Relationship between no-visitation policy and the development of delirium in patients admitted to the intensive care unit.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic, many hospitals imposed a no-visitation policy for visiting patients in hospitals to prevent the transmission of SARS-CoV-2 among visitors and patients. The objective of this study was to investigate the association between the no-visitation policy and delirium in intensive care unit (ICU) patients. METHODS: This was a single-center, before-after comparative study. Patients were admitted to a mixed medical-surgical ICU from September 6, 2019 to October 18, 2020. Because no-visitation policy was implemented on February 26, 2020, we compared patients admitted after this date (after phase) with the patients admitted before the no-visitation policy (before phase) was implemented. The primary outcome was the incidence of delirium during the ICU stay. Cox regression was used for the primary analysis and was calculated using hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates were age, sex, APACHE II, dementia, emergency surgery, benzodiazepine, and mechanical ventilation use. RESULTS: Of the total 200 patients consecutively recruited, 100 were exposed to a no-visitation policy. The number of patients who developed delirium during ICU stay during the before phase and the after phase were 59 (59%) and 64 (64%), respectively (P = 0.127). The adjusted HR of no-visitation policy for the number of days until the first development of delirium during the ICU stay was 0.895 (0.613-1.306). CONCLUSION: The no-visitation policy was not associated with the development of delirium in ICU patients.

Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is frequently implicated as a precipitant of delirium, which refers to an acute confusional state that is associated with high mortality, increased length of stay, and long-term cognitive decline. The pathogenesis of delirium is thought to involve cytokine-mediated neuronal dysfunction of the frontal cortex and hippocampus. We hypothesized that systemic IL-6 inhibition would mitigate delirium-like phenotypes in a mouse model of UTI. METHODS: C57/BL6 mice were randomized to either: (1) non-UTI control, (2) UTI, and (3) UTI + anti-IL-6 antibody. UTI was induced by transurethral inoculation of 1 × 108 Escherichia coli. Frontal cortex and hippocampus-mediated behaviors were evaluated using functional testing and corresponding structural changes were evaluated via quantification of neuronal cleaved caspase-3 (CC3) by immunohistochemistry and western blot. IL-6 in the brain and plasma were evaluated using immunohistochemistry, ELISA, and RT-PCR. RESULTS: Compared to non-UTI control mice, mice with UTI demonstrated significantly greater impairments in frontal and hippocampus-mediated behaviors, specifically increased thigmotaxis in Open Field (p < 0.05) and reduced spontaneous alternations in Y-maze (p < 0.01), while treatment of UTI mice with systemic anti-IL-6 fully reversed these functional impairments. These behavioral impairments correlated with frontal and hippocampal neuronal CC3 changes, with significantly increased frontal and hippocampal CC3 in UTI mice compared to non-UTI controls (p < 0.0001), and full reversal of UTI-induced CC3 neuronal changes following treatment with systemic anti-IL-6 antibody (p < 0.0001). Plasma IL-6 was significantly elevated in UTI mice compared to non-UTI controls (p < 0.01) and there were positive and significant correlations between plasma IL-6 and frontal CC3 (r2 = 0.5087/p = 0.0028) and frontal IL-6 and CC3 (r2 = 0.2653, p < 0.0001). CONCLUSIONS: These data provide evidence for a role for IL-6 in mediating delirium-like phenotypes in a mouse model of UTI. These findings provide pre-clinical justification for clinical investigations of IL-6 inhibitors to treat UTI-induced delirium.

IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury.

Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 is upregulated in mechanical ventilation-induced lung injury (VILI) and may contribute to delirium, it is not known whether the inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model, VILI was simulated in anesthetized adult mice using a 35 cc/kg tidal volume mechanical ventilation model. There were two control groups, as follow: 1) spontaneously breathing or 2) anesthetized and mechanically ventilated with 10 cc/kg tidal volume to distinguish effects of anesthesia from VILI. Two hours before inducing VILI, mice were treated with either anti-IL-6 antibody, anti-IL-6 receptor antibody, or saline. Neuronal injury, stress, and inflammation were assessed using immunohistochemistry. CC3 (cleaved caspase-3), a neuronal apoptosis marker, was significantly increased in the frontal (P < 0.001) and hippocampal (P < 0.0001) brain regions and accompanied by significant increases in c-Fos and heat shock protein-90 in the frontal cortices of VILI mice compared with control mice (P < 0.001). These findings were not related to cerebral hypoxia, and there was no evidence of irreversible neuronal death. Frontal and hippocampal neuronal CC3 were significantly reduced with anti-IL-6 antibody (P < 0.01 and P < 0.0001, respectively) and anti-IL-6 receptor antibody (P < 0.05 and P < 0.0001, respectively) compared with saline VILI mice. In summary, VILI induces potentially reversible neuronal injury and inflammation in the frontal cortex and hippocampus, which is mitigated with systemic IL-6 inhibition. These data suggest a potentially novel neuroprotective role of systemic IL-6 inhibition that justifies further investigation.

Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice.

Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1ß, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.

Comparison of the prevalence and associated factors of hyperactive delirium in advanced cancer patients between inpatient palliative care and palliative home care.

BACKGROUND: Hyperactive delirium is known to increase family distress and the burden on health care providers. We compared the prevalence and associated factors of agitated delirium in advanced cancer patients between inpatient palliative care and palliative home care on admission and at 3 days before death. METHODS: This was a post hoc exploratory analysis of two multicenter, prospective cohort studies of advanced cancer patients, which were performed at 23 palliative care units (PCUs) between Jan and Dec 2017, and on 45 palliative home care services between July and Dec 2017. RESULTS: In total, 2998 patients were enrolled and 2829 were analyzed in this study: 1883 patients in PCUs and 947 patients in palliative home care. The prevalence of agitated delirium between PCUs and palliative home care was 5.2% (95% CI: 4.2% - 6.3%) vs. 1.4% (0.7% - 2.3%) on admission (p < 0.001) and 7.6% (6.4% - 8.9%) vs. 5.4% (4.0% - 7.0%) 3 days before death (p < 0.001). However, multivariate logistic regression analysis revealed that the place of care was not significantly associated with the prevalence of agitated delirium at 3 days before death after adjusting for prognostic factors, physical risk factors, and symptoms. CONCLUSIONS: There was no significant difference in the prevalence of agitated delirium at 3 days before death between inpatient palliative care and palliative home care after adjusting for the patient background, prognostic factors, symptoms, and treatment.

Preoperative brain MRI features and occurrence of postoperative delirium.

OBJECTIVE: Delirium is a frequent complication after surgery with important negative outcomes for affected patients and society. However, it is still largely unknown why some patients have a predisposition for delirium and others not. To increase our understanding of the neural substrate of postoperative delirium, we studied the association between preoperative brain MRI features and the occurrence of delirium after major surgery. METHODS: A group of 413 patients without dementia (Mean 72 years, SD: 5) was included in a prospective observational two-center study design. The study was conducted at Charité Universitätsmedizin (Berlin, Germany) and the University Medical Center Utrecht (Utrecht, The Netherlands). We measured preoperative brain volumes (total brain, gray matter, white matter), white matter hyperintensity volume and shape, brain infarcts and cerebral perfusion, and used logistic regression analysis adjusted for age, sex, intracranial volume, study center and type of surgery. RESULTS: Postoperative delirium was present in a total of 70 patients (17%). Preoperative cortical brain infarcts increased the risk of postoperative delirium, although this did not reach statistical significance (OR (95%CI): 1.63 (0.84-3.18). Furthermore, we found a trend for an association of a more complex shape of white matter hyperintensities with occurrence of postoperative delirium (OR (95%CI): 0.97 (0.95-1.00)). Preoperative brain volumes, white matter hyperintensity volume, and cerebral perfusion were not associated with occurrence of postoperative delirium. CONCLUSION: Our study suggests that patients with preoperative cortical brain infarcts and those with a more complex white matter hyperintensity shape may have a predisposition for developing delirium after major surgery.

Elevated Level of Serum C-reactive Protein Predicts Postoperative Delirium among Patients Receiving Cervical or Lumbar Surgery.

OBJECTIVE: To explore the relationship between elevated serum C-reactive protein (CRP) level and postoperative delirium (POD). METHODS: 206 patients scheduled to receive cervical or lumbar vertebra surgery under general anesthesia for more than 2 hours in a single medical center were observed and analyzed. Patients' serum CRP, delirious status (using the confusion assessment method (CAM)), and delirious score (using the memorial delirium assessment scale (MDAS)) were examined before surgery and 1-2 days after surgery. The association of a serum CRP elevation value from before to after surgery (D-CRP) with delirium occurrence within 2 days after surgery was assessed with a binary logistic regression model, while the association of D-CRP with the postoperative delirious score was assessed with a linear regression model. The effect of D-CRP on predicting delirium occurrence was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: D-CRP was significantly positively associated with postoperative delirium occurrence (OR = 1.047, 95%CI = 1.013, 1.082), and D-CRP was also significantly linearly associated with the postoperative delirious score (ß = 0.014, 95%CI = 0.006, 0.023). AUC of ROC was 0.711 (P = 0.014), suggesting that D-CRP had moderate efficacy on predicting postoperative delirium occurrence (P < 0.05). CONCLUSIONS: Elevated serum CRP after surgery may be a risk factor for and a predictor of postoperative delirium.

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

BACKGROUND: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. METHODS: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. FINDINGS: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. INTERPRETATION: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. FUNDING: National Institute of Nursing Research.

Postoperative anaemia might be a risk factor for postoperative delirium and prolonged hospital stay: A secondary analysis of a prospective cohort study.

BACKGROUND: Postoperative anaemia is a frequent surgical complication and in contrast to preoperative anaemia has not been validated in relation to mortality, morbidity and its associated health economic effect. Postoperative anaemia can predispose postoperative delirium through impairment of cerebral oxygenation. The aim of this secondary analysis is to investigate the association of postoperative anaemia in accordance with the sex specific World Health Organization definition of anaemia to postoperative delirium and its impact on the duration of hospital stay. METHODS: A secondary analysis of the prospective multicentric observational CESARO-study was conducted. 800 adult patients undergoing elective surgery were enrolled from various operative disciplines across seven hospitals ranging from university hospitals, district general hospitals to specialist clinics of minimally invasive surgery in Germany. Patients were classified as anaemic according to the World Health Organization parameters, setting the haemoglobin level cut off below 12g/dl for females and below 13g/dl for males. Focus of the investigation were patients with acute anaemia. Patients with present preoperative anaemia or missing haemoglobin measurement were excluded from the sample set. Delirium screening was established postoperatively for at least 24 hours and up to three days, applying the validated Nursing Delirium Screening Scale. RESULTS: The initial sample set contained 800 patients of which 183 were suitable for analysis in the study. Ninety out of 183 (49.2%) suffered from postoperative anaemia. Ten out of 93 (10.9%) patients without postoperative anaemia developed a postoperative delirium. In the group with postoperative anaemia, 28 (38.4%) out of 90 patients suffered from postoperative delirium (odds ratio 3.949, 95% confidence interval, (1.358-11.480)) after adjustment for NYHA-stadium, severity of surgery, cutting/suture time, duration of anaesthesia, transfusion of packed red cells and sedation status with Richmond Agitation Scale after surgery. Additionally, patients who suffered from postoperative anaemia showed a significantly longer duration of hospitalisation (7.75 vs. 12.42 days, odds ratio = 1.186, 95% confidence interval, 1.083-1.299, after adjustments). CONCLUSION: The study results reveal that postoperative anaemia is not only a frequent postsurgical complication with an incidence probability of almost 50%, but could also be associated with a postoperative delirium and a prolonged hospitalisation.

Older Adults in the Cardiac Intensive Care Unit: Factoring Geriatric Syndromes in the Management, Prognosis, and Process of Care: A Scientific Statement From the American Heart Association.

Longevity is increasing, and more adults are living to the stage of life when age-related biological factors determine a higher likelihood of cardiovascular disease in a distinctive context of concurrent geriatric conditions. Older adults with cardiovascular disease are frequently admitted to cardiac intensive care units (CICUs), where care is commensurate with high age-related cardiovascular disease risks but where the associated geriatric conditions (including multimorbidity, polypharmacy, cognitive decline and delirium, and frailty) may be inadvertently exacerbated and destabilized. The CICU environment of procedures, new medications, sensory overload, sleep deprivation, prolonged bed rest, malnourishment, and sleep is usually inherently disruptive to older patients regardless of the excellence of cardiovascular disease care. Given these fundamental and broad challenges of patient aging, CICU management priorities and associated decision-making are particularly complex and in need of enhancements. In this American Heart Association statement, we examine age-related risks and describe some of the distinctive dynamics pertinent to older adults and emerging opportunities to enhance CICU care. Relevant assessment tools are discussed, as well as the need for additional clinical research to best advance CICU care for the already dominating and still expanding population of older adults.

Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

BACKGROUND: Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. SUBJECTS, MATERIALS, AND METHODS: We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). RESULTS: Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. CONCLUSION: Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. IMPLICATIONS FOR PRACTICE: Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Dopaminergic Hyperactivity in Neurological Patients with Delirium.

BACKGROUND: Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. AIM: To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. METHODS: A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. RESULTS: 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. CONCLUSIONS: In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.

Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limited attempts have been made to study this cognitive domain in preclinical models. Here we implemented the 5-choice serial reaction time task (5-CSRTT) to evaluate attention in a clinically relevant mouse model following orthopedic surgery. The 5-CSRTT showed a time-dependent impairment in the number of responses made by the mice acutely after orthopedic surgery, with maximum impairment at 24 h and returning to pre-surgical performance by day 5. Similarly, the latency to the response was also delayed during this time period but returned to pre-surgical levels within several days. While correct responses decreased following surgery, the accuracy of the response (e.g., selection of the correct nose-poke) remained relatively unchanged. In a separate cohort we evaluated neuroinflammation and blood-brain barrier (BBB) dysfunction using clarified brain tissue with light-sheet microscopy. CLARITY revealed significant changes in microglial morphology and impaired astrocytic-tight junction interactions using high-resolution 3D reconstructions of the neurovascular unit. Deposition of IgG, fibrinogen, and autophagy markers (TFEB and LAMP1) were also altered in the hippocampus 24 h after surgery. Together, these results provide translational evidence for the role of peripheral surgery contributing to delirium-like behavior and disrupted neuroimmunity in adult mice.

Central nervous system localisation of chronic lymphocytic leukaemia, description of two very distinct cases and a review of the literature.

Central nervous system (CNS) localisation of chronic lymphocytic leukaemia (CLL) can induce various neurological symptoms. Unfamiliarity with this manifestation causes diagnostic delay. We present two cases of leptomeningeal CLL. These cases and our literature review emphasise that CNS localisation of CLL should be considered in patients with any neurological symptom, irrespectively of the stage and systemic activity of CLL.

Parkinson's disease-related non-motor features as risk factors for post-operative delirium in spinal surgery.

BACKGROUND: The clinical features of postoperative delirium are similar to the core features of alpha synuclein-related cognitive disorders, such as Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Therefore, we hypothesized that the non-motor symptoms (NMSs) in Parkinson's disease (PD), which precede the cardinal motor features of PD, are likely to be risk factors for developing postoperative delirium. We investigated the association between PD-related NMSs and postoperative delirium in old people undergoing elective spinal surgery. METHODS: This study was a prospective study. Participants were aged 65 years and older and scheduled to undergo elective spinal surgery. During the enrollment period, 338 individuals were screened, 104 participants were included in the analysis. We assessed eight easily-assessed and representative PD-related NMSs 1 day before the scheduled surgery using tests or questionnaires for each symptom. The presence of delirium was determined by using the short version of the Confusion Assessment Method (CAM). RESULTS: Fifteen (14.4%) of the 104 participants (age, 71.7 ± 4.7 years; men, 34.6%) met the CAM criteria for post-operative delirium. Multivariate logistic analysis showed that decreased olfactory function (odds ratio [OR] 0.63, 95% CI 0.44-0.91) and exhibiting rapid eye movement sleep behavior disorder (RBD, OR 1.45, 95% CI 1.09-1.93) were significantly independent predictors of postoperative delirium. CONCLUSIONS: Our study shows that hyposmia and RBD are significantly independent risk factors for postoperative delirium in general elderly population. Considering that NMSs may represent burden of alpha synuclein deposit, we postulate that an underlying alpha synucleinopathy may correlates with postoperative delirium. SIGNIFICANCE: This study gives a novel insight for the risk factor of postoperative delirium.

Advance Directives, Hospitalization, and Survival Among Advanced Cancer Patients with Delirium Presenting to the Emergency Department: A Prospective Study.

BACKGROUND: To improve the management of advanced cancer patients with delirium in an emergency department (ED) setting, we compared outcomes between patients with delirium positively diagnosed by both the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS), or group A (n = 22); by the MDAS only, or group B (n = 22); and by neither CAM nor MDAS, or group C (n = 199). MATERIALS AND METHODS: In an oncologic ED, we assessed 243 randomly selected advanced cancer patients for delirium using the CAM and the MDAS and for presence of advance directives. Outcomes extracted from patients' medical records included hospital and intensive care unit admission rate and overall survival (OS). RESULTS: Hospitalization rates were 82%, 77%, and 49% for groups A, B, and C, respectively (p = .0013). Intensive care unit rates were 18%, 14%, and 2% for groups A, B, and C, respectively (p = .0004). Percentages with advance directives were 52%, 27%, and 43% for groups A, B, and C, respectively (p = .2247). Median OS was 1.23 months (95% confidence interval [CI] 0.46-3.55) for group A, 4.70 months (95% CI 0.89-7.85) for group B, and 10.45 months (95% CI 7.46-14.82) for group C. Overall survival did not differ significantly between groups A and B (p = .6392), but OS in group C exceeded those of the other groups (p < .0001 each). CONCLUSION: Delirium assessed by either CAM or MDAS was associated with worse survival and more hospitalization in patients with advanced cancer in an oncologic ED. Many advanced cancer patients with delirium in ED lack advance directives. Delirium should be assessed regularly and should trigger discussion of goals of care and advance directives. IMPLICATIONS FOR PRACTICE: Delirium is a devastating condition among advanced cancer patients. Early diagnosis in the emergency department (ED) should improve management of this life-threatening condition. However, delirium is frequently missed by ED clinicians, and the outcome of patients with delirium is unknown. This study finds that delirium assessed by the Confusion Assessment Method or the Memorial Delirium Assessment Scale is associated with poor survival and more hospitalization among advanced cancer patients visiting the ED of a major cancer center, many of whom lack advance directives. Therefore, delirium in ED patients with cancer should trigger discussion about advance directives.

Morte do sujeito: representação e limite real na clínica das psicoses / Death of the subject: representation and real limit in the clinic of psychosis

Aborda-se a formulação lacaniana de que, em Schreber, houve um momento de 'morte do sujeito' que permitiu a construção do delírio estabilizador. Se o advento do sujeito é tributário da 'morte da coisa' perpetrada pelo significante, Lacan fala aqui da psicose, constituída pela não simbolização da castração. Discute-se a noção de 'segunda morte', forjada a propósito de Sócrates, de Antígona e do Cotard, e a Bejahung como afirmação primordial que inclui a negatividade. Conclui-se que a 'morte do sujeito' pode ser uma abertura para a representação ou um limite real para o psicótico, expondo às passagens ao ato e evoluções demenciais.

The paper discusses Lacan's proposal that Schreber's stabilization was made possible by a moment of 'death of the subject.' The advent of the subject is related with the 'death' of the thing itself perpetrated by the signifier. Here, Lacan mentions its relation to psychosis, in which there's a non-symbolization of castration. We discuss the notion of 'second death', related to Socrates, Antigone and Cotard, and the Bejahung as an original affirmation which includes the negativeness. We conclude that the 'death of the subject' can be an opening to the representation or a 'real' limit to the psychotic, presenting the risk of passages to the act and 'dementia-like' evolutions.

Risk factors for delirium after on-pump cardiac surgery: a systematic review.

INTRODUCTION: As evidence-based effective treatment protocols for delirium after cardiac surgery are lacking, efforts should be made to identify risk factors for preventive interventions. Moreover, knowledge of these risk factors could increase validity of etiological studies in which adjustments need to be made for confounding variables. This review aims to systematically identify risk factors for delirium after cardiac surgery and to grade the evidence supporting these associations. METHOD: A prior registered systematic review was performed using EMBASE, CINAHL, MEDLINE and Cochrane from 1990 till January 2015 ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007371 ). All studies evaluating patients for delirium after cardiac surgery with cardiopulmonary bypass (CPB) using either randomization or multivariable data analyses were included. Data was extracted and quality was scored in duplicate. Heterogeneity impaired pooling of the data; instead a semi-quantitative approach was used in which the strength of the evidence was graded based on the number of investigations, the quality of studies, and the consistency of the association reported across studies. RESULTS: In total 1462 unique references were screened and 34 were included in this review, of which 16 (47 %) were graded as high quality. A strong level of evidence for an association with the occurrence of postoperative delirium was found for age, previous psychiatric conditions, cerebrovascular disease, pre-existent cognitive impairment, type of surgery, peri-operative blood product transfusion, administration of risperidone, postoperative atrial fibrillation and mechanical ventilation time. Postoperative oxygen saturation and renal insufficiency were supported by a moderate level of evidence, and there is no evidence that gender, education, CPB duration, pre-existent cardiac disease or heart failure are risk factors. CONCLUSION: Of many potential risk factors for delirium after cardiac surgery, for only 11 there is a strong or moderate level of evidence. These risk factors should be taken in consideration when designing future delirium prevention strategies trials or when controlling for confounding in future etiological studies.

The impact of lymphopenia on delirium in ICU patients.

BACKGROUND: Immunosuppressed states may predispose patients to development of acute brain injury during times of critical illness. Lymphopenia is a non-specific yet commonly used bedside marker of immunosuppressed states. METHODS: We examined whether lymphopenia would predict development of acute brain dysfunction (delirium and/or coma) in 518 patients enrolled in the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study in medical and surgical ICUs of a tertiary care, university-based medical center. Utilizing proportional odds logistic regression and Cox proportional hazards survival analysis, we assessed the relationship between pre-enrollment lymphocytes and subsequent cognitive outcomes including delirium- and coma-free days (DCFDs) and 30-day mortality. RESULTS: There were no statistically significant associations between lymphocytes and DCFDs (p = 0.17); additionally, the relationship between lymphocytes and mortality was not statistically significant (p = 0.71). Among 259 patients without history of cancer or diabetes, there was no statistically significant association between lymphocytes and DCFDs (p = 0.07). CONCLUSION: lymphopenia, a commonly used bedside marker of immunosuppression, does not appear to be a marker of risk for acute brain injury (delirium/coma) or 30-day mortality in general medical/surgical ICU patients.

Preoperative brain magnetic resonance imaging and postoperative delirium after off-pump coronary artery bypass grafting: a prospective cohort study.

BACKGROUND: Delirium after cardiac surgery is a serious complication, increasing morbidity and mortality. Despite its high expectations, off-pump coronary artery bypass grafting (OPCAB) has largely failed to reduce the incidence of postoperative neurological complications. To further investigate the reasons for this failure, we used perioperative brain magnetic resonance imaging (MRI) to determine the relation between MRI findings and postoperative delirium. METHODS: Altogether, 98 patients undergoing elective OPCAB were enrolled in this prospective observational study. Patients underwent brain MRI and magnetic resonance angiography (MRA) before and after surgery to identify cerebral infarction, white matter lesions, and intracranial artery stenosis. Postoperative delirium in the intensive care unit was measured using the delirium rating scale. The relation between postoperative delirium and MRI findings was examined using logistic regression. RESULTS: Magnetic resonance imaging and MRA was completed in 88 (90%) of the patients. New ischemic lesions were present in seven (7.9%) patients. Delirium rating scale scores of 0, 1-7, and ≥ 8 were found in 25 (31%), 48 (60%), and seven (9%) patients, respectively. Multivariate logistic regression analysis revealed that new ischemic lesions (odds ratio [OR] 11.07, 95% confidence interval [CI]: 1.53 to 80.03; P = 0.017), carotid artery stenosis (OR 7.06, 95% CI: 1.59 to 31.13; P = 0.010), history of myocardial infarction (OR 3.78, 95% CI: 1.05 to 13.65; P = 0.043), and deep subcortical white matter hyperintensity (OR 3.04, 95% CI: 1.14 to 8.12; P = 0.027) were significantly associated with postoperative delirium. CONCLUSIONS: Magnetic resonance imaging findings of new cerebral ischemic lesions, carotid stenosis, and deep subcortical white matter hyperintensity correlated significantly with postoperative delirium in patients who had undergone OPCAB surgery.