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

Allometric growth patterns in hatchery-reared larvae of the catfish Lophiosilurus alexandri (Pisces: Pseudopimelodidae)

The aim of the present study was to characterize the relationships that occur between morphometric variables of larvae of Lophiosilurus alexandri Steindachner, 1876 through their allometric growth analysis. Total length, head length and body height were correlated with standard length, head height and body height, as well as eye diameter and head height with head length. The results revealed allometric positive relation during the initial development, where the b coefficient varied between 1.10 and 2.81. The variable pre-anal distance in relation to the standard length and the snout length in relation to the head length revealed an allometric negative relation, where the b coefficient was 0.85 and 0.94, respectively

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