Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium.
ABSTRACT: OBJECTIVE:Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium. METHODS:This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver). RESULTS:103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient's caregiver, the patient's cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months. CONCLUSIONS:Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.au.
Project description:BACKGROUND: The practice of low vs. high sedation dosing strategy may impact the cognitive and mental health function in the intensive care unit (ICU). We aim to demonstrate that high sedation strategy will result in change of mental health function in ICU patients. METHODS: We performed a systemic search and meta-analysis of medical databases in MEDLINE (from 1966 to March 2013) and EMBASE (from 1980 to March 2013), as well as the Cochrane Library using the MESH terms "Intensive Care Unit," and "Mental Health, for assessing the impact of sedation on posttraumatic stress disorder (PTSD) or anxiety/depression and delirium in the mix ICU setting including cardiac surgery patients. A total of 1216 patients were included in the final analysis. RESULTS: We included 11 studies in the final analysis and concluded that high dose sedation strategy resulted in higher incidence of cognitive dysfunction with P value of 0.009. The result for subgroup of delirium showed P = 0.11 and PTSD/depression or anxiety of P = 0.001, Heterogeneity I2 was 64%. Overall analysis was statistically significant with a P value of 0.002. CONCLUSION: High sedation dosing strategy will negatively affect cognitive function in critically ill patients. Large randomized trials are needed to address cognitive dysfunction in subgroup of patients with delirium.
Project description:In the intensive care unit (ICU), critical illness delirium occurs in the context of multiple comorbidities, multi-organ failure, and invasive management techniques, such as mechanical ventilation, sedation, and lack of sleep. Delirium is characterized by an acute confusional state defined by fluctuating mental status, inattention, and either disorganized thinking or an altered level of consciousness. The long-term cognitive and psychosocial function of patients that experience delirium in the ICU is of crucial interest because preliminary data suggest a strong association between ICU-related delirium and long-term cognitive impairment.The aim of this study is to explore the relationship between delirium in the ICU and adverse outcomes by following mechanically ventilated patients for one year following their discharge from the ICU and collecting data on their long-term cognition and psychosocial function.This study will be conducted by enrolling patients in two tertiary ICUs in Australia. We aim to recruit 200 patients who have been mechanically ventilated for more than 24 hours. Data will be collected at the following three time points: (1) at discharge where they will be administered the Mini-Mental State Examination (MMSE); (2) at 6 months after discharge from the ICU discharge where the Impact of Events Scale Revised (IES-R) and the Telephone Inventory for Cognitive Status (TICS) tests will be administered; and (3) at 12 months after discharge from the ICU where the patients will be administered the TICS and IES-R tests, as well as the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). The IQCODE will be administered to their "person responsible" or the significant other of the patient.Long-term cognition and psychosocial function will be the primary outcome of this study. Mortality will also be investigated as a secondary outcome. Active enrollment will take place until the end of September 2016 and data collection will conclude at the end of September 2017. The analysis and results are expected to be available by March 2018.Delirium during mechanical ventilation has been linked to longer ICU and hospital stays, higher financial burdens, increased risks of long-term cognitive impairment (ie, dementia), poor functional outcomes and quality of life, and decreased survival. However, delirium during mechanical ventilation in the ICU is not well understood. This study will advance our knowledge of the comprehensive, long-term effects of delirium on cognitive and psychosocial function.Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001116415; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371216 (Archived by WebCite at http://www.webcitation.org/ 6nfDkGTcW).
Project description:Delirium occurs frequently in critically ill patients and is associated with disease severity and infection. Although several pathways for delirium have been described, biomarkers associated with delirium in intensive care unit (ICU) patients is not well studied. We examined plasma biomarkers in delirious and nondelirious patients and the role of these biomarkers on long-term cognitive function.In an exploratory observational study, we included 100 ICU patients with or without delirium and with ("inflamed") and without ("noninflamed") infection/systemic inflammatory response syndrome (SIRS). Delirium was diagnosed by using the confusion-assessment method-ICU (CAM-ICU). Within 24 hours after the onset of delirium, blood was obtained for biomarker analysis. No differences in patient characteristics were found between delirious and nondelirious patients. To determine associations between biomarkers and delirium, univariate and multivariate logistic regression analyses were performed. Eighteen months after ICU discharge, a cognitive-failure questionnaire was distributed to the ICU survivors.In total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-? were significantly associated with delirium in inflamed patients (n = 46). In the noninflamed group of patients (n = 54), IL-8, IL-1ra, IL-10 ratio A?1-42/40, and ratio A?N-42/40 were significantly associated with delirium. In multivariate regression analysis, IL-8 was independently associated (odds ratio, 9.0; 95% confidence interval (CI), 1.8 to 44.0) with delirium in inflamed patients and IL-10 (OR 2.6; 95% CI 1.1 to 5.9), and A?1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-? forms, but not human Tau or S100-?, were significantly correlated with self-reported cognitive impairment 18 months after ICU discharge, whereas inflammatory markers were not correlated to impaired long-term cognitive function.In inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and A?1-42/40 were associated with delirium. This suggests that the underlying mechanism governing the development of delirium in inflamed patients differs from that in noninflamed patients. Finally, elevated levels of amyloid-? correlated with long-term subjective cognitive-impairment delirium may represent the first sign of a (subclinical) dementia process. Future studies must confirm these results.The study was registered in the Clinical Trial Register (NCT00604773).
Project description:The effects of non-sedation on cognitive function in critically ill patients on mechanical ventilation are not yet certain. This trial is a substudy of the NONSEDA trial where critically ill patients are randomized to non-sedation or to sedation with a daily wake-up attempt during mechanical ventilation in the intensive care unit (ICU). The aim of this substudy is to assess the effects of non-sedation versus sedation with a daily wake-up attempt on long-term cognitive function.This is an investigator-initiated, randomized, clinical, parallel-group, superiority trial, including 200 patients. Inclusion criteria will be adult patients who are intubated and on mechanical ventilation with an expected duration of more than 24 hours. Exclusion criteria will be patients who are comatose at admission and patients with conditions requiring therapeutic coma (i.e., severe head trauma, status epilepticus, patients treated with therapeutic hypothermia and patients with severe hypoxia). The experimental intervention will be non-sedation supplemented with pain management during mechanical ventilation. The control intervention will be sedation with a daily wake-up attempt. The primary outcome will be cognitive function 3 months after discharge from intensive care. The secondary outcomes will be the results of seven specific cognitive tests, performed 3 months after discharge from intensive care, and the association between hypoactive and agitated delirium during ICU admission and long-term cognitive function.If non-sedation can improve long-term cognitive function, it could be an approach worth considering for a larger group of critically ill patients.The study has been approved by the relevant scientific ethics committee and is registered at ClinicalTrials.gov (ID: NCT02035436 , registered on 10 January 2014).
Project description:To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation.Prospective cohort study.Medical intensive care unit in a large community hospital in the United States.Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessments 3 and 12 mos after discharge.Of 126 eligible patients, 99 survived>or=3 months after critical illness; long-term cognitive outcomes were obtained for 77 (78%) patients. Median age was 61 yrs, 51% were admitted with sepsis/acute respiratory distress syndrome, and median duration of delirium was 2 days. At 3-mo and 12-mo follow-up, 79% and 71% of survivors had cognitive impairment, respectively (with 62% and 36% being severely impaired). After adjusting for age, education, preexisting cognitive function, severity of illness, severe sepsis, and exposure to sedative medications in the intensive care unit, increasing duration of delirium was an independent predictor of worse cognitive performance-determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition-at 3-mo (p=.02) and 12-mo follow-up (p=.03). Duration of mechanical ventilation, alternatively, was not associated with long-term cognitive impairment (p=.20 and .58).In this study of mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was independently associated with long-term cognitive impairment, a common public health problem among intensive care unit survivors.
Project description:<h4>Introduction</h4>Hospital mortality for critically ill patients has decreased significantly throughout the developed world over the past two decades, attributable to improvements in the quality of intensive care, advances in critical care medicine and technologies that provide long-term multiorgan support. However, the long-term outcomes of intensive care unit (ICU) survivors is emerging as a real issue. Cognitive and physical impairments suffered by ICU survivors are common including profound weakness, pain and delirium which are inextricably linked. This study aims to determine the effectiveness of the Assess, prevent and manage pain; Both spontaneous awakening and spontaneous breathing trials; Choice of sedation and analgesia; Delirium: assess, prevent and manage; Early mobility and exercise; Family engagement and empowerment (ABCDEF) bundle in reducing ICU-related short-term and long-term consequences of critical illness through a randomised controlled trial (RCT).<h4>Methods and analysis</h4>The study will be a single-centre, prospective RCT. A total of 150 participants will be recruited and randomised to either receive the ABCDEF bundle protocol or non-protocolised standard care for the duration of the participant's admission in the ICU. The primary outcome is delirium status measured using the Confusion Assessment Measure for ICU (CAM-ICU). Secondary outcomes include physical function measured by the Functional Independence Measure and quality of life measured by the European Quality of Life five dimensions, five-level questionnaire. A mixed-method process evaluation will contribute to understanding the experience of health teams who implement the ABCDEF bundle into practice.<h4>Ethics and dissemination</h4>Ethics approval was provided by the Metro South Health Human Research Ethics Committee (HREC) (EC00167) and the Griffith University's HREC prior to study commencement.Study results will be disseminated by presentations at conferences and via publications to peer-review journals.<h4>Trial registration number</h4>ACTRN12620000736943; Pre-results.
Project description:Few studies have examined the epidemiology of post-intensive care syndrome in Japan. This study investigated the mental health and quality of life of patients living at home in Japan after intensive care unit (ICU) discharge. Additionally, we examined whether unplanned admission to the ICU was associated with more severe post-traumatic stress disorder (PTSD), anxiety, and depressive symptoms. An ambidirectional cohort study was conducted at 12 ICUs in Japan. Patients who stayed in the ICU for > 3 nights and were living at home for 1 year afterward were included. One year after ICU discharge, we retrospectively screened patients and performed a mail survey on a monthly basis, including the Impact of Event Scale-Revised (IER-S), the Hospital Anxiety Depression Scale (HADS), and the EuroQOL-5 Dimension (EQ-5D-L) questionnaires. Patients' characteristics, delirium and coma status, drugs used, and ICU and hospital length of stay were assessed from medical records. Descriptive statistics and multilevel linear regression modeling were used to examine our hypothesis. Among 7,030 discharged patients, 854 patients were surveyed by mail. Of these, 778 patients responded (response rate = 91.1%). The data from 754 patients were analyzed. The median IES-R score was 3 (interquartile range [IQR] = 1‒9), and the prevalence of suspected PTSD was 6.0%. The median HADS anxiety score was 4.00 (IQR = 1.17‒6.00), and the prevalence of anxiety was 16.6%. The median HADS depression score was 5 (IQR = 2‒8), and the prevalence of depression was 28.1%. EQ-5D-L scores were lower in our participants than in the sex- and age-matched Japanese population. Unplanned admission was an independent risk factor for more severe PTSD, anxiety, and depressive symptoms. Approximately one-third of patients in the general ICU population experienced mental health issues one year after ICU discharge. Unplanned admission was an independent predictor for more severe PTSD symptoms.
Project description:<h4>Objective</h4>We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI).<h4>Summary background data</h4>After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors.<h4>Methods</h4>We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3- and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms (RBANS) global score. Covariates adjusted using multivariable linear regression included age, sex, race, AHRQ socioeconomic index, Charlson comorbidity, Framingham stroke risk, Sequential Organ Failure Assessment, duration of coma, delirium, hypoxemia, sepsis, education level, hospital type, insurance status, discharge disposition, and ICU drug exposures.<h4>Results</h4>Of 1040 patients, 71% experienced delirium, and 47% and 41% of survivors had RBANS scores >1 standard deviation below normal at 3- and 12 months, respectively. Adjusted analysis indicated that delirium, non-White race, lower education, and civilian hospitals (as opposed to VA), were associated with at least a half standard deviation lower RBANS scores at 3- and 12 months (P ≤ 0.03). Sex, AHRQ socioeconomic index, insurance status, and discharge disposition were not associated with RBANS scores.<h4>Conclusions</h4>Socioeconomic and clinical risk factors, such as race, education, hospital type, and delirium duration, were linked to worse PICS ICU-related, LTCI. Further efforts may focus on improved identification of higher-risk groups to promote survivorship through emerging improvements in cognitive rehabilitation.
Project description:BACKGROUND:Venovenous extracorporeal membrane oxygenation (VV-ECMO) is associated with a significant morbidity. There is the need to investigate long-term cognitive outcome among ARDS survivors treated with VV-ECMO. We aimed to compare the prevalence of long-term cognitive dysfunction and neuropsychological impairment using a highly specific test in severe ARDS survivors treated or not treated with VV-ECMO. METHODS:Severe ARDS survivors treated between 2011 and 2017 in an ECMO Regional Referral Center were prospectively evaluated 2 years after their ICU discharge. Patients underwent an in-person interview and examination. The primary outcome was cognitive function, assessed by the Wechsler Adult Intelligence Scale 4th edition (WAIS-IV). Secondary outcomes included anxiety, depression, post-traumatic stress disorder (PTSD) and quality-of-life. RESULTS:We investigated 40 consecutive patients surviving from severe ARDS treated (N?=?22) or not (N?=?18) with VV-ECMO at a median [interquartile range] of 20 [17-22] and 22 [18-23] months after ICU discharge, respectively. Regarding the main outcome, cognitive function was below normal ranges in 12 (55%) ECMO patients and 10 (56%) non-ECMO patients (p?=?0.95). Eight (36%) ECMO patients had moderate-to-severe depressive symptoms as compared with 7 (39%) non-ECMO patients (p?=?0.87). Twelve (55%) ECMO patients and eight (44%) non-ECMO patients had moderate-to-severe anxiety symptoms (p?=?0.53). Seven (33%) ECMO patients and eight (44%) non-ECMO patients presented a PTSD (p?=?0.48). Health-related quality of life did not differ between the two groups. CONCLUSIONS:Using the WAIS-IV, VV-ECMO treatment does not appear to worsen long-term cognitive and neuropsychological outcomes in severe ARDS patients.
Project description:Delirium is a form of acute brain injury that occurs in up to 80% of critically ill patients. It is a source of enormous societal and financial burdens due to increased mortality, prolonged intensive care unit (ICU) and hospital stays, and long-term neuropsychological and functional deficits in ICU survivors. These poor outcomes are not only independently associated with the development of delirium but are also associated with increasing delirium duration. Therefore, interventions should strive both to prevent the occurrence of ICU delirium and to limit its persistence. Both patient-centered and ICU-acquired risk factors need to be addressed early in the ICU course to maximize the efficacy of prevention strategies and to improve long-term outcomes of ICU patients. In this article, we review strategies for early detection of patients who are delirious and who are at high risk for developing delirium, and we present a clinically useful ICU delirium prevention and reduction strategy for clinicians to incorporate into their daily practice.