Epidemiology and outcomes of patients with tuberculosis requiring extracorporeal membrane oxygenation: An ELSO registry analysis.

PURPOSE: This study aimed to analyze data from the Extracorporeal Life Support Organization (ELSO) registry to elucidate the epidemiology and outcomes of patients with tuberculosis necessitating extracorporeal membrane oxygenation (ECMO), an intervention typically employed in treating severe acute respiratory distress syndrome (ARDS), but infrequently reported in tuberculosis contexts. METHODS: A retrospective analysis was conducted utilizing the ELSO registry data spanning from 2003 to 2022, specifically targeting patients with tuberculosis who underwent ECMO. Primary outcomes included survival to hospital discharge, while secondary outcomes encompassed pre-ECMO support, ECMO duration, complications, and discharge destinations. Univariate and multivariate Cox proportional hazard regression analyses were employed to identify factors influencing survival rates. RESULTS: The analysis included 169 patients with tuberculosis, with a median ECMO support duration of 233 h. The weaning success rate was recorded at 62.7 %, and 55 % of patients achieved survival to hospital discharge. Complications arose in 69.8 % of cases, predominantly mechanical complications (46.6 %). Multivariate Cox regression analysis identified complications (HR: 0.448, 95 % CI: 0.222-0.748, P=0.001), infections (HR: 0.483, 95 % CI: 0.241-0.808, P=0.001), and prolonged intervals from admission to ECMO initiation (HR: 0.698, 95 % CI: 0.396-0.901, P=0.018) as significant factors correlated with decreased survival likelihood. CONCLUSION: ECMO presents as a viable treatment option for patients with tuberculosis; however, timely initiation and meticulous management are critical to mitigate complications and enhance patient outcomes. IMPLICATION FOR CLINICAL PRACTICE: Accurate identification of optimal ECMO initiation timing for eligible patients with tuberculosis can significantly enhance clinical outcomes in critical care settings, such as intensive care units.

Neurological monitoring and management for adult extracorporeal membrane oxygenation patients: Extracorporeal Life Support Organization consensus guidelines.

BACKGROUND: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Epidemiology of acute hypoxaemic respiratory failure in Australian and New Zealand intensive care units during 2005-2022. A binational, registry-based study.

PURPOSE: Acute hypoxaemic respiratory failure (AHRF) is a common reason for intensive care unit (ICU) admission. However, patient characteristics, outcomes, and trends over time are unclear. We describe the epidemiology and outcomes of patients with AHRF over time. METHODS: In this binational, registry-based study from 2005 to 2022, we included all adults admitted to an Australian or New Zealand ICU with an arterial blood gas within the first 24 h of ICU stay. AHRF was defined as a partial pressure of oxygen/inspired oxygen ratio (PaO2/FiO2) ≤ 300. The primary outcome was adjusted in-hospital mortality, categorised based on PaO2/FiO2 (mild: 200-300, moderate: 100-200, and severe < 100, and non-linearly). We investigated how adjusted mortality evolved based on temporal trends (by year of admission), sex, age, admission diagnosis and the receipt of mechanical ventilation. RESULTS: Of 1,560,221 patients, 826,106 (52.9%) were admitted with or developed AHRF within the first 24 h of ICU stay. Of these 826,106 patients, 51.4% had mild, 39.3% had moderate, and 9.3% had severe AHRF. Compared to patients without AHRF (5.3%), patients with mild (8%), moderate (14.2%) and severe (29.9%) AHRF had higher in-hospital mortality rates. As PaO2/FiO2 ratio decreased, adjusted in-hospital mortality progressively increased, particularly below an inflection point at a PaO2/FiO2 ratio of 200. The adjusted in-hospital mortality for all patients decreased over time (13.3% in 2005 to 8.2% in 2022), and this trend was similar in patients with and without AHRF. CONCLUSION: The healthcare burden due to AHRF may be larger than expected, and mortality rates remain high in severe AHRF. Although mortality has decreased over time, this may reflect improvements in ICU care in general, rather than specifically in AHRF. More research is required to earlier identify AHRF and stratify these patients at risk of deterioration early, and to validate our findings.

Respiratory Support in COVID-19-Related Respiratory Failure: Lessons Learnt.

The COVID-19 pandemic has undeniably changed the way intensivists manage acute hypoxaemic respiratory failure. Paradigms had evolved particularly in the way we support patients with respiratory failure, and the adjunctive therapies which can be used. Many questions have been answered, and many more generated, from the last few years. For example, is COVID-19 acute respiratory failure and acute respiratory distress syndrome similar to non-COVID-19? How can we personalize therapy in patients with COVID-19, and what are some new statistical tools that we can use to aid in this approach? Is intubation and invasive mechanical ventilation the only way to support patients with acute respiratory failure, or can we turn to other modalities of respiratory support? And what about patients with the most severe form of respiratory failure, how can we support them? In this chapter, we explore the lessons learnt, identifying gaps and advances in knowledge in terms of the pathophysiology of acute respiratory failure, its prognostic factors, oxygen supports, and other therapies. We also touch on how physicians treating patients can tap on international networks to create a "whole that is more than the sum of its parts", and impart clinical insights on the management of acute respiratory failure. Finally, we highlight the importance of a cautious skepticism in our approach to both clinical medicine and evidence-based medicine, highlighting how evidence in a pandemic can rapidly evolve both within an ICU, and longitudinally around the world.

Management of cardiogenic shock: state-of-the-art.

The management of cardiogenic shock is an ongoing challenge. Despite all efforts and tremendous use of resources, mortality remains high. Whilst reversing the underlying cause, restoring/maintaining organ perfusion and function are cornerstones of management. The presence of comorbidities and preexisting organ dysfunction increases management complexity, aiming to integrate the needs of vital organs in each individual patient. This review provides a comprehensive overview of contemporary literature regarding the definition and classification of cardiogenic shock, its pathophysiology, diagnosis, laboratory evaluation, and monitoring. Further, we distill the latest evidence in pharmacologic therapy and the use of mechanical circulatory support including recently published randomized-controlled trials as well as future directions of research, integrating this within an international group of authors to provide a global perspective. Finally, we explore the need for individualization, especially in the face of neutral randomized trials which may be related to a dilution of a potential benefit of an intervention (i.e., average effect) in this heterogeneous clinical syndrome, including the use of novel biomarkers, artificial intelligence, and machine learning approaches to identify specific endotypes of cardiogenic shock (i.e., subclasses with distinct underlying biological/molecular mechanisms) to support a more personalized medicine beyond the syndromic approach of cardiogenic shock.

Myopericarditis following COVID-19 vaccination in children: a systematic review and meta-analysis.

INTRODUCTION: Myopericarditis is a rare but serious coronavirus disease 2019 (COVID-19) vaccine-related adverse event primarily affecting adolescents. Given recent approvals for childhood vaccination, we performed a meta-analysis investigating myopericarditis following messenger ribonucleic acid COVID-19 vaccination in children aged <19 years, focusing on its overall risk and high-risk subgroups. METHODS: We searched MEDLINE via PubMed, Embase and Scopus from inception to 1 August 2022 for observational studies reporting myopericarditis in temporal relation to paediatric COVID-19 vaccination. We conducted random-effects meta-analyses (DerSimonian and Laird) on myopericarditis (primary outcome), myocarditis and pericarditis (secondary outcomes). RESULTS: Of 2115 studies, 12 (59,229,160 doses) studies were included in our analysis. There were 19.8 (95% confidence interval [CI]: 10.4-37.6) myopericarditis cases reported per million doses in children, compared to 23.7 (95% CI: 12.2-46.1) cases in adults (eight studies, 376,899,888 doses; P = 0.70). Compared to the second dose (34.4, 95% CI: 15.2-77.8), the number of cases post-first dose was significantly lower (9.1, 95% CI: 4.4-18.8; P = 0.017), while the number of cases post-third dose was not higher than that of post-second dose (28.4, 95% CI: 10.4-61.8; P = 0.57, global P = 0.031). Males were at higher risk of myopericarditis (67.4, 95% CI: 36.5-124.5) than females (6.9, 95% CI: 3.1-15.3; P < 0.0001). Finally, the number of cases was higher (overall P < 0.0001) among children aged ≥12 years (39.9, 95% CI: 24.1-66.0) than among children aged <12 years (3.0, 95% CI: 2.3-3.9). CONCLUSION: Our meta-analysis showed 19.8 cases of myopericarditis per million doses among children, not significantly different from that of adults. Higher risk subgroups included adolescents, males, and those receiving their second dose of vaccination.

Definition and management of right ventricular injury in adult patients receiving extracorporeal membrane oxygenation for respiratory support using the Delphi method: a PRORVnet study. Expert position statements.

PURPOSE: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an integral part of the management algorithm of patients with severe respiratory failure refractory to evidence-based conventional treatments. Right ventricular injury (RVI) pertaining to abnormalities in the dimensions and/or function of the right ventricle (RV) in the context of VV-ECMO significantly influences mortality. However, in the absence of a universally accepted RVI definition and evidence-based guidance for the management of RVI in this very high-risk patient cohort, variations in clinical practice continue to exist. METHODS: Following a systematic search of the literature, an international Steering Committee consisting of eight healthcare professionals involved in the management of patients receiving ECMO identified domains and knowledge gaps pertaining to RVI definition and management where the evidence is limited or ambiguous. Using a Delphi process, an international panel of 52 Experts developed Expert position statements in those areas. The process also conferred RV-centric overarching open questions for future research. Consensus was defined as achieved when 70% or more of the Experts agreed or disagreed on a Likert-scale statement or when 80% or more of the Experts agreed on a particular option in multiple-choice questions. RESULTS: The Delphi process was conducted through four rounds and consensus was achieved on 31 (89%) of 35 statements from which 24 Expert position statements were derived. Expert position statements provided recommendations for RVI nomenclature in the setting of VV-ECMO, a multi-modal diagnostic approach to RVI, the timing and parameters of diagnostic echocardiography, and VV-ECMO settings during RVI assessment and management. Consensus was not reached on RV-protective driving pressure thresholds or the effect of prone positioning on patient-centric outcomes. CONCLUSION: The proposed definition of RVI in the context of VV-ECMO needs to be validated through a systematic aggregation of data across studies. Until further evidence emerges, the Expert position statements can guide informed decision-making in the management of these patients.

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Immunomodulators in patients receiving extracorporeal membrane oxygenation for COVID-19: a propensity-score adjusted analysis of the ELSO registry.

BACKGROUND: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 increased over the course of the pandemic. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19. METHODS: We retrospectively analysed the Extracorporeal Life Support Organisation registry from 1 January, 2020, through 31 December, 2021, to compare the outcomes of patients who received no immunomodulators, only corticosteroids, only other immunomodulators (selective interleukin blockers, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulin), and a combination of corticosteroids and other immunomodulators administered either before or during ECMO. We used Cox regression models to estimate survival time until 90 days. We estimated the propensity score of receiving different immunomodulators using multinomial regression, and incorporated these scores into the regression models. RESULTS: We included 7181 patients in the final analysis; 6169 patients received immunomodulators either before or during ECMO. The 90-day survival was 58.1% (95%-CI 55.1-61.2%) for patients receiving no immunomodulators, 50.7% (95%-CI 49.0-52.5%) for those receiving only corticosteroids, 62.2% (95%-CI 57.4-67.0%) for those receiving other immunomodulators, and 48.5% (95%-CI 46.7-50.4%) for those receiving corticosteroids and other immunomodulators. Compared to patients without immunomodulators, patients receiving either corticosteroids alone (HR: 1.13, 95%-CI 1.01-1.28) or with other immunomodulators (HR: 1.21, 95%-CI: 1.07-1.54) had significantly shorter survival time, while patients receiving only other immunomodulators had significantly longer survival time (HR: 0.79, 95%-CI: 0.66-0.96). The receipt of immunomodulators (across all three groups) was associated with an increase in secondary infections. CONCLUSIONS: In this cohort study, we found that immunomodulators, in particular corticosteroids, were associated with significantly higher mortality amongst patients receiving ECMO for COVID-19, after adjusting for potential confounding variables and propensity score. In addition, patients receiving corticosteroids with or without other immunomodulators had longer ECMO runs, which has potential implications for resource allocation. While residual confounding likely remains, further studies are required to evaluate the timing of immunomodulators and better understand the possible mechanisms behind this association, including secondary infections.

Pharmacotherapy for Venous Thromboprophylaxis following Total Hip or Knee Arthroplasty: A Systematic Review and Network Meta-analysis.

The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.

Outcomes of Adult Patients With COVID-19 Transitioning From Venovenous to Venoarterial or Hybrid Extracorporeal Membrane Oxygenation in the Extracorporeal Life Support Organization Registry.

This retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry evaluates the outcomes and identifies risk factors associated with conversion from initial venovenous extracorporeal membrane oxygenation (ECMO) support to venoarterial or hybrid ECMO in patients with coronavirus disease 2019 (COVID-19). We collected deidentified data on all adult patients (≥18 years old) diagnosed with COVID who received venovenous extracorporeal membrane oxygenation between March 2020 and November 2022. Patients initially placed on an ECMO configuration other than venovenous (VV) ECMO were excluded from the analysis. Our analysis included data from 12,850 patients, of which 393 (3.1%) transitioned from VV ECMO to an alternative mode. The primary outcome measure was in-hospital mortality, and the conversion group exhibited a higher in-hospital mortality rate. We also examined baseline variables, including demographic information, biochemical labs, and inotrope requirements. Univariate analysis revealed that pre-ECMO arrest, the need for renal replacement therapy, and the use of inotropic agents, particularly milrinone, were strongly associated with the risk of conversion. Notably, even after implementing a 3:1 propensity score matching, the impact of conversion on both mortality and complications remained substantial. Our study underscores an elevated risk of mortality for COVID-19 patients initially treated with VV ECMO who subsequently require conversion to VA-ECMO or hybrid ECMO.

Extracorporeal cardiopulmonary resuscitation versus conventional CPR in cardiac arrest: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR). METHODS: We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days-1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality. RESULTS: We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50-0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45-0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day-1-year survival remained unchanged. CONCLUSIONS: We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.

Extracorporeal Life Support Organization Registry International Report 2022: 100,000 Survivors.

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers.

Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.