CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 6, November/December 2022 302 AFRICA which has been postulated to cause delirium and cognitive dysfunction.19 Inflammation and oxidative stress also play an important role in the pathogenesis of delirium.9 The neuroinflammatory hypothesis is currently one of the potential explanations for the pathophysiology of delirium.20,21 Acute peripheral inflammatory activation leads to increased pro-inflammatory cytokine and mediator levels in the central nervous system, leading to neuronal and synaptic dysfunction. These changes are subsequently associated with cognitive and neurobehavioural changes.22 Pro-inflammatory cytokines, including interleukin-1b, tumour necrosis factor-α and interleukin-6 generated from peripheral cells interact with the brain and are predictors for delirium. CRP is an important prototype marker for inflammation, which is mainly controlled by various cytokines including interleukin-6.23 Slor et al. observed that POD was associated with systematic inflammatory response and increased CRP levels in older hip-fracture patients.24 Similar to their observations, Vasunilashorn et al. found that elevated levels of pre-operative CRP predicted POD in patients undergoing non-cardiac surgery.25 In contrast to these findings, Lemstra et al. did not observe an association between pre-operative CRP levels and POD.26 In our study, we found an association between pre- and postoperative CRP levels and POD in cardiac surgery patients; however, this association was not significant in mulvariate regression analysis. ESR, which is an indirect acute-phase reactant, is commonly used in clinical practice. The role of ESR as a predictor of POD has not been evaluated in clinical studies.27,28 In this study, we observed for the first time that pre- and early postoperative ESR were independent predictors of POD in patients operated on for isolated CABG. The activity, density and size of thrombocytes may vary; larger thrombocytes are more active than smaller ones, containing more secretion granules and mitochondria.29 MPV, which is routinely measured in CBC devices, was shown to be a prognostic marker in various forms of cardiovascular disease.30 MPV is a parameter of thrombocyte function and activation, which plays an important role in the pathophysiology of cardiovascular complications.31 MPV was shown to be a risk factor for stroke among patients with a history of cerebrovascular disease.32 Previously, Saskin et al. observed that pre-operative CRP and MPV levels were predictors of postoperative AF in CABG patients.31 MPV is a predictor of vascular risk in patients with neurocognitive dysfunction.33 Qiu et al. observed that MPV levels were independent predictors of post-stroke depression.34 We observed in this study for the first time the predictive role of elevated MPV levels on POD. NLR, which is an easily applied marker of inflammation calculated from CBC has been shown to be a predictor of adverse events and mortality in various cardiovascular diseases.35 Several studies have shown the relationship between increased NLR and cerebrovascular diseases, schizophrenia and Alzheimer’s disease.9 In a pilot study, Egberts et al. observed an association between NLR and delirium in elderly patients.14 NLR was found to be an independent predictor of POD in elderly patients undergoing total hip arthroplasty for hip fracture.36 Similarly, we observed in our study that NLR on the first postoperative day was an independent predictor of POD in patients undergoing isolated CABG. PLR has been used to predict the prognosis of patients with various forms of cardiovascular disease and also patients undergoing cardiovascular surgery.12,37 Jiang et al. observed that increased PLR was a predictor of delirium in critically ill patients.21 In another study, Kotfis et al. found that decreased PLR was a predictor of POD in patients undergoing cardiac surgery.9 In our study, we found increased pre- and early postoperative PLR to be an independent predictor of POD. Duration of operation and CPB times were longer in the cognitive-dysfunction group. Also, the average number of grafts used were higher in this group of patients. Eva et al. evaluated predictors of POD in patients undergoing CABG and found that the duration of operation and CPB times were longer and the number of grafts were higher.38 Herrmann et al. evaluated aortic cross-clamp times in patients undergoing cardiac surgery and did not find a statistically significant relationship with POD.39 In our study, aortic cross-clamp times, CPB times and the number of distal anastomoses were not statistically different between the groups. Scoring systems are commonly used in the ICU to predict status and prognosis of the patients after cardiac surgery. Lin et al. observed in patients with POD that APACHE II scores were significantly higher when compared with the control group in patients undergoing vascular interventions.40 APACHE II is one of the most commonly used scores to predict POD in the ICU.41 In our study, we found APACHE II score to be an independent predictor of POD in patients undergoing CABG. Moreover, delirium has been suggested to be related to higher mortality and morbidity rates. Although it has such clinical importance, delirium is not noticed in many patients by the clinicians.38 In parallel with previous findings in the literature, we observed that POD was associated with prolonged ICU and hospital stay.42 There are limitations to this study. This was a single-centre, retrospective, observational study conducted with a limited number of patients. Because of the study design, we could not perform a causal relationship. Potential confounders that could have affected the inflammatory status of the patients might have affected our results. Conclusion POD is a commonly observed situation after cardiovascular surgery, which is associated with significant morbidity and mortality. Inflammation is an important underlying factor for POD. In this study, we observed MPV, NLR, PLR and ESR levels to be potential predictors of POD. These parameters can easily be calculated from CBC and routine blood samples. Although our results are promising, further studies are needed to clarify this issue. References 1. Greaves D, Psaltis PJ, Davis DHJ, Ross TJ, Ghezzi ES, Lampit A, et al. Risk factors for delirium and cognitive decline following coronary artery bypass grafting surgery: a systematic review and meta-analysis. J Am Heart Assoc 2020; 9(22): e017275. 2. Wimmer-Greinnecter G, Matheis G, Breden M. Breden canfes after cardiopulmonary bypass for coronary bypass grafting. Thorac Cardiovasc Surg 1998; 46: 207–212. 3. Şaşkın H, Özcan KS, Düzyol Ç, Maçika H, Aksoy R, İdiz M. An easily overlooked clinical phenomenon after coronary artery bypass graft surgery: postoperative delirium. Turk Gogus Kalp Dama 2016; 24(2): 248–257.
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