Low-dose CT for quantitative analysis in acute respiratory distress syndrome

Introduction: The clinical use of serial quantitative computed tomography (CT) to characterize lung disease and guide the optimization of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) is limited by the risk of cumulative radiation exposure and by the difficulties and risks related to transferring patients to the CT room. We evaluated the effects of tube current-time product (mAs) variations on quantitative results in healthy lungs and in experimental ARDS in order to support the use of low-dose CT for quantitative analysis. Methods: In 14 sheep chest CT was performed at baseline and after the induction of ARDS via intravenous oleic acid injection. For each CT session, two consecutive scans were obtained applying two different mAs: 60 mAs was paired with 140, 15 or 7.5 mAs. All other CT parameters were kept unaltered (tube voltage 120 kVp, collimation 32x0.5 mm, pitch 0.85, matrix 512x512, pixel size 0.625x0.625 mm ). Quantitative results obtained at different mAs were compared via Bland-Altman analysis. Results: Good agreement was observed between 60 mAs and 140 mAs and between 60 mAs and 15 mAs (all biases less than 1%). A further reduction of mAs to 7.5 mAs caused an increase in the bias of poorly and non aerated tissue (-2.9 and 2.4%, respectively) and determined a significant widening of the limits of agreement for the same compartments (-10.5 - 4.8 % for poorly aerated and -5.9 - 10.8% for non aerated tissue). Estimated mean effective dose at 140, 60, 15 and 7.5 mAs corresponded to 17.8, 7.4, 2.0 and 0.9 millisievert, respectively. Image noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield Units, respectively. Conclusions: A reduction of effective dose up to 70% has been achieved with minimal effects on lung quantitative results. Low-dose computed tomography provides accurate quantitative results and could be used to characterize lung compartment distribution and possibly monitor time-course of ARDS with a lower risk of exposure to ionizing radiation. A further radiation dose reduction is associated with lower accuracy in quantitative results

Extracorporeal gas exchange and spontaneous breathing for the treatment of acute respiratory distress syndrome : an alternative to mechanical ventilation?

OBJECTIVES: Venovenous extracorporeal gas exchange is increasingly used in awake, spontaneously breathing patients as a bridge to lung transplantation. Limited data are available on a similar use of extracorporeal gas exchange in patients with acute respiratory distress syndrome. The aim of this study was to investigate the use of extracorporeal gas exchange in awake, spontaneously breathing sheep with healthy lungs and with acute respiratory distress syndrome and describe the interactions between the native lung (healthy and diseased) and the artificial lung (extracorporeal gas exchange) in this setting. DESIGN: Laboratory investigation. SETTING: Animal ICU of a governmental laboratory. SUBJECTS: Eleven awake, spontaneously breathing sheep on extracorporeal gas exchange. INTERVENTIONS: Sheep were studied before (healthy lungs) and after the induction of acute respiratory distress syndrome via IV injection of oleic acid. Six gas flow settings (1-10 L/min), resulting in different amounts of extracorporeal CO2 removal (20-100% of total CO2 production), were tested in each animal before and after the injury. MEASUREMENTS AND MAIN RESULTS: Respiratory variables and gas exchange were measured for every gas flow setting. Both healthy and injured sheep reduced minute ventilation according to the amount of extracorporeal CO2 removal, up to complete apnea. However, compared with healthy sheep, sheep with acute respiratory distress syndrome presented significantly increased esophageal pressure variations (25 \ub1 9 vs 6 \ub1 3 cm H2O; p 80% of total CO2 production). CONCLUSIONS: Spontaneous ventilation of both healthy sheep and sheep with acute respiratory distress syndrome can be controlled via extracorporeal gas exchange. If this holds true in humans, extracorporeal gas exchange could be used in awake, spontaneously breathing patients with acute respiratory distress syndrome to support gas exchange. A deeper understanding of the pathophysiology of spontaneous breathing during acute respiratory distress syndrome is however warranted in order to be able to propose extracorporeal gas exchange as a safe and valuable alternative to mechanical ventilation for the treatment of patients with acute respiratory distress syndrome

Enhanced extracorporeal CO2 removal by regional blood acidification : Effect of infusion of three metabolizable acids

Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 \ub1 3.6 to 50.6 \ub1 7.4, 49.8 \ub1 5.6, and 52.0 \ub1 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3- of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids

Non-invasive carbon dioxide monitoring in a porcine model of acute lung injury due to smoke inhalation and burns

In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. Eight anesthetized Yorkshire pigs underwent mechanical ventilation, wood-bark smoke inhalation injury, and 40% total body surface area thermal injury. tPCO2 was measured with a SenTec system (SenTec AG, Therwil, Switzerland) and EtCO2 with a Capnostream-20 (Oridion Medical, Jerusalem, Israel). These values were compared with PaCO2 measurements from an arterial blood gas analyzer. Paired measurements of EtCO2-PaCO2 (n = 276) and tPCO2-PaCO2 (n = 250) were recorded in the PaCO2 range of 25 to 85 mmHg. Overlapping data sets were analyzed based on respiratory and hemodynamic status of animals. Acute lung injury was defined as PaO2/FIO2 64 300 mmHg; hemodynamic instability was defined as mean arterial pressure 64 60 mmHg. Before ALI, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.45; P < 0.0001), which deteriorated after onset of ALI (R = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R = 0.51, P < 0.0001), which was sustained after onset of ALI (R = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under unstable conditions, reevaluation of patient status and increased caution in the interpretation of results are required

Electron Microscopy as a Tool for Assessment of Anticoagulation Strategies during Extracorporeal Life Support : The Proof Is on the Membrane

Extracorporeal life support (ECLS) is fast becoming more common place for use in adult patients failing mechanical ventilation. Management of coagulation and thrombosis has long been a major complication in the use of ECLS therapies. Scanning electron microscopy (SEM) of membrane oxygenators (MOs) after use in ECLS circuits can offer novel insight into any thrombotic material deposition on the MO. In this pilot study, we analyzed five explanted MOs immediately after use in a sheep model of different acute respiratory distress syndrome (ARDS). We describe our methods of MO dissection, sample preparation, image capture, and results. Of the five MOs analyzed, those that received continuous heparin infusion showed very little thrombosis formation or other clot material, whereas those that were used with only initial heparin bolus showed readily apparent thrombotic material

Extracorporeal carbon dioxide removal enhanced by lactic acid infusion in spontaneously breathing conscious sheep

Background: The authors studied the effects on membrane lung carbon dioxide extraction (VCO2ML), spontaneous ventilation, and energy expenditure (EE) of an innovative extracorporeal carbon dioxide removal (ECCO2R) technique enhanced by acidification (acid load carbon dioxide removal [ALCO2R]) via lactic acid. Methods: Six spontaneously breathing healthy ewes were connected to an extracorporeal circuit with blood flow 250 ml/min and gas flow 10 l/min. Sheep underwent two randomly ordered experimental sequences, each consisting of two 12-h alternating phases of ALCO2R and ECCO2R. During ALCO2R, lactic acid (1.5 mEq/min) was infused before the membrane lung. Caloric intake was not controlled, and animals were freely fed. VCO2ML, natural lung carbon dioxide extraction, total carbon dioxide production, and minute ventilation were recorded. Oxygen consumption and EE were calculated. Results: ALCO2R enhanced VCO2ML by 48% relative to ECCO2R (55.3 \ub1 3.1 vs. 37.2 \ub1 3.2 ml/min; P less than 0.001). During ALCO2R, minute ventilation and natural lung carbon dioxide extraction were not affected (7.88 \ub1 2.00 vs. 7.51 \ub1 1.89 l/min, P = 0.146; 167.9 \ub1 41.6 vs. 159.6 \ub1 51.8 ml/min, P = 0.063), whereas total carbon dioxide production, oxygen consumption, and EE rose by 12% each (223.53 \ub1 42.68 vs. 196.64 \ub1 50.92 ml/min, 215.3 \ub1 96.9 vs. 189.1 \ub1 89.0 ml/min, 67.5 \ub1 24.0 vs. 60.3 \ub1 20.1 kcal/h; P less than 0.001). Conclusions: ALCO2R was effective in enhancing VCO2ML. However, lactic acid caused a rise in EE that made ALCO2R no different from standard ECCO2R with respect to ventilation. The authors suggest coupling lactic acid-enhanced ALCO2R with active measures to control metabolism

Modular extracorporeal life support : effects of ultrafiltrate recirculation on the performance of an extracorporeal carbon dioxide removal device

The combination of extracorporeal carbon dioxide removal (ECCO2R) and hemofiltration is a possible therapeutic strategy for patients needing both lung and renal support. We tested the effects of the recirculation of ultrafiltrate on membrane lung (ML) CO2 removal (VCO2ML). Three conscious, spontaneously breathing sheep were connected to a commercially produced ECCO2R device (Hemolung; Alung Technologies, Pittsburgh, PA) with a blood flow of 250 ml/min and a gas flow of 10 L/min. A hemofilter (NxStage, NxStage Medical, Lawrence, MA) was interposed in series after the ML. Ultrafiltrate flow was generated and recirculated before the ML. We tested four ultrafiltrate flows (0, 50, 100, and 150 ml/min) for 25 min each, eight times per animal, resulting in 24 randomized test repetitions. We recorded VCO2ML, hemodynamics and ventilatory variables, and natural lung CO2 transfer (VCO2NL) and collected arterial and circuitry blood samples. VCO2ML was unchanged by application of ultrafiltrate recirculation (40.5 \ub1 4.0, 39.7 \ub1 4.2, 39.8 \ub1 4.2, and 39.2 \ub1 4.1 ml/min, respectively, at ultrafiltrate flow of 0, 50, 100, and 150 ml/min). Minute ventilation, respiratory rate, VCO2NL, and arterial blood analyses were not affected by ultrafiltrate recirculation. In the tested configuration, ultrafiltrate recirculation did not affect VCO2ML. This modular technology may provide a suitable platform for coupling CO2 removal with various forms of blood purification

eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling

Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]