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.

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.

FRailty in Australian patients admitted to Intensive care unit after eLective CANCER-related SURGery: a retrospective multicentre cohort study (FRAIL-CANCER-SURG study).

BACKGROUND: The association between frailty and short-term and long-term outcomes in patients receiving elective surgery for cancer remains unclear, particularly in those admitted to the ICU. METHODS: In this multicentre retrospective cohort study, we included adults ≥16 yr old admitted to 158 ICUs in Australia from January 1, 2018 to March 31, 2022 after elective surgery for cancer. We investigated the association between frailty and survival time up to 4 yr (primary outcome), adjusting for a prespecified set of covariates. We analysed how this association changed in specific subgroups (age categories [<65, 65-80, ≥80 yr], and those who survived hospitalisation), and over time by splitting the survival information at monthly intervals. RESULTS: We included 35,848 patients (median follow-up: 18.1 months [inter-quartile range: 8.3-31.1 months], 19,979 [56.1%] male, median age 69.0 yr [inter-quartile range: 58.8-76.0 yr]). Some 3502 (9.8%) patients were frail (defined as clinical frailty scale ≥5). Frailty was associated with lower survival (hazard ratio: 1.72, 95% confidence interval [CI]: 1.59-1.86 compared with clinical frailty scale ≤4); this was concordant across several sensitivity analyses. Frailty was most strongly associated with mortality early on in follow-up, up to 10 months (hazard ratio: 1.39, 95% CI: 1.03-1.86), but this association plateaued, and its predictive capacity subsequently diminished with time up until 4 yr (1.96, 95% CI: 0.73-5.28). Frailty was associated with similar effects when stratified based on age, and in those who survived hospitalisation. CONCLUSIONS: Frailty was associated with poorer outcomes after an ICU admission after elective surgery for cancer, particularly in the short term. However, its predictive capacity with time diminished, suggesting a potential need for longitudinal reassessment to ensure appropriate prognostication in this population.

DUETS for Light's in separating exudate from transudate.

BACKGROUND: Fifty years since its inception, Light's criteria have aided in classifying pleural effusions (PEs) as exudates if 1 or more criteria are met. Thoracic ultrasound (US) emerges as a non-invasive technique for point of care use especially if pleural procedures are contemplated. OBJECTIVE: We aimed to develop a score based on radiological and US features that could separate exudates from transudates without serum and pleural fluid biochemical tests necessary for Light's criteria. METHODS: A prospective review of consecutive patients with PE who underwent thoracocentesis was performed. CXRs were evaluated for laterality followed by US for echogenicity, pleural nodularity, thickening and septations. PE was classified as exudate or transudate according to Light's criteria and corroborated with albumin gradient. A score combining radiological and US features was developed. RESULTS: We recruited 201 patients with PE requiring thoracocentesis. Mean age was 64 years, 51% were females, 164 (81.6%) were exudates, and 37 (18.4%) were transudates. Assigning 1-point for Diaphragmatic nodularity, Unilateral, Echogenicity, Pleural Thickening and Septations, DUETS ranged from 1 to 5. DUETS ≥2 indicated high likelihood for exudate (PPV 98.8%, NPV 100%) with 1% misclassification versus 6.9% using Light's criteria (p < 0.001). CONCLUSION: DUETS separated exudates from transudates with good accuracy, and could obviate paired serum and pleural fluid tests necessary for Light's criteria computation. Our study reflected real world practice where DUETS performed better than Light's criteria for PE that arose from more than one disease processes, and in the evaluation of patients with PE who have received diuretics.

Preoperative anemia and anemia treatment in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: We aimed to conduct a systematic review and meta-analysis to assess the effects of anemia and anemia severity on patient outcomes in cardiac surgery and determine whether preoperative treatments confer postoperative benefit. SOURCE: We searched four international databases for observational and randomized studies published until 1 October 2022. Study quality was assessed via Newcastle-Ottawa scores and the Cochrane Risk-of-Bias 2 tool and certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations approach. We conducted random-effects meta-analyses for our primary outcome of mortality, for secondary outcomes including length of stay (LOS) in the hospital and intensive care unit, and for postsurgical complications. As part of a secondary analysis, we analyzed short-term preoperative anemia treatments and conducted trial sequential analysis of randomized trials to assess the efficacy of these treatment programs. PRINCIPAL FINDINGS: We included 35 studies (159,025 patients) in our primary meta-analysis. Preoperative anemia was associated with increased mortality (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.2 to 2.9; P < 0.001, high certainty). Study-level meta-regression revealed lower hemoglobin levels and studies with lower proportions of male patients to be associated with increased risk of mortality. Preoperative anemia was also associated with an increase in LOS and postsurgical complications. Our secondary analysis (seven studies, 1,012 patients) revealed short-term preoperative anemia treatments did not significantly reduce mortality (OR, 1.1; 95% CI, 0.65 to 1.9; P = 0.69). Trial sequential analysis suggested that there was insufficient evidence to conclude if treatment programs yield any benefit or harm. CONCLUSIONS: Preoperative anemia is associated with mortality and morbidity after cardiac surgery. More research is warranted to test the efficacy of current anemia treatment programs. STUDY REGISTRATION: PROSPERO (CRD42022319431); first submitted 17 April 2023.

RéSUMé: OBJECTIF: Notre objectif était de mener une revue systématique et une méta-analyse pour évaluer les effets de l'anémie et de la gravité de l'anémie sur les devenirs des patient·es en chirurgie cardiaque et déterminer si les traitements préopératoires conféraient un bénéfice postopératoire. SOURCES: Nous avons réalisé des recherches dans quatre bases de données internationales pour en extraire des études observationnelles et randomisées publiées jusqu'au 1er octobre 2022. La qualité des études a été évaluée à l'aide des scores de Newcastle-Ottawa et de l'outil Cochrane 2 sur le risque de biais, et la certitude des données probantes a été évaluée selon l'approche GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Nous avons réalisé des méta-analyses à effets aléatoires pour notre critère d'évaluation principal de mortalité, pour les critères d'évaluation secondaires, notamment la durée du séjour à l'hôpital et à l'unité de soins intensifs, et pour les complications postopératoires. Dans le cadre d'une analyse secondaire, nous avons examiné les traitements préopératoires de l'anémie à court terme et effectué une analyse séquentielle d'études randomisées afin d'évaluer l'efficacité de ces modalités de traitement. CONSTATATIONS PRINCIPALES: Nous avons inclus 35 études portant sur 159 025 patient·es dans notre méta-analyse. L'anémie préopératoire était associée à une augmentation de la mortalité (rapport de cotes [RC], 2,5; intervalle de confiance [IC] à 95 %, 2,2 à 2,9; P < 0,001, certitude élevée). La méta-régression au niveau de l'étude a révélé que des taux d'hémoglobine plus faibles et des études avec des proportions plus faibles de patients masculins étaient associées à un risque accru de mortalité. L'anémie préopératoire était également associée à une augmentation de la durée de séjour et des complications postopératoires. Notre analyse secondaire (sept études, 1012 patient·es) a révélé que les traitements préopératoires de l'anémie à court terme ne réduisaient pas significativement la mortalité (RC, 1,1; IC 95 %, 0,65 à 1,9; P = 0,69). L'analyse séquentielle des études a suggéré qu'il n'y avait pas suffisamment de données probantes pour conclure si les modalités de traitement entraînaient un bénéfice ou un préjudice. CONCLUSION: L'anémie préopératoire est associée à la mortalité et à la morbidité après une chirurgie cardiaque. D'autres recherches sont justifiées pour tester l'efficacité des programmes actuels de traitement de l'anémie. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022319431); première soumission le 17 avril 2023.

Frailty in Critically Ill Patients with COVID-19: The Lessons Learned.

The coronavirus disease 2019 (COVID-19) pandemic has unquestionably transformed the field of intensive care medicine. Never have we witnessed millions of patients develop acute respiratory failure in such a short span of time. This led to extensive resource constraints and difficulty in treating patients. However, this also gave rise to several innovations that have spurred the development and progress of intensive care medicine as a specialty. In this chapter, we explore an overview of frailty, the impact of frailty in patients with severe COVID-19 respiratory failure, and the available supports, by summarising the current literature. This chapter also discusses the lessons learnt from each of the sections that can be applied to daily clinical practice. The chapter also proposes insights into future research.

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.

Evaluating the accuracy of a self-administered smartphone hearing test application in a geriatric population.

BACKGROUND: As the global population ages, hearing loss becomes increasingly prevalent, and is associated with neurocognitive and psychiatric comorbidities, impacting quality of life. Early screening and timely intervention might prevent or delay cognitive decline, a gap in care that can potentially be addressed by self-administered smartphone hearing tests. OBJECTIVE: This study aims to evaluate the accuracy of Mimi™ (Berlin, Germany), a commercially available self-administered smartphone hearing test compared to pure tone audiogram (PTA) in terms of both hearing levels and hearing thresholds in our local geriatric population > 65 years-old. METHOD: Fifty-two participants above 65 years of age requiring conventional audiograms were recruited from a National Referral University Hospital Otolaryngology clinic from March to June 2022. All participants were administered the conventional PTA tests in a sound-proof booth conducted by audiology technicians followed by Mimi™ Hearing Test in a quiet clinic room. Comparisons between the hearing levels of both tests were analyzed using Spearman's rank correlation coefficient, Bland-Altman plots and Gwet's Kappa which looked at concordance. Hearing thresholds were then analysed using the Wilcoxon signed rank (SR) test. RESULTS: Mimi™ showed strong to very strong correlation with good agreement compared to readings obtained from formal PTA. Concordance in determining hearing loss also showed substantial to almost perfect agreement at each individual frequency, with values of kappa falling between 0.735-0.857. In terms of thresholds, there were no significant differences in thresholds given by both tests except for 2.0 kHz, HFPTA and 4FPTA (p < 0.05). CONCLUSION: Mimi™ serves as a good screening tool for detection of moderate hearing loss for early pickup and treatment except at higher frequencies. The smartphone hearing test is also less accurate in determining the extent of hearing loss and formal PTA after hearing loss is detected on screening should still be standard of care.

The interplay between frailty status and persistent critical illness on the outcomes of patients with critical COVID-19: A population-based retrospective cohort study.

OBJECTIVES: Persistent critical illness (PerCI) occurs when the patient's prolonged intensive care unit (ICU) stay results in complications that become the primary drivers of their condition, rather than the initial reason for their admission. Patients with frailty have a higher risk of developing and dying from PerCI. We aimed to investigate the interplay of frailty and PerCI in critically ill patients with COVID-19. METHOD: We conducted a retrospective multicentre cohort study including 103 Australian and New Zealand ICUs over the period of January 2020 to December 2021. We included all adult patients with COVID-19 and documented the Clinical Frailty Scale (frail ≥ 5). PerCI is defined as an ICU length of stay of ≥10 days. We aimed to investigate the hospital mortality with and without PerCI across varying degrees of frailty and examined the potential interaction effect between frailty status and PerCI. RESULTS: The prevalence of PerCI was similar between patients with and without frailty (25.4% vs. 27.9%; p = 0.44). Hospital mortality was higher in patients with PerCI than in those without (28.8% vs. 9.3%; p < 0.001). Mortality in patients with PerCI also increased with increasing frailty (p < 0.001). Frailty independently predicted hospital mortality. When adjusted for Australia and New Zealand risk of death mortality prediction model and sex, the impact of frailty was no different in patients with and without PerCI (odds ratio = 1.30 [95% confidence interval: 1.14-1.49] vs. (odds ratio = 1.46 [95% confidence interval: 1.29-1.64]). Furthermore, increasing frailty did not influence mortality in patients with PerCI more (or less) than in those without PerCI (pinteraction = 0.82). CONCLUSIONS: The presence of frailty independently predicted hospital mortality in patients with PerCI with COVID-19, but the impact of frailty on mortality was no different in those who developed PerCI from those without PerCI.

Thoracic Epidural Anesthesia in Cardiac Surgery: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Research on fast-track recovery protocols postulates that thoracic epidural anesthesia (TEA) in cardiac surgery contributes to improved postoperative outcomes. However, concerns about TEA's safety hinder its widespread usage. We conducted a systematic review and meta-analysis to assess the benefits and risks of TEA in cardiac surgery. METHODS: We searched 4 databases for randomized controlled trials (RCTs) assessing the use of TEA against only general anesthesia (GA) in adults undergoing cardiac surgery, up till June 4, 2022. We conducted random-effects meta-analyses, evaluated risk of bias using the Cochrane Risk-of-Bias 2 tool, and rated certainty of evidence via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Primary outcomes were intensive care unit (ICU), hospital length of stay, extubation time (ET), and mortality. Other outcomes included postoperative complications. Trial sequential analysis (TSA) was conducted on all outcomes to elicit statistical and clinical benefit. RESULTS: Our meta-analysis included 51 RCTs (2112 TEA patients and 2220 GA patients). TEA significantly reduced ICU length of stay (-6.9 hours; 95% confidence interval [CI], -12.5 to -1.2; P = .018), hospital length of stay (-0.8 days; 95% CI, -1.1 to -0.4; P < .0001), and ET (-2.9 hours; 95% CI, -3.7 to -2.0; P < .0001). However, we found no significant change in mortality. TSA found that the cumulative Z-curve passed the TSA-adjusted boundary for ICU length of stay, hospital length of stay, and ET, suggesting a clinical benefit. TEA also significantly reduced pain scores, pooled pulmonary complications, transfusion requirements, delirium, and arrhythmia, without additional complications such as epidural hematomas, of which the risk was estimated to be <0.14%. CONCLUSIONS: TEA reduces ICU and hospital length of stay, and postoperative complications in patients undergoing cardiac surgery with minimal reported complications such as epidural hematomas. These findings favor the use of TEA in cardiac surgery and warrant consideration for use in cardiac surgeries worldwide.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS. METHODS: MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. RESULTS: Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy. CONCLUSIONS: Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

Extracorporeal membrane oxygenation in patients with hematologic malignancies: a systematic review and meta-analysis.

Hematological malignancies (HM) have been, until recently, viewed as contraindications to extracorporeal membrane oxygenation (ECMO) due to bleeding and infectious complications. However, conflicting literature regarding whether ECMO should be used for patients with HM still exists. We conducted a random effects meta-analysis to investigate the outcomes of patients with HM on ECMO. We searched Medline, Embase, Scopus, and Cochrane through 10 October 2021. Risk of bias and certainty of evidence were assessed using the JBI checklists and GRADE approach respectively. Thirteen observational studies (422 patients with HM, 9778 controls without HM) were included. The pooled in-hospital mortality for patients with HM and those with hematopoietic stem cell transplants for HM indications needing ECMO were 79.1% (95%CI: 70.2-86.9%) and 87.7% (95%CI: 80.4-93.8%), respectively. Subgroup analyses found that mortality was higher in adults than children (85.1% vs 67.9%, pinteraction = 0.003), and in Asia compared to North America and Europe (93.8% vs 69.6%, pinteraction < 0.001). Pooled ECMO duration was 10.0 days (95%CI: 7.5-12.5); pooled ICU and hospital lengths of stay were 19.8 days (95%CI: 12.4-27.3) and 43.9 days (95%CI: 29.4-58.4) respectively. Age (regression coefficient [B]: 0.008, 95%CI: 0.003-0.014), proportion of males (B: 1.799, 95%CI: 0.079-3.519), and ECMO duration (B: - 0.022, 95%CI: - 0.043 to - 0.001) were significantly associated with higher mortality. In-hospital mortality of patients with HM who needed ECMO was 79.1%, with better outcomes in children, and in North America and Europe. ECMO should not be regarded as routine support therapy in these patients but can be carefully considered on a case-by-case basis.

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. METHODS: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. RESULTS: Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8-52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. CONCLUSIONS: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Direct oral anticoagulants in atrial fibrillation following cardiac surgery: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have been increasingly used as anticoagulation therapy in the postoperative period. However, their effectiveness in post-cardiac surgical atrial fibrillation is yet to be determined. METHODS: We conducted a meta-analysis, searching three international databases from 1 January 2003 to 26 January 2022 for studies reporting on DOACs in at least 10 adult patients (>18 yr of age) with post-cardiac surgical atrial fibrillation. The primary outcomes were major neurological events and bleeding; secondary outcomes were mortality, hospital and ICU length of stay, cost, and other complications from therapy. We included studies of any design, including RCTs, cohort studies with and without propensity score matching methods, and single-armed case series. RESULTS: Twelve studies (8587 DOACs; 8315 warfarin) were included in this meta-analysis. The incidences of postoperative bleeding and major neurological events with DOACs were 7.3% (95% confidence interval [CI]: 3.4-14.7%) and 2.2% (95% CI: 0.9-4.9%), respectively. The incidence of major neurological events was lower in high-risk patients, including those with hypertension and higher CHA2DS2-VASc score, whereas patients with prior transient ischaemic attack or stroke had higher incidence of bleeding. Trial sequential analysis revealed that the cumulative Z-curve crossed the conventional boundary of benefit. Compared with warfarin, DOACs reduced the risk of bleeding (relative risk [RR] 0.74; 95% CI: 0.62-0.89; P=0.0011) and major neurological events (RR 0.63; 95% CI: 0.48-0.83; P=0.0012) but not mortality (RR 1.02; 95% CI: 0.77-1.35; P=0.090). CONCLUSIONS: DOACs reduced bleeding and major neurological events in patients with post-cardiac surgical atrial fibrillation, appearing safer than warfarin in this context. However, which specific DOAC provides the most effective anticoagulation in this patient population needs further investigation. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021282777.

Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION: Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01). CONCLUSIONS: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Prone positioning (PP) improves oxygenation and respiratory mechanics and is associated with lower mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS). Despite this, some patients develop refractory hypoxemia and hypercapnia requiring venovenous extracorporeal membrane oxygenation (VV ECMO) support and are usually cared for in supine position. The physiologic and outcome benefits of routine PP of patients during VV ECMO remains unclear. Hence, we conducted the systematic review and meta-analysis to evaluate the outcome benefits of PP for patients with ARDS being treated with VV ECMO. METHODS: After registration with PROSPERO (CRD42020199723), MEDLINE, EMBASE, Scopus and Cochrane databases were searched for relevant studies that reported PP in more than 10 adult patients supported with VV ECMO from origin to 1 March 2021. Studies were reviewed for quality using appropriate Joanna Briggs Institute (JBI) checklists, and certainty of evidence was assessed using the GRADE approach. The random-effects model (DerSimonian and Laird) was used. The primary outcome of interest was cumulative survival. Secondary outcomes were intensive care unit length of stay (ICU LOS) and ECMO duration. Changes in arterial blood gas (ABG) values, ventilator mechanics and complication rates were also studied. RESULTS: Of 812 potentially relevant publications, 12 studies (640 patients) met our inclusion criteria. Due to overlapping study populations, 11 studies were included in the final meta-analysis. Cumulative survival in patients that underwent PP was 57% (95% CI 41.9-71.4, high certainty). Patients that underwent PP had longer ICU LOS (+ 14.5 days, 95% CI 3.4-25.7, p = 0.01) and ECMO duration (+ 9.6 days, 95% CI 5.5-13.7, p < 0.0001). After PP, patients had significantly higher PaO2/FiO2 ratio, lower PaCO2 and reduced ventilator driving pressure, and no major complications were reported. CONCLUSIONS: PP during VV ECMO appears safe with a cumulative survival of 57% and may result in longer ECMO runs and ICU LOS. However, evidence from appropriately designed randomized trials is needed prior to widespread adoption of PP on VV ECMO.

Venoarterial extracorporeal membrane oxygenation as mechanical circulatory support in adult septic shock: a systematic review and meta-analysis with individual participant data meta-regression analysis.

BACKGROUND: While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival. METHODS: We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. DATA SYNTHESIS: We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%-72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%-60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%-73.0%) and North America (45.5%, 95%-CI: 16.7%-75.8%). GRADE assessment indicated high certainty of evidence for pooled survival. CONCLUSIONS: When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.

Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: There are several reports of extracorporeal membrane oxygenation (ECMO) use in patients with coronavirus disease 2019 (COVID-19) who develop severe acute respiratory distress syndrome (ARDS). We conducted a systematic review and meta-analysis to guide clinical decision-making and future research. METHODS: We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019 to 10 January 2021 for observational studies or randomised clinical trials examining ECMO in adults with COVID-19 ARDS. We performed random-effects meta-analyses and meta-regression, assessed risk of bias using the Joanna Briggs Institute checklist and rated the certainty of evidence using the GRADE approach. Survival outcomes were presented as pooled proportions while continuous outcomes were presented as pooled means, both with corresponding 95% confidence intervals [CIs]. The primary outcome was in-hospital mortality. Secondary outcomes were duration of ECMO therapy and mechanical ventilation, weaning rate from ECMO and complications during ECMO. RESULTS: We included twenty-two observational studies with 1896 patients in the meta-analysis. Venovenous ECMO was the predominant mode used (98.6%). The pooled in-hospital mortality in COVID-19 patients (22 studies, 1896 patients) supported with ECMO was 37.1% (95% CI 32.3-42.0%, high certainty). Pooled mortality in the venovenous ECMO group was 35.7% (95% CI 30.7-40.7%, high certainty). Meta-regression found that age and ECMO duration were associated with increased mortality. Duration of ECMO support (18 studies, 1844 patients) was 15.1 days (95% CI 13.4-18.7). Weaning from ECMO (17 studies, 1412 patients) was accomplished in 67.6% (95% CI 50.5-82.7%) of patients. There were a total of 1583 ECMO complications reported (18 studies, 1721 patients) and renal complications were the most common. CONCLUSION: The majority of patients received venovenous ECMO support for COVID-19-related ARDS. In-hospital mortality in patients receiving ECMO support for COVID-19 was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related ARDS. Increasing age was a risk factor for death. Venovenous ECMO appears to be an effective intervention in selected patients with COVID-19-related ARDS. PROSPERO CRD42020192627.

Vascular Complications of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Regression Analysis.

OBJECTIVES: Perform a systematic review and meta-analysis of vascular complications associated with extracorporeal membrane oxygenation and identify prognostic and predictive factors. DATA SOURCES: Systematic search for publications reporting vascular complications on extracorporeal membrane oxygenation, published from 1972 to January 31, 2020, was conducted via PubMed, Scopus, and Embase. STUDY SELECTION: Of 4,076 references screened, 47 studies with 6,583 patients were included in final analyses. Studies with fewer than 10 patients were excluded. DATA EXTRACTION: Relevant data, including demographics, comorbidities, extracorporeal membrane oxygenation and cannulation characteristics, occurrence rates of early and late vascular complications, patient outcomes, and use of distal perfusion cannula, were extracted from selected articles into an excel sheet specifically designed for this review. DATA SYNTHESIS: Random-effects meta-analyses and meta-regression analyses were undertaken. Overall pooled estimate of vascular complications in our meta-analysis was 29.5% (95% CI, 23.6-35.9%). Two-thousand three-hundred forty-seven vascular complications in 6,124 venoarterial extracorporeal membrane oxygenation patients compared with 95 in 459 venovenous extracorporeal membrane oxygenation patients (odds ratio, 2.35; 95% CI, 1.87-2.96; p < 0.0001) were analyzed. Successful weaning off extracorporeal membrane oxygenation occurred in 60.6% of pooled patients; 46.2% were eventually discharged. Pooled prevalences of vascular complications like significant bleeding, limb ischemia, and cannula site bleeding were 15.4% (95% CI, 8.6-23.7%), 12.6% (95% CI, 10.0-15.5%), and 12.6% (95% CI, 9.6-18.5%), respectively. Meta-analysis showed that the use of distal perfusion cannula was associated with lower odds of limb ischemia (odds ratio, 1.93; 95% CI, 1.17-2.47; p = 0.03) Meta-regression showed that male sex, smoking, advanced age, and comorbidities contributed to higher in-hospital mortality, while distal perfusion cannula was protective. CONCLUSIONS: Nearly a third of patients on extracorporeal membrane oxygenation develop vascular complications; elderly males with comorbidities appear vulnerable. The use of distal perfusion cannulas caused significant reduction in limb ischemia and mortality.