Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves.

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25-32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia.

BACKGROUND: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined. METHODS: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO2/FiO2 ratio < 100 with FiO2 > 80% after a single awake prone positioning session. Patients with an increase in PaO2/FiO2 ratio > 20% were considered as responders. RESULTS: Overall, almitrine increased the PaO2/FiO2 ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders. CONCLUSIONS: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.

Impact of sex differences on cardiac injury in critically ill patients with COVID-19.

BACKGROUND: COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients' outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear. METHODS: In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated. RESULTS: We included 198 patients with a median age of 66 (56-73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40-0.80) vs. 0.80 (0.50-1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88-246) vs. 111 (62-192) mg/L, p = 0.03); D-Dimers (1293 (709-2523) vs. 900 (560-1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06-5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01-73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42-1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes. CONCLUSIONS: Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study.

BACKGROUND: Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. METHODS: This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. RESULTS: In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16-24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. CONCLUSIONS: In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.

Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]).

OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp o2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7; p = 0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Assessment of current practice for ß-lactam therapeutic drug monitoring in French ICUs in 2021: a nationwide cross-sectional survey.

BACKGROUND: Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize ß-lactam treatment in adult ICU patients. OBJECTIVES: To describe the current practice of ß-lactam monitoring in French ICUs. METHODS: A nationwide cross-sectional survey was conducted from February 2021 to July 2021 utilizing an online questionnaire that was sent as an email link to ICU specialists (one questionnaire per ICU). RESULTS: Overall, 119 of 221 (53.8%) French ICUs participated. Eighty-seven (75%) respondents reported having access to ß-lactam TDM, including 52 (59.8%) with on-site access. ß-Lactam concentrations were available in 24-48 h and after 48 h for 36 (41.4%) and 26 (29.9%) respondents, respectively. Most respondents (n = 61; 70.1%) reported not knowing whether the ß-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the ß-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%). CONCLUSIONS: Despite the publication of international guidelines, ß-lactam TDM is not optimally used in French ICUs. The two major barriers are ß-lactam TDM interpretation and the required time for results.

Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial.

BACKGROUND: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments. METHODS: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5. RESULTS: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26-8.83; p < 0.01). CONCLUSION: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.

Renal Replacement Therapy for Acute Kidney Injury in French Intensive Care Units: A Nationwide Survey of Practices.

BACKGROUND: The frequency of acute kidney injury (AKI) can be as high as 50% in the intensive care unit (ICU). Despite the publication of national guidelines in France in 2015 for the use of RRT, there are no data describing the implementation of these recommendations in real-life. METHODS: We performed a nationwide survey of practices from November 15, 2019, to January 24, 2020, in France. An electronic questionnaire based on the items recommended in the national guidelines was sent using an online survey platform, to the chiefs of all ICUs in France. The questionnaire comprised a section for the Department Chief about local organization and facilities, and a second section destined for individual physicians about their personal practices. RESULTS: We contacted the Department Chief in 356 eligible ICUs, of whom 88 (24.7%) responded regarding their ICU organization. From these 88 ICUs, 232/285 physicians (82%) completed the questionnaire regarding individual practices. The practices reported by respondent physicians were as follows: intermittent RRT was first-line choice in >75% in a patient with single organ (kidney) failure at the acute phase, whereas continuous RRT was predominant (>75%) in patients with septic shock or multi-organ failure. Blood and dialysate flow for intermittent RRT were 200-300 mL/min and 400-600 mL/min, respectively. The dose of dialysis for continuous RRT was 25-35 mL/kg/h (65%). Insertion of the dialysis catheter was mainly performed by the resident under echographic guidance, in the right internal jugular vein. The most commonly used catheter lock was citrate (53%). The most frequently cited criterion for weaning from RRT was diuresis, followed by a drop in urinary markers (urea and creatinine). CONCLUSION: This study shows a satisfactory level of reported compliance with French guidelines and recent scientific evidence among ICU physicians regarding initiation of RRT for AKI in the ICU.

Non-invasive ventilation versus high-flow nasal oxygen for postextubation respiratory failure in ICU: a post-hoc analysis of a randomized clinical trial.

BACKGROUND: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. METHODS: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. RESULTS: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, - 11% [95% CI, - 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, - 28% [95% CI, - 54 to - 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). CONCLUSIONS: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment.

BACKGROUND: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. METHODS: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). RESULTS: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. CONCLUSIONS: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530 .

Impact of take-home messages written into slide presentations delivered during lectures on the retention of messages and the residents' knowledge: a randomized controlled study.

BACKGROUND: Lectures with slide presentations are widely used to teach evidence-based medicine to large groups. Take-home messages (THMs) are poorly identified and recollected by students. We investigated whether an instruction to list THMs in written form on slides would improve the retention thereof by residents, and the residents' level of knowledge, 1 month after lectures. METHODS: Prospective blinded randomized controlled study was conducted. Twelve lectures (6 control and 6 intervention lectures) were delivered to 73 residents. For the intervention lectures, the lecturers were instructed to incorporate clear written THMs into their slide presentations. The outcomes were ability of resident to recollect THMs delivered during a lecture (as assessed by accordance rate between the lecturers' and residents' THMs) and knowledge (as assessed by multiple choice questions (MCQs)). RESULTS: Data for 3738 residents' THMs and 3410 MCQs were analyzed. The intervention did not significantly increase the number of THMs written on slides (77% (n = 20/26), 95% CI 56-91 vs 64% (n = 18/28), 95% CI 44-81, p = 0.31) nor THMs retention (13% (n = 238/1791), 95% CI 12-15 vs 17% (n = 326/1947), 95% 15-18, p = 0.40) nor knowledge (63.8 ± 26.2 vs 61.1 ± 31.4 /100 points, p = 0.75). In multivariable analyses performed with all THMs written on slides from the two groups, a superior knowledge was associated with notetaking during lectures (OR 1.88, 95% CI 1.41-2.51) and THMs retention (OR 2.17, 95% CI 1.54-3.04); and THMs retention was associated with written THMs (OR 2.94, 95% CI 2.20-3.93). CONCLUSIONS: In lectures delivered to residents, a third of the THMs were not in written form. An intervention based on an explicit instruction to lecturers to provide THMs in written form in their slide presentations did not result in increased use of written THMs into the slide presentation or improvement of the THMs retention or level of knowledge. However, we showed that there was a strong positive association between writing THMs on a slide, retention of THMs and residents' knowledge. Further researches are needed to assess interventions to increase written THMs in lectures by faculty. TRIAL REGISTRATION: ClinicalTrials.gov NCT01795651 (Fev 21, 2013).

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.

BACKGROUND: Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. FINDINGS: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. INTERPRETATION: In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. FUNDING: French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial.

Importance: High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. Objective: To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and Participants: Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. Interventions: Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen alternating with NIV (n = 342) immediately after extubation. Main Outcomes and Measures: The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. Results: Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P = .25). Conclusions and Relevance: In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial Registration: ClinicalTrials.gov Identifier: NCT03121482.

Transient and Persistent Acute Kidney Injury and the Risk of Hospital Mortality in Critically Ill Patients: Results of a Multicenter Cohort Study.

OBJECTIVE: To assess the prognostic impact of transient and persistent acute kidney injury in critically ill patients. DESIGN: Retrospective analysis of prospectively collected patient data SETTING: : Six hospital ICUs. PATIENTS: Critically-ill patients with ICU stay longer than three days. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Assessment of hospital survival with respect to acute kidney injury duration. A total of 447 patients were included in this study, including 283 patients (63.3%) with an acute kidney injury at admission (175 and 108 patients with persistent and transient acute kidney injury, respectively). Patients with persistent acute kidney injury more frequently had stage 3 acute kidney injury (42.9% vs 30.6%; p = 0.04). Hospital survival was 76.2% (n = 125) in patients without acute kidney injury, 70.4% (n = 76) in patients with transient acute kidney injury, and 61.1% (n = 107) in patients with persistent acute kidney injury. After adjustment for confounding factors, the factors associated with lower hospital survival were the need for vasopressors (odds ratio, 0.65; 95% CI, 0.43-0.98) and the presence of persistent acute kidney injury (odds ratio, 0.58; 95% CI, 0.36-0.95). When included in the final model, stage 3 acute kidney injury was independently associated with a lower hospital survival (odds ratio, 0.83; 95% CI, 0.70-0.98), and persistent acute kidney injury was no longer associated with outcome. CONCLUSION: Two thirds of the critically ill patients with acute kidney injury have persistent acute kidney injury. Although mortality increased progressively with the duration of acute kidney injury, we found no independent association between this duration and patient outcome when the acute kidney injury severity is taken into account. Our results suggest that the classical "prerenal acute kidney injury" and "acute tubular necrosis" paradigm might be of limited interest from a pathophysiological or prognostic point of view.

Monitoring CO2 in shock states.

The primary end point when treating acute shock is to restore blood circulation, mainly by reaching macrocirculatory parameters. However, even if global haemodynamic goals can be achieved, microcirculatory perfusion may remain impaired, leading to cellular hypoxia and organ damage. Interestingly, few methods are currently available to measure the adequacy of organ blood flow and tissue oxygenation. The rise in tissue partial pressure of carbon dioxide (CO2) has been observed when tissue perfusion is decreased. In this regard, tissue partial pressure of CO2 has been proposed as an early and reliable marker of tissue hypoxia even if the mechanisms of tissue partial pressure in CO2 rise during hypoperfusion remain unclear. Several technologies allow the estimation of CO2 content from different body sites: vascular, tissular (in hollow organs, mucosal or cutaneous), and airway. These tools remain poorly evaluated, and some are used but are not widely used in clinical practice. The present review clarifies the physiology of increasing tissue CO2 during hypoperfusion and underlines the specificities of the different technologies that allow bedside estimation of tissue CO2 content.

Value and Variability of Pulse Shape Indicator for Estimating Mean Arterial Pressure in the Radial and Femoral Arteries.

BACKGROUND: The form factor (FF) is a pulse shape indicator that corresponds to the fraction of pulse pressure added to diastolic blood pressure to estimate the time-averaged mean arterial pressure (MAP). Our invasive study assessed the FF value and variability at the radial and femoral artery levels and evaluated the recommended fixed FF value of 0.33. METHODS AND RESULTS: Hemodynamically stable patients were prospectively included in 2 intensive care units. FF was documented at baseline and during dynamic maneuvers. A total of 632 patients (64±16 years of age, 66% men, MAP=81±14 mm Hg) were included. Among them, 355 (56%) had a radial catheter and 277 (44%) had a femoral catheter. The FF was 0.34±0.06. In multiple linear regression, FF was influenced by biological sex (P<0.0001) and heart rate (P=0.04) but not by height, weight, or catheter location. The radial FF was 0.35±0.06, whereas the femoral FF was 0.34±0.05 (P=0.08). Both radial and femoral FF were higher in women than in men (P<0.05). When using the 0.33 FF value to estimate MAP, the error was -0.4±4.0 mm Hg and -0.1±2.9 mm Hg at the radial and femoral level, respectively, and the MAP estimate still demonstrated high accuracy and good precision even after changes in norepinephrine dose, increase in positive end-expiratory pressure level, fluid administration, or prone positioning (n=218). CONCLUSIONS: Despite higher FF in women and despite interindividual variability in FF, using a fixed FF value of 0.33 yielded accurate and precise estimations of MAP. This finding has potential implications for blood pressure monitoring devices and the study of pulse wave amplification.

Right ventricular injury in critically ill patients with COVID-19: a descriptive study with standardized echocardiographic follow-up.

PURPOSE: Patients with COVID-19 admitted to intensive care unit (ICU) may have right ventricular (RV) injury. The main goal of this study was to investigate the incidence of RV injury and to describe the patient trajectories in terms of RV injury during ICU stay. METHODS: Prospective and bicentric study with standardized transthoracic echocardiographic (TTE) follow-up during ICU stay with a maximum follow-up of 28 days. The different patterns of RV injury were isolated RV dilation, RV dysfunction (tricuspid annular plane systolic excursion < 17 mm and/or systolic tricuspid annular velocity < 9.5 cm/s and/or RV fractional area change < 35%) without RV dilation, RV dysfunction with RV dilation and acute cor pulmonale (ACP, RV dilatation with paradoxical septal motion). The different RV injury patterns were described and their association with Day-28 mortality was investigated. RESULTS: Of 118 patients with complete echocardiographic follow-up who underwent 393 TTE examinations during ICU stay, 73(62%) had at least one RV injury pattern during one or several TTE examinations: 29(40%) had isolated RV dilation, 39(53%) had RV dysfunction without RV dilation, 10(14%) had RV dysfunction with RV dilation and 2(3%) had ACP. Patients with RV injury were more likely to have cardiovascular risk factors, to be intubated and to receive norepinephrine and had a higher Day-28 mortality rate (27 vs. 7%, p < 0.01). RV injury was isolated in 82% of cases, combined with left ventricular systolic dysfunction in 18% of cases and 10% of patients with RV injury experienced several patterns of RV injury during ICU stay. The number of patients with de novo RV injury decreased over time, no patient developed de novo RV injury after Day-14 regardless of the RV injury pattern and 20(31%) patients without RV injury on ICU admission developed RV injury during ICU stay. Only the combination of RV dysfunction with RV dilation or ACP (aHR = 3.18 95% CI(1.16-8.74), p = 0.03) was associated with Day-28 mortality. CONCLUSION: RV injury was frequent in COVID-19 patients, occurred within the first two weeks after ICU admission and was most often isolated. Only the combination of RV dysfunction with RV dilation or ACP could potentially be associated with Day-28 mortality. Clinical trial registration NCT04335162.

Bedside adjustment of proportional assist ventilation to target a predefined range of respiratory effort.

OBJECTIVES: During proportional assist ventilation with load-adjustable gain factors, peak respiratory muscle pressure can be estimated from the peak airway pressure and the percentage of assistance (gain). Adjusting the gain can, therefore, target a given level of respiratory effort. This study assessed the clinical feasibility of titrating proportional assist ventilation with load-adjustable gain factors with the goal of targeting a predefined range of respiratory effort. DESIGN: Prospective, multicenter, clinical observational study. SETTINGS: Intensive care departments at five university hospitals. PATIENTS: Patients were included after meeting simple criteria for assisted mechanical ventilation. INTERVENTIONS: Patients were ventilated in proportional assist ventilation with load-adjustable gain factors. The peak respiratory muscle pressure, estimated in cm H2O as (peak airway pressure-positive end-expiratory pressure)×[(100-gain)/gain], was calculated from a grid at the bedside. The gain adjustment algorithm was defined to target a peak respiratory muscle pressure between 5 and 10 cm H2O. Additional recommendations were available in case of hypoventilation or hyperventilation. RESULTS: Fifty-three patients were enrolled. Median time spent under proportional assist ventilation with load-adjustable gain factors was 3 days (interquartile range, 1-5). Gain was adjusted 1.0 (0.7-1.8) times per day, according to the peak respiratory muscle pressure target range in 91% of cases and because of hypoventilation or hyperventilation in 9%. Thirty-four patients were ventilated with proportional assist ventilation with load-adjustable gain factors until extubation, which was successful in 32. Eighteen patients required volume assist-controlled reventilation because of clinical worsening and need for continuous sedation. One patient was intolerant to proportional assist ventilation with load-adjustable gain factors. CONCLUSIONS: This first study assessing the clinical feasibility of titrating proportional assist ventilation with load-adjustable gain factors in an attempt to target a predefined range of effort showed that adjusting the level of assistance to maintain a predefined boundary of respiratory muscle pressure is feasible, simple, and often sufficient to ventilate patients until extubation.