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.
Sepsis is the leading cause of death in the intensive care unit and ranks in the top 10 causes of death in general worldwide. Proinflammatory mediators are related to symptoms observed early in ...patients with sepsis, such as fever and hemodynamic instability. However, in recent years it has become clear that most septic patients do not die from an overwhelming proinflammatory immune response but in an immunosuppressive state, which can last for days or even weeks, and that results in increased susceptibility to secondary (opportunistic) infections. Although infection control and supportive therapies will remain the cornerstone of treatment, especially in the early phase of sepsis, the identification of this so-called "immunoparalysis" is currently causing a paradigm shift in the adjunctive treatment of sepsis from therapies that suppress the immune system toward immunostimulation. In this Critical Care Perspective we give an overview of the pathophysiology of sepsis, with a focus on immunosuppressive mechanisms that play an important role in outcome. In addition, we present an appraisal of the recent advances in immunotherapy as an adjunctive treatment for sepsis.
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.
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.
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.
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.
Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. ...However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.
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.
Nurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the 'worry or concern' sign to the Rapid Response System provides ...opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration. The aim of this systematic review is to identify the signs and symptoms that trigger nurses' worry or concern about a patient's condition.
We searched the databases PubMed, CINAHL, Psychinfo and Cochrane Library (Clinical Trials) using synonyms related to the three concepts: 'nurses', 'worry/concern' and 'deterioration'. We included studies concerning adult patients on general wards in acute care hospitals. The search was performed from the start of the databases until 14 February 2014.
The search resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative and four mixed-methods designs) were included in the review. A total of 37 signs and symptoms reflecting the nature of the criterion worry or concern emerged from the data and were summarized in 10 general indicators. The results showed that worry or concern can be present with or without change in vital signs.
The signs and symptoms we found in the literature reflect the nature of nurses' worry or concern, and nurses may incorporate these signs in their assessment of the patient and their decision to call for assistance. The fact that it is present before changes in vital signs suggests potential for improving care in an early stage of deterioration.
Background
This study aimed to improve the PREPARE model, an existing linear regression prediction model for long‐term quality of life (QoL) of intensive care unit (ICU) survivors by incorporating ...additional ICU data from patients' electronic health record (EHR) and bedside monitors.
Methods
The 1308 adult ICU patients, aged ≥16, admitted between July 2016 and January 2019 were included. Several regression‐based machine learning models were fitted on a combination of patient‐reported data and expert‐selected EHR variables and bedside monitor data to predict change in QoL 1 year after ICU admission. Predictive performance was compared to a five‐feature linear regression prediction model using only 24‐hour data (R2 = 0.54, mean square error (MSE) = 0.031, mean absolute error (MAE) = 0.128).
Results
The 67.9% of the included ICU survivors was male and the median age was 65.0 IQR: 57.0–71.0. Median length of stay (LOS) was 1 day IQR 1.0–2.0. The incorporation of the additional data pertaining to the entire ICU stay did not improve the predictive performance of the original linear regression model. The best performing machine learning model used seven features (R2 = 0.52, MSE = 0.032, MAE = 0.125). Pre‐ICU QoL, the presence of a cerebro vascular accident (CVA) upon admission and the highest temperature measured during the ICU stay were the most important contributors to predictive performance. Pre‐ICU QoL's contribution to predictive performance far exceeded that of the other predictors.
Conclusion
Pre‐ICU QoL was by far the most important predictor for change in QoL 1 year after ICU admission. The incorporation of the numerous additional features pertaining to the entire ICU stay did not improve predictive performance although the patients' LOS was relatively short.
Reversal of sepsis-induced immunoparalysis may reduce the incidence of secondary infections and improve outcome. Although IFN-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF) restore ...immune competence of ex vivo stimulated leukocytes of patients with sepsis, effects on immunoparalysis in vivo are not known.
To investigate the effects of IFN-γ and GM-CSF on immunoparalysis in vivo in humans.
We performed a double-blind, placebo-controlled, randomized study in 18 healthy male volunteers that received Escherichia coli endotoxin (LPS; 2 ng/kg, intravenously) on days 1 and 7 (visits 1 and 2). On days 2, 4, and 6, subjects received subcutaneous injections of IFN-γ (100 μg/day; n = 6), GM-CSF (4 μg/kg/day; n = 6), or placebo (NaCl 0.9%; n = 6).
In the placebo group, immunoparalysis was illustrated by a 60% (48-71%) reduction of LPS-induced tumor necrosis factor (TNF)-α plasma concentrations during visit 2 (P = 0.03), whereas the antiinflammatory IL-10 response was not significantly attenuated (39% 2-65%; P = 0.15). In contrast, in the IFN-γ group, TNF-α concentrations during visit 2 were not significantly attenuated (28% 1-47%; P = 0.09), whereas the IL-10 response was significantly lower (reduction of 54% 47-66%; P = 0.03). Compared with the placebo group, the reduction in the LPS-induced TNF-α response during visit 2 was significantly less pronounced in the IFN-γ group (P = 0.01). Moreover, compared with placebo, treatment with IFN-γ increased monocyte HLA-DR expression (P = 0.02). The effects of GM-CSF tended in the same direction as IFN-γ, but were not statistically significant compared with placebo.
IFN-γ partially reverses immunoparalysis in vivo in humans. These results suggest that IFN-γ is a promising treatment option to reverse sepsis-induced immunoparalysis.
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