Evaluation of Suvorexant and Lemborexant for the Prevention of Delirium in Adult Critically Ill Patients at an Advanced Critical Care Center
Ayaka MatsuokaShuko TobitaRintaro SogawaKota ShinadaToru Murakawa‐HirachiChisato ShimanoeAkira MonjiYoshito MizoguchiToru MiikeYuichiro Sakamoto
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Objective: There is limited evidence for the efficacy of the novel dual orexin receptor antagonists (DORAs) suvorexant and lemborexant in preventing delirium. We examined the efficacy of DORAs in preventing delirium in critically ill patients at an advanced emergency and critical care center. Methods: In this retrospective observational study, patients 18 years of age or older admitted to the emergency center between July 2018 and November 2021 with hospitalization duration of at least 72 h were included. Kaplan-Meier curves were plotted and log rank tests were performed to compare between patients with and without DORA treatment. Cox regression analyses adjusting for factors associated with delirium risk were also performed. Results: Of the 633 enrolled patients, 82 were treated with suvorexant and 41 with lemborexant. Cox regression analysis showed that, without adjustment, the hazard ratios (95% CIs) for the development of delirium were 0.56 (0.36–0.86) for patients treated with suvorexant and 0.26 (0.11–0.62) for those treated with lemborexant. After adjustment for delirium risk factors, the hazard ratios (95% CIs) remained low at 0.34 (0.20–0.58) for suvorexant and 0.21 (0.08–0.52) for lemborexant. Conclusions: Both suvorexant and lemborexant may be effective in preventing delirium in critically ill adult patients in an advanced critical care center.The prognostic significance of delirium in hospitalized elderly has not yet been fully clarified.The present study was designed to evaluate the relationship between prevalent delirium (PrD), incident delirium (InD) and final outcome.A historical cohort of 261 patients was selected. delirium was diagnosed using the Confusion Assessment Method.The total frequency of delirium detected was 42.5%-31.4% PrD and 16.2% InD. Among patients with InD, the average length of hospital stay was 9.1 days longer than for patients without delirium (p=0.002), and the hospital mortality associated with InD was 48% versus 2.7% for those without delirium (p< 0.001). However, no difference was observed between patients with PrD and those without delirium.These results suggest that, when investigating delirium and prognosis amongst hospitalized elderly, it is fundamental to differentiate in terms of time of onset. Furthermore, the absence of delirium seems to be an important protective factor.O significado do prognóstico de delirium em idosos hospitalizados ainda não está completamente elucidado.O presente estudo foi designado para avaliar a relação entre delirium prevalente (DeP), delirium incidente (DeI) e o desfecho final.Uma coorte histórica de 261 pacientes foi selecionada. delirium foi diagnosticado pelo Confusion Assessment Method.A freqüência total de delirium foi de 42.5%, DeP 31.4%, e DeI 16.2%. Para pacientes com DeI, a média de duração de hospitalização foi 9.1 dias maior do que aqueles sem delirium (p=0.002), e a mortalidade hospitalar associada a DeI foi de 48.3% contra 2.7% dos livres de delirium (p< 0.001). Contudo, não houve diferença entre pacientes com DeP e sem delirium.Os resultados sugerem que, ao estudar delirium e prognóstico entre idosos hospitalizados, é fundamental diferenciar o problema quanto ao seu momento de início. Além disso, não apresentar delirium parece constituir-se num fator protetor importante.
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Delirium is a common problem and cause of distress among patients with palliative care needs. The focus to date has been on managing the patient with agitated, hyperactive delirium, as these patients are very noticeable within the palliative care setting. This study in two parts shows that palliative care patients with agitated delirium are a minority of the total proportion of those with delirium. Part I: 100 acute admissions to a specialist palliative care unit were assessed and while 29% were found to have delirium, 86% of these had the hypoactive subtype of delirium. We also demonstrated a positive correlation between high ratings on a depression screening tool and delirium severity ratings. Part II: 8 specialist palliative care units took part in a point prevalence study of delirium over a 48-hour period. One hundred and nine patients were assessed and while 29.4% of these inpatients had delirium, 78% of them had the hypoactive subtype. Patients with hypoactive delirium may be much less noticeable or may be misdiagnosed as having depression or fatigue and the results of this study would advocate the routine use of delirium screening tools in all palliative care settings.
Depression
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Studies of outcome have started to challenge the assumption that delirium is a truly reversible disorder with a good prognosis. Prospective outcome studies of delirium are required to describe its prognosis. The evidence is that delirium recovers slowly and often incompletely. Delirious patients stay longer in hospital than those without delirium. High mortality rates seen in delirium may be contributed to by the delirium itself. The prognosis of delirium is almost certainly not therefore, one of early full recovery. Rather, delirium is a condition with a slow recovery and one that often fails to resolve completely.
Excess mortality
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Background: Delirium in advanced cancer inpatient ranges between 13% and 85%. Reasons for this variability on the reported data could be related to the setting where they are admitted. Methods: This is an observational, comparative, prospective study on delirium diagnosis and delirium course of advanced cancer inpatients in two different palliative care settings. Hospice (C1) versus palliative care supportive team (C2). Differences between delirium precipitants, delirium treatment, and delirium survival were observed. Results: From 582 consecutive admissions, 494 from C1 and 88 from C2, finally 227 patients met inclusion criteria, were entered in the study. Total population delirium rate at admission, if we add both centers, was 57 patients (25%), 46 (26%) from C1 and 11 (22%) from C2; no statistically significant differences between delirium rate at admission between the two centers were found (χ2). When delirium course between delirious patients admitted in C1 and C2 was analyzed, a significantly higher rate of delirium reversibility was found in C2 [11/14 (78%)] versus [9/65 (14%)] in C1 (χ2p ≤ 0.001). Conclusion: The frequency of delirium at admission and during the hospitalization in advanced cancer patients does not seem to be related to the setting, what seems to be related is the delirium course.
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Background Although most people with relapsing onset multiple sclerosis (R-MS) eventually transition to secondary progressive multiple sclerosis (SPMS), little is known about disability progression in SPMS. Methods All R-MS patients in the Cardiff MS registry were included. Cox proportional hazards regression was used to examine a) hazard of converting to SPMS and b) hazard of attaining EDSS 6.0 and 8.0 in SPMS. Results 1611 R-MS patients were included. Older age at MS onset (hazard ratio [HR] 1.02, 95%CI 1.01–1.03), male sex (HR 1.71, 95%CI 1.41–2.08), and residual disability after onset (HR 1.38, 95%CI 1.11–1.71) were asso- ciated with increased hazard of SPMS. Male sex (EDSS 6.0 HR 1.41 [1.04–1.90], EDSS 8.0 HR 1.75 [1.14–2.69]) and higher EDSS at SPMS onset (EDSS 6.0 HR 1.31 [1.17–1.46]; EDSS 8.0 HR 1.38 [1.19–1.61]) were associated with increased hazard of reaching disability milestones, while older age at SPMS was associated with a lower hazard of progression (EDSS 6.0 HR 0.94 [0.92–0.96]; EDSS 8.0: HR 0.92 [0.90–0.95]). Conclusions Different factors are associated with hazard of SPMS compared to hazard of disability progres- sion after SPMS onset. These data may be used to plan services, and provide a baseline for comparison for future interventional studies and has relevance for new treatments for SPMS RobertsonNP@cardiff.ac.uk
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to determine the presentation, course and duration of delirium in hospitalized older people. observational cohort study. inpatient surgical and medical wards at a university hospital. 432 people over the age of 65. all participants were screened daily for confusion and, in those who were confused, delirium was ascertained using the Diagnostic and Statistical Manual of Mental Disorders (DSM) ITI-R criteria. Those who were found to be delirious were followed daily while in hospital for evidence of delirium. The Delirium Rating Scale (DRS) was used to describe the clinical characteristics of delirium. about 15% of subjects had delirium. Sixty-nine percent of delirious subjects had delirium on a single day. The DRS total was higher on the first day of delirium for those with delirium on multiple days than those with delirium on a single day (P = 0.03). Among those with delirium on multiple days, there were no patterns of change over time in specific DRS items. delirium in hospitalized older people is common and has a varied presentation and time course. Clinicians and researchers need to consider this great heterogeneity when caring for patients and when studying delirium.
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Interest in and the quantity of publications on delirium in critically ill patients have grown increasingly over the last decade. Critically ill patients have traditionally been sedated to facilitate mechanical ventilation. This practice impeded the recognition of delirium in the critically ill patients, and consequently the disorder was underdiagnosed. Delirium in the critically ill patients is associated with increased morbidity and mortality. Less sedation, guided by protocols with daily wake up trials, and validated delirium scoring systems, have improved the opportunities to diagnose and monitor delirium in the critically ill patients.
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The hazard ratio and median survival time are the routine indicators in survival analysis. We briefly introduced the relationship between hazard ratio and median survival time and the role of proportional hazard assumption. We compared 110 pairs of hazard ratio and median survival time ratio in 58 articles and demonstrated the reasons for the difference by examples. The results showed that the hazard ratio estimated by the Cox regression model is unreasonable and not equivalent to median survival time ratio when the proportional hazard assumption is not met. Therefore, before performing the Cox regression model, the proportional hazard assumption should be tested first. If proportional hazard assumption is met, Cox regression model can be used; if proportional hazard assumption is not met, restricted mean survival times is suggested.风险比（hazard ratio，HR）和中位生存时间是生存分析时的常规分析和报告指标。本文简要介绍了HR和中位生存时间的关系以及比例风险假定在这两者之间的作用，分析了检索出的58篇文献中的110对风险比和中位生存时间比的差异，并通过实例阐明了产生这种差异的原因。结果表明，在不满足比例风险假定时，Cox回归模型计算得到的风险比是不合理的，且与中位生存时间之比不等价。因此，在使用Cox回归模型前，应先进行比例风险假定的检验，只有符合比例风险假定时才能使用该模型；当不符合比例风险假定时，建议使用限制性平均生存时间。.
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Delirium is a troubling complication in hospitalized older patients with cancer. Although preventable and potentially reversible, delirium may be prolonged. Persistent delirium at the time of hospital discharge is common and associated with multiple adverse outcomes. We conducted a secondary data analysis to examine delirium resolution in 43 hospitalized older patients with cancer who had prevalent or incident delirium. We describe trajectories of delirium resolution and evaluate differences in patients with and without delirium resolution. Delirium was assessed using the NEECHAM confusion scale. Forty-one of the 43 patients had delirium during hospitalization before discharge; 2 had delirium only at the time of discharge. Although delirium resolved in 13 patients, a significant majority (70%) had delirium at discharge. Patients with delirium resolution were less functionally impaired before hospitalization and exhibited fewer etiologic risk patterns at admission. Mild delirium was more likely to resolve than severe delirium. All patients with chronic cognitive impairment had persistent delirium. Care for hospitalized older patients with cancer should incorporate delirium prevention and intervention strategies. Caregiver education, communication between providers, and follow-up are critical when delirium persists. Additional research focusing on the management and impact of persistent delirium in hospitalized older patients with cancer is needed.
Confusion
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