Dataset Information

Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study.

ABSTRACT: BACKGROUND:Neuroinflammation is thought to play an important role in the pathogenesis of ICU-acquired delirium, but the association between inflammatory and brain-specific proteins and ICU delirium is poor. We investigated whether or not serial determinations of markers may improve this association. METHODS:Critically ill patients with a high risk of ICU delirium and with an ICU length of stay of at least 6 days were included in the study. Blood was drawn on days 1, 2, 4 and 6 after ICU admission and analyzed for different markers of inflammation and several brain proteins. Differences in courses over time prior to and following the onset of delirium and absolute differences over time were analyzed in patients with and without delirium using repeated measurement analysis of variance. In addition, a cross-sectional analysis of levels of these markers before the first onset of delirium was performed. RESULTS:Fifty patients were included in this study. In the longitudinal analysis, there were no differences in the levels of any of the markers immediately prior to and following the onset of delirium, but overall, median levels of adiponectin (9019 (IQR 5776-15,442) vs. 6148 (IQR 4447-8742) ng/ml, p?=?0.05) were significantly higher in patients with delirium compared to patients without delirium. In the cross-sectional analysis, median levels of the brain protein Tau (90 (IQR 46-224) vs. 31 (IQR 31-52) pg/ml, p?=?0.009) and the ratio Tau/amyloid ?1-42 (1.42 ((IQR 0.9-2.57) vs. 0.68 (IQR 0.54-0.96), p?=?0.003) were significantly higher in patients with hypoactive delirium compared to patients without. Levels of neopterin (111 (IQR 37-111) vs. 29 (IQR 16-64) mmol/l, p?=?0.004) and IL-10 (28 (IQR 12-39) vs. 9 (IQR 4-12) pg/ml, p?=?0.001) were significantly higher in patients with hypoactive delirium compared to patients with mixed-type delirium. CONCLUSIONS:While there are differences in markers (adiponectin and several brain proteins) between patients with and without delirium, the development of delirium is not preceded by a change in the biomarker profile of inflammatory markers or brain proteins. Patients with hypoactive delirium account for the observed differences in biomarkers. TRIAL REGISTRATION:ClinicalTrials.gov, NCT 01274819 . Registered on 12 January 2011.

SUBMITTER: Simons KS

PROVIDER: S-EPMC5970442 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study.

Simons Koen S KS van den Boogaard Mark M Hendriksen Eva E Gerretsen Jelle J van der Hoeven Johannes G JG Pickkers Peter P de Jager Cornelis P C CPC

Critical care (London, England) 20180525 1

<h4>Background</h4>Neuroinflammation is thought to play an important role in the pathogenesis of ICU-acquired delirium, but the association between inflammatory and brain-specific proteins and ICU delirium is poor. We investigated whether or not serial determinations of markers may improve this association.<h4>Methods</h4>Critically ill patients with a high risk of ICU delirium and with an ICU length of stay of at least 6 days were included in the study. Blood was drawn on days 1, 2, 4 and 6 aft ...[more]

PMID: 29801516

Similar Datasets

Project description:ObjectivesWe examined the relationship between dominant sedation strategy, risk of delirium and patient-centred outcomes in adults admitted to intensive care units (ICUs).DesignRetrospective propensity-matched cohort study.SettingMechanically ventilated adults (≥ 18 years) admitted to four Canadian hospital medical/surgical ICUs from 2014 to 2016 in Calgary, Alberta, Canada.Participants2837 mechanically ventilated adults (≥ 18 years) requiring admission to a medical/surgical ICU were evaluated for the relationship between sedation strategy and delirium.InterventionsNone.Primary and secondary outcome measuresThe primary exposure was dominant sedation strategy, defined as the sedative infusion, including midazolam, propofol or fentanyl, with the longest duration before the first delirium assessment. The primary outcome was 'ever delirium' identified using the Intensive Care Delirium Screening Checklist. Secondary outcomes included mortality, length of stay (LOS), ventilation duration and days with delirium. The cohort was analysed in two propensity score (patient characteristics and therapies received) matched cohorts (propofol vs fentanyl and propofol vs midazolam).Results2837 patients (60.7% male; median age 57 years (IQR 43-68)) were considered for propensity matching. In propensity score-matched cohorts(propofol vs midazolam, n=712; propofol vs fentanyl, n=1732), the odds of delirium were significantly higher with midazolam (OR 1.46 (95% CI 1.06 to 2.00)) and fentanyl (OR 1.22 (95% CI 1.00 to 1.48)) compared with propofol dominant sedation strategies. Dominant sedation strategy with midazolam and fentanyl were associated with a longer duration of ventilation compared with propofol. Fentanyl was also associated with increased ICU mortality (OR 1.50, 95% CI 1.07 to 2.12)) ICU and hospital LOS compared with a propofol dominant sedation strategy.ConclusionsWe identified a novel association between fentanyl dominant sedation strategies and an increased risk of delirium, a composite outcome of delirium or death, duration of mechanical ventilation, ICU LOS and hospital LOS. Midazolam dominant sedation strategies were associated with increased delirium risk and mechanical ventilation duration.

Project description:ObjectivesThe pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown.DesignThis was a prospective exploratory study.SettingA multidisciplinary ICU at an academic medical center in Phoenix, AZ.PatientsCritically ill patients older than or equal to 18 years old admitted to the ICU.InterventionsNone.Measurements and main resultsScreening for delirium was performed using the Confusion Assessment Method for the ICU tool. The levels of C-C motif ligand 2 (CCL2), C-C motif ligand 3, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 10, and interleukin-8 were measured in serum samples obtained within 12 hours of ICU admission. Univariate and multivariate analyses were performed to assess the association of delirium with patient data pertaining to hospital course, laboratory values, vital signs, medication administration, and levels of the aforementioned chemokines. Forty-one of 119 patients (34.5%) in the study cohort developed ICU delirium. Each chemokine studied was associated with delirium on univariate analyses; however, CCL2 was the only chemokine found to be independently associated with the development of delirium on multivariable analysis. The association of increased CCL2 levels with delirium remained robust in various models controlling for age, presence of shock, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation IV score, mean arterial pressure at presentation, lowest mean arterial pressure, and total opioid, midazolam, propofol, and dexmedetomidine exposure.ConclusionsThe demonstrated relationship between CCL2 and delirium suggests this chemokine may play a role in the development of delirium and warrants further investigation.

Project description:IntroductionDelirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate objective assessment of the pupillary light responses in comatose patients in the intensive care unit (ICU). Whether automated pupillometry might predict delirium in critically ill patients is not known. We hypothesise that automated pupillometry could predict the occurrence of delirium in critically ill patients without primary brain injury, requiring more than 48 hours of invasive mechanical ventilation in the ICU.Methods and analysisThe PupillOmetry for preDIction of DeliriUM in ICU (PODIUM) study is a prospective cohort study, which will be conducted in eight French ICUs in the Paris area. We aim to recruit 213 adult patients requiring invasive mechanical ventilation for more than 48 hours. Automated pupillometry (Neurological Pupil Index; NPi-200, Neuroptics) will be assessed two times per day for 7 days. Delirium will be assessed using the Confusion Assessment Method in ICU two times per day over 14 days in non-comatose patients (Richmond Agitation and Sedation Scale ≥-3).The predictive performances of the seven automated pupillometry parameters (ie, pupillary diameter, variation of the pupillary diameter, pupillary constriction speed, pupillary dilatation speed, photomotor reflex latency, NPi and symmetry of pupillary responses) measured to detect the delirium occurrence within 14 days will be the main outcomes. Secondary outcomes will be the predictive performances of the seven automated pupillometry parameters to detect complications related to delirium, ICU length of stay, mortality, functional and cognitive outcomes at 90 days.Ethics and disseminationThe PODIUM study has been approved by an independent ethics committee, the Comité de Protection des Personnes (CPP) OUEST IV-NANTES (CPP21.02.15.45239 32/21_3) on 06 April 2021). Participant recruitment started on 15 April 2022. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration numberNCT05248035; clinicaltrials.gov.

Project description:Abnormal secretion of catecholamines is well known to cause delirium. In particular, disturbances of catecholamine balance can cause ICU-acquired delirium. The aim of this study was to evaluate the association between the serum levels of catecholamines and the risk of occurrence of ICU-acquired delirium separately in patients who had/had not received exogenous catecholamines before ICU admission.DesignA secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial.SettingICU of an academic hospital.PatientsICU patients in whom the serum levels of catecholamines were measured at ICU admission.InterventionsNone.Measurements and main resultsWe evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[-] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(-) group (odds ratio, 2.58; 95% CI, 1.02-6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88-1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (p interaction = 0.017).ConclusionsThe serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.

Project description:BackgroundNeurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.MethodsWe conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.ResultsThe 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.Conclusions and relevanceDelirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.Trial registrationNA.

Dataset Information

Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study.

Publications

Temporal biomarker profiles and their association with ICU acquired delirium: a cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets