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.

Prevalence and Risk Factors for Thrombotic Complications Following Venovenous Extracorporeal Membrane Oxygenation: A CT Scan Study.

OBJECTIVES: The aims of this study were to: 1) analyze the cannula-associated deep vein thrombosis frequency after venovenous extracorporeal membrane oxygenation using a CT scan and 2) identify the associated risk factors for cannula-associated deep vein thrombosis. DESIGN: Retrospective observational analysis at a single center. SETTING: Tertiary referral university teaching hospital. PATIENTS: Patients under venovenous extracorporeal membrane oxygenation with a femorofemoral or femorojugular cannulation admitted for acute respiratory distress syndrome or primary graft dysfunction after pulmonary transplantation. CT scan was performed within 4 days after decannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 105 of 228 patients screened. Bacterial pneumonia was the main indication of venovenous extracorporeal membrane oxygenation (46.7%). CT scans were performed at a median of 2 days (1-3 d) after decannulation. Cannula-associated deep vein thrombosis was found in 75 patients (71.4%) despite it having a mean activated partial thromboplastin time ratio of 1.60 ± 0.31. Femorofemoral cannulation induced femoral cannula-associated deep vein thrombosis more frequently than femorojugular cannulation (69.2% vs 63.1%, respectively; p = 0.04). Seventeen of the 105 patients (16.2%) had a pulmonary embolism. Multivariate logistic regression analysis showed that higher the percentage of thrombocytopenia less than 100 G/L during extracorporeal membrane oxygenation period, lower the risk for developing cannula-associated deep vein thrombosis (hazard ratio, 0.98; 95% CI, 0.98-1.00; p = 0.02). CONCLUSIONS: Cannula-associated deep vein thrombosis after venovenous extracorporeal membrane oxygenation is a frequent complication. This plead for a systematic vascular axis imaging after venovenous extracorporeal membrane oxygenation. Thrombocytopenia is associated with a reduction in the occurrence of thrombotic events.

Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults.

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.

Influence of Shift Duration on Cognitive Performance of Emergency Physicians: A Prospective Cross-Sectional Study.

STUDY OBJECTIVE: The relationship between tiredness and medical errors is now commonly accepted. The main objective of this study is to evaluate the cognitive performance of emergency physicians after a night shift of 14 hours (H14) and after a work shift of 24 hours (H24) and to compare it with tests performed after a rest night at home (H0). METHODS: Forty emergency physicians (19 staff physicians and 21 residents) were randomly evaluated at H0, H14, and H24. Four cognitive abilities (processing speed, working memory capacity, perceptual reasoning, and cognitive flexibility) were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. RESULTS: No cognitive ability was significantly altered after H14 compared with H0. Three of 4 cognitive abilities were impaired at H24 compared with H0: processing speed (11.2 [SD 2.7] versus 12.4 [SD 3.2]; mean difference=-1.2 [95% confidence interval -1.9 to -0.5]), working memory capacity (10.1 [SD 2.9] versus 11.6 [SD 3.0]; mean difference=-1.5 [95% confidence interval -2.2 to -0.8]), and perceptual reasoning (8.4 [SD 2.7] versus 10.6 [SD 2.8]; mean difference=-2.2 [95% confidence interval -3.4 to -1.0]). Cognitive abilities were not different between residents and staff physicians (except for perceptual reasoning) and were not affected by the amount of sleep during the night shift. CONCLUSION: The cognitive abilities of emergency physicians were significantly altered after a 24-hour shift, whereas they were not significantly different from the rested condition after a 14-hour night shift. Limiting 24-hour shift work for emergency physicians should be considered and further evaluated.

High Prevalence of Mycoplasma faucium DNA in the Human Oropharynx.

Mycoplasma faucium has recently been associated with brain abscesses and seems to originate from the mouth. We evaluated its prevalence by quantitative real-time PCR (qPCR) in the oropharynxes of 644 subjects and found that 25% harbored M. faucium, probably constituting the gateway for entrance of the bacteria into cerebral abscesses.

Functional outcome of prolonged refractory status epilepticus.

INTRODUCTION: To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors. METHODS: Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome. RESULTS: 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04). CONCLUSION: Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

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.

Impaired virulence and fitness of a colistin-resistant clinical isolate of Acinetobacter baumannii in a rat model of pneumonia.

We compared the fitness and lung pathogenicity of two isogenic clinical isolates of Acinetobacter baumannii, one resistant (ABCR) and the other susceptible (ABCS) to colistin. In vitro, ABCR exhibited slower growth kinetics than ABCS. In a rat model of pneumonia, ABCR was associated with less pronounced signs of infection (lung bacterial count, systemic dissemination, and lung damage) and a better outcome (ABCR and ABCS mortality rates, 20 and 50%, respectively [P = 0.03]).

Neuromuscular blockers in early acute respiratory distress syndrome.

BACKGROUND: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial.

IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758.

Effects of ambient air pollutants on ARDS incidence and outcome: a narrative review.

BACKGROUND: Exposure to air pollutants promotes inflammation, cancer, and mortality in chronic diseases. Acute respiratory distress syndrome (ARDS) is a common condition among intensive care unit patients and is associated with a high mortality rate. ARDS is characterized by significant lung inflammation, which can be replicated in animal models by acute exposure to high doses of various air pollutants. Recently, several clinical studies have been conducted in different countries to investigate the role of chronic or acute air pollutant exposure in enhancing both ARDS incidence and severity. RESULTS: Chronic exposure studies have mainly been conducted in the US and France. The results of these studies suggest that some air pollutants, notably ozone, nitrogen dioxide, and particulate matter, increase susceptibility to ARDS and associated mortality. Furthermore, their impact may differ according to the cause of ARDS. A cohort study conducted in an urbanized zone in China showed that exposure to very high levels of air pollutants in the few days preceding intensive care unit admission was associated with an increased incidence of ARDS. The effects of acute exposure are more debatable regarding ARDS incidence and severity. CONCLUSION: There is a likely relationship between air pollutant exposure and ARDS incidence and severity. However, further studies are required to determine which pollutants are the most involved and which patients are the most affected. Due to the prevalence of ARDS, air pollutant exposure may have a significant impact and could be a key public health issue.

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.

[Tagravpa: Help table and grid for identifying the risk of aggravation and early rehospitalization of elderly persons 75 years and older referred to emergency departments and/or hospitalized in care units]. / Tagravpa : Tableau d'aide et grille de repérage du risque d'aggravation et de réhospitalisation précoce des personnes âgées de 75 ans et plus adressées aux urgences et/ou hospitalisées dans les unités de soins.

People aged 75 and over, frail or dependent are the most frequently hospitalized, particularly via the emergency department, and are sometimes readmitted to hospital less than a month after their discharge. Article 70 of the 2012 social security financing act has set up experiments aimed at improving the care pathway for the elderly. In this context, Marseille University Hospital has developed a table of help and grid for identifying the risk of aggravation of the elderly (Tagravpa). Comprising nine medical-psycho-social items, the grid enables the identification of the risk of aggravation to which is associated a score for identifying the risk of early re-hospitalization for the modeling of care pathways. A study was conducted in two departments. In cardiology for readmission at 1 month the results showed a grid positivity threshold of 6 for sensitivity measured at 56,6% (95% CI: 22,7-84,7) and specificity of 61,5% (95% CI: 40,7-79,1). In Emergency Department the results showed a positivity threshold of 4 for sensitivity at 83,3% (95% CI: 57,7-95,6) and specificity at 45,5% (95% CI: 36,8-54,3). This grid, called TAGRAVPA appears as a simple tool for identifying the risk of early re-hospitalization. It is applicable in a hospital environment, whatever the department and allows the initiation of an adapted path for the elderly person hospitalized or returning home from the emergency department.

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.

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.

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.

Right ventricular function during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of mean airway pressure under high-frequency oscillatory ventilation on right ventricular function. DESIGN: Prospective randomized study. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Sixteen consecutive patients within the first 48 hrs of mainly pulmonary acute respiratory distress syndrome. INTERVENTIONS: After a 6-hr-period of protective conventional mechanical ventilation, patients were submitted to three 1-hr periods of high-frequency oscillatory ventilation (+5, +10, +15) in a randomized order, with a mean airway pressure level determined by adding 5, 10, or 15 cm H2O to the mean airway pressure recorded during conventional mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Mean airway pressure was 18±3 cm H2O during conventional mechanical ventilation and was increased until 33±3 cm H2O at high-frequency oscillatory ventilation+15. Right ventricular function was assessed using transesophageal echocardiography. During conventional mechanical ventilation, nine patients presented a right ventricular dysfunction (right ventricular end-diastolic area/left ventricular end-diastolic area ratio>0.6) of whom four patients had a right ventricular failure (right ventricular end-diastolic area/left ventricular end-diastolic area ratio>0.9). High-frequency oscillatory ventilation+10 and +15 further worsened right ventricular function, resulting in about a 40% increase in right ventricular end-diastolic area/left ventricular end-diastolic area ratio and a 30% increase in end-diastolic eccentricity index when compared with conventional mechanical ventilation or high-frequency oscillatory ventilation+5 periods. At high-frequency oscillatory ventilation+15, 15 patients had right ventricular dysfunction and nine had right ventricular failure. High-frequency oscillatory ventilation did not improve oxygenation whatever the mean airway pressure level. A significant redistribution of tidal variation to the posterior parts of the lung was observed on electrical impedance tomography measurements when increasing mean airway pressure. However, this redistribution was not observed in patients who presented a worsening of right ventricular function (right ventricular end-diastolic area/left ventricular end-diastolic area increase>40%) at high-frequency oscillatory ventilation+15. CONCLUSIONS: In patients with mainly pulmonary acute respiratory distress syndrome, using high mean airway pressure under high-frequency oscillatory ventilation can worsen right ventricular function when compared with protective conventional mechanical ventilation, notably in patients in whom high-frequency oscillatory ventilation produced less alveolar recruitment of the posterior parts of the lungs. This study highlights the interest of monitoring right ventricular function during high-frequency oscillatory ventilation.

Interferon-γ production by natural killer cells and cytomegalovirus in critically ill patients.

OBJECTIVE: The mechanisms involved in cytomegalovirus reactivation in critically ill patients who were previously immunocompetent are still unknown. The current study was designed to evaluate the possible role of natural killer cells in the reactivation of cytomegalovirus in these patients. DESIGN: Prospective observational. SETTING: : A medical intensive care unit of a university hospital. PATIENTS: Fifty-one subjects, including 15 patients who experienced cytomegalovirus reactivation (cases) during their intensive care unit stay and 15 patients who matched intensive care unit controls, selected from a cohort of consecutive nonimmunocompromised intensive care unit patients, as well as healthy controls. INTERVENTIONS: Tests included weekly systematic immunomonitoring and routine screening for cytomegalovirus infection until discharge from the intensive care unit or death. The immunophenotype and functions of natural killer cells were performed by flow cytometry, and serum levels of pro- and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: The overall occurrence of cytomegalovirus reactivation in the cohort was 27%. No differences of natural killer cell effector functions were observed at admission between cases and controls. Instead, before cytomegalovirus reactivation, the ability of natural killer cells to secrete interferon-γ was significantly reduced in cases as compared with controls upon stimulation with antibody-coated target cells (p = .029) and with K562 cell stimulation (p = .029). No phenotypic or quantitative differences were observed between cases and controls. Cases exhibited higher levels of interleukin 10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus reactivation. CONCLUSIONS: Impaired natural killer cell function with reduced interferon-γ secretion precedes the occurrence of cytomegalovirus reactivation among previously immunocompetent critically ill patients.

Antibacterial efficacy of inhaled squalamine in a rat model of chronic Pseudomonas aeruginosa pneumonia.

OBJECTIVES: Squalamine is a steroid extracted from sharks with proven in vitro antibacterial activity. We assessed its efficacy in reducing the lung bacterial load and histological lesions when given via inhalation in a rat model of chronic Pseudomonas aeruginosa pneumonia. METHODS: Sprague-Dawley rats were inoculated by tracheal intubation with 150 µL of a solution containing 10(8) cfu/mL of agar bead-embedded P. aeruginosa strain PAO1. MICs of squalamine and colistin for this strain were 2-8 and 0.5-1 mg/L, respectively. Starting the day after infection, the animals were treated twice daily with aerosolized squalamine (3 mg), colistin (160 mg) or 0.9% saline for 6 days. The bacterial load and lung histological lesions were evaluated on the seventh day. RESULTS: Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (6 × 10(2)-2 × 10(3)), 10(3) (9 × 10(2)-6 × 10(3)) and 10(5) (9 × 10(4)-2 × 10(5)) cfu/lung, respectively; P < 0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups. CONCLUSIONS: In a model of chronic P. aeruginosa pneumonia, treatment twice daily with a squalamine aerosol for 6 days leads to a significant reduction in the pulmonary bacterial count and pneumonia lesions with an efficacy comparable to that of colistin.