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Abstract Background Peripheral veno-arterial extracorporeal membrane oxygenation (pECMO) has become the first-line device in refractory cardiogenic shock (rCS). Some pECMO complications can preclude any bridging strategies and a peripheral-to-central ECMO (cECMO) switch can be considered as a bridge-to-decision. We conducted this study to appraise the in-hospital survival and the bridging strategies in patients undergoing peripheral-to-central ECMO switch. Methods This retrospective monocenter study included patients admitted to a ECMO-dedicated intensive care unit from February 2006 to January 2023. Patients with rCS requiring pECMO switched to cECMO were included. Patients were not included when the cECMO was the first mechanical circulatory support. Results Eighty patients, with a median [IQR25-75] age of 44 [29–53] years at admission and a female-to-male sex ratio of 0.6 were included in the study. Refractory pulmonary edema was the main switching reason. Thirty patients (38%) were successfully bridged to: heart transplantation (n = 16/80, 20%), recovery (n = 10/80, 12%) and ventricle assist device (VAD, n = 4/30, 5%) while the others died on cECMO (n = 50/80, 62%). The most frequent complications were the need for renal replacement therapy (76%), hemothorax or tamponade (48%), need for surgical revision (34%), mediastinitis (28%), and stroke (28%). The in-hospital and one-year survival rates were 31% and 27% respectively. Myocardial infarction as the cause of the rCS was the only variable independently associated with in-hospital mortality (HR 2.5 [1.3–4.9], p = 0.009). Conclusions The switch from a failing pECMO support to a cECMO as a bridge-to-decision is a possible strategy for a very selected population of young patients with a realistic chance of heart function recovery or heart transplantation. In this setting, cECMO allows patients triage preventing from wasting expensive and limited resources.

Abstract Background The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied. Methods Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. Results 292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84–1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. Conclusions Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.

Abstract Background By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion.

Abstract Objective To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence. Methods Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence. Results Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7–13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Abstract Background Venovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes. Methods Patients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound. Results Sixty-three patients were included after a median of 4 days (3–6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days). Conclusions Sixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing. ClinicalTrials.gov Identifier NCT04613752 (date of registration February 15, 2021).

Abstract Background Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. Methods This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for

Abstract Background Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). Methods Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. Results Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p

Abstract Background The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. Objectives To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. Methods The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel’s questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. Results In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. Conclusion Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Abstract 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.

Abstract Background Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a randomized trial with observational data. Methods All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitié-Salpêtrière Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confounding at baseline. Results Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR = 0.91, [0.57; 1.45], p = 0.659 in multivariable analysis), or 30-day mortality (OR = 1.03, [0.52; 2.03], p = 0.940) and 1-year mortality (OR = 1.00, [0.53; 1.89], p = 0.999). Conclusions Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan.

Abstract Aims Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the ‘optimal’ flow. We aimed to describe the evolution of VA‐ECMO flows in a cardiogenic shock population and determine the risk factors of ‘high‐ECMO flow’. Methods and results A 7 year database of patients supported with VA‐ECMO was used. Based on the median flow during the first 48 h of the VA‐ECMO run, patients were classified as ‘high‐flow’ or ‘low‐flow’, respectively, when median ECMO flow was ≥3.6 or

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an established rescue therapy in the management of refractory acute respiratory distress syndrome (ARDS). Although ECMO played an important role in previous respiratory viral epidemics, concerns about the benefits and usefulness of this technique were raised during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the mortality rate initially reported in small case series from China was concerning and exceeded 90%. A few months later, the critical care community published the findings from several observational cohorts on the use of extracorporeal membrane oxygenation (ECMO) in COVID-19-related ARDS. Contrary to the preliminary results, data from the first surge supported the use of ECMO in experienced centers because the mortality rate was comparable to those from the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial or other large prospective studies. However, the mortality rate of the population with severe disease evolved during the pandemic, in conjunction with changes in the management of the disease and the occurrence of new variants. The results from subsequent studies confirmed that the outcomes mainly depend on strict patient selection and center expertise. In comparison with non-COVID-related ARDS, the duration of ECMO for COVID-related ARDS was longer and increased over time. Clinicians and decision-makers must integrate this finding in the ECMO decision-making process to plan their ICU capacity and resource allocation. This narrative review summarizes the current evidence and specific considerations for ECMO use in COVID-19-associated ARDS.

Abstract Introduction Studies regarding coronavirus disease 2019 (COVID-19) were mainly performed in the initial wave, but some small-scale data points to prognostic differences for patients in successive waves. We therefore aimed to study the impact of time on prognosis of ICU-admitted COVID-19 patients. Method We performed a national retrospective cohort study, including all adult patients hospitalized in French ICUs from March 1, 2020 to June 30, 2021, and identified three surge periods. Primary and secondary outcomes were in-hospital mortality and need for invasive mechanical ventilation, respectively. Results 105,979 critically ill ICU-admitted COVID-19 patients were allocated to the relevant three surge periods. In-hospital mortality for surges 1, 2, and 3 was, respectively, 24%, 27%, and 24%. Invasive mechanical ventilation was the highest level of respiratory support for 42%, 32%, and 31% (p

Abstract Background Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. Methods We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. Results Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70–0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50–86], specificity of 85% [55–98], a negative predictive value of 58% [36–93] and a positive predictive value 90% [67–96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12–0.75], p = 0.01). Conclusion In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

Abstract Purpose This scoping review aims to identify and describe knowledge gaps and research priorities in veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods An expert panel was recruited consisting of eight international experts from different backgrounds. First, a list of priority topics was made. Second, the panel developed structured questions using population, intervention, comparison and outcomes (PICO) format. All PICOs were scored and prioritized. For every selected PICO, a structured literature search was performed. Results After an initial list of 49 topics, eight were scored as high-priority. For most of these selected topics, current literature is limited to observational studies, mainly consisting of retrospective cohorts. Only for ECPR and anticoagulation, randomized controlled trials (RCTs) have been performed or are ongoing. Per topic, a summary of the literature is stated including recommendations for further research. Conclusions This scoping review identifies and presents an overview of knowledge gaps and research priorities in VA-ECMO. Current literature is mostly limited to observational studies, although with increasing attention for this patient population, more RCTs are finishing or ongoing. Translational research, from preclinical trials to high-quality or randomized controlled trials, is important to improve the standard practices in this critically ill patient population. Take-home message This scoping review identifies and presents an overview of research gaps and priorities in VA-ECMO. Translational research, from preclinical trials to high-quality or randomized controlled trials, is important to improve the standard practices in this critically ill patient population.

Abstract Background Although rarely addressed in the literature, a key question in the care of critically pregnant women with severe acute respiratory distress syndrome (ARDS), especially at the time of extracorporeal membrane oxygenation (ECMO) decision, is whether delivery might substantially improve the mother’s and child’s conditions. This multicenter, retrospective cohort aims to report maternal and fetal short- and long-term outcomes of pregnant women with ECMO-rescued severe ARDS according to the timing of the delivery decision taken before or after ECMO cannulation. Methods We included critically ill women with ongoing pregnancy or within 15 days after a maternal/child-rescue-aimed delivery supported by ECMO for a severe ARDS between October 2009 and August 2021 in four ECMO centers. Clinical characteristics, critical care management, complications, and hospital discharge status for both mothers and children were collected. Long-term outcomes and premature birth complications were assessed. Results Among 563 women on venovenous ECMO during the study period, 11 were cannulated during an ongoing pregnancy at a median (range) of 25 (21–29) gestational weeks, and 13 after an emergency delivery performed at 32 (17–39) weeks of gestation. Pre-ECMO PaO2/FiO2 ratio was 57 (26–98) and did not differ between the two groups. Patients on ECMO after delivery reported more major bleeding (46 vs. 18%, p = 0.05) than those with ongoing pregnancy. Overall, the maternal hospital survival was 88%, which was not different between the two groups. Four (36%) of pregnant women had a spontaneous expulsion on ECMO, and fetal survival was higher when ECMO was set after delivery (92% vs. 55%, p = 0.03). Among newborns alive, no severe preterm morbidity or long-term sequelae were reported. Conclusion Continuation of the pregnancy on ECMO support carries a significant risk of fetal death while improving prematurity-related morbidity in alive newborns with no difference in maternal outcomes. Decisions regarding timing, place, and mode of delivery should be taken and regularly (re)assess by a multidisciplinary team in experienced ECMO centers.

Abstract Background Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. Methods Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. Results Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. Conclusions HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Introduction Delirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate objective assessment of the pupillary light responses in comatose patients in the intensive care unit (ICU). Whether automated pupillometry might predict delirium in critically ill patients is not known. We hypothesise that automated pupillometry could predict the occurrence of delirium in critically ill patients without primary brain injury, requiring more than 48 hours of invasive mechanical ventilation in the ICU.Methods and analysis The PupillOmetry for preDIction of DeliriUM in ICU (PODIUM) study is a prospective cohort study, which will be conducted in eight French ICUs in the Paris area. We aim to recruit 213 adult patients requiring invasive mechanical ventilation for more than 48 hours. Automated pupillometry (Neurological Pupil Index; NPi-200, Neuroptics) will be assessed two times per day for 7 days. Delirium will be assessed using the Confusion Assessment Method in ICU two times per day over 14 days in non-comatose patients (Richmond Agitation and Sedation Scale ≥−3).The predictive performances of the seven automated pupillometry parameters (ie, pupillary diameter, variation of the pupillary diameter, pupillary constriction speed, pupillary dilatation speed, photomotor reflex latency, NPi and symmetry of pupillary responses) measured to detect the delirium occurrence within 14 days will be the main outcomes. Secondary outcomes will be the predictive performances of the seven automated pupillometry parameters to detect complications related to delirium, ICU length of stay, mortality, functional and cognitive outcomes at 90 days.Ethics and dissemination The PODIUM study has been approved by an independent ethics committee, the Comité de Protection des Personnes (CPP) OUEST IV—NANTES (CPP21.02.15.45239 32/21_3) on 06 April 2021). Participant recruitment started on 15 April 2022. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT05248035; clinicaltrials.gov.

Abstract With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28–42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk. Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Abstract Background Amniotic fluid embolism (AFE) is a rare but often catastrophic complication of pregnancy that leads to cardiopulmonary dysfunction and severe disseminated intravascular coagulopathy (DIC). Although few case reports have reported successful use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) with AFE, concerns can be raised about the increased bleeding risks with that device. Methods This study included patients with AFE rescued by VA-ECMO hospitalized in two high ECMO volume centers between August 2008 and February 2021. Clinical characteristics, critical care management, in-intensive care unit (ICU) complications, and hospital outcomes were collected. ICU survivors were assessed for health-related quality of life (HRQL) in May 2021. Results During that 13-year study period, VA-ECMO was initiated in 54 parturient women in two high ECMO volume centers. Among that population, 10 patients with AFE [median (range) age 33 (24–40), SAPS II at 69 (56–81)] who fulfilled our diagnosis criteria were treated with VA-ECMO. Pregnancy evolved for 36 (30–41) weeks. Seven patients had a cardiac arrest before ECMO and two were cannulated under cardiopulmonary resuscitation. Pre-ECMO hemodynamic was severely impaired with an inotrope score at 370 (55–1530) μg/kg/min, a severe left ventricular ejection fraction measured at 14 (0–40)%, and lactate at 12 (2–30) mmol/L. 70% of these patients were alive at hospital discharge despite an extreme pre-ECMO severity and massive blood product transfusion. However, HRQL was lower than age-matched controls and still profoundly impaired in the role-physical, bodily pain, and general health components after a median of 44 months follow-up. Conclusion In this rare per-delivery complication, our results support the use of VA-ECMO despite intense DIC and ongoing bleeding. Future studies should focus on customized, patient-centered, rehabilitation programs that could lead to improved HRQL in this population.

Abstract Background Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. Methods We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to “conventional” ECMO management (Supine group) in patients with severe ARDS. Results 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42–1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). Conclusions In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Background and Aims: Apolipoprotein A1 (A1) and haptoglobin (HP) serum levels are associated with the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have constructed and validated a multivariable risk calculator (A1HPV6) integrating A1, HP, alpha2-macroglobulin, and gamma glutamyl transferase to improve the performances of virological biomarkers. Methods: In a prospective observational study of hospitalized patients with nonsevere SARS-CoV-2 infection, A1HPV6 was constructed in 127 patients and validated in 116. The specificity was assessed in 7482 controls representing the general population. The primary diagnostic endpoint was the area under the receiver operating characteristic curve in patients with positive SARS-CoV-2 PCR. The primary prognostic endpoint was the age-and-sex adjusted risk of A1HPV6 to predict patients with WHO-stage > 4 (W > 4) severity. We assessed the kinetics of the A1HPV6 components in a nonhuman primate model (NHP), from baseline to 7 days (D7) after SARS-CoV-2 infection. Results: The area under the receiver operating characteristic curve for A1HPV6 was 0.99 (95% CI 0.97–0.99) in the validation subset, which was not significantly different from that in the construction subset, 0.99 (0.99–0.99; P = .80), like for sensitivity 92% (85–96) vs 94% (88–97; P = .29). A1HPV6 was associated with W > 4, with a significant odds ratio of 1.3 (1.1–1.5; 0.002). In NHP, A1 levels decreased (P < .01) at D2 and normalized at D4; HP levels increased at D2 and peaked at D4. In patients, A1 concentration was very low at D2 vs controls (P < .01) and increased at D14 (P < .01) but was still lower than controls; HP increased at D2 and remained elevated at D14. Conclusion: These results validate the diagnostic and prognostic performances of A1HPV6. Similar kinetics of apolipoprotein A1, HP, and alpha-2-macroglobulin were observed in the NHP model. ClinicalTrials.gov number, NCT01927133.

Abstract Background Predicting outcomes of critically ill intensive care unit (ICU) patients with coronavirus-19 disease (COVID-19) is a major challenge to avoid futile, and prolonged ICU stays. Methods The objective was to develop predictive survival models for patients with COVID-19 after 1-to-2 weeks in ICU. Based on the COVID–ICU cohort, which prospectively collected characteristics, management, and outcomes of critically ill patients with COVID-19. Machine learning was used to develop dynamic, clinically useful models able to predict 90-day mortality using ICU data collected on day (D) 1, D7 or D14. Results Survival of Severely Ill COVID (SOSIC)-1, SOSIC-7, and SOSIC-14 scores were constructed with 4244, 2877, and 1349 patients, respectively, randomly assigned to development or test datasets. The three models selected 15 ICU-entry variables recorded on D1, D7, or D14. Cardiovascular, renal, and pulmonary functions on prediction D7 or D14 were among the most heavily weighted inputs for both models. For the test dataset, SOSIC-7’s area under the ROC curve was slightly higher (0.80 [0.74–0.86]) than those for SOSIC-1 (0.76 [0.71–0.81]) and SOSIC-14 (0.76 [0.68–0.83]). Similarly, SOSIC-1 and SOSIC-7 had excellent calibration curves, with similar Brier scores for the three models. Conclusion The SOSIC scores showed that entering 15 to 27 baseline and dynamic clinical parameters into an automatable XGBoost algorithm can potentially accurately predict the likely 90-day mortality post-ICU admission (sosic.shinyapps.io/shiny). Although external SOSIC-score validation is still needed, it is an additional tool to strengthen decisions about life-sustaining treatments and informing family members of likely prognosis.

Abstract Background Extracorporeal membrane oxygenation (ECMO) was frequently used to treat patients with severe coronavirus disease-2019 (COVID-19)-associated acute respiratory distress (ARDS) during the initial outbreak. Care of COVID-19 patients evolved markedly during the second part of 2020. Our objective was to compare the characteristics and outcomes of patients who received ECMO for severe COVID-19 ARDS before or after July 1, 2020. Methods We included consecutive adults diagnosed with COVID-19 in Paris–Sorbonne University Hospital Network ICUs, who received ECMO for severe ARDS until January 28, 2021. Characteristics and survival probabilities over time were estimated during the first and second waves. Pre-ECMO risk factors predicting 90-day mortality were assessed using multivariate Cox regression. Results Characteristics of the 88 and 71 patients admitted, respectively, before and after July 1, 2020, were comparable except for older age, more frequent use of dexamethasone (18% vs. 82%), high-flow nasal oxygenation (19% vs. 82%) and/or non-invasive ventilation (7% vs. 37%) after July 1. Respective estimated probabilities (95% confidence intervals) of 90-day mortality were 36% (27–47%) and 48% (37–60%) during the first and the second periods. After adjusting for confounders, probability of 90-day mortality was significantly higher for patients treated after July 1 (HR 2.27, 95% CI 1.02–5.07). ECMO-related complications did not differ between study periods. Conclusions 90-day mortality of ECMO-supported COVID-19–ARDS patients increased significantly after July 1, 2020, and was no longer comparable to that of non-COVID ECMO-treated patients. Failure of prolonged non-invasive oxygenation strategies before intubation and increased lung damage may partly explain this outcome.

Abstract Background Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. Methods International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. Results Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p

Abstract Background While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival. Methods We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. Data synthesis We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%–50.1%). Survival among patients with left ventricular ejection fraction (LVEF) 35% (32.1%, 95%-CI: 8.69%–60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%–26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%–73.0%) and North America (45.5%, 95%-CI: 16.7%–75.8%). GRADE assessment indicated high certainty of evidence for pooled survival. Conclusions When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.

Abstract Purpose At the critical care level, the flu surveillance system is limited in France, with heterogeneous regional modalities of implementation. Materials, patients and methods We aimed at assessing the relevance of the Assistance Publique-Hôpitaux de Paris (AP-HP) clinical data warehouse for estimating the burden of the influenza epidemic on medical adult critical care units of the AP-HP, and outcome of patients during the flu season 2017–2018. This exploratory multi-site epidemiological study comprised all consecutive adult stays (n = 320) in 18 medical intensive care units (ICU) or intermediate care wards (ICW) for probable or confirmed Influenza virus infection during the 2017–2018 flu season. Results Patients admitted to ICU/ICW had low vaccination coverage (21%), required life support in 60% of cases, stayed in the ICU for a median of 8 days, and had high 28-day mortality rate (19.7%; 95% confidence interval 15.5–24.5). Early prognostic factors included age, core temperature, the acute organ failures score, and the early administration of antiviral therapy. Conclusions Data directly extracted from the electronic medical records stored in the data warehouse provide detailed clinical, care pathway and prognosis information. The real-time availability should enable to detect and assess the burden of the most severe cases. By a firmer and more acute monitoring and adjustment of care and patient management, hospitals could generate more ICU/ICW capacities, sensitize their emergency department and contribute to the recommendations from health authorities. This pilot study is of particular relevance in the context of emerging epidemics of severe acute respiratory diseases.

Abstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO2/FiO2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO2/FiO2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p

Abstract Background Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can require intensive care unit (ICU) admission because of multiorgan involvement with end-organ failure(s). Critically ill SRD patients requiring extracorporeal membrane oxygenation (ECMO) were studied to gain insight into their characteristics and outcomes. Methods This French monocenter, retrospective study included all SRD patients requiring venovenous (VV)- or venoarterial (VA)-ECMO admitted to a 26-bed ECMO-dedicated ICU from January 2006 to February 2020. The primary endpoint was in-hospital mortality. Results Ninety patients (male/female ratio: 0.5; mean age at admission: 41.6 ± 15.2 years) admitted to the ICU received VA/VV-ECMO, respectively, for an SRD-related flare (n = 69, n = 38/31) or infection (n = 21, n = 10/11). SRD was diagnosed in-ICU for 31 (34.4%) patients. In-ICU and in-hospital mortality rates were 48.9 and 51.1%, respectively. Nine patients were bridged to cardiac (n = 5) or lung transplantation (n = 4), or left ventricular assist device (n = 2). The Cox multivariable model retained the following independent predictors of in-hospital mortality: in-ICU SRD diagnosis, day-0 Simplified Acute Physiology Score (SAPS) II score ≥ 70 and arterial lactate ≥ 7.5 mmol/L for VA-ECMO–treated patients; diagnosis other than vasculitis, day-0 SAPS II score ≥ 70, ventilator-associated pneumonia and arterial lactate ≥ 7.5 mmol/L for VV-ECMO–treated patients. Conclusions ECMO support is a relevant rescue technique for critically ill SRD patients, with 49% survival at hospital discharge. Vasculitis was independently associated with favorable outcomes of VV-ECMO–treated patients. Further studies are needed to specify the role of ECMO for SRD patients.

Abstract Background With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO2 removal (ECCO2R). However, current evidence in these indications is limited. A European ECCO2R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. Methods A modified Delphi-based method was used to collate European experts’ views to better understand how ECCO2R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. Results Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO2R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO2R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO2R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO2 levels. Driving pressure (≥ 14 cmH2O) followed by plateau pressure (P plat; ≥ 25 cmH2O) was considered the most important criteria for ECCO2R initiation. Key treatment targets for patients with ARDS undergoing ECCO2R included pH (> 7.30), respiratory rate ( 7.30–7.35), respiratory rate (

Abstract The use of extracorporeal cardiopulmonary resuscitation (ECPR) to restore circulation during cardiac arrest is a time-critical, resource-intensive intervention of unproven efficacy. The current COVID-19 pandemic has brought additional complexity and significant barriers to the ongoing provision and implementation of ECPR services. The logistics of patient selection, expedient cannulation, healthcare worker safety, and post-resuscitation care must be weighed against the ethical considerations of providing an intervention of contentious benefit at a time when critical care resources are being overwhelmed by pandemic demand.

Abstract Background The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR–based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4–5 h. We performed this study to evaluate the concordance between the multiplex PCR–based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP. Methods All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared. Results Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa. Conclusions Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa.

Abstract Objectives Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to treat patients with refractory severe heart failure. Large animal models are developed to help understand physiology and build translational research projects. In order to better understand those experimental models, we conducted a systematic literature review of animal models combining heart failure and VA-ECMO. Studies selection A systematic review was performed using Medline via PubMed, EMBASE, and Web of Science, from January 1996 to January 2019. Animal models combining experimental acute heart failure and ECMO were included. Clinical studies, abstracts, and studies not employing VA-ECMO were excluded. Data extraction Following variables were extracted, relating to four key features: (1) study design, (2) animals and their peri-experimental care, (3) heart failure models and characteristics, and (4) ECMO characteristics and management. Results Nineteen models of heart failure and VA-ECMO were included in this review. All were performed in large animals, the majority (n = 13) in pigs. Acute myocardial infarction (n = 11) with left anterior descending coronary ligation (n = 9) was the commonest mean of inducing heart failure. Most models employed peripheral VA-ECMO (n = 14) with limited reporting. Conclusion Among models that combined severe heart failure and VA-ECMO, there is a large heterogeneity in both design and reporting, as well as methods employed for heart failure. There is a need for standardization of reporting and minimum dataset to ensure translational research achieve high-quality standards.

Abstract Background Prone positioning (PP) during veno-venous ECMO is feasible, but its physiological effects have never been thoroughly evaluated. Our objectives were to describe, through electrical impedance tomography (EIT), the impact of PP on global and regional ventilation, and optimal PEEP level. Methods A monocentric study conducted on ECMO-supported severe ARDS patients, ventilated in pressure-controlled mode, with 14-cmH2O driving pressure and EIT-based “optimal PEEP”. Before, during and after a 16-h PP session, EIT-based distribution and variation of tidal impedance, VTdorsal/VTglobal ratio, end-expiratory lung impedance (EELI) and static compliance were collected. Subgroup analyses were performed in patients who increased their static compliance by ≥ 3 mL/cmH2O after 16 h of PP. Results For all patients (n = 21), tidal volume and EELI were redistributed from ventral to dorsal regions during PP. EIT-based optimal PEEP was significantly lower in PP than in supine position. Median (IQR) optimal PEEP decreased from 14 (12–16) to 10 (8–14) cmH2O. Thirteen (62%) patients increased their static compliance by ≥ 3 mL/cmH2O after PP on ECMO. This subgroup had higher body mass index, more frequent viral pneumonia, shorter ECMO duration, and lower baseline VTdorsal/VTglobal ratio than patients with compliance ≤ 3 mL/cmH2O (P

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.

Background: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial.Methods: PCR-positive in- and outpatients with symptomatic COVID-19 from a large French University hospital were systematically interviewed for their smoking status, use of e-cigarette, and nicotinic substitutes. The rates of daily smokers in in- and outpatients were compared using the same smoking habit questionnaire to those in the 2019 French general population, after standardisation for sex and age.Results: The inpatient group was composed of 340 patients, median age of 66 years: 203 men (59.7%) and 137 women (40.3%), median age of both 66 years, with a rate of 4.1% daily smokers (CI 95% [2.3–6.9]) (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age of 44 years: 62 men (44.6%, median age of 43 years) and 77 women (55.4%, median age of 44 years). The daily smoker rate was 6.1% (CI 95% [2.7–11.6], 5.1% of men and 6.8% of women). Amongst inpatients, daily smokers represented 2.2 and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in patients with symptomatic COVID-19, as compared to that in the French general population after standardisation by age and sex, with standardised incidence ratios (SIRs) of 0.24 [0.12–0.48] for outpatients and 0.24 [0.14–0.40] for inpatients.Conclusions: Daily smoker rate in patients with symptomatic COVID-19 is lower as compared to the French general population

Abstract Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.

Abstract Fifteen recommendations and a therapeutic algorithm regarding the management of acute respiratory distress syndrome (ARDS) at the early phase in adults are proposed. The Grade of Recommendation Assessment, Development and Evaluation (GRADE) methodology has been followed. Four recommendations (low tidal volume, plateau pressure limitation, no oscillatory ventilation, and prone position) had a high level of proof (GRADE 1 + or 1 −); four (high positive end-expiratory pressure [PEEP] in moderate and severe ARDS, muscle relaxants, recruitment maneuvers, and venovenous extracorporeal membrane oxygenation [ECMO]) a low level of proof (GRADE 2 + or 2 −); seven (surveillance, tidal volume for non ARDS mechanically ventilated patients, tidal volume limitation in the presence of low plateau pressure, PEEP > 5 cmH2O, high PEEP in the absence of deleterious effect, pressure mode allowing spontaneous ventilation after the acute phase, and nitric oxide) corresponded to a level of proof that did not allow use of the GRADE classification and were expert opinions. Lastly, for three aspects of ARDS management (driving pressure, early spontaneous ventilation, and extracorporeal carbon dioxide removal), the experts concluded that no sound recommendation was possible given current knowledge. The recommendations and the therapeutic algorithm were approved by the experts with strong agreement.

Abstract Objectives Extracorporeal membrane oxygenation (ECMO) is an increasingly accepted means of supporting those with severe acute respiratory distress syndrome (ARDS). Given the high mortality associated with ARDS, numerous animal models have been developed to support translational research. Where ARDS is combined with ECMO, models are less well characterized. Therefore, we conducted a systematic literature review of animal models combining features of experimental ARDS with ECMO to better understand this situation. Data sources MEDLINE and Embase were searched between January 1996 and December 2018. Study selection Inclusion criteria: animal models combining features of experimental ARDS with ECMO. Exclusion criteria: clinical studies, abstracts, studies in which the model of ARDS and ECMO has been reported previously, and studies not employing veno-venous, veno-arterial, or central ECMO. Data extraction Data were extracted to fully characterize models. Variables related to four key features: (1) study design, (2) animals and their peri-experimental care, (3) models of ARDS and mechanical ventilation, and (4) ECMO and its intra-experimental management. Data synthesis Seventeen models of ARDS and ECMO were identified. Twelve were published after 2009. All were performed in large animals, the majority (n = 10) in pigs. The median number of animals included in each study was 17 (12–24), with a median study duration of 8 h (5–24). Oleic acid infusion was the commonest means of inducing ARDS. Most models employed peripheral veno-venous ECMO (n = 12). The reporting of supportive measures and the practice of mechanical ventilation were highly variable. Descriptions of ECMO equipment and its management were more complete. Conclusion A limited number of models combine the features of experimental ARDS with ECMO. Among those that do, there is significant heterogeneity in both design and reporting. There is a need to standardize the reporting of pre-clinical studies in this area and to develop best practice in their design.

Abstract Background Structural neurological complications (ischemic stroke and intracranial bleeding) and their risk factors in patients receiving venoarterial-extracorporeal membrane oxygenation (VA-ECMO) are poorly described. Our objective was to describe frequencies, outcomes and risk factors for neurological complications (ischemic stroke and intracranial bleeding) in patients receiving VA-ECMO. Methods Retrospective observational study conducted, from 2006 to 2014, in a tertiary referral center on patients who developed a neurological complication(s) on VA-ECMO. Results Among 878 VA-ECMO-treated patients, 65 (7.4%) developed an ECMO-related brain injury: 42 (5.3%) ischemic strokes and 20 (2.8%) intracranial bleeding, occurring after a median [25th;75th percentile] of 11 [6;18] and 5 [2;9] days of support, respectively. Intracranial bleeding but not ischemic stroke was associated with higher mortality. Multivariable analysis retained only platelet level > 350 giga/L as being associated with ischemic stroke. Female sex, central VA-ECMO and platelets

Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03573739.

Abstract Background Amikacin infusion requires targeting a peak serum concentration (Cmax) 8–10 times the minimal inhibitory concentration, corresponding to a Cmax of 60–80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin Cmax in critically ill patients on ECMO and to identify relative risk factors. Methods This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and Cmax was measured 30 min after the end of the infusion. Independent predicators of Cmax

Abstract Background Extracorporeal carbon-dioxide removal (ECCO2R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) ( 20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, Pplat and driving pressure, arterial blood gases, and ECCO2R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO2R and mechanical ventilation were also recorded. Results While VT was reduced from 6 to 4 ml/kg and Pplat kept

Abstract Background Despite quick implementation of reperfusion therapies, a few patients with high-risk, acute, massive, pulmonary embolism (PE) remain highly hemodynamically unstable. Others have absolute contraindication to receive reperfusion therapies. Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) might lower their right ventricular overload, improve hemodynamic status, and restore tissue oxygenation. Methods ECMO-related complications and 90-day mortality were analyzed for 17 highly unstable, ECMO-treated, massive PE patients admitted to a tertiary-care center (2006–2015). Hospital- discharge survivors were assessed for long-term health-related quality of life. A systematic review of this topic was also conducted. Results Seventeen high-risk PE patients [median age 51 (range 18–70) years, Simplified Acute Physiology Score II (SAPS II) 78 (45–95)] were placed on VA-ECMO for 4 (1–12) days. Among 15 (82%) patients with pre-ECMO cardiac arrest, seven (41%) were cannulated during cardiopulmonary resuscitation, and eight (47%) underwent pre-ECMO thrombolysis. Pre-ECMO median blood pressure, pH, and blood lactate were, respectively: 42 (0–106) mmHg, 6.99 (6.54–7.37) and 13 (4–19) mmol/L. Ninety-day survival was 47%. Fifteen (88%) patients suffered in-ICU severe hemorrhages with no impact on survival. Like other ECMO-treated patients, ours reported limitations of all physical domains but preserved mental health 19 (4–69) months post-ICU discharge. Conclusions VA-ECMO could be a lifesaving rescue therapy for patients with high-risk, acute, massive PE when thrombolytic therapy fails or the patient is too sick to benefit from surgical thrombectomy. Because heparin-induced clot dissolution and spontaneous fibrinolysis allows ECMO weaning within several days, future studies should investigate whether VA-ECMO should be the sole therapy or completed by additional mechanical clot-removal therapies in this setting.