Preoperative inflammatory mediators and postoperative delirium: systematic review and meta-analysis

Noah, Moronke A.; Almghairbi, Dalal; Evley, Rachel; Moppett, Iain

doi:10.1016/j.bja.2021.04.033

Cited by 59 publications

(53 citation statements)

References 42 publications

(137 reference statements)

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“…62 Indeed, a recent meta-analysis showed that higher levels of IL-6 are associated with postoperative delirium. 69 Interestingly, we observe lower levels of lymphocytes in older patients in the preoperative period, consistent with previous studies investigating changes in key immune cell populations, and support the development of immunosenescence with increasing age. 70 There is also evidence of changes in the distribution of lymphocyte subtypes in older individuals, and cytokines such as IL-6 are known to affect the differentiation of lymphocyte subpopulations.…”

Section: Discussionsupporting

confidence: 91%

A Systematic Review and Meta-Analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers

Patel

Zhang

Liao

et al. 2021

Anesthesia &Amp; Analgesia

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BACKGROUND: Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. METHODS: MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12–24 hours, 1–3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. RESULTS: Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12–24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). CONCLUSIONS: Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.

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Section: Discussionsupporting

confidence: 91%

A Systematic Review and Meta-Analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers

Patel

Zhang

Liao

et al. 2021

Anesthesia &Amp; Analgesia

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“…Previous reports indicate that delirium is associated with increases in immune-inflammatory biomarkers, including interleukin (IL)-1, IL-6, soluble tumor necrosis factor (TNF) receptor, and other cytokines [ 7 , 8 ]. Additionally, meta-analyses have reported that POD is correlated with the concentrations of peripheral and cerebrospinal fluid (CSF) inflammatory markers, including C-reactive protein (CRP), IL-6, -8, and -10, and TNF-α [ 9 , 10 ]. These studies showed that certain inflammatory markers are associated with POD.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have shown that peripheral inflammatory markers, such as the NLR and PLR, are associated with the development of POD after hip surgery, cardiac surgery, and esophagectomy [ 15 , 16 , 17 , 18 ]. Other studies have reported that the association between the preoperative blood levels of inflammatory mediators and POD may be affected by the type of surgery [ 9 , 10 ]. The special circumstances associated with certain types of surgery may contribute to the etiology of POD.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Inflammatory Markers and the Risk of Postoperative Delirium in Patients Undergoing Lumbar Spinal Fusion Surgery

Yang

Lee

Kwon

et al. 2022

JCM

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We investigated the possible associations between postoperative delirium (POD) and routinely available preoperative inflammatory markers in patients undergoing lumbar spinal fusion surgery (LSFS) to explore the role of neuroinflammation and oxidative stress as risk factors for POD. We analyzed 11 years’ worth of data from the Smart Clinical Data Warehouse. We evaluated whether preoperative inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the CRP-to-albumin ratio (CAR), affected the development of POD in patients undergoing LSFS. Of the 3081 subjects included, 187 (7.4%) developed POD. A significant increase in NLR, MLR, and CAR levels was observed in POD patients (p < 0.001). A multivariate analysis showed that the second, third, and highest quartiles of the NLR were significantly associated with the development of POD (adjusted OR (95% CI0: 2.28 (1.25–4.16], 2.48 (1.3–4.73], and 2.88 (1.39–5.96], respectively). A receiver operating characteristic curve analysis showed that the discriminative ability of the NLR, MLR, and CAR for predicting POD was low, but almost acceptable (AUC (95% CI]: 0.60 (0.56–0.64], 0.61 (0.57–0.65], and 0.63 (0.59–0.67], respectively, p < 0.001). Increases in preoperative inflammatory markers, particularly the NLR, were associated with the development of POD, suggesting that a proinflammatory state is a potential pathophysiological mechanism of POD.

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“…Accumulating evidence suggests that systemic and neuroinflammation play a key role in the development of delirium [ 7 – 10 ]. Many human studies have investigated inflammatory cytokines in delirium subjects [ 11 , 12 ]. Although a meta-analysis showed increased levels of IL-6 in blood from POD patients, the evidence for other inflammatory markers is still unclear [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many human studies have investigated inflammatory cytokines in delirium subjects [ 11 , 12 ]. Although a meta-analysis showed increased levels of IL-6 in blood from POD patients, the evidence for other inflammatory markers is still unclear [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium

et al. 2021

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The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

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Preoperative inflammatory mediators and postoperative delirium: systematic review and meta-analysis

Cited by 59 publications

References 42 publications

A Systematic Review and Meta-Analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers

A Systematic Review and Meta-Analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers

Preoperative Inflammatory Markers and the Risk of Postoperative Delirium in Patients Undergoing Lumbar Spinal Fusion Surgery

DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium

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