Factors Affecting the Discrepancy Between Coagulation Times on Extracorporeal Circulation Using Unfractionated Heparin in Children and Young Adults.

In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial thromboplastin time (APTT) may diverge, confounding anticoagulant adjustments. We aimed to explore the factors explaining this discrepancy in children and young adults. This retrospective observational study, conducted at an urban regional tertiary hospital, included consecutive pediatric patients who received UFH during extracorporeal circulation (continuous kidney replacement therapy or extracorporeal membrane oxygenation) between April 2017 and March 2021. After patients whose ACT and APTT were not measured simultaneously or who were also taking other anticoagulants were excluded, we analyzed 94 samples from 23 patients. To explain the discrepancy between ACT and APTT, regression equations were created using a generalized linear model (family = gamma, link = logarithmic) with ACT as the response variable. Other explanatory variables included age, platelet count, and antithrombin. Compared to APTT alone as an explanatory variable, the Akaike information criterion and pseudo-coefficient of determination improved from 855 to 625 and from 0.01 to 0.42, respectively, when these explanatory variables were used. In conclusion, we identified several factors that may explain some of the discrepancy between ACT and APTT in the routinely measured tests. Evaluation of these factors may aid in appropriate adjustments in anticoagulation therapy.

[Perfusion Methods and Reconstruction Techniques for Performing Aortic Arch Surgery with Isolated Left Vertebral Artery].

In our institution, when we perform aortic arch surgery with isolated left vertebral artery using an extracorporeal circulation, we select an interposed saphenous vein graft technique. This technique has a relatively short clamping time and allows for selective cerebral perfusion and flexible choice of reconstruction site. Although other techniques, such as an island reconstruction, have been reported, we do not perform it often due to its longer ischemic time of the left vertebral artery. On the other hand, we use a direct reconstruction technique in cases where an extracorporeal circulation is not used. This direct reconstruction technique in cases of isolated left vertebral artery could reduce the time and number of clamping it.

[Clinical value of the implication of extracorporeal carbon dioxide removal in patients with acute respiratory distress syndrome].

Extracorporeal carbon dioxide removal (ECCO2R) is a respiratory support technique based on extra-pulmonary gas exchange, which can effectively remove carbon dioxide generated in-vivo, reducing the requirements of respiratory support from mechanical ventilation. With improvements in extracorporeal life support technologies and increasing clinical experience, ECCO2R has potential value in clinical application with acute respiratory distress syndrome (ARDS). This review article discusses the principles of ECCO2R, its relevant indications for ARDS, clinical evidence, existing issues, and future directions, aiming to provide more references for the application in ARDS.

Develop of endocavitary suction device for MiECC on minimally invasive mitral valve surgery.

The minimally invasive extracorporeal circulation (MiECC) system was developed to minimize the contact of blood with air and foreign surfaces during conventional cardiopulmonary bypass (CPB). It is also aimed to reduce the inflammatory response by further increasing the biocompatibility of the components that make up the MiECC circuits. The Minithoracotomy (MTH) approach for mitral valve disease remains associated with prolonged operative times, but it is beneficial in terms of reduced postoperative complications (renal failure, atrial fibrillation, blood transfusion, wound infection), length of stay in intensive care unit (ICU) and in hospitalization, with finally a reduction in global cost. Combining the use of the MiECC technique with minimally invasive mitral valve surgery (MIMVS) could open up new research scenarios. Although considerable progress has been made in the standardization of the surgical technique, limitations remain to be filled in the setting of Endo-cavitary aspiration for the association of MiECC with MIMVS. In this paper we introduce invention refers to a device and an air-closed endocavitary aspiration system for cardiac chamber surgery, as well as a method aimed at eliminating gaseous micro-embolic activity, hemolysis and CO2 aspiration and alteration of carbon dioxide production (VCO2) the parameters for goal directed perfusion. The system allows the surgery of the cardiac chambers to be associated with a minimally invasive extra-corporeal circulation circuit.

A Split-Lung Ex Vivo Perfusion Model for Time- and Cost-Effective Evaluation of Therapeutic Interventions to the Human Donor Lung.

With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed. A split-lung EVLP model, which allows stable perfusion and ventilation of two single lungs from the same donor, offers advantages scientifically, financially and in time to yield results. Identical parallel circuits allow one to receive an intervention and the other to act as a control, removing inter-donor variation between study groups. Continuous hemodynamic and airway parameters are recorded and blood gas, perfusate, and tissue sampling are facilitated. Pulmonary edema is assessed directly using ultrasound, and indirectly using the lung tissue wet:dry ratio. Evans blue dye leaks into the tissue and can quantify vascular endothelial permeability. The split-lung ex vivo perfusion model offers a cost-effective, reliable platform for testing therapeutic interventions with relatively small sample sizes.

Evaluation of CO2 removal rate of ECCO2R for a renal replacement therapy platform in an experimental setting.

BACKGROUND: A critical parameter of extracorporeal CO2 removal (ECCO2R) applications is the CO2 removal rate (VCO2). Low-flow venovenous extracorporeal support with large-size membrane lung remains undefined. This study aimed to evaluate the VCO2 of a low-flow ECCO2R with large-size membrane lung using a renal replacement therapy platform in an experimental animal model. METHODS: Twelve healthy pigs were placed under mechanical ventilation and connected to an ECCO2R-CRRT system (surface area = 1.8 m2; OMNIset®, BBraun, Germany). Respiratory settings were reduced to induce two degrees of hypercapnia. VCO2 was recorded under different combinations of PaCO2 (50-69 or 70-89 mm Hg), extracorporeal blood flow (ECBF; 200 or 350 mL/min), and gas flow (4, 6, or 10 L/min). RESULTS: VCO2 increased with ECBF at all three gas flow rates. In severe hypercapnia, the increase in sweep gas flow from 4 to 10 L/min increased VCO2 from 86.38 ± 7.08 to 96.50 ± 8.71 mL/min at an ECBF of 350 mL/min, whereas at ECBF of 200 mL/min, any increase was less effective. But in mild hypercapnia, the increase in sweep gas flow result in significantly increased VCO2 at two ECBF. VCO2 increased with PaCO2 from 50-69 to 70-89 mm Hg at an ECBF of 350 mL/min, but not at ECBF of 200 mL/min. Post-membrane lung PCO2 levels were similar for different levels of premembrane lung PCO2 (p = 0.08), highlighting the gas exchange diffusion efficacy of the membrane lung in gas exchange diffusion. In severe hypercapnia, the reduction of PaCO2 elevated from 11.5% to 19.6% with ECBF increase only at a high gas flow of 10 L/min (p < 0.05) and increase of gas flow significantly reduced PaCO2 only at a high ECBF of 350 mL/min (p < 0.05). CONCLUSIONS: Low-flow venovenous extracorporeal ECCO2R-CRRT with large-size membrane lung is more efficient with the increase of ECBF, sweep gas flow rate, and the degree of hypercapnia. The influence of sweep gas flow on VCO2 depends on the ECBF and degree of hypercapnia. Higher ECBF and gas flow should be chosen to reverse severe hypercapnia.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine.

OBJECTIVE: Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia. METHODS: Swine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation. RESULTS: Recipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours. CONCLUSIONS: We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.

High-molecular-weight linear polymers improve microvascular perfusion after extracorporeal circulation.

High-molecular-weight linear polymers (HMWLPs) have earned the name "drag-reducing polymers" because of their ability to reduce drag in turbulent flows. Recently, these polymers have become popular in bioengineering applications. This study investigated whether the addition of HMWLP in a venoarterial extracorporeal circulation (ECC) model could improve microvascular perfusion and oxygenation. Golden Syrian hamsters were instrumented with a dorsal skinfold window chamber and subjected to ECC using a circuit comprised of a peristaltic pump and a bubble trap. The circuit was primed with lactated Ringer solution (LR) containing either 5 ppm of polyethylene glycol (PEG) with a low molecular weight of 500 kDa (PEG500k) or 5 ppm of PEG with a high molecular weight of 3,500 kDa (PEG3500k). After 90 min of ECC at 15% of the animal's cardiac output, the results showed that the addition of PEG3500k to LR improved microvascular blood flow in arterioles and venules acutely (2 h after ECC), whereas functional capillary density showed improvement up to 24 h after ECC. Similarly, PEG3500k improved venular hemoglobin O2 saturation on the following day after ECC. The serum and various excised organs all displayed reduced inflammation with the addition of PEG3500k, and several of these organs also had a reduction in markers of damage with the HMWLPs compared to LR alone. These promising results suggest that the addition of small amounts of PEG3500k can help mitigate the loss of microcirculatory function and reduce the inflammatory response from ECC procedures.NEW & NOTEWORTHY High-molecular-weight linear polymers have gained traction in bioengineering applications. The addition of PEG3500k to lactated Ringer solution (LR) improved microvascular blood flow in arterioles and venules acutely after extracorporeal circulation (ECC) in a hamster model and improved functional capillary density up to 24 h after ECC. PEG3500k improved venular hemoglobin O2 saturation and oxygen delivery acutely after ECC and reduced inflammation in various organs compared to LR alone.

Dilemmas of Adopting Goal-Directed Perfusion in Extracorporeal Circulation: A Narrative Review.

OBJECTIVE: Extracorporeal circulation (ECC) is generally based on standards established in the last decade. In recent years, a concept of perfusion management during ECC, goal-directed perfusion (GDP), has emerged to create optimal conditions for oxygen delivery and extraction, initiated by Rannuci et al. The aim of the present work was to determine whether the ECC procedure can truly be optimized with the current state of knowledge and understanding of human physiology. METHODS: Discussed articles from 2017 to 2022 were selected from the MEDLINE (PubMed) database using the keywords "cardiopulmonary bypass" AND "cardiac surgery" AND "oxygen delivery" with the conditions of "clinical trial" OR "randomized controlled trial." RESULTS: The concept of GDP is an attempt to reproduce the physiological conditions of tissue respiration during ECC. Published articles, also due to their retrospective nature, are based on standards and recommendations that do not fully fit the field of physiological circulation. There are still insufficient tools to assess the relationship between volemia, perfusion pressure, and pump performance. Limitations include indications for vasoactive drugs. Methodology has rarely taken into account the period of starting and stopping the heart-lung machine, the most pronounced periods of circulatory destabilization with reduced oxygen delivery. CONCLUSIONS: Problems associated with ECC such as acute kidney injury, liver failure, vasoplegic syndrome, and others must await its resolution. The use of advanced monitoring technology and data engineering may allow the development of baseline hemodynamic models, which may make the ECC procedure more physiologic and thus improve the safety of the procedure.

Establishment of an Ex Vivo Lung Perfusion Rat Model for Translational Insights in Lung Transplantation.

Since the establishment of lung transplantation as a therapeutic strategy for advanced lung diseases, the scientific community is faced with the problem of a low number of lungs considered viable for the donation process. In recent decades, however, this scenario has been positively changed, given the development of ex vivo lung perfusion (EVLP) as a strategy for evaluating and reconditioning marginal lungs. The establishment of EVLP in large transplant centers has favored an increase in the number of lung transplants, both by increasing the diagnostic accuracy of lung function and by constituting an effective platform for the reconditioning of lung grafts. In this context, faced with ethical and logistical issues, as well as in the study of immunological factors associated with lung transplantation, the development of rodent EVLP models has become important, given their reliability, the possibility of genetic manipulation, and lower costs. This paper describes a protocol for establishing a rat EVLP model and shows the inflammatory profile associated with the perfused lungs. This will help propagate knowledge about the rat EVLP model, promoting our understanding of the biological responses associated with that revolutionary technique.

XPS™ Jensen lung as a low-cost, high-fidelity training adjunct to ex-vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables lung resuscitation before transplantation, and training is key, particularly in low-volume settings. To enable technique refinement and continuing education, we sought to demonstrate the value of a low-cost, high-fidelity EVLP simulator that would allow reproducible clinical scenarios. METHODS: In partnership with our EVLP manufacturer, we utilized the XPS™ Jensen Lung with our clinical system. The Jensen Lung has two simulated lung bladders and an in-line polymethylpentene fiber oxygenator. It allows titration of ventilator support which aids in accurate clinical simulation. For simulations, blood gases (BGs) were obtained and compared with integrated in-line perfusate gas monitors (PGMs). PaO2 , PCO2 , and pH were measured and compared. RESULTS: The PGM and BG values were not significantly different throughout the range of FiO2 and sweep gas flow rates evaluated. The "delta" PaO2 was measured between LA and PA and did not show any change between approaches. The pH measurement between BG and PGM was not significantly different. CONCLUSIONS: The XPS™ Jensen Lung simulator allows for a high-fidelity simulator of clinical EVLP. The correlation of the PGM and the BG measurement of the PaO2 and pH allow for a low-cost simulation, as the PGMs are in line in the circuit, and enable real-time tracking of perfusate gas parameters with the PGM. Implementation of a standardized clinical EVLP training program allows the maintenance of technique and enables clinical simulation training without the need for costly animal perfusions and the use of multiple BG measurements.

Identification of regional variation in gene expression and inflammatory proteins in donor lung tissue and ex vivo lung perfusate.

OBJECTIVE: Diagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate. METHODS: Eight human donor lungs declined for transplantation were air inflated, flash frozen, and partitioned from apex to base. Biopsies were then sampled throughout the lung. Perfusate was sampled from 4 lung lobes in 8 additional donor lungs subjected to ex vivo lung perfusion. The levels of interleukin-6, interleukin-8, interleukin-10, and interleukin-1ß were measured using quantitative reverse transcription polymerase chain reaction from lung biopsies and enzyme-linked immunosorbent assay from ex vivo lung perfusion perfusate. RESULTS: The median intra-biopsy equal-variance P value was .50 for messenger RNA biomarkers in tissue biopsies. The median intra-biopsy coefficient of variance was 18%. In donors with no apparent focal injuries, the biopsies in each donor showed no difference in various lung slices, with a coefficient of variance of 20%. The exception was biopsies from the lingula and injured focal areas that demonstrated larger differences. Cytokines in ex vivo lung perfusion perfusate showed minimal variation among different lobes (coefficient of variance = 4.9%). CONCLUSIONS: Cytokine gene expression in lung biopsies was consistent, and the biopsy analysis reflects the whole lung, except when specimens were collected from the lingula or an area of focal injury. Ex vivo lung perfusion perfusate also provides a representative measurement of lung inflammation from the draining lobe. These results will reassure clinicians that a lung biopsy or an ex vivo lung perfusion perfusate sample can be used to inform donor lung selection.

Current status and future potential of ex vivo lung perfusion in clinical lung transplantation.

Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.

Nonischemic Donor Heart Preservation: New Milestone in Heart Transplantation History.

Heart transplantation is considered the gold standard for the treatment of advanced end-stage heart failure. However, standard donors after brain death are decreasing, whereas patients on the heart transplant waitlist are constantly rising. The introduction of the ex vivo machine perfusion device has been a turning point; in fact, these systems are able to significantly reduce ischemic times and have a potential effect on ischemia-related damage reduction. From a clinical standpoint, these machines show emerging results in terms of heart donor pool expansion, making marginal donors and donor grafts after circulatory death suitable for donation. This article aims to review mechanisms and preclinical and clinical outcomes of currently available ex vivo perfusion systems, and to explore the future fields of application of these technologies.

Combined extracorporeal CO2 removal and renal replacement therapy in a pregnant patient with COVID-19: a case report.

Background. Pregnant women are at high risk of Coronavirus disease 2019 (COVID-19) complications, including acute respiratory distress syndrome. Currently, one of the cornerstones in the treatment of this condition is lung-protective ventilation (LPV) with low tidal volumes. However, the occurrence of hypercapnia may limit this ventilatory strategy. So, different extracorporeal CO2 removal (ECCO2R) procedures have been developed. ECCO2R comprises a variety of techniques, including low-flow and high-flow systems, that may be performed with dedicated devices or combined with continuous renal replacement therapy (CRRT). Case description. Here, we report a unique case of a pregnant patient affected by COVID-19 who required extracorporeal support for multiorgan failure. While on LPV, because of the concomitant hypercapnia and acute kidney injury, the patient was treated with an ECCO2R membrane inserted in series after a hemofilter in a CRRT platform. This combined treatment reducing hypercapnia allowed LPV maintenance at the same time while providing kidney replacement and ensuring maternal and fetal hemodynamic stability. Adverse effects consisted of minor bleeding episodes due to the anticoagulation required to maintain the extracorporeal circuit patency. The patient's pulmonary and kidney function progressively recovered, permitting the withdrawal of any extracorporeal treatment. At the 25th gestational week, the patient underwent spontaneous premature vaginal delivery because of placental abruption. She gave birth to an 800-gram female baby, who three days later died because of multiorgan failure related to extreme prematurity. Conclusions. This case supports using ECCO2R-CRRT combined treatment as a suitable approach in the management of complex conditions, such as pregnancy, even in the case of severe COVID-19.

A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions.

In clinical practice, extracorporeal circulation (ECC) is associated with coagulopathy and inflammation, eventually leading to organ injuries without preventive systemic pharmacological treatment. Relevant models are needed to reproduce the pathophysiology observed in humans and preclinical tests. Rodent models are less expensive than large models but require adaptations and validated comparisons to clinics. This study aimed to develop a rat ECC model and to establish its clinical relevance. One hour of veno-arterial ECC or a sham procedure were achieved on mechanically ventilated rats after cannulations with a mean arterial pressure objective > 60 mmHg. Five hours post-surgery, the rats' behavior, plasmatic/blood biomarkers, and hemodynamics were measured. Blood biomarkers and transcriptomic changes were compared in 41 patients undergoing on-pump cardiac surgery. Five hours post-ECC, the rats presented hypotension, hyperlactatemia, and behavioral alterations. The same patterns of marker measurements (Lactate dehydrogenase, Creatinine kinase, ASAT, ALAT, and Troponin T) were observed in both rats and human patients. Transcriptome analyses showed similarity in both humans and rats in the biological processes involved in the ECC response. This new ECC rat model seems to resemble both ECC clinical procedures and the associated pathophysiology, but with early organ injury corresponding to a severe phenotype. Although the mechanisms at stake in the post-ECC pathophysiology of rats or humans need to be described, this new rat model appears to be a relevant and costless preclinical model of human ECC.

Ex vivo lung perfusion: a procedural guide.

Available donor organs for lung transplantation are scarce. Ex vivo lung perfusion provides a platform to preserve, assess, and recondition donor lungs and can thereby aid in enlarging the donor pool. This video tutorial discusses the indications, preparation, and surgical technique for and the initiation, maintenance and termination of the ex vivo lung perfusion procedure.

Swine intestinal segment perfusion model for the evaluation of nutrients bioaccessibility.

Nutrition science requires more science-based evidences for the development of effective functional diets. To reduce animals for experimental purposes innovative reliable and informative models, simulating the complex intestinal physiology, are needed. The aim of this study was to develop a swine duodenum segment perfusion model for the evaluation of nutrient bioaccessibility and functionality across time. At the slaughterhouse, one sow intestine was harvested following Maastricht criteria for organ donation after circulatory death (DCD) for transplantation purposes. Duodenum tract was isolated and perfused in sub-normothermic conditions with heterologous blood after cold ischemia induction. Duodenum segment perfusion model was maintained under controlled pressure conditions through extracorporeal circulation for 3 hours. Blood samples from extracorporeal circulation and luminal content samples were collected at regular intervals for the evaluation of glucose concentration by glucometer, minerals (Na+, Ca2+, Mg2+, K+) by ICP-OES, lactate-dehydrogenase and nitrite oxide by spectrophotometric methods. Dacroscopic observation showed peristaltic activity caused by intrinsic nerves. Glycemia decreased over time (from 44.00±1.20 mg/dL to 27.50±0.41; p < 0.01), suggesting glucose utilization by the tissue confirming the organ viability in line with histological examinations. At the end of the experimental period, intestinal mineral concentrations were lower than their level in blood plasma suggesting their bioaccessibility (p < 0.001). A progressive increase of LDH concentration over time was observed in the luminal content probably related to a loss of viability (from 0.32±0.02 to 1.36±0.02 OD; p < 0.05) confirmed by histological findings that revealed a de-epithelization of the distal portion of duodenum. Isolated swine duodenum perfusion model satisfied the criteria for studying bioaccessibility of nutrients, offering a variety of experimental possibilities in line with 3Rs principle.

Efficacy and Safety of a Low-Flow Extracorporeal Carbon Dioxide Removal System in Acute Respiratory Failure, a Pilot Study in China.

BACKGROUND: Low-flow extracorporeal carbon dioxide removal (LF-ECCO2R) has the potential to play an important role in the management of adults with acute respiratory failure. However, it has never been tested in China. The study aimed at exploring the safety and efficacy on LF-ECCO2R for acute respiratory failure in a Chinese tertiary intensive care unit (ICU). MATERIALS AND METHODS: We performed a retrospective case note review of patients admitted to our tertiary regional ICU and commenced on LF-ECCO2R from June 2020 to September 2021. The LF-ECCO2R device we used was ProLUNG® system (Estor S.p.A., Milan, Italy). The device employed a nonporous poly-4-methyl-1-pentene membrane lung with a surface area of 1.81 m2 and run at an extracorporeal blood flow between 100 and 450 mL/min. Demographic and physiologic data (including ventilation parameters and arterial blood gases) as well as the outcome of LF-ECCO2R treatment were recorded. RESULTS: A total of 12 cases were included. A statistically significant reduction in respiratory rate, driving pressure, PaCO2, and blood lactate was observed. In addition, there was a statistically significant improvement in pH and PaO2/FiO2. Six out of 12 patients (50%) were discharged alive from ICU. Three complications related to LF-ECCO2R were reported, none resulting in serious adverse outcomes. CONCLUSION: Our clinical series indicated that LF-ECCO2R seemed to be safely applied in patients with acute respiratory failure. The efficacy of CO2 removal as well as the improved respiratory parameters was also observed. However, large-scale randomized clinical trials are needed to confirm the effects.

Diagnostic and Therapeutic Implications of Ex Vivo Lung Perfusion in Lung Transplantation: Potential Benefits and Inherent Limitations.

Ex vivo lung perfusion (EVLP), a technique in which isolated lungs are continually ventilated and perfused at normothermic temperature, is emerging as a promising platform to optimize donor lung quality and increase the lung graft pool. Over the past few decades, the EVLP technique has become recognized as a significant achievement and gained much attention in the field of lung transplantation. EVLP has been demonstrated to be an effective platform for various targeted therapies to optimize donor lung function before transplantation. Additionally, some physical parameters during EVLP and biological markers in the EVLP perfusate can be used to evaluate graft function before transplantation and predict posttransplant outcomes. However, despite its advantages, the clinical practice of EVLP continuously encounters multiple challenges associated with both intrinsic and extrinsic limitations. It is of utmost importance to address the advantages and disadvantages of EVLP for its broader clinical usage. Here, the pros and cons of EVLP are comprehensively discussed, with a focus on its benefits and potential approaches for overcoming the remaining limitations. Directions for future research to fully explore the clinical potential of EVLP in lung transplantation are also discussed.