Biomarkers associated with delirium in critically ill patients and their relation with long-term subjective cognitive dysfunction; indications for different pathways governing delirium in inflamed and noninflamed patients

Abstract

IntroductionDelirium occurs frequently in critically ill patients and is associated with disease severity and infection. Although several pathways for delirium have been described, biomarkers associated with delirium in intensive care unit (ICU) patients is not well studied. We examined plasma biomarkers in delirious and nondelirious patients and the role of these biomarkers on long-term cognitive function.MethodsIn an exploratory observational study, we included 100 ICU patients with or without delirium and with ("inflamed") and without ("noninflamed") infection/systemic inflammatory response syndrome (SIRS). Delirium was diagnosed by using the confusion-assessment method-ICU (CAM-ICU). Within 24 hours after the onset of delirium, blood was obtained for biomarker analysis. No differences in patient characteristics were found between delirious and nondelirious patients. To determine associations between biomarkers and delirium, univariate and multivariate logistic regression analyses were performed. Eighteen months after ICU discharge, a cognitive-failure questionnaire was distributed to the ICU survivors.ResultsIn total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-β were significantly associated with delirium in inflamed patients (n = 46). In the noninflamed group of patients (n = 54), IL-8, IL-1ra, IL-10 ratio Aβ1-42/40, and ratio AβN-42/40 were significantly associated with delirium. In multivariate regression analysis, IL-8 was independently associated (odds ratio, 9.0; 95% confidence interval (CI), 1.8 to 44.0) with delirium in inflamed patients and IL-10 (OR 2.6; 95% CI 1.1 to 5.9), and Aβ1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-β forms, but not human Tau or S100-β, were significantly correlated with self-reported cognitive impairment 18 months after ICU discharge, whereas inflammatory markers were not correlated to impaired long-term cognitive function.ConclusionsIn inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and Aβ1-42/40 were associated with delirium. This suggests that the underlying mechanism governing the development of delirium in inflamed patients differs from that in noninflamed patients. Finally, elevated levels of amyloid-β correlated with long-term subjective cognitive-impairment delirium may represent the first sign of a (subclinical) dementia process. Future studies must confirm these results.The study was registered in the Clinical Trial Register (NCT00604773).

Encefalopatia septyczna a majaczenie stanu ciężkiego

“…W rozpoznaniu SAD stosuje się skale majaczenia dedykowane dla intensywnej terapii, które mogą wskazywać na patologię w zakresie OUN jeszcze przed rozpoznaniem sepsy [16,17].…”

“…W grupie 170 pacjentów z sepsą 42% miało podwyższony poziom białka S100β w surowicy, a u 53% w ciągu 72 godz. od przyjęcia podwyższony był poziom NSE [16]. Badanie przeprowadzone przez van den Boogaard i wsp.…”

“…Badanie przeprowadzone przez van den Boogaard i wsp. wykazało, że zwiększenie poziomu IL-8 w osoczu było związane z majaczeniem u pacjentów septycznych, podczas gdy u osób z majaczeniem, ale bez stanu zapalnego, podwyższone były poziomy IL-10 i beta-amyloidu β [16]. Co więcej, pacjenci z majaczeniem w stanie zapalnym, u których później wystąpiły zaburzenia poznawcze, mieli podwyższony poziom amyloidu beta [19].…”

Prevention and Management of Delirium in Geriatric Rehabilitation

“…26 Increased cortisol levels have been associated with patients developing delirium due to surgery, ICU admission, or stroke. 26,[34][35][36] The third pathway, the infl ammatory pathway, can be considered a subcategory of the stress pathway, but is more specifi cally a neuroinfl ammatory response. The neuroinfl ammatory response can be triggered by systemic infl ammatory stimuli (cytokines and prostaglandins) due to sepsis or surgery, crossing the blood-brain barrier as well as direct brain trauma.…”

Blood-Cerebrospinal Fluid Barrier Integrity in Delirium Determined by Q-Albumin

“…Inflammation as a causative factor is one of the leading hypotheses. Even though systemic inflammatory signals can affect the brain in various ways when the blood-brain barrier systems are intact, it has been hypothesised that an increased permeability could further facilitate signalling of systemic inflammation to the brain and thus be a factor in the delirium pathophysiology [4,5,6]. The prevalence of blood-brain barrier system dysfunction is found to increase with age [7,8] and dementia [9,10,11].…”