Evolution of distal limb perfusion management in adult peripheral venoarterial extracorporeal membrane oxygenation with femoral artery cannulation.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Left atrium veno-arterial extra corporeal membrane oxygenation as temporary mechanical support for cardiogenic shock: A case report.

BACKGROUND: Veno-arterial extra corporeal membrane oxygenation (VA-ECMO) support is commonly complicated with left ventricle (LV) distension in patients with cardiogenic shock. We resolved this problem by transeptally converting VA-ECMO to left atrium veno-arterial (LAVA)-ECMO that functioned as a temporary paracorporeal left ventricular assist device to resolve LV distension. In our case LAVA-ECMO was also functioning as a bridge-to-transplant device, a technique that has been scarcely reported in the literature. CASE SUMMARY: A 65 year-old man suffered from acute myocardial injury that required percutaneous stents. Less than two weeks later, noncompliance to antiplatelet therapy led to stent thrombosis, cardiogenic shock, and cardiac arrest. Femoro-femoral VA-ECMO support was started, and the patient underwent a second coronary angiography with re-stenting and intra-aortic balloon pump placement. The VA-ECMO support was complicated by left ventricular distension which we resolved via LAVA-ECMO. Unfortunately, episodes of bleeding and sepsis complicated the clinical picture and the patient passed away 27 d after initiating VA-ECMO. CONCLUSION: This clinical case demonstrates that LAVA-ECMO is a viable strategy to unload the LV without another invasive percutaneous or surgical procedure. We also demonstrate that LAVA-ECMO can also be weaned to a left ventricular assist device system. A benefit of this technique is that the procedure is potentially reversible, should the patient require VA-ECMO support again. A transeptal LV venting approach like LAVA-ECMO may be indicated over ImpellaTM in cases where less LV unloading is required and where a restrictive myocardium could cause LV suctioning. Left ventricular over-distention is a well-known complication of peripheral VA-ECMO in cardiogenic shock and LAVA ECMO through transeptal cannulation offers a novel and safe approach for treating LV overloading, without the need of an additional percutaneous access.

Evaluation of a new magnetically suspended centrifugal neonatal pump in healthy animals using a veno-venous extracorporeal membrane oxygenation configuration.

BACKGROUND: The objective of this animal study was to evaluate the hemodynamic performance of a new centrifugal pump for extra-corporeal membrane oxygenation (ECMO) support in neonates. METHODS: Six healthy swines were supported with veno-venous ECMO with the New Born ECMOLife centrifugal pump (Eurosets, Medolla, Italy) at different flow rates: 0.25, 0.5, 0.6, and 0.8 L/min; three animals were evaluated at low-flows (0.25 and 0.5 L/min) and three at high-flows (0.6 and 0.8 L/min). Each flow was maintained for 4 hours. Blood samples were collected at different time-points. Hematological and biochemical parameters and ECMO parameters [flow, revolutions per minute (RPM), drainage pressure, and the oxygenator pressure drop] were evaluated. RESULTS: The increase of the pump flow from 0.25 to 0.5 L/min or from 0.6 to 0.8 L/min required significantly higher RPM and produced significantly higher pump pressures [from 0.25 to 0.5 L/min: 1470 (1253-1569) versus 2652 (2589-2750) RPM and 40 (26-57) versus 125 (113-139) mmHg, respectively; p < .0001 for both - from 0.60 to 0.8 L/min: 1950 (1901-2271) versus 2428 (2400-2518) RPM and 66 (62-86) versus 106 (101-113) mmHg, respectively; p < .0001 for both]. Median drainage pressure significantly decreased from -18 (-22; -16) mmHg to -55 (-63; -48) mmHg when the pump flow was increased from 0.25 to 0.5 L/min (p < .0001). When pump flow increased from 0.6 to 0.8 L/min, drainage pressure decreased from -32 (-39; -24) mmHg to -50 (-52; -43) mmHg, (p < .0001). Compared to pre-ECMO values, the median levels of lactate dehydrogenase, d-dimer, hematocrit, and platelet count decreased after ECMO start at all flow rates, probably due to hemodilution. Plasma-free hemoglobin, instead, showed a modest increase compared to pre-ECMO values during all experiments at different pump flow rates. However, these changes were not clinically relevant. CONCLUSIONS: In this animal study, the "New Born ECMOLife" centrifugal pump showed good hemodynamic performance. Long-term studies are needed to evaluate biocompatibility of this new ECMO pump.

Safety and Effectiveness of Carbon Dioxide Removal CO2RESET Device in Critically Ill Patients.

BACKGROUND: In this retrospective study, we report the effectiveness and safety of a dedicated extracorporeal carbon dioxide removal (ECCO2R) device in critically ill patients. METHODS: Adult patients on mechanical ventilation due to acute respiratory distress syndrome (ARDS) or decompensated chronic obstructive pulmonary disease (dCOPD), who were treated with a dedicated ECCO2R device (CO2RESET, Eurosets, Medolla, Italy) in case of hypercapnic acidemia, were included. Repeated measurements of CO2 removal (VCO2) at baseline and 1, 12, and 24 h after the initiation of therapy were recorded. RESULTS: Over a three-year period, 11 patients received ECCO2R (median age 60 [43-72] years) 3 (2-39) days after ICU admission; nine patients had ARDS and two had dCOPD. Median baseline pH and PaCO2 levels were 7.27 (7.12-7.33) and 65 (50-84) mmHg, respectively. With a median ECCO2R blood flow of 800 (500-800) mL/min and maximum gas flow of 6 (2-14) L/min, the VCO2 at 12 h after ECCO2R initiation was 157 (58-183) mL/min. Tidal volume, respiratory rate, and driving pressure were significantly reduced over time. Few side effects were reported. CONCLUSIONS: In this study, a dedicated ECCO2R device provided a high VCO2 with a favorable risk profile.

Higher mean cerebral oxygen saturation shortly after extracorporeal cardiopulmonary resuscitation in patients who regain consciousness.

INTRODUCTION: In cardiac arrest, cerebral ischemia and reperfusion injury mainly determine the neurological outcome. The aim of this study was to investigate the relation between the course of cerebral oxygenation and regain of consciousness in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR). We hypothesized that rapid cerebral oxygenation increase causes unfavorable outcomes. METHODS: This prospective observational study was conducted in three European hospitals. We included adult ECPR patients between October 2018 and March 2020, in whom cerebral regional oxygen saturation (rSO2 ) measurements were started minutes before ECPR initiation until 3 h after. The primary outcome was regain of consciousness, defined as following commands, analyzed using binary logistic regression. RESULTS: The sample consisted of 26 ECPR patients (23% women, Agemean 46 years). We found no significant differences in rSO2 values at baseline (49.1% versus 49.3% for regain versus no regain of consciousness). Mean cerebral rSO2 values in the first 30 min after ECPR initiation were higher in patients who regained consciousness (38%) than in patients who did not regain consciousness (62%, odds ratio 1.23, 95% confidence interval 1.01-1.50). CONCLUSION: Higher mean cerebral rSO2 values in the first 30 min after initiation of ECPR were found in patients who regained consciousness.

Lung mesenchymal cells from patients with COVID-19 driven lung fibrosis: Several features with CTD-ILD derived cells but with higher response to fibrogenic signals and might be more pro-inflammatory.

A subset of severe COVID19 patients develop pulmonary fibrosis, but the pathophysiology of this complication is still unclear. We previously described the possibility to isolate lung mesenchymal cells (LMC) by culturing broncho-alveolar lavage (BAL) cells from patients with pulmonary fibrosis or chronic lung allograft dysfunction. Aim of this study was to investigate the possibility to isolate and characterize LMC from BAL of patients that, two months after discharge for severe COVID19, show CT signs of post-COVID19 fibrosis (Post-COVID) and in some cases has been considered transplant indication. Results were compared with those from BAL of patients with collagen tissue disease-associated interstitial fibrosis (CTD-ILD). BAL fluid levels of TGFß, VEGF, TIMP2, RANTES, IL6, IL8, and PAI1 were assessed. LMC were cultured and expanded, phenotyped by flow cytometry, and tested for osteogenic and adipogenic differentiation. Finally, we tested immunomodulatory and proliferative capabilities, collagen I production + /- TGF-beta stimulation. BAL cytokine and growth factor levels were comparable in the two groups. Efficiency of isolation from BAL was 100% in post-COVID compared to 63% in CTD-ILD. LMC from post-COVID were positive for CD105, CD73, CD90, and negative for CD45, CD34, CD19 and HLA-DR as in CTD-ILD samples. Post-COVID LMC displayed higher collagen production with respect to CTD-ILD LMC. Immunomodulatory capacity towards lymphocytes was very low, while Post-COVID LMC significantly upregulated pro-inflammatory cytokine production by healthy PBMCs. Our preliminary data suggest that LMC from post-COVID19 fibrosis patients share several features with CTD-ILD ones but might have a higher response to fibrogenic signals and pro-inflammatory profile.

Prevalence and Complications of Aberrant Subclavian Artery in Patients With Heritable and Nonheritable Arteriopathies.

BACKGROUND: An aberrant subclavian artery (ASA) (or lusoria) is the most common congenital anomaly of the aortic arch (0.5%-2.2%; female-to-male ratio 2:1 to 3:1). ASA can become aneurysmal and result in dissection, involving Kommerell's diverticulum when present and the aorta. Data of its significance in genetic arteriopathies are not available. OBJECTIVES: The purpose of this study was to assess the prevalence and complications of ASA in gene-positive and -negative nonatherosclerotic arteriopathies. MATERIALS: The series includes 1,418 consecutive patients with gene-positive (n = 854) and gene-negative arteriopathies (n = 564) diagnosed as part of institutional work-up for nonatherosclerotic syndromic and nonsyndromic arteriopathies. Comprehensive evaluation includes genetic counseling, next-generation sequencing multigene testing, cardiovascular and multidisciplinary assessment, and whole-body computed tomography angiography. RESULTS: ASA was found in 34 of 1,418 cases (2.4%), with a similar prevalence in gene-positive (n = 21 of 854, 2.5%) and gene-negative (n = 13 of 564, 2.3%) arteriopathies. Of the former 21 patients, 14 had Marfan syndrome, 5 had Loeys-Dietz syndrome, 1 had type-IV Ehlers-Danlos syndrome, and 1 had periventricular heterotopia type 1. ASA did not segregate with genetic defects. Dissection occurred in 5 of 21 patients with genetic arteriopathies (23.8%; 2 Marfan syndrome and 3 Loeys-Dietz syndrome), all with associated Kommerell's diverticulum. No dissections occurred in gene-negative patients. At baseline, none of the 5 patients with ASA dissection fulfilled criteria for elective repair according to guidelines. CONCLUSIONS: The risk of complications of ASA is higher in patients with genetic arteriopathies and is difficult to predict. In these diseases, imaging of the supra-aortic trunks should enter baseline investigations. Determination of precise indications for repair can prevent unexpected acute events such as those described.

The use of induced hypothermia in extracorporeal membrane oxygenation: A narrative review.

Despite venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) being increasingly used in patients with severe acute respiratory disease syndrome, severe cardiogenic shock, and refractory cardiac arrest, mortality rates still remain high mainly because of the severity of the underlying disease and the numerous complications associated with initiation of ECMO. Induced hypothermia might minimize several pathological pathways present in patients requiring ECMO; even though numerous studies conducted in the experimental setting have reported promising results, there are currently no recommendations suggesting the routine use of this therapy in patients requiring ECMO. In this review, we summarized the existing evidence on the use of induced hypothermia in patients requiring ECMO. Induced hypothermia was a feasible and relatively safe intervention in this setting; however, the effects on clinical outcomes remain uncertain. Whether controlled normothermia has an impact on these patients compared with no temperature control remains unknown. Further randomized controlled trials are required to better understand the role and impact of such therapy in patients requiring ECMO according to the underlying disease.

Extracorporeal life support provision in COVID-19 patients - An international EuroELSO 2022 update survey.

INTRODUCTION: An analysis on the ECLS use for patients with respiratory or cardiac support in COVID-19 based on an international response to EuroELSO survey, aims to generate a more comprehensive understanding of ECLS role during the recent viral pandemic. METHODS: EuroELSO announced the survey at the 10th annual congress in London, May 2022. The survey covered 26 multiple-choice questions. RESULTS: The survey returned 69 questionnaires from 62 centers across 22 European countries and seven centers across five non-European countries. Most of the centers providing ECLS for COVID-19 patients had more than 30 runs for respiratory support since December 2019. In the same period, at least 31 runs in adult COVID-19 patients have been performed in 48 of 69 centers (69.6%). The reported pediatric data from 18 centers is limited to less than the patients per center. CONCLUSION: Majority of the COVID-19 patients received respiratory ECLS support and adult patients dominated. The indications and contraindications are broadly aligned with available guidelines. Most of the centers considered age >65 or biological age as a relative or absolute contraindication for ECLS in COVID-19. ECLS withdrawal criteria in COVID-19 are controversial because the long-term outcomes after ECLS in COVID-19 and the impact of critical illness and the impact of long-COVID are still not known.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

Safety and Effectiveness of Veno-Venous Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy.

Patients receiving extracorporeal membrane oxygenation (ECMO) often suffer from acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT). In our clinical practice, we connected the inlet line of a CRRT machine to the postoxygenator Luer port and the outlet line to the inlet Luer port of the oxygenator. In this case series, we analyzed the interaction between the two machines. Between December 31, 2017, and December 31, 2019, we enrolled 15 patients from the ICU of the San Matteo Hospital, Pavia, Italy. All of them suffered from severe acute respiratory distress syndrome and AKI stage 3. We analyzed 570 hours of CRRT combined with venovenous ECMO and collected 261,751 CRRT data. No discontinuation of CRRT occurred before 48 hours. Most of the alarms occurred within 24 hours of the connection: 22/10,831 (0.2%) showed an outranged inlet pressure, 11/10831 (0.11%) showed an outranged transmembrane pressure, 14/10,831 (0.13%) showed an outranged inlet pressure, and 138/10,831 (1.27%) an outranged effluent pressure. The rate per minute set for the ECMO circuit was correlated with the inlet (ß = 5.38; CI, 95% 1.42-9.35; p = 0.008), transmembrane (ß = 4.6; CI, 95% 1.97-7.24; p = 0.001), effluent (ß = 3.02; CI, 95% 1.15-4.90; p = 0.002), and outlet pressures (ß = 597; CI, 95% 2.31-9.63; p = 0.001) of the CRRT circuit. We reported that our configuration could be safe and effective, however well-designed studies would be beneficial for determining the potential risks and benefits.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe.

BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients. METHODS: This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time. RESULTS: Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1 L/min has been associated with a daily Hpt consumption of 93.371 mg/dL (p = 0.001). CONCLUSIONS: Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.

Systematic review and meta-analysis comparing low-flow duration of extracorporeal and conventional cardiopulmonary resuscitation.

OBJECTIVES: After cardiac arrest, a key factor determining survival outcomes is low-flow duration. Our aims were to determine the relation of survival and low-flow duration of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) and if these 2 therapies have different short-term survival curves in relation to low-flow duration. METHODS: We searched Embase, Medline, Web of Science and Google Scholar from inception up to April 2021. A linear mixed-effect model was used to describe the course of survival over time, based on study-specific and time-specific aggregated survival data. RESULTS: We included 42 observational studies reporting on 1689 ECPR and 375 751 CCPR procedures. Of the included studies, 25 included adults, 13 included children and 4 included both. In adults, survival curves decline rapidly over time (ECPR 37.2%, 29.8%, 23.8% and 19.1% versus CCPR-shockable 36.8%, 7.2%, 1.4% and 0.3% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR with initial shockable rhythms (CCPR-shockable). In children, survival curves decline rapidly over time (ECPR 43.6%, 41.7%, 39.8% and 38.0% versus CCPR-shockable 48.6%, 20.5%, 8.6% and 3.6% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR-shockable. CONCLUSIONS: The short-term survival of ECPR and CCPR-shockable patients both decline rapidly over time, in adults as well as in children. This decline of short-term survival in relation to low-flow duration in ECPR was slower than in conventional cardiopulmonary resuscitation. TRIAL REGISTRATION: Prospero: CRD42020212480, 2 October 2020.

Sars-Cov 2 versus Flu: ECMO-associated bloodstream infections.

SARS-CoV-2 and flu may lead to severe acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO). The aim of the present study is to compare the incidence of bloodstream infections (BSIs) and outcome in patients with flu and SARS-CoV-2 infection hospitalized in ICU and undergoing ECMO. This study is a retrospective analysis of the San Matteo COVID-19 Registry (SMACORE) cohort. The study was conducted from January 2018 to April 2020. Demographic data and microbiological data were recorded during hospitalization. BSIs occurring during ECMO were analyzed. Eighteen patients treated with ECMO, 22 subjects with SARS-CoV-2 infection and 7 with flu, median age 61years for SARS-CoV-2 and 50 for flu (p=NS). Median ECMO duration was similar in the two pathologies. Median time to bloodstream infection from ECMO initiation was similar. Bloodstream infection incidence rate was 2.65 per 100 patients/days for flu and 2.2 per 100 patients/days for SARS-CoV-2. Global infection rate was 5 per 100 patients/days for SARS-CoV-2 patients and 5.3 per 100 patients/days for flu. Mortality during ECMO was 40.9% (5 out of 22 patients) for SARS-CoV-2 infection while none died among flu patients. ECMO-associated mortality was higher in SARS-CoV-2 infection compared with flu infection.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.