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Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown., Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?, Study Design and Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao 2 to Fio 2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H 2 O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed., Results: A total of 2,466 patients were enrolled. Median baseline Pao 2 to Fio 2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H 2 O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR., Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes., Trial Registry: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov., (Copyright © 2021. Published by Elsevier Inc.)

Background: The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers., Methods: Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter., Results: Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS)., Conclusion: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.

To evaluate the interaction between patient and ventilator during widely varying levels of pressure support (PS) ventilation, we studied 33 patients who had undergone aortocoronary bypass. All patients were without preoperative evidence of lung disease and had left ventricular ejection fractions greater than 45 percent. We assessed both changes in ventilatory pattern and the use of an extension of the Campbell technique to determine the components of the mechanical work of breathing (WOB). Patients were placed on 0, 10, 20, and 30 cm H2O of PS. We found that increasing the pressure support level (PSL) did not change minute ventilation, PCO2, or pH despite large changes in both rate and depth of breathing. The inspiratory time fraction was consistently and progressively reduced as PS increased. Although mean inspiratory flow (MIF) increased by 75 +/- 9 (SE) percent as the PSL increased to 30 cm H2O, mean airway pressure rose only 3.5 +/- 0.1 cm H2O. Observed changes in the resistive and elastic components of WOB at PSL greater than 0 were consistent with values predicted from baseline observations and changes in VT and MIF demonstrating that the Campbell technique of separating resistive and elastic components of the patient's WOB during unassisted ventilation can be extended to the analysis of WOB during mechanical ventilation. We were surprised to observe that although inspiratory WOB fell 67 +/- 13 percent as the PSL increased to 30 cm H2O, postinspiratory work by the inspiratory muscles (WOBPIIM) did not show significant change. The persistence and substantial values of WOBPIIM in some patients suggested the presence of significant patient-ventilator dyssynchrony, especially at higher levels of PS. Total inspiratory WOB per minute, including both patient WOB and WOB by the ventilator, increased by 186 +/- 29 percent, demonstrating that PS results in a respiratory pattern requiring substantially greater total mechanical work.

Intralipid (20 percent, 500 ml) was infused fast (5 h) or slow (10 h) randomly in patients with lung injury to relate changes in plasma prostaglandin (PG) concentrations to gas exchange and pulmonary hemodynamics. Data were collected at baseline, midpoint of infusion, and 2 h following infusion. Vasodilator and vasoconstrictor PG metabolites, 6-keto-PGF1 alpha, and thromboxane B2, respectively, were measured in radial arterial blood samples. Slow Intralipid infusion increased shunt fraction (QS/QT) without changing mean pulmonary artery pressure (MPAP), whereas fast Intralipid infusion increased MPAP without changing QS/QT. Prostaglandin levels did not change significantly during either infusion. However, in both groups when the PG substrate was removed, hemodynamic and metabolite values decreased in parallel. In conclusion, we were unable to demonstrate a cause and effect relationship between plasma levels of 6-keto-PGF1 alpha and thromboxane B2 and the observed pulmonary hemodynamic response to slow or fast Intralipid infusion.

The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane.

The impact of the pericardium on right ventricular performance in the presence of normal filling pressures was evaluated using a rapid response RVEF thermodilution pulmonary artery catheter and TEE. In eight patients with normal right coronary arteries undergoing coronary artery bypass surgery, hemodynamic measurements revealed increased right ventricular end-diastolic and end-systolic volumes with diminished RVEF after opening the pericardium. In eight additional patients with right coronary artery disease, directionally similar changes in right ventricular volume were seen. Ejection fraction, however, was unchanged possibly due to altered right ventricular compliance. Echocardiogram evaluation of right ventricular area changes in patients with compromised right coronary systems corresponded to ejection fraction determinations obtained with thermodilution technique.

To evaluate the effect of administration of dobutamine on gas exchange in patients with one-lung atelectasis during pneumonectomy, ten patients with normal pulmonary function and localized carcinoma of the lung were studied during pulmonary resection. With each patient in the lateral decubitus position, hemodynamic profiles and oxygen transport data were recorded before and after administration of dobutamine at 5 micrograms/kg/min. Patients were ventilated with one-lung anesthesia and administration of 100 percent oxygen. With infusion of dobutamine, the heart rate, cardiac index, and LVSWI significantly increased. Mean arterial pressure increased while PAP fell. Systemic and pulmonary vascular resistance also declined. Arterial oxygenization and delivery improved, while oxygen uptake was unchanged. Pulmonary shunt fraction was significantly reduced. While the mechanism for shunt reduction in our patients is unclear, operative factors may include pulmonary vasodilation with dobutamine inhibition of HPV. The negative impact of reduced HPV may have been lessened by gravitational distribution of blood flow and dobutamine-mediated reduction in PAP in our patients.

Cardiovascular collapse due to pulmonary hyperinflation was noted in a patient with chronic obstructive pulmonary disease following median sternotomy for cardiac surgery. Treatment included bronchodilator therapy to reduce airway obstruction, limitation of minute ventilation, and increasing time available for exhalation. High inspiratory flow rates and expiratory retard may be beneficial.