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Purpose of reviewCoronavirus disease 2019 (COVID-19) pandemic changed the way we had to approach hospital- and intensive care unit (ICU)-related resource management, especially for demanding techniques required for advanced support, including extracorporeal membrane oxygenation (ECMO).Recent findingsAvailability of ICU beds and ECMO machines widely varies around the world. In critical conditions, such a global pandemic, the establishment of contingency capacity tiers might help in defining to which conditions and subjects ECMO can be offered. A frequent reassessment of the resource saturation, possibly integrated within a regional healthcare coordination system, may be of help to triage the patients who most likely will benefit from advanced techniques, especially when capacities are limited.SummaryIndications to ECMO during the pandemic should be fluid and may be adjusted over time. Candidacy of patients should follow the same prepandemic rules, taking into account the acute disease, the burden of any eventual comorbidity and the chances of a good quality of life after recovery; but the current capacity of healthcare system should also be considered, and frequently reassessed, possibly within a wide hub-and-spoke healthcare system.

Purpose of reviewCoronavirus disease 2019 (COVID-19) pandemic changed the way we had to approach hospital- and intensive care unit (ICU)-related resource management, especially for demanding techniques required for advanced support, including extracorporeal membrane oxygenation (ECMO).Recent findingsAvailability of ICU beds and ECMO machines widely varies around the world. In critical conditions, such a global pandemic, the establishment of contingency capacity tiers might help in defining to which conditions and subjects ECMO can be offered. A frequent reassessment of the resource saturation, possibly integrated within a regional healthcare coordination system, may be of help to triage the patients who most likely will benefit from advanced techniques, especially when capacities are limited.SummaryIndications to ECMO during the pandemic should be fluid and may be adjusted over time. Candidacy of patients should follow the same prepandemic rules, taking into account the acute disease, the burden of any eventual comorbidity and the chances of a good quality of life after recovery; but the current capacity of healthcare system should also be considered, and frequently reassessed, possibly within a wide hub-and-spoke healthcare system.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS).METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398).FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome.INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

BackgroundThe optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS).MethodsWe searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month’s duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398).FindingsOf 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI −2.15 to 3.38); p=0.68), PaO2 (−0.00 mm Hg (95% CI −4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI −0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome.InterpretationOronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

Disclaimer:This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

OBJECTIVES: Data about inhospital outcomes in bleeding complications during extracorporeal life support (ECLS) have been poorly investigated.DESIGN: Retrospective observational study.SETTING: Patients reported in Extracorporeal Life Support Organization Registry.PATIENTS: Data of 53.644 adult patients (greater than or equal to 18 yr old) mean age 51.4 ± 15.9 years, 33.859 (64.5%) male supported with single ECLS run between 01.01.2000 and 31.03.2020, and 19.748 cannulated for venovenous (V-V) ECLS and 30.696 for venoarterial (V-A) ECLS.INTERVENTIONS: Trends in bleeding complications, bleeding risk factors, and mortality.MEASUREMENT AND MAIN RESULTS: Bleeding complications were reported in 14.786 patients (27.6%), more often in V-A ECLS compared with V-V (30.0% vs 21.9%; p < 0.001). Hospital survival in those who developed bleeding complications was lower in both V-V ECLS (49.6% vs 66.6%; p < 0.001) and V-A ECLS (33.9 vs 44.9%; p < 0.001). Steady decrease in bleeding complications in V-V and V-A ECLS was observed over the past 20 years (coef., -1.124; p < 0.001 and -1.661; p < 0.001). No change in mortality rates was reported over time in V-V or V-A ECLS (coef., -0.147; p = 0.442 and coef., -0.195; p = 0.139).Multivariate regression revealed advanced age, ecls duration, surgical cannulation, renal replacement therapy, prone positioning as independent bleeding predictors in v-v ecls and female gender, ecls duration, pre-ecls arrest or bridge to transplant, therapeutic hypothermia, and surgical cannulation in v-a ecls.CONCLUSIONS: A steady decrease in bleeding over the last 20 years, mostly attributable to surgical and cannula-site-related bleeding has been found in this large cohort of patients receiving ECLS support. However, there is not enough data to attribute the decreasing trends in bleeding to technological refinements alone. Especially reduction in cannulation site bleeding is also due to changes in timing, patient selection, and ultrasound guided percutaneous cannulation. Other types of bleeding, such as CNS, have remained stable, and overall bleeding remains associated with a persistent increase in mortality.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of Pa-CO(2) in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NW in patients with COPD and chronic stable hypercapnic respiratory failure.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited. Target Audience: Patients with COPD, clinicians who care for them, and policy makers. Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework. Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of Pa-CO(2) in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty). Conclusions: This expert panel provides evidence-based recommendations addressing the use of NW in patients with COPD and chronic stable hypercapnic respiratory failure.

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9-29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6-61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8-34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8-5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations.

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations. Electronic supplementary material The online version of this article (10.1007/s00134-020-06031-4) contains supplementary material, which is available to authorized users.

Background A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. Main text While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. Conclusions A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Study objective: Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO).Design: Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020.Setting: Patients on ECMO support. Patients: Anticoagulation management on ECMO patients.Interventions: Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review.Measurements: The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcomes were blood-product transfusions, cerebrovascular accidents, mortality on ECMO, ECMO duration, intensive care unit and hospital discharge rates, and in-hospital mortality.Main results: Thirty-one trials enrolling 1684 participants were included in the systematic review. Four trials enrolling 547 subjects were included in the meta-analysis. The use of a POC testing device resulted in improved detection of surgical bleeding (RR: 0.68, 95% CI 0.49 to 0.94, I2 = 0%; chi 2 test for heterogeneity, P = 0.02). The use of POC-guided algorithms did not affect bleeding (RR:0.78, 95% CI 0.58 to 1.04, I2 = 47%; chi 2 test for heterogeneity, P = 0.09), thrombosis events (RR:1.35, 95% CI 0.86 to 2.12, I2 = 37%; chi 2 test for heterogeneity, P = 0.19), or ECMO circuit/change (RR:0.90, 95% CI 0.48 to 1.71, I2 = 28%; chi 2 test for heterogeneity, P = 0.75).Conclusion: Routine use of POC tests did not improve the main clinical outcomes beyond suggesting a diagnosis of surgical bleeding in ECMO patients.

Extracorporeal membrane oxygenation (ECMO) in the veno-arterial (VA) configuration is an established method for the treatment of refractory cardiogenic shock. Such a condition characterizes the postoperative course of approximatively 1% of cardiac surgery patients. Although some studies have reported ECMO-related short-term results, little is known about the long-term outcomes of VA-ECMO therapy in the post-cardiotomy setting. Therefore, an extensive literature search was conducted regarding articles published after 1990 reporting postoperative ECMO use. PubMed, EMBASE and Web of Science were searched for sources. In-hospital mortality was high in post-cardiotomy VA-ECMO patients, ranging from 24.8% to 52%. Long-term results were poorly reported. However, based on the limited information available, hospital survivors showed a favorable outcome, with improvement in overall clinical condition, quality of life and limited hospital readmission for cardiac-related events. To conclude, in-hospital outcome in post-cardiotomy ECMO is often unfavorable, post-discharge results show satisfactory condition, with stable improvement of overall patient clinical status and low rate of hospital readmission and cardiac-related adverse events. Data reporting is, however, scarce and hence new and detailed studies are still warranted to investigate such aspects.

From the birth of the Extracorporeal Life Support Organization (ELSO) Registry in 1989, collecting the most relevant information about extracorporeal life support (ECLS) for refractory cardiac or respiratory compromise, was created in order to provide useful information and benchmark for ECLS users. Throughout the years, the Registry has continuously developed, achieving in 2018 more than 100,000 patients included with almost 500 ELSO centers around the world. Based on the relevance and impact of database analysis, and due to the growing need for more advanced and high-quality clinical investigations, the ELSO Registry is under substantial re-engineering which will allow and provide the ELSO members and the scientific community an enhanced scientific tool to elucidate various aspects of the ECLS settings, including trends and disease-specific information, to perform benchmarking about our own results and outcomes as compared to regional or worldwide results, and to provide an invaluable source of data for clinical investigations.

Thrombocytopenia and impaired platelet function are known as intrinsic drawbacks of cardiac surgery and extracorporeal life supports (ECLS). A number of different factors influence platelet count and function including the inflammatory response to a cardiopulmonary bypass (CPB) or to ECLS, hemodilution, hypothermia, mechanical damage and preoperative treatment with platelet-inhibiting agents. Moreover, although underestimated, heparin-induced thrombocytopenia is still a hiccup in the perioperative management of cardiac surgical and, above all, ECLS patients. Moreover, recent investigations have highlighted how platelet disorders also affect patients undergoing biological prosthesis implantation. Though many hypotheses have been suggested, the mechanism underlying thrombocytopenia and platelet disorders is still to be cleared. This narrative review aims to offer clinicians a summary of their major causes in the cardiac surgery setting.

Thrombocytopenia and impaired platelet function are known as intrinsic drawbacks of cardiac surgery and extracorporeal life supports (ECLS). A number of different factors influence platelet count and function including the inflammatory response to a cardiopulmonary bypass (CPB) or to ECLS, hemodilution, hypothermia, mechanical damage and preoperative treatment with platelet-inhibiting agents. Moreover, although underestimated, heparin-induced thrombocytopenia is still a hiccup in the perioperative management of cardiac surgical and, above all, ECLS patients. Moreover, recent investigations have highlighted how platelet disorders also affect patients undergoing biological prosthesis implantation. Though many hypotheses have been suggested, the mechanism underlying thrombocytopenia and platelet disorders is still to be cleared. This narrative review aims to offer clinicians a summary of their major causes in the cardiac surgery setting.

Study objective Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO). Design Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020. Setting Patients on ECMO support. Patients Anticoagulation management on ECMO patients. Interventions Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review. Measurements The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcomes were blood-product transfusions, cerebrovascular accidents, mortality on ECMO, ECMO duration, intensive care unit and hospital discharge rates, and in-hospital mortality. Main results Thirty-one trials enrolling 1684 participants were included in the systematic review. Four trials enrolling 547 subjects were included in the meta-analysis. The use of a POC testing device resulted in improved detection of surgical bleeding (RR: 0.68, 95% CI 0.49 to 0.94, I2 = 0%; χ2 test for heterogeneity, P = 0.02). The use of POC-guided algorithms did not affect bleeding (RR:0.78, 95% CI 0.58 to 1.04, I2 = 47%; χ2 test for heterogeneity, P = 0.09), thrombosis events (RR:1.35, 95% CI 0.86 to 2.12, I2 = 37%; χ2 test for heterogeneity, P = 0.19), or ECMO circuit/change (RR:0.90, 95% CI 0.48 to 1.71, I2 = 28%; χ2 test for heterogeneity, P = 0.75). Conclusion Routine use of POC tests did not improve the main clinical outcomes beyond suggesting a diagnosis of surgical bleeding in ECMO patients.

Introduction: Gastrointestinal bleeding is a life-threatening complication in patients undergoing extracorporeal membrane oxygenation support. Despite data on increased mortality due to gastrointestinal bleeding, there is little data on the treatment of such conditions under extracorporeal membrane oxygenation, and on the possibilities of advanced endoscopic therapy to non-invasively solve these bleeding complications. No clear treatment in the case of extracorporeal membrane oxygenation support is recommended in the guidelines. Methods: Retrospective observational cohort study including 134 veno-venous extracorporeal membrane oxygenation patients for acute respiratory failure from 2009 to 2018 at IRCCS-ISMETT (Italy). Patients were divided into two groups according to gastrointestinal bleeding episodes and reviewed for type of endoscopic therapy. Gastrointestinal bleeding group was characterized for pre–extracorporeal membrane oxygenation characteristics, management variables—including amount of transfusions and clinical outcomes. Results: Fourteen (14) patients (10.4%) experienced upper (n = 13) or lower (n = 1) gastrointestinal bleeding. Gastrointestinal bleeding and no-gastrointestinal bleeding group had similar characteristics apart from higher creatinine in the gastrointestinal bleeding group (1.9 mg/dL (1.3-4.9) vs 1.2 mg/dL (0.7-1.8), p = 0.03). In 3 of the 14 patients (21%), endoscopy showed no signs of active bleeding (nasogastric or feeding tube decubitus), and no specific intervention was performed. Active bleeding was recognized in 11 of the 14 patients (79 %). No patients died of fatal bleeding in the gastrointestinal bleeding group. Endoscopic therapy was feasible, with a complete bleeding control in all the cases: five Hemospray®, two fibrin glue, two metallic clips, one combined approach metallic clips with epinephrine, and one cyanoacrylate. The extracorporeal membrane oxygenation course was significantly longer in the gastrointestinal bleeding group: 19.5 (15-36) days vs 13.5 (8-25) days, p = 0.01. No significant differences in mortality were found between the two groups (all p values > 0.05). Conclusion: Advanced endoscopic therapy during veno-venous extracorporeal membrane oxygenation may contribute to reducing the negative effects on mortality for gastrointestinal bleeding episodes.

Objectives: Although acute brain injury is common in patients receiving extracorporeal membrane oxygenation, little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial extracorporeal membrane oxygenation support. Design: Retrospective analysis. Setting: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. Patients: Patients more than 18 years old supported with a single run of venoarterial extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Of 10,342 venoarterial extracorporeal membrane oxygenation patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported acute brain injury during venoarterial extracorporeal membrane oxygenation decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-extracorporeal membrane oxygenation pH (adjusted odds ratio, 0.21; 95% CI, 0.09-0.49;p

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited. Target Audience: Patients with COPD, clinicians who care for them, and policy makers. Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework. Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of Pa-CO(2) in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty). Conclusions: This expert panel provides evidence-based recommendations addressing the use of NW in patients with COPD and chronic stable hypercapnic respiratory failure.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

The substantial increase in the number of patients receiving extracorporeal membrane oxygenation over the last decade has led to an evolution of indications and an expansion into wider patient groups. One of the unanticipated benefits of the increase in extracorporeal membrane oxygenation has been a change in the understanding of the natural history of many respiratory diseases. Development in technology and materials, reduced extracorporeal membrane oxygenation–specific complications, and improvement of critical care, in general, have facilitated longer extracorporeal membrane oxygenation runs, and the definition of prolonged extracorporeal membrane oxygenation was recently expanded to continuous support for more than 28 days. This survey aimed to describe European ECMO centers’ perception and arbitrary definition of prolonged extracorporeal membrane oxygenation, patient management, and futility. Of 94 center responses, 37% regarded 14-21 days, 30% 21-28 days, and 28% >28 days as prolonged treatment. Bridge to recovery (64%) or to transplantation (20%) was the most common causes. Awake, and ambulation while on extracorporeal membrane oxygenation was reported from 34% of the centers. In case of perceived futility, decision to withdraw was taken in 65% of the centers in agreement between profession and family and in 30% by profession only. One-fourth of the centers did not discontinue support. Large differences prevail among European ECMO centers concerning local perception and patient management in prolonged extracorporeal membrane oxygenation.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

Background and objective: Obesity hypoventilation syndrome (OHS) can be treated with either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) therapy; the device choice has important economic and operational implications. Methods: This multicentre interventional trial investigated the safety and short-term efficacy of switching stable OHS patients who were on successful NIV therapy for ≥3 months to CPAP therapy. Patients underwent an autotitrating CPAP night under polysomnography (PSG); if the ensuing parameters were acceptable, they were sent home on a fixed CPAP for a 4–6-week period. It was hypothesized that blood gas analysis, PSG parameters and lung function tests would remain unchanged. Results: A total of 42 OHS patients were recruited, of whom 37 patients were switched to CPAP therapy. All patients had a history of severe obstructive sleep apnoea syndrome; chronic obstructive pulmonary disease (COPD) (Global Initiative for Obstructive Lung Disease (GOLD) I/II) was present in 52%. Regarding the primary outcome, 30 of 42 patients (71%, 95% CI: 55–84%) maintained daytime partial pressure of carbon dioxide (PaCO2) levels ≤45 mm Hg after the home CPAP period. There was no further impairment in quality of life, sleep parameters or lung function. Interestingly, 24 patients (65%) preferred CPAP as their long-term therapy, despite the high pressure levels used (mean: 13.8 ± 1.8 mbar). After the CPAP period, 7 of 37 patients were categorized as CPAP failure, albeit only due to mild hypercapnia (mean: 47.9 ± 2.7 mm Hg). Conclusion: It is feasible to switch most stable OHS patients from NIV to CPAP therapy, a step that could significantly reduce health-related costs. The auto-adjusted CPAP device, used in combination with the analysis of the PSG and capnometry, is a valid titration method in OHS patients.

Surfactant protein B (SP-B) is essential in transferring surface-active phospholipids from membrane-based surfactant complexes into the alveolar air-liquid interface. This allows maintaining the mechanical stability of the surfactant film under high pressure at the end of expiration; therefore, SP-B is crucial in lung function. Despite its necessity, the structure and the mechanism of lipid transfer by SP-B have remained poorly characterized. Earlier, we proposed higher-order oligomerization of SP-B into ring-like supramolecular assemblies. In the present work, we used coarse-grained molecular dynamics simulations to elucidate how the ring-like oligomeric structure of SP-B determines its membrane binding and lipid transfer. In particular, we explored how SP-B interacts with specific surfactant lipids, and how consequently SP-B reorganizes its lipid environment to modulate the pulmonary surfactant structure and function. Based on these studies, there are specific lipid-protein interactions leading to perturbation and reorganization of pulmonary surfactant layers. Especially, we found compelling evidence that anionic phospholipids and cholesterol are needed or even crucial in the membrane binding and lipid transfer function of SP-B. Also, on the basis of the simulations, larger oligomers of SP-B catalyze lipid transfer between adjacent surfactant layers. Better understanding of the molecular mechanism of SP-B will help in the design of therapeutic SP-B-based preparations and novel treatments for fatal respiratory complications, such as the acute respiratory distress syndrome. (C) 2020 The Author(s). Published by Elsevier Ltd.

Improvement in hypercapnia does not predict survival in COPD patients on chronic noninvasive ventilation Tim Raveling,1 Gerrie Bladder,2 Judith M Vonk,3,4 Jellie A Nieuwenhuis,2,3 Fransien M Verdonk-Struik,5 Peter J Wijkstra,2,3 Marieke L Duiverman2,3 1Faculty of Medical Sciences, University of Groningen, Groningen, the Netherlands; 2Department of Pulmonary Diseases and Home Mechanical Ventilation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 3Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, Groningen, the Netherlands; 4Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 5Primary Care Group Gelders Rivierenland, Ochten, the Netherlands Purpose: It has recently been shown that chronic noninvasive ventilation (NIV) improves a number of outcomes including survival, in patients with stable hypercapnic COPD. However, the mechanisms responsible for these improved outcomes are still unknown. The aim of the present study was to identify parameters associated with: 1) an improved arterial partial pressure of carbon dioxide (PaCO2) and 2) survival, in a cohort of hypercapnic COPD patients treated with chronic NIV. Patients and methods: Data from 240 COPD patients treated with chronic NIV were analyzed. Predictors for the change in PaCO2 and survival were investigated using multivariate linear and Cox regression models, respectively. Results: A higher level of bicarbonate before NIV initiation, the use of higher inspiratory ventilator pressures, the presence of anxiety symptoms, and NIV initiated following an exacerbation compared to NIV initiated in stable disease were associated with a larger reduction in PaCO2. A higher body mass index, a higher FEV1, a lower bicarbonate before NIV initiation, and younger age and NIV initiation in stable condition were independently associated with better survival. The change in PaCO2 was not associated with survival, neither in a subgroup of patients with a PaCO2 >7.0 kPa before the initiation of NIV. Conclusion: Patients with anxiety symptoms and a high bicarbonate level at NIV initiation are potentially good responders in terms of an improvement in hypercapnia. Also, higher inspiratory ventilator pressures are associated with a larger reduction in PaCO2. However, the improvement in hypercapnia does not seem to be associated with an improved survival and emphasizes the need to look beyond PaCO2 when considering NIV initiation. Keywords: carbon dioxide, home mechanical ventilation, exacerbation, bicarbonate, chronic obstructive pulmonary disease, respiratory insufficiency

Extracorporeal membrane oxygenation (ECMO) is becoming a common procedure to support patients with severe cardio-circulatory or respiratory failure as well as in case of combined compromise of the two systems. Deciding which ECMO configuration and proceeding with an uneventful implantation, however, may present minor or major shortcomings. Cannulation techniques should be tailored to specific patient conditions to provide sufficient regional and systemic perfusion, both of which must be comprehensively monitored. Changes in the patient's status or suboptimal ECMO-related support, however, may occur and should trigger re-appraisal of the cannulation strategy and circuit configuration. This dynamic management, based around the adequacy of end organ perfusion and patient requirements, may dictate ECMO configuration and cannulation changes. In these circumstances, adjunct of a cannula in the venous or arterial vasculature may represent a mandatory procedure to solve unfavorable hemodynamic status or enhance ECMO efficiency. These type of ECMO configurations, different from basic one, and called hybrid configurations, may represent, therefore, a critical aspect of optimal ECMO management towards optimized and successful temporary support.The aim of this review is to critically appraise and summarize the existing literature on adult ECMO configuration including cannulation strategies and circuit arrangement, and highlighting more complex pattern required in some specific clinical settings.

Background: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. Methods: We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. Results: The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. Conclusions: A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data., SCOPUS: ar.j, info:eu-repo/semantics/published

Recently, clear benefits have been shown from long-term noninvasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure. In our opinion, these benefits are confirmed and nocturnal NIV using sufficiently high inspiratory pressures should be considered in COPD patients with chronic hypercapnic respiratory failure in stable disease, preferably combined with pulmonary rehabilitation. In contrast, clear benefits from (continuing) NIV at home after an exacerbation in patients who remain hypercapnic have not been shown. In this review we will discuss the results of five trials investigating the use of home nocturnal NIV in patients with prolonged hypercapnia after a COPD exacerbation with acute hypercapnic respiratory failure. Although some uncontrolled trials might have shown some benefits of this therapy, the largest randomized controlled trial did not show benefits in terms of hospital readmission or death. However, further studies are necessary to select the patients that optimally benefit, select the right moment to initiate home NIV, select the optimal ventilatory settings, and to choose optimal follow up programmes. Furthermore, there is insufficient knowledge about the optimal ventilatory settings in the post-exacerbation period. Finally, we are not well informed about exact reasons for readmission in patients on NIV, the course of the exacerbation and the treatment instituted. A careful follow up might probably be necessary to prevent deterioration on NIV early.

Recently, clear benefits have been shown from long-term noninvasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure. In our opinion, these benefits are confirmed and nocturnal NIV using sufficiently high inspiratory pressures should be considered in COPD patients with chronic hypercapnic respiratory failure in stable disease, preferably combined with pulmonary rehabilitation. In contrast, clear benefits from (continuing) NIV at home after an exacerbation in patients who remain hypercapnic have not been shown. In this review we will discuss the results of five trials investigating the use of home nocturnal NIV in patients with prolonged hypercapnia after a COPD exacerbation with acute hypercapnic respiratory failure. Although some uncontrolled trials might have shown some benefits of this therapy, the largest randomized controlled trial did not show benefits in terms of hospital readmission or death. However, further studies are necessary to select the patients that optimally benefit, select the right moment to initiate home NIV, select the optimal ventilatory settings, and to choose optimal follow up programmes. Furthermore, there is insufficient knowledge about the optimal ventilatory settings in the post-exacerbation period. Finally, we are not well informed about exact reasons for readmission in patients on NIV, the course of the exacerbation and the treatment instituted. A careful follow up might probably be necessary to prevent deterioration on NIV early.

Large dual-lumen veno-venous (VV) extracorporeal membrane oxygenation (ECMO) cannulas may increase venous pressure in the brain, contributing to intracranial hemorrhage (ICH). A retrospective cohort study was performed using the extracorporeal life support organization (ELSO) registry. Propensity score matching was used to control for confounding. The rate of ICH and rates of hemolysis, cannula complications, and mortality were compared between patients with a 27 French dual-lumen cannula and patients with a 31 French dual-lumen cannula. Seven hundred forty-four patients were included in the propensity score-matched cohort. Patients were well matched except there was some residual imbalance in body weight and sex. Patients with a 31 French cannula had an ICH rate of 4.3% compared with 1.6% in patients with a 27 French cannula (p = 0.03). There were no differences in hemolysis, cannula complications, or mortality between groups. After controlling for body weight and sex in the matched cohort, ICH odds remained higher in patients with a 31 French cannula; odds ratio = 2.74, (95% CI = 1.06-7.09, p = 0.03). Our study data suggest that large dual-lumen VV ECMO cannulas are associated with more ICH, and thus, smaller cannulas may be preferable when feasible.

Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.

Extracorporeal membrane oxygenation (ECMO) is becoming a common procedure to support patients with severe cardio-circulatory or respiratory failure as well as in case of combined compromise of the two systems. Deciding which ECMO configuration and proceeding with an uneventful implantation, however, may present minor or major shortcomings. Cannulation techniques should be tailored to specific patient conditions to provide sufficient regional and systemic perfusion, both of which must be comprehensively monitored. Changes in the patient's status or suboptimal ECMO-related support, however, may occur and should trigger re-appraisal of the cannulation strategy and circuit configuration. This dynamic management, based around the adequacy of end organ perfusion and patient requirements, may dictate ECMO configuration and cannulation changes. In these circumstances, adjunct of a cannula in the venous or arterial vasculature may represent a mandatory procedure to solve unfavorable hemodynamic status or enhance ECMO efficiency. These type of ECMO configurations, different from basic one, and called hybrid configurations, may represent, therefore, a critical aspect of optimal ECMO management towards optimized and successful temporary support. The aim of this review is to critically appraise and summarize the existing literature on adult ECMO configuration including cannulation strategies and circuit arrangement, and highlighting more complex pattern required in some specific clinical settings.

Background Although high-intensity non-invasive ventilation has been shown to improve outcomes in stable COPD, it may adversely affect cardiac performance. Therefore, the aims of the present pilot study were to compare cardiac and pulmonary effects of 6 weeks of low-intensity non-invasive ventilation and 6 weeks of high-intensity non-invasive ventilation in stable COPD patients. Methods In a randomised crossover pilot feasibility study, the change in cardiac output after 6 weeks of each NIV mode compared to baseline was assessed with echocardiography in 14 severe stable COPD patients. Furthermore, CO during NIV, gas exchange, lung function, and health-related quality of life were investigated. Results Three patients dropped out: two deteriorated on low-intensity non-invasive ventilation, and one presented with decompensated heart failure while on high-intensity non-invasive ventilation. Eleven patients were included in the analysis. In general, cardiac output and NTproBNP did not change, although individual effects were noticed, depending on the pressures applied and/or the co-existence of heart failure. High-intensity non-invasive ventilation tended to be more effective in improving gas exchange, but both modes improved lung function and the health-related quality of life. Conclusions Long-term non-invasive ventilation with adequate pressure to improve gas exchange and health-related quality of life did not have an overall adverse effect on cardiac performance. Nevertheless, in patients with pre-existing heart failure, the application of very high inspiratory pressures might reduce cardiac output. Trial registration The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00007977). Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0542-9) contains supplementary material, which is available to authorized users.

Congenital diaphragmatic hernia is an uncommon congenital anomaly of the diaphragm with pulmonary hypoplasia and persistent pulmonary hypertension as serious consequences. Despite recent advances in therapy, congenital diaphragmatic hernia remains a challenging condition. Best treatment strategies are still largely unknown, and practice strategies vary widely among different centres. Additionally, as congenital diaphragmatic hernia is a relatively uncommon condition, it is difficult to recruit sufficient numbers of patients for clinical trials. In recent years, survival rates of congenital diaphragmatic hernia patients appear to have increased. With the progressively improved survival rates, the long-term prognosis and quality of life of patients have become an increasingly important issue. Survivors have been shown to be at risk for many long-term morbidities, which highlights the importance of long-term follow-up of these children. The aim of this review is to give an overview of the current knowledge regarding congenital diaphragmatic hernia.

Both chronic obstructive pulmonary disease (COPD) and sudden cardiac death (SCD) are major health burdens. A number of studies have addressed their interrelationship, but currently no systematic review has been published. Our objective is to give an overview of the literature of the association between COPD and SCD. A search on PubMed with both MeSH headings and free-text keywords was performed. We selected all original articles of studies in humans that assessed COPD on the one hand and SCD, electrocardiographic markers for SCD, ventricular arrhythmias, or asystole on the other. The electronic search yielded 251 articles, from which 27 full publications were selected after careful evaluation of the full-text articles. In these studies, COPD was associated with a prolonged and shortened QT interval. In patients with a myocardial infarction (MI), COPD was associated with an increased risk of ventricular arrhythmias and decreased survival. COPD was a risk factor for SCD both in cardiovascular patient groups and in community-based studies, independent from cardiovascular risk profile. Studies of the potential impact of respiratory treatment on the occurrence of SCD showed conflicting results. In conclusion, cumulating evidence associates COPD with an increased risk of SCD. Asystole and pulseless electric activity could be more common than VT/VF in deaths associated with COPD. Underlying mechanisms explaining this association require further investigation.

Indexación: Web of Science y Scopus. A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol . kg(-1) . h(-1) coupled to hemofiltration (THAM+HF group) at 100 mL . kg(-1) . h(-1). After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P

Introduction.Pneumocystispneumonia (PCP) is rising in the non-HIV population and associates with higher morbidity and mortality. The aggressive immunosuppressive regimens, as well as the lack of stablished guidelines for chemoprophylaxis, are likely contributors to this increased incidence. Herein, we have explored the underlying conditions, immunosuppressive therapies, and clinical outcomes of PCP in HIV-negative patients.Methods. Retrospective analysis of PCP in HIV-negative patients at Mayo Clinic from 2006–2010. The underlying condition, immunosuppressive therapies, coinfection, and clinical course were determined. PCP diagnosis required symptoms of pneumonia and identification of the organisms by visualization or by a real-time polymerase chain reaction.Results. A total of 128 cases of PCP were identified during the study period. Hematological malignancies were the predisposing condition for 50% of the patients. While 87% had received corticosteroids or other immunosuppressive therapies for >4 weeks prior to the diagnosis, only 7 were receiving PCP prophylaxis. Up to 43% of patients were not on daily steroids. Sixty-seven patients needed Intensive Care Unit (ICU) and 53 received mechanical ventilation. The mortality for those patients requiring ICU was 40%.Conclusions. PCP diagnosis in the HIV-negative population requires a high level of suspicion even if patients are not receiving daily corticosteroids. Mortality remains high despite adequate treatment.

Study objectives: The potential benefits of noninvasive positive pressure ventilation (NIPPV) for patients with COPD remains inconclusive, as most studies have included only a small number of patients. We therefore undertook a meta-analysis of randomized controlled trials (RCTs) that compared nocturnal NIPPV with conventional management in patients with COPD and stable respiratory failure.Design: RCTs were identified from several sources, such as MEDLINE, EMBASE, and CINAHL. In addition, records were identified through hand searching of abstracts from meetings of the American Thoracic Society, the American College of Chest Physicians, and the European Respiratory Society.Patients: Patients with COPD according to the definition of the American Thoracic Society.Interventions: NIPPV applied via a nasal or facemask for at least 5 h/d for at least 3 weeks. Patients in the actively treated group continued to receive the usual management for COPD. The control group received the same management as the study group but did not receive NIPPV.Measurements and results: PaCO2, PaO2, 6-min walking distance (6MWD), respiratory muscle function, FEV1, vital capacity, and sleep efficiency (time asleep as a percentage of total time in bed) were used as outcome measures. The publications were reduced to 10 potentially eligible articles from 164 publications retrieved from computer searches and 8 further abstracts. Four trials were finally included in the meta-analysis. The only outcome for which the confidence intervals excluded zero was maximal inspiratory pressure (PImax). The confidence intervals for the other outcomes included zero. The mean treatment effects for FEVI and PImax were small, whereas it was moderate for the 6MWD. Small negative effects were found for the outcomes of vital capacity, PaCO2, and sleep efficiency.Conclusions: This meta-analysis of 3 months of NIPPV in patients with stable COPD showed that ventilatory support did not improve lung function, gas exchange, or sleep efficiency. The high upper limit of the confidence interval for the 6MWD suggested that some people do improve their walking distance. The small overall sample size precluded a clear clinical direction regarding the effects of NIPPV in patients with COPD.

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (Paco 2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H 2 O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H 2 O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco 2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration clinicaltrials.gov Identifier:NCT00990132

Background: No externally validated risk score for postoperative pulmonary complications (PPCs) is currently available. The authors tested the generalizability of the Assess Respiratory Risk in Surgical Patients in Catalonia risk score for PPCs in a large European cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe). Methods: Sixty-three centers recruited 5,859 surgical patients receiving general, neuraxial, or plexus block anesthesia. The Assess Respiratory Risk in Surgical Patients in Catalonia factors (age, preoperative arterial oxygen saturation in air, acute respiratory infection during the previous month, preoperative anemia, upper abdominal or intrathoracic surgery, surgical duration, and emergency surgery) were recorded, along with PPC occurrence (respiratory infection or failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis). Discrimination, calibration, and diagnostic accuracy measures of the Assess Respiratory Risk in Surgical Patients in Catalonia score’s performance were calculated for the Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe cohort and three subsamples: Spain, Western Europe, and Eastern Europe. Results: The full Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe data set included 5,099 patients; 725 PPCs were recorded for 404 patients (7.9%). The score’s discrimination was good: c-statistic (95% CI), 0.80 (0.78 to 0.82). Predicted versus observed PPC rates for low, intermediate, and high risk were 0.87 and 3.39% (score Conclusions: The Assess Respiratory Risk in Surgical Patients in Catalonia score predicts three levels of PPC risk in hospitals outside the development setting. Performance differs between geographic areas.

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of CM-CSF in patients with idiopathic AP. Fourteen patients received 5 mug/kg/d CM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]Do(2)), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 mug/kg/d CM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for CM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 mug/kg/d GM-CSF, and one of four patients responded after dose escalation (20 mug/kg/d). The overall response rate was 43% (mean improvement in [A-a]Do(2) = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. CM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was CM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM-CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Background Non-invasive positive pressure ventilation (NIPPV) is effective in treating acute exacerbations of chronic obstructive pulmonary disease (COPD). Nocturnal non-invasive positive pressure ventilation (nocturnal-NIPPV) has been proposed as an intervention for stable hypercapnic patients with COPD. Objectives To assess the effects of nocturnal-NIPPV at home via nasal mask or face mask in people with COPD by using a meta-analysis based on individual patient data (IPD). Search methods We searched the Cochrane Airways Group Specialised Register. We performed the latest search in August 2012. Selection criteria Randomised controlled trials in people with stable COPD that compared nocturnal-NIPPV at home for at least five hours per night, for at least three consecutive weeks plus standard therapy with standard therapy alone. Data collection and analysis IPD were collected and two review authors assessed risk of bias independently. Main results This update of the systematic review on nocturnal-NIPPV in COPD (Wijkstra 2002), has led to the inclusion of three new studies, leading to seven included studies on 245 people. We obtained IPD for all participants in all included studies. The 95% confidence interval (CI) of all outcomes included zero. These included partial pressure of CO2 and O2 in arterial blood, six-minute walking distance (6MWD), health-related quality of life (HRQoL), forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximal inspiratory pressure (PImax) and sleep efficiency. The mean effect on 6MWD was small at 27.7 m and not statistically significant. Given the width of the 95% CI (-28.1 to 66.3 m), the real effect of NIPPV on 6MWD is uncertain and we cannot exclude an effect that is clinically significant (considering that the minimal clinically difference on 6MWD is around 26 m). Authors' conclusions Nocturnal-NIPPV at home for at least three months in hypercapnic patients with stable COPD had no consistent clinically or statistically significant effect on gas exchange, exercise tolerance, HRQoL, lung function, respiratory muscle strength or sleep efficiency. Meta-analysis of the two new long-term studies did not show significant improvements in blood gases, HRQoL or lung function after 12 months of NIPPV. However, the small sample sizes of these studies preclude a definite conclusion regarding the effects of NIPPV in COPD.

Background: NKX2-1 mutations have been described in several patients with primary congenital hypothyroidism, respiratory distress, and benign hereditary chorea, which are classical manifestations of the brain-thyroid-lung syndrome (BTLS). Methods: The NKX2-1 gene was sequenced in the members of a Brazilian family with clinical features of BTLS, and a novel monoallelic mutation was identified in the affected patients. We introduced the mutation in an expression vector for the functional characterization by transfection experiments using both thyroidal and lung-specific promoters. Results: The mutation is a deletion of a cytosine at position 834 (ref. sequence NM-003317) (c.493delC) that causes a frameshift with formation of an abnormal protein from amino acid 165 and a premature stop at position 196. The last amino acid of the nuclear localization signal, the whole homeodomain, and the carboxy-terminus of NKX2-1 are all missing in the mutant protein, which has a premature stop codon at position 196 (p.Arg165Glyfs*32). The p.Arg165Glyfs*32 mutant does not bind DNA, and it is unable to transactivate the thyroglobulin (Tg) and the surfactant protein-C (SP-C) promoters. Interestingly, a dose-dependent dominant negative effect of the p.Arg165Glyfs*32 was demonstrated only on the Tg promoter, but not on the SP-C promoter. This effect was also noticed when the mutation was tested in presence of PAX8 or cofactors that synergize with NKX2-1 (P300 and TAZ). The functional effect was also compared with the data present in the literature and demonstrated that, so far, it is very difficult to establish a specific correlation among NKX2-1 mutations, their functional consequence, and the clinical phenotype of affected patients, thus suggesting that the detailed mechanisms of transcriptional regulation still remain unclear. Conclusions: We describe a novel NKX2-1 mutation and demonstrate that haploinsufficiency may not be the only explanation for BTLS. Our results indicate that NKX2-1 activity is also finely regulated in a tissue-specific manner, and additional studies are required to better understand the complexities of genotype-phenotype correlations in the NKX2-1 deficiency syndrome. © Copyright 2013, Mary Ann Liebert, Inc. 2013.