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.

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.

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.

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.

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.

Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs.

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXIIa) with sub-nanomolar activity (Ki = 370 ± 40 pM) and a high stability (t1/2 > 5 days in plasma), allowing for the preclinical evaluation of a first synthetic FXIIa inhibitor. This 1899 Da molecule, termed FXII900, efficiently blocks FXIIa in mice, rabbits, and pigs. We found that it reduces ferric-chloride-induced experimental thrombosis in mice and suppresses blood coagulation in an extracorporeal membrane oxygenation (ECMO) setting in rabbits, all without increasing the bleeding risk. This shows that FXIIa activity is controllable in vivo with a synthetic inhibitor, and that the inhibitor FXII900 is a promising candidate for safe thromboprotection in acute medical conditions.

Idiopathic pulmonary fibrosis patient supported with extracorporeal membrane oxygenation for 403 days while waiting for a lung transplant: A case report.

According to the Extracorporeal Life Support Organization, the average duration of veno-venous extracorporeal membrane oxygenation (V-V ECMO) in adults with acute respiratory failure is 10.5-13.5 days. Some patients on V-V ECMO may not recover in such a short period of time, and recently, there have been more reports of prolonged V-V ECMO. However, we do not know how long it is feasible to wait for native lung recovery or lung transplant (LTx) with the use of ECMO. We describe a patient with acute exacerbation of idiopathic pulmonary fibrosis supported by ECMO for 403 days while waiting for a LTx. In this case, we kept the patient awake, and he was communicating frequently with his family. We changed the membrane oxygenator 23 times and the cannula 10 times without complication. However, we terminated the treatment on day 403 of ECMO because there was no access site for cannula insertion due to blockage by a venous thrombotic occlusion, making it impossible to continue this bridge to lung transplantation. It has become possible to maintain patients on ECMO for extended periods of time, but it is difficult to manage ECMO for more than one year without the development of a more durable lung support system.

Venovenous Extracorporeal Membrane Oxygenation as a Treatment for Obesity Hypoventilation Syndrome.

The mortality rate for respiratory failure resulting from obesity hypoventilation syndrome is high if it requires ventilator management. We describe a case of severe acute respiratory failure resulting from obesity hypoventilation syndrome (BMI, 60.2 kg/m2) successfully treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). During ECMO management, a mucus plug was removed by bronchoscopy daily and 18 L of water was removed using diuretics, resulting in weight loss of 24 kg. The patient was weaned from ECMO on day 5, extubated on day 16, and discharged on day 21. The fundamental treatment for obesity hypoventilation syndrome in morbidly obese patients is weight loss. VV-ECMO can be used for respiratory support until weight loss has been achieved.

A Case of Leptospirosis-Associated Severe Pulmonary Hemorrhagic Syndrome Successfully Treated with Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: In patients with leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS), hypoxemia is the most common cause of death despite maximal mechanical ventilation. CASE: A 50-year-old male sushi chef who had never traveled outside Japan presented with a 2-day history of fever and muscle pain. On admission, the patient had thrombocytopenia, renal insufficiency, and jaundice. His condition continued to deteriorate, with decreasing platelet count, worsening renal function, hyperbilirubinemia, hypotension, and respiratory distress. On day 5 after onset of symptoms, he required intubation and mechanical ventilation. Bronchoscopy showed diffuse endobronchial bleeding. His respiratory status worsened rapidly with a partial pressure of arterial oxygen to fraction of inspired oxygen ratio of 70, necessitating venovenous extracorporeal membrane oxygenation (V-V ECMO) and treatment with an inotrope, renal replacement therapy, and broad-spectrum antibiotics including benzylpenicillin. Anticoagulation was maintained at the minimum level. His condition improved, and he was weaned off ECMO on day 15 and discharged on day 19 after onset of symptoms. The leptospirosis diagnosis was confirmed by leptospiral DNA detection in urine samples by polymerase chain reaction and the results of paired serum antibody titer testing. CONCLUSIONS: V-V ECMO may prevent mortality in patients with leptospirosis-induced SPHS that does not respond to conventional therapy.

Successful use of veno-venous extracorporeal membrane oxygenation as a bridge to lung T transplantation in a patient with pulmonary fibrosis.

As the Japanese organ donor allocation system does not permit the allocation of lungs at a priority level to patients on extracorporeal membrane oxygenation (ECMO), many of these patients die before suitable donor lungs become available. We report our first experience with ECMO as a bridge to lung transplantation (LTx) from a brain-dead donor. A 40-year-old man with interstitial lung disease who was listed for LTx 3 years previously, experienced progressive deterioration of respiratory function. He was mechanically ventilated at another hospital and was transported to our hospital due to severe hypoxemia. He underwent veno-venous ECMO and was extubated 2 h after the ECMO therapy was initiated. He was conscious, could consume food and liquids, and could exercise normally while awaiting LTx. Lungs from a marginal donor became available on day 18 after ECMO initiation. He was transported to the transplantation center and successfully underwent LTx.

Impact of mobilisation therapy on the haemodynamic and respiratory status of elderly intubated patients in an intensive care unit: A retrospective analysis.

OBJECTIVES: This study identified respiratory and haemodynamic parameters affected by limited mobilisation therapy in elderly, critically ill, intubated patients in an intensive care unit. METHODS: Over 18 months, we retrospectively assessed physiological changes during 43 mobilisation therapy sessions in 23 patients requiring mechanical ventilation for >48h. We compared heart rate, mean arterial blood pressure, respiratory rate, partial pressure of oxygen in arterial blood/inspired fraction of oxygen and lactate before and after mobilisation therapy, which entailed sitting on the edge of a hospital bed without back support. We analysed baseline characteristics and therapy duration. RESULTS: Patients' median age was 75 (interquartile range: 65-79) years, and the median Acute Physiology and Chronic Health Evaluation II score was 27 (26-31). Average therapy duration was 1h (0.5-2h). Therapy did not significantly modify heart rate or arterial blood pressure but increased the partial pressure of oxygen in arterial blood/inspired fraction of oxygen ratio significantly, from 218.8 (135.4-271.7) to 237.3 (167.2-284.9; p=0.007), indicating improved lung function. CONCLUSION: In this retrospective review, mobilisation therapy had no adverse effect on elderly, critically ill, intubated patients' haemodynamic status and appeared to improve the PaO2/FIO2 ratio; further research is required to confirm this finding.

Successful application of venoarterial-venous extracorporeal membrane oxygenation in the reversal of severe cardiorespiratory failure.

Typical configurations of extracorporeal membrane oxygenation (ECMO) include venovenous (VV) and venoarterial (VA) configurations; however, other configurations of ECMO may be necessary in certain situations. We performed VA ECMO for a 71-year-old man who experienced refractory hypoxaemia associated with a brief cardiac arrest after resection of the small intestine showing necrosis. As the cardiac function improved, the patient showed a complication of poor oxygenation in the upper body due to insufficient respiratory function. Therefore, we performed VA-venous ECMO, which further improved his cardiac function and allowed him to be converted to VV ECMO. It is very important to consider different configuration strategies of ECMO by adjusting the patient's cardiopulmonary conditions appropriately.

Septic shock due to Aeromonas hydrophila bacteremia in a patient with alcoholic liver cirrhosis: a case report.

INTRODUCTION: Aeromonas hydrophila sometimes causes bacteremia, which can be fatal in compromised patients, such as those with liver cirrhosis. We present a case of septic shock due to Aeromonas hydrophila bacteremia in a patient with liver cirrhosis, which was successfully treated with rapid resuscitation and critical care. CASE PRESENTATION: A 71-year-old Japanese man with liver cirrhosis was transported to our emergency center by ambulance after presenting with gait difficulties and fever. On arrival, he exhibited shock and severe lactic acidosis, which was suggestive of sepsis, and was immediately resuscitated and administered empiric antibiotic therapy. He also displayed catecholamine-resistant hypotension, which was successfully treated with critical care including supportive therapies, such as polymyxin B hemoperfusion and cytokine-absorbing hemofiltration. Aeromonas hydrophila was detected in his initial blood cultures. CONCLUSIONS: Aeromonas septicemia should be considered in patients with alcoholic liver cirrhosis who have profound shock. In addition to goal-directed therapy and the prompt administration of empiric antibiotic therapy, aggressive critical care involving multiple supportive therapies can save such patients.

A case of right atrial angiosarcoma: The utility of PET and CT fusion imaging in detecting a malignant cardiac tumor.

A 49-year-old woman was admitted to the hospital because of cardiac tamponade. The hemorrhagic pericardial effusion was cytologically negative for malignant cells. Cardiac magnetic resonance imaging showed two masses in the anterior and lateral right atrium; however, positron emission tomography (PET) image using 18F-fluorodeoxyglucose revealed strong uptake in the anterior right atrium, without other tumors or metastasis. Intraoperatively, the lateral mass was confirmed as a thrombus, whereas the anterior mass was removed surgically and was diagnosed as an angiosarcoma with histopathological examination. However, she was re-admitted to the hospital 1 month after the operation because of cerebral hemorrhage, suspicious of distant metastasis. PET is useful for the detection of cardiac angiosarcoma.

Therapeutic efficacy of leukocytapheresis for procoagulant microparticles during hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) presents with signs of persistent remittent fever, hepatosplenomegaly, pancytopenia, hepatic dysfunction, and disseminated intravascular coagulation because of hypercytokinemia caused by activated T lymphocytes and macrophages. In recent years leukocytapheresis using a leukocyte removal filter (known as lymphocytapheresis, LCAP) has been applied to the treatment of various autoimmune diseases. The removal of activated monocytes during LCAP treatment appears useful for hypercytokinemia. We experienced a 32-year-old Japanese man with HPS with elevated tissue factor-enriched monocyte-derived microparticles (MDMPs) and pro-inflammatory cytokines/chemokines. Improvements in the level of MDMPs and hypercytokinemia were observed after LCAP treatment. LCAP treatment performed for HPS can be considered a therapeutic strategy for patients with a risk of fetal hemorrhage.