological symptoms including anxiety, memory impairment, personality change, and mental confusion all of which lead to increased medical costs, reduced life independence, and are associated with mortality [4]. Currently, several types of POCD-related disorders have been listed, of which delirium and dementia are the most well-known. In addition, the cognitive decline caused by anesthesia or surgery could be followed by delirium or dementia [5][6].

Delirium is considered an acute fluctuating alteration in mental state that manifests as a disturbance in consciousness and cognitive function. There is a suggestion that delirium has a high incidence rate in hospitalized patients and is followed by increased rates of morbidity and mortality, and prolonged residence in the intensive care unit (ICU) and the hospital, thereby higher costs for both the patient and the government [7]. Postoperative delirium (POD) is described as a common complication after cardiac surgery [8] in which geriatric patients, cardiac surgery patients, and patients hospitalized in ICU are highly at risk of developing POD [9][10]. POD patients are widely believed to have longer hospital stays, a higher risk of dementia, and a higher risk of mortality [11].

Delirium can progress to dementia, which is characterized by the loss of cognitive functions including remembering, thinking, and reasoning. The development of dementia after delirium is of great concern to both third leading cause the patient and public health since the significant morbidity, mortality, and caregiver burden associated with dementia have been documented [ 12][13].

Importantly, dementia has recently ranked as the third leading cause of death in the United States [14]. Annually, more than 47 million people suffer from dementia which is equivalent to 5% of the world’s elderly population [15].

More importantly, it is expected that the incidence of dementia will increase substantially in the following years due to an aging population [14].

Recent studies have demonstrated that cardiac surgery could be associated with increased levels of biomarkers related to neurodegeneration including neurofilament light chain and Tau [16][17][18]. Despite the mentioned importance of postoperative delirium and dementia after cardiac surgery, the etiology of its occurrence has not been elucidated, and contradictory propositions have been hypothesized. Therefore, the present study attempted to clarify the main causes of postoperative delirium and dementia after cardiac surgery and compensatory pre-, intra-, and post-operative proceedings to prevent/reduce its incidence by reviewing the randomized controlled trials.

Cardiac Surgery Leads to Delirium and Dementia

In general, the pre-surgery cognitive state, the application of anesthetics, procedures and injuries during surgery, along with induced inflammation and stress are the most important assumptions about the etiology of cardiac surgery-related cognitive impairment. However, contradictions still exist in this regard, as new findings consistently weaken certain hypotheses and strengthen others. Thereby, the current study will review randomized controlled trials to analyze the assumptions about the etiology of postoperative delirium and dementia in patients undergoing cardiac surgery and then will assess the necessary proceedings to confront it.

Initially, it was thought that anesthetics used beforecardiac surgery would be the most important cause of POCD and subsequent POD and post-operative dementia, although subsequent studies have shown that the surgical process is associated with inflammation, oxidative stress, hypoxemia, and damage to the blood-brain barrier (BBB) as a causative agent, too [5][6]. It seems that patients who have an underlying neurodegenerative complication, although not manifested yet, are more susceptible to experiencing a condition known as a second hit. In fact, second hits are able to accelerate the process of neurodegeneration by the induction of cognitive decline after cardiac surgery [19]. The measurement of pre-and post-surgery levels of a critical biomarker of Alzheimer’s disease, cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), in patients with POCD can be considered the most important finding supporting this hypothesis [20].

Induction of inflammation can be described as a common feature of surgical procedures, especially cardiac surgery, which can be assumed as a bridge between surgery and POCD, POD, and postoperative dementia due to the involvement of inflammation in the development of neurodegenerative disorders [21][22][23]. C-reactive protein (CRP), for example, is an appropriate marker of inflammation in patients with delirium particularly those undergoing surgery [24]. Moreover, a dramatic elevation in the levels of inflammatory markers including interleukin-6 (IL-6), fibroblast growth factor 21 (FGF21) and 23, and CC-chemokine ligand 2 (CCL2) is reported [25][26][27]. Furthermore, glial fibrillary acidic protein (GFAP) is a neuroinflammatory marker that could represent the link between inflammation and neurodegenerative complications [28].

Risk Factors of Postoperative Delirium and Dementia after Cardiac Surgery

The determination of the association between the operative procedure, anesthetics, inflammation, and so forth, also postoperative neurological complications could benefit the understanding of the etiology of POD and postoperative dementia, however, it requires comprehensive studies. Indeed, multidisciplinary studies are needed to explore the overlap between preexisting cognitive impairment and POCD, POD, and postoperative dementia in the fields of anesthesia, surgery, and old age psychiatry and neurology. The intradisciplinary alignment of the terminology and diagnostic criteria may improve our understanding of the etiology, biomarkers, and preventive strategies [5][29].

Understanding the cause of cognitive impairment after cardiac surgery can lead to the determination of relevant biomarkers. As a result, the potential biomarkers might estimate the probability of POD and the development of POD to dementia in patients undergoing cardiac surgery before and after the procedure [30][31].

Although the relevant biomarkers have not been fully understood, it is documented that elder hospitalized patients with delirium represent a remarkable 12-fold increase in developing dementia, hence delirium could be considered a reliable marker of postoperative dementia [32][33]. Along with that, several attempts have recently been made to identify risk factors associated with POD and dementia after cardiac surgery. Although scientists believed that underlying cognitive impairments before surgery, whose symptoms did not manifest were responsible for POD and dementia after cardiac surgery, Lewis et al. reported evidence against this belief [34].

By examining 320 patients who underwent cardiac surgery, it was found that 15.6% of patients had depression before surgery and 13.4% of patients experienced depression after surgery. Interestingly, preoperative depression was mainly associated with increased anxiety and decreased self-ratings on several quality-of-life domains, while the experience of postoperative depression four weeks after surgery was associated with neurocognitive complications including as poor memory, attention, processing speed, verbal fluency, and fine motor speed [34]. As a result, it can be assumed that although preoperative depression does not cause further neurocognitive disorders, postoperative depression could be related to several cognitive impairments, hence following the patients’ condition in terms of depression after surgery can be a preventive approach to confront delirium and dementia. In addition, a 5-year follow-up study of 114 elderly patients aged 70 and over who underwent cardiac surgery showed that preoperative mild cognitive impairment might be a risk factor for delirium and dementia after cardiac surgery [35].

Also, 87% of the patients who had experienced dementia within 5 years after surgery had experienced POD, too [35]. Therefore, POD can be considered a potential risk factor for the development of dementia after cardiac surgery. In fact, assessment of the preoperative cognitive function in elderly patients undergoing cardiac surgery should be screened. Moreover, patients who have experienced POD should be followed up to enable the early detection of dementia symptoms and to prevent the subsequent drastic consequences. In addition to pre- and postoperative cognitive status, a number of cardiac and inflammatory biomarkers can be considered risk factors for POD and subsequent dementia. CRP, for example, is considered the most reliable preoperative biomarker for the prediction of POD in patients undergoing noncardiac surgery [ 36]. Similarly, the increased levels of IL-2 and TNF-α were significantly associated with POD in patients undergoing coronary artery bypass grafting, and more importantly, researchers have provided cutoff scores for increased risk [37].

In patients undergoing cardiac surgery, particularly those experiencing cardiopulmonary bypass, a systematic stress and subsequently systematic inflammatory response occurs accompanied by elevated levels of inflammatory markers including cytokines and chemokines. Also that could contribute to devastating processes including the dysfunction of endothelial and the disruption of BBB [38]. Consequently, these processes could be followed by the susceptibility of the brain to neuronal damage by neuroinflammatory mediators and the activation of microglia leading to the development of POD [39]. In addition, plasma levels of several neurotransmitters including reduced cholinesterase and increased dopamine could be considered biomarkers of POD [39][40]. On the contrary, Wiberg et al., by studying 193 patients undergoing coronary artery bypass grafting and/or aortic valve replacement, demonstrated that higher (70-80 mmHg) or lower (40-50 mmHg) scores of mean arterial pressure during cardiopulmonary bypass had no significant association with cerebral injury biomarkers including neuron-specific enolase, tau, neurofilament light, and the glial marker known as glial fibrillary acidic protein [41]. In this sense, it is encouraged to conduct further randomized controlled trials measuring pre, inter, and postoperative heart-related markers and assess their association with biomarkers of cerebral injury and outcomes of pre and post surgery brain imaging tests.

Preventive Interventions for Delirium and Dementia after Cardiac Surgery

Although the etiology, risk factors, and biomarkers of delirium and dementia after cardiac surgery are still not fully understood, interventions have been conducted in several randomized controlled trials to prevent postoperative cognitive impairment in patients undergoing cardiac surgery. In addition to addressing undesirable neurocognitive consequences after surgery, such interventions can elucidate the causes of occurrence and make available risk factors. The randomized controlled trials conducted so far have attempted to prevent delirium and dementia after heart surgery through two types of interventions, including pharmacological interventions and non-pharmacological (operative) interventions reviewed below.

Pharmacological Interventions

Anesthesia and cardiac surgery procedures have been hypothesized as the main possible causes of cognitive post surgery impairments due to inducing systematic inflammation and oxidative stress. Therefore, in several studies, researchers have attempted to reduce or eliminate the neurocognitive adverse effects of surgery through pharmacological interventions capable of reducing inflammation and stress. Ketamine is an anesthetic with anti-inflammatory properties that can reduce POD in animal studies [42][ 43]. Moreover, a human study revealed that adding ketamine to routine anesthetics could reduce POD from 31% in the placebo group to 3% [44]. A randomized controlled trial on patients aged 65 years and older undergoing cardiac surgery with cardiopulmonary bypass demonstrated that during cardiopulmonary bypass the infusion of ketamine (31.25%) significantly reduced 24-h POD after surgery compared to propofol (56.25%) [45].

The application of sedative compounds is another pharmacological intervention that has been studied to reduce or eliminate neurocognitive consequences. Dexmedetomidine, an α2 adrenoceptor agonist, is frequently administered to patients in the intensive care unit due to its sedative and analgesic properties [46][47]. Perioperative administration of dexmedetomidine was accompanied by desired outcomes including reduction of opioid utilization, improvement of postoperative analgesia, and suppression of inflammation all of which are considered possible causes of cognitive impairment [48][49]. In addition, postoperative administration of dexmedetomidine led to a lower risk of suffering from mental complaints in patients who underwent cardiac surgery [50].

A single-center, double-blind, randomized controlled clinical trial on 508 patients undergoing cardiac surgery, of which 251 people received dexmedetomidine and 257 participated in the placebo group, revealed that psychological impairment could be significantly reduced in the dexmedetomidine group relative to the placebo group [51]. Similarly, another single-blinded, prospective, randomized controlled trial in 183 elder patients 60 years or older undergoing cardiac surgery, of which 91 patients in the dexmedetomidine group and others received propofol, demonstrated that this sedative agent compared to propofol reduced the incidence (17.5% compared to 31.5%), delayed onset (day 2 versus day 1), and shortened duration of POD (2 days versus 3 days) [52].

Moreover, the participation of 46 patients who underwent coronary artery bypass graft surgery participated in a randomized controlled trial, suggested that dexmedetomidine compared to typical anesthesia could increase the levels of neural protective biomarkers including matrix metalloproteinase-12 and myelin basic protein [53]. However, a higher rate of hypotension was reported as an adverse effect of dexmedetomidine administration requiring further studies to elucidate other possible side effects [51].

Piracetam is a derivative of the neurotransmitter γ-aminobutyric acid with cerebroprotective properties that its administration leads to better cognitive function in patients undergoing coronary artery bypass surgery and reduces the early postoperative substantial decline of neuropsychological performances [54]. Melatonin is a pineal gland hormone thought to be important in sleep/wake regulation which has been used in a wide range of studies from neurological disorders to environmental improvements [55][56].

Several studies over the past decade have shown that the administration of this hormone can significantly reduce POD and post-surgery sleep/wake complications [55]. However, a randomized double-blind controlled clinical trial 7 days of treatment with melatonin starting 2 days before the surgery did not support the prophylactic application of this hormone to prevent POD [57].

Similarly, a double-blind, randomized, controlled study showed that dietary melatonin therapy in patients with mild cognitive impairment can significantly increase hippocampal volume and significantly reduce CSF T-tau protein levels [58].

Because mild cognitive impairment is a transitory state to dementia, while delirium is a reliable risk factor for progression to dementia, administration of melatonin is associated with cardiac surgery, although no confirmatory studies have been performed. Insulin is another hormone its administration at normoglycemia during cardiac surgery may lead to the prevention of short- and long-term memory decline postoperatively [59].

A randomized, double-blind controlled trial revealed that the administration of insulin intranasally during cardiac surgery in patients with type 2 diabetes does not cause hypoglycemia which could be important for neural cells [60].

Non-pharmacological Interventions

Non-pharmacological interventions to reduce delirium and dementia after cardiac surgery can be divided into three categories: pre-, intra-, and post-surgery interventions. However, most of the interventions are related to the procedures during and after surgery.

Cognitive training is a well-studied peri and intraoperative intervention though to be able to durably improve cognitive reserve in POCD and POD and thereby could potentially reduce the risk of postoperative cognitive impairment in patients undergoing cardiac surgery. A randomized, single-center, controlled trial studied the perioperative cognitive training efficacy in 65 patients elderly aged 60-90. The findings showed that this program could significantly reduce the risk of POCD and POD although further studies were encouraged [ 61].

In addition, another randomized clinical trial on 60 elderly patients revealed that postoperative cognitive training could improve health-related quality of life and reduce cognitive failure three months after heart valve surgery [62]. Early mobilization was another strategy that Shirvani et al. introduced to reduce POD via a double-blind randomized clinical trial on 92 patients undergoing coronary artery bypass grafting [63].

Other interventions have been focused on cerebral oxygenation. A randomized controlled pilot study on 82 patients, older than 65, who underwent coronary artery bypass graft surgery on cardiopulmonary bypass revealed that the incidence of POD in the intervention group of patients, was significantly lower (2.4%) compared to controls (20%) in patients whose regional cerebral tissue desaturations of more than 15% of the pre-induction value or below 50% were avoided [64].

Similarly, the optimization of cerebral oxygenation and observance of intraoperative oxygen concentration are considered strategies for reducing the risk of postoperative impairment of cognitive ability in elderly patients undergoing cardiac surgery [65][ 66]. In addition, hemodilution during coronary artery bypass grafting using cardiopulmonary bypass (maintaining the hematocrit above 25% by transfusion of packed red blood cells), performing an aortic off-pump coronary artery bypass instead of conventional procedure, and the application of conservative strategies (coronary angiogram only if recurrent ischemia or heart failure) instead of invasive approaches (routine coronary angiogram) are among the most important interventions conducted to reduce the risk of delirium and dementia after heart surgery [67][68][69].

Conclusion

Delirium and dementia are among the most important neurocognitive complications after cardiac surgery. However, the major causative factors are not fully understood, nor are the risk factors and biomarkers. The present study revealed that despite the valuable efforts during recent years, the etiology and definitive diagnosis of these complications, especially in elderly people who do not manifest symptoms of precognitive disorders, requires further investigations. In addition, pharmacological interventions including sedative agents or adjuvant anesthetics along with non-pharmacological interventions such as cognitive training, cerebral oxygenation, novel surgical approaches, and hemodilution can significantly reduce the risk of postoperative delirium and dementia.

Conflict of Interest

The authors declare that there are no conflicts of interests.

References

  1. Otomo S, Maekawa K, Baba T, Goto T, Yamamoto T. Evaluation of the risk factors for neurological and neurocognitive impairment after selective cerebral perfusion in thoracic aortic surgery . Anesth. 2020;(34):527–36. doi: 10.1007/s00540-020-02783-x. [DOI] [PubMed] [Google Scholar]
  2. Yuhe K, Chew STH, Ang AS, Ng RRG, Boonkiangwong N, Liu W. Comparison of postoperative cognitive decline in patients undergoing conventional vs miniaturized cardiopulmonary bypass: A randomized, controlled trial . Ann Card Anaesth. 2020;3(23):309–309. doi: 10.4103/aca.ACA_192_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Wang P, Yin X, Chen G, Li L, Le Y, Xie Z. Perioperative probiotic treatment decreased the incidence of postoperative cognitive impairment in elderly patients following non-cardiac surgery: A randomised double-blind and placebo-controlled trial . Clin Nutr. 2021;1(40):64–71. doi: 10.1016/j.clnu.2020.05.001. [DOI] [PubMed] [Google Scholar]
  4. Wen Y. Anesthesia with propofol and sevoflurane on postoperative cognitive function of elderly patients undergoing general thoracic surgery . Pak J Pharm Sci. 2017;(30):1107–1110. [PubMed] [Google Scholar]
  5. Evered L, Scott DA, Silbert B. Cognitive decline associated with anesthesia and surgery in the elderly: does this contribute to dementia prevalence . Curr Opin Psychiatry. 2017;3(30):220–6. doi: 10.1097/YCO.0000000000000321. [DOI] [PubMed] [Google Scholar]
  6. Avidan MS, Evers AS. Review of clinical evidence for persistent cognitive decline or incident dementia attributable to surgery or general anesthesia . J Alzheimers Dis. 2011;2(24):201–16. doi: 10.3233/JAD-2011-101680. [DOI] [PubMed] [Google Scholar]
  7. Dubiel C, Hiebert BM, Stammers AN, Sanjanwala RM, Tangri N, Singal RK. Delirium definition influences prediction of functional survival in patients one-year postcardiac surgery . J Thorac Cardiovasc Surg. 2022;2(163):725–34. doi: 10.1016/j.jtcvs.2020.07.028. [DOI] [PubMed] [Google Scholar]
  8. Kotfis K, Szylińska A, Listewnik M, Strzelbicka M, Brykczyński M, Rotter I. Early delirium after cardiac surgery: an analysis of incidence and risk factors in elderly (≥ 65 years) and very elderly (≥ 80 years) patients . Clin Interv Aging. 2018:1061–70. doi: 10.2147/CIA.S166909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Igwe EO, Nealon J, Mohammed M, Hickey B, Chou K-R, Chen K-H. Multi-disciplinary and pharmacological interventions to reduce post-operative delirium in elderly patients: A systematic review and meta-analysis . J Clin Anesth. 2020;(67):110004–110004. doi: 10.1016/j.jclinane.2020.110004. [DOI] [PubMed] [Google Scholar]
  10. Krewulak KD, Stelfox HT, Ely EW, Fiest KM. Risk factors and outcomes among delirium subtypes in adult ICUs: a systematic review . J Crit Care. 2020;(56):257–64. doi: 10.1016/j.jcrc.2020.01.017. [DOI] [PubMed] [Google Scholar]
  11. Fuchs S, Bode L, Ernst J, Marquetand J, von Känel, Böttger S. Delirium in elderly patients: prospective prevalence across hospital services . Gen Hosp Psychiatry. 2020;(67):19–25. doi: 10.1016/j.genhosppsych.2020.08.010. [DOI] [PubMed] [Google Scholar]
  12. Aung Thein, Pereira JV, Nitchingham A, Caplan GA. A call to action for delirium research: meta-analysis and regression of delirium associated mortality . BMC Geriatri. 2020;(20):1–12. doi: 10.1186/s12877-020-01723-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chiao CY, Wu HS, Hsiao CY. Caregiver burden for informal caregivers of patients with dementia: A systematic review . Int Nur Rev. 2015;3(62):340–50. doi: 10.1111/inr.12194. [DOI] [PubMed] [Google Scholar]
  14. Kramarow EA, Tejada-Vera B. Dementia mortality in the United States, 2000-2017 . National Vital Statistics Reports: From the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System . 2019;2(68):1–29. [PubMed] [Google Scholar]
  15. Prince M, Guerchet M, Prina M. The epidemiology and impact of dementia-current state and future trends . WHO Thematic Briefing. 2015;(1):1–1. [Google Scholar]
  16. Alifier M, Olsson B, Andreasson U, Cullen NC, Czyżewska J, Jakubów P. Cardiac surgery is associated with biomarker evidence of neuronal damage . J Alzheimers Dis. 2020;4(74):1211–20. doi: 10.3233/JAD-191165. [DOI] [PubMed] [Google Scholar]
  17. Chan CK, Song Y, Greene R, Lindroth H, Khan S, Rios G. Meta-analysis of ICU delirium biomarkers and their alignment with the NIA-AA research framework . Am J Crit Care. 2021;4(30):312–9. doi: 10.4037/ajcc2021771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. DiMeglio M, Furey W, Hajj J, Lindekens J, Patel S, Acker M. Observational study of long-term persistent elevation of neurodegeneration markers after cardiac surgery . Sci Rep. 2019;1(9):7177–7177. doi: 10.1038/s41598-019-42351-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Deiner S, Baxter MG, Mincer JS, Sano M, Hall J, Mohammed I. Human plasma biomarker responses to inhalational general anaesthesia without surgery . Br J Anaesth. 2020;3(125):282–90. doi: 10.1016/j.bja.2020.04.085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Evered L, Silbert B, Scott DA, Ames D, Maruff P, Blennow K. Cerebrospinal fluid biomarker for Alzheimer disease predicts postoperative cognitive dysfunction . Anesthesiol. 2016;2(124):353–61. doi: 10.1097/ALN.0000000000000953. [DOI] [PubMed] [Google Scholar]
  21. Furon Y, Dang Van, Blanchard S, Saulnier P, Baufreton C. Effects of high-intensity inspiratory muscle training on systemic inflammatory response in cardiac surgery-A randomized clinical trial . Physiother Theory Pract. 2023:1–11. doi: 10.1080/09593985.2022.2163212. [DOI] [PubMed] [Google Scholar]
  22. Habes QL, Kant N, Beunders R, van Groenendael, Gerretsen J, Kox M. Relationships Between Systemic Inflammation Intestinal Damage and Postoperative Organ Dysfunction in Adults Undergoing Low-Risk Cardiac Surgery . Heart Lung Circ. 2023;3(32):395–404. doi: 10.1016/j.hlc.2022.12.006. [DOI] [PubMed] [Google Scholar]
  23. Zhu Y, Zhou M, Jia X, Zhang W, Shi Y, Bai S. Inflammation disrupts the brain network of executive function after cardiac surgery . Ann Surg. 2023;3(277):e689–e689. doi: 10.1097/SLA.0000000000005041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sun Y, Peng H-P, Wu T-T. Postoperative C-Reactive Protein Predicts Postoperative Delirium in Colorectal Cancer Following Surgery . Clin Interv Aging. 2023:559–70. doi: 10.2147/CIA.S387117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Liu D, Szeto WY, Laudanski K. Elevated Serum Fibroblast Growth Factor 23 (FGF-23) Perseveres into a Convalescence Period After Elective Cardiac Surgery, with Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Cartilage Oligomeric Matrix Protein (COMP) Being Part of the Peri-Surgical Pro-Arteriosclerotic Inflammatory Response . Med Sci Monit. 2023;(29):e937934–1. doi: 10.12659/MSM.937934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Su L-J, Chen M-J, Yang R, Zou H, Chen T-T, Li S-L. Plasma biomarkers and delirium in critically ill patients after cardiac surgery: A prospective observational cohort study . Heart & Lung. 2023;(59):139–45. doi: 10.1016/j.hrtlng.2023.02.010. [DOI] [PubMed] [Google Scholar]
  27. Xie M, Lin Z, Ji X, Luo X, Zhang Z, Sun M. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2 . Elsevier. 2023;1(79):109–125. doi: 10.1016/j.jhep.2023.02.036. [DOI] [PubMed] [Google Scholar]
  28. Maes M, Thisayakorn P, Thipakorn Y, Tantavisut S, Sirivichayakul S, Vojdani A. Reactivity to neural tissue epitopes, aquaporin 4 and heat shock protein 60 is associated with activated immune–inflammatory pathways and the onset of delirium following hip fracture surgery . Eur Geriatr Med. 2023;1(14):99–112. doi: 10.1007/s41999-022-00729-y. [DOI] [PubMed] [Google Scholar]
  29. Fong TG, Inouye SK. The inter-relationship between delirium and dementia: the importance of delirium prevention . Nat Rev Neuro. 2022;10(18):579–96. doi: 10.1038/s41582-022-00698-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McKay TB, Rhee J, Colon K, Adelsberger K, Turco I, Mueller A. Preliminary study of serum biomarkers associated with delirium after major cardiac surgery . J Cardiothorac Vasc Anesth. 2022;1(36):118–24. doi: 10.1053/j.jvca.2021.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang S, Greene R, Song Y, Chan C, Lindroth H, Khan S. Postoperative delirium and its relationship with biomarkers for dementia: a meta-analysis . Int Psychogeriatr. 2022;4(34):377–90. doi: 10.1017/S104161022100274X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pereira JVB, Aung Thein, Nitchingham A, Caplan GA. Delirium in older adults is associated with development of new dementia: a systematic review and meta-analysis . Int J Geriatr Psychiatry. 2021;7(36):993–1003. doi: 10.1002/gps.5508. [DOI] [PubMed] [Google Scholar]
  33. Sadlonova M, Vogelgsang J, Lange C, Günther I, Wiesent A, Eberhard C. Identification of risk factors for delirium, cognitive decline, and dementia after cardiac surgery (FINDERI—find delirium risk factors):a study protocol of a prospective observational study. . BMC Cardiovasc Disord. 2022;1(22):299. doi: 10.1186/s12872-022-02732-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lewis C, Dokucu ME, Brown CH, Balmert L, Srdanovic N, Madhan AS. Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial . BMC anesthesiol. 2022;1(22):1–12. doi: 10.1186/s12871-022-01672-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lingehall HC, Smulter NS, Lindahl E, Lindkvist M, Engström KG, Gustafson YG. Preoperative cognitive performance and postoperative delirium are independently associated with future dementia in older people who have undergone cardiac surgery: a longitudinal cohort study . Crit Care Med. 2017;8(45):1295–1295. doi: 10.1097/CCM.0000000000002483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ayob F, Lam E, Ho G, Chung F, El-Beheiry H, Wong J. Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review . BMC anesthesiol. 2019;1(19):1–16. doi: 10.1186/s12871-019-0693-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kazmierski J, Banys A, Latek J, Bourke J, Jaszewski R. Raised IL-2 and TNF-α concentrations are associated with postoperative delirium in patients undergoing coronary-artery bypass graft surgery . Int Psychogeriatr. 2014;5(26):845–55. doi: 10.1017/S1041610213002378. [DOI] [PubMed] [Google Scholar]
  38. Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery . Circ. 2009;2(119):229–36. doi: 10.1161/CIRCULATIONAHA.108.795260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Cerejeira J, Nogueira V, Luís P, Vaz-Serra A, Mukaetova-Ladinska EB. The cholinergic system and inflammation: common pathways in delirium pathophysiology . J Am Geriatr Soc. 2012;4(60):669–75. doi: 10.1111/j.1532-5415.2011.03883.x. [DOI] [PubMed] [Google Scholar]
  40. Gaudreau J-D, Gagnon P. Psychotogenic drugs and delirium pathogenesis: the central role of the thalamus . Med Hypotheses. 2005;3(64):471–5. doi: 10.1016/j.mehy.2004.08.007. [DOI] [PubMed] [Google Scholar]
  41. Wiberg S, Holmgaard F, Blennow K, Nilsson JC, Kjaergaard J, Wanscher M. Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial . Interact Cardiovasc Thorac Surg. 2021;2(32):229–35. doi: 10.1093/icvts/ivaa264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Dale O, Somogyi AA, Li Y, Sullivan T, Shavit Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery A systematic review and meta-analysis . Anesth Analg. 2012;4(115):934–43. doi: 10.1213/ANE.0b013e3182662e30. [DOI] [PubMed] [Google Scholar]
  43. Loix S, De Kock, Henin P. The anti-inflammatory effects of ketamine: state of the art . Acta Anaesthesiol Belg. 2011;1(62):47–58. [PubMed] [Google Scholar]
  44. Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass . J Cardiothorac Vasc Anesth. 2009;5(23):651–7. doi: 10.1053/j.jvca.2008.12.021. [DOI] [PubMed] [Google Scholar]
  45. Siripoonyothai S, Sindhvananda W. Comparison of postoperative delirium within 24 hours between ketamine and propofol infusion during cardiopulmonary bypass machine: a randomized controlled trial . Ann Card Anaesth. 2021;3(24):294–294. doi: 10.4103/aca.ACA_85_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Jacob Y, Schneider B, Spies C, Heinrich M, von Haefen, Kho W. In a secondary analysis from a randomised, double-blind placebo-controlled trial Dexmedetomidine blocks cholinergic dysregulation in delirium pathogenesis in patients with major surgery . Sci Rep. 2023;1(13):3971–3971. doi: 10.1038/s41598-023-30756-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Loomba RS, Villarreal EG, Dhargalkar J, Rausa J, Dorsey V, Farias JS. The effect of dexmedetomidine on renal function after surgery: A systematic review and meta-analysis . J Clin Pharm Ther. 2022;3(47):287–97. doi: 10.1111/jcpt.13527. [DOI] [PubMed] [Google Scholar]
  48. Ueki M, Kawasaki T, Habe K, Hamada K, Kawasaki C, Sata T. The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass . Anesth. 2014;7(69):693–700. doi: 10.1111/anae.12636. [DOI] [PubMed] [Google Scholar]
  49. Wang K, Wu M, Xu J, Wu C, Zhang B, Wang G. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis . Br J Anaesth. 2019;6(123):777–94. doi: 10.1016/j.bja.2019.07.027. [DOI] [PubMed] [Google Scholar]
  50. Zi J, Yi oF, Dong C, Zhao Y, Li D, Tan Q. Anxiety administrated by dexmedetomidine to prevent new-onset of postoperative atrial fibrillation in patients undergoing off-pump coronary artery bypass graft . Int Heart J. 2020;2(61):263–72. doi: 10.1536/ihj.19-132. [DOI] [PubMed] [Google Scholar]
  51. Dong C-h, Gao C-n, An X-h, Li N, Yang L, Li D-c. Nocturnal dexmedetomidine alleviates post–intensive care syndrome following cardiac surgery: a prospective randomized controlled clinical trial . BMC Med. 2021;1(19):1–14. doi: 10.1186/s12916-021-02175-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V. Dexmedetomidine versus propofol sedation reduces delirium after cardiac surgery: a randomized controlled trial . Anesthesiol. 2016;2(124):362–8. doi: 10.1097/ALN.0000000000000951. [DOI] [PubMed] [Google Scholar]
  53. Kowalczyk M, Panasiuk-Kowalczyk A, Stadnik A, Guz M, Cybulski M, Jeleniewicz W. Dexmedetomidine Increases MMP-12 and MBP Concentrations after Coronary Artery Bypass Graft Surgery with Extracorporeal Circulation Anaesthesia without Impacting Cognitive Function: A Randomised Control Trial . Int J Environ Res Public Health. 2022;24(19):16512–16512. doi: 10.3390/ijerph192416512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Holinski S, Claus B, Alaaraj N, Dohmen PM, Kirilova K, Neumann K. Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery . Med Sci Monit. 2008;11(14):PI53–7. [PubMed] [Google Scholar]
  55. Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial . Int J Geriatr Psychiatry. 2011;7(26):687–94. doi: 10.1002/gps.2582. [DOI] [PubMed] [Google Scholar]
  56. Rostami S, Azhdarpoor A, Baghapour MA, Dehghani M, Samaei MR, Jaskulak M. The effects of exogenous application of melatonin on the degradation of polycyclic aromatic hydrocarbons in the rhizosphere of Festuca . Environ Pollut. 2021;(274):116559–116559. doi: 10.1016/j.envpol.2021.116559. [DOI] [PubMed] [Google Scholar]
  57. Ford AH, Flicker L, Kelly R, Patel H, Passage J, Wibrow B. The Healthy Heart-Mind trial: randomized controlled trial of melatonin for prevention of delirium . J Am Geriatr Soc. 2020;1(68):112–9. doi: 10.1111/jgs.16162. [DOI] [PubMed] [Google Scholar]
  58. Xu L, Yu H, Sun H, Hu B, Geng Y. Dietary melatonin therapy alleviates the lamina cribrosa damages in patients with mild cognitive impairments: A double-blinded, randomized controlled study . Med Sci Monit. 2020;(26):e923232–1. doi: 10.12659/MSM.923232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Badenes R, Qeva E, Giordano G, Romero-García N, Bilotta F. Intranasal insulin administration to prevent delayed neurocognitive recovery and postoperative neurocognitive disorder: A narrative review . Int J Environ Res Public Health. 2021;5(18):2681–2681. doi: 10.3390/ijerph18052681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Roque P, Yosuke N, Tamaki S, Wykes L, Akiko K, Hiroshi Y. Intranasal administration of 40 and 80 units of insulin does not cause hypoglycemia during cardiac surgery: a randomized controlled trial . Can J Anaesth. 2021;7(68):991–9. doi: 10.1007/s12630-021-01969-5. [DOI] [PubMed] [Google Scholar]
  61. O’Gara BP, Mueller A, Gasangwa DVI, Patxot M, Shaefi S, Khabbaz K. Prevention of early postoperative decline: a randomized, controlled feasibility trial of perioperative cognitive training . Anesth Analg. 2020;3(130):586–586. doi: 10.1213/ANE.0000000000004469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Butz M, Gerriets T, Sammer G, El-Shazly J, Tschernatsch M, Schramm P, Doeppner TR, Braun T, Boening A, Mengden T, Choi YH. The impact of postoperative cognitive training on health-related quality of life and cognitive failures in daily living after heart valve surgery: A randomized clinical trial . Brain and Behavior. 2023;3(13):e2915–e2915. doi: 10.1002/brb3.2915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shirvani F, Naji SA, Davari E, Sedighi M. Early mobilization reduces delirium after coronary artery bypass graft surgery . Asian Cardiovasc Thorac Ann. 2020;9(28):566–71. doi: 10.1177/0218492320947230. [DOI] [PubMed] [Google Scholar]
  64. Kunst G, Gauge N, Salaunkey K, Spazzapan M, Amoako D, Ferreira N, Green DW, Ballard C. Intraoperative optimization of both depth of anesthesia and cerebral oxygenation in elderly patients undergoing coronary artery bypass graft surgery—a randomized controlled pilot trial . Journal of cardiothoracic and vascular anesthesia. 2020;5(34):1172–81. doi: 10.1053/j.jvca.2019.10.054. [DOI] [PubMed] [Google Scholar]
  65. Shaefi S, Shankar P, Mueller AL, O’Gara BP, Spear K, Khabbaz KR, Bagchi A, Chu LM, Banner-Goodspeed V, Leaf DE, Talmor DS. Intraoperative oxygen concentration and neurocognition after cardiac surgery: a randomized clinical trial . Anesthesiology. 2021;2(134):189–201. doi: 10.1097/ALN.0000000000003650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Uysal S, Lin HM, Trinh M, Park CH, Reich DL. Optimizing cerebral oxygenation in cardiac surgery: A randomized controlled trial examining neurocognitive and perioperative outcomes . The Journal of Thoracic and Cardiovascular Surgery. 2020;3(159):943–53. doi: 10.1016/j.jtcvs.2019.03.036. [DOI] [PubMed] [Google Scholar]
  67. Sanchis J, Núñez E, Barrabés JA, Marín F, Consuegra-Sánchez L, Ventura S, Valero E, Roqué M, Bayés-Genís A, Del Blanco, Dégano I. Randomized comparison between the invasive and conservative strategies in comorbid elderly patients with non-ST elevation myocardial infarction . European journal of internal medicine. 2016;(35):89–94. doi: 10.1016/j.ejim.2016.07.003. [DOI] [PubMed] [Google Scholar]
  68. Soliman R, Saad D, Abukhudair W, Abdeldayem S. The neurocognitive outcomes of hemodilution in adult patients undergoing coronary artery bypass grafting using cardiopulmonary bypass . Ann Card Anaesth. 2022;2(25):133–133. doi: 10.4103/aca.aca_206_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Szwed K, Pawliszak W, Szwed M, Tomaszewska M, Anisimowicz L, Borkowska A. Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial . The Journal of Thoracic and Cardiovascular Surgery. 2021;4(161):1275–82. doi: 10.1016/j.jtcvs.2019.09.081. [DOI] [PubMed] [Google Scholar]

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