Progressive changes in pulmonary gas exchange during invasive respiratory support for COVID-19 associated acute respiratory failure: A retrospective study of the association with 90-day mortality.

BACKGROUND: Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90-day survival in patients with COVID-19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support. METHODS: In this single-center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU-admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90-day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression. RESULTS: Almost 20,000 blood gases in 130 patients were analyzed. The overall 90-day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77-0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20-2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90-day mortality was 0.82 [0.75-0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42-2.73] for every 0.1 increase in Vd/Vt. CONCLUSION: The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID-19 ARDS were significant predictors for 90-day mortality.

Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia.

How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod DK, Meshram T, et al. Author Response: Beyond the Nasal Prongs: A Joust of Oxygen Delivery Methods in Post-op Hypoxemia. Indian J Crit Care Med 2024;28(6):626-627.

Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study.

Background: Acute hypoxemic respiratory failure is among the more commonly occurring complications in postoperative patients. Supplemental oxygen and addressing the primary etiology form the basis of its treatment. Materials and methods: We conducted an open-labeled randomized control trial with 90 adult patients and compared three oxygen delivery vehicles (ODV), i.e., noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and venturi mask (VM) in postoperative hypoxemic patients. The primary outcome variable was a change in the P/F ratio after 2 hours of use of ODV. Results: It was observed that the change in P/F ratio after 2 hours was similar in all three ODV groups (p = 0.274). The mean values of the post-ODV P/F ratio were comparable with the pre-ODV P/F ratio in all three modalities. The P/F ratio after HFNC was 358.08 ± 117.95; after NIV was 357.60 ± 220.67; and after VM was 355.47 ± 101.90 (p = 0.997). Conclusion: Among HFNC, NIV, and VM, none of the devices proved superior to the other for use in postoperative hypoxemia. How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S, Rathod D, Meshram T, et al. Comparison of Oxygen Delivery Devices in Postoperative Patients with Hypoxemia: An Open-labeled Randomized Controlled Study. Indian J Crit Care Med 2024;28(3):294-298.

Oxygenation Index, Oxygen Saturation Index vs PaO2/FiO2 *PEEP: A Secondary Analysis of OXIVA-CARDS Study.

Background: The classification of Berlin definition is based on the PaO2/FiO2 ratio, which has been found to have a poor association with mortality. Airway pressures reflect lung compliance and the settings of mechanical ventilators. In this study, we aimed to investigate the change in the severity of COVID-19-associated acute respiratory distress syndrome (ARDS) classification using [PaO2/FiO2 × PEEP] (P/FP) ratio compared to the traditional P/F ratio, and whether the P/FP ratio improves the predictive validity of in-hospital mortality. Methods: Our study sample included patients from the OXIVA-CARDS study. In this secondary analysis, we examined the oxygenation index and oxygen saturation index in relation to the P/FP ratio, as well as the risk of P/FP in mortality. We used Pearson's correlation to assess the relationships between various parameters. Receiver operating characteristic analysis with Youden's index was used to compare the prognostic value of the oxygenation index (OI), oxygen saturation index (OSI), P/F ratio, P/FP ratio, and SaO2/FiO2 ratio for predicting overall mortality. Multiple logistic regression was also performed to determine the impact of mean airway pressure (Pmean), S/F ratio, OI, and P/FP ratio on mortality. Results: A total of 201 patients (with 1543 measurements) were included in the analysis. Overall, 522 (34%) were reclassified into either more or less severe categories. Patients who were classified as having severe ARDS based on the P/FP ratio had significantly lower P/FP ratio, oxygenation index, and A-a O2 gradient as compared to those classified as having severe ARDS based on the P/F ratio (p < 0.05) at all levels of ARDS severity. On multivariate regression analysis, only the OI significantly impacted mortality (p < 0.05). Conclusion: We observed that the oxygen index and oxygen saturation index were more sensitive than the PaO2/FiO2 ratio and P/FP ratio. Additionally, only the oxygenation index had a significant impact on mortality. By including airway pressures in the calculation of the OI, its predictive ability is enhanced compared to using the S/F ratio, P/F ratio, or P/FP ratio. Highlights: The sensitivity of mortality by including Pmean is higher as compared to when only PEEP is taken into consideration. P/FP is a weak predictor of mortality as compared to OI and OSI. How to cite this article: Vadi SMR, Sanwalka N, Suthar D. Oxygenation Index, Oxygen Saturation Index vs PaO2/FiO2 *PEEP: A Secondary Analysis of OXIVA-CARDS Study. Indian J Crit Care Med 2024;28(10):917-922.

Estimating the best fraction of inspired oxygen for calculation of PaO2/FiO2 ratio in acute respiratory distress syndrome due to COVID-19 pneumonia.

Background: The ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2) is an indicator of pulmonary shunt fraction. PaO2/FiO2 (P/F) ratio is used to classify severity of acute respiratory distress syndrome (ARDS). With the same shunt fraction, P/F ratio decreases with increases in FiO2 which may lead to errors in classifying severity of ARDS. The effect of FiO2 on P/F ratio has not been investigated in COVID-19 pneumonia. In this study, we estimated the best FiO2 for the calculation of P/F ratio in a sample of patients with ARDS due to COVID-19 pneumonia. Materials and Methods: Blood gas and ventilatory data of 108 COVID-19 ARDS patients were analyzed in a cross-sectional observational study. Using Oxygen Status Algorithm the calculated shunt fraction served a basis for calculating P/F ratio for different FiO2. The severity of ARDS determined by P/F ratios at each FiO2s was compared with the shunt-based severity to find the optimum FiO2 for calculation of P/F ratio so the resulting classification has the best match with the reference classification. Results: A FiO2 of 1.0 for calculation of P/F ratio and ARDS classification showed the best match with shunt-based ARDS classification. A regression model was obtained with the PaO2, patient's original FiO2, Hemoglobin concentration, and SaO2 as the independent predictors of the P/F ratio for the FiO2 of 1.0. Conclusion: This study shows a FiO2 of 1.0 as the best value for correct calculation of P/F ratio and proper classification of ARDS.

Association between PaO2/FiO2 ratio and thrombotic events in COVID-19 patients.

PaO2/FiO2 (P/F ratio) is considered a marker of hypoxia/hypoxemia and mortality. Several prothrombotic changes are associated with the decrease of P/F ratio. The role of P/F ratio in patients with arterial and venous thrombosis remains unclear. The aim of this study was to assess in patients with coronavirus disease 2019 (COVID-19), the association between P/F ratio and arterial/venous thrombosis. One thousand and four hundred and six COVID-19 patients were recruited; 289 (21%) patients had P/F ratio < 200 and 1117 (79%) ≥ 200. Compared to the patients with P/F ratio ≥ 200, those with P/F ratio < 200 were older and with higher levels of glycemia, D-dimer and lower levels of albumin. Multiple linear regression analysis showed that albumin (standardized coefficient ß:  0.156; SE: 0.001; p = 0.0001) and D-dimer (standardized coefficient ß: -0.135; SE: 0.0001; p = 0.0001) were associated with P/F ratio. During the hospitalization 159 patients were transferred in intensive care unit (ICU), 253 patients died, 156 patients had arterial or venous thrombotic events. A bivariate logistic analysis was performed to analyze the predictors of thrombosis in COVID-19 patients; P/F ratio < 200 (Odds Ratio: [OR] 1.718, 95% Confidence Interval [CI] 1.085-2.718, p = 0.021), albumin (OR 1.693, 95% CI 1.055-2.716, p = 0.029), D-dimer (OR 3.469, 95% CI 2.110-5.703, p < 0.0001), coronary artery disease (CAD) (OR 1.800, 95% CI 1.086-2.984, p = 0.023) and heart failure (OR 2.410 95% CI 1.385-4.193, p = 0.002) independently predicted thrombotic events in this population. This study suggests that the P/F ratio is associated with thrombotic events by promoting a hypercoagulation state in patients hospitalized for COVID-19.

Use of Remdesivir in Patients Hospitalized for COVID-19 Pneumonia: Effect on the Hypoxic and Inflammatory State.

Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19.

Successful Outcome of Mother and Baby in a Woman With Severe COVID-19 Pneumonia in the Third Trimester of Pregnancy Who Required Extracorporeal Membrane Oxygenation Therapy.

Some studies have reported increased severe coronavirus disease (COVID-19) infection in the third trimester of pregnancy. Therefore, prenatal care in the third trimester requires careful judgment. It has been reported that extracorporeal membrane oxygenation (ECMO) therapy is useful for severe coronavirus disease 2019 (COVID-19) pneumonia; however, the optimal timing for the initiation of ECMO is controversial because the risks and benefits to the mother and fetus require careful consideration. We report a good outcome for mother and baby in a pregnant woman with severe COVID-19 pneumonia at 29 weeks gestation, who underwent urgent delivery and required ECMO therapy. A 34-year-old woman tested positive for COVID-19 at 27 weeks gestation. Despite treatment with remdesivir and prednisolone, her respiratory condition worsened. Consequently, she underwent emergent endotracheal intubation at 28 weeks and 2 days. Although the PaO2/FiO2 (P/F ratio) improved temporarily after endotracheal intubation, her respiratory condition progressively worsened. At 29 weeks gestation, an emergency cesarean section was performed and ECMO was initiated the next day. Although hematoma was observed after ECMO initiation, her respiratory condition improved. She was discharged home 54 days after the cesarean delivery without any complications. The neonate was intubated and transferred to the neonatal intensive care unit and was ultimately discharged home without any complications. Considering the risks and benefits of ECMO for the mother and fetus in the third trimester, ECMO should be initiated after delivery for better outcomes. The P/F ratio may be useful for an appropriate decision regarding delivery and the initiation of ECMO.

The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome.

Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.

Interleukin 18 and IL-18 BP response to Sars-CoV-2 virus infection.

The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.

Role of fecal calprotectin as a hypoxic intestinal damage biomarker in COVID-19 patients.

BACKGROUND: Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. METHODS: We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. RESULTS: Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 µg/g (5.2-120.9), mild ARDS 54.30 µg/g (5.2-1393.7), moderate ARDS 169.6 µg/g (43.4-640.5), and severe ARDS 451.6 µg/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). CONCLUSION: Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio.

The Characteristics of Patients with Severe COVID-19 Pneumonia Treated with Direct Hemoperfusion Using Polymyxin B-Immobilized Fiber Column (PMX-DHP).

Purpose: The characteristics of patients with severe COVID-19 pneumonia who underwent direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), in addition to steroids and immunomodulators, remain unclear. Patients and Methods: We conducted a retrospective observational study on 31 patients with severe COVID-19 pneumonia treated with PMX-DHP in an intensive care unit (ICU) from December 2020 to September 2021. Results: Outcomes 28 days after admission to the ICU were 20 in the survival group and 11 in the death group. Parameters significantly different between the survival and death group before PMX-DHP were percentage of invasive mechanical ventilation (25% vs 72.7%, P = 0.0209), PaO2/FIO2 (P/F) ratio (104.5 vs 75, P = 0.0317), and sequential organ failure assessment (SOFA) score (2 vs 3, P = 0.0356). Invasive mechanical ventilation avoidance rate was significantly different between the survival (100%) and death group (0%) (P = 0.0012). P/F ratio, respiratory ratio (RR), and lymphocyte counts improved significantly after PMX-DHP for all patients. The lymphocyte counts changed significantly in the survival (P < 0.0001), but not the death group (P = 0.7927). Conclusion: PMX-DHP, in addition to steroids and immunomodulators, may improve oxygenation and alleviate tachypnea by modulating the lymphocyte numbers and levels of various mediator against severe COVID-19 pneumonia. It may be better to perform PMX-DHP before multi organ dysfunction and lung injury has progressed. Furthermore, the early increase in lymphocyte counts after PMX-DHP might be an indicate a positive outcome.

Vaccination Status and Number of Vaccine Doses Are Independently Associated with the PaO2/FiO2 Ratio on Admission in Hospitalized COVID-19 Patients.

INTRODUCTION: Coronavirus Disease-19 (COVID-19) vaccines reduce the risk of severe disease and mortality. However, the association between vaccination status and number of doses and the PaO2/FiO2 ratio, a clinical measure of hypoxemia associated with an increased risk of intensive care treatment and mortality, has not been investigated. METHODS: We retrospectively assessed a consecutive series of 116 patients admitted to hospital with a primary diagnosis of COVID-19 between January and April 2022. Demographic, clinical, and laboratory data were collected within 24 h from admission. RESULTS: There was a significant positive relationship between the number of vaccine doses and the PaO2/FiO2 ratio (r = 0.223, p = 0.012). This association remained significant after adjusting for confounders. Vaccinated patients had significantly higher PaO2/FiO2 ratios than the unvaccinated (median: 250; IQR: 195-309 vs. 200; IQR: 156-257, p = 0.013). CONCLUSION: These results highlight the importance of the number of vaccine doses received in reducing the degree of hypoxia on admission in hospitalized COVID-19 patients.

The Association Between Oxygenation Status at 24 h After Diagnosis of Pulmonary Acute Respiratory Distress Syndrome and the 30-Day Mortality among Pediatric Oncological Patients.

Background: Pediatric oncology patients with acute respiratory distress syndrome (ARDS) secondary to pneumonia are at high risk of mortality. Our aim was to describe the epidemiology of ARDS in this clinical population and to identify the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates, stratified by the severity of ARDS. Methods: This was a retrospective cohort study of 82 pediatric oncology patients, with a median age of 4 years, admitted to our pediatric intensive care unit with a diagnosis of ARDS between 2013 and 2021. Demographic and clinical factors were compared between the survivor (n = 52) and non-survivor (n = 30) groups. Univariate and multivariate Cox proportional hazards regression models were used to determine the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates. Results: The mean airway pressure at ARDS diagnosis, PaO2/FiO2 (P/F) ratio, oxygenation index (OI) value, peak inspiratory pressure, and lactate level at 24 h after ARDS diagnosis, as well as complications (i.e., septicemia and more than two extrapulmonary organ failures) and adjunctive continuous renal replacement therapy, were significant mortality risk factors. After adjusting for other covariates, the oxygenation status P/F ratio (Hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.96-1.00, P = 0.043) and OI value (HR = 1.12, 95% CI = 1.02-1.23, P = 0.016) at 24 h remained independent mortality risk factors. According to the Kaplan-Meier survival curve, a low P/F ratio (≤ 150) and high OI (>10) were associated with a higher risk of 30-day mortality (50.9 and 52.9%, respectively; both P < 0.05). Conclusion: The P/F ratio and OI value measured at 24 h after ARDS diagnosis can provide a better stratification of patients according to ARDS disease severity to predict the 30-day mortality risk.

A Simple Non-Invasive Score Based on Baseline Parameters Can Predict Outcome in Patients with COVID-19.

We evaluated the role of CRP and other laboratory parameters in predicting the worsening of clinical conditions during hospitalization, ICU admission, and fatal outcome among patients with COVID-19. Consecutive adult inpatients with SARS-CoV-2 infection and respiratory symptoms treated in three different COVID centres were enrolled, and they were tested for laboratory parameters within 48 h from admission. Three-hundred ninety patients were enrolled. Age, baseline CRP, and LDH were associated with a P/F ratio < 200 during hospitalization. Male gender and CRP > 60 mg/L were shown to be independently associated with ICU admission. Lymphocytes < 1000 cell/µL were associated with the worst P/F ratio. CRP > 60 mg/L predicted exitus. We subsequently devised an 11-points numeric ordinary scoring system based on age, sex, CRP, and LDH at admission (ASCL score). Patients with an ASCL score of 0 or 2 were shown to be protected against a P/F ratio < 200, while patients with an ASCL score of 6 to 8 were shown to be at risk for P/F ratio < 200. Patients with an ASCL score ≥ 7 had a significantly increased probability of death during hospitalization. In conclusion, patients with elevated CRP and LDH and an ASCL score > 6 at admission should be prioritized for careful respiratory function monitoring and early treatment to prevent a progression of the disease.

Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States. Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression-Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio. Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I. Conclusion: In patients hospitalized with COVID-19 and mild-to-moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit-risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Impact of cytidine diphosphocholine on oxygenation in client-owned dogs with aspiration pneumonia.

BACKGROUND: New drugs for veterinary patients with acute respiratory distress syndrome (ARDS) are urgently needed. Early or late postinfection treatment of influenza-infected mice with the liponucleotide cytidine diphosphocholine (CDP-choline) resulted in decreased hypoxemia, pulmonary edema, lung dysfunction, and inflammation without altering viral replication. These findings suggested CDP-choline could have benefit as adjunctive treatment for ARDS in veterinary patients (VetARDS). OBJECTIVES: Determine if parenterally administered CDP-choline can attenuate mild VetARDS in dogs with aspiration pneumonia. ANIMALS: Dogs admitted to a veterinary intensive care unit (ICU) for aspiration pneumonia. METHODS: Subjects were enrolled in a randomized, double-blinded, placebo-controlled trial of treatment with vehicle (0.1 mL/kg sterile 0.9% saline, IV; n = 8) or CDP-choline (5 mg/kg in 0.1 mL/kg 0.9% saline, IV; n = 9) q12h over the first 48 hours after ICU admission. RESULTS: No significant differences in signalment or clinical findings were found between placebo- and CDP-choline-treated dogs on admission. All dogs exhibited tachycardia, tachypnea, hypertension, hypoxemia, hypocapnia, lymphopenia, and neutrophilia. CDP-choline administration resulted in rapid, progressive, and clinically relevant increases in oxygenation as determined by pulse oximetry and ratios of arterial oxygen partial pressure (Pa O2 mmHg) to fractional inspired oxygen (% Fi O2 ) and decreases in alveolar-arterial (A-a) gradients that did not occur in placebo (saline)-treated animals. Treatment with CDP-choline was also associated with less platelet consumption over the first 48 hours, but had no detectable detrimental effects. CONCLUSIONS AND CLINICAL IMPORTANCE: Ctyidine diphosphcholine acts rapidly to promote gas exchange in dogs with naturally occurring aspiration pneumonia and is a potential adjunctive treatment in VetARDS patients.

Association of Pulmonary Artery Pressure Change With Post-Lung Transplantation Survival: Retrospective Analysis of China Registry.

Background: Extracorporeal membrane oxygenation (ECMO) has been used as intraoperative hemodynamic support in patients with end-stage lung diseases and pulmonary hypertension undergoing lung transplantation (LT). Objectives: The aim of this study was to identify the association of pulmonary artery pressure change during ECMO and post-LT survival. Methods: The study investigators collected and analyzed the data from Chinese Lung Transplantation Registry. Patients who have severe pulmonary hypertension with intraoperative ECMO support were enrolled. Post-LT mortality and morbidity were further collected and compared. Results: A total of 208 recipients were included in the study, during which 53 deaths occurred post-LT. All the patients had severe pulmonary hypertension and were supported by intraoperative ECMO. Using eXtreme Gradient Boosting, or XGboost, model method, 20 variables were selected and ranked. Changes of mean pulmonary artery pressure at the time of ECMO support and ECMO wean-off (ΔmPAP) were related to post-LT survival, after adjusting for potential confounders (recipient age, New York Heart Association functional class status before LT, body mass index, pre-LT hypertension, pre-LT steroids, and pre-LT ECMO bridging). A nonlinear relationship was detected between ΔmPAP and post-LT survival, which had an inflection point of 35 mm Hg. Recipients with ΔmPAP ≦35 mm Hg had higher mortality rate calculated through the Kaplan-Meier estimator (P = 0.041). Interaction analysis showed that recipients admitted in LT center with high case volume (≥50 cases/year) and ΔmPAP >35 mm Hg had better long-term survival. The trend was reversed in recipients who were admitted in LT center with low case volume (<50 cases/year). Conclusions: The relationship between ΔmPAP and post-LT survival was nonlinear. Optimal perioperative ECMO management strategy with experienced team is further warranted.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

PMX-DHP Therapy for Dyspnea and Deoxygenation in Severe COVID-19 Pneumonia: A Case Series.

Hypercytokinemia induced by coronavirus disease-19 (COVID-19) is associated with severe pulmonary involvement, which may lead to respiratory failure. These conditions play an important role in the worsening of clinical symptoms in patients with severe COVID-19. There is no established treatment for hypercytokinemia. We report on two patients whose clinical symptoms improved after direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), following the administration of the anti-inflammatory agent tocilizumab. Case A was a 70-year-old man diagnosed with COVID-19 pneumonia. Despite treatment with ciclesonide and favipiravir, supplemental oxygen was administered due to the worsening of dyspnea with tachypnea. Although tocilizumab was started on day 6, the patient deteriorated into deoxygenation, presenting with the PaO2/FIO2 (P/F) ratio of 92. On days 8 and 10, the patient received PMX-DHP therapy. On day 11, his dyspnea improved. On day 13, his P/F ratio began to improve, and oxygen therapy was discontinued on day 18. The patient recovered without requiring mechanical ventilation. Case B was a 70-year-old man diagnosed with COVID-19 pneumonia and treated with favipiravir, starting on day 0. Despite starting ciclesonide inhalation and tocilizumab on day 2, his P/F ratio was 53. On day 5, he received PMX-DHP therapy. On day 6, his dyspnea improved, as did his P/F ratio, reaching 81 on day 8. Finally, his clinical symptoms resolved, and he was discharged from the intensive care unit without requiring mechanical ventilation. These cases indicate that PMX-DHP therapy might be a suitable treatment option for dyspnea and deoxygenation in COVID-19 pneumonia, especially in cases where an anti-inflammatory agent, such as tocilizumab, has failed to achieve the desired effect.