We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Background Long-term health sequelae of COVID-19 may be multiple but have thus far not been systematically studied. Methods All patients discharged after COVID-19 from the Radboud university medical centre, Nijmegen, The Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, non-admitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest CT/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status and quality of life (QoL). Results 124 patients (age 59±14 years, 60% male) were included; 27 with mild, 51 with moderate, 26 with severe and 20 with critical disease. Lung diffusion capacity was below lower limit of normal in 42% of discharged patients. Ninety-nine percent of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild diseases. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients, and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of the patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%) and QoL (72%). Conclusions This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex-COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery.

Specificity of the CAM-ICU as performed in routine practice seems to be high but sensitivity is low. This hampers early detection of delirium by the CAM-ICU.

Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers.Design Observational multicentre study.Setting Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals).Participants 3056 intensive care patients aged 18 years or over.Main outcome measure Development of delirium (defined as at least one positive delirium screening) during patients' stay in intensive care. ResultsThe model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors-age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses ' and physicians' predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. ConclusionThe PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study). IntroductionDelirium, characterised by an acute onset of fluctuating changes in mental status and changed levels of consciousness and inattentiveness, 1 has a high incidence rate in critically ill patients. [2][3][4] It is a serious disorder associated with prolonged stays in intensive care units and hospitals, higher costs, and increased morbidity and mortality. Several tools are available for assessing delirium in intensive care patients, of which the confusion assessment method-intensive care unit (CAM-ICU) has the highest sensitivity and specificity. 6 7 Screening intensive care patients is important, [8][9][10] so that timely treatment can be provided. However, preventive measures for delirium may also reduce its incidence, severity, and duration, as determined in other groups of patients.11 12 General preventive measures in all intensive care patients are time consuming and may expose a substantial number of patients to unnecessary risks such as the adverse Methods Study designThis was an observational multicentre study in which we firstly developed the PREdi...

IMPORTANCE One-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown.OBJECTIVE To assess the occurrence of physical, mental, and cognitive symptoms among patients with COVID-19 at 1 year after ICU treatment. DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURES Patients with COVID-19 who received ICU treatment and survived 1 year after ICU admission. MAIN OUTCOMES AND MEASURES The main outcomes were self-reported occurrence of physical symptoms (frailty [Clinical Frailty Scale score Ն5], fatigue [Checklist Individual Strength-fatigue subscale score Ն27], physical problems), mental symptoms (anxiety [Hospital Anxiety and Depression {HADS} subscale score Ն8], depression [HADS subscale score Ն8], posttraumatic stress disorder [mean Impact of Event Scale score Ն1.75]), and cognitive symptoms (Cognitive Failure Questionnaire-14 score Ն43) 1 year after ICU treatment and measured with validated questionnaires. RESULTS 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%]). CONCLUSIONS AND RELEVANCEIn 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.

clinicaltrials.gov Identifier: NCT01785290.

IntroductionDelirium 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.MethodsIn 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.ResultsIn total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-β 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 Aβ1-42/40, and ratio AβN-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 Aβ1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-β forms, but not human Tau or S100-β, 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.ConclusionsIn inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and Aβ1-42/40 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-β 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).

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