Pharmacological interventions for the treatment of delirium in critically ill adults.
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ABSTRACT:
SUBMITTER: Burry L
PROVIDER: S-EPMC6719921 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Pharmacological interventions for the treatment of delirium in critically ill adults.
Burry Lisa L Hutton Brian B Williamson David R DR Mehta Sangeeta S Adhikari Neill Kj NK Cheng Wei W Ely E Wesley EW Egerod Ingrid I Fergusson Dean A DA Rose Louise L
The Cochrane database of systematic reviews 20190903
<h4>Background</h4>Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this ...[more]
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Project description:PurposeTo compare the effects of prevention interventions on delirium occurrence in critically ill adults.MethodsMEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects.ResultsEighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21-0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08-0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06-0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10-0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09-0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64-0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61-0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care.ConclusionCompared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.
| S-EPMC8356549 | biostudies-literature
Project description:Delirium is a common yet under-diagnosed syndrome of acute brain dysfunction, which is characterized by inattention, fluctuating mental status, altered level of consciousness, or disorganized thinking. Although our recognition of risk factors for delirium has progressed, our understanding of the underlying pathophysiologic mechanisms remains limited. Improvements in monitoring and assessment for delirium (particularly in the intensive care setting) have resulted in validated and reliable tools such as arousal scales and bedside delirium monitoring instruments. Once delirium is recognized and the modifiable risk factors are addressed, the next step in management (if delirium persists) is often pharmacological intervention. The sedatives, analgesics, and hypnotics most often used in the intensive care unit (ICU) to achieve patient comfort are all too frequently deliriogenic, resulting in a longer duration of ICU and hospital stay, and increased costs. Therefore, identification of safe and efficacious agents to reduce the incidence, duration, and severity of ICU delirium is a hot topic in critical care. Recognizing that there are no medications approved by the Food and Drug Administration (FDA) for the prevention or treatment of delirium, we chose anti-psychotics and alpha-2 agonists as the general pharmacological focus of this article because both were subjects of relatively recent data and ongoing clinical trials. Emerging pharmacological strategies for addressing delirium must be combined with nonpharmacological approaches (such as daily spontaneous awakening trials and spontaneous breathing trials) and early mobility (combined with the increasingly popular approach called: Awakening and Breathing Coordination, Delirium Monitoring, Early Mobility, and Exercise [ABCDE] of critical care) to develop evidence-based approaches that will ensure safer and faster recovery of the sickest patients in our healthcare system.
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Project description:Delirium among critically ill patients is common. Presence of delirium imparts a poorer prognosis to patients, including longer ICU and hospital length of stay, increased risk of institutionalization, higher health related costs, and elevated mortality. Even with such grave consequences, the rates of delirium diagnosis are dire. The importance of early recognition through validated tools and appropriate management of this life-threatening condition cannot be over emphasized. This article provides an overview of delirium pathophysiology, diagnosis, and management with a focus on critically ill patients.
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Project description:Critically ill patients frequently experience pain, agitation, delirium, and sleep deprivation, which have been linked to increased mortality and unfavorable clinical outcomes. To address these challenges, the Pain, Agitation, Delirium, and Sleep Deprivation (PADS) protocol was developed, aiming to mitigate mortality and improve clinical outcomes. This study focuses on assessing the protocol's impact using a robust before-and-after study design in the medical and surgical intensive care units (ICUs) at Ramathibodi Hospital. Using an observational approach, this study compares clinical outcomes before and after implementing the PADS protocol in the ICUs. Two patient cohorts were identified: the "before" group, comprising 254 patients with retrospective data collected between May 2018 and September 2019, and the "after" group, consisting of 255 patients for whom prospective data was collected from May to September 2020. Analysis reveals improvements in the after group. Specifically, there was a significant increase in 14-day ICU-free days (9.95 days vs. 10.40 days, p value = 0.014), a decrease in delirium incidence (18.1% vs. 16.1%, p value < 0.001), and a significant reduction in benzodiazepine usage (38.6% vs. 24.6%, p value = 0.001) within the after group. This study emphasizes the protocol's potential to improve patient care and highlights its significance in the ICU context.
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Project description:ObjectivesHaloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality.DesignPost hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial.SettingFourteen Dutch ICUs between July 2013 and December 2016.PatientsOne-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days.InterventionsPatients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion.Measurements and main resultsPatients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence.ConclusionsTreatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results.
| S-EPMC8282692 | biostudies-literature
Project description:BackgroundDelirium occurs at high rates among patients in intensive care units and increases the risk of morbidity and mortality. The purpose of this study was to investigate the effects of environmental interventions on delirium.MethodsThis prospective cohort study enrolled 192 patients admitted to the surgical intensive care unit (SICU) during the pre-intervention (June 2013 to October 2013) and post-intervention (June 2014 to October 2014) periods. Environmental interventions involved a cognitive assessment, an orientation, and a comfortable environment including proper sleep conditions. The primary outcomes were the prevalence, duration, and onset of delirium.ResultsThere were no statistically significant differences in incidence rate, time of delirium onset, general characteristics, and mortality between the pre-intervention and post-intervention groups. The durations of delirium were 14.4±19.1 and 7.7±7.3 days in the pre-intervention and post-intervention groups, respectively, a significant reduction (P=0.027). The lengths of SICU stay were 20.0±22.9 and 12.6±8.7 days for the pre-intervention and post-intervention groups, respectively, also a significant reduction (P=0.030).ConclusionsThe implementation of an environmental intervention program reduced the duration of delirium and length of stay in the SICU for critically ill surgical patients.
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Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator
2015-10-24 | E-GEOD-74224 | biostudies-arrayexpress
Project description:Delirium is common during critical illness and is associated with morbidity and mortality, but its pathophysiology is unknown. We tested whether dysfunctional cerebral autoregulation (CA) contributes to the development of delirium. Adult patients (n = 40) with respiratory failure and/or shock were prospectively enrolled. Continuous recordings of regional cerebral oxygen saturation (rSO2) were obtained by near-infrared spectroscopy (NIRS) during the first 72 h of intensive care unit (ICU) admission. CA function was estimated by the cerebral oximetry index (COx), which is the time-varying correlation between rSO2 and mean arterial pressure (MAP). Delirium was assessed daily. The median ICU stay was seven days (IQR 4-13). Twenty-four patients (60%) screened positive for delirium on at least one day during their stay. Taking positive COx values to reflect periods of CA dysfunction, we found that the cumulative duration of CA dysfunction during the first one to three days in the ICU was significantly associated with the subsequent development of delirium. Additionally, we assessed two alternative methods for estimating optimal MAP targets in individual patients. In summary, early disturbances in CA may contribute to delirium, and NIRS-derived rSO2 may be used to identify individual perfusion targets in critically ill patients.
| S-EPMC6893984 | biostudies-literature
Project description:BackgroundDelirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness.MethodsWe will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity.DiscussionThis review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium.Systematic review registrationPROSPERO CRD42019118808.
| S-EPMC7275448 | biostudies-literature
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples
2015-10-24 | GSE74224 | GEO