Exploring the impact of dexmedetomidine on short-term outcomes in critically ill sepsis-associated encephalopathy patients.

OBJECTIVE: Dexmedetomidine has demonstrated potential in preclinical medical research as a protective agent against inflammatory injuries and a provider of neuroprotective benefits. However, its effect on the short-term prognosis of patients with sepsis-associated encephalopathy remains unclear. This study aims to explore the underlying value of dexmedetomidine in these patients. PATIENTS AND METHODS: This study enrolled patients with sepsis-associated encephalopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and they were divided into two groups based on dexmedetomidine therapy during hospitalization. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to balance the inter-group baseline differences. Kaplan-Meier (KM) curves with log-rank test and subgroup analysis were also employed. The primary outcome was 28-day mortality, and the secondary outcomes were in-hospital mortality, intensive care unit (ICU) stay time, hospital stay time, and the incidence of ventilator-associated pneumonia (VAP). RESULTS: After PSM, 1,075 pairs of patients were matched. In contrast to the non-dexmedetomidine cohort, the dexmedetomidine cohort did not exhibit a shortened ICU [4.65 (3.16, 8.55) vs. 6.14 (3.66, 11.04), p<0.001] and hospital stay duration [10.04 (6.55, 15.93) vs. 12.76 (7.92, 19.95), p<0.001], and there was an elevated incidence of VAP [90 (8.4%) vs. 135 (12.6%), p=0.002]. The log-rank test for the KM curves of dexmedetomidine use and 28-day mortality was statistically significant (p<0.001). The results showed that dexmedetomidine was associated with improved 28-day mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.35-0.61, p<0.001] and in-hospital mortality (HR 0.50, 95% CI 0.37-0.67, p<0.001) after adjusting for various confounders. In the following subgroup analysis, dexmedetomidine infusion was associated with decreased 28-day mortality in most subgroups. CONCLUSIONS: Dexmedetomidine administration was significantly associated with reduced short-term mortality among patients with sepsis-associated encephalopathy in the ICU. However, it also prolonged ICU and hospital stays and increased the incidence of VAP.

Elevated Intracranial Pressure Level Is a Risk Factor for Sepsis-associated Encephalopathy: A Prospective Cohort Study.

BACKGROUND/AIM: Cerebral edema is common in patients with sepsis-associated encephalopathy (SAE) and is a major cause of elevated intracranial pressure (ICP); however, the relationship between elevated ICP and SAE is unclear. The aim of this study was to investigate the association between optic nerve sheath diameter (ONSD), a surrogate of ICP, and the incidence of SAE. PATIENTS AND METHODS: A prospective observational study was performed in a medical-surgical adult intensive care unit (ICU). All patients in the ICU who were consecutively diagnosed with sepsis during the study period were evaluated for eligibility. Ultrasound measurements of ONSD were performed within 6 h of enrollment and every two days thereafter until the patient developed SAE. Clinical and blood test data were collected throughout this period. Patients underwent a daily conscious and cognitive assessment. SAE was diagnosed as delirium or Glasgow Coma Scale (GCS) <15 points. Multivariate modified Poisson regression analysis was performed to identify risk factors for SAE. RESULTS: A total of 123 patients with sepsis were included in the analysis. 58 patients (47.2%) developed SAE. The levels of ONSD0 (the first measured value) and ONSDmax (the maximum measured value) in the SAE group were significantly higher than those in the non-SAE group (5.23±0.52 mm vs. 5.85±0.54 mm for ONSD0 and 5.41±0.46 mm vs. 6.09±0.58 mm for ONSDmax, respectively; all p-values <0.001). The area under the curves (AUCs) for the ONSD0 and ONSDmax values in predicting SAE were 0.801 (95%CI=0.723-0.880, p<0.001) and 0.829 (95%CI=0.754-0.903, p<0.001), respectively. A higher ONSD0 level was significantly associated with an increased risk of SAE (adjusted risk ratio 3.241; 95%CI=1.686-6.230, p<0.001). CONCLUSION: The levels of ONSD correlate with risk of SAE, indicating that increased ICP level is an independent risk factor for the development of SAE. Dynamic monitoring of ONSD/ICP has a high predictive value for SAE. Measures to prevent increases in ICP are helpful to reduce the incidence of SAE in sepsis patients.

The expression of CD86 in CD3+CD56+ NKT cells is associated with the occurrence and prognosis of sepsis-associated encephalopathy in sepsis patients: a prospective observational cohort study.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.

Neurological complications of sepsis.

PURPOSE OF REVIEW: Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of hospital and ICU admission. The central and peripheral nervous system may be the first organ system to show signs of dysfunction, leading to clinical manifestations such as sepsis-associated encephalopathy (SAE) with delirium or coma and ICU-acquired weakness (ICUAW). In the current review, we want to highlight developing insights into the epidemiology, diagnosis, prognosis, and treatment of patients with SAE and ICUAW. RECENT FINDINGS: The diagnosis of neurological complications of sepsis remains clinical, although the use of electroencephalography and electromyography can support the diagnosis, especially in noncollaborative patients, and can help in defining disease severity. Moreover, recent studies suggest new insights into the long-term effects associated with SAE and ICUAW, highlighting the need for effective prevention and treatment. SUMMARY: In this manuscript, we provide an overview of recent insights and developments in the prevention, diagnosis, and treatment of patients with SAE and ICUAW.

Prediction and risk assessment of sepsis-associated encephalopathy in ICU based on interpretable machine learning.

Sepsis-associated encephalopathy (SAE) is a major complication of sepsis and is associated with high mortality and poor long-term prognosis. The purpose of this study is to develop interpretable machine learning models to predict the occurrence of SAE after ICU admission and implement the individual prediction and analysis. Patients with sepsis admitted to ICU were included. SAE was diagnosed as glasgow coma score (GCS) less than 15. Statistical analysis at baseline was performed between SAE and non-SAE. Six machine learning classifiers were employed to predict the occurrence of SAE, and the adjustment of model super parameters was performed by using Bayesian optimization method. Finally, the optimal algorithm was selected according to the prediction efficiency. In addition, professional physicians were invited to evaluate our model prediction results for further quantitative assessment of the model interpretability. The preliminary analysis of variance showed significant differences in the incidence of SAE among patients with pathogen infection. There were significant differences in physical indicators like respiratory rate, temperature, SpO2 and mean arterial pressure (P < 0.001). In addition, the laboratory results were also significantly different. The optimal classification model (XGBoost) indicated that the best risk factors (cut-off points) were creatinine (1.1 mg/dl), mean respiratory rate (18), pH (7.38), age (72), chlorine (101 mmol/L), sodium (138.5 k/ul), SAPSII score (23), platelet count (160), and phosphorus (2.4 and 5.0 mg/dL). The ranked features derived from the best model (AUC is 0.8837) were mechanical ventilation, duration of mechanical ventilation, phosphorus, SOFA score, and vasopressin usage. The SAE risk prediction model based on XGBoost created here can make very accurate predictions using simple indicators and support the visual explanation. The interpretable model was effectively evaluated by professional physicians and can help them predict the occurrence of SAE more intuitively.

Identification of sepsis-associated encephalopathy risk factors in elderly patients: a retrospective observational cohort study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis that affects upwards of half of all sepsis patients. Few studies have examined the etiology and risk factors of SAE among elderly patients. This study was designed to explore the epidemiology of SAE and the risk factors associated with its development in elderly populations. METHODS: This was a retrospective analysis of elderly sepsis patients admitted to our intensive care unit between January 2017 and January 2022. We then compared non-SAE and SAE groups concerning baseline clinicopathological findings, underlying diseases, infection site, disease type, disease severity, biochemical findings, and 28-day mortality. We further stratified patients in the SAE group based on whether or not they survived for 28 days, and we compared the above data between these groups. RESULTS: Of the 222 elderly sepsis patients, 132 (59.46%) had SAE. SAE patients were found to be significantly older than non-SAE patients. Both age and blood sodium concentrations were found to be associated with SAE risk, while elderly sepsis patients without underlying chronic obstructive pulmonary disease (COPD) have a relatively higher risk of developing SAE. The SAE group also had a significantly higher rate of 28-day mortality, and sequential organ failure assessment (SOFA) scores were a risk factor associated with 28-day mortality. DISCUSSION: Among elderly sepsis patients, SAE risk increases with advancing age, higher blood sodium concentrations, and without underlying COPD. SAE incidence is associated with a poorer prognosis, and SOFA scores are independent predictors of increased mortality among elderly SAE patients.

Posterior Reversible Encephalopathy in Sepsis-Associated Encephalopathy: Experience from a Single Center.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is frequently encountered in sepsis and is often accompanied by neuroimaging findings indicating ischemia, hemorrhage, and edema. Posterior reversible encephalopathy syndrome (PRES) has been vastly underrecognized in previously reported cohorts of patients with sepsis and SAE. Our aim was to determine the prevalence and distinguishing clinical, neuroimaging, and electroencephalography features of PRES in SAE. METHODS: In this prospective observational study, patients with radiologically identified PRES were selected from a consecutively enrolled cohort of 156 patients with SAE and assessed for neurological outcome using the extended Glasgow Outcome Scale for 12 months. Patients with SAE and PRES and other types of brain lesions were compared in terms of clinical and diagnostic workup features. RESULTS: Fourteen of 156 patients (8.9%) were determined to be radiologically compatible with PRES, whereas 48 patients displayed other types of acute brain lesions. Patients with PRES often showed lesions in atypical regions, including frontal lobes, the corpus callosum, and the basal ganglia. Source of infection was mostly gram-negative bacteria originating from pneumonia or intraabdominal infections. Patients with PRES were not different from other patients with SAE with brain lesions in terms of features of sepsis and neurological outcome. However, patients with PRES showed increased prevalence of seizures and intraabdominal source of infection. CONCLUSIONS: PRES is highly prevalent in SAE, often encompasses unusual brain regions, and usually presents with generalized seizures. Patients with SAE and PRES do not appear to have distinguishing clinical and diagnostic workup features. However, generalized seizures may serve as warning signs for presence of PRES in patients with SAE.

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may result in worse outcomes. This study was designed to determine the epidemiology, clinical features, and risk factors of SAE. METHODS: This was a retrospective study of all patients with sepsis who were admitted to the Critical Care Medicine Department of Hangzhou First People's Hospital Affiliated with Zhejiang University School of Medicine from January 2015 to December 2019. RESULTS: A total of 291 sepsis patients were screened, and 127 (43.6%) were diagnosed with SAE. There were significant differences in median age, proportion of underlying diseases such as hypertension, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gastrointestinal infections, detection rate of Enterococcus, and 28-day mortality between the SAE and non-SAE groups. Both the SOFA score and APACHE II score were independent risk factors for SAE in patients with sepsis. All 127 SAE patients were divided into survival and non-survival groups. The age, SOFA score, and APACHE II score were independently associated with 28-day mortality in SAE patients. CONCLUSION: In the present retrospective study, nearly half of patients with sepsis developed SAE, which was closely related to poor outcomes. Both the SOFA score and APACHE II score were independent risk factors for predicting the occurrence and adverse outcome of SAE.

The dynamic change of serum S100B levels from day 1 to day 3 is more associated with sepsis-associated encephalopathy.

We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of <15, or at least one positive CAM-ICU score were thought to have brain dysfunction. 59 patients were diagnosed with SAE and the rest 45 patients were diagnosed with non-SAE. Serum S100B was measured on day 1 and 3 after ICU admission. Primary outcomes included brain dysfunction and 28-day/180-day mortality. The SAE group showed a significantly higher APACHE II score, SOFA scores, length of ICU stay, 28-day and 180-day mortality, serum S100B levels on day 1 and day 3. S100B levels on day 1 of 0.226 µg/L were diagnostic for SAE with 80.0% specificity and 66.1% sensitivity, and the area under (AUC) the curve was 0.728, S100B levels on day 3 of 0.144 µg/L were diagnostic for SAE with 84.44% specificity and 69.49% sensitivity, and the AUC was 0.819. In addition, the AUC for S100B on day 3 for predicting 180-day mortality was larger than for S100B on day 1 (0.731 vs. 0.611). Multiple logistic regression analysis showed that S100B3 (p = 0.001) but not S100B1 (p = 0.927) were independently correlated with SAE. Kaplan-Meier survival analysis showed that patients with S100B levels higher than 0.144 µg/L had a lower probability of survival at day 180. There were more patients with encephalopathy and a higher 28-day or 180-day mortality in the ΔS100B + group than in the ΔS100B- group. Multiple logistic regression analysis showed that SAE and IL-6 on day 3 were independently correlated with S100B dynamic increase. These findings suggest that elevated serum S100B levels on day 3 and the dynamic changes of serum S100B levels from day three to one were more associated with brain dysfunction and mortality than that on day 1 in patients with sepsis.

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.

Sepsis-associated encephalopathy: A review of literature.

Sepsis is a leading cause of death in medical and surgical intensive care units (ICUs). Disturbance of consciousness of varying severity is an early warning sign of developing sepsis in the majority of cases. Sepsis-associated encephalopathy (SAE) is the most frequent type of encephalopathy in the ICU and is defined as a state of diffuse cerebral dysfunction caused by the inflammatory response of the body to various infections, where the inflammatory process does not affect the central nervous system (CNS) directly and the primary symptom is a disturbed level of consciousness. The aim of this comprehensive review was to collect the latest scientific knowledge regarding the epidemiology, clinical aspects, pathogenesis, diagnosis, and possible prevention strategies related to SAE.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PURPOSE: Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. METHODS: We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. RESULTS: We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). CONCLUSIONS: Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Focal epileptic seizures, electroencephalography and outcome of sepsis associated encephalopathy-A pilot study.

OBJECTIVES: Sepsis associated encephalopathy (SAE) represents a diffuse and/or multifactorial cerebral dysfunction during response to systemic infection. Study aim was to compare clinical and electroencephalogram (EEG) characteristics and intrahospital survival rate among SAE patients. PATIENTS AND METHODS: A prospective study, during 42 months' period, included 39 SAE patients assigned in two groups according the outcome (survival: 19, and death: 20 patients). All the patients' features were registered: demography, neurological status, infection type, seizure appearance, brain computerized tomography (CT), EEG, EEG reactivity, Glasgow Coma Score (GCS) and Acute Physiology and Chronic Health Evaluation II (APACHE II) Score. The analysis included EEGs obtained during patients' consciousness change (improvement or deterioration) and the level of consciousness during and at the end of hospitalization. RESULTS: SAE was detected in 29.5% of patients with encephalopathy (2.8% of all patients hospitalized). Patients with lethal outcome were more likely to be female (p=0.0011), to have focal seizures (p=0.034), lower values of GCS during hospitalization (p<0.05) and longer lasting nosocomial infections (p=0.029). At the time of clinical exacerbation, patients were more likely to have suppression on EEG and less likely theta activity. Delta waves, TW waves and suppression of EEG activity were the most common findings 24h prior to death (p=0.0004). The lack of EEG reactivity was associated with death (p=0.00043). CONCLUSION: Presence of focal seizures, EEG suppression at the time of exacerbation in SAE elderly patients, particularly women, with longer infection duration and lower values of GCS, is associated with intrahospital death.

[Sepsis associated encephalopathy is an independently risk factor for nosocomial coma in patients with supratentorial intracerebral hemorrhage: a retrospective cohort study of 261 patients].

OBJECTIVE: To investigate whether the presence of sepsis associated encephalopathy (SAE) would predict nosocomial coma (NC) and poor outcome in patients with supratentorial intracerebral hemorrhage (SICH). METHODS: A retrospective cohort study was conducted. The adult acute SICH patients with or without coma admitted to intensive care unit (ICU) of Shuyang People' Hospital Affiliated to Xuzhou Medical University from December 2012 to December 2015 were enrolled. Brain computed tomography (CT) scans were analyzed and the patients were divided into pre-hospital coma (PC) and NC groups. The clinical data and the incidence of SAE of patients in two groups were compared, and the 30-day prognosis was followed up. Univariate and Cox regression analyses were performed to analyze whether SAE would predict NC and poor outcome in patients with SICH. RESULTS: A total of 330 patients with acute SICH and coma were enrolled, excluding 60 cases of infratentorial cerebral hemorrhage, 3 cases of primary intraventricular hemorrhage, and 6 cases of unknown volume hematoma. Finally, 261 patients were included, with 111 patients of NC events, and 150 patients of PC events. 69 (62.2%) SAE in SICH with NC and 33 (22.2%) SAE in SICH with PC was diagnosed, and the incidence of SAE between two groups was statistically significant (P < 0.01). Compared with PC group, SICH patients in the NC group had lower incidence of hypertension (81.1% vs. 96.0%), longer time from onset to NC [days: 2.3 (23.9) vs. 0 (0.5)] and length of ICU stay [days: 5.0 (34.0) vs. 3.0 (12.0)], higher initial Glasgow coma score (GCS, 10.2±1.5 vs. 6.6±1.6) and sequential organ failure assessment (SOFA) score [4.0 (6.0) vs. 3.0 (3.0)], lower initial National Institutes of Health Stroke Scale (NIHSS) score (19.4±6.6 vs. 30.2±6.8), as well as more frequent sepsis (78.4% vs. 38.0%), vegetative state (24.3% vs. 14.0%), acute respiratory failure (24.3% vs. 10.0%), pneumonia (37.8% vs. 24.0%), septic shock (8.1% vs. 0), acute liver failure (5.4% vs. 0), hypernatremia (8.1% vs. 0), CT indicating that more frequent vasogenic edema (64.9% vs. 16.0%) and white matter lesion (13.5% vs. 2.0%), and less mannitol usage (94.6% vs. 100.0%), and less brain midline shift (32.4% vs. 68.0%) and hematoma enlargement (8.1% vs. 30.0%), less hematoma volume (mL: 28.0±18.8 vs. 38.3±24.4) in CT, and higher 30-day mortality (54.1% vs. 26.0%) with statistical differences (all P < 0.05). It was shown by Cox regression analyses that SAE [hazard ratio (HR) = 3.5, 95% confidence interval (95%CI) = 1.346-6.765, P = 0.000] and SOFA score (HR = 1.8, 95%CI = 1.073-1.756, P = 0.008) were independent risk factors of death of SICH patients with NC, and hematoma enlargement was independent risk factor of death of SICH patients with PC (HR = 3.0, 95%CI = 1.313-5.814, P = 0.000). CONCLUSIONS: SAE is the independent factor of inducing NC event and poor prognosis in SICH patients.

Neuroinflammation in sepsis: sepsis associated delirium.

Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement of the central nervous system (CNS) during sepsis. The purpose of this review is to provide a concise overview of SAD including the epidemiology and current diagnostic criteria for SAD. We present in detail the pathophysiology with regards to blood-brain-barrier breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about 50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology of SAD is poorly understood, but involves microvascular, metabolic and, not least, inflammatory mechanisms leading to CNS dysfunction. These mechanisms can be different in SAD compared to ICU delirium associated with other conditions. SAD is diagnosed clinically using validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which have good specificity but low sensitivity. Neuroimaging studies and EEG (Electroencephalography) can be useful complement to clinical evaluation to define the severity of the condition. Prompt diagnosis and eradication of septic foci whenever possible is vital. Preventive measures for SAD in the critically ill patient requiring long-term sedation include maintaining light levels of sedation using non-benzodiazepine sedatives (either propofol or dexmedetomidine). Early mobilization of patients in the ICU is also recommended. Antipsychotic drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but firm evidence of their efficacy is lacking.

Statins and delirium during critical illness: a multicenter, prospective cohort study.

OBJECTIVE: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium. DESIGN: Multicenter, prospective cohort study. SETTING: Medical and surgical ICUs in two large tertiary care hospitals in the United States. PATIENTS: Patients with acute respiratory failure or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions). CONCLUSIONS: In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.