The Inflammatory Nature of Post-surgical Delirium Predicts Benefit of Agents With Anti-TNF Effects, Such as Dexmedetomidine

Clark, Ian A.; Vissel, Bryce

doi:10.3389/fnins.2018.00257

Cited by 15 publications

(12 citation statements)

References 67 publications

(80 reference statements)

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“…IL-6, CXCL8 and TNF-α), Th1 and Th17 activation and T cell growth (positively), and inversely with IL-4 and sIL-1RA. These findings extend those of previous papers showing that alterations in peripheral levels of IRS cytokines, namely IL-1β, IL-6, CXCL8, IL-10, and TNF-α, and also C-reactive protein (CRP) and NLR are associated with the onset of delirium [3, 18, 19, 39, 40].…”

Section: Discussionsupporting

confidence: 90%

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Thisayakorn

Thipakorn

Tantavisut

et al. 2022

Preprint

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The objectives of this study were to delineate whether delirium is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, Thelper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and Tregulatory profiles. We recruited 65 elderly patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. The pain scores during delirium were significantly and positively associated with CXCL8 and CCL3 and negatively with IL-4 and sIL-1RA. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. In conclusion, post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

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Section: Discussionsupporting

confidence: 90%

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Thisayakorn

Thipakorn

Tantavisut

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…IL-6, CXCL8 and TNF-α), Th1 and Th17 activation and T cell growth (positively), and inversely with IL-4 and sIL-1RA. These ndings extend those of previous papers showing that alterations in peripheral levels of IRS cytokines, namely IL-1β, IL-6, CXCL8, IL-10, and TNF-α, and also C-reactive protein (CRP) and NLR are associated with the onset of delirium [3,18,19,39,40]. M1-associated cytokines including IL-1β, IL-6, CXCL8, and TNF-α, play a key role in the immune response to injuries.…”

Section: Discussionsupporting

confidence: 89%

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Thisayakorn

Thipakorn

Tantavisut

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: The objectives of this study were to delineate whether delirium is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, Thelper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and Tregulatory profiles. Methods: We recruited 65 elderly patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. Results: We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. The pain scores during delirium were significantly and positively associated with CXCL8 and CCL3 and negatively with IL-4 and sIL-1RA. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. Conclusions: Post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

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“…Dexmedetomidine, a highly selective alpha-2 adrenoreceptor agonist, has the positive sedation, anti-anxiety, and analgesic effects [12, 13, 37]. Thus, dexmedetomidine has been widely used in surgical patients.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing noncardiac surgery: A meta-analysis of randomized controlled trials

Zeng

et al. 2019

PLoS ONE

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Background Postoperative delirium (POD) among the elderly population that undergoes noncardiac surgery is significantly associated with adverse clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of dexmedetomidine for the prophylaxis of POD among the elderly population after noncardiac surgery. Methods We searched Embase, PubMed, and the Cochrane Library from inception date to March 2019 for randomized controlled trials (RCTs) that compared dexmedetomidine and placebo for the prevention of POD and evaluated the major cardiovascular outcomes among elderly people after noncardiac surgery. Two authors independently screened the studies and extracted data from the published articles. The main outcome was the incidence of POD. The secondary outcomes included the occurrence of bradycardia, hypotension, hypertension, tachycardia, myocardial infarction, stroke, hypoxaemia, and all-cause mortality. Results A total of 6 RCTs with 2102 participants were included. Compared with placebo, dexmedetomidine significantly reduced the prevalence of POD (RR = 0.61, 95% CI 0.34–0.76, P = 0.001, I 2 = 66%), and the risk of tachycardia (RR = 0.48, 95% CI 0.30–0.76, P = 0.002, I 2 = 0%), hypertension (RR = 0.59, 95% CI 0.44–0.79, P < 0.001, I 2 = 20%), stroke (RR = 0.22, 95% CI 0.06–0.76, P = 0.02, I 2 = 0%), and hypoxaemia (RR = 0.50, 95% CI 0.32–0.78, P = 0.002, I 2 = 0%) in elderly patients who underwent noncardiac surgery. However, dexmedetomidine accelerated the occurrence of bradycardia (RR = 1.36, 95% CI 1.11–1.67, P = 0.003, I 2 = 0%). Furthermore, no significant differences were observed in the incidence of hypotension, myocardial infarction, and all-cause mortality between the dexmedetomidine and placebo groups. Conclusions Among elderly patients after noncardiac surgery, the prophylactic use of dexmedetomidine, compared with the use of placebo, was related to a decline in the incidence of POD.

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The Inflammatory Nature of Post-surgical Delirium Predicts Benefit of Agents With Anti-TNF Effects, Such as Dexmedetomidine

Cited by 15 publications

References 67 publications

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

Dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing noncardiac surgery: A meta-analysis of randomized controlled trials

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