Pleural lung sliding quantification using a speckle tracking technology: A feasibility study on 30 healthy volunteers.

INTRODUCTION: Speckle tracking technology quantifies lung sliding and detects lung sliding abolition in case of pneumothorax on selected ultrasound loops through the analysis of acoustic markers. OBJECTIVES: We aimed to test the ability of speckle tracking technology to quantify lung sliding using a pleural strain value (PS). METHODS: We performed a prospective study in 30 healthy volunteers in whom we assessed the pleural speckle tracking using ultrasound loops. Seven breathing conditions with and without non-invasive ventilation were tested. Two observers analyzed the ultrasound loops in four lung areas (anterior and posterior, left and right) and compared the obtained PS values. The first endpoint was to determine the feasibility of the PS measurement in different breathing conditions. The secondary endpoints were to assess the intra- and inter-observer's reliability of the measurement to compare PS values between anterior and posterior lung areas and to explore their correlations with the measured tidal volume. RESULTS: We analyzed 1624 ultrasound loops from 29 patients after one volunteer's exclusion. Feasibility of this method was rated at 90.8 [95%CI: 89.6 - 92.4]%. The intra-observer reliability measured through Intraclass Correlation Coefficients was 0.96 [95%CI: 0.91-0.98] and 0.93 [95%CI: 0.86-0.97] depending on the operator. The inter-observer reliability was 0.89 [95%CI: 0.78-0.95]. The PS values were significantly lower in the anterior lung areas compared with the posterior areas in all breathing conditions. A weak positive correlation was found in all the lung areas when a positive end expiratory pressure was applied with r = 0.26 [95%CI: 0.12;0.39]; p < 0.01. CONCLUSION: Speckle tracking lung sliding quantification with PS was applicable in most conditions with an excellent intra- and inter-observer reliability. More studies in patients under invasive mechanical ventilation are needed to explore the correlation between PS values of pleural sliding and tidal volumes. CLINICAL REGISTRATION: NCT05415605.

Prospective Multicenter Study on Early Proximal Tubular Injury in COVID-19-Related Acute Respiratory Distress Syndrome.

Introduction: During COVID-19, renal impairment is associated with poor prognosis in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Methods: In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation (MV) for ARDS were enrolled in 3 ICUs. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis (UPE) and quantification, was performed within 24 hours after MV onset. Results: From March 2020 to December 2021, 135 patients were enrolled as follows: 100 with COVID-19 ARDS and 35 with non-COVID-19 ARDS. UPE found more tubular dysfunction in patients with COVID-19 (68% vs. 21.4%, P < 0.0001) and more normal profiles in patients without COVID-19 (65.0% vs. 11.2%, P = 0.0003). Patients with COVID-19 significantly displayed early urinary leakage of tubular proteins such as beta-2-microglobulin (ß2m) and free light chains, tended to display acute kidney injury (AKI) more frequently (51.0% vs. 34.3%, P = 0.088), had longer MV (20 vs. 9 days, P < 0.0001) and longer ICU stay (26 vs. 15 days, P < 0.0001). In COVID-19 ARDS, leakage of free lambda light chain was associated with the onset of Kidney Disease: Improving Global Outcomes (KDIGO) ≥2 AKI (odds ratio [OR]: 1.014, 95% confidence interval [CI] 1.003-1.025, P = 0.011). Conclusion: Patients with COVID-19-related ARDS display a proximal tubular dysfunction before the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable noninvasive tool to assess proximal tubular dysfunction in the ICU.

Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study.

BACKGROUND: The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes. METHODS: We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes. RESULTS: Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047). CONCLUSION: The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.

Outcomes of Severe ARDS COVID-19 Patients Denied for Venovenous ECMO Support: A Prospective Observational Comparative Study.

Background: Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods: We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results: In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions: Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19.

High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

Rationale: Airway occlusion pressure at 100 ms (P0.1) reflects central respiratory drive. Objectives: We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). Methods: We performed a secondary analysis of a prospective cohort study conducted in 10 ICUs in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the next day. Measurements and Main Results: Among 260 patients assessed after a median time of ventilation of 4 days, P0.1 was 1.9 (1-3.5) cm H2O at enrollment, 24% had P0.1 values >3.5 cm H2O, 37% had P0.1 values between 1.5 and 3.5 cm H2O, and 39% had P0.1 values <1.5 cm H2O. In multivariable linear regression, independent factors associated with P0.1 were the presence of dyspnea (P = 0.037), respiratory rate (P < 0.001), and PaO2 (P = 0.008). Ninety-day mortality was 33% in patients with P0.1 > 3.5 cm H2O versus 19% in those with P0.1 between 1.5 and 3.5 cm H2O and 17% in those with P0.1 < 1.5 cm H2O (P = 0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (hazard ratio per 1 cm H2O, 1.19 [95% confidence interval, 1.04-1.37]; P = 0.011). P0.1 was also independently associated with a longer duration of MV (hazard ratio per 1 cm H2O, 1.10 [95% confidence interval, 1.02-1.19]; P = 0.016). Conclusions: In patients receiving invasive MV, abnormally high P0.1 values may suggest dyspnea and are associated with higher mortality and prolonged duration of MV.

Microvesicles Are Associated with Early Veno Venous ECMO Circuit Change during Severe ARDS: A Prospective Observational Pilot Study.

BACKGROUND: Veno venous Extra Corporeal Membrane Oxygenation (vvECMO) is associated with frequent hematological ECMO-related complications needing ECMO circuit change. Microvesicles (MVs) interplay during the thrombosis-fibrinolysis process. The main objective of the study was to identify subpopulations of MVs associated with indications of early vvECMO circuit change. METHODS: This is a prospective observational monocenter cohort study. Blood gas was sampled on the ECMO circuit after the membrane oxygenator to measure the PO2 post oxy at inclusion, day 3, day 7 and the day of ECMO circuit removal. Blood samples for MV analysis were collected at inclusion, day 3, day 7 and the day of ECMO circuit removal. MV subpopulations were identified by flow cytometry. RESULTS: Nineteen patients were investigated. Seven patients (37%) needed an ECMO circuit change for hemolysis (n = 4), a pump thrombosis with fibrinolysis (n = 1), persistent thrombocytopenia with bleeding (n = 1) and a decrease of O2 transfer (n = 1). Levels of leukocyte and endothelial MVs were significantly higher at inclusion for patients who thereafter had an ECMO circuit change (p = 0.01 and p = 0.001). The areas under the received operating characteristics curves for LeuMVs and EndoMVs sampled the day of cannulation and the need for ECMO circuit change were 0.84 and 0.92, respectively. PO2 post oxy did not significantly change except for in one patient during the ECMO run. CONCLUSIONS: Our pilot study supports the potential interest of subpopulations of microvesicles early associated with hematological ECMO-related complications. Our results warrant further studies.

COVID-19 among undocumented migrants admitted to French intensive care units during the 2020-2021 period: a retrospective nationwide study.

BACKGROUND: Before the Coronavirus Disease 2019 (COVID-19) pandemic in France, undocumented migrants had a higher risk than general population for being admitted to the intensive care unit (ICU) because of acute respiratory failure or severe infection. Specific data concerning the impact of COVID-19 on undocumented migrants in France are lacking. We aimed to analyze the mortality and respiratory severity of COVID-19 in this specific population. We retrospectively included all undocumented adult migrants admitted in French ICUs from March 2020 through April 2021 using the French nationwide hospital information system (Programme de Médicalisation des Systèmes d'Information). We focused on admissions related to COVID-19. Undocumented migrants were compared to the general population, first in crude analysis, then after matching on age, severity and main comorbidities. The primary outcome was the ICU mortality from COVID-19. Secondary objectives were the incidence of acute respiratory distress syndrome (ARDS), the need for mechanical ventilation (MV), the duration of MV, ICU and hospital stay. RESULTS: During the study period, the rate of ICU admission among patients hospitalized for COVID-19 was higher for undocumented migrants than for general population (463/1627 (28.5%) vs. 81 813/344 001 (23.8%); p < 0.001). Although ICU mortality was comparable after matching (14.3% for general population vs. 13.3% for undocumented migrants; p = 0.50), the incidence of ARDS was higher among undocumented migrants (odds ratio, confidence interval (OR (CI)) 1.25 (1.06-1.48); p = 0.01). Undocumented migrants needed more frequently invasive MV (OR (CI) 1.2 (1.01-1.42); p = 0.04 than general population. There were no differences between groups concerning duration of MV, ICU and hospital length of stay. CONCLUSION: During the first waves of COVID-19 in France, undocumented migrants had a mortality similar to the general population but a higher risk for ICU admission and for developing an ARDS. These results highlight the need for reinforcing prevention and improving primary healthcare access for people in irregular situation.

Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock.

CONTEXT: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. DESIGN: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed. CLINICAL TRIAL REGISTRATION: NCT05366452.

Rationale and evidence for the use of new beta-lactam/beta-lactamase inhibitor combinations and cefiderocol in critically ill patients.

BACKGROUND: Healthcare-associated infections involving Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) phenotype are associated with impaired patient-centered outcomes and poses daily therapeutic challenges in most of intensive care units worldwide. Over the recent years, four innovative ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of certain DTR-GNB infections. The literature addressing their microbiological spectrum, pharmacokinetics, clinical efficacy and safety was exhaustively audited by our group to support the recent guidelines of the French Intensive Care Society on their utilization in critically ill patients. This narrative review summarizes the available evidence and unanswered questions on these issues. METHODS: A systematic search for English-language publications in PUBMED and the Cochrane Library database from inception to November 15, 2022. RESULTS: These drugs have demonstrated relevant clinical success rates and a reduced renal risk in most of severe infections for whom polymyxin- and/or aminoglycoside-based regimen were historically used as last-resort strategies-namely, ceftazidime-avibactam for infections due to Klebsiella pneumoniae carbapenemase (KPC)- or OXA-48-like-producing Enterobacterales, meropenem-vaborbactam for KPC-producing Enterobacterales, ceftazidime-avibactam/aztreonam combination or cefiderocol for metallo-ß-lactamase (MBL)-producing Enterobacterales, and ceftolozane-tazobactam, ceftazidime-avibactam and imipenem-relebactam for non-MBL-producing DTR Pseudomonas aeruginosa. However, limited clinical evidence exists in critically ill patients. Extended-infusion scheme (except for imipenem-relebactam) may be indicated for DTR-GNB with high minimal inhibitory concentrations and/or in case of augmented renal clearance. The potential benefit of combining these agents with other antimicrobials remains under-investigated, notably for the most severe presentations. Other important knowledge gaps include pharmacokinetic information in particular situations (e.g., pneumonia, other deep-seated infections, and renal replacement therapy), the hazard of treatment-emergent resistance and possible preventive measures, the safety of high-dose regimen, the potential usefulness of rapid molecular diagnostic tools to rationalize their empirical utilization, and optimal treatment durations. Comparative clinical, ecological, and medico-economic data are needed for infections in whom two or more of these agents exhibit in vitro activity against the causative pathogen. CONCLUSIONS: New BL/BLI combinations and cefiderocol represent long-awaited options for improving the management of DTR-GNB infections. Several research axes must be explored to better define the positioning and appropriate administration scheme of these drugs in critically ill patients.

Response to Prone Position in COVID-19 and Non-COVID-19 Patients with Severe ARDS Supported by vvECMO.

BACKGROUND: For moderate to severe acute respiratory distress syndrome (ARDS), lung-protective ventilation combined with prolonged and repeated prone position (PP) is recommended. For the most severe patients for whom this strategy failed, venovenous extracorporeal membrane oxygenation (vv-ECMO) allows a reduction in ventilation-induced lung injury and improves survival. Some aggregated data have suggested a benefit regarding survival in pursuing PP during vv-ECMO. The combination of PP and vv-ECMO has been also documented in COVID-19 studies, although there is scarce evidence concerning respiratory mechanics and gas exchange response. The main objective was to compare the physiological response of the first PP during vv-ECMO in two cohorts of patients (COVID-19-related ARDS and non-COVID-19 ARDS) regarding respiratory system compliance (CRS) and oxygenation changes. METHODS: This was a single-center, retrospective, and ambispective cohort study in the ECMO center of Marseille, France. ECMO was indicated according to the EOLIA trial criteria. RESULTS: A total of 85 patients were included, 60 in the non-COVID-19 ARDS group and 25 in the COVID-19-related ARDS group. Lung injuries of the COVID-19 cohort exhibited significantly higher severity with a lower CRS at baseline. Concerning the main objective, the first PP during vv-ECMO was not associated with a change in CRS or other variation in respiratory mechanic variables in both cohorts. By contrast, oxygenation was improved only in the non-COVID-19 ARDS group after a return to the supine position. Mean arterial pressure was higher during PP as compared with a return to the supine position in the COVID-19 group. CONCLUSION: We found distinct physiological responses to the first PP in vv-ECMO-supported ARDS patients according to the COVID-19 etiology. This could be due to higher severity at baseline or specificity of the disease. Further investigations are warranted.

Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Awake prone position in COVID-19 acute respiratory failure: a randomised crossover study using electrical impedance tomography.

Background: The goal of this study was to determine whether an awake prone position (aPP) reduces the global inhomogeneity (GI) index of ventilation measured by electrical impedance tomography (EIT) in COVID-19 patients with acute respiratory failure (ARF). Methods: This prospective crossover study included COVID-19 patients with COVID-19 and ARF defined by arterial oxygen tension:inspiratory oxygen fraction (P aO2 :F IO2 ) of 100-300 mmHg. After baseline evaluation and 30-min EIT recording in the supine position (SP), patients were randomised into one of two sequences: SP-aPP or aPP-SP. At the end of each 2-h step, oxygenation, respiratory rate, Borg scale and 30-min EIT were recorded. Results: 10 patients were randomised in each group. The GI index did not change in the SP-aPP group (baseline 74±20%, end of SP 78±23% and end of aPP 72±20%, p=0.85) or in the aPP-SP group (baseline 59±14%, end of aPP 59±15% and end of SP 54±13%, p=0.67). In the whole cohort, P aO2 :F IO2 increased from 133±44 mmHg at baseline to 183±66 mmHg in aPP (p=0.003) and decreased to 129±49 mmHg in SP (p=0.03). Conclusion: In spontaneously breathing nonintubated COVID-19 patients with ARF, aPP was not associated with a decrease of lung ventilation inhomogeneity assessed by EIT, despite an improvement in oxygenation.

High-level burnout in physicians and nurses working in adult ICUs: a systematic review and meta-analysis.

PURPOSE: The prevalence of burnout in intensive care unit (ICU) professionals is difficult to establish due to the variety of survey instruments used, the heterogeneity of the targeted population, the design of the studies, and the differences among countries regarding ICU organization. METHODS: We performed a systematic review and meta-analysis examining the prevalence of high-level burnout in physicians and nurses working in adult ICUs, including only studies that use the Maslach Burnout Inventory (MBI) as a tool to evaluate burnout and involving at least 3 different ICUs. RESULTS: Twenty-five studies with a combined population of 20,723 healthcare workers from adult ICUs satisfied the inclusion criteria. Combining 18 studies including 8187 ICU physicians, 3660 of them reported a high level of burnout (prevalence 0.41, range 0.15-0.71, 95% CI [0.33; 0.5], I2 97.6%, 95% CI [96.9%; 98.1%]). The heterogeneity can be at least in part explained by the definition of burnout used and the response rate as confirmed by the multivariable metaregression done. In contrast, there was no significant difference regarding other factors such as the study period (before or during the coronavirus disease 2019 (COVID-19) pandemic), the income of the countries, or the Healthcare Access and Quality (HAQ) index. Combining 20 studies including 12,536 ICU nurses, 6232 of nurses were reporting burnout (prevalence 0.44, range 0.14-0.74, [95% CI 0.34; 0.55], I2 98.6% 95% CI [98.4%; 98.9%]). The prevalence of high-level burnout in ICU nurses for studies performed during the COVID-19 pandemic was higher than that reported for studies performed before the COVID-19 pandemic (0.61 [95% CI, 0.46; 0.75] and 0.37 [95% CI, 0.26; 0.49] respectively, p = 0.003). As for physicians, the heterogeneity is at least in part explained by the definition used for burnout using the MBI but not by the number of participants. When compared, the prevalence of high-level burnout was not different between ICU physicians and ICU nurses. However, the proportion of ICU nurses with a high level of emotional exhaustion was higher than for ICU physicians (0.42 [95% CI, 0.37; 0.48] and 0.28 [0.2; 0.39], respectively, p = 0.022). CONCLUSION: According to this meta-analysis, the prevalence of high-level burnout is higher than 40% in all ICU professionals. However, there is a great heterogeneity in the results. To evaluate and to compare preventive and therapeutic strategies, there is the need to use a consensual definition of burnout when using the MBI instrument.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study.

BACKGROUND: Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. METHODS: We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. RESULTS: Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75-24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47-84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27-18.6)] as being independently associated with in-ICU mortality. CONCLUSIONS: SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

Incidence, Outcomes and Risk Factors of Recurrent Ventilator Associated Pneumonia in COVID-19 Patients: A Retrospective Multicenter Study.

Background: High incidence of ventilator associated pneumonia (VAP) has been reported in critically ill patients with COVID-19. Among these patients, we aimed to assess the incidence, outcomes and risk factors of VAP recurrences. Methods: We conducted an observational retrospective study in three French intensive care units (ICUs). Patients admitted for a documented COVID-19 from March 2020 to May 2021 and requiring mechanical ventilation (MV) for ≥48 h were included. The study main outcome was the incidence of VAP recurrences. Secondary outcomes were the duration of MV, ICU and hospital length of stay and mortality according to VAP and recurrences. We also assessed the factors associated with VAP recurrences. Results: During the study period, 398 patients met the inclusion criteria. A total of 236 (59%) of them had at least one VAP episode during their ICU stay and 109 (46%) of these patients developed at least one recurrence. The incidence of VAP recurrence considering death and extubation as competing events was 29.6% (IC = [0.250−0.343]). Seventy-eight percent of recurrences were due to the same bacteria (relapses). Patients with a VAP recurrence had a longer duration of MV as compared with one VAP and no VAP patients (41 (25−56) vs. 16 (8−30) and 10 (5−18) days; p < 0.001) and a longer ICU length of stay (46 (29−66) vs. 22 (12−36) and 14 (9−25) days; p < 0.001). The 90-day mortality was higher in the recurrence group as compared with the no VAP group only (31.2 vs. 21.0% (p = 0.021)). In a multivariate analysis including bacterial co-infection at admission, the use of immunosuppressive therapies and the bacteria responsible for the first VAP episode, the duration of MV was the only factor independently associated with VAP recurrence. Conclusion: In COVID-19 associated respiratory failure, recurrences affected 46% of patients with a first episode of VAP. VAP recurrences were mainly relapses and were associated with a prolonged duration of MV and ICU length of stay but not with a higher mortality. MV duration was the only factor associated with recurrences.

Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: a randomized controlled study.

BACKGROUND: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. METHODS: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). RESULTS: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). CONCLUSIONS: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www. CLINICALTRIALS: gov ( NCT03918603 ). Registered 17 April 2019.

Effects of a Chair Positioning Session on Awake Non-Intubated COVID-19 Pneumonia Patients: A Multicenter, Observational, and Pilot Study Using Lung Ultrasound.

BACKGROUND: LUS is a validated tool for the management of COVID-19 pneumonia. Chair positioning (CP) may have beneficial effects on oxygenation and lung aeration, and may be an easier alternative to PP. This study assessed the effects of a CP session on oxygenation and lung aeration (LA) changes in non-intubated COVID-19 patients. METHODS: A retrospective multicenter study was conducted in an ICU. We analyzed data from LUS exams and SpO2:FiO2 performed before/after a CP session in non-intubated COVID-19 patients. Patients were divided into groups of responders or non-responders in terms of oxygenation or LA. RESULTS: Thirty-three patients were included in the study; fourteen (44%) were oxygenation non-responders and eighteen (56%) were oxygenation responders, while thirteen (40.6%) and nineteen (59.4%) patients were classified as LA non-responders and responders, respectively. Changes in oxygenation and LA before/after a CP session were not correlated (r = -0.19, p = 0.3, 95% CI: -0.5-0.17). The reaeration scores did not differ between oxygenation responders and non-responders (1 (-0.75-3.75) vs. 4 (-1-6), p = 0.41). The LUS score was significantly correlated with SpO2:FiO2 before a CP session (r = 0.37, p = 0.04, 95% CI: 0.03-0.64) but not after (r = 0.17, p = 0.35, 95% CI: -0.19-0.50). CONCLUSION: A CP session was associated with improved oxygenation and LA in more than half of the non-intubated COVID-19 patients.

Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically Ill Patients with COVID-19.

Background: Acute kidney injury (AKI) is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe AKI in critically ill COVID-19 patients. Methods: In this cohort study, data from consecutive patients older than 18 years admitted to 6 ICUs for COVID-19-related ARDS requiring invasive mechanical ventilation were included. The incidence and severity of AKI, defined according to the 2012 KDIGO definition, were monitored during the entire ICU stay until day 90. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included. Results: 164 patients were included in the final analysis; 97 (59.1%) displayed AKI, of which 39 (23.8%) had severe stage 3 AKI, and 21 (12.8%) required renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with angiotensin-converting enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307−13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044−1.241), p = 0.003) and iNO (OR: 5.694 (1.953−16.606), p = 0.001). Prone positioning (OR: 0.234 (0.057−0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053−0.713), p = 0.014) were associated with a decreased risk of severe AKI. Conclusions: Dexamethasone was associated with the prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19-related ARDS.