A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure.
We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios.
A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. \"Higher extraction\" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R.
ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. \"Higher extraction\" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R\'s effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

UNASSIGNED: Acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by poor oxygenation due to non-compliant lungs secondary diffuse alveolar damage. Encouragingly, the incidence of ARDS has declined steadily recently, attributed mainly to implementation of keystone guidelines and continuous research efforts. Mechanical ventilation is the cornerstone of supportive care for ARDS patients. This review aims to consolidate the current knowledge on pneumothorax (PNX) and pneumomediastinum (PMD) and to enhance the understanding of the readers. The objectives are to (I) explore the etiology and risk factors of PNX and PMD, (II) discuss the various diagnostic modalities available, (III) evaluate management options, and (IV) recent advancements.
UNASSIGNED: A search of the literature was conducted using PubMed, MEDLINE, and Google Scholar for relevant articles pertaining to PNX and PMD in ARDS population. The clinical presentation, diagnostic and management strategies of PNX, PMD, and ARDS were summarized, and all authors reviewed the selection and decide which studies to include.
UNASSIGNED: The adoption of lung-protective ventilation strategies, based on the review of literature from the recent years, shows that it has played a significant role in reducing the occurrence of barotrauma, such as PNX and PMD. However, PNX and PMD remains to be a challenging complication to manage. With a specific focus on PNX and PMD, this review provides valuable insights into effectively managing and understanding these critical complications among ARDS patients.
UNASSIGNED: ARDS, with its evolving definition, continues to pose a life-threatening threat. Despite the widespread adoption of lung-protective ventilation strategies, PNX and PMD present persistent challenges in management. Further research is imperative to enhance the risk assessment of ARDS patients prone to developing PNX and PMD and to institute more effective prevention and treatment measures.

BACKGROUND: Noninvasive methods of respiratory support, including noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen (HFNO), are potential strategies to prevent progression to requirement for invasive mechanical ventilation in acute hypoxaemic respiratory failure. The COVID-19 pandemic provided an opportunity to understand the utility of noninvasive respiratory support among a homogeneous cohort of patients with contemporary management of acute respiratory distress syndrome. We performed a network meta-analysis of studies evaluating the efficacy of NIV (including CPAP) and HFNO, compared with conventional oxygen therapy (COT), in patients with COVID-19.
METHODS: PubMed, Embase, and the Cochrane library were searched in May 2023. Standard random-effects meta-analysis was used first to estimate all direct pairwise associations and the results from all studies were combined using frequentist network meta-analysis. Primary outcome was treatment failure, defined as discontinuation of HFNO, NIV, or COT despite progressive disease. Secondary outcome was mortality.
RESULTS: We included data from eight RCTs with 2302 patients, (756 [33%] assigned to COT, 371 [16%] to NIV, and 1175 [51%] to HFNO). The odds of treatment failure were similar for NIV (P=0.33) and HFNO (P=0.25), and both were similar to that for COT (reference category). The odds of mortality were similar for all three treatments (odds ratio for NIV vs COT: 1.06 [0.46-2.44] and HFNO vs COT: 0.97 [0.57-1.65]).
CONCLUSIONS: Noninvasive ventilation, high-flow nasal oxygen, and conventional oxygen therapy are comparable with regards to treatment failure and mortality in COVID-19-associated acute respiratory failure.
UNASSIGNED: CRD42023426495.

To investigate the diagnostic and prognostic value of angiopoietin-2 (Ang-2) for acute respiratory distress syndrome (ARDS).
Seven databases (4 English and 3 Chinese databases) were searched, the quality was evaluated by QUADAS-2 and GRADE profile. The bivariate model was employed to combine area under the curve (AUC), pooled sensitivity (pSEN) and pooled specificity (pSPE), the Fagan\'s nomogram was employed for evaluating clinical utility. This study was registered in PROSPERO (NO.CRD42022371488).
18 eligible studies comprising 27 datasets (12 diagnostic and 15 prognostic datasets) were included for meta-analysis. For diagnostic analysis, Ang-2 yielded an AUC of 0.82, with a pSEN of 0.78 and a pSPE of 0.74; in clinical utility analysis, a pretest probability of 50% regulated the post probability positive (PPP) of 75% and the post probability negative (PPN) of 23%. In prognostic analysis, Ang-2 yielded an AUC of 0.83, with a pSEN of 0.69, a pSPE of 0.81, and good clinical utility (a pretest probability of 50% regulated the PPP of 79% and the PPN of 28%). Heterogeneity existed in both diagnostic and prognostic analysis.
Ang-2 demonstrates promising diagnostic and prognostic capabilities as a noninvasive circulating biomarker for ARDS, especially in the Chinese population. It is advisable to dynamically monitor Ang-2 in critically ill patients both suspected and with confirmed ARDS.

Refractory hypoxemia in patients with acute respiratory distress syndrome treated with mechanical ventilation is one of the most challenging conditions in human and veterinary intensive care units. When a conventional lung protective approach fails to restore adequate oxygenation to the patient, the use of recruitment maneuvers and positive end-expiratory pressure to maximize alveolar recruitment, improve gas exchange and respiratory mechanics, while reducing the risk of ventilator-induced lung injury has been suggested in people as the open lung approach. Although the proposed physiological rationale of opening and keeping open previously collapsed or obstructed airways is sound, the technique for doing so, as well as the potential benefits regarding patient outcome are highly controversial in light of recent randomized controlled trials. Moreover, a variety of alternative therapies that provide even less robust evidence have been investigated, including prone positioning, neuromuscular blockade, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, and unconventional ventilatory modes such as airway pressure release ventilation. With the exception of prone positioning, these modalities are limited by their own balance of risks and benefits, which can be significantly influenced by the practitioner\'s experience. This review explores the rationale, evidence, advantages and disadvantages of each of these therapies as well as available methods to identify suitable candidates for recruitment maneuvers, with a summary on their application in veterinary medicine. Undoubtedly, the heterogeneous and evolving nature of acute respiratory distress syndrome and individual lung phenotypes call for a personalized approach using new non-invasive bedside assessment tools, such as electrical impedance tomography, lung ultrasound, and the recruitment-to-inflation ratio to assess lung recruitability. Data available in human medicine provide valuable insights that could, and should, be used to improve the management of veterinary patients with severe respiratory failure with respect to their intrinsic anatomy and physiology.

UNASSIGNED: Since the outbreak of the 2019 novel coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) and sepsis resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have surged in intensive care units around the world. The heterogeneity of ARDS and sepsis has long been observed, and multiple subphenotypes and endotypes correlated with different outcomes and treatment response have been identified in the search for treatable traits. Despite their similarity to typical ARDS and sepsis, COVID-19-associated ARDS and sepsis harbor distinct features, raising the question as to whether they could be considered as subphenotypes or endotypes of the historical syndromes and, accordingly, benefit from specific therapeutic strategies. This review aimed to summarize and discuss the current knowledge of COVID-19-associated critical illness and the intrinsic subphenotypes or endotypes.
UNASSIGNED: Literature on the pathogenesis of COVID-19 and the subphenotyping of COVID-19-associated critical illness was derived from the PubMed database and reviewed.
UNASSIGNED: Accumulating evidence, varying from clinical observation to basic research, has contributed to revealing the fundamental pathophysiological features of severe COVID-19 and has advanced our knowledge of the disease. COVID-19-associated ARDS and sepsis exhibit some distinctive features compared to the classic syndromes, including remarkable vascular abnormality and coagulopathy, and distinct respiratory mechanics and immune response. Some conventional subphenotypes derived from classic ARDS and sepsis have been validated in COVID-19, while novel subphenotypes and endotypes have also been identified in patients with this disease, who experience variable clinical outcomes and treatment responses.
UNASSIGNED: Subphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.

UNASSIGNED: Acute respiratory distress syndrome (ARDS) is a heterogeneous illness that has a high mortality rate. The role and predictive value of soluble thrombomodulin (sTM) in ARDS mortality is disputable, so the present study aimed to evaluate the association and predictive value of sTM for the in-hospital mortality of ARDS.
UNASSIGNED: PubMed, Web of Science, Embase, Cochrane Library, Chongqing VIP, WanFang, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature databases were searched for relevant literature published before October 10, 2022. Relevant observable studies were included for analysis. The Newcastle-Ottawa Scale and QUAPAS (Quality Assessment of Prognostic Accuracy Studies) were employed to appraise the quality of the included studies.
UNASSIGNED: Thirteen articles were included in the present study. The eligible studies were of moderate to high quality [Newcastle-Ottawa Scale (NOS) 5-8 scores], and the high risk of bias in the included studieson predictive value was mainly distributed in participant and analysis domains of QUAPAS. There were 1,992 patients with ARDS, and 538 died. Our meta-analysis demonstrated that nonsurvivors had more significantly increased sTM levels than did survivors [standardized mean difference (SMD) =1.473; 95% CI: 0.874-2.072; P<0.001]. Elevated sTM levels had an independent correlation with higher mortality in patients with ARDS [pooled odds ratio (OR) =2.126; 95% CI: 1.548-2.920; P<0.001]. sTM showed satisfactory performance in predicting the mortality of ARDS [summary receiver operating characteristic curve (SROC) =0.78; 95% CI: 0.64-0.89]. The pooled sensitivity was 72% (95% CI: 66-77%), and the pooled specificity was 77% (95% CI: 72-82%). Subgroup analysis showed no significant difference in the sTM levels between nonsurvivors and survivors in terms of patients with direct ARDS (SMD =0.813; 95% CI: -0.673 to 2.229; P=0.253).
UNASSIGNED: sTM is associated with hospital mortality in ARDS and shows moderate predictive performance. As a result, it is a potential candidate for predicting the mortality of ARDS. However, caution is needed when sTM is used to predict adverse outcomes in patients with direct ARDS.

UNASSIGNED: Acute respiratory distress syndrome (ARDS) occurs in different populations, and it is very challenging to manage heterogeneous patient groups. Artificial intelligence (AI) aids in interpreting complex data of patients with ARDS and can be used to detect adverse events as it can automatically capture complex relationships. This review aimed to explore the application and progress of AI in ARDS (e.g., subgroup classification of patients with ARDS via unsupervised clustering and supervised predictive models for early detection) and identify the current ARDS-related problems that can be solved using AI.
UNASSIGNED: This comprehensive and narrative review was performed to obtain information about the application of AI in ARDS and summarize its subtypes and predictive models.
UNASSIGNED: The current applications of AI and machine learning in ARDS include ARDS subgroup classification, diagnosis, and survival prediction. In this review, the current problems that should be addressed by AI in ARDS were identified, and our findings may serve as a useful reference for its translational use in the ARDS field.
UNASSIGNED: Owing to the discovery of hyper- and hypoinflammatory subtypes, individualized treatment of ARDS is possible, and diagnosis and survival prediction are essential in disease management and planning. However, prospective studies should clarify the reliability and generalizability of the results using AI and machine learning and performing bedside testing in larger populations to establish a more stable and time-resilient model. Therefore, a consensus on conducting and reporting machine learning studies in medicine should be urgently established.

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.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. It may occur during the pancytopenia phase following allogeneic hematopoietic cell transplantation (HCT). ARDS is rare following HCT. Mesenchymal stromal cells (MSCs) have strong anti-inflammatory effect and first home to the lung following intravenous infusion. MSCs are safe to infuse and have almost no side effects. During the Covid-19 pandemic many patients died from ARDS. Subsequently MSCs were evaluated as a therapy for Covid-19 induced ARDS. We report three patients, who were treated with MSCs for ARDS following HCT. Two were treated with MSCs derived from the bone marrow (BM). The third patient was treated with MSCs obtained from the placenta, so-called decidua stromal cells (DSCs). In the first patient, the pulmonary infiltrates cleared after infusion of BM-MSCs, but he died from multiorgan failure. The second patient treated with BM-MSCs died of aspergillus infection. The patient treated with DSCs had a dramatic response and survived. He is alive after 7 years with a Karnofsky score of 100%. We also reviewed experimental and clinical studies using MSCs or DSCs for ARDS. Several positive reports are using MSCs for sepsis and ARDS in experimental animals. In man, two prospective randomized placebo-controlled studies used adipose and BM-MSCs, respectively. No difference in outcome was seen compared to placebo. Some pilot studies used MSCs for Covid-19 ARDS. Positive results were achieved using umbilical cord and DSCs however, optimal source of MSCs remains to be elucidated using randomized trials.