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Objective: To evaluate the independent influence of fluid balance on outcomes for patients with acute lung injury. Design: Secondary analysis of a prospective cohort study conducted between March 1996 and March 1999. Setting: The study involved 10 academic clinical centers (with 24 hospitals and 75 Intensive Care Units). Patients: All patients for whom fluid balance data existed (844) from the 902 patients enrolled in the National Heart Lung Blood Institute's ARDS Network ventilator-tidal volume trial. Interventions: The study had no interventions. Measurements/Results: On the first day of study enrollment, 683 patients were, on average, more than 3.5 L in positive fluid balance compared to 161 patients in negative fluid balance (P < .001). Cumulative negative fluid balance on day 4 of the study was associated with an independently lower hospital mortality (OR, 0.50; 95% CI, 0.28-0.89; P < .001) more ventilator and intensive care unit-free days. Conclusions: Negative cumulative fluid balance at day 4 of acute lung injury is associated with significantly lower mortality, independent of other measures of severity of illness. [ABSTRACT FROM AUTHOR]

Inhalable nitric oxide (iNO) is a lifesaving, FDA-approved drug to improve oxygenation in persistent pulmonary hypertension of the newborn. iNO also has many other applications in lung diseases owing to its vasodilatory and antimicrobial effects. However, its wider therapeutic application is often prohibited by the high cost and logistical barriers of traditional NO/N 2 gas tanks. Development of low-cost, portable and tankless nitric oxide (NO) generators is a critical need to advance iNO therapy. Here, we describe the feasibility of NO generation by the controlled reduction of nitrite (NO 2 - ) ions. This was accomplished by using ascorbate to reduce NO 2 - ions mediated by a copper(I/II) redox pair complexed by an azo-crown ether ligand ([Cu(II)L] 2+ /[Cu(I)L] + ) in the solution phase. We found that oxalate, a decomposition product of ascorbate, interferes with the NO generation from the copper-ligand complex. This interference was mitigated, and the reaction was further optimized. NO generation through this method was found to be highly controllable via its proportionality to the flow rate of NO 2 - injected into a reaction chamber containing the reducing components. Hence, this simple approach adds to the current collection of innovative methods under development to obviate the use of NO tanks for iNO delivery.

Extracorporeal Carbon Dioxide Removal (ECCO 2 R) systems support patients with severe respiratory failure. Concurrent ambulation and physical therapy improve patient outcomes, but these procedures are limited by the complexity and size of the extracorporeal systems and rapid changes in patient metabolism and the acid-base balance. Here, we present the first prototype of a wearable ECCO 2 R system capable of adjusting to a patient's changing metabolic needs. Exhaust gas CO 2 (EGCO 2 ) partial pressure is used as an analog for blood CO 2 partial pressure (pCO 2 ). Twin blowers modulate sweep gas through the AL to achieve a desired target EGCO 2 . The integrated system was tested in vitro for 24 h with water, under varying simulated metabolic conditions and target EGCO 2 values, and in a single test with whole blood. When challenged with changing inlet water pCO 2 levels in in vitro tests, the system adjusted the sweep gas to achieve target EGCO 2 within 1 min. Control runs with a fixed sweep gas (without negative feedback) demonstrated higher EGCO 2 levels when challenged with higher water flow rates. A single in vitro test with whole ovine blood confirmed functionality in blood. This is the first step toward wearable ECCO 2 R systems that automatically respond to changing metabolism. Such devices would facilitate physical therapy and grant greater autonomy to patients.

The goal of the low-resistance pediatric artificial lung (PAL-LR) is to serve as a pumpless bridge-to-transplant device for children with end-stage lung failure. The PAL-LR doubles the exposed fiber length of the previous PAL design. In vitro and in vivo studies tested hemocompatibility, device flow, gas exchange and pressure drop performance. For in vitro tests, average rated blood flow (outlet SO2 of 95%) was 2.56 ± 0.93 L/min with a pressure drop of 25.88 ± 0.90 mm Hg. At the targeted pediatric flow rate of 1 L/min, the pressure drop was 8.6 mm Hg compared with 25 mm Hg of the PAL. At rated flow, the average O2 and CO2 transfer rates were 101.75 ± 10.81 and 77.93 ± 8.40 mL/min, respectively. The average maximum O2 and CO2 exchange efficiencies were 215.75 ± 22.93 and 176.99 ± 8.40 mL/(min m2), respectively. In vivo tests revealed an average outlet SO2 of 100%, and average pressure drop of 2 ± 0 mm Hg for a blood flow of 1.07 ± 0.02 L/min. Having a lower resistance, the PAL-LR is a promising step closer to a pumpless artificial membrane lung that alleviates right ventricular strain associated with idiopathic pulmonary hypertension., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Heart transplantation is always an emergency because the transplant needs to occur within 6 h after procurement to prevent primary graft dysfunction. Static cold storage (SCS) is the gold-standard preservation method. This study describes the outcomes of hearts preserved after prolonged SCS (12 and 24 h); those are then resuscitated with a novel normothermic ex situ heart perfusion (NEHP) system., Methods: Anesthetized piglets (n = 10) were used as heart donors. Hearts were procured and stored at 5 °C CoStorSol following standard SCS protocols. Two groups were studied: SCS-12 h and SCS-24 h. After SCS, 8 h of NEHP (37 °C blood-based perfusate) was performed at 0.7-1.0 mL/min/g of cardiac tissue. NEHP parameters were monitored continuously. Results were corroborated with 3 additional hearts transplanted orthotopically in healthy recipients (n = 3) after SCS (24 h) + NEHP (5 h). Recipients were observed for 90 min after weaning off cardiopulmonary bypass support., Results: All hearts (after 12 and 24 h of SCS) regained normal function and metabolism within 10 min and retained it throughout 8 h of NEHP. No differences were observed in NEHP parameters and histopathology between groups. Three hearts were successfully transplanted after a total ~30 h of preservation (24 h of SCS + 5 h of NEHP + 1 h of second cold ischemia time). The 3 recipients were weaned off cardiopulmonary bypass with mild vasopressor support., Conclusions: NEHP has the potential to routinely resuscitate porcine hearts that have undergone SCS for up to 24 h, restoring them to viable function. By objectively assessing heart function before transplant, NEHP may enhance the success rate of transplants. If these resuscitated hearts can be successfully transplanted, it would support the effectiveness of NEHP in ensuring heart viability., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

This study presents the utilization of a novel, highly lipophilic nitric oxide (NO) donor molecule, S-nitroso-1-adamantanethiol (SNAT), for developing an NO-emitting polymer surface aimed at preventing thrombus formation and bacterial infection in extracorporeal circuits (ECCs). S-nitroso-1-adamantanethiol, a tertiary nitrosothiol-bearing adamantane species, was synthesized, characterized, and used to impregnate polyvinyl chloride (PVC) tubing for subsequent in vivo evaluation. The impregnation process with SNAT preserved the original mechanical strength of the PVC. In vitro assessments revealed sustained NO release from the SNAT-impregnated PVC tubing (iSNAT), surpassing or matching endothelial NO release levels for up to 42 days. The initial NO release remained stable even after 1 year of storage at -20°C. The compatibility of iSNAT with various sterilization techniques (OPA Plus, hydrogen peroxide, EtO) was tested. Acute in vivo experiments in a rabbit model demonstrated significantly reduced thrombus formation in iSNAT ECCs compared with controls, indicating the feasibility of iSNAT to mitigate coagulation system activation and potentially eliminate the need for systemic anticoagulation. Moreover, iSNAT showed substantial inhibition of microbial biofilm formation, highlighting its dual functionality. These findings underscore the promising utility of iSNAT for long-term ECC applications, offering a multifaceted approach to enhancing biocompatibility and minimizing complications., Competing Interests: Disclosure: O.L.C., R.G., R.H.B., S.P.S., G.L., and M.E.M. are inventors on US Provisional Patent PCT/US2024/031413 which is related to this work. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation., (© 2024. The Author(s).)

Background: Cold static storage and normothermic ex vivo heart perfusion are routinely limited to 6 h. This report describes intermittent left atrial (LA) perfusion that allows cardiac functional assessment in a working heart mode., Methods: Using our adult porcine model, general anesthesia was induced and a complete cardiectomy was performed following cardioplegic arrest. Back-table instrumentation was completed and normothermic ex vivo heart perfusion (NEHP) was initiated in a nonworking heart mode (Langendorff). After 1 h of resuscitation and recovery, LA perfusion was initiated and the heart was transitioned to a coronary flow-only working heart mode for 30 min. Baseline working heart parameters were documented and the heart was returned to nonworking mode. Working heart assessments were performed for 30 min every 6 h for 24 h., Results: Twenty-four-hour NEHP on 9 consecutive hearts (280 ± 42.1 g) was successful and no significant differences were found between working heart parameters at baseline and after 24 h of perfusion. There was no difference between initial and final measurements of LA mean pressures (5.0 ± 3.1 versus 9.0 ± 6.5 mm Hg, P  = 0.22), left ventricular systolic pressures (44.3 ± 7.2 versus 39.1 ± 9.0 mm Hg, P  = 0.13), mean aortic pressures (30.9 ± 5.8 versus 28.1 ± 8.1 mm Hg, P  = 0.37), and coronary resistance (0.174 ± 0.046 versus 0.173 ± 0.066 mL/min/g, P  = 0.90). There were also no significant differences between lactate (2.4 ± 0.5 versus 2.6 ± 0.4 mmol/L, P  = 0.17) and glucose (173 ± 75 versus 156 ± 70 mg/dL, P  = 0.37)., Conclusions: A novel model using intermittent LA perfusion to create a coronary flow-only working heart mode for assessment of ex vivo cardiac function has been successfully developed., Competing Interests: R.H.B. and A.R.-P. received supplies from Xvivo and Terumo for the ECLS Lab. A.R.-P. is member of the Advisory Board of the New Leadership Academy, University of Utah, and is a paid consultant with Terumo Cardiovascular. D.E.M. is the owner of Daris LLC, which sold the Mflow Organ Perfusion System to the University of Michigan. D.E.M. also has patents pending on an Automatic Perfusion System and a Method for rapid and accurate determination of average fluid circuit pressure and flowrate. D.H.D. receives royalties from Thompson Surgical and has unpaid board and committee positions with the American Association for Thoracic Surgery, American Society of Echocardiography, and Society of Thoracic Surgeons. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts ( n  = 42) of different sizes (6-55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions ( n  = 15); (2) NEHP + plasma exchange ( n  = 5); (3) NEHP + hemofiltration ( n  = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration ( n  = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion ( n  = 7). All hearts with NEHP + interventions ( n  = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group ( n  = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Spencer, Wilhelm, Stephan, Urrea, Palacio, Bartlett, Drake and Rojas-Pena.)

Introduction: A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model., Methods: Extremely premature lambs ( n = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.5 ± 0.35 kg. Lambs were cannulated using 10-14Fr cannulae for drainage via the right jugular vein and reinfusion via the umbilical vein. Lambs were intubated and lungs were filled with perfluorodecalin to a meniscus with a pressure of 5-8 cm H 2 O. The first option for transfusion was fetal whole blood from twins followed by maternal red blood cells. Arterial blood gases were used to titrate AP support to maintain fetal blood gas values., Results: The mean survival time on circuit was 119.6 ± 39.5 h. Hemodynamic parameters and lactate were stable throughout. As more adult blood transfusions were given to maintain hemoglobin at 10 mg/dL, the HbF% declined, reaching 40% by post operative day 7. The HbF% was inversely proportional to flow rates as higher flows were required to maintain adequate oxygen saturation and perfusion., Conclusions: Transfusion of adult blood led to decreased fetal hemoglobin concentration during AP support. The HbF% was inversely proportional to flow rates. Future directions include strategies to decrease the priming volume and establishing a fetal blood bank to have blood rich in HbF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Extracorporeal Circulation in Neonatal Respiratory Failure: A Prospective Randomized Study. By RH Bartlett, DW Roloff, RG Cornell, AF Andrews, PW Dillon, JB Zwischenberger. Pediatrics 1985; 76:479-87. Extracorporeal membrane oxygenation (ECMO) is the use of mechanical devices to replace cardiac and pulmonary function in critical care. In the 1960s, laboratory research showed that extracorporeal circulation could be maintained for days using a membrane oxygenator. In the 1970s, the first clinical trials showed that ECMO could sustain life in severe cardiac and pulmonary failure for days or weeks, leading to organ recovery. From 1980 to 2000, ECMO became standard practice for neonatal and pediatric respiratory and cardiac failure. The critical clinical trial was a prospective randomized trial of ECMO in newborn respiratory failure, published in 1985. This is the classic article reviewed in this publication. This was the first use of a randomized, adaptive design trial to minimize the potential ethical dilemma inherent to clinical trials in which the endpoint is death. Other randomized trials followed, and ECMO is now standard practice for severe respiratory and cardiac failure in all age groups., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Objective: Donor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data., Methods: We analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance., Results: DCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth., Conclusions: DCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives., Competing Interests: D.H.D. reported patent royalties from Thompson Surgical Instruments. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

The Extracorporeal Life Support Organization (ELSO) maintains the world's largest extracorporeal membrane oxygenation (ECMO) registry by volume, center participation, and international scope. This 2022 ELSO Registry Report describes the program characteristics of ECMO centers, processes of ECMO care, and reported outcomes. Neonates (0-28 days), children (29 days-17 years), and adults (≥18 years) supported with ECMO from 2009 through 2022 and reported to the ELSO Registry were included. This report describes adjunctive therapies, support modes, treatments, complications, and survival outcomes. Data are presented descriptively as counts and percent or median and interquartile range (IQR) by year, group, or level. Missing values were excluded before calculating descriptive statistics. Complications are reported per 1,000 ECMO hours. From 2009 to 2022, 154,568 ECMO runs were entered into the ELSO Registry. Seven hundred and eighty centers submitted data during this time (557 in 2022). Since 2009, the median annual number of adult ECMO runs per center per year increased from 4 to 15, whereas for pediatric and neonatal runs, the rate decreased from 12 to 7. Over 50% of patients were transferred to the reporting ECMO center; 20% of these patients were transported with ECMO. The use of prone positioning before respiratory ECMO increased from 15% (2019) to 44% (2021) for adults during the coronavirus disease-2019 (COVID-19) pandemic. Survival to hospital discharge was greatest at 68.5% for neonatal respiratory support and lowest at 29.5% for ECPR delivered to adults. By 2022, the Registry had enrolled its 200,000th ECMO patient and 100,000th patient discharged alive. Since its inception, the ELSO Registry has helped centers measure and compare outcomes across its member centers and strategies of care. Continued growth and development of the Registry will aim to bolster its utility to patients and centers., Competing Interests: Disclosure: J.E.T. is the Chair of the Registry Committee of the Extracorporeal Life Support Organization (ELSO). P.S.B. receives salary support from ELSO. G.M. is the President of ELSO. M.P. is the Immediate past President of ELSO. D.B. receives research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. M.A., A.H., and K.R. are the Immediate Past Co-Chairs of the Scientific Oversight Committee of ELSO. P.R. is the Executive Director of ELSO. C.S. is the Chief Executive Officer (CEO) of ELSO. N.A.B. is the President of European Chapter of ELSO. N.A.B. has been on the medical advisory boards for Xenios and Baxter. T.M. is on the Board of Directors of ELSO. R.D.G. is the President of the Latin-American Chapter of ELSO. P.M.K. is the President of the South West Asia and Africa Chapter of ELSO. J.F.F. is the President of Asia-Pacific Chapter of ELSO. P.M.A.A. is Treasurer of ELSO Board of Directors. P.M.A.A. is funded by U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301, NIH (R13HD104432) and FDA UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation (U01FD004979/U01FD005978). None of the funding sources were involved in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript. No other conflicts of interest reported. R.P.B. is a member of the Board of Directors for ELSO and receives funding from the National Heart, Lung, And Blood Institute (R01 HL153519)., (Copyright © ASAIO 2024.)

Background: Clinical translation of the extracorporeal artificial placenta (AP) is impeded by the high risk for intracranial hemorrhage in extremely premature newborns. The Nitric Oxide Surface Anticoagulation (NOSA) system is a novel non-thrombogenic extracorporeal circuit. This study aims to test the NOSA system in the AP without systemic anticoagulation., Methods: Ten extremely premature lambs were delivered and connected to the AP. For the NOSA group, the circuit was coated with DBHD-N 2 O 2 /argatroban, 100 ppm nitric oxide was blended into the sweep gas, and no systemic anticoagulation was given. For the Heparin control group, a non-coated circuit was used and systemic anticoagulation was administered., Results: Animals survived 6.8 ± 0.6 days with normal hemodynamics and gas exchange. Neither group had any hemorrhagic or thrombotic complications. ACT (194 ± 53 vs. 261 ± 86 s; p < 0.001) and aPTT (39 ± 7 vs. 69 ± 23 s; p < 0.001) were significantly lower in the NOSA group than the Heparin group. Platelet and leukocyte activation did not differ significantly from baseline in the NOSA group. Methemoglobin was 3.2 ± 1.1% in the NOSA group compared to 1.6 ± 0.6% in the Heparin group (p < 0.001)., Conclusions: The AP with the NOSA system successfully supported extremely premature lambs for 7 days without significant bleeding or thrombosis., Impact: The Nitric Oxide Surface Anticoagulation (NOSA) system provides effective circuit-based anticoagulation in a fetal sheep model of the extracorporeal artificial placenta (AP) for 7 days. The NOSA system is the first non-thrombogenic circuit to consistently obviate the need for systemic anticoagulation in an extracorporeal circuit for up to 7 days. The NOSA system may allow the AP to be implemented clinically without systemic anticoagulation, thus greatly reducing the intracranial hemorrhage risk for extremely low gestational age newborns. The NOSA system could potentially be applied to any form of extracorporeal life support to reduce or avoid systemic anticoagulation., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Competing Interests: Disclosure: The authors have no conflicts of interest to report.

Background: Historically, cardiac transplantation relied on cold static storage at 5 °C for ex vivo myocardial preservation. Currently, machine perfusion is the standard of care at many transplant centers. These storage methods are limited to 12 hours. We sought to evaluate the efficacy of hemofiltration and filtrate replacement in adult porcine hearts using normothermic heart perfusion (NEVHP) for 24 hours., Methods: We performed 24-hour NEVHP on 5 consecutive hearts. After anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, unloaded mode. After 1 hour, plasma exchange was performed, and hemofiltration was initiated. Heart function parameters and arterial blood gasses were obtained hourly., Results: All hearts (n = 5) were viable at the 24-hour mark. The average left ventricular systolic pressure at the beginning of the prep was 36.6 ± 7.9 mm Hg compared with 27 ± 5.5 mm Hg at the end. Coronary resistance at the beginning of prep was 0.79 ± 0.10 mm Hg/L/min and 0.93 ± 0.28 mm Hg/L/min at the end. Glucose levels averaged 223 ± 13.9 mg/dL, and the lactate average at the termination of prep was 2.6 ± 0.3 mmol/L., Conclusions: We successfully perfused adult porcine hearts at normothermic temperatures for 24 hours with results comparable to our pediatric porcine heart model. The next step in our research is NEVHP evaluation in a working mode using left atrial perfusion., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during ECPR improve recovery of brain and heart function in a porcine model of prolonged out-of-hospital CA., Design: Randomized interventional trial., Setting: University laboratory., Subjects: Swine., Interventions: In a blinded study, 48 swine were subjected to 8 minutes of ventricular fibrillation CA followed by 30 minutes of goal-directed CPR and 8 hours of ECPR. Animals were randomized into four groups ( n = 12) and given either placebo (P) or argatroban (ARG; 350 mg/kg) at minute 12 of CA and either placebo (P) or streptokinase (STK, 1.5 MU) at the onset of ECPR., Measurements and Main Results: Primary outcomes included recovery of cardiac function measured by cardiac resuscitability score (CRS: range 0-6) and recovery of brain function measured by the recovery of somatosensory-evoked potential (SSEP) cortical response amplitude. There were no significant differences in recovery of cardiac function as measured by CRS between groups ( p = 0.16): P + P 2.3 (1.0); ARG + P = 3.4 (2.1); P + STK = 1.6 (2.0); ARG + STK = 2.9 (2.1). There were no significant differences in the maximum recovery of SSEP cortical response relative to baseline between groups ( p = 0.73): P + P = 23% (13%); ARG + P = 20% (13%); P + STK = 25% (14%); ARG + STK = 26% (13%). Histologic analysis demonstrated reduced myocardial necrosis and neurodegeneration in the ARG + STK group relative to the P + P group., Conclusions: In this swine model of prolonged CA treated with ECPR, early intra-arrest anticoagulation during goal-directed CPR and thrombolytic therapy during ECPR did not improve initial recovery of heart and brain function but did reduce histologic evidence of ischemic injury. The impact of this therapeutic strategy on the long-term recovery of cardiovascular and neurological function requires further investigation., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

On the 50th anniversary of the Society of Critical Care Medicine's journal Critical Care Medicine, critical care pioneers reflect on the importance of the journal to their careers and to the development of the field of adult and pediatric critical care., Competing Interests: Dr. Bartlett received support for article research from the National Institutes of Health. Dr. Jacobi received funding from Visante, Pfizer Hospital Products Division, AcelRx, and La Jolla Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: For children with end-stage lung disease that cannot wean from extracorporeal life support (ECLS), a wearable artificial lung would permit extubation and provide a bridge to recovery or transplantation. We evaluate the function of the novel Pediatric MLung-a low-resistance, pumpless artificial lung developed specifically for children-in healthy animal subjects., Methods: Adolescent "mini sheep" weighing 12-20 kg underwent left thoracotomy, cannulation of the main pulmonary artery (PA; inflow) and left atrium (outflow), and connection to the MLung., Results: Thirteen sheep were studied; 6 were supported for 7 days. Mean PA pressure was 23.9 ± 6.9 mmHg. MLung blood flow was 633±258 mL/min or 30.0 ± 16.0% of CO. MLung pressure drop was 4.4 ± 3.4 mmHg. Resistance was 7.2 ± 5.2 mmHg/L/min. Device outlet oxygen saturation was 99.0 ± 3.3% with inlet saturation 53.8 ± 7.3%. Oxygen delivery was 41.1 ± 18.4 mL O 2 /min (maximum 84.9 mL/min) or 2.8 ± 1.5 mL O 2 /min/kg. Platelet count significantly decreased; no platelet transfusions were required. Plasma free hemoglobin significantly increased only on day 7, at which point 2 of the animals had plasma free hemoglobin levels above 50 mg/dL., Conclusion: The MLung provides adequate gas exchange at appropriate blood flows for the pediatric population in a PA-to-LA configuration. Further work remains to improve the biocompatibility of the device., Level of Evidence: N/A., Competing Interests: Declaration of Competing Interest Brian P. Fallon, Alex J. Thompson, Aaron R. Prater, Skylar Buchan, Trevor Alberts, Alvaro Rojas-Pena, and Ronald B Hirschl have no interests to declare. Robert H. Bartlett is the holder of a patent for “Gated-concentric artificial lung” (U.S. patent number 10,589,015)., (Copyright © 2022. Published by Elsevier Inc.)

Artificial lung (AL) systems provide respiratory support to patients with severe lung disease, but none can adapt to the changing respiratory needs of the patients. Precisely, none can automatically adjust carbon dioxide (CO2) removal from the blood in response to changes in patient activity or disease status. Because of this, all current systems limit patient comfort, activity level, and rehabilitation. A portable servoregulation controller that automatically modulates CO2 removal in ALs to meet the real-time metabolic demands of the patient is described. The controller is based on a proportional-integral-derivative (PID) based closed-loop feedback control system that modulates sweep gas (air) flow through the AL to maintain a target exhaust gas CO2 partial pressure (target EGCO2 or tEGCO2). The presented work advances previous research by (1) using gas-side sensing that avoids complications and clotting associated with blood-based sensors, (2) incorporating all components into a portable, battery-powered package, and (3) integrating smart moisture removal from the AL to enable long term operation. The performance of the controller was tested in vitro for ∼12 h with anti-coagulated bovine blood and 5 days with distilled water. In tests with blood, the sweep gas flow was automatically adjusted by the controller rapidly (<2 min) meeting the specified tEGCO2 level when confronted with changes in inlet blood partial pressure of CO2 (pCO2) levels at various AL blood flows. Overall, the CO2 removal from the AL showed a strong correlation with blood flow rate and blood pCO2 levels. The controller successfully operated continuously for 5 days when tested with water. This study demonstrates an important step toward ambulatory AL systems that automatically modulate CO2 removal as required by lung disease patients, thereby allowing for physiotherapy, comfort, and activity.