Pilot Testing of a Lightweight, Pulmonary Assist System in an Ambulatory Sheep Model of Destination Therapy Respiratory Support.

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.9 m 2 surface area) gas exchanger, the pulmonary assist device, with a modified Heart Assist 5 pump fitting in a small wearable pack. Prototype PAS were attached to two sheep in venovenous configuration for 7 and 14 days, evaluating ability to remain thrombus free; maintain gas exchange and blood flow resistance; avoid biocompatibility-related complications while allowing safe ambulation. The PAS achieved 1.56 L/min of flow at 10.8 kRPM with a 24 Fr cannula in sheep one and 2.0 L/min at 10.5 kRPM with a 28 Fr cannula in sheep 2 without significant change. Both sheep walked freely, demonstrating the first application of truly ambulatory ECMO in sheep. While in vitro testing evaluated PAS oxygen transfer rates of 104.6 ml/min at 2 L/min blood flow, oxygen transfer rates averaged 60.6 ml/min and 70.6 ml/min in studies 1 and 2, due to average hemoglobin concentrations lower than humans (8.9 and 10.5 g/dl, respectively). The presented cases support uncomplicated ambulation using the PAS.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Chemotherapy-induced leukopenic septic shock treated with veno-arterial extracorporeal membrane oxygenation: A case report.

We present a case of chemotherapy-induced leukopenic septic shock treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Although the indication for VA-ECMO for septic shock in immunosuppressed states remains controversial, her relatively young age and a slightly increasing leukocyte count led to VA-ECMO induction and resulted in recovery.

Factor XII Silencing Using siRNA Prevents Thrombus Formation in a Rat Model of Extracorporeal Life Support.

Heparin anticoagulation increases the bleeding risk during extracorporeal life support (ECLS). This study determined whether factor XII (FXII) silencing using short interfering RNA (siRNA) can provide ECLS circuit anticoagulation without bleeding. Adult male, Sprague-Dawley rats were randomized to four groups (n = 3 each) based on anticoagulant: (1) no anticoagulant, (2) heparin, (3) FXII siRNA, or (4) nontargeting siRNA. Heparin was administered intravenously before and during ECLS. FXII or nontargeting siRNA were administered intravenously 3 days before the initiation of ECLS via lipidoid nanoparticles. The rats were placed on pumped, arteriovenous ECLS for 8 hours or until the blood flow resistance reached three times its baseline resistance. Without anticoagulant, mock-oxygenator resistance tripled within 7 ± 2 minutes. The resistance in the FXII siRNA group did not increase for 8 hours. There were no significant differences in resistance or mock-oxygenator thrombus volume between the FXII siRNA and the heparin groups. However, the bleeding time in the FXII siRNA group (3.4 ± 0.6 minutes) was significantly shorter than that in the heparin group (5.5 ± 0.5 minutes, p < 0.05). FXII silencing using siRNA provided simpler anticoagulation of ECLS circuits with reduced bleeding time as compared to heparin. http://links.lww.com/ASAIO/A937.

A case of severe respiratory failure due to interstitial pneumonia successfully bridged to lung transplantation from a brain-dead donor using 109-day veno-arterial extracorporeal membrane oxygenation.

In Japan, successful cases of a bridge to lung transplantation (BTT) by extracorporeal membrane oxygenation (ECMO) are rare. We present the case of a man in his thirties, diagnosed with interstitial pneumonia 6 years prior and registered for lung transplant 1 year prior due to disease progression despite treatment. Due to the patient's worsening respiratory failure, he was transferred to our hospital for BTT by ECMO. Since long-term management was expected and pulmonary hypertension was present, veno-arterial (V-A) ECMO was conducted using the right atrial blood outflow via the right internal jugular vein and right axillary artery inflow via a vascular graft. After tracheostomy, he was managed as "Awake ECMO". In addition, interprofessional collaboration such as physiotherapist rehabilitation, nurses, and liaison teams prevented muscle weakness and supported the mental aspect. We were able to minimize complications such as severe infections and bleeding. A compatible brain-dead donor was found on day 108 after introducing ECMO, and the patient was transferred to a transplant facility on day 109. The peripheral upper V-A ECMO is one of the configurations suitable for long-term BTT management.

Early predictors of oxygenator exchange during veno-venous extracorporeal membrane oxygenation: A retrospective analysis.

INTRODUCTION: Oxygenator exchange during extracorporeal membrane oxygenation (ECMO) is a life-threatening procedure. D-dimer has been used to predict oxygenator failure, but it is a parameter used a few days before oxygenator exchange. This study investigated parameters before and immediately after ECMO initiation that predict oxygenator exchange. METHODS: This was a single-center, retrospective study of 28 patients who received veno-venous ECMO with heparin/silicone-coated polypropylene oxygenator (NSH-R HPO-23WH-C; Senko Medical Inc., Tokyo, Japan), due to acute respiratory failure, from April 2015 to March 2020. Clinical data before ECMO initiation and during the first 3 days on ECMO were compared between the patients with oxygenator exchange (exchange group) and those without oxygenator exchange (non-exchange group). RESULTS: Nine (32%) patients required oxygenator exchange. The exchange group had significantly higher white blood cell count (WBC) (16,944 ± 2423/µL vs 10,342 ± 1442/µL, p < 0.05) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (31 ± 5 vs 25 ± 8, p < 0.05) before ECMO initiation than the non-exchange group. The partial pressure of oxygen at the outlet of the oxygenator (PO2 outlet) and activated partial thromboplastin time (aPTT) during the first 3 days on ECMO were significantly lower in the exchange group than in the non-exchange group. CONCLUSIONS: High WBC and APACHE II score before ECMO initiation, low PO2 outlet, and aPTT during the first 3 days on ECMO were associated with oxygenator exchange during veno-venous ECMO. These parameters could be used to avoid unexpected oxygenator exchange.

The Need for an Adult Intensive Care Unit Boot Camp for Residents and Fellows: A Cross-Sectional Survey among Intensive Care Unit Directors.

BACKGROUND: The concept of "see one, do one, teach one" raises concerns regarding patient safety in the intensive care unit (ICU) and highlights the need for prior preparation of residents/fellows for ICU rotation. This study assessed the need for an adult pre-ICU "boot camp" training course. METHODS: An online questionnaire regarding the current ICU training and desirable course framework was distributed via e-mail to the ICU directors of 269 educational centers certified by the Japanese Society of Intensive Care Medicine. RESULTS: The response rate was 39% (106/269). The number of residents/fellows undergoing ICU rotation was 5.5 (IQR 2-12) /ICU/year, and the majority (63%) were second to fourth year post-graduate residents and fellows. ICU directors opined that of the fundamental critical care skills, residents/fellows performed well or very well in only seven out of 29 skills (24%). Only 18% of the ICU directors had an established ICU training curriculum. Overall, 72% of the directors were interested in the boot camp. The desirable course framework was 3-5 hours per day with simulations and lectures. The core skills that directors considered as important to acquire during ICU rotation were central venous catheter insertion, tracheal intubation, defibrillation, initiation of mechanical ventilation, physical examination of critically ill patients, and shock assessment. CONCLUSIONS: Residents/fellows began ICU rotations with suboptimal skills as reported by ICU directors. In addition, most of the ICUs had not established a training curriculum. Therefore, having an ICU boot camp is necessary to enhance critical care skills and to decrease medical errors.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Catheter-related thrombosis after cardiac surgery in patients with both central venous and pulmonary artery catheters inserted into the right internal jugular vein: a single-center, prospective, observational study.

Central venous catheters (CVCs) and pulmonary artery catheters (PACs) are widely used in intensive care and perioperative management. The detection and prevention of catheter-related thrombosis (CRT) are important because CRT is a complication of catheter use and can cause pulmonary embolism and bloodstream infection. Currently, there is no evidence for CRT in patients using both CVC and PAC. We conducted a single-center, prospective, observational study to identify the incidence, timing, and risk factors for CRT in patients undergoing cardiovascular surgery and using a combination of CVC and PAC through the right internal jugular vein (RIJV). Out of 50 patients, CRT was observed using ultrasonography in 39 patients (78%), and the median time of CRT formation was 1 day (interquartile range: 1-1.5) after catheter insertion. The mean duration of PAC placement was 3 days (interquartile range: 2-5), and the maximum diameter of CRT was 12 mm (interquartile range: 10-15). In short-axis images, CRT occupied more than half of the cross-sectional area of the RIJV in five patients (10%), and CRT completely occluded the RIJV in one patient (2%). Platelet count, duration of PAC placement, and intraoperative bleeding amount were found to be high-risk indicators of CRT. In conclusion, patients who underwent cardiovascular surgery and using both CVC and PAC had a high incidence of CRT. Avoiding unnecessary PAC placement and early removal of catheters in patients at high risk of developing CRT may prevent the development of CRT.

Assessment of 28-Day In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019: An International Cohort Study.

Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES: To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES: Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS: One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16-1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67-0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15-1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11-1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19-2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8-14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52-0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88-0.97; p = 0.003). CONCLUSIONS AND RELEVANCE: This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

Lung transplant after long-term veno-venous extracorporeal membrane oxygenation: a case report.

BACKGROUND: Although the number of patients who undergo extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is increasing worldwide, there are few reports on lung transplantation after long-term ECMO (more than 1 month). We report a rare case of successful bilateral lung transplantation in a Japanese patient after 5 months of veno-venous (VV)-ECMO support. CASE PRESENTATION: A 27-year-old man who underwent bone marrow transplantation (BMTx) with fully matched human leukocyte antigen typing was diagnosed with bronchiolitis obliterans caused by chronic graft-versus-host disease 3 years after the BMTx. One year later, his respiratory condition had exacerbated, with carbon dioxide retention that required conventional mechanical ventilation. He was then deemed a suitable candidate for lung transplantation by a multidisciplinary transplantation selection committee. While waiting for donor lungs, his hypercapnia and acidosis became barely manageable under care with mechanical ventilation and ultimately he was switched to VV-ECMO. He remained on VV-ECMO for the next 5 months, during which period the circuit was switched nine times. In addition, sophisticated intensive care was required to manage multiple episodes of sepsis and coagulopathy. A suitable donor was identified 5 months later, and bilateral lung transplantation was initiated with continuous VV-ECMO. The procedure itself was extremely challenging owing to severe adhesions resulting from previous thoracotomy, inflammation, infection, and intrapulmonary hemorrhage. The operative time for the transplantation was about 19 h. Currently, at 2 years 8 months postoperatively, the patient is alive and well. CONCLUSION: Transplant surgery in this patient was extremely challenging because of the presence of severe pleural adhesions and stiff native lungs secondary to hemorrhagic complications due to the prolonged ECMO support. Surgeons must recognize that lung transplantation after long-term ECMO bridging can be technically more complicated and challenging than shorter-term ECMO.

Hospital survival outcomes in acute respiratory distress syndrome patients receiving veno-venous extracorporeal membrane oxygenation for longer than 28 days: A retrospective study.

The successful use of prolonged (ie, >28 days) veno-venous extracorporeal membrane oxygenation (V-V ECMO) is being increasingly reported. However, limited data are available on its outcomes. This study investigated the outcomes of acute respiratory distress syndrome (ARDS) patients on prolonged ECMO support. We retrospectively evaluated 57 patients requiring V-V ECMO for ARDS between 2015 and 2020. The patients were divided into two groups according to ECMO duration: (a) ≤28 days group (n = 43, 75%) or (b) >28 days (n = 14, 25%) group. Clinical characteristics, complications, and outcomes between these two groups were statistically compared. There were no significant differences in demographics, comorbidity, ARDS etiology, and severity scores between the two groups. However, the mechanical ventilation period before ECMO initiation was significantly longer in the >28 days group than in the ≤28 days group (10.5 days vs. 1 day; P < .05). The incidence of positive bacterial blood culture results during ECMO was significantly higher in the >28 days group than in the ≤28 days group (43% vs. 9%; P < .05). Additionally, the hospital survival rate was significantly lower in the >28 days group than in the ≤28 days ECMO group (21% vs. 60%; P < .05). Prolonged ECMO was associated with worse hospital survival outcomes. Early initiation of ECMO along with meticulous care and appropriate treatment against infection during ECMO could improve the hospital survival of ARDS patients on prolonged ECMO support.

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients.

BACKGROUND: Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. METHODS: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. RESULTS: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52-71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: - 11.8 to - 7.4 mL/cmH2O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease - 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI - 0.48 to - 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02-1.28, p = 0.018). CONCLUSIONS: This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study . TRIAL REGISTRATION: ACTRN12620000421932.

Establishment and evaluation of a rat model of extracorporeal membrane oxygenation (ECMO) thrombosis using a 3D-printed mock-oxygenator.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) research using large animals requires a significant amount of resources, slowing down the development of new means of ECMO anticoagulation. Therefore, this study developed and evaluated a new rat ECMO model using a 3D-printed mock-oxygenator. METHODS: The circuit consisted of tubing, a 3D-printed mock-oxygenator, and a roller pump. The mock-oxygenator was designed to simulate the geometry and blood flow patterns of the fiber bundle in full-scale oxygenators but with a low (2.5 mL) priming volume. Rats were placed on arteriovenous ECMO at a 1.9 mL/min flow rate at two different heparin doses (n = 3 each): low (15 IU/kg/h for eight hours) versus high (50 IU/kg/h for one hour followed by 25 IU/kg/h for seven hours). The experiment continued for eight hours or until the mock-oxygenator failed. The mock-oxygenator was considered to have failed when its blood flow resistance reached three times its baseline resistance. RESULTS: During ECMO, rats maintained near-normal mean arterial pressure and arterial blood gases with minimal hemodilution. The mock-oxygenator thrombus weight was significantly different (p < 0.05) between the low (0.02 ± 0.006 g) and high (0.003 ± 0.001 g) heparin delivery groups, and blood flow resistance was also larger in the low anticoagulation group. CONCLUSIONS: This model is a simple, inexpensive system for investigating new anticoagulation agents for ECMO and provides low and high levels of anticoagulation that can serve as control groups for future studies.

Iliopsoas Hematoma in Patients Undergoing Venovenous ECMO.

BACKGROUND: Iliopsoas hematoma occasionally occurs in patients receiving anticoagulation therapy. It may be a life-threatening complication and can cause disseminated intravascular coagulation, which could develop into abdominal compartment syndrome. The incidence of and factors associated with iliopsoas hematoma during venovenous extracorporeal membrane oxygenation (ECMO) have not been well studied. OBJECTIVES: To describe the incidence of iliopsoas hematoma and associated factors among patients undergoing venovenous ECMO. METHODS: A retrospective cohort study was conducted at Nippon Medical School Hospital from April 2015 to October 2018. All patients (>18 years old) with iliopsoas hematoma received a diagnosis based on computed tomography. RESULTS: During the study period, 54 patients were supported with venovenous ECMO. Iliopsoas hematoma occurred in 8 of those patients (15%), none of whom had disseminated intravascular coagulopathy or abdominal compartment syndrome develop. Univariate analysis indicated that management of ECMO while the patient was awake and mobilization beyond sitting on the edge of the bed were significantly different (P < .05) in patients with and patients without iliopsoas hematoma. Mortality, however, did not differ significantly between the 2 groups. CONCLUSIONS: Our findings emphasize that recognizing factors associated with iliopsoas hematoma and detecting them early are crucial during venovenous ECMO in order to treat patients with iliopsoas hematoma appropriately.

Artificial lungs--Where are we going with the lung replacement therapy?

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy.

Successful Intensive Care Treatment of Severe Lactic Acidosis and Tumor Lysis Syndrome Related to Intravascular Lymphoma.

Intravascular lymphoma is a rare disease that progresses to multiple organ dysfunction caused primarily by tumor cell proliferation in small blood vessels. Few studies have investigated critical care management of intravascular lymphoma. We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived. A 64-year-old man with impaired consciousness was diagnosed as having intravascular large B-cell lymphoma by means of a random skin biopsy. The patient arrived at our hospital's intensive care unit (ICU) with impaired consciousness, respiratory failure that required mechanical ventilation, and lactic acidosis that required renal replacement therapy. Mechanical ventilation and renal replacement therapy were continued in the ICU, and his respiratory status and circulatory dynamics eventually stabilized. However, his impaired consciousness and hyperlactatemia did not improve until after the start of chemotherapy with doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab. Although he developed tumor lysis syndrome immediately after chemotherapy, his systemic condition was gradually stabilized by continued critical care management primarily comprising renal replacement therapy. He was weaned from ventilator support after a tracheotomy and moved to the general ward. Hematopoietic malignancy with hyperlactatemia has a very poor prognosis; however, hyperlactatemia and impaired consciousness were dramatically improved in this patient by critical care management and chemotherapy.

[Successful lung transplantation after long-term ventilator and extracorporeal membrane oxygenation support in a patient with severe bronchiolitis obliterans following allogeneic bone marrow transplantation].

A 29-year-old man was diagnosed with acute myeloid leukemia at 20 years of age; he achieved a second complete remission at 22 years of age after an allogeneic unrelated bone marrow transplantation. After 14 months, he developed bronchiolitis obliterans (BO) due to chronic graft-versus-host disease. Home ventilator management was continuously performed for 3 years, but the patient required extracorporeal membrane oxygenation (ECMO) after progression to type 2 respiratory failure. A matched brain-dead lung donor was found after 5 months of intensive care management on ECMO, and bilateral lung transplantation was successfully performed. BO is a progressive refractory respiratory disease with poor prognosis. Careful management of infection, monitoring organ function, and lung transplantation at the appropriate time of initiation of mechanical ventilation or ECMO may save a patient's life. However, it is crucial to collaborate with higher education institutions or medical professionals in other departments.

Factors Affecting the Absorption of Midazolam to the Extracorporeal Membrane Oxygenation Circuit.

Sedatives are administered during extracorporeal membrane oxygenation (ECMO) therapy to ensure patient safety, reduce the metabolic rate and correct the oxygen supply-demand balance. However, the concentrations of sedatives can be decreased due to absorption into the circuit. This study examined factors affecting the absorption of a commonly used sedative, midazolam (MDZ). Using multiple ex vivo simulation models, three factors that may influence MDZ levels in the ECMO circuit were examined: polyvinyl chloride (PVC) tubing in the circuit, use of a membrane oxygenator in the circuit, and heparin coating of the circuit. We also assessed changes in drug concentration when MDZ was re-injected in a circuit. The MDZ level decreased to approximately 60% of the initial concentration in simulated circuits within the first 30 minutes. The strongest factor in this phenomenon was contact with the PVC tubing. Membrane oxygenator use tended to increase MDZ loss, whereas heparin circuit coating had no influence on MDZ absorption. Similar results were obtained when a second dose of MDZ was injected to the second-use circuits.