Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.

Unloading the Left Ventricle in Venoarterial ECMO: In Whom, When, and How?

Venoarterial extracorporeal membrane oxygenation provides cardiorespiratory support to patients in cardiogenic shock. This comes at the cost of increased left ventricle (LV) afterload that can be partly ascribed to retrograde aortic flow, causing LV distension, and leads to complications including cardiac thrombi, arrhythmias, and pulmonary edema. LV unloading can be achieved by using an additional circulatory support device to mitigate the adverse effects of mechanical overload that may increase the likelihood of myocardial recovery. Observational data suggest that these strategies may improve outcomes, but in whom, when, and how LV unloading should be employed is unclear; all techniques require balancing presumed benefits against known risks of device-related complications. This review summarizes the current evidence related to LV unloading with venoarterial extracorporeal membrane oxygenation.

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.

Behavioural and physiological impacts of low salinity on the sea urchin Echinus esculentus.

Reduced seawater salinity as a result of freshwater input can exert a major influence on the ecophysiology of benthic marine invertebrates, such as echinoderms. While numerous experimental studies have explored the physiological and behavioural effects of short-term, acute exposure to low salinity in echinoids, surprisingly few have investigated the consequences of chronic exposure, or compared the two. In this study, the European sea urchin, Echinus esculentus, was exposed to low salinity over the short term (11‰, 16‰, 21‰, 26‰ and 31‰ for 24 h) and longer term (21, 26 and 31‰ for 25 days). Over the short term, oxygen consumption, activity coefficient and coelomic fluid osmolality were directly correlated with reduced salinity, with 100% survival at ≥21‰ and 0% at ≤16‰. Over the longer term at 21‰ (25 days), oxygen consumption was significantly higher, feeding was significantly reduced and activity coefficient values were significantly lower than at control salinity (31‰). At 26‰, all metrics were comparable to the control by the end of the experiment, suggesting acclimation. Furthermore, beneficial functional resistance (righting ability and metabolic capacity) to acute low salinity was observed at 26‰. Osmolality values were slightly hyperosmotic to the external seawater at all acclimation salinities, while coelomocyte composition and concentration were unaffected by chronic low salinity. Overall, E. esculentus demonstrate phenotypic plasticity that enables acclimation to reduced salinity around 26‰; however, 21‰ represents a lower acclimation threshold, potentially limiting its distribution in coastal areas prone to high freshwater input.

State of the art: Monitoring of the respiratory system during veno-venous extracorporeal membrane oxygenation.

Monitoring the patient receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is challenging due to the complex physiological interplay between native and membrane lung. Understanding these interactions is essential to understand the utility and limitations of different approaches to respiratory monitoring during ECMO. We present a summary of the underlying physiology of native and membrane lung gas exchange and describe different tools for titrating and monitoring gas exchange during ECMO. However, the most important role of VV ECMO in severe respiratory failure is as a means of avoiding further ergotrauma. Although optimal respiratory management during ECMO has not been defined, over the last decade there have been advances in multimodal respiratory assessment which have the potential to guide care. We describe a combination of imaging, ventilator-derived or invasive lung mechanic assessments as a means to individualise management during ECMO.

The intricate physiology of veno-venous extracorporeal membrane oxygenation: an overview for clinicians.

During veno-venous extracorporeal membrane oxygenation (V-V ECMO), blood is drained from the central venous circulation to be oxygenated and decarbonated by an artificial lung. It is then reinfused into the right heart and pulmonary circulation where further gas-exchange occurs. Each of these steps is characterized by a peculiar physiology that this manuscript analyses, with the aim of providing bedside tools for clinical care: we begin by describing the factors that affect the efficiency of blood drainage, such as patient and cannulae position, fluid status, cardiac output and ventilatory strategies. We then dig into the complexity of extracorporeal gas-exchange, with particular reference to the effects of extracorporeal blood-flow (ECBF), fraction of delivered oxygen (FdO2) and sweep gas-flow (SGF) on oxygenation and decarbonation. Subsequently, we focus on the reinfusion of arterialized blood into the right heart, highlighting the effects on recirculation and, more importantly, on right ventricular function. The importance and challenges of haemodynamic monitoring during V-V ECMO are also analysed. Finally, we detail the interdependence between extracorporeal circulation, native lung function and mechanical ventilation in providing adequate arterial blood gases while allowing lung rest. In the absence of evidence-based strategies to care for this particular group of patients, clinical practice is underpinned by a sound knowledge of the intricate physiology of V-V ECMO.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Extracorporeal carbon dioxide removal (ECCO 2 R) devices are effective in reducing hypercapnia and mechanical ventilation support but have not been shown to reduce mortality. This may be due to case selection, device performance, familiarity, or the management. The objective of this study is to investigate the effectiveness and safety of a single ECCO 2 R device (Hemolung) in patients with acute respiratory failure and identify variables associated with survival that could help case selection in clinical practice as well as future research. DESIGN: Multicenter, multinational, retrospective review. SETTING: Data from the Hemolung Registry between April 2013 and June 2021, where 57 ICUs contributed deidentified data. PATIENTS: Patients with acute respiratory failure treated with the Hemolung. The characteristics of patients who survived to ICU discharge were compared with those who died. Multivariable logistical regression analysis was used to identify variables associated with ICU survival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 159 patients included, 65 (41%) survived to ICU discharge. The survival was highest in status asthmaticus (86%), followed by acute respiratory distress syndrome (ARDS) (52%) and COVID-19 ARDS (31%). All patients had a significant reduction in Pa co2 and improvement in pH with reduction in mechanical ventilation support. Patients who died were older, had a lower Pa o2 :F io2 (P/F) and higher use of adjunctive therapies. There was no difference in the complications between patients who survived to those who died. Multivariable regression analysis showed non-COVID-19 ARDS, age less than 65 years, and P/F at initiation of ECCO 2 R to be independently associated with survival to ICU discharge (P/F 100-200 vs <100: odds ratio, 6.57; 95% CI, 2.03-21.33). CONCLUSIONS: Significant improvement in hypercapnic acidosis along with reduction in ventilation supports was noted within 4 hours of initiating ECCO 2 R. Non-COVID-19 ARDS, age, and P/F at commencement of ECCO 2 R were independently associated with survival.

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.

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.

"Bridging the Gap" international ECLS training and simulation - evaluation of the 10th educational corner on EuroELSO congress 2022 in London, United Kingdom.

Introduction: Simulation training offers an authentic team-based learning opportunity without risk to real patients. The Educational Corner at the annual congress of the European Branch of Extracorporeal Life Support Organisation (EuroELSO) provided an opportunity for multiple simulation training sessions facilitated by experts from all over the world.Aim: We aimed to review the educational impact of EuroELSO Educational Corner and whether it provides a quality ECLS training to a wide spectrum of multidisciplinary international attendees utilising high and low fidelity simulation, workshops and hands on sessions.Methods: During the congress, 43 sessions were conducted dedicated to ECLS education with identified educational objectives. The sessions focused on management of adults and children on V-V or V-A ECMO. Adult sessions covered emergencies on mechanical circulatory support with management of LVAD and Impella, managing refractory hypoxemia on V-V ECMO, emergencies on ECMO, renal replacement therapy on ECMO, V-V ECMO, ECPR cannulation and performing perfect simulation. Paediatric sessions covered ECPR neck and central cannulation, renal replacement on ECMO, troubleshooting, cannulation workshop, V-V recirculation, ECMO for single ventricle, PIMS-TS and CDH, ECMO transport and neurological injury.Results: The Educational Corner was attended by more than 400 participants over the two congress days. Majority of responders (88%) reported that training sessions met the set educational goals and objectives and that this would change their current practice. Almost all (94%) reported that they received useful information and 95% would recommend the session to their colleagues.Conclusion: The Educational Corner, as an integral component of the annual EuroELSO congress, achieved the set educational goals and provided quality education based on the recipient survey. Structured multidisciplinary ECLS education with standardised curriculum and feedback is an important key step in delivering quality training to an international audience. Standardisation of European ECLS education remains an important focus of the EuroELSO.

Physiotherapy for patients on extracorporeal membrane oxygenation support: How, When, and Who. An international EuroELSO survey.

BACKGROUND AND PURPOSE: Extracorporeal membrane oxygenation (ECMO) continues to play an essential role in organ support in cardiogenic shock or acute respiratory distress syndrome and bridging to transplantation. The main purpose of the present survey was to define which clinical and organizational practices are adopted for the administration of physiotherapy in adult patients undergoing ECMO support worldwide. METHODS: This international survey was conceived in November 2021. The survey launch was announced at the 10th EuroELSO (European ELSO chapter) Congress, London, May 2022. RESULTS: The survey returned 32 questionnaires from 29 centers across 14 countries. 17 centers (53.1%) had more than 30 intensive care unit beds available and most (46.8%) were able to care for five to 10 patients on extracorporeal life support simultaneously. The predominant physiotherapist-to-patient ratio was 1:>5 (37.5%); physiotherapy was available 5/7 days and 7/7 days by 31.2% and 25% respectively. Respiratory physiotherapy was not defined by a specific protocol in most centers (46.8%) while 31.2% declared that the treatment commences less than 12 h after sedation is stopped/reduced. Mostly, early physiotherapy in non-cooperative ventilated patients was provided within the first 48 h (68.6%) and consisted of as passive range of motion, in-bed positioning, and splinting. Postural passages and sitting were provided to patients and walking was included in those advanced motor activities which are part of the treatment. CONCLUSION: Physiotherapy in patients on ECLS is feasible, however substantial variability exists between centers with a trend of delivering not protocolized and understaffed rehabilitation practices.

Relationship Between Skeletal Muscle Area and Density and Clinical Outcome in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate the prevalence of low skeletal muscle index (area normalized for height) and density, their trajectory of change, and to determine associations with clinical outcome in adults with severe respiratory failure requiring venovenous extracorporeal membrane oxygenation. DESIGN: Prospective observational study. PATIENTS: Adults receiving venovenous extracorporeal membrane oxygenation for a minimum of 72 hours and a maximum of 6 months between September 2010 and June 2017, who had a CT scan which included the third lumbar vertebra. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle index and density was determined using Slice-O-Matic V5.0 (TomoVision, Montreal, QC, Canada). Low skeletal muscle index and density were defined using published criteria. Regression models were used to assess for associations between muscle index and density and clinical outcome. Two-hundred fifteen patients, median (interquartile range) age 46 years (35.0-57.0 yr) were included. Forty-five patients (21.1%) had low skeletal muscle index, and 48 (22.3%) had low skeletal muscle density on commencement of venovenous extracorporeal membrane oxygenation. Low skeletal muscle index was more prevalent in males (28.8% vs 11.6%; χ2 = 9.4; p = 0.002) and was associated with a longer duration of venovenous extracorporeal membrane oxygenation (B = 5.0; 95% CI, 0.2-9.9; p = 0.042). Higher skeletal muscle density was independently associated with ICU survival (odds ratio 1.6 per 10 Hounsfield units; 95% CI, 1.1-2.5; p = 0.025). No relationship was observed between skeletal muscle index nor density and physical function. Adequacy of energy and protein did not influence change in skeletal muscle index or density. CONCLUSIONS: Low skeletal muscle index at the commencement of venovenous extracorporeal membrane oxygenation was associated with a longer duration of venovenous extracorporeal membrane oxygenation, whereas preserved skeletal muscle density was associated with improved survival.

A Comparison of Thrombosis and Hemorrhage Rates in Patients With Severe Respiratory Failure Due to Coronavirus Disease 2019 and Influenza Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation is a lifesaving therapy for patients with severe acute respiratory distress syndrome refractory to conventional mechanical ventilation. It is frequently complicated by both thrombosis and hemorrhage. A markedly prothrombotic state associated with high rates of venous thromboembolism has been described in patients with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) infection. These rates have currently not been described during extracorporeal membrane oxygenation in comparison to other viral pneumonias. DESIGN: Retrospective observational study. SETTING: Single high-volume tertiary critical care department at a university hospital. PATIENTS: Patients 16 years old or greater receiving venovenous extracorporeal membrane oxygenation between March 1, 2020, and May 31, 2020, with coronavirus disease 2019 were compared with a cohort of patients with influenza pneumonia between June 1, 2012, and May 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The rates of venous thromboembolism and hemorrhage were compared in patients with coronavirus disease 2019 against a historic population of patients with influenza pneumonia who required extracorporeal membrane oxygenation. There were 51 patients who received extracorporeal membrane oxygenation due to coronavirus disease 2019 and 80 patients with influenza. At cannulation for extracorporeal membrane oxygenation, 37% of patients with coronavirus disease 2019 compared with 8% of patients with influenza had filling defects on CT pulmonary angiography (p = 0.0001). Catheter-associated deep vein thrombosis shown on ultrasound Doppler after decannulation was present in 53% with coronavirus disease 2019 versus 25% with influenza (p = 0.01). The rates of intracranial hemorrhage at the time of cannulation were 16% with coronavirus disease 2019 and 14% with influenza (p = 0.8). Elevated d-dimer levels were seen in both conditions and were significantly higher in those with pulmonary thromboembolism than those without in coronavirus disease 2019 (p = 0.02). Fibrinogen and C-reactive protein levels were significantly higher in those with coronavirus disease 2019 than influenza (p < 0.01). CONCLUSIONS: Significant rates of pulmonary thromboembolism and of catheter-associated deep vein thrombosis were seen in both viral infections but were greater in those requiring the use of extracorporeal membrane oxygenation in coronavirus disease 2019 than for influenza.

Bedside noninvasive monitoring of mechanically ventilated patients.

PURPOSE OF REVIEW: Among noninvasive lung imaging techniques that can be employed at the bedside electrical impedance tomography (EIT) and lung ultrasound (LUS) can provide dynamic, repeatable data on the distribution regional lung ventilation and response to therapeutic manoeuvres.In this review, we will provide an overview on the rationale, basic functioning and most common applications of EIT and Point of Care Ultrasound (PoCUS, mainly but not limited to LUS) in the management of mechanically ventilated patients. RECENT FINDINGS: The use of EIT in clinical practice is supported by several studies demonstrating good correlation between impedance tomography data and other validated methods of assessing lung aeration during mechanical ventilation. Similarly, LUS also correlates with chest computed tomography in assessing lung aeration, its changes and several pathological conditions, with superiority over other techniques. Other PoCUS applications have shown to effectively complement the LUS ultrasound assessment of the mechanically ventilated patient. SUMMARY: Bedside techniques - such as EIT and PoCUS - are becoming standards of the care for mechanically ventilated patients to monitor the changes in lung aeration, ventilation and perfusion in response to treatment and to assess weaning from mechanical ventilation.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Nonantibiotic Pharmacological Treatment of Severe Chronic Obstructive Pulmonary Disease Exacerbations.

Severe, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a rapid deterioration of the respiratory symptoms of patients with COPD, requiring hospital admission and escalation of pharmacological and nonpharmacological care including the more severe cases of respiratory failure and admission to an intensive care unit (ICU). These events severely impact patients' quality of life and prognosis. This review will describe the nonantibiotic, pharmacological treatment options available for critically ill patients with AECOPD. The aim of treatment is to alleviate symptoms, improve patient's functional and respiratory status, reduce mortality, reduce the risk or the duration of invasive mechanical ventilation, and prevent reexacerbations. Inhaled bronchodilators (i.e., short-acting ß2-agonists and anticholinergics) and systemic corticosteroids are the main drugs used in the treatment of AECOPD. These drugs are also used in the treatment of stable COPD and in the treatment of AECOPD patients in the non-ICU or community setting. Other drugs are essentially only used in the ICU setting such as inhaled anesthetic agents, ketamine, intravenous methylxanthines, and magnesium. Finally, recently developed drugs, such as the specific phosphodiesterase-4 inhibitors, may play a role in the prevention of relapsing AECOPD following a critical event than the treatment of the exacerbation itself. Although they significantly improve the survival of critically ill patients with AECOPD, none of available drugs, alone or combined, is able to significantly modify the prognosis of patients with COPD. This remains an open challenge for the current and future generations of researchers and clinicians.

In vivo carbon dioxide clearance of a low-flow extracorporeal carbon dioxide removal circuit in patients with acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Veno-venous extracorporeal carbon dioxide removal allows clearance of CO2 from the blood and is becoming popular to enhance protective mechanical ventilation and assist in the management of acute exacerbations of chronic obstructive pulmonary disease, including the prevention of intubation. The main factor determining CO2 transfer across a membrane lung for any given blood flow rate and venous CO2 content is the sweep gas flow rate. The in vivo characteristics of CO2 clearance using ultra-low blood flow devices in patients with acute exacerbations of chronic obstructive pulmonary disease has not been previously described. METHODS: Patients commenced on extracorporeal carbon dioxide removal for acute exacerbations of chronic obstructive pulmonary disease recruited to a randomized controlled trial of non-invasive ventilation versus extracorporeal carbon dioxide removal had pre- and post-membrane circuit gases measured after each increment of sweep gas flow to allow calculation of the transmembrane CO2 clearance. This was compared with the clearance reported by the device and also corrected to inlet PCO2 to allow characterization of the CO2 clearance of the device at different sweep gas flow rates. RESULTS: CO2 clearance was calculated using both the transmembrane CO2 whole-blood content difference and CO2 clearance reported by the device. The two methods demonstrated a linear relationship and agreement with a bias of 14 mL/minute (SD = ±10) and an R2 of 0.92. The membrane CO2 clearance was non-linear with nearly two thirds of total clearance achieved with sweep gas flow below 2 L/minute (VCO2 of 40 ± 16.7 mL/minute) and a plateau above 5 L/minute sweep gas flow (VCO2 64 ± 1 2.4 mL/minute). CONCLUSION: The extracorporeal carbon dioxide removal device used in the study provides efficient clearance of CO2 at low sweep flow rates which then plateaus. This has implications for how the device may be used in clinical practice, particularly during the weaning phase where the final discontinuation of the device may take longer than anticipated. (ClinicalTrials.gov: NCT02086084, registered 13 March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084 ).

In-vitro performance of a low flow extracorporeal carbon dioxide removal circuit.

INTRODUCTION: Extracorporeal gas exchange requires the passage of oxygen and carbon dioxide (CO2) across an artificial membrane. Current European Union regulations do not require the transfer to be assessed in models using clinically relevant haemoglobin, making it difficult for clinicians to understand the CO2 clearance of a membrane, and how it changes in relation to sweep gas flow through the membrane. The characteristics of membrane CO2 clearance are described using a single membrane at different sweep gas flows in an in vitro model with clinically relevant haemoglobin concentrations using three separate methods of calculating CO2 clearance. METHODS: To define the CO2 removal characteristics of the extra-corporeal CO2 removal (ECCO2R) device, we devised an in-vitro gas exchange circuit formed by a dedicated ECCO2R circuit (ALung, Pittsburgh, USA) in series with two membrane oxygenators. The system was primed with donated expired human red cells provided by the local blood bank. The experimental set-up allowed constant CO2 input (via one membrane oxygenator) with variable removal from a portion of the blood in a manner which was analogous to that seen in vivo. Blood gases were measured from different ports in the circuit in order to measure the experimental membrane CO2 clearance (VCO2). RESULTS: Results demonstrate that the relationship between VCO2 and gas flow at a constant blood flow of 0.4 L/minute with a haemoglobin of 7 g/dL increases sharply from a gas flow of 0 to 2 L/min but plateaus at gas flows >4 L/minute. VCO2, calculated using three different methods, showed a strong linear correlation with minimal bias. CONCLUSIONS: The CO2 clearance of the membrane used in this bench test is non-linear. This has implications for clinical practice, especially during the weaning phase of the device.