Acute Brain Dysfunction Research Articles

Delirium in the ICU

Introduction: Delirium, the most prevalent form of acute brain dysfunction in the Intensive Care Unit (ICU) is characterized by inattention, changes in cognition and at times thought and perceptual disturbances (e.g., delusions and hallucinations). Recent estimates of delirium prevalence suggest around 70% of patients on mechanical ventilation will experience delirium during their critical illness and almost a third of days in the ICU are days spent with delirium1,2. There are at least three distinct motor subtypes of delirium: hypoactive (decreased movement), hyperactive (increased movement and at times agitation) and mixed (features of both). The hypoactive form predominates, is under-diagnosed and is associated with worse outcomes. Recent work has suggested that another psychomotor disturbance, catatonia may co-occur in up to a third of patients with delirium in the ICU3. Risk factors: Risk factors for the development of delirium include: pre-existing dementia, advanced age, hypertension, pre-critical illness emergency surgery or trauma, increased severity of illness, mechanical ventilation, metabolic acidosis, prior delirium or coma and use of certain delirium potentiating drugs such as anti-cholinergic and sedative hypnotic medications. Mechanisms: Exact mechanisms leading to the development of delirium are unknown, however early evidence suggests neural disconnectivity of the dorsolateral prefrontal cortex and the posterior cingulate cortex. Reversible reduction of functional connectivity of subcortical regions and neuroinflammation leading to hippocampal and extra-hippocampal dysfunction, may play potential roles. Overall all brain volume loss and disruption in white matter tracts may be associated with new onset dementia in survivors of critical illness. Due to the heterogeneous phenotype of delirium, there may be multiple causative neurobiological mechanisms contributing to its development, instead of one unifying pathway. Morbidity and mortality: Delirium is associated with significant morbidity and mortality. Much of the critical care literature about delirium has focused on the exposure of delirium and its relationship with acquired disabilities, as well as its effect on in-hospital and post-discharge excess mortality. Delirium is known to be predictive of new-onset dementia4, depression, excess mortality, longer lengths of stay, institutionalization at discharge, inability to return to work and increased cost of care in the hospital. Prevention and treatment: Despite scant evidence, antipsychotic medications have historically been the treatment of choice for delirium, however recent findings suggest that typical and atypical antipsychotics have no effect on delirium duration in the ICU5. As delirium is characterized by alterations in the sleep wake cycle, some studies have explored the role of melatonin or ramelton in the prevention or treatment of delirium, with early promising results. Non-pharmacological interventions such as complete adherence to the ABCDEF (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) bundle have shown benefit in reducing delirium prevalence in the ICU2.

Frailty, Acute Organ Dysfunction, and Increased Disability After Hospitalization in Older Adults Who Survive Critical Illness: A Prospective Cohort Study.

We aimed to describe the association between prehospital frailty (PHF), acute organ dysfunction (AOD), and posthospital disability (PHD) outcome in older adults admitted to the intensive care unit (ICU). In a prospective observational cohort study, we assessed PHF using the Clinical Frailty Scale (CFS) and assessed the level of AOD using Sequential Organ Failure Assessment (SOFA) scores on ICU day 1. We assessed Activities of Daily Living disability levels through to 6 months after discharge and used generalized estimating equations (log link and negative binomial family) to determine the independent association of PHF and AOD with PHD. Of the 302 patients enrolled, 221 (73.1%) survived the hospitalization. Prehospital frailty was associated with PHD (adjusted incident rate ratio [aIRR] 95% confidence interval [95% CI] per unit increase in CFS 1.38 [1.15-1.67], P = .001). Total day 1 SOFA score was weakly associated with PHD, (aIRR [95% CI] 1.05 [1.00-1.10], P = .037) while day 1 SOFA neurologic score was strongly associated with PHD (aIRR [95% CI] 1.42 [1.24-1.62] per unit increase in SOFA neurologic score, P < .001), and these effects were independent of PHF and other premorbid factors. Both PHF and early acute brain dysfunction are important factors associated with increasing PHD in older adults who survive critical illness.

Innovative ICU Solutions to Prevent and Reduce Delirium and Post-Intensive Care Unit Syndrome.

Delirium, the most common form of acute brain dysfunction affecting up to 80% of intensive care unit (ICU) patients, has been shown to predict long-term cognitive impairment, one of the domains in "Post-ICU Syndrome" (PICS). The ICU environment affects several potentially modifiable risk factors for delirium, such as disorientation and disruption, of the sleep-wake cycle. Innovative solutions aim to transform standard concepts of ICU room design to limit potential stressors, and utilizing the patient care space as a treatment tool, exerting positive, therapeutic effects. The main areas affected by most architectural and interior design modifications are sound environment, light control, floor planning, and room arrangement. Implementation of corresponding solutions is challenging considering the significant medical and technical demands of ICUs. This article discusses innovative concepts and promising approaches in ICU design that may be used to prevent stress and to support the healing process of patients, potentially limiting the impact of delirium and PICS.

The Relationship Between the Level of Inflammation Biomarkers at Admission to the Intensive Care Unit and the Duration of Acute Brain Dysfunction in Sepsis Patients

The Relationship Between the Level of Inflammation Biomarkers at Admission to the Intensive Care Unit and the Duration of Acute Brain Dysfunction in Sepsis Patients

Diagnosing acute brain dysfunction due to sepsis.

Developments in the management of critically ill patients suffering organ dysfunctions have demonstrated that brain is the prominent organ to be effected during critical illness. Acute brain dysfunction due to pathologic neuroinflammatory processes associated with sepsis is commonly seen and related to morbidity and mortality in the ICU treatment. Studies reported that survivors of sepsis may suffer long-term cognitive dysfunction that affects quality of life. However, there are no specific approaches to diagnose acute brain dysfunction in the early phase to target protective measures. In recent years, imaging methods and biomarkers are the most important issues of studies. This review will address the current diagnostic approaches to acute brain dysfunction related to sepsis.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. Multicenter, prospective cohort study. The emergency department and ICUs of 15 medical centers. Mechanically ventilated adult emergency department patients. None. All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Thermolabile polymorphism of carnitine palmitoyltransferase 2: A genetic risk factor of overall acute encephalopathy

ObjectivesAcute encephalopathy is an acute brain dysfunction after preceding infection, consisting of multiple syndromes. Some syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), are severe with poor outcome, whereas others, such as clinically mild encephalitis/encephalopathy with reversible splenial lesion (MERS), are mild with favorable outcome. Previous study reported the association of the thermolabile polymorphism in Carnitine Palmitoyltransferase 2 (CPT2) gene and severe syndromes of acute encephalopathy. To further explore the pathogenetic role of CPT2 in acute encephalopathy, we conducted a case-control association study of a typical thermolabile CPT2 polymorphism, rs2229291, in 416 patients of acute encephalopathy, including both severe and mild syndromes. MethodsThe case cohort consisted of 416 patients, including AESD, MERS, and other syndromes. The control subjects were 100 healthy Japanese. rs2229291 was genotyped by Sanger sequencing. Genetic distribution was compared between the patients and controls using Cochran-Armitage trend test. ResultsMinor allele frequency of rs2229291 was significantly higher in AESD (p = 0.044), MERS (p = 0.015) and entire acute encephalopathy (p = 0.044) compared to the controls. The polymorphism showed no significant association with influenza virus, or with outcome. ConclusionsThis study provided evidence that CPT2 is a susceptibility gene for overall acute encephalopathy, including both severe and mild syndromes, and suggested that impairment of mitochondrial metabolism is common to various syndromes of acute encephalopathy.

Current controversies and future perspectives on treatment of intensive care unit delirium in adults.

Delirium is the most frequent manifestation of acute brain dysfunction in intensive care unit (ICU). Although antipsychotics are widely used to treat this serious complication, recent evidence has emphasized that these agents did not reduce ICU delirium (ICU-D) prevalence and did not improve survival, length of ICU or hospital stay after its occurrence. Of note, no pharmacological strategy to prevent or treat delirium has been identified, so far. In this scenario, new scientific evidences are urgently needed. Investigations on specific ICU-D subgroups, or focused on different clinical settings, and studies on medications other than antipsychotics, such as dexmedetomidine or melatonin, may represent interesting fields of research. In the meantime, because there is some evidence that ICU-D can be effectively prevented, the literature suggests strengthening all the strategies aimed at prevention through no-pharmacological approaches mostly focused on the correction of risk factors. The more appropriate strategy useful to treat established delirium remains the use of antipsychotics managed by choosing the right doses after a careful case-by-case analysis. While the evidence regarding the use of dexmedetomidine is still conflicting and sparse, this drug offers interesting perspectives for both ICU-D prevention and treatment. This paper aims to provide an overview of current pharmacological approaches of evidence-based medicine practice. The state of the art of the on-going clinical research on the topic and perspectives for future research are also addressed.

Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis

Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure. In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method. Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients. Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.

Type D personality is a predictor of prolonged acute brain dysfunction (delirium/coma) after cardiovascular surgery

BackgroundPrevious studies have shown a relationship between delirium and depressive symptoms after cardiac surgery with distress personalities linking to negative surgical outcomes. The aim of the present study is to further investigate the association between patients with Type D (distressed) personality with regards to delirium after cardiac surgery.MethodsWe conducted a consecutive-sample observational cohort pilot study with an estimated 142 patients needed. Enrollment criteria included patients aged ≥18 years who were undergoing planned cardiovascular, thoracic and abdominal artery surgery between October 2015 to August 2016 at the University of Tsukuba Hospital, Japan. All patients were screened by Type-D Personality Scale-14 (DS14) as well as the Hospital Anxiety and Depression Scale (HADS) the day before surgery. Following surgery, daily data was collected during recovery and included severity of organ dysfunction, sedative/analgesic exposure and other relevant information. We then evaluated the association between Type D personality and delirium/coma days (DCDs) during the 7-day study period. We applied regression and mediation modeling for this study.ResultsA total of 142 patients were enrolled in the present study and the total prevalence of delirium was found to be 34% and 26% of the patients were Type D. Non-Type D personality patients experienced an average of 1.3 DCDs during the week after surgery while Type D patients experienced 2.1 days over the week after surgery. Multivariate analysis showed that Type D personality was significantly associated with increased DCDs (OR:2.8, 95%CI:1.3–6.1) after adjustment for depressive symptoms and clinical variables. Additionally, there was a significant Type D x depression interaction effect (OR:1.7, 95% CI:1.2–2.2), and depressive symptoms were associated with DCDs in Type D patients, but not in non-Type D patients. Mediation modeling showed that depressive symptoms partially mediated the association of Type D personality with DCDs (Aroian test =0.04).ConclusionsType D personality is a prognostic predictor for prolonged acute brain dysfunction (delirium/coma) in cardiovascular patients independent from depressive symptoms and Type D personality-associated depressive symptoms increase the magnitude of acute brain dysfunction.

Use of the brief Confusion Assessment Method in a veteran palliative care population: A pilot validation study.

Many patients with advanced serious illness or at the end of life experience delirium, a potentially reversible form of acute brain dysfunction, which may impair ability to participate in medical decision-making and to engage with their loved ones. Screening for delirium provides an opportunity to address modifiable causes. Unfortunately, delirium remains underrecognized. The main objective of this pilot was to validate the brief Confusion Assessment Method (bCAM), a two-minute delirium-screening tool, in a veteran palliative care sample. This was a pilot prospective, observational study that included hospitalized patients evaluated by the palliative care service at a single Veterans' Administration Medical Center. The bCAM was compared against the reference standard, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Both assessments were blinded and conducted within 30 minutes of each other. We enrolled 36 patients who were a median of 67 years (interquartile range 63-73). The primary reasons for admission to the hospital were sepsis or severe infection (33%), severe cardiac disease (including heart failure, cardiogenic shock, and myocardial infarction) (17%), or gastrointestinal/liver disease (17%). The bCAM performed well against the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, for detecting delirium, with a sensitivity (95% confidence interval) of 0.80 (0.4, 0.96) and specificity of 0.87 (0.67, 0.96). Delirium was present in 27% of patients enrolled and never recognized by the palliative care service in routine clinical care. The bCAM provided good sensitivity and specificity in a pilot of palliative care patients, providing a method for nonpsychiatrically trained personnel to detect delirium.

Effectiveness of Melatonin for the Prevention of Intensive Care Unit Delirium.

Intensive care unit (ICU) delirium is an acute brain dysfunction that has been associated with increased mortality, prolonged ICU and hospital lengths of stay, and development of post-ICU cognitive impairment. Melatonin may help to restore sleep and reduce the occurrence of ICU delirium. The purpose of this study was to evaluate the effectiveness of melatonin for the prevention of ICU delirium in critically ill adults. Retrospective, observational cohort study. Large academic medical center. A total of 232 adults were included who were admitted to the medical-surgical or cardiac ICUs between 2013 and 2017 who had a negative Confusion Assessment Method for the ICU (CAM-ICU). Of those, patients who received melatonin for at least 48 hours were included in the melatonin group (n=117). Patients were included in the control group if they were admitted to the ICU for at least 4 days (average time of melatonin initiation) and did not receive melatonin or antipsychotics within the first 4 days of their ICU stay (n=115). The primary outcome was development of delirium, which was assessed by using the CAM-ICU twice daily by nursing staff. The development of delirium was significantly lower in the melatonin group: 9 (7.7%) versus 28 (24.3%) patients (p=0.001). This finding remained significant in multivariate logistic models controlling for age, sex, history of hypertension, need for emergent surgery, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, ICU length of stay, dexmedetomidine use, and benzodiazepine use. For those patients who developed delirium, patients in the control group had, on average, 20.9 delirium-free days without coma in 28days compared with 19.9days in the melatonin group (p=0.72). In the melatonin group, melatonin was used for a mean±SD of 6.3±7.9days, with a median dose of 3.5mg/night (range: 1-10mg). The development of ICU delirium was significantly lower in the melatonin group compared with that in the control group. To our knowledge, this is one of the only studies that has examined the use of melatonin for the prevention of ICU delirium. Melatonin may be a promising agent for the prevention of ICU delirium; however, a randomized study is needed to further validate its efficacy.

Delirium Monitoring: Yes or No? That Is The Question.

Delirium, one of the most common manifestations of acute brain dysfunction, is a serious complication in patients receiving care throughout the hospital and a strong predictor of worse outcome. Although delirium monitoring is advocated in numerous evidence-based guidelines as part of routine clinical care, it is still not widely and consistently performed at the bedside in different patient care settings. In a debate on delirium monitoring in hospitalized patients at the 7th American Delirium Society meeting in Nashville, Tennessee, June 2017, areas related to the feasibility, acceptability, and effectiveness of routine delirium monitoring of hospitalized patients were identified, and arguments both for (pro) and against (con) the practice were presented. These arguments and others arising in the discussion were subsequently expanded. The goals were to present a conversation among clinicians and researchers from different settings and to identify the evidence-practice gaps for delirium monitoring for future research and organizational quality improvement programs. Further research is needed to determine whether or not delirium monitoring should become routine clinical care for every patient in every hospital setting.

3217 Catatonia, Delirium and Coma: Implications for Mortality

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.

Probenecid Relieves Cerebral Dysfunction of Sepsis by Inhibiting Pannexin 1-Dependent ATP Release.

Acute brain dysfunction and the following neurological manifestation are common complications in septic patients, which are associated with increased morbidity and mortality. However, the therapeutic strategy of this disorder remains a major challenge. Given the emerging role of a clinically approved drug, probenecid (PRB) has been recently identified as an inhibitor of pannexin 1 (PANX1) channel, which restrains extracellular ATP release-induced purinergic pathway activation and inflammatory response contributing to diverse pathological processes. In this study, we explored whether PRB administration attenuated neuroinflammatory response and cognitive impairment during sepsis. In mice suffered from cecal ligation and puncture (CLP)-induced sepsis, treatment with PRB improved memory retention and lessened behavioral deficits. This neuroprotective effect was coupled with restricted overproduction of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and interleukin (IL)-1β in the hippocampus. Since this damped neuroinflammation was replicated by inhibition of ATP release, it suggested that PANX1 channel modulates a purinergic-related pathway contributing to the neurohistological damage. Therefore, we identified PRB could be a promising therapeutic approach for the therapy of cerebral dysfunction of sepsis.

Cerebral Multimodal Monitoring in Sepsis: An Experimental Study.

Acute brain dysfunction is a complication of sepsis, and its pathophysiology remains poorly understood. We studied the brain metabolism in a resuscitated animal model of sepsis. Twelve anesthetized, mechanically ventilated, and invasively monitored pigs were allocated to a sham procedure (N = 5) or sepsis (N = 7). Sepsis was induced through fecal inoculation in the peritoneum. Fluid resuscitation was maintained during the entire study period. Animals were observed until spontaneous death or for a maximum of 24 h. In addition to global hemodynamic and laboratory assessment, intracranial pressure and cerebral microdialysis (MD) were evaluated at baseline, 6, 12, 18, and 24 h after sepsis induction. After euthanasia, the brain was rapidly removed and a fragment from the frontal cortex was analyzed for markers of neuroinflammation, metabolism, and neurotransmission. Septic animals developed a hyperdynamic state associated with increased arterial lactate. Cerebral microdialysis showed unchanged levels of lactate/pyruvate ratios and brain glucose between the groups. Brain/serum glucose ratios were increased in the septic animals during the study period despite a progressive decrease in serum glucose. Moreover, extracellular glutamine levels were elevated starting at 6 h after sepsis. Tissue analysis showed elevated glutamate, glutamine, and glutamine synthetase in the sepsis group. However, C-Fos, a marker of neuronal activity, was unchanged between groups. In this animal model of resuscitated sepsis, we found increased oxidative stress and alterations in neuroenergetics characterized by exacerbated activity of the glutamate/glutamine cycle and increased glucose utilization by the brain, however without any evidence of decompensated energy metabolism.

Delirium: An Acute Confusional State

Delirium is a frequent ineffectiveness in brain functioning. It is a disturbance in attention and awareness that develops over a short period of time and it is a neurocognitive disorder. Delirium provides an idiosyncratic chance for a better understanding of the neurocognitive reserve. Acute illness considered as a basis of delirium and it is usually activated by head trauma and recent surgeries. Delirium like dementia is clearly remarkable by a general disability in which a condition of being unable to perform as a consequence of physical and mental unfitness. It has also been observed that delirium can increase the rate of development of dementia. Unfortunately, the development of delirium or acute brain dysfunction is considered a non-essential component of a critical or unfavorable disease. The agitation and inactivity that is occurred in a delirium can increase the risk or danger of complications. Delirium is a major cause and the problem of hospitalization and should be considered a medical crisis. For these reasons its identification, prescription, and effective treatment are essential. For delirium treatment, the most common antipsychotic drugs are used. Emerging pharmacological strategies which include various antipsychotics drugs for addressing delirium should be combined with non-pharmacological approaches which are designed as a first line interventions.

Chapter 19 - Delirium in the critically ill patient

Delirium is an acute and transient brain dysfunction that is characterized by disturbances in consciousness, affecting both its content (i.e., attention) and level (i.e., arousal). It affects as many as 50% of those admitted to an intensive care unit (ICU). Once believed to be an inconsequential outcome of critical illness, it is now recognized that delirium is harmful in both the short- and long-term. Despite occurring frequently in critically ill patients, delirium often goes unrecognized. Well-validated delirium screening tools, designed for use in the ICU, should be used to reliably detect delirium. The first step in delirium treatment is to identify and address potentially modifiable risk factors. Multiple trials have shown that benzodiazepines are a risk factor for delirium in a dose-dependent manner. Sedation with nonbenzodiazepine-based strategies are an effective means by which to reduce delirium. Nonpharmacologic strategies such as those which seek to reduce sensory impairment, sleep deprivation, and immobility are effective. Pharmacologic treatment with antipsychotics, though commonly used, is not supported by findings from placebo-controlled trials. Recent data support from multiple trials support the use of the "ABCDEF bundle" as a means by which to reduce delirium.

Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment.

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB’s role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

The rationale of flexible ICU visiting hours for delirium prevention

Delirium is a frequent and severe form of acute brain dysfunction that occurs in the critically ill (1). It currently represents a major challenge for critical care professionals as it is associated with increased mortality, longer intensive care unit (ICU) and hospital stay, increased risk of long-term cognitive impairment, and higher costs of care (2,3). Disappointingly, pharmacologic interventions have a limited role in the prevention and treatment of delirium (4). Conversely, many non-pharmacologic interventions such as reorientation activities, cognitive stimulation, early mobilization, sleep hygiene, and flexibilization of family visits have gained increasing attention due to its low cost and potential to prevent or limit delirium among ICU patients (5,6).