The frequency of sepsis-associated delirium in intensive care unit and its effect on nurse workload.

AIM: To determine the frequency of sepsis-associated delirium (SAD) in the intensive care unit and its effect on nurse workload. DESIGN: A cross-sectional and correlational design was used. METHODS: The study was conducted with 158 patients in the adult intensive care unit of a hospital between October 28 and July 28, 2022. Data analysis included frequency, chi-squared/fisher's exact test, independent samples t-test, correlation analysis, simple and multiple linear regression analyses. The study adhered to the STROBE guidelines. RESULTS: Sepsis was detected in 12.7% of the patients, delirium in 39.9%, and SAD in 10.1%. SAD was more common in males (19%) and 56.3% of the patients were admitted to the unit from the emergency department. Patients developing SAD had significantly higher age and mean sequential organ failure evaluation, acute physiology and chronic health evaluation II, and C-reactive protein and lactate scores, but their Glasgow Coma Scale scores were significantly low. There was a moderate positive relationship between the patients' Sequential Organ Failure Assessment score and the presence of SAD. The most common source of infection in patients diagnosed with SAD was bloodstream infection (44.4%). SAD significantly increased nurse workload and average care time (1.8 h) and it explained 22.8% of the total variance in nurse workload. Additionally, the use of antibiotics, vasopressors and invasive mechanical ventilation significantly increased nurse workload. CONCLUSION: In the study, in patients who developed SAD increased nurse workload and average care time significantly. Preventive nursing approaches and effective management of SAD can reduce the rate of development of SAD and nurse workload. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: It is important to work with routine screening, prevention and patient-nurse ratio appropriate to the workload for SAD.

Predictive Ability of Amplitude Integrated Electroencephalography for Adverse Outcomes in Neonates with Sepsis-Associated Encephalopathy: A Cohort Study.

The authors examined the prevalence of abnormal amplitude integrated electroencephalography (aEEG) patterns in neonates diagnosed with sepsis-associated encephalopathy (SAE). They recorded 36626 min of aEEG in 75 study neonates. Encephalopathy was defined by the Brighton Collaboration Neonatal Encephalopathy criteria. Neonates with primary outcome [either non-survivors or survivors with abnormal neurological examination at discharge using Amiel-Tison assessment tool, n = 58, (77%)] were compared with 17 survivors having normal neurological examination at discharge. Severely abnormal aEEG patterns (isoelectric voltage, continuous low voltage, burst suppression) collectively represented 31% of total 36626 min aEEG tracings. Neonates experiencing primary outcome had significantly higher Burdjalov scores than survivors with normal neurological exam (p value 0.01). After adjusting for gestational age, birth weight, and invasive ventilation, severely abnormal aEEG (aOR 5.8, 95% CI 1.7-19.5, p value 0.005) and Burdjalov score (aOR 0.77, 95% CI 0.63-0.95, p value 0.01) were independently associated with death or abnormal neurological examination at discharge.

Combining biomarkers of BNIP3 L, S100B, NSE, and accessible measures to predict sepsis-associated encephalopathy: a prospective observational study.

BACKGROUND: Accurate identification of delirium in sepsis patients is crucial for guiding clinical diagnosis and treatment. However, there are no accurate biomarkers and indicators at present. We aimed to identify which combinations of cognitive impairment-related biomarkers and other easily accessible assessments best predict delirium in sepsis patients. METHODS: One hundred and one sepsis patients were enrolled in a prospective study cohort. S100B, NSE, and BNIP3 L biomarkers were detected in plasma and cerebrospinal fluid and patients' optic nerve sheath diameter (ONSD). The optimal biomarkers identified by Logistic regression are combined with other factors such as ONSD to filter out the perfect model to predict delirium in sepsis patients through Logistic regression, Naïve Bayes, decision tree, and neural network models. MAIN RESULTS: Among all biomarkers, compared with BNIP3 L (AUC = .706, 95% CI = .597-.815) and NSE (AUC = .711, 95% CI = .609-.813) in cerebrospinal fluid, plasma S100B (AUC = .729, 95% CI = .626-.832) had the best discrimination performance for delirium in sepsis patients. Logistic regression analysis showed that the combination of cerebrospinal fluid BNIP3 L with plasma S100B, ONSD, neutrophils, and age provided the best discrimination to cognitive impairment in sepsis patients (accuracy = .901, specificity = .923, sensitivity = .911), which was better than Naïve Bayes, decision tree, and neural network models. Neutrophils, ONSD, and cerebrospinal fluid BNIP3 L were consistently the major contributors in a few models. CONCLUSIONS: The logistic regression showed that the combination model was strongly correlated with cognitive dysfunction in sepsis patients.

Extracellular Vesicles as Possible Plasma Markers and Mediators in Patients with Sepsis-Associated Delirium-A Pilot Study.

Patients with sepsis-associated delirium (SAD) show severe neurological impairment, often require an intensive care unit (ICU) stay and have a high risk of mortality. Hence, useful biomarkers for early detection of SAD are urgently needed. Extracellular vesicles (EVs) and their cargo are known to maintain normal physiology but also have been linked to numerous disease states. Here, we sought to identify differentially expressed proteins in plasma EVs from SAD patients as potential biomarkers for SAD. Plasma EVs from 11 SAD patients and 11 age-matched septic patients without delirium (non-SAD) were isolated by differential centrifugation, characterized by nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis. Differential EV protein expression was determined by mass spectrometry and the resulting proteomes were characterized by Gene Ontology term and between-group statistics. As preliminary results because of the small group size, five distinct proteins showed significantly different expression pattern between SAD and non-SAD patients (p ≤ 0.05). In SAD patients, upregulated proteins included paraoxonase-1 (PON1), thrombospondin 1 (THBS1), and full fibrinogen gamma chain (FGG), whereas downregulated proteins comprised immunoglobulin (IgHV3) and complement subcomponent (C1QC). Thus, plasma EVs of SAD patients show significant changes in the expression of distinct proteins involved in immune system regulation and blood coagulation as well as in lipid metabolism in this pilot study. They might be a potential indicator for to the pathogenesis of SAD and thus warrant further examination as potential biomarkers, but further research is needed to expand on these findings in longitudinal study designs with larger samples and comprehensive polymodal data collection.

A nomogram for predicting sepsis-associated delirium: a retrospective study in MIMIC III.

OBJECTIVE: To develop a nomogram for predicting the occurrence of sepsis-associated delirium (SAD). MATERIALS AND METHODS: Data from a total of 642 patients were retrieved from the Medical Information Mart for Intensive Care (MIMIC III) database to build a prediction model. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of SAD. The performance of the nomogram was assessed in terms of discrimination and calibration by bootstrapping with 1000 resamples. RESULTS: Multivariate logistic regression identified 4 independent predictors for patients with SAD, including Sepsis-related Organ Failure Assessment(SOFA) (p = 0.004; OR: 1.131; 95% CI 1.040 to 1.231), mechanical ventilation (P < 0.001; OR: 3.710; 95% CI 2.452 to 5.676), phosphate (P = 0.047; OR: 1.165; 95% CI 1.003 to 1.358), and lactate (P = 0.023; OR: 1.135; 95% CI 1.021 to 1.270) within 24 h of intensive care unit (ICU) admission. The area under the curve (AUC) of the predictive model was 0.742 in the training set and 0.713 in the validation set. The Hosmer - Lemeshow test showed that the model was a good fit (p = 0.471). The calibration curve of the predictive model was close to the ideal curve in both the training and validation sets. The DCA curve also showed that the predictive nomogram was clinically useful. CONCLUSION: We constructed a nomogram for the personalized prediction of delirium in sepsis patients, which had satisfactory performance and clinical utility and thus could help clinicians identify patients with SAD in a timely manner, perform early intervention, and improve their neurological outcomes.

Immunological risk factors for sepsis-associated delirium and mortality in ICU patients.

Background: A major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized. Methods: This study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University. Comorbidity, including sepsis and SAD, of this cohort was diagnosed and recorded. Furthermore, peripheral blood samples were collected on days 1, 3, and 5 of admission for peripheral immune profiling with blood routine examination, flow cytometry, ELISA, RNA-seq, and qPCR. Results: The patients with SAD had higher mortality during ICU admission and within 28 days of discharge. Compared with survivors, nonsurvivors had higher neutrophilic granulocyte percentage, higher CRP concentration, lower monocyte count, lower monocyte percentage, lower C3 complement level, higher CD14loCD16+ monocytes percentage, and higher levels of IL-6 and TNFα. The CD14hiCD16- monocyte percentage manifested favorable prediction values for the occurrence of SAD. Differentially expressed genes between the nonsurvival and survival groups were mainly associated with immune response and metabolism process. The longitudinal expression pattern of SLC2A1 and STIMATE were different between nonsurvivors and survivors, which were validated by qPCR. Conclusions: Nonsurvival critical patients have a distinct immune profile when compared with survival patients. CD14hiCD16- monocyte prevalence and expression levels of SLC2A1 and STIMATE may be predictors of SAD and 28-day mortality in ICU patients.

Relationship Between Cerebral Hemodynamics, Tissue Oxygen Saturation, and Delirium in Patients With Septic Shock: A Pilot Observational Cohort Study.

Background: Septic shock patients have tendencies toward impairment in cerebral autoregulation and imbalanced cerebral oxygen metabolism. Tissue Oxygen Saturation (StO2) and Transcranial Doppler (TCD) monitoring were undertaken to observe the variations of cerebral hemodynamic indices and cerebral/peripheral StO2 to find risk factors that increase the sepsis-associated delirium (SAD). Materials and Methods: The research cohort was chosen from septic shock patients received in the Department of Critical Care Medicine, Xiangya Hospital, Central South University between May 2018 and March 2019. These patients were separated into two groups, SAD and non-SAD as assessed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Comparisons were made between the two groups in terms of peripheral StO2, fluctuations in regional cerebral oxygen saturation (rSO2), cerebral vascular automatic regulation function [Transient Hyperemic Response Ratio (THRR) index], cerebral hemodynamic index, organ function indicators, blood gas analysis indices, and patient characteristics. Results: About 39% of the patients (20/51) suffered from SAD. Nearly 43% of the patients died within 28 days of admission (22/51). Individuals in the SAD cohort needed a longer period of mechanical ventilation [5 (95% CI 2, 6) vs. 1 days (95% CI 1, 4), p = 0.015] and more time in ICU [9 (95% CI 5, 20) vs. 5 days (95% CI 3, 9), p = 0.042]; they also experienced more deaths over the 28-day period (65 vs. 29%, p = 0.011). The multivariate regression analysis indicated that independent variables associated with SAD were THRR index [odds ratio (OR) = 5.770, 95% CI: 1.222-27.255; p = 0.027] and the mean value for rSO2 was < 55% (OR = 3.864, 95% CI: 1.026-14.550; p = 0.046). Conclusion: Independent risk factors for SAD were mean cerebral oxygen saturation below 55% and cerebrovascular dysregulation (THRR < 1.09).

Incidence, risk factors, and outcomes for sepsis-associated delirium in patients with mechanical ventilation: A sub-analysis of a multicenter randomized controlled trial.

PURPOSE: This study aimed to investigate incidence, risk factors, and outcomes for sepsis-associated delirium (SAD) in mechanically ventilated patients. MATERIALS AND METHODS: We performed a retrospective post-hoc analysis of the DExmedetomidine for Sepsis in Intensive care unit Randomized Evaluation (DESIRE) trial. Outcomes included 28-day mortality, ventilator-free days, length of ICU stay, self-extubation, and re-intubation. Multivariable analysis was performed to identify variables independently associated with SAD. RESULTS: We retrospectively divided the patients into two groups: delirium group (n = 89) and non-delirium group (n = 98). There were no significant differences between the groups in 28-day mortality, self-extubation, and re-intubation. The number of ventilator-free days was significantly less in the delirium vs. non-delirium group (17 vs. 22 days, p = .006), and the length of ICU stay was significantly longer in the delirium group (10 vs. 5 days, p = .04). Multivariable analyses revealed that emergency surgery, more doses of midazolam, and fentanyl were independent predictors for SAD. CONCLUSIONS: SAD was associated with a less number of ventilator-free days and longer length of ICU stay. Emergency surgery, more doses of midazolam, and fentanyl may be independent risk factors for SAD in mechanically ventilated patients with sepsis.

Lymphocyte and NK Cell Counts Can Predict Sepsis-Associated Delirium in Elderly Patients.

Background: Sepsis-associated delirium (SAD) is prevalent in elderly patients and is recognized as brain dysfunction associated with increased inflammatory response in the central nervous system during sepsis. Neuroinflammation was demonstrated to be part of its mechanism and we aimed to validate the role of immunity imbalance in a combined retrospective and prospective cohort study. Methods: We performed a retrospective study analyzing the association between SAD and lymphocyte counts in the peripheral blood, alongside a prospective trial evaluating the quantitative changes in lymphocyte subsets and their predictive value for early diagnosis of SAD. Results: In the retrospective study, among 1,010 enrolled adult patients (age ≥65 years), 297 patients were diagnosed with delirium during intensive care unit (ICU) stay and lymphocyte counts at ICU admission in the SAD group were significantly higher than in non-delirious counterparts (1.09 ± 0.32 vs. 0.82 ± 0.24, respectively, p = 0.001). In the prospective study, lymphocyte counts [0.83 (0.56, 1.15) vs. 0.72 (0.40, 1.06) × 109/L, p = 0.020] and natural killer (NK) cell counts [96 (68, 118) vs. 56 (26, 92) cells/µl, p = 0.024] were significantly higher in the SAD group. The area under the curve value of NK cell count was 0.895 [95% confidence interval (CI): 0.857, 0.933] and of lymphocyte count was 0.728 (95% CI: 0.662, 0.795). An NK cell count cut-off value of 87 cells/ml in septic patients at ICU admission was predictive of delirium with a sensitivity of 80.2% and specificity of 80.8%. Conclusions: We found that lymphocyte and NK cell counts were significantly higher in senior patients with SAD and that NK cell count may be valuable for the prediction of SAD within elderly patient cohorts.

Sepsis associated delirium mimicking postoperative delirium as the initial presenting symptom of urosepsis in a patient who underwent nephrolithotomy.

We report a case of 70 years old male who underwent percutaneous nephrolithotomy for renal calculi. After an uneventful recovery from anaesthesia, the patient developed delirium which manifested as restlessness, agitation, irritability and combative behavior. All other clinical parameters including arterial blood gas, chest X-ray and core temperature were normal and the patient remained haemodynamically stable. But 45 min later the patient developed florid manifestations of septic shock. He was aggressively managed in a protocolized manner as per the Surviving Sepsis Guidelines in the Critical Care Unit and recovered completely. There are no case reports showing postoperative delirium as the only initial presentation of severe sepsis, with other clinical parameters remaining normal. Both urosepsis and sepsis associated delirium have very high mortality. High index of suspicion and a protocolized approach in the management of sepsis can save lives.