Associations Between Physical, Cognitive, and Mental Health Domains of Post-Intensive Care Syndrome and Quality of Life: A Longitudinal Multicenter Cohort Study.

OBJECTIVES: To explore associations between the physical, cognitive, and mental post-intensive care syndrome (PICS) health domains with changes in health-related quality of life (HRQoL) following ICU admission. DESIGN: A longitudinal prospective multicenter cohort study. SETTING/PATIENTS: Patients (n = 4092) from seven Dutch ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At ICU admission, 3 and 12 months post-ICU, patients completed validated questionnaires regarding physical health problems, cognitive health problems, mental health problems, and HRQoL. Composite scores were created for the physical health domain (physical problems and fatigue) and mental health domain (anxiety, depression, and post-traumatic stress disorder). Adjusted multivariable linear regression analyses were performed, including covariables (e.g., patient characteristics, disease severity, pre-ICU HRQoL, etc.) to explore associations between the physical, cognitive, and mental health domains of PICS and changes in HRQoL at 3 and 12 months post-ICU. At 3 months (n = 3368), physical health problems (ß = -0.04 [95% CI, -0.06 to 0.02]; p < 0.001), cognitive health problems (ß = -0.05 [95% CI, -0.09 to -0.02]; p < 0.001), and mental health problems (ß = -0.08 [95% CI, -0.10 to -0.05]; p < 0.001) were negatively associated with changes in HRQoL. Also, at 12 months (n = 2950), physical health problems (ß = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001), cognitive health problems (ß = -0.04 [95% CI, -0.08 to -0.01]; p < 0.015), and mental health problems (ß = -0.06 [95% CI, -0.08 to -0.03]; p < 0.001) were negatively associated with changes in HRQoL. CONCLUSIONS: PICS symptoms in the physical, cognitive, and mental domains are all negatively associated with changes in HRQoL at 3 and 12 months post-ICU. At 3 months, PICS symptoms in the mental domain seem to have the largest negative associations. At 12 months, the associations of PICS in the mental and physical domains are the same. This implies that daily ICU care and follow-up care should focus on preventing and mitigating health problems across all three PICS domains to prevent a decrease in HRQoL.

Discrepancy Between Functional Outcomes and Perceived Health post-ICU: A Prospective Cohort Study.

RATIONALE: Despite functional impairments, ICU survivors can perceive their quality of life as acceptable. OBJECTIVES: To investigate discrepancies between calculated health, based on self-reported physical, mental and cognitive functioning, and perceived health one year after ICU admission. METHODS: Data from an ongoing prospective multicenter cohort study, MONITOR-IC, were used. Patient-reported physical, mental and cognitive functioning, and perceived health (EQ-VAS, range 0-100) one year post-ICU of patients admitted to one of eleven participating ICUs between July 2016 and September 2021 were analyzed. The relationship between functional outcomes and perceived health was modeled using linear regression. Calculated health for each patient was estimated using this model and compared to patients' perceived health, the difference reflecting a discrepancy. Based on a minimal clinically important difference of eight points, three groups were defined: patients who rated their health better than calculated (positive discrepancy), patients who rated their health worse than calculated (negative discrepancy), and patients whose perceived health was concordant with their calculated health. RESULTS: 2,545 patients were analyzed, of whom 45.0% (n = 1,146) showed a discrepancy between calculated and perceived health. Patients with a negative discrepancy rated their health significantly lower (median 50, IQR 36 - 66) than patients with a positive discrepancy (median 84, IQR 75 - 90). Importantly, there were no significant differences in physical, mental and cognitive functioning between patients with a negative and positive discrepancy. Patients with a negative discrepancy had a higher education level and were more often unemployed. CONCLUSIONS: One year post-ICU, almost half of ICU survivors showed a discrepancy between calculated health and perceived health.

Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors.

BACKGROUND: With survival rates of critical illness increasing, quality of life measures are becoming an important outcome of ICU treatment. Therefore, to study the impact of critical illness on quality of life, we explored quality of life before and 1 year after ICU admission in different subgroups of ICU survivors. METHODS: Data from an ongoing prospective multicenter cohort study, the MONITOR-IC, were used. Patients admitted to the ICU in one of eleven participating hospitals between July 2016 and June 2021 were included. Outcome was defined as change in quality of life, measured using the EuroQol five-dimensional (EQ-5D-5L) questionnaire, and calculated by subtracting the EQ-5D-5L score 1 day before hospital admission from the EQ-5D-5L score 1 year post-ICU. Based on the minimal clinically important difference, a change in quality of life was defined as a change in EQ-5D-5L score of ≥ 0.08. Subgroups of patients were based on admission diagnosis. RESULTS: A total of 3913 (50.6%) included patients completed both baseline and follow-up questionnaires. 1 year post-ICU, patients admitted after a cerebrovascular accident, intracerebral hemorrhage, or (neuro)trauma, on average experienced a significant decrease in quality of life. Conversely, 11 other subgroups of ICU survivors reported improvements in quality of life. The largest average increase in quality of life was seen in patients admitted due to respiratory disease (mean 0.17, SD 0.38), whereas the largest average decrease was observed in trauma patients (mean -0.13, SD 0.28). However, in each of the studied 22 subgroups there were survivors who reported a significant increase in QoL and survivors who reported a significant decrease in QoL. CONCLUSIONS:  This large prospective multicenter cohort study demonstrated the diversity in long-term quality of life between, and even within, subgroups of ICU survivors. These findings emphasize the need for personalized information and post-ICU care. TRIAL REGISTRATION: The MONITOR-IC study was registered at ClinicalTrials.gov: NCT03246334 on August 2nd 2017.

One-year outcomes in COVID-19 and non-COVID-19 intensive care unit survivors.

PURPOSE: To determine differences in one-year multi-domain health outcomes in COVID-19 and non-COVID-19 intensive care unit (ICU) survivors. MATERIALS AND METHODS: Adult ICU survivors treated for COVID-19 were compared to a control group consisting of survivors admitted for respiratory distress due to other causes, i.e. non-COVID-19 ARDS or pneumonia. Occurrence of physical (frailty, fatigue, physical symptoms), mental (anxiety, depression, post-traumatic stress) and cognitive symptoms, and quality of life (QoL) scores were measured, using validated questionnaires, before and one year after ICU treatment. RESULTS: In total, 506 COVID-19 survivors could be compared to 228 non-COVID-19 survivors. At one-year follow-up, COVID-19 ICU survivors had less physical (76.2% vs. 86.9%, p = 0.001) and mental symptoms (32.0% vs. 47.1%, p < 0.001) than the control group. Cognitive symptoms were comparable (22.5% vs. 17.2%, p = 0.12). However, compared to pre-ICU health symptoms and scores, COVID-19 survivors experienced an increase in symptom occurrence rates in all domains and a decrease in QoL, whereas the control group only experienced an increase in mental and cognitive symptoms, with a similar QoL at one-year follow-up. CONCLUSIONS: COVID-19 ICU survivors experience equal or less health problems but a greater decline in QoL one year after ICU admission compared to non-COVID-19 ARDS or pneumonia survivors.

Effect of a Standardized Family Participation Program in the ICU: A Multicenter Stepped-Wedge Cluster Randomized Controlled Trial.

OBJECTIVES: To determine the effect of a standardized program for family participation in essential care activities in the ICU on symptoms of anxiety, depression, posttraumatic stress and satisfaction among relatives, and perceptions and experiences of ICU healthcare providers (HCPs). DESIGN: Multicenter stepped-wedge cluster randomized controlled trial. SETTING: Seven adult ICUs, one university, and six general teaching hospitals. PARTICIPANTS: Three hundred six relatives and 235 ICU HCPs. INTERVENTIONS: A standardized program to facilitate family participation inpatient communication, amusement/distraction, comfort, personal care, breathing, mobilization, and nutrition. MEASUREMENTS AND MAIN RESULTS: Data were collected through surveys among relatives and ICU HCPs. There were no significant differences in symptoms of anxiety in relatives in the intervention period compared with the control period (median Hospital Anxiety and Depression Scale [HADS] 5 [interquartile range (IQR) 2-10] vs 6 [IQR 3-9]; median ratio [MR] 0.72; 95% CI, 0.46-1.13; p = 0.15), depression (median HADS 4 [IQR 2-6] vs 3 [IQR 1-6]; MR 0.85; 95% CI, 0.55-1.32; p = 0.47) or posttraumatic stress (median Impact of Event Scale-Revised score 0.45 [IQR 0.27-0.82] vs 0.41 [IQR 0.14-1]; MR 0.94; 95% CI, 0.78-1.14; p = 0.54). Reported satisfaction was slightly lower in the intervention period (mean 8.90 [ sd 1.10] vs mean 9.06 [ sd 1.10], difference -0.60; 95% CI, -1.07 to -0.12; p = 0.01). ICU HCPs perceived that more relatives knew how to participate: 47% in the intervention period versus 22% in the control period (odds ratio [OR] 3.15; 95% CI, 1.64-6.05; p < 0.01). They also reported relatives having sufficient knowledge (41% vs 16%; OR 3.56; 95% CI, 1.75-7.25; p < 0.01) and skills (44% vs 25%; OR 2.38; 95% CI, 1.22-4.63; p = 0.01) to apply family participation. CONCLUSIONS: Application of a standardized program to facilitate family participation did not change mental health symptoms in relatives of ICU patients 3 months after discharge. ICU HCPs reported increased clarity, knowledge, and skills among relatives and ICU HCPs.

Development and External Validation of a Prediction Model for Quality of Life of ICU Survivors: A Subanalysis of the MONITOR-IC Prospective Cohort Study.

OBJECTIVES: To develop and externally validate a prediction model for ICU survivors' change in quality of life 1 year after ICU admission that can support ICU physicians in preparing patients for life after ICU and managing their expectations. DESIGN: Data from a prospective multicenter cohort study (MONITOR-IC) were used. SETTING: Seven hospitals in the Netherlands. PATIENTS: ICU survivors greater than or equal to 16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcome was defined as change in quality of life, measured using the EuroQol 5D questionnaire. The developed model was based on data from an academic hospital, using multivariable linear regression analysis. To assist usability, variables were selected using the least absolute shrinkage and selection operator method. External validation was executed using data of six nonacademic hospitals. Of 1,804 patients included in analysis, 1,057 patients (58.6%) were admitted to the academic hospital, and 747 patients (41.4%) were admitted to a nonacademic hospital. Forty-nine variables were entered into a linear regression model, resulting in an explained variance ( R2 ) of 56.6%. Only three variables, baseline quality of life, admission type, and Glasgow Coma Scale, were selected for the final model ( R2 = 52.5%). External validation showed good predictive power ( R2 = 53.2%). CONCLUSIONS: This study developed and externally validated a prediction model for change in quality of life 1 year after ICU admission. Due to the small number of predictors, the model is appealing for use in clinical practice, where it can be implemented to prepare patients for life after ICU. The next step is to evaluate the impact of this prediction model on outcomes and experiences of patients.

Mental health symptoms in family members of COVID-19 ICU survivors 3 and 12 months after ICU admission: a multicentre prospective cohort study.

PURPOSE: Long-term mental outcomes in family members of coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors are unknown. Therefore, we assessed the prevalence of mental health symptoms, including associated risk factors, and quality of life (QoL) in family members of COVID-19 ICU survivors 3 and 12 months post-ICU. METHODS: A prospective multicentre cohort study in ICUs of ten Dutch hospitals, including adult family members of COVID-19 ICU survivors admitted between March 1, and July 1, 2020. Symptom prevalence rates of anxiety, depression (Hospital Anxiety and Depression Scale) and Post-Traumatic Stress Disorder (Impact of Event Scale-6), and QoL (Short Form-12) before ICU admission (baseline), and after 3 and 12 months were measured. Additionally, associations between family and patient characteristics and mental health symptoms were calculated. RESULTS: A total of 166 out of 197 (84.3%) included family members completed the 12-month follow-up of whom 46.1% and 38.3% had mental health symptoms 3 and 12 months post-ICU, respectively; both higher compared to baseline (22.4%) (p < 0.001). The mental component summary score of the SF-12 was lower at 12-month follow-up compared with baseline [mean difference mental component score: - 5.5 (95% confidence interval (CI) - 7.4 to - 3.6)]. Furthermore, 27.9% experienced work-related problems. Symptoms of anxiety (odds ratio (OR) 9.23; 95% CI 2.296-37.24; p = 0.002) and depression (OR 5.96; 95% CI 1.29-27.42; p = 0.02) prior to ICU admission were identified as risk factors for mental health symptoms after 12 months. CONCLUSION: A considerable proportion of family members of COVID-19 survivors reported mental health symptoms 3 and 12 months after ICU admission, disrupting QoL and creating work-related problems.

Clinical Outcomes Among Patients With 1-Year Survival Following Intensive Care Unit Treatment for COVID-19.

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 ≥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. 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 RELEVANCE: 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 Impact of Nursing Delirium Preventive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial.

Rationale: Delirium is common in critically ill patients and is associated with deleterious outcomes. Nonpharmacological interventions are recommended in current delirium guidelines, but their effects have not been unequivocally established. Objectives: To determine the effects of a multicomponent nursing intervention program on delirium in the ICU. Methods: A stepped-wedge cluster-randomized controlled trial was conducted in ICUs of 10 centers. Adult critically ill surgical, medical, or trauma patients at high risk of developing delirium were included. A multicomponent nursing intervention program focusing on modifiable risk factors was implemented as standard of care. The primary outcome was the number of delirium-free and coma-free days alive in 28 days after ICU admission. Measurements and Main Results: A total of 1,749 patients were included. Time spent on interventions per 8-hour shift was median (interquartile range) 38 (14-116) minutes in the intervention period and median 32 (13-73) minutes in the control period (P = 0.44). Patients in the intervention period had a median of 23 (4-27) delirium-free and coma-free days alive compared with a median of 23 (5-27) days for patients in the control group (mean difference, -1.21 days; 95% confidence interval, -2.84 to 0.42 d; P = 0.15). In addition, the number of delirium days was similar: median 2 (1-4) days (ratio of medians, 0.90; 95% confidence interval, 0.75 to 1.09; P = 0.27). Conclusions: In this large randomized controlled trial in adult ICU patients, a limited increase in the use of nursing interventions was achieved, and no change in the number of delirium-free and coma-free days alive in 28 days could be determined. Clinical trial registered with www.clinicaltrials.gov (NCT03002701).

New Physical, Mental, and Cognitive Problems 1 Year after ICU Admission: A Prospective Multicenter Study.

Rationale: Comprehensive studies addressing the incidence of physical, mental, and cognitive problems after ICU admission are lacking. With an increasing number of ICU survivors, an improved understanding of post-ICU problems is necessary. Objectives: To determine the occurrence and cooccurrence of new physical, mental, and cognitive problems among ICU survivors 1 year after ICU admission, their impact on daily functioning, and risk factors associated with 1-year outcomes. Methods: Prospective multicenter cohort study, including ICU patients ⩾16 years of age, admitted for ⩾12 hours between July 2016 and June 2019. Patients, or proxies, rated their health status before and 1 year after ICU admission using questionnaires. Measurements and Main Results: Validated questionnaires were used to measure frailty, fatigue, new physical symptoms, anxiety and depression, post-traumatic stress disorder, cognitive impairment, and quality of life. Of the 4,793 patients included, 2,345 completed the questionnaires both before and 1 year after ICU admission. New physical, mental, and/or cognitive problems 1 year after ICU admission were experienced by 58% of the medical patients, 64% of the urgent surgical patients, and 43% of the elective surgical patients. Urgent surgical patients experienced a significant deterioration in their physical and mental functioning, whereas elective surgical patients experienced a significant improvement. Medical patients experienced an increase in symptoms of depression. A significant decline in cognitive functioning was experienced by all types of patients. Pre-ICU health status was strongly associated with post-ICU health problems. Conclusions: Overall, 50% of ICU survivors suffer from new physical, mental, and/or cognitive problems. An improved insight into the specific health problems of ICU survivors would enable more personalized post-ICU care.

Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study.

BACKGROUND: A subset of critically ill COVID-19 patients develop a hyperinflammatory state. Anakinra, a recombinant interleukin-1 receptor antagonist, is known to be effective in several hyperinflammatory diseases. We investigated the effects of anakinra on inflammatory parameters and clinical outcomes in critically ill, mechanically ventilated COVID-19 patients with clinical features of hyperinflammation. METHODS: In this prospective cohort study, 21 critically ill COVID-19 patients treated with anakinra were compared to a group of standard care. Serial data of clinical inflammatory parameters and concentrations of multiple circulating cytokines were determined and aligned on start day of anakinra in the treatment group, and median start day of anakinra in the control group. Analysis was performed for day - 10 to + 10 relative to alignment day. Clinical outcomes were analyzed during 28 days. Additionally, three sensitivity analyses were performed: (1) using propensity score-matched groups, (2) selecting patients who did not receive corticosteroids, and (3) using a subset of the control group aimed to match the criteria (fever, elevated ferritin) for starting anakinra treatment. RESULTS: Baseline patient characteristics and clinical parameters on ICU admission were similar between groups. As a consequence of bias by indication, plasma levels of aspartate aminotransferase (ASAT) (p = 0.0002), ferritin (p = 0.009), and temperature (p = 0.001) were significantly higher in the anakinra group on alignment day. Following treatment, no relevant differences in kinetics of circulating cytokines were observed between both groups. Decreases of clinical parameters, including temperature (p = 0.03), white blood cell counts (p = 0.02), and plasma levels of ferritin (p = 0.003), procalcitonin (p = 0.001), creatinine (p = 0.01), and bilirubin (p = 0.007), were more pronounced in the anakinra group. No differences in duration of mechanical ventilation or ICU length of stay were observed between groups. Sensitivity analyses confirmed these results. CONCLUSIONS: Anakinra is effective in reducing clinical signs of hyperinflammation in critically ill COVID-19 patients. A randomized controlled trial is warranted to draw conclusion about the effects of anakinra on clinical outcomes.

Physical, Mental, and Cognitive Health Status of ICU Survivors Before ICU Admission: A Cohort Study.

OBJECTIVES: Although patient's health status before ICU admission is the most important predictor for long-term outcomes, it is often not taken into account, potentially overestimating the attributable effects of critical illness. Studies that did assess the pre-ICU health status often included specific patient groups or assessed one specific health domain. Our aim was to explore patient's physical, mental, and cognitive functioning, as well as their quality of life before ICU admission. DESIGN: Baseline data were used from the longitudinal prospective MONITOR-IC cohort study. SETTING: ICUs of four Dutch hospitals. PATIENTS: Adult ICU survivors (n = 2,467) admitted between July 2016 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients, or their proxy, rated their level of frailty (Clinical Frailty Scale), fatigue (Checklist Individual Strength-8), anxiety and depression (Hospital Anxiety and Depression Scale), cognitive functioning (Cognitive Failure Questionnaire-14), and quality of life (Short Form-36) before ICU admission. Unplanned patients rated their pre-ICU health status retrospectively after ICU admission. Before ICU admission, 13% of all patients was frail, 65% suffered from fatigue, 28% and 26% from symptoms of anxiety and depression, respectively, and 6% from cognitive problems. Unplanned patients were significantly more frail and depressed. Patients with a poor pre-ICU health status were more often likely to be female, older, lower educated, divorced or widowed, living in a healthcare facility, and suffering from a chronic condition. CONCLUSIONS: In an era with increasing attention for health problems after ICU admission, the results of this study indicate that a part of the ICU survivors already experience serious impairments in their physical, mental, and cognitive functioning before ICU admission. Substantial differences were seen between patient subgroups. These findings underline the importance of accounting for pre-ICU health status when studying long-term outcomes.