Extracorporeal Life Support Organization Center of Excellence recognition is associated with improved failure to rescue after cardiac arrest.

OBJECTIVE: The influence of Extracorporeal Life Support Organization (ELSO) center of excellence (CoE) recognition on failure to rescue after cardiac surgery is unknown. We hypothesized that ELSO CoE would be associated with improved failure to rescue. METHODS: Patients undergoing a Society of Thoracic Surgeons index operation in a regional collaborative (2011-2021) were included. Patients were stratified by whether or not their operation was performed at an ELSO CoE. Hierarchical logistic regression analyzed the association between ELSO CoE recognition and failure to rescue. RESULTS: A total of 43,641 patients were included across 17 centers. In total, 807 developed cardiac arrest with 444 (55%) experiencing failure to rescue after cardiac arrest. Three centers received ELSO CoE recognition, and accounted for 4238 patients (9.71%). Before adjustment, operative mortality was equivalent between ELSO CoE and non-ELSO CoE centers (2.08% vs 2.36%; P = .25), as was the rate of any complication (34.5% vs 33.8%; P = .35) and cardiac arrest (1.49% vs 1.89%; P = .07). After adjustment, patients undergoing surgery at an ELSO CoE facility were observed to have 44% decreased odds of failure to rescue after cardiac arrest, relative to patients at non-ELSO CoE facility (odds ratio, 0.56; 95% CI, 0.316-0.993; P = .047). CONCLUSIONS: ELSO CoE status is associated with improved failure to rescue following cardiac arrest for patients undergoing cardiac surgery. These findings highlight the important role that comprehensive quality programs serve in improving perioperative outcomes in cardiac surgery.

Discordance among assays for monitoring? Anticoagulation during extracorporeal life support.

OBJECTIVES: The optimal method for monitoring of anticoagulation in patients on extracorporeal life support (ECLS) is unknown. The objective of this study was to assess the relationship between anti-factor Xa level (anti-Xa; IU/mL) and activated partial thromboplastin time (aPTT; seconds) for monitoring intravenous unfractionated heparin anticoagulation in adult ECLS patients. METHODS: Charts of all adult patients cannulated for ECLS from 2015 through 2017 were reviewed and laboratory and heparin infusion data were extracted for analysis. Time matched pairs of anti-Xa and aPTT were considered concordant if both laboratory values were within the same clinically utilized range. A hierarchical logistic regression model was used to determine factors associated with discordance while accounting for patient level effects. RESULTS: A total of 1016 paired anti-Xa and aPTT values from 65 patients were evaluated. 500 (49.2%) paired samples were discordant with a degree of variability on linear regression (r2 = 0.315). The aPTT fell into a higher therapeutic range compared to the anti-Xa in 31.6% and lower in 17.3%. Logistic regression demonstrated that discordance was independently associated with time from initiation of ECLS (OR 1.17 per day, p < 0.001), average heparin infusion rate (OR 1.25 per U/kg/hr, p < 0.001), and INR (OR 3.22, p < 0.001). CONCLUSIONS: Nearly half of all aPTT and anti-Xa values were in discordant ranges and discordance is more likely as the time on ECLS and the INR level increase. The use of either assay in isolation to guide heparin anticoagulation may lead to misestimation of the degree of anticoagulation in complex ECLS patients.

Gastric Aspiration and Ventilator-Induced Model of Acute Respiratory Distress Syndrome in Swine.

INTRODUCTION: Mainstays of current treatment for acute respiratory distress syndrome (ARDS) focus on supportive care and rely on intrinsic organ recovery. Animal models of ARDS are often limited by systemic injury. We hypothesize that superimposing gastric aspiration and ventilator-induced injury will induce a lung-specific injury model of severe ARDS. MATERIALS AND METHODS: Adult swine (n = 8) were subject to a 12 h injury development period followed by 24 h of post-injury monitoring. Lung injury was induced with gastric secretions (3 cc/kg body weight/lung, pH 1-2) instilled to bilateral mainstem bronchi under direct bronchoscopic vision. Ventilator settings within the injury period contradicted baseline settings using high tidal volumes and low positive end-expiratory pressure. Baseline settings were restored following the injury period. Arterial oxygenation and lung compliance were monitored. RESULTS: At 12 h, PaO2/FiO2 ratio and static and dynamic compliance were significantly reduced from baseline (P < 0.05). During the postinjury period, animals showed no signs of recovery in PaO2/FiO2 ratio and lung compliance. Lung edema (wet/dry weight ratio) of injured lungs was significantly elevated versus noninjured lungs (8.5 ± 1.7 versus 5.6 ± 0.3, P = 0.009). Expression of proinflammatory cytokines IL-6 and IL-8 were significantly elevated in injured lungs (P < 0.05). CONCLUSIONS: Twelve hours of high tidal volume and low positive end-expiratory pressure in conjunction with low-pH gastric content instillation produces significant acute lung injury in swine. This large animal model may be useful for testing severe ARDS treatment strategies.

Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome.

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO2/FiO2 ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO2/FiO2 ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.

Antithrombin supplementation in adult patients receiving extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation is associated with an increased risk of thrombosis and hemorrhage. Acquired antithrombin deficiency often occurs in patients receiving extracorporeal membrane oxygenation, necessitating supplementation to restore adequate anticoagulation. Criteria for antithrombin supplementation in adult extracorporeal membrane oxygenation patients are not well defined. METHODS: In this retrospective observational study, adult patients receiving antithrombin supplementation while supported on extracorporeal membrane oxygenation were evaluated. Antithrombin was supplemented when anti-Xa levels were subtherapeutic with unfractionated heparin infusion rates of 15-20 units/kg/h and measured antithrombin activity <50%. Patients were evaluated for changes in degree of anticoagulation and signs of bleeding 24 hours pre- and post-antithrombin supplementation. RESULTS: A total of 14 patients received antithrombin supplementation while on extracorporeal membrane oxygenation. The median percentage of time therapeutic anti-Xa levels were maintained was 0% (0-43%) and 40% (9-84%) in the pre-antithrombin and post-antithrombin groups, respectively (p = 0.13). No difference was observed in the number of patients attaining a single therapeutic anti-Xa level (pre-antithrombin = 6, post-antithrombin = 13; p = 0.37) or unfractionated heparin infusion rate (pre-antithrombin = 7.35 (1.95-10.71) units/kg/h, post-antithrombin = 6.81 (3.45-12.58) units/kg/h; p = 0.33). Thirteen patients (92%) achieved an antithrombin activity at goal following supplementation. Antithrombin activity was maintained within goal range 52% of the time during the replacement period. Four bleeding events occurred pre-antithrombin and 10 events post-antithrombin administration (p = 0.26) with significantly more platelets administered post-antithrombin (pre-antithrombin = 0.5 units, post-antithrombin = 4.5 units; p = 0.01). CONCLUSION: Therapeutic anticoagulation occurred more frequently following antithrombin supplementation; however, this difference was not statistically significant. More bleeding events occurred following antithrombin supplementation while observing an increase in platelet transfusions.

Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death.

BACKGROUND: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs. METHODS: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion. RESULTS: After transplant, left lung-specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 ± 87.7 mm Hg vs. 252.7 ± 166.0 mm Hg, p = 0.017; 4-hour: 429.7 ± 93.6 mm Hg vs. 231.5 ± 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 ± 9.4 ml/cm H2O vs. 10.2 ± 3.5 ml/cm H2O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 ± 0.7 vs. 8.8 ± 1.1, p = 0.040) and interleukin-1ß expression (927 ± 300 pg/ng protein vs. 2,070 ± 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group. CONCLUSIONS: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.

Effective and Safe Use of Glucocorticosteroids for Rescue of Late ARDS.

We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS.

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

OBJECTIVE: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS: Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS: Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. CONCLUSIONS: Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.