Delirium after Cardiac Surgery in Older Patients : Predictors of occurrence and outcome

As early as in Hippocrates’ medical writings, clinical pictures of patients experiencing delirium were described . The syndrome we currently refer to as delirium was originally based on two distinct syndromes. A syndrome called Phrenitis, in which patients showed cognitive disturbances, exited and restless behaviour, with disruption of sleep, and a syndrome called Lethargus, in which patients were somnolent, apathetic, listless and showed slow mentation. Although it was known that Phrenitis could change into Lethargus, and vice versa, it was not until the late eighteenth century that both terms were displaced by the single term delirium. There is some uncertainty whether the word ‘delirium’ is derived from the Greek word ληρος, meaning empty drivel , or from the Latin word for disturbance of mind, deliratio . Even in ancient times it was known that the emergence of a delirium was a bad prognostic sign and often a herald of death, but the pathophysiology remained obscure. Based on meticulous observations of patients, the German psychiatrist Bonhoeffer reported in 1910 that the presence of the symptom clouding of consciousness could discriminate organic-psychiatric disorders from functional or endogenous psychiatric disorders . Furthermore, he postulated that toxic substances originating from disease processes in the body or brain might cause delirium. A theory that is remarkably similar to the present-day inflammatory delirium theory, in which cytokines produced by glia cells induce delirium . Engel and Romano in 1959 further elaborated on the delirium concept by describing the association between a reduced level of consciousness and the degree of slowing of the electro-encephalogram (EEG) . Combined with the finding that slowing of the EEG was associated with derangements of cerebral metabolism, this provided additional evidence that delirium should be regarded as a syndrome of cerebral insufficiency. Currently, delirium is the most frequently occurring organic-psychiatric syndrome in the general hospital. The incidence of delirium in the general hospital ranges from 5 to 32% , but in specific populations, such as older patients (aged 65 years or more) or patients in the intensive care unit (ICU), the incidence of delirium can be much higher

Music to prevent deliriUm during neuroSurgerY (MUSYC) Clinical trial:A study protocol for a randomised controlled trial

INTRODUCTION: Delirium is a neurocognitive disorder characterised by an acute and temporary decline of mental status affecting attention, awareness, cognition, language and visuospatial ability. The underlying pathophysiology is driven by neuroinflammation and cellular oxidative stress. Delirium is a serious complication following neurosurgical procedures with a reported incidence varying between 4% and 44% and has been associated with increased length of hospital stay, increased amount of reoperations, increased costs and mortality. Perioperative music has been reported to reduce preoperative anxiety, postoperative pain and opioid usage, and attenuates stress response caused by surgery. We hypothesize that this beneficial effect of music on a combination of delirium eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. METHODS: This protocol concerns a single-centred prospective randomised controlled trial with 6 months follow-up. All adult patients undergoing a craniotomy at the Erasmus Medical Center in Rotterdam are eligible. The music group will receive recorded music through an overear headphone before, during and after surgery until postoperative day 3. Patients can choose from music playlists, offered based on music importance questionnaires administered at baseline. The control group will receive standard of clinical care Delirium is assessed by the Delirium Observation Scale and confirmed by a delirium-expert psychiatrist according to the DSM-5 criteria. Risk factors correlated with the onset of delirium, such as cognitive function at baseline, preoperative anxiety, perioperative medication use, depth of anaesthesia and postoperative pain, and delirium-related health outcomes such as length of stay, daily function, quality of life (ie, EQ-5D, EORTC questionnaires), costs and cost-effectiveness are collected. ETHICS AND DISSEMINATION: This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Center Rotterdam, The Netherlands, approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBERS: NL8503 and NCT04649450

Perspectives of patients, relatives and nurses on rooming-in for adult patients: A scoping review of the literature

Aim: To explore the perspectives of patients, their relatives and nurses on rooming-in for adult patients. Background: The practice of having family stay overnight with an adult patient in hospital is quite new. To support rooming-in programs, the perspectives from all stakeholders should be taken into account. Methods: All types of studies on rooming-in in adult healthcare settings were included in this scoping review. Rooming-in has been defined as the practice where ‘family members or trusted others are facilitated to continuously stay with the patient and are provided with facilities to sleep in the patient's room’. Results: Seven studies were included: one randomized controlled trial, three qualitative studies, and three correspondence articles. Generally, patients felt safe in the presence of a family member, but could also feel restricted in their freedom and privacy. Family members saw a benefit for the patient, considered rooming-in a moral duty, and were happy to help. Nonetheless, family members reported rooming-in as physically and emotionally stressful. Nurses described that patients were less anxious and more easily adjusted to the hospital environment. Conclusions: The reviewed studies suggest that patients, family members, and nurses have both positive and negative experiences with rooming-in. The concept

Differences in potential biomarkers of delirium between acutely ill medical and elective cardiac surgery patients

Background/aims: The pathophysiology of delirium is poorly understood. Increasing evidence suggests that different pathways might be involved in the pathophysiology depending on the population studied. The aim of the present study was to investigate potential differences in mean plasma levels of neopterin, amino acids, amino acid ratios and homovanillic acid between two groups of patients with delirium. Methods: Data from acutely ill medical patients aged 65 years and older, and patients aged 70 years and older undergoing elective cardiac surgery, were used. Differences in biomarker levels between the groups were investigated using univariate ANOVA with adjustments for age, sex, comorbidities, C-reactive protein (CRP) and the estimated glomerular filtration rate (eGFR), where appropriate. Linear regression analysis was used to identify potential determinants of the investigated biochemical markers. Results: Eighty patients with delirium were included (23 acutely ill medical patients and 57 elective cardiac surgery patients). After adjustment, higher mean neopterin levels (93.1 vs 47.3 nmol/L, P=0.001) and higher phenylalanine/tyrosine ratios (1.39 vs 1.15, P=0.032) were found in acutely ill medical patients when compared to elective cardiac surgery patients. CRP levels were positively correlated with neopterin levels in acutely ill medical patients, exp

Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium

Purpose: To characterize the pharmacogenomic response of low-dose haloperidol for delirium treatment in critically ill adults. Materials and methods: Single-center, pilot study of a convenience sample of ICU adults with delirium treated with low-dose IV haloperidol. Patients were evaluated for delirium with the ICDSC every 8 h. Serum haloperidol concentrations were collected on ICU days 2–6, CYP2D6 and CYP3A4 genotypes were characterized and patients were categorized as extensive (EM), intermediate (IM) or poor metabolizers (PM). Results: The 22 patients (median age 67 [IQR 48,77] years; median APACHE III 81[IQR 54,181]; CYP2D6 [EM = 12, IM = 7, PM = 3], CYP3A [EM = 18, IM = 4]) received a median [IQR] daily haloperidol dose of 3.0 [2.4, 4.5] mg. After adjusting for age, SOFA, and ICU day, neither an association between CYP2D6 (IM p = .67/PM p = .25) or CYP3A4 (IM p = .44) metabolizer status and serum haloperidol concentrations was found. After adjusting for age, SOFA, and ICU day, neither an association between daily haloperidol dose (p = .77) or ICDSC score (p = .13) and serum haloperidol concentrations was found. No patient experienced QTc interval prolongation (≥500 ms). Conclusions: This pilot study, the first to evaluate the pharmacogenomic response of low-dose haloperidol when used to treat delirium in the ICU, suggests CYP2D6/CYP3A4 metabolizer status does not affect the serum haloperidol concentrations

Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands

Introduction Delirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of nonpharmacological strategies to reduce delirium. The routine use of scheduled haloperidol to treat delirium is not recommended given a lack of evidence regarding its ability to resolve delirium nor improve relevant short-term and longer-term outcomes. This study aims to evaluate the efficacy and safety of haloperidol for the treatment of delirium in adult critically ill patients to reduce days spent with coma or delirium. Methods and analysis EuRIDICE is a prospective, multicentre, randomised, double-blind, placebo-controlled trial. Study population consists of adult intensive care unit (ICU) patients without acute neurological injury who have delirium based on a positive Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU) assessment. Intervention is intravenous haloperidol 2.5mg (or matching placebo) every 8 hours, titrated daily based on ICDSC or CAMICU positivity to a maximum of 5mg every 8 hours, until delirium resolution or ICU discharge. Main study endpoint is delirium and coma-free days (DCFD) up to 14 days after randomisation. Secondary endpoints include (1) 28-day and 1-year mortality, (2) cognitive and functional performance at 3 and 12 months, (3) patient and family delirium and ICU experience, (4) psychological sequelae during and after ICU stay, (4) safety concerns associated with haloperidol use and (5) cost-effectiveness. Differences in DCFDs between haloperidol and placebo group will be analysed using Poisson regression analysis. Study recruitment started in February 2018 and continues. Ethics and dissemination The study has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam (MEC2017-511) and by the Institutional Review Boards of the participating sites. Its results will be disseminated via peer-reviewed publication and conference presentations

Improvement of care for ICU patients with delirium by early screening and treatment: study protocol of iDECePTIvE study

BACKGROUND: Delirium in critically ill patients has a strong adverse impact on prognosis. In spite of its recognized importance, however, delirium screening and treatment procedures are often not in accordance with current guidelines. This implementation study is designed to assess barriers and facilitators for guideline adherence and next to develop a multifaceted tailored implementation strategy. Effects of this strategy on guideline adherence as well as important clinical outcomes will be described. METHODS: Current practices and guideline deviations will be assessed in a prospective baseline measurement. Barriers and facilitators will be identified from a survey among intensive care health care professionals (intensivists and nurses) and focus group interviews with selected health care professionals (n=60). Findings will serve as a foundation for a tailored guideline implementation strategy. Adherence to the guideline and effects of the implementation strategies on relevant clinical outcomes will be piloted in a before-after study in six intensive care units (ICUs) in the southwest Netherlands. The primary outcomes are adherence to screening and treatment in line with the Dutch ICU delirium guideline. Secondary outcomes are process measures (e.g. attendance to training and knowledge) and clinical outcomes (e.g. incidence of delirium, hospital-mortality changes, and length of stay). Primary and secondary outcome data will be collected at four time points including at least 924 patients. Furthermore, a process evaluation will be done, including an economical evaluation. DISCUSSION: Little is known on effective implementation of delirium management in the critically ill. The proposed multifaceted implementation strategy is expected to improve process measures such as screening adherence in line with the guideline and may improve clinical outcomes, such as mortality and length of stay. This ICU Delirium in Clinical Practice Implementation Evaluation study (iDECePTIvE-study) will generate important knowledge for ICU health care providers on how to improve their clinical practice to establish optimum care for delirious patients. TRIALS REGISTRATION: Clinical Trials NCT01952899.status: publishe

Studies on the Fattening and Growth-Stimulating Functions of Estrogen on Cockerels (3) : To What Extent Endocrine Glands Interact in the Lipemia Response to Estrogen

textabstractPurpose 'Phenocopy' frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum