Consistent patterns in the inconsistent associations of Insulin-like growth factor 1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin 6 (IL-6) levels with delirium in surgical populations. A systematic review and meta-analysis

Adamis, Dimitrios; Gool, Willem A. van; Eikelenboom, Piet

doi:10.1016/j.archger.2021.104518

Cited by 16 publications

(16 citation statements)

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“…Inflammatory factors can directly interfere with neural activity and synaptic junction function in patients, such as high levels of IL-1 β in the hippocampus can reduce synaptic plasticity, hinder potential transmission, and lead to impaired learning and memory function in patients; elevated TNF- α levels can also stimulate nerve cells other than neurons in the brain, regenerate actin, present degenerative changes in the nervous system, and induce the production of POD [ 32 ]. Therefore, active monitoring of the levels of the above inflammatory factors after surgery plays a role in predicting delirium, considering that nonsteroidal anti-inflammatory drugs can inhibit the formation and release of the above inflammatory factors, and timely application of drug intervention after surgery can prevent the occurrence of POD to a certain extent [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Correlation Analysis of Inflammatory Markers CRP and IL‐6 and Postoperative Delirium (POD) in Elderly Patients: A Meta‐Analysis of Observational Studies

Huang

Feng

2022

Journal of Environmental and Public Health

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Background. Postoperative delirium (POD) is very common in the elderly surgical population, and its occurrence is associated with multiple factors such as preoperative, intraoperative, and postoperative factors, and the increase of serum inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) is considered to be associated with the occurrence of POD, but the results of multiple studies are inconsistent. In this study, we investigated the correlation between inflammatory markers CRP and IL-6 and POD in elderly patients by literature search and meta-analysis. Methods. We searched PubMed, Web of Science, the Cochrane library, Embase, Ovid, and Springer Link for cohort studies or case-control studies that investigated the factors involved in the occurrence of POD, used the Newcastle-Ottawa Scale (NOS) to assess the quality of the selected literature, and combined the differences in serum CRP and IL-6 levels between POD and non-POD patients after surgery to evaluate the predictive value of CRP and IL-6 for the occurrence of POD. Results. This research comprised 16 papers for quantitative analysis, with a total of 2967 patients, 758 with POD and 2209 with non-POD. There were 16 cohort studies (100%) and 0 case-control studies (0%) across all the collected literatures; there were 15 prospective cohort studies and 1 retrospective cohort research. A meta-analysis revealed a statistically significant difference in serum IL-6 levels between POD patients after surgery and non-POD patients [ MD = 115.68 , 95% CI (25.70, 206.66), Z = 2.52 , P = 0.012 ], as well as a statistically significant difference in serum CRP levels [ MD = 27.67 , 95% CI (12.77, 42.58), Z = 3.64 , P = 0.0003 ]. Discussion. Early after surgery, serum IL-6 and CRP levels were considerably higher in POD patients than in non-POD patients, indicating that early serum inflammatory variables are likely to be predictors of POD. After surgery, the levels of the aforementioned inflammatory factors should be actively monitored to forecast the emergence of delirium, and active treatment should be used to limit the creation and release of the aforementioned inflammatory factors.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Correlation Analysis of Inflammatory Markers CRP and IL‐6 and Postoperative Delirium (POD) in Elderly Patients: A Meta‐Analysis of Observational Studies

Huang

Feng

2022

Journal of Environmental and Public Health

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“…However, midazolam treatment had no influence on the expression of these cytokines. IL-6 seems to be of particular interest as it seems to be a consistent predictor of delirium in surgical samples [40]. Therefore, we can conclude that midazolam does not strongly contribute to pro-inflammatory signaling, being discussed as additional factors in the development of POD [12][13][14].…”

Section: Discussionmentioning

confidence: 87%

Midazolam impacts acetyl—And butyrylcholinesterase genes: An epigenetic explanation for postoperative delirium?

et al. 2022

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Midazolam is a widely used short-acting benzodiazepine. However, midazolam is also criticized for its deliriogenic potential. Since delirium is associated with a malfunction of the neurotransmitter acetylcholine, midazolam appears to interfere with its proper metabolism, which can be triggered by epigenetic modifications. Consequently, we tested the hypothesis that midazolam indeed changes the expression and activity of cholinergic genes by acetylcholinesterase assay and qPCR. Furthermore, we investigated the occurrence of changes in the epigenetic landscape by methylation specific PCR, ChiP-Assay and histone ELISA. In an in-vitro model containing SH-SY5Y neuroblastoma cells, U343 glioblastoma cells, and human peripheral blood mononuclear cells, we found that midazolam altered the activity of acetylcholinesterase /buturylcholinesterase (AChE / BChE). Interestingly, the increased expression of the buturylcholinesterase evoked by midazolam was accompanied by a reduced methylation of the BCHE gene and the di-methylation of histone 3 lysine 4 and came along with an increased expression of the lysine specific demethylase KDM1A. Last, inflammatory cytokines were not induced by midazolam. In conclusion, we found a promising mechanistic link between midazolam treatment and delirium, due to a significant disruption in cholinesterase homeostasis. In addition, midazolam seems to provoke profound changes in the epigenetic landscape. Therefore, our results can contribute to a better understanding of the hitherto poorly understood interactions and risk factors of midazolam on delirium.

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“… 34 Dimitrios Adamis reported that high levels of CRP are associated with delirium in acute orthopaedic and elective abdominal operations. 35 However, Mehmet Alper ÇINAR1and et al reported that there was no difference between POD and non-POD group on the blood level of CRP. 28 Therefore, CRP was also selected as a detection indicator in our study.…”

Section: Discussionmentioning

confidence: 97%

“… 36 , 37 High levels of IL-6 seem a consistent predictor for delirium in surgical samples. 35 Kazmierski et al reported an elevation of TNF-α levels in the postoperative period in coronary artery bypass graft (CABG) patients with delirium. 30 Ganna Androsova1 mentioned IL-6 and TNF-α could be biomarkers in predicting delirium.…”

Section: Discussionmentioning

confidence: 99%

Detection Analysis of Perioperative Plasma and CSF Reveals Risk Biomarkers of Postoperative Delirium of Parkinson’s Disease Patients Undergoing Deep Brain Stimulation of the Subthalamic Nuclei

Zhou¹,

Ma²,

Yu³

et al. 2022

CIA

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Objective This study aimed to explore possible biomarkers of postoperative delirium (POD) of Parkinson’s disease (PD) patients received deep brain stimulation (DBS) of the subthalamic nuclei. Materials and methods This nested case control study analyzed perioperative plasma and cerebral spinal fluid (CSF) of patients (n = 40) who developed POD undergone DBS surgery (n = 10) and those who did not (n = 30). Blood sample was collected before surgery and on the first day postoperative, CSF sample was collected at the beginning of the operation. POD was assessed by the Confusion Assessment Method (CAM) twice a day between 7:00 am and 7:00 pm after the surgery until discharge. Plasma and CSF sample from the two groups were analyzed to investigate possible biomarkers for POD in PD patients. Results There was no difference between POD and Non-POD groups on the concentration of Interleukin 6 and Tumor Necrosis Factor-α in CSF, preoperative plasma and postoperative plasma. There was no difference between POD and Non-POD groups on the concentration of S100 calcium-binding protein β protein (S100β) and Neurofilament light chain (NFL) in preoperative plasma and postoperative plasma. The concentration of C-reactive protein (CRP), NFL and S100β were significant higher in POD group than non-POD group in CSF. The concentration of CRP was significantly higher in POD group than non-POD group in preoperative plasma and postoperative plasma. CSF concentration of S100β might be a potential biomarker for POD via the receiver operating characteristic curve analysis and the area under the curve value of 0.973. Conclusion For PD patients received DBS surgery, CSF S100β might be a marker for aiding detection of high-risk patients with delirium. This requires further confirmation in clinical trials.

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Consistent patterns in the inconsistent associations of Insulin-like growth factor 1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin 6 (IL-6) levels with delirium in surgical populations. A systematic review and meta-analysis

Cited by 16 publications

References 70 publications

[Retracted] Correlation Analysis of Inflammatory Markers CRP and IL‐6 and Postoperative Delirium (POD) in Elderly Patients: A Meta‐Analysis of Observational Studies

[Retracted] Correlation Analysis of Inflammatory Markers CRP and IL‐6 and Postoperative Delirium (POD) in Elderly Patients: A Meta‐Analysis of Observational Studies

Midazolam impacts acetyl—And butyrylcholinesterase genes: An epigenetic explanation for postoperative delirium?

Detection Analysis of Perioperative Plasma and CSF Reveals Risk Biomarkers of Postoperative Delirium of Parkinson’s Disease Patients Undergoing Deep Brain Stimulation of the Subthalamic Nuclei

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