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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.

Purpose To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures ( P L ). Methods A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P L and driving pressure, were assessed and compared. Delta P L (∆ P L ) was defined as inspiratory P L minus expiratory P L . Results Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ∆ P L related to NMBA administration. Conclusions NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts.

Background The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated. Methods A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. Results All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p  < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p  < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p  < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p  = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift. Conclusions The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients’ safety and physicians’ health should be further evaluated.

Purpose Patients with severe acute respiratory distress syndrome (ARDS) are candidates for extracorporeal membrane oxygenation (ECMO) therapy. The evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. This study was designed to identify early factors associated with hospital mortality in ARDS patients treated with ECMO and retrieved from referring hospitals. Methods Data from 85 consecutive ARDS patients equipped with ECMO by our mobile team and consequently admitted to our ICU were prospectively collected and analyzed. Results The main ARDS etiologies were community-acquired bacterial pneumonia (35 %), influenza pneumonia (23 %) (with 12 patients having been treated during the first half of the study period), and nosocomial pneumonia (14 %). The median (interquartile range) time between contact from the referring hospital and patient cannulation was 3 (1–4) h. ECMO was venovenous in 77 (91 %) patients. No complications occurred during transport by our mobile unit. Forty-eight patients died at the hospital (56 %). Based on a multivariate logistic regression, a score including age, SOFA score, and a diagnosis of influenza pneumonia was constructed. The probability of hospital mortality following ECMO initiation was 40 % in the 0–2 score class ( n  = 58) and 93 % in the 3–4 score class ( n  = 27). Patients with an influenza pneumonia diagnosis and a SOFA score before ECMO of less than 12 had a mortality rate of 22 %. Conclusions Age, SOFA score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ARDS patients considered for retrieval under ECMO from distant hospitals.

PurposeLittle is known on the incidence of discomfort during the end-of-life of intensive care unit (ICU) patients and the impact of sedation on such discomfort. The aim of this study was to assess the incidence of discomfort events according to levels of sedation.MethodsPost-hoc analysis of an observational prospective multicenter study comparing immediate extubation vs. terminal weaning for end-of-life in ICU patients. Discomforts including gasps, significant bronchial obstruction or high behavioural pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. Level of sedation was assessed using the Richmond Agitation–Sedation Scale (RASS) and deep sedation was considered for a RASS − 5. Psychological disorders in family members were assessed up until 12 months after the death.ResultsAmong the 450 patients included in the original study, 226 (50%) experienced discomfort after mechanical ventilation withdrawal. Patients with discomfort received lower doses of midazolam and equivalent morphine, and were less likely to have deep sedation than patients without discomfort (59% vs. 79%, p < 0.001). After multivariate logistic regression, extubation (as compared terminal weaning) was the only factor associated with discomfort, whereas deep sedation and administration of vasoactive drugs were two factors independently associated with no discomfort. Long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others.ConclusionDiscomfort was frequent during end-of-life of ICU patients and was mainly associated with extubation and less profound sedation.

Acute lung injury (ALI) is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC) on mechanical tension and barrier integrity in human alveolar epithelial cells (A549) exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml) or vehicle (control). Subsequently, thrombin (50 nM) or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

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.

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.