One-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown.
To assess the occurrence of physical, mental, and cognitive symptoms among ...patients with COVID-19 at 1 year after ICU treatment.
An exploratory prospective multicenter cohort study conducted in ICUs of 11 Dutch hospitals. Patients (N = 452) with COVID-19, aged 16 years and older, and alive after hospital discharge following admission to 1 of the 11 ICUs during the first COVID-19 surge (March 1, 2020, until July 1, 2020) were eligible for inclusion. Patients were followed up for 1 year, and the date of final follow-up was June 16, 2021.
Patients with COVID-19 who received ICU treatment and survived 1 year after ICU admission.
The main outcomes were self-reported occurrence of physical symptoms (frailty Clinical Frailty Scale score ≥5, fatigue Checklist Individual Strength-fatigue subscale score ≥27, physical problems), mental symptoms (anxiety Hospital Anxiety and Depression {HADS} subscale score ≥8, depression HADS subscale score ≥8, posttraumatic stress disorder mean Impact of Event Scale score ≥1.75), and cognitive symptoms (Cognitive Failure Questionnaire-14 score ≥43) 1 year after ICU treatment and measured with validated questionnaires.
Of the 452 eligible patients, 301 (66.8%) patients could be included, and 246 (81.5%) patients (mean SD age, 61.2 9.3 years; 176 men 71.5%; median ICU stay, 18 days IQR, 11 to 32) completed the 1-year follow-up questionnaires. At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% 95% CI, 68.3% to 79.6%), mental symptoms were reported by 64 of 244 patients (26.2% 95% CI, 20.8% to 32.2%), and cognitive symptoms were reported by 39 of 241 patients (16.2% 95% CI, 11.8% to 21.5%). The most frequently reported new physical problems were weakened condition (95/244 patients 38.9%), joint stiffness (64/243 patients 26.3%) joint pain (62/243 patients 25.5%), muscle weakness (60/242 patients 24.8%) and myalgia (52/244 patients 21.3%).
In this exploratory study of patients in 11 Dutch hospitals who survived 1 year following ICU treatment for COVID-19, physical, mental, or cognitive symptoms were frequently reported.
The purpose of this guideline is to present evidence-based and consensus-based recommendations for the prevention and treatment of postoperative delirium. The cornerstones of the guideline are the ...preoperative identification and handling of patients at risk, adequate intraoperative care, postoperative detection of delirium and management of delirious patients. The scope of this guideline is not to cover ICU delirium. Considering that many medical disciplines are involved in the treatment of surgical patients, a team-based approach should be implemented into daily practice. This guideline is aimed to promote knowledge and education in the preoperative, intraoperative and postoperative setting not only among anaesthesiologists but also among all other healthcare professionals involved in the care of surgical patients.
Summary Background Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to have an important role in the ...development of delirium. We aimed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients. Methods Patients (aged ≥18 years) who were diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated between November, 2008, and January, 2010. Patients were randomised (1:1 ratio) to receive an increasing dose of rivastigmine or placebo, starting at 0·75 mL (1·5 mg rivastigmine) twice daily and increasing in increments to 3 mL (6 mg rivastigmine) twice daily from day 10 onwards, as an adjunct to usual care based on haloperidol. The trial pharmacist generated the randomisation sequence by computer, and consecutively numbered bottles of the study drug according to this sequence to conceal allocation. The primary outcome was the duration of delirium during hospital admission. Analysis was by intention to treat. Duration of delirium was censored for patients who died or were discharged from hospital while delirious. Patients, medical staff, and investigators were masked to treatment allocation. Members of the data safety and monitoring board (DSMB) were unmasked and did interim analyses every 3 months. This trial is registered with ClinicalTrials.gov , number NCT00704301. Findings Although a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n=54 on rivastigmine, n=50 on placebo), the DSMB recommended that the trial be halted because mortality in the rivastigmine group (n=12, 22%) was higher than in the placebo group (n=4, 8%; p=0·07). Median duration of delirium was longer in the rivastigmine group (5·0 days, IQR 2·7–14·2) than in the placebo group (3·0 days, IQR 1·0–9·3; p=0·06). Interpretation Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients. Funding ZonMw, the Netherlands Brain Foundation, and Novartis.
Although numerous risk factors for delirium in the ICU have been proposed, the strength of evidence supporting each risk factor remains unclear. This study systematically identifies risk factors for ...delirium in critically ill adults where current evidence is strongest.
CINAHL, EMBASE, MEDLINE, the Cochrane Central Register for Controlled Trials, and the Cochrane Database of Systematic Reviews.
Studies published from 2000 to February 2013 that evaluated critically ill adults, not undergoing cardiac surgery, for delirium, and used either multivariable analysis or randomization to evaluate variables as potential risk factors for delirium.
Data were abstracted in duplicate, and quality was scored using Scottish Intercollegiate Guidelines Network checklists (i.e., high, acceptable, and low). Using a best-evidence synthesis each variable was evaluated using 3 criteria: the number of studies investigating it, the quality of these studies, and whether the direction of association was consistent across the studies. Strengths of association were not summarized. Strength of evidence was defined as strong (consistent findings in ≥2 high quality studies), moderate (consistent findings in 1 high quality study and ≥1 acceptable quality studies), inconclusive (inconsistent findings or 1 high quality study or consistent findings in only acceptable quality/low quality studies) or no evidence available.
Among 33 studies included, 70% were high quality. There was strong evidence that age, dementia, hypertension, pre-ICU emergency surgery or trauma, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, metabolic acidosis, delirium on the prior day, and coma are risk factors for delirium, that gender is not associated with delirium, and that use of dexmedetomidine is associated with a lower delirium prevalence. There is moderate evidence that multiple organ failure is a risk factor for delirium.
Only 11 putative risk factors for delirium are supported by either strong or moderate level of evidence. These factors should be considered when designing delirium prevention strategies or controlling for confounding in future etiologic studies.
As evidence-based effective treatment protocols for delirium after cardiac surgery are lacking, efforts should be made to identify risk factors for preventive interventions. Moreover, knowledge of ...these risk factors could increase validity of etiological studies in which adjustments need to be made for confounding variables. This review aims to systematically identify risk factors for delirium after cardiac surgery and to grade the evidence supporting these associations.
A prior registered systematic review was performed using EMBASE, CINAHL, MEDLINE and Cochrane from 1990 till January 2015 ( http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007371 ). All studies evaluating patients for delirium after cardiac surgery with cardiopulmonary bypass (CPB) using either randomization or multivariable data analyses were included. Data was extracted and quality was scored in duplicate. Heterogeneity impaired pooling of the data; instead a semi-quantitative approach was used in which the strength of the evidence was graded based on the number of investigations, the quality of studies, and the consistency of the association reported across studies.
In total 1462 unique references were screened and 34 were included in this review, of which 16 (47 %) were graded as high quality. A strong level of evidence for an association with the occurrence of postoperative delirium was found for age, previous psychiatric conditions, cerebrovascular disease, pre-existent cognitive impairment, type of surgery, peri-operative blood product transfusion, administration of risperidone, postoperative atrial fibrillation and mechanical ventilation time. Postoperative oxygen saturation and renal insufficiency were supported by a moderate level of evidence, and there is no evidence that gender, education, CPB duration, pre-existent cardiac disease or heart failure are risk factors.
Of many potential risk factors for delirium after cardiac surgery, for only 11 there is a strong or moderate level of evidence. These risk factors should be taken in consideration when designing future delirium prevention strategies trials or when controlling for confounding in future etiological studies.
Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in ...hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.
Delirium is associated with impaired outcome, but it is unclear whether this relationship is limited to in-hospital outcomes and whether this relationship is independent of the severity of underlying ...conditions. The aim of this study was to investigate the association between delirium in the intensive care unit (ICU) and long-term mortality, self-reported health-related quality of life (HRQoL), and self-reported problems with cognitive functioning in survivors of critical illness, taking severity of illness at baseline and throughout ICU stay into account.
A prospective cohort study was conducted. We included patients who survived an ICU stay of at least a day; exclusions were neurocritical care patients and patients who sustained deep sedation during the entire ICU stay. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM-ICU) and additionally, patients who received haloperidol were considered delirious. Twelve months after ICU admission, data on mortality were obtained and HRQoL and cognitive functioning were measured with the European Quality of Life - Six dimensions self-classifier (EQ-6D). Regression analyses were used to assess the associations between delirium and the outcome measures adjusted for gender, type of admission, the Acute Physiology And Chronic Health Evaluation IV (APACHE IV) score, and the cumulative Sequential Organ Failure Assessment (SOFA) score throughout ICU stay.
Of 1101 survivors of critical illness, 412 persons (37%) had been delirious during ICU stay, and 198 (18%) died within twelve months. When correcting for confounders, no significant association between delirium and long-term mortality was found (hazard ratio: 1.26; 95% confidence interval (CI) 0.93 to 1.71). In multivariable analysis, delirium was not associated with HRQoL either (regression coefficient: -0.04; 95% CI -0.10 to 0.01). Yet, delirium remained associated with mild and severe problems with cognitive functioning in multivariable analysis (odds ratios: 2.41; 95% CI 1.57 to 3.69 and 3.10; 95% CI 1.10 to 8.74, respectively).
In this group of survivors of critical illness, delirium during ICU stay was not associated with long-term mortality or HRQoL after adjusting for confounding, including severity of illness throughout ICU stay. In contrast, delirium appears to be an independent risk factor for long-term self-reported problems with cognitive functioning.
Purpose
There is increasing evidence that critical illness and treatment in an intensive care unit (ICU) may result in significant long-term morbidity. The purpose of this systematic review was to ...summarize the current literature on long-term cognitive impairment in ICU survivors.
Methods
PubMed/MEDLINE, CINAHL, Cochrane Library, PsycINFO and Embase were searched from January 1980 until July 2012 for relevant articles evaluating cognitive functioning after ICU admission. Publications with an adult population and a follow-up duration of at least 2 months were eligible for inclusion in the review. Studies in cardiac surgery patients or subjects with brain injury or cardiac arrest prior to ICU admission were excluded. The main outcome measure was cognitive functioning.
Results
The search strategy identified 1,128 unique studies, of which 19 met the selection criteria and were included. Only one article compared neuropsychological test performance before and after ICU admission. The 19 studies that were selected reported a wide range of cognitive impairment in 4–62 % of the patients after a follow-up of 2–156 months.
Conclusion
The results of most studies of the studies reviewed suggest that critical illness and ICU treatment are associated with long-term cognitive impairment. Due to the complexity of defining cognitive impairment, it is difficult to standardize definitions and to reach consensus on how to categorize neurocognitive dysfunction. Therefore, the magnitude of the problem is uncertain.
Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium.
To determine whether prophylactic use of haloperidol ...improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days.
Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017.
Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride.
The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay.
All 1789 randomized patients (mean, age 66.6 years SD, 12.6; 1099 men 61.4%) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 0.3% for the 2-mg haloperidol group vs 1 0.1% for the placebo group).
Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults.
clinicaltrials.gov Identifier: NCT01785290.
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