Guideline adherence in the management of acute pulmonary oedema: Study protocol for a French survey involving cardiologists, emergency physicians and intensivists.

BACKGROUND: Because of their high morbidity and mortality, patients with acute pulmonary oedema (APE) require early recognition of symptoms, identification of precipitating factors and admission to specialized care units (cardiac critical care or intensive care). APE is at the crossroads of different specialties (cardiology, emergency medicine and intensive care medicine). Although multidisciplinary expertise and management may be a strength, it can also be a source of confusion, with unexpected heterogeneity in patient care. We hypothesized that the management of severe APE may be heterogeneous between specialties and, in some situations, may differ from international recommendations. AIM: We designed a survey to compare management of different APE phenotypes according to the physicians' medical specialty, and to compare the results with what experts would do and European guidelines. METHODS: Four clinical cases of typical APE with questions pertaining to the latest guidelines were designed by a Scientific Committee designated by the French Scientific Societies for Cardiology, Emergency Medicine and Intensive Care Medicine. We focused on oxygenation and ventilation strategies, management of precipitating factors, including timing of coronary revascularization, use of diuretics and management of diuretic resistance, and discharge coverage. From 20 June 2022 until 09 September 2022, the four cases of APE (two during hypertensive crises, two during acute coronary syndromes) were proposed to French physicians involved in APE care, and to experts, using an open online survey. To avoid any diagnostic ambiguity, the diagnosis of APE was given at the beginning of each clinical case. RESULTS: The intention is to present the results at national and international conferences and publish them in a peer-reviewed journal. CONCLUSIONS: The results of this survey are intended to pave the way for the generation of novel hypotheses for future clinical trials in case of equipoise between subsets of therapeutic procedures in APE.

Risk factors for poor performance in finger cuff non-invasive monitoring of arterial pressure: A prospective multicenter study.

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.

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Prospective comparison of prognostic scores for prediction of outcome after out-of-hospital cardiac arrest: results of the AfterROSC1 multicentric study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. METHODS: We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. RESULTS: During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76-0.83], whereas AUROCs from other scores varied from 0.79 [0.75-0.83] to 0.88 [0.86-0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. CONCLUSIONS: In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891.

Noninvasive Monitoring of Arterial Pressure: Finger or Lower Leg As Alternatives to the Upper Arm: A Prospective Study in Three ICUs.

OBJECTIVES: When the upper arm is inaccessible for measurements of arterial pressure (AP), the best alternative site is unknown. We performed a between-site comparison of the agreement between invasive and noninvasive readings of AP taken at the lower leg, the finger, and the upper arm. The risk associated with measurement errors and the trending ability were also assessed. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Patients having an arterial catheter and an arm circumference less than 42 cm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three triplicates of AP measurements were collected via an arterial catheter (reference AP), a finger cuff system (ClearSight; Edward Lifesciences, Irvine, CA), and an oscillometric cuff (at the lower leg then the upper arm). Trending ability was assessed through an additional set of measurements after a cardiovascular intervention. The default bed backrest angle was respected. Failure to measure and display AP occurred in 19 patients (13%) at the finger, never at other sites. In 130 patients analyzed, the agreement between noninvasive and invasive readings was worse at the lower leg than that observed at the upper arm or the finger (for mean AP, bias ± sd of 6.0 ± 15.8 vs 3.6 ± 7.1 and 0.1 ± 7.4 mm Hg, respectively; p < 0.05), yielding a higher frequency of error-associated clinical risk (no risk for 64% vs 84% and 86% of measurements, respectively, p < 0.0001). According to the International Organization for Standardization (ISO) 81060-2:2018 standard, mean AP measurements were reliable at the upper arm and the finger, not the lower leg. In 33 patients reassessed after a cardiovascular intervention, both the concordance rate for change in mean AP and the ability to detect a therapy-induced significant change were good and similar at the three sites. CONCLUSIONS: As compared with lower leg measurements of AP, finger measurements were, when possible, a preferable alternative to upper arm ones.

Subjective and objective survival prediction in mechanically ventilated critically ill patients: a prospective cohort study.

BACKGROUND: ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. METHODS: We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. RESULTS: Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70-0.78]), junior physicians (0.78 [0.74-0.81]) and attending physicians (0.75 [0.72-0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67-0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. CONCLUSIONS: Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582 , retrospectively registered October 31st 2013.

Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial.

INTRODUCTION: Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients' response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids. METHODS AND ANALYSIS: RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%-10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids' effect in each subset, and (2) measure of interaction. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04280497).

Relying on pulse oximetry to avoid hypoxaemia and hyperoxia: A multicentre prospective cohort study in patients with circulatory failure.

PURPOSE: The purpose of this study was to assess the predictive performance of pulse oximetry (SpO2) to rule out hypoxaemia and hyperoxia in critically ill patients. METHODS: SpO2, arterial oxygenation (SaO2), and arterial partial pressure of oxygen (PaO2) were prospectively and simultaneously measured every 6 h during the first 24 h of intensive care unit admission in a multicentre cohort of critically ill patients suffering acute circulatory failure. Likelihood ratios associated with different cutoff values of SpO2 to rule out hypoxaemia (SaO2 < 90% or PaO2 < 60 mmHg) or hyperoxia (SaO2 > 95% or PaO2 > 100 mmHg) and post-test probabilities were calculated. Mean bias between SpO2 and SaO2 and agreement interval were calculated. Area under the receiver operating characteristics associated with SpO2 to predict different threshold values of SaO2 and PaO2 were calculated. RESULTS: Five hundred seventy-one patients (mean [standard deviation] Simplified Acute Physiology Score II: 58.7 [20.1]; mechanically ventilated 75.6%) with 2643 available SaO2 and PaO2 samples and corresponding 2643 SpO2 values were analysed. Mean bias between SpO2 and SaO2 was 1.1%, and its agreement interval ranged from -8.2 to +11.1%. SpO2 cutoff values of 88%, 90%, and 92% left the possibility that 8%-13% of patients had hypoxaemia. SpO2 < 95% left the possibility that 31% of patients had hyperoxia. All calculated areas under the receiver operating characteristics showed a lower limit of their 95% confidence interval below 0.85 CONCLUSION: In this cohort of patients with circulatory failure, SpO2 had poor discriminative ability to rule out hypoxaemia and hyperoxia. Overconfidence upon SpO2 monitoring may be dangerous.

Assessing oral comprehension with an eye tracking based innovative device in critically ill patients and healthy volunteers: a cohort study.

PURPOSE: Communication of caregivers and relatives to patients is a major difficulty in intensive care units (ICU). Patient's comprehension capabilities are variable over time and traditional comprehension tests cannot be implemented. Our purpose was to evaluate an oral comprehension test adapted for its automatic implementation using eye-tracking technology among ICU patients. METHODS: Prospective bi-centric cohort study was conducted on 60 healthy volunteers and 53 ICU patients. Subjects underwent an oral comprehension test using an eye-tracking device: Their results and characteristics were collected. The total duration of the test was 2 and a half minutes. RESULTS: While performing the test, 48 patients (92%) received invasive ventilation. Among healthy volunteers, the median rate of right answers was very high (93% [interquartile range 87, 100]), whereas it was lower (33% [20, 67]) for patients. For both groups, a significantly lower right answers rate was observed with advancing age (67% [27, 80] vs. 27% [20, 38] among patients and 93% [93, 100] vs. 87% [73, 93] among healthy volunteers, below and above 60 years of age, respectively) and in case of lack of a bachelor's degree (60% [38, 87] vs. 27% [20, 57] among patients and 93% [93, 100] vs. 87% [73, 93] among healthy volunteers). For patients, the higher the severity of disease was, the lower the rate of correct answers was. CONCLUSION: The eye-tracking-adapted comprehension test is easy and fast to use among ICU patients, and results seem coherent with various potential levels of comprehension as hypothesized in this study.

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

Eye tracking communication with intubated critically ill patients: a proof-of-concept multicenter pilot study.

BACKGROUND: Communication is essential to establish patient-caregivers relationship in the intensive care unit. Intubated patients are not able to speak because the tracheal tube prevents vocalization. Use of communication tools such as eye tracking device could improve communication with intubated patients. The objective of this feasibility pilot study was to demonstrate that an eye tracking device specifically developed for the intensive care could be used easily by awake intubated patient with a very short training time. METHODS: This prospective multicenter study was conducted in four intensive care units. We included awake adult intubated patients. The device used included an eye-tracking infrared detection and a communication interface specifically developed. RESULTS: A total of 151 patients were included: the median age of patients was 66 years (56-72) and 97 (64%) were male, 97 patients (64%) succeed totally (installation; calibration, succeed to select all three icons), 124 (82%) succeed to select at least one icon, and 111 (74%) succeed to point to at least two icons. The main reasons for failure to use the device were: difficulties to open or to keep the eyes open, difficulties to installing the device occurred, and patient fatigue. CONCLUSIONS: This study shows that the use of an eye tracking technology device specifically designed for the intensive care setting, with a short training is easy to use for intubated patient. Patients, relatives and caregivers showed high satisfaction.

Sensitivity and specificity of heat and moisture exchange filters sampling for SARS-CoV-2 detection in mechanically ventilated COVID-19 patients.

We assessed the sensitivity and specificity of SARS-CoV-2 detection by polymerase chain reaction in heat and moisture exchange filters (HMEF) in mechanically ventilated COVID-19 patients. We showed that testing HMEF might obviate the need for a tracheal sample to affirm that a patient is not ready to end isolation.

Effect of a Musical Intervention During the Implantation of a Central Venous Catheter or a Dialysis Catheter in the Intensive Care Unit: A Prospective Randomized Pilot Study.

BACKGROUND: Listening to music may reduce anxiety during medical procedures. However, the magnitude of any effect may differ with respect to patient and procedure. We evaluated the effect of a musical intervention on patient anxiety during a central venous catheter or dialysis catheter implantation in an intensive care unit. METHODS: A prospective single-center controlled open-label 2-arm randomized trial was conducted in a medical intensive care unit (ICU) from February 2018 to February 2019. Patients undergoing central venous catheterization were randomized to listening to music or not during the procedure. Patients randomized to music listened to the Music Care application via headphones. The primary outcome was the change in anxiety assessed on a 100-mm Visual Analogue Scale between the beginning and end of the catheterization procedure. Secondary outcomes included postprocedural pain. RESULTS: We included 37 patients in the musical intervention group and 35 in the standard care group. The primary reasons for intensive care unit admission were the need for a central catheter for chemotherapy for hematologic malignancy and sepsis and/or septic shock in both groups. Postprocedural anxiety and pain assessments were missing in 1 (2.7%) and 4 (11.4%) patients in the intervention and standard care groups. We found no between-group difference in change in anxiety score: median -1 (interquartile range, -3 to 0) vs 0 (-3 to 0) in the musical intervention and standard care groups (median difference, -1 [-2 to 0]) (P = .24). Postprocedural pain score did not differ between the groups: median 0 (0-2) and 0 (0-3.75) in the musical intervention and standard care groups (median difference, -0 [0-0]) (P = .40). To account for missing outcome assessments, sensitivity analyses were performed using 2 extreme scenarios, one favoring the standard care group (scenario 1) and the other favoring the intervention group (scenario 2). In either scenario, change in anxiety score did not differ between the intervention and standard care groups: -1 (-3 to 0) vs 0 (-4 to 0) (P = .88) in scenario 1 and -1 (-3 to 0) vs 0 (-2.75 to 1) (P = .07) in scenario 2. CONCLUSIONS: In this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared with usual care.

Deleterious synergistic effects of acute heart failure and diabetes mellitus in patients with acute coronary syndrome: Data from the FAST-MI Registries.

BACKGROUND: Diabetes mellitus (DM) predisposes patients to acute myocardial infarction (AMI) and acute heart failure (AHF). AIMS: To assess correlates of AHF occurring at the early stage of AMI and synergism between early AHF and DM on 5-year mortality. METHODS: FAST-MI 2005 and 2010 included 7839 consecutive patients admitted for AMI. RESULTS: Overall, 2151 patients (27.4%) had a history of diabetes mellitus (DM), of whom 629 (29.2%) were on insulin. Patients with versus without DM were older (mean age: 70.0 vs. 64.7years; P<0.001), with more comorbidities and more severe coronary artery disease. Early AHF (pulmonary oedema or cardiogenic shock) was the most frequent in-hospital complication (12.5%) and was twice as frequent in patients with versus without DM (20.2% vs. 9.6%; adjusted odds ratio: 1.66, 95% confidence interval [CI]: 1.43-1.94; P<0.001). Among in-hospital survivors, patients with DM without AHF and those with AHF without DM had 50% increases in 5-year mortality (adjusted hazard ratio [aHR]: 1.50, 95% CI: 1.32-1.69 and aHR: 1.46, 95% CI: 1.23-1.74; both P<0.001) versus patients without DM or AHF; with the risk among those with DM and AHF being doubled (aHR: 1.97, 95% CI: 1.66-2.34; P<0.0001). CONCLUSION: Early AHF is the most frequent complication of AMI and is twice as common in patients with versus without DM. After adjustment, early AHF and DM are associated with reduced 5-year survival with synergistic effects in patients with both conditions. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov (NCT00673036 and NCT01237418).

Characteristics and Outcomes of Patients in the ICU With Respiratory Syncytial Virus Compared With Those With Influenza Infection: A Multicenter Matched Cohort Study.

BACKGROUND: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness. RESEARCH QUESTION: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection? STUDY DESIGN AND METHODS: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection). RESULTS: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model. INTERPRETATION: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection.

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.

Insights from patients screened but not randomised in the HYPERION trial.

BACKGROUND: Few data are available about outcomes of patients screened for, but not enrolled in, randomised clinical trials. METHODS: We retrospectively reviewed patients who had non-inclusion criteria for the HYPERION trial comparing 33 °C to 37 °C in patients comatose after cardiac arrest in non-shockable rhythm, due to any cause. A good neurological outcome was defined as a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 1144 patients with non-inclusion criteria, 1130 had day-90 information and, among these, 158 (14%) had good functional outcomes, compared to 7.9% overall in the HYPERION trial (10.2% with and 5.7% without hypothermia). Considerable centre-to-centre variability was found in the proportion of non-included patients who received hypothermia (0% to 83.8%) and who had good day-90 functional outcomes (0% to 31.3%). The proportion of patients with a good day-90 functional outcome was significantly higher with than without hypothermia (18.5% vs. 11.9%, P = 0.003). CONCLUSION: Our finding of better functional outcomes without than with inclusion in the HYPERION trial, despite most non-inclusion criteria being of adverse prognostic significance (e.g., long no-flow and low-flow times and haemodynamic instability), raises important questions about the choice of patient selection criteria and the applicability of trial results to everyday practice. At present, reserving hypothermia for patients without predictors of poor prognosis seems open to criticism.

Early versus differed arterial catheterisation in critically ill patients with acute circulatory failure: a multicentre, open-label, pragmatic, randomised, non-inferiority controlled trial: the EVERDAC protocol.

INTRODUCTION: The use of peripheral indwelling arterial catheter for haemodynamic monitoring is widespread in the intensive care unit and is recommended in patients with shock. However, there is no evidence that the arterial catheter could improve patient's outcome, whereas the burden of morbidity generated is significant (pain, thrombosis, infections). We hypothesise that patients with shock may be managed without an arterial catheter. METHODS AND ANALYSIS: The EVERDAC study is an investigator-initiated, pragmatic, multicentre, randomised, controlled, open-label, non-inferiority clinical trial, comparing a less invasive intervention (ie, no arterial catheter insertion until felt absolutely needed, according to predefined safety criteria) or usual care (ie, systematic arterial catheter insertion in the early hours of shock). 1010 patients will be randomised with a 1:1 ratio in two groups according to the strategy. The primary outcome is all-cause mortality by 28 days after inclusion. A health economic analysis will be carried out. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee (Comité de Protection des Personnes Île de France V, registration number 61606 CAT 2, 19 july 2018) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03680963.

Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol.

INTRODUCTION: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia. METHODS AND ANALYSIS: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2016-001054-17 and NCT03149640.

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).