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Purpose: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS)., Methods: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO 2 /FiO 2  < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60., Results: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups., Conclusions: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels., (© 2024. The Author(s).)

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. L. is a consultant on the Advisory Board of Philips. In addition, K. L. received, during the past 3 years, congress registration from Pfizer (once in 2022) and both congress registration and travel fees from Advanz Pharma/Correvio (once in 2021) and from AOP Health (once in 2024). B. R. received, during the past 5 years, lecture fees from Fisher&Paykel, Baxter, LFB, and Aspen, research grants from Baxter and Aguettant, and consulting fees from LFB, Aguettant, and Astra Zeneca. None declared (A. A., G. N., J. E. D., T. B.)

Purpose: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear., Methods: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality., Results: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048)., Conclusion: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality., (© 2024. The Author(s).)

Background: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population., Methods: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality., Results: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO 2 /FiO 2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO 2 /FiO 2 (p = 0.118), and treatment arm (p = 0.046)., Conclusions: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality., Trial Registration: clinicaltrials.gov Identifier # NCT01320384., (© 2024. The Author(s).)

Purpose: The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described., Methods: We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019., Results: French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17-0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients., Conclusions: The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals., (© 2024. The Author(s).)

Introduction: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease., Methods and Analysis: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored., Ethics and Dissemination: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences., Trial Registration Number: NCT04754711., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Compared to the invasive technique, non-invasive monitoring of arterial pressure favors easier and faster implementation while potentially sacrificing some reliability. This may be particularly true for the Clearsight™ system (Edwards Lifesciences), which enables continuous monitoring. We evaluated the risk factors for its poor performance., Methods: Patients with an arterial catheter and stable mean arterial pressure (MAP) over a 5-min period were included. Six pairs of invasive and Clearsight measurements of MAP were collected and the bias between the two techniques was calculated. Poor performance of the Clearsight™ system was defined as either a failure to measure and display MAP or displaying an erroneous MAP (individual bias > 5 mmHg). Fingertip perfusion was assessed using the plethysmographic perfusion index (PI) and the capillary refill time (CRT)., Results: Among 152 ICU patients (MAP of 81 ± 14 mmHg, norepinephrine in 78 [51%]), 78 (51%) experienced a poor performance of the Clearsight™ system: failure to display MAP in 19 (13%) patients, and erroneous value displayed in 59 (44%). In multivariate analysis, PI ≤ 0.85% (adjusted odds ratio [aOR] = 2.94 [95% confidence interval (95%CI):1.34;6.45]), CRT > 4 s (aOR = 5.28 [95%CI 1.39;20.05]), and the presence of hand edema (aOR = 2.06 [95%CI 1.01;4.21]) were associated with a higher likelihood of poor performance. Cardiac arrhythmia (aOR = 1.39 [95%CI 0.64;3.02]) and other tested variables were not associated with poor performance., Conclusions: Half of the included patients exhibited poor Clearsight™ system performance. Our results caution against using finger cuff arterial pressure monitoring in patients with low PI (≤0.85%), protracted CRT (>4 s), or hand edema., Registration: ClinicalTrials.gov, NCT04269382, Dr. G. Muller, February 13, 2020. https://classic., Clinicaltrials: gov/ct2/show/NCT04269382., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable., Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm., Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis., Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score., Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation., Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5., Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups., Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.