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Purpose: Data are scarce regarding the experience of critically ill patients at high risk of death. Identifying their concerns could allow clinicians to better meet their needs and align their end-of-life trajectory with their preferences and values. We aimed to identify concerns expressed by conscious patients at high risk of dying in the intensive care unit (ICU). Methods: Multiple source multicentre study. Concerns expressed by patients were collected from five different sources (literature review, panel of 50 ICU experts, prospective study in 11 ICUs, in-depth interviews with 17 families and 15 patients). All qualitative data collected were analyzed using thematic content analysis. Results: The five sources produced 1307 concerns that were divided into 7 domains and 41 sub-domains. After removing redundant items and duplicates, and combining and reformulating similar items, 28 concerns were extracted from the analysis of the data. To increase accuracy, they were merged and consolidated, and resulted in a final list of 15 concerns pertaining to seven domains: concerns about loved-ones; symptom management and care (including team competence, goals of care discussions); spiritual, religious, and existential preoccupations (including regrets, meaning, hope and trust); being oneself (including fear of isolation and of being a burden, absence of hope, and personhood); the need for comforting experiences and pleasure; dying and death (covering emotional and practical concerns); and after death preoccupations. Conclusion: This list of 15 concerns may prove valuable for clinicians as a tool for improving communication and support to better meet the needs of patients at high risk of dying. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. Methods: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. Results: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2–3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13–18.90, and OR = 3.66, 95% CI 1.33–10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19–9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. Conclusion: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge. [ABSTRACT FROM AUTHOR]

Background: The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics. Methods: In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality. Results: Among 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable. Conclusions: In ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen. [ABSTRACT FROM AUTHOR]

Previous studies assessing mental health symptoms in ARDS survivors did not report any significant difference in the prevalence and the severity of PTSD-related symptoms between COVID-19-ARDS and other ARDS etiologies [[3]]. Along this line, plasma concentration of C-reactive protein (CRP) has been associated with the development of PTSD-symptoms in war zone-deployed Marines [[4]], with each tenfold increment in CRP concentration being associated with an odds ratio of PTSD symptoms of 1.51 (95% CI 1.15-1.97). [Extracted from the article]

Purpose: Little is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess the incidence of discomfort events according to levels of sedation.Methods: Post-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation-Sedation Scale (RASS) and deep sedation was considered for a RASS - 5. Psychological disorders in family members were assessed up until 12 months after the death.Results: Among the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%, p < 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others.Conclusion: Discomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation. [ABSTRACT FROM AUTHOR]

Objectives: In the last decades, the number of cancer patients admitted in intensive care units (ICUs) for septic shock has dramatically increased. However, prognosis data remain scarce.Methods: To assess the 180-day mortality rate in cancer patients admitted to the ICU for septic shock, a 5-year prospective study was performed. All adult patients admitted for septic shock were included and categorized into the following two groups and four subgroups: cancer patients (solid tumor or hematological malignancy) and non-cancer patients (immunocompromised or not). Data were collected and compared between the groups. Upon early ICU admission, the decision to forgo life-sustaining therapy (DFLST) or not was made by consultation among hematologists, oncologists, and the patients or their relatives.Results: During the study period, 496 patients were admitted for septic shock: 252 cancer patients (119 hematological malignancies and 133 solid tumors) and 244 non-cancer patients. A DFLST was made for 39% of the non-cancer patients and 52% of the cancer patients. The 180-day mortality rate among the cancer patients was 51% and 68% for those with hematological malignancies and solid cancers, respectively. The mortality rate among the non-cancer patients was 44%. In a multivariate analysis, the performance status, Charlson comorbidity index, simplified acute physiology score 2, sequential organ failure assessment score, and DFLST were independent predictors of 180-day mortality.Conclusions: Despite early admission to the ICU, the 180-day mortality rate due to septic shock was higher in cancer patients compared with non-cancer patients, due to excess mortality in the patients with solid tumors. The long-term prognosis of cancer patients with septic shock is modulated by their general state, severity of organ failure, and DFLST. [ABSTRACT FROM AUTHOR]

Purpose: Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.Methods: A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852).Results: Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2-6) versus 4 days (IQR 2-7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59-14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07-13.31); p = 0.04].Conclusions: Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy. [ABSTRACT FROM AUTHOR]

Purpose: Family members of patients who die in the intensive care unit (ICU) may experience symptoms of stress, anxiety, depression, posttraumatic stress disorder (PTSD), and/or prolonged grief. We evaluated whether grief symptoms were alleviated if the physician and the nurse in charge at the time of death sent the closest relative a handwritten condolence letter.Methods: Multicenter randomized trial conducted among 242 relatives of patients who died at 22 ICUs in France between December 2014 and October 2015. Relatives were randomly assigned to receiving (n = 123) or not receiving (n = 119) a condolence letter. The primary endpoint was the Hospital Anxiety and Depression Score (HADS) at 1 month. Secondary endpoints included HADS, complicated grief (ICG), and PTSD-related symptoms (IES-R) at 6 months. Observers were blinded to group allocation.Results: At 1 month, 208 (85.9%) relatives completed the HADS; median score was 16 [IQR, 10-22] with and 14 [8-21.5] without the letter (P = 0.36). Although scores were higher in the intervention group, there were no significant differences regarding the HADS-depression subscale (8 [4-12] vs. 6 [2-12], mean difference 1.1 [-0.5 to 2.6]; P = 0.09) and prevalence of depression symptoms (56.0 vs. 42.4%, RR 0.76 [0.57-1.00]; P = 0.05). At 6 months, 190 (78.5%) relatives were interviewed. The intervention significantly increased the HADS (13 [7-19] vs. 10 [4-17.5], P = 0.04), HADS-depression subscale (6 [2-10] vs. 3 [1-9], P = 0.02), prevalence of depression symptoms (36.6 vs. 24.7%, P = 0.05) and PTSD-related symptoms (52.4 vs. 37.1%, P = 0.03).Conclusions: In relatives of patients who died in the ICU, a condolence letter failed to alleviate grief symptoms and may have worsened depression and PTSD-related symptoms. Trial registration Clinicaltrials.gov Identifier: NCT02325297. [ABSTRACT FROM AUTHOR]

Purpose: To develop an instrument designed specifically to assess the experience of relatives of patients who die in the intensive care unit (ICU).Methods: The instrument was developed using a mixed methodology and validated in a prospective multicentre study. Relatives of patients who died in 41 ICUs completed the questionnaire by telephone 21 days after the death, then completed the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised and Inventory of Complicated Grief after 3, 6, and 12 months.Results: A total of 600 relatives were included, 475 in the main cohort and 125 in the reliability cohort. The 15-item questionnaire, named CAESAR, covered the patient's preferences and values, interactions with/around the patient and family satisfaction. We defined three groups based on CAESAR score tertiles: lowest (≤59, n = 107, 25.9 %), middle (n = 185, 44.8 %) and highest (≥69, n = 121, 29.3 %). Factorial analysis showed a single dimension. Cronbach's alpha in the main and reliability cohorts was 0.88 (0.85-0.90) and 0.85 (0.79-0.89), respectively. Compared to a high CAESAR score, a low CAESAR score was associated with greater risks of anxiety and depression at 3 months [1.29 (1.13-1.46), p = 0.001], post-traumatic stress-related symptoms at 3 [1.34 (1.17-1.53), p < 0.001], 6 [OR = 1.24 (1.06-1.44), p = 0.008] and 12 [OR = 1.26 (1.06-1.50), p = 0.01] months and complicated grief at 6 [OR = 1.40 (1.20-1.63), p < 0.001] and 12 months [OR = 1.27 (1.06-1.52), p = 0.01].Conclusions: The CAESAR score 21 days after death in the ICU is strongly associated with post-ICU burden in the bereaved relatives. The CAESAR score should prove a useful primary endpoint in trials of interventions to improve relatives' well-being. [ABSTRACT FROM AUTHOR]

Objective: Biomarkers allowing accurate early staging of septic shock patients are lacking despite their obvious interest for patient management. Experimental models of septic shock in mouse previously noted a decrease in dendritic cell numbers. The aim of the study was to find a rapid reproducible biological test for an assessment of disease severity.Design: Evaluation of peripheral blood dendritic cell counts by flow cytometry using three commercially available kits.Patients and Participants: Forty-two consecutive septic shock patients were studied prospectively.Measurements and Results: Early low dendritic cell counts were correlated to disease severity as assessed by Simplified Acute Physiology Score or Sequential Organ Failure Assessment and predicted fatal outcome. The correlation was still present when the results were adjusted for age.Conclusion: The monitoring of blood dendritic cell count may provide an early and valuable assessment of the severity of the host response against infection and may influence the therapeutic management of septic shock patients. [ABSTRACT FROM AUTHOR]