Delirium as late manifestation of infective endocarditis after transcatheter aortic valve implantation.

More than one-third of the cases of infective endocarditis (IE) occur in older patients. The disease is often characterized by atypical symptoms. The incidence of neurological complications is high and represents a strong independent predictor of severe outcomes and mortality. IE is a rare but serious complication of transcatheter aortic valve implantation (TAVI). A persistent delirium as a unique manifestation of post-TAVI IE in an older patient is presented in this clinical case.

Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan.

BACKGROUND: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients. METHODS: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models. RESULTS: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001). CONCLUSIONS: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies.

Systemic interleukin-6 inhibition ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury.

Acute neuropsychiatric impairments occur in over 70% of patients with acute lung injury. Mechanical ventilation is a well-known precipitant of acute lung injury and is strongly associated with the development of acute delirium and anxiety phenotypes. In prior studies, we demonstrated that IL-6 mediates neuropathological changes in the frontal cortex and hippocampus of animals with mechanical ventilation-induced brain injury; however, the effect of systemic IL-6 inhibition on structural and functional acute neuropsychiatric phenotypes is not known. We hypothesized that a murine model of mechanical ventilation-induced acute lung injury (VILI) would induce neural injury to the amygdala and hippocampus, brain regions that are implicated in diverse neuropsychiatric conditions, and corresponding delirium- and anxiety-like functional impairments. Furthermore, we hypothesized that these structural and functional changes would reverse with systemic IL-6 inhibition. VILI was induced using high tidal volume (35 cc/kg) mechanical ventilation. Cleaved caspase-3 (CC3) expression was quantified as a neural injury marker and found to be significantly increased in the VILI group compared to spontaneously breathing or anesthetized and mechanically ventilated mice with 10 cc/kg tidal volume. VILI mice treated with systemic IL-6 inhibition had significantly reduced amygdalar and hippocampal CC3 expression compared to saline-treated animals and demonstrated amelioration in acute neuropsychiatric behaviors in open field, elevated plus maze, and Y-maze tests. Overall, these data provide evidence of a pathogenic role of systemic IL-6 in mediating structural and functional acute neuropsychiatric symptoms in VILI and provide preclinical justification to assess IL-6 inhibition as a potential intervention to ameliorate acute neuropsychiatric phenotypes following VILI.

Psychiatric reaction of an intensive care unit survivor in the context of coronavirus disease 2019: a case report.

BACKGROUND: The coronavirus disease 2019 pandemic has had a serious impact on global mental health, particularly in intensive care unit survivors. Given the lethal potential and unpredictability of coronavirus disease 2019, a high risk of posttraumatic stress disorder was identified in the beginning of the crisis. There are insufficient details in current literature and no official guidelines available for the treatment and follow-up of acute stress disorder and the prevention of posttraumatic stress disorder for intensive care unit survivors in the context of coronavirus disease 2019. CASE PRESENTATION: We hereby describe a 67-year-old Swiss patient presenting a psychiatric reaction in the context of coronavirus disease 2019. He was admitted to the intensive care unit due to severe acute respiratory distress syndrome from severe acute respiratory syndrome coronavirus 2 and intubated for 13 days. Afterwards, there was a severe worsening of acute renal failure prompting hemodialysis, and he developed delirium. Psychiatric liaison was requested 4 days post-intubation because the patient presented residual symptoms of delirium, false memories about the real context of his medical care, and ideas of persecution toward medical caregivers. He suffered from a very strong peritraumatic reaction, then developed an acute stress disorder linked with his care on the intensive care unit. We looked for strategies to prevent progression from acute stress disorder to posttraumatic stress disorder. We proceeded to the following therapeutic interventions: intensive psychiatric follow-up, intensive care unit diary, and low-dose antipsychotic treatment. The aim of our psychotherapeutic approach was to allow him to increase his feeling of security and to cope with the reality of his traumatic experience. He showed clinical improvement in his mental state after 3 months, despite several predictive factors of evolution to post-intensive care unit posttraumatic stress disorder. CONCLUSION: This case report illustrates how a delusional clinical presentation after intensive care in the context of coronavirus disease 2019 can hide psychotraumatic symptoms. It is important to highlight that the intensive care unit diary completed by the intensive care team and the follow-up by the psychiatric liaison team helped the patient reconstruct an appropriate and coherent account. Further studies are needed to determine the psychiatric effects of coronavirus disease 2019 and to assess early and appropriate psychiatric intervention for patients hospitalized for coronavirus disease 2019 to prevent posttraumatic stress disorder.

Delirium as a Presenting Symptom of COVID-19.

BACKGROUND: Delirium is a common neurologic manifestation of coronavirus disease 2019 (COVID-19) in older adults who present to the emergency department (ED). OBJECTIVE: To investigate clinical characteristics associated with delirium as a presenting symptom of COVID-19 in older adults and develop a logistic regression to predict the likelihood of delirium. METHOD: We compared clinical characteristics in an age- and gender-matched sample of 68 delirious individuals with 68 nondelirious individuals (Mage = 78) who presented to the ED with COVID-19. RESULTS: The delirious group was more likely to have neurologic, psychiatric, and cardiovascular comorbidities; a prior history of delirium; and deliriogenic medications in their medication list. They were less likely to present with respiratory symptoms and more likely to present with sepsis, hypoxia, higher heart rate, and higher sodium. The delirious group had higher mortality (51%) than the nondelirious group (32%). Delirium developed within an average of 2 days of initial COVID-19 symptom onset, with symptom onset to ED within an average of 4 days and symptom onset to death within an average of 11 days. Logistic regression based on five delirium predictors correctly predicted 80% of those with delirium (75% sensitivity at 86% specificity). CONCLUSION: Our results are largely consistent with prior studies and suggest that delirium is a common, early occurring, and lethal manifestation of COVID-19 in older adults presenting to the ED, in most cases causing acute on chronic neurocognitive dysfunction strongly influenced by inflammatory and hypoxic-ischemic mechanisms.

Prevalence, classification, risk factors and outcome impact of delirium in patients with COVID-19: a meta-analysis protocol for systematic review.

INTRODUCTION: Previous studies have shown mixed results that delirium may result in a high risk of adverse clinical outcomes in patients with COVID-19. The aim of this meta-analysis is to summarise the evidence of prevalence, classification, risk factors and outcomes impact of delirium in adult patients with COVID-19. METHODS: A systematic search will be performed in PubMed, EMBase, ISI Knowledge via Web of Science and preprint databases (MedRxiv and BioRxiv) (from inception until June 2021) to identify all cohort studies concerning delirium in adult patients with COVID-19. The primary outcome will be the prevalence of delirium with different classifications (hyperactive, hypoactive or mixed type). The secondary outcomes will include the association of risk factors and the association with all-cause mortality during hospitalisation. Univariable or multivariable meta-regression and subgroup analyses will be conducted for the study design and patient characteristics. Sensitivity analyses were used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of primary and secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval is not an essential element for the systematic review protocol in accordance with the Institutional Review Board /Independent Ethics Committee of Beijing Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42020224871.

Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: One year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to summarize the frequency of neurologic manifestations reported in patients with COVID-19 and to investigate the association of these manifestations with disease severity and mortality. METHODS: We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with I 2, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. RESULTS: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91). DISCUSSION: Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181867.

Delirium occurrence and association with outcomes in hospitalized COVID-19 patients.

Delirium is reported to be one of the manifestations of coronavirus infectious disease 2019 (COVID-19) infection. COVID-19 hospitalized patients are at a higher risk of delirium. Pathophysiology behind the association of delirium and COVID-19 is uncertain. We analyzed the association of delirium occurrence with outcomes in hospitalized COVID-19 patients, across all age groups, at Mayo Clinic hospitals.A retrospective study of all hospitalized COVID-19 patients at Mayo Clinic between March 1, 2020 and December 31, 2020 was performed. Occurrence of delirium and outcomes of mortality, length of stay, readmission, and 30-day mortality after hospital discharge were measured. Chi-square test, student t-test, survival analysis, and logistic regression analysis were performed to measure and compare outcomes of delirium group adjusted for age, sex, Charlson comorbidity score, and COVID-19 severity with no-delirium group.A total of 4351 COVID-19 patients were included in the study. Delirium occurrence in the overall study population was noted to be 22.4%. The highest occurrence of delirium was also noted in patients with critical COVID-19 illness severity. A statistically significant OR 4.35 (3.27-5.83) for in-hospital mortality and an OR 4.54 (3.25-6.38) for 30-day mortality after discharge in the delirium group were noted. Increased hospital length of stay, 30-day readmission, and need for skilled nursing facility on discharge were noted in the delirium group. Delirium in hospitalized COVID-19 patients is a marker for increased mortality and morbidity. In this group, outcomes appear to be much worse when patients are older and have a critical severity of COVID-19 illness.

Delirium and long term cognition in critically ill patients.

Delirium, a form of acute brain dysfunction, is very common in the critically ill adult patient population. Although its pathophysiology is poorly understood, multiple factors associated with delirium have been identified, many of which are coincident with critical illness. To date, no drug or non-drug treatments have been shown to improve outcomes in patients with delirium. Clinical trials have provided a limited understanding of the contributions of multiple triggers and processes of intensive care unit (ICU) acquired delirium, making identification of therapies difficult. Delirium is independently associated with poor long term outcomes, including persistent cognitive impairment. A longer duration of delirium is associated with worse long term cognition after adjustment for age, education, pre-existing cognitive function, severity of illness, and exposure to sedatives. Interestingly, differences in prevalence are seen between ICU survivor populations, with survivors of acute respiratory distress syndrome experiencing higher rates of cognitive impairment at early follow-up compared with mixed ICU survivor populations. Although cognitive performance improves over time for some ICU survivors, impairment is persistent in others. Studies have so far been unable to identify patients at higher risk of long term cognitive impairment; this is an active area of scientific investigation.

The COVID-19 conundrum: Where both the virus and treatment contribute to delirium.

Whereas hospitalists and intensivists are treating the life-threatening respiratory conditions that often accompany COVID-19, delirium prevention, identification, and treatment may inadvertently be taking a backseat. However, delirium identification is important as it can serve as a key marker for hospital providers to identify COVID patients at risk for poor outcomes including ICU stay and death.2 COVID delirium has been difficult to manage because some COVID treatment methods are inherently deliriogenic and some medications traditionally used to manage delirium have been rendered ineffective among this population. Inpatient neurology and psychiatry practitioners are having to postulate new treatment techniques; one such medication algorithm can be found within this piece. It is important that delirium doesn't get lost in the chaos that is management of the COVID patient.

Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness - A case series.

BACKGROUND: There is still a lot unknown about the novel Coronavirus Disease 19 (COVID-19) and its effects in humans. This pandemic has posed several challenging clinical situations to healthcare providers. OBJECTIVE: We hope to highlight the distinctive challenges that COVID-19 presents in patients with serious mental illness and what steps primary medical teams can take to co-manage these patients with the psychiatry consultants. METHODS: We present a retrospective chart review of four patients who were on psychotropic polypharmacy and admitted to our hospital from the same long-term psychiatric facility with COVID-19 delirium and other associated medical complications. RESULTS: We illustrate how the primary medical teams and psychiatrists collaborated in clinical diagnosis, treatment, and management. CONCLUSIONS: Patients with serious mental illness and COVID-19 infection require active collaboration between primary medical teams and psychiatrists for diagnostic clarification, reduction of psychotropic polypharmacy to avoid adverse effects and drug-drug interactions, prevention of psychiatric decompensation, and active management of agitation while balancing staff and patient safety concerns.

Delirium and Adverse Outcomes in Hospitalized Patients with COVID-19.

BACKGROUND: Little is known about the association between acute mental changes and adverse outcomes in hospitalized adults with COVID-19. OBJECTIVES: To investigate the occurrence of delirium in hospitalized patients with COVID-19 and explore its association with adverse outcomes. DESIGN: Longitudinal observational study. SETTING: Tertiary university hospital dedicated to the care of severe cases of COVID-19 in São Paulo, Brazil. PARTICIPANTS: A total of 707 patients, aged 50 years or older, consecutively admitted to the hospital between March and May 2020. MEASUREMENTS: We completed detailed reviews of electronic medical records to collect our data. We identified delirium occurrence using the Chart-Based Delirium Identification Instrument (CHART-DEL). Trained physicians with a background in geriatric medicine completed all CHART-DEL assessments. We complemented our baseline clinical information using telephone interviews with participants or their proxy. Our outcomes of interest were in-hospital death, length of stay, admission to intensive care, and ventilator utilization. We adjusted all multivariable analyses for age, sex, clinical history, vital signs, and relevant laboratory biomarkers (lymphocyte count, C-reactive protein, glomerular filtration rate, D-dimer, and albumin). RESULTS: Overall, we identified delirium in 234 participants (33%). On admission, 86 (12%) were delirious. We observed 273 deaths (39%) in our sample, and in-hospital mortality reached 55% in patients who experienced delirium. Delirium was associated with in-hospital death, with an adjusted odds ratio of 1.75 (95% confidence interval = 1.15-2.66); the association held both in middle-aged and older adults. Delirium was also associated with increased length of stay, admission to intensive care, and ventilator utilization. CONCLUSION: Delirium was independently associated with in-hospital death in adults aged 50 years and older with COVID-19. Despite the difficulties for patient care during the pandemic, clinicians should routinely monitor delirium when assessing severity and prognosis of COVID-19 patients.

Delirium Assessment in Critically Ill Older Adults: Considerations During the COVID-19 Pandemic.

Older adults are particularly vulnerable during the Coronavirus disease 2019 (COVID-19) pandemic, because higher age increases risk for both delirium and COVID-19-related death. Despite the health care system limitations and the clinical challenges of the pandemic, delirium screening and management remains an evidence-based cornerstone of critical care. This article discusses practical recommendations for delirium screening in the COVID-19 pandemic era, tips for training health care workers in delirium screening, validated tools for detecting delirium in critically ill older adults, and approaches to special populations of older adults (eg, sensory impairment, dementia, acute neurologic injury).