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.

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.

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.

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.

Hypocalcemia-induced seizure with Fahr's syndrome.

INTRODUCTION: Fahr's syndrome is a rare but severe brain complication of hypoparathyroidism and its consequences. CASE PRESENTATION: A 72-year-old female patient was hospitalized in intensive care unit after two generalized seizures along with a severe hypocalcemia, due to hypoparathyroidism following a thyroidectomy for benign nodules and poor compliance with calcium treatment with treatment due to cognitive disorders. Brain CT showed cortical atrophy and extensive bilateral symmetrical calcifications of the cerebellum, thalami and basal ganglia, typical of Fahr's syndrome. CONCLUSION: Nephrologists should be aware Fahr's syndrome in patients with hypoparathyroidism, it is associated with an increased risk of seizures. Thus, the control of calcemia in hypoparathyroidism is important, especially in patients with brain calcifications.

Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves.

The demographics and outcomes of ICU patients admitted for a COVID-19 infection have been characterized in extensive reports, but little is known about antimicrobial stewardship for these patients. We designed this retrospective, observational study to investigate our hypothesis that the COVID-19 pandemic has disrupted antimicrobial stewardship practices and likely affected the rate of antibiotic de-escalation (ADE), patient outcomes, infection recurrence, and multidrug-resistant bacteria acquisition. We reviewed the prescription of antibiotics in three ICUs during the pandemic from March 2020 to December 2021. All COVID-19 patients with suspected or proven bacterial superinfections who received antibiotic treatment were included. The primary outcome was the rate of ADE, and secondary outcomes included the rate of appropriate empirical treatment, mortality rates and a comparison with a control group of infected patients before the COVID-19 pandemic. We included 170 COVID-19 patients who received antibiotic treatment for a suspected or proven superinfection, of whom 141 received an empirical treatment. For the latter, antibiotic treatment was de-escalated in 47 (33.3%) patients, escalated in 5 (3.5%) patients, and continued in 89 (63.1%) patients. The empirical antibiotic treatment was appropriate for 87.2% of cases. ICU, hospital, and day 28 and day 90 mortality rates were not associated with the antibiotic treatment strategy. The ADE rate was 52.2% in the control group and 27.6% in the COVID-19 group (p < 0.001). Our data suggest that empirical antibiotic treatment was appropriate in most cases. The ADE rates were lower in the COVID-19 group than in the control group, suggesting that the stress associated with COVID-19 affected our practices.

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.

Impact of obesity on survival in COVID-19 ARDS patients receiving ECMO: results from an ambispective observational cohort.

BACKGROUND: Since March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival. RESULTS: Between March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3-10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62-81), median PaCO2 of 58 mmHg (IQR 51-66) and a median arterial pH of 7.33 (IQR 7.25-7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644-0.934), p = 0.007) and 0.631 (0.462-0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004-1.285), p = 0.044 and 1.187 (1.035-1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance. CONCLUSION: In this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.

Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study.

BACKGROUND: Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. RESULTS: Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA-) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0-21) vs. 0 (0-11) days; p = 0.009) and a reduced ICU length of stay (20 (11-44) vs. 32 (17-46) days; p = 0.01). Mortality did not differ between groups. CONCLUSIONS: In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.