Modifiable Risk Factors For Delirium Research Articles

The Impact of Non-Pharmacological Interventions on Delirium in Neurological Intensive Care Unit Patients: A Single-Center Interrupted Time Series Trial.

Background: Delirium is a pathobiological brain process that is frequently observed in Intensive Care Unit (ICU) patients, and is associated with longer hospitalization as well as long-term cognitive impairment. In neurological ICU patients, delirium may be more treatment-resistant due to the initial brain injury. This study examined the effects of a multicomponent non-pharmacological nursing intervention program on delirium in neurological ICU patients. Methods: A single-center interrupted time series trial was conducted in adult neurological ICU patients at high risk for developing delirium who were non-delirious at admission. A multicomponent nursing intervention program focusing on modifiable risk factors for delirium, including the optimalization of vision, hearing, orientation and cognition, sleep and mobilization, was implemented as the standard of care, and its effects were studied. The primary outcome was the number of delirium-free and coma-free days alive at 28 days after ICU admission. The secondary outcomes included delirium incidence and duration, ICU and hospital length-of-stay and duration of mechanical ventilation. Results: Of 289 eligible patients admitted to the ICU, 130 patients were included, with a mean age of 68 ± 11 years, a mean APACHE-IV score of 79 ± 25 and a median predicted delirium risk (E-PRE-DELIRIC) score of 42 [IQR 38-50]). Of these, 73 were included in the intervention period and 57 in the control period. The median delirium- and coma-free days alive were 15 days [IQR 0-26] in the intervention group and 10 days [IQR 0-24] in the control group (level change -0.48 days, 95% confidence interval (95%CI) -7 to 6 days, p = 0.87; slope change -0.95 days, 95%CI -2.41 to 0.52 days, p = 0.18). Conclusions: In neurological ICU patients, our multicomponent non-pharmacological nursing intervention program did not change the number of delirium-free and coma-free days alive after 28 days.

Opioids increase the risk of delirium in critically ill patients: A propensity score analysis.

Medications are biologically plausible and potentially modifiable risk factors for delirium. Therapies for delirium might involve more specific strategies such as avoiding the use of delirium-inducing drugs to reduce the incidence of delirium. The association between opioid exposure within 24 hours prior to delirium assessment and the risk of delirium was studied. Using three large databases, the MIMIC III v1.4, MIMIC-IV v0.4 and eICU Collaborative Research, we performed a multicenter, observational cohort study with two cohorts to estimate the relative risks of outcomes among patients administered opioids within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included mortality, length of intensive care unit (ICU) stay, length of hospitalization, and odds of being discharged home. Propensity matching successfully balanced the covariates for the 9,529 patients in each group. Opioid use was associated with a significantly higher risk for delirium than not using opioids (p<0.001). Additionally, treatment with opioids was associated with higher mortality and a longer ICU stay (p<0.001) than treatment without opioids. However, patients treated with opioids were more likely to be discharged home (p<0.001). Opioids may be an independent risk factor for delirium in critically ill patients.

A complex intervention to promote prevention of delirium in older adults by targeting caregiver\u2019s participation during and after hospital discharge \u2013 study protocol of the TRAnsport and DElirium in older people (TRADE) project

BackgroundAmong potentially modifiable risk factors for delirium, transfers between wards, hospitals and other facilities have been mentioned with low evidence. TRADE (TRAnsport and DElirium in older people) was set up to investigate i) the impact of transfer and/or discharge on the onset of delirium in older adults and ii) feasibility and acceptance of a developed complex intervention targeting caregiver’s participation during and after hospital discharge or transfer on cognition and the onset of delirium in older adults.MethodsThe study is designed according to the guidelines of the UK Medical Research Council (MRC) for development and evaluation of complex interventions and comprises two steps: development and feasibility/piloting. The development phase includes i) a multicenter observational prospective cohort study to assess delirium incidence and cognitive decline associated with transfer and discharge, ii) a systematic review of the literature, iii) stakeholder focus group interviews and iv) an expert workshop followed by a Delphi survey. Based on this information, a complex intervention to better and systematically involve family caregivers in discharge and transport was developed. The intervention will be tested in a pilot study using a stepped wedge design with a detailed process and health economic evaluation. The study is conducted at four acute care hospitals in southwest Germany. Primary endpoints are the delirium incidence and cognitive function. Secondary endpoints include prevalence of caregiver companionship, functional decline, cost and cost effectiveness, quality of discharge management and quality of admission management in admitting hospitals or nursing homes. Data will be collected prior to discharge as well as after 3, 7 and 90 days.DiscussionTRADE will help to evaluate transfer and discharge as a possible risk factor for delirium. In addition, TRADE evaluates the impact and modifiability of caregiver’s participation during patient’s transfer or discharge on delirium incidence and cognitive decline providing the foundation for a confirmatory implementation study.Trial registrationDRKS (Deutsches Register für klinische Studien) DRKS00017828. Registered on 17th September 2019. Retrospectively registered.

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

BackgroundTo date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae.MethodsThis multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression.FindingsBetween Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU.InterpretationAcute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.FundingNone.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.

Incidence and Risk Factors of Delirium in the Intensive Care Unit: A Prospective Cohort.

Purpose The purpose of this study was to determine the incidence, risk factors, and impact of delirium on outcomes in ICU patients. In addition, the scoring systems were measured consecutively to characterize how these scores changed with time in patients with and without delirium. Material and Methods. A prospective cohort study enrolling 400 consecutive patients admitted to the ICU between 2018 and 2019 due to trauma or surgery. Patients were followed up for the development of delirium over ICU days using the Confusion Assessment Method (CAM) for the ICU and Intensive Care Delirium Screening Checklist (ICDSC). Cox model logistic regression analysis was used to explore delirium risk factors. Results Delirium occurred in 108 (27%) patients during their ICU stay, and the median onset of delirium was 4 (IQR 3–4) days after admission. According to multivariate cox regression, the expected hazard for delirium was 1.523 times higher in patients who used mechanical ventilator as compared to those who did not (HR: 1.523, 95% CI: 1.197-2.388, P < 0.001). Conclusion Our findings suggest that an important opportunity for improving the care of critically ill patients may be the determination of modifiable risk factors for delirium in the ICU. In addition, the scoring systems (APACHE IV, SOFA, and RASS) are useful for the prediction of delirium in critically ill patients.

Sedation in mechanically ventilated patients with COVID-19

Sedation in mechanically ventilated patients with COVID-19

Innovative ICU Solutions to Prevent and Reduce Delirium and Post-Intensive Care Unit Syndrome.

Delirium, the most common form of acute brain dysfunction affecting up to 80% of intensive care unit (ICU) patients, has been shown to predict long-term cognitive impairment, one of the domains in "Post-ICU Syndrome" (PICS). The ICU environment affects several potentially modifiable risk factors for delirium, such as disorientation and disruption, of the sleep-wake cycle. Innovative solutions aim to transform standard concepts of ICU room design to limit potential stressors, and utilizing the patient care space as a treatment tool, exerting positive, therapeutic effects. The main areas affected by most architectural and interior design modifications are sound environment, light control, floor planning, and room arrangement. Implementation of corresponding solutions is challenging considering the significant medical and technical demands of ICUs. This article discusses innovative concepts and promising approaches in ICU design that may be used to prevent stress and to support the healing process of patients, potentially limiting the impact of delirium and PICS.

Modifiable Risk Factors for Delirium in Critically Ill Trauma Patients: A Multicenter Prospective Study.

Intensive care unit (ICU)-acquired delirium has been associated with increased morbidity and mortality. Prevention strategies including modification of delirium risk factors are emphasized by practice guidelines. No study has specifically evaluated modifiable delirium risk factors in trauma ICU patients. Our goal was to evaluate modifiable risk factors for delirium among trauma patients admitted to the ICU. Prospective observational study. Two level 1 trauma ICU centers. Patients 18 years of age or older admitted for trauma including mild to moderate traumatic brain injury were eligible for the study. Delirium was assessed daily using the confusion assessment method for the ICU (CAM-ICU). The effect of modifiable risk factors was assessed using multivariate Cox regression analysis adjusting for severity of illness and significant nonmodifiable risk factors. A total of 58 of 150 recruited patients (38.7%; 95% confidence interval [CI] 30.9-46.5) screened positive for delirium during ICU stay. When adjusting for significant nonmodifiable risk factors, physical restraints (hazard ratio [HR]: 2.13; 95% CI: 1.07-4.24) and active infection or sepsis (HR: 2.12; 95% CI: 1.18-3.81) significantly increased the risk of delirium, whereas opioids (HR: 0.35; 95% CI: 0.13-0.98), episodes of hypoxia (HR: 0.55; 95% CI: 0.31-0.95), access to a television/radio in the room (HR: 0.26; 95% CI: 0.11-0.62), and number of hours mobilized per day (HR: 0.77; 95% CI: 0.68-0.88) were associated with significantly less risk of delirium. We have identified modifiable risk factors for delirium. Future studies should aim at implementing strategies to modify these risk factors and evaluate their impact on the risk of delirium.

The impact of nUrsiNg DEliRium Preventive INnterventions in the Intensive Care Unit (UNDERPIN-ICU): A study protocol for a multi-centre, stepped wedge randomized controlled trial

BackgroundDelirium is a common disorder in Intensive Care Unit (ICU) patients and is associated with serious short- and long-term consequences, including re-intubations, ICU readmissions, prolonged ICU and hospital stay, persistent cognitive problems, and higher mortality rates. Considering the high incidence of delirium and its consequences, prevention of delirium is imperative. This study focuses on a program of standardized nursing and physical therapy interventions to prevent delirium in the ICU, called UNDERPIN-ICU (nUrsiNg DEliRium Preventive INterventions in the ICU). Objective: To determine the effect of the UNDERPIN-ICU program on the number of delirium-coma-free days in 28days and several secondary outcomes, such as delirium incidence, the number of days of survival in 28 and 90days and delirium-related outcomes. Design and settingA multicenter stepped wedge cluster randomized controlled trial. MethodsEight to ten Dutch ICUs will implement the UNDERPIN-ICU program in a randomized order. Every two months the UNDERPIN-ICU program will be implemented in an additional ICU following a two months period of staff training. UNDERPIN-ICU consists of standardized protocols focusing on several modifiable risk factors for delirium, including cognitive impairment, sleep deprivation, immobility and visual and hearing impairment. ParticipantsICU patients aged ≥18years (surgical, medical, or trauma) and at high risk for delirium, E-PRE-DELIRIC ≥35%, will be included, unless delirium was detected prior ICU admission, expected length of ICU stay is less then one day or when delirium assessment is not possible. DiscussionFor every intervention the balance between putative benefit and potential unwanted side effects needs to be considered. In non-ICU patients, it has been shown that a similar program resulted in a significant reduction of delirium incidence and duration. Recent small studies using multi component interventions to prevent delirium in ICU patients have also shown beneficial effect, without unwanted side effects. We therefore feel that the proportionality of potential positive effects of the UNDERPIN-ICU program, weighed against potential unwanted side effects is favourable. Since this has not been rigorously proven in ICU patients, we will study the effects of this program in ICU patients using a stepped wedge design. Trial registrationThe study is registered in the clinical trials registry: https://clinicaltrials.gov/. Reporting methodStandard Protocol Items: Recommendations for Interventional Trails (SPIRIT).

Modifiable risk factors for delirium in critically ill trauma patients: a multicenter prospective study

Delirium is associated with significant morbidity and mortality in critically ill medical and surgical patients. However, patients suffering from trauma are generally excluded from these studies. Our objectives were to assess the incidence of delirium and identify modifiable risk factors associated with delirium among critically ill trauma patients.

A multifaceted educational intervention to prevent delirium in older inpatients: A before and after study

BackgroundSystematically targeting modifiable risk factors for delirium may reduce its incidence. However, research interventions have not become part of routine clinical practice. Particular approaches to the education of clinical staff may improve their practice and patient outcomes. ObjectivesTo evaluate the effectiveness of a multifaceted educational program in preventing delirium in hospitalised older patients and improving staff practice, knowledge and confidence. DesignA before and after study. SettingA 22-bed general medical ward of a district hospital in Sydney, Australia. ParticipantsPatients were aged 65 years and over and not delirious upon admission. Of 568 eligible patients, 129 were recruited pre-intervention (3 withdrew initial consent) and 129 patients post-intervention. MethodsPrior to the intervention, in order to establish a baseline, patients were assessed early after admission and again at discharge. The intervention was a one-hour lecture on delirium focusing on prevention for medical and nursing staff followed by weekly interactive tutorials with delirium resource staff and ward modifications. Following the initial education session, data were gathered in a second group of medical ward patients at the same time-points to ascertain the effectiveness of the intervention. Pre and post-intervention data were analysed to determine change in staff objective knowledge and self-ratings of confidence and clinical practice in relation to delirium. The main outcome measures were incident delirium and change in staff practice, confidence and knowledge. ResultsThe mean age of patients was 81. The pre and post-intervention groups were comparable, aside from greater co morbidity in the pre-intervention group (F(1, 253)=9.20, p=0.003). Post-intervention there was a significant reduction in incident delirium (19% vs. 10.1%, X2=4.14, p=0.042), and improved function on discharge (mean improvement 5.3 points, p<0.001, SD 13.31, 95% CI −7.61 to −2.97). Staff objective knowledge of delirium improved post-intervention and their confidence assessing and managing delirious patients. Staff addressed more risk factors for delirium post-intervention (8.1 vs. 9.8, F(1, 253)=73.44, p<0.001). ConclusionsA low-cost educational intervention reduced the incidence of delirium and improved function in older medical patients and staff knowledge and practice addressing risk factors for delirium. The program is readily transferable to other settings, but requires replication due to limitations of the before and after design.

Delirium, Neurotransmission, and Network Connectivity

Delirium, Neurotransmission, and Network Connectivity

The cost-effectiveness of multi-component interventions to prevent delirium in older people undergoing surgical repair of hip fracture

This article summarizes the detailed cost-effectiveness analysis of delirium prevention interventions in people undergoing surgical repair of hip fracture. We compared a multi-component delirium prevention intervention with usual care using a model based on a decision tree analysis. The model was used to estimate the incremental net monetary benefit (INMB). The robustness of the cost-effectiveness result was explored using deterministic and probabilistic sensitivity analyses. The multi-component prevention intervention was cost-effective when compared to usual care. It was associated with an INMB of £8,180 using a cost-effectiveness threshold of £20,000 per QALY. It remained cost-effective in the majority of the deterministic sensitivity analyses and was cost-effective in 96.4 % of the simulations carried out in the probabilistic sensitivity analysis. We have demonstrated the cost-effectiveness of a multi-component delirium prevention intervention that targets modifiable risk factors for delirium in older people undergoing surgical repair of hip fracture. It is an attractive intervention for practitioners and health care policy makers as they address the double burden of hip fracture and delirium.

Pathophysiology of acute brain dysfunction

To survey the recent medical literature examining the pathophysiology of acute brain dysfunction (delirium and coma) in the ICU. Clinical risk factors for brain dysfunction in the ICU continue to be elucidated and prediction models developed. Multiple studies have identified sedatives, especially benzodiazepines, as modifiable risk factors for delirium. Imaging studies examining global brain disorders have demonstrated white matter lesions and brain atrophy to be associated with delirium. Endothelial dysfunction, increased blood-brain barrier permeability, and reduced blood flow have also been implicated in cerebral perfusion abnormalities associated with brain dysfunction. The response of the brain to inflammation, including activation of microglia and neuronal apoptosis, leads to synaptic and neurochemical disturbances. Decreased availability of acetylcholine during critical illness leads to decreased counter-regulatory activity in response to inflammatory disease states, likely causing additional injury and further neurotransmitter imbalances. Dopamine, norepinephrine, and serotonin excess and their respective amino acid precursors have also been associated with brain dysfunction. The multifactorial pathophysiology of acute brain dysfunction remains incompletely understood. Multiple clinical risk factors have been identified and numerous pathophysiologic pathways have been hypothesized. Future research is required to investigate the roles of these pathways on differing clinical presentations, potential therapeutic options, and patient outcomes.

Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population*

There is a high prevalence of delirium in older medical intensive care unit (ICU) patients and delirium is associated with adverse outcomes. We need to identify modifiable risk factors for delirium, such as medication use, in the ICU. The objective of this study was to examine the impact of benzodiazepine or opioid use on the duration of ICU delirium in an older medical population. Prospective cohort study. Fourteen-bed medical intensive care unit in an urban university teaching hospital. 304 consecutive admissions age 60 and older. None. The main outcome measure was duration of ICU delirium, specifically the first episode of ICU delirium. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. Our main predictor was receiving benzodiazepines or opioids during ICU stay. A multivariable model was developed using Poisson rate regression. Delirium occurred in 239 of 304 patients (79%). The median duration of ICU delirium was 3 days with a range of 1-33 days. In a multivariable regression model, receipt of a benzodiazepine or opioid (rate ratio [RR] 1.64, 95% confidence interval [CI] 1.27-2.10) was associated with increased delirium duration. Other variables associated with delirium duration in this analysis include preexisting dementia (RR 1.19, 95% CI 1.07-1.33), receipt of haloperidol (RR 1.35, 95% CI 1.21-1.50), and severity of illness (RR 1.01, 95% CI 1.00-1.02). The use of benzodiazepines or opioids in the ICU is associated with longer duration of a first episode of delirium. Receipt of these medications may represent modifiable risk factors for delirium. Clinicians caring for ICU patients should carefully evaluate the need for benzodiazepines, opioids, and haloperidol.

The Importance of Diagnosing and Managing ICU Delirium

ICU delirium represents a form of brain dysfunction that in many cohorts has been diagnosed in 60 to 85% of patients receiving mechanical ventilation. This organ dysfunction is grossly underrecognized because a majority of patients have hypoactive or "quiet" delirium characterized by "negative" symptoms (eg, inattention and a flat affect) not alarming the treating team. Hyperactive delirium, formerly called ICU psychosis, stands out because of symptoms such as agitation that may cause harm to self or staff, but is actually rare relative to hypoactive delirium and associated with a better prognosis. Delirium is often incorrectly thought to be transient and of little consequence. After adjusting for numerous covariates, delirium is a strong, independent predictor of prolonged length of stay, reintubation, higher mortality, and cost of care. Expanded work on patient safety and recommendations by professional societies have established the importance of delirium monitoring and recommended it as standard practice in ICUs all over the world. This evidence-based review for physicians, nurses, respiratory therapists, and pharmacists will outline why it is imperative that patients be routinely monitored for delirium. This review will discuss modifiable risk factors for delirium, such as metabolic disturbances or potent sedative and analgesic medications. Attention to mitigating risk factors, along with recommended pharmacologic approaches such as antipsychotic medications, may provide resolution of delirium in some patients, while others will persist with refractory brain dysfunction and long-term cognitive impairment following critical illness.