Giving a voice to patients at high risk of dying in the intensive care unit: a multiple source approach.

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.

Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

Admission criteria and management of critical care patients in a pandemic context: position of the Ethics Commission of the French Intensive Care Society, update of April 2021.

Intensive care unit professionals have experience in critical care and its proportionality, collegial decision-making, withholding or withdrawal of treatment deemed futile, and communication with patients' relatives. These elements rely on ethical values from which we must not deviate in a pandemic situation. The recommendations made by the Ethics Commission of the French Intensive Care Society reflect an approach of responsibility and solidarity towards our citizens regarding the potential impact of a pandemic on critical care resources in France, with the fundamental requirement of respect for human dignity and equal access to health care for all.

Management by the intensivist of gastrointestinal bleeding in adults and children.

Intensivists are regularly confronted with the question of gastrointestinal bleeding. To date, the latest international recommendations regarding prevention and treatment for gastrointestinal bleeding lack a specific approach to the critically ill patients. We present recommendations for management by the intensivist of gastrointestinal bleeding in adults and children, developed with the GRADE system by an experts group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), with the participation of the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP), the French Society of Emergency Medicine (SFMU), the French Society of Gastroenterology (SNFGE), and the French Society of Digestive Endoscopy (SFED). The recommendations cover five fields of application: management of gastrointestinal bleeding before endoscopic diagnosis, treatment of upper gastrointestinal bleeding unrelated to portal hypertension, treatment of upper gastrointestinal bleeding related to portal hypertension, management of presumed lower gastrointestinal bleeding, and prevention of upper gastrointestinal bleeding in intensive care.

Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection.

Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and procalcitonin (PCT) are often considered to be specific markers for infection. We evaluated plasma levels of sTREM-1 and PCT in patients with systemic inflammatory response syndrome but no sepsis. Noninfected patients undergoing elective heart surgery with cardiopulmonary bypass (n = 76) and patients admitted after out-of-hospital cardiac arrest (n = 54) were followed up for 3 days. Patients with severe sepsis (n = 55) and healthy volunteers (n = 31) were included as positive and negative controls, respectively. Plasma levels of PCT were higher in sepsis patients than in patients who survived after cardiac arrest or after heart surgery. In contrast, peak plasma levels of sTREM-1 in heart surgery and in cardiac arrest patients overlapped with those measured in patients with sepsis. Both sTREM-1 and PCT were significantly higher in cardiac arrest patients who died of refractory shock than in those who died of neurological failure or survived without major neurological damage. In the cardiac arrest patients with refractory shock, sTREM-1 and PCT levels were similar to those in the patients with severe sepsis. In conclusion, sTREM-1 and PCT are not specific for infection and can increase markedly in acute inflammation without infection.

Risk of post-traumatic stress symptoms in family members of intensive care unit patients.

RATIONALE: Intensive care unit (ICU) admission of a relative is a stressful event that may cause symptoms of post-traumatic stress disorder (PTSD). OBJECTIVES: Factors associated with these symptoms need to be identified. METHODS: For patients admitted to 21 ICUs between March and November 2003, we studied the family member with the main potential decision-making role. MEASUREMENTS: Ninety days after ICU discharge or death, family members completed the Impact of Event Scale (which evaluates the severity of post-traumatic stress reactions), Hospital Anxiety and Depression Scale, and 36-item Short-Form General Health Survey during a telephone interview. Linear regression was used to identify factors associated with the risk of post-traumatic stress symptoms. MAIN RESULTS: Interviews were obtained for family members of 284 (62%) of the 459 eligible patients. Post-traumatic stress symptoms consistent with a moderate to major risk of PTSD were found in 94 (33.1%) family members. Higher rates were noted among family members who felt information was incomplete in the ICU (48.4%), who shared in decision making (47.8%), whose relative died in the ICU (50%), whose relative died after end-of-life decisions (60%), and who shared in end-of-life decisions (81.8%). Severe post-traumatic stress reaction was associated with increased rates of anxiety and depression and decreased quality of life. CONCLUSION: Post-traumatic stress reaction consistent with a high risk of PTSD is common in family members of ICU patients and is the rule among those who share in end-of-life decisions. Research is needed to investigate PTSD rates and to devise preventive and early-detection strategies.

Influence of overweight on ICU mortality: a prospective study.

STUDY OBJECTIVE: Overweight patients seem to have a poorer outcome and a higher risk of complications during their stay in the ICU. We conducted a prospective study in order to examine the relationship between body mass index (BMI) and mortality among these patients. DESIGN: Prospective clinical study. SETTING: A 24-bed medical ICU in a university-affiliated hospital. METHODS: All patients hospitalized in the ICU over a 1-year period were included except those dying or being discharged from the hospital within 24 h of admission. Overweight patients were defined as those having a BMI > 75th percentile of this selected ICU population. Other data collected were demographic and ICU-related data. The Mann-Whitney test was used to compare numeric data between groups (ie, obese and nonobese populations). Variables that were significantly associated with ICU mortality by univariate analysis were entered into a multiple logistic regression model, allowing the determination of independent predictors. RESULTS: Eight hundred thirteen patients were included in the study. The limit of the upper quartile of the BMI was 27. This value was used to separate obese (n = 215) and nonobese (n = 598) groups. Significant differences between obese and nonobese patients were observed in age, length of stay in the ICU, simplified acute physiology score (SAPS) II, and ICU mortality. The observed mortality of obese patients was significantly higher than that predicted by SAPS II (32% vs 18%, respectively; p = 0.001). No difference was observed in frequency of nosocomial infection or duration of mechanical ventilation for mortality in ICU patients. Using a multivariate analysis, the predictive factors of mortality were SAPS II (p < 0.0001) and BMI > 27 (p < 0.01). CONCLUSION: This is the first prospective study showing high BMI value as an independent prognostic factor of mortality for ICU patients. The prognostic scoring systems currently in use, which were designed to predict the mortality of ICU patients, do not include BMI or do not consider obesity. These may underestimate, therefore, the risk for the specific population of obese patients.

Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: an alternative mechanism of HBx-related pathogenesis.

The role of the hepatitis B virus X protein (HBx) in the pathogenesis of hepatitis B virus (HBV) infection remains unclear. HBx exhibits pleiotropic biological effects, whose in vivo relevance is a matter for debate. In the present report, we have used a combination of HBx-expressing transgenic mice and liver cell transplantation to investigate the in vivo impact of HBx expression on liver cell proliferation and viability in a regenerative context. We show that moderate HBx expression inhibits liver regeneration after partial hepatectomy in HBx-expressing transgenic mice. We also demonstrate that the transplantation of HBx-expressing liver cells, isolated from HBx transgenic mice, is sufficient to inhibit overall recipient liver regeneration after partial hepatectomy. Moreover, the injection of serum samples drawn from HBx-expressing transgenic mice mimicked the inhibitory effect of HBx on liver regeneration. Finally, the incubation of primary rat hepatocytes with the supernatant of HBx-expressing liver cells inhibits cellular DNA synthesis. Taken together, our results demonstrate a paracrine inhibitory effect of HBx on liver cell proliferation and lead us to propose HBV as one of the few viruses implicated in human cancer which act, at least in part, through paracrine biological pathways.

Liver repopulation by Bcl-x(L) transgenic hepatocytes.

Liver repopulation could constitute a potential therapeutic alternative to liver transplantation in the future. Therefore, the development of liver repopulation strategies is of major interest. We have previously reported that Bcl-2-expressing hepatocytes are resistant to Fas-mediated apoptosis and that these hepatocytes, when transplanted into the spleen, are able to repopulate the liver of normal mice submitted to Fas-mediated apoptosis. We now show that Bcl-x(L)-overexpressing hepatocytes are able to repopulate up to 10% of a normal mouse liver treated with successive injections of anti-Fas antibody. We show that a twofold overexpression of Bcl-x(L) is sufficient to confer a selective advantage to hepatocytes submitted to anti-Fas antibody. Moreover, repopulation percentages obtained here were comparable to those obtained when Bcl-2 hepatocytes were transplanted, suggesting that both proteins are equivalent in conferring a selective advantage to hepatocytes submitted to anti-Fas antibody.