Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0-6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0-6.6 mL/kg) ( p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% ( n = 1,721) to 72.5% ( n = 1,846) ( p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% ( n = 222) to 6.7% ( n = 174) ( p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H 2 O ( p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91-1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.

Optical, flow, and thermal analysis of a phototherapy extracorporeal membrane oxygenator for treating carbon monoxide poisoning.

BACKGROUND: Extracorporeal membrane oxygenators (ECMO) are currently utilized to mechanically ventilate blood when lung or lung and heart function are impaired, like in cases of acute respiratory distress syndrome (ARDS). ARDS can be caused by severe cases of carbon monoxide (CO) inhalation, which is the leading cause of poison-related deaths in the United States. ECMOs can be further optimized for severe CO inhalation using visible light to photo-dissociate CO from hemoglobin (Hb). In previous studies, we combined phototherapy with an ECMO to design a photo-ECMO device, which significantly increased CO elimination and improved survival in CO-poisoned animal models using light at 460, 523, and 620 nm wavelengths. Light at 620 nm was the most effective in removing CO. OBJECTIVE: The aim of this study is to analyze the light propagation at 460, 523, and 620 nm wavelengths and the 3D blood flow and heating distribution within the photo-ECMO device that increased CO elimination in CO-poisoned animal models. METHODS: Light propagation, blood flow dynamics, and heat diffusion were modeled using the Monte Carlo method and the laminar Navier-Stokes and heat diffusion equations, respectively. RESULTS: Light at 620 nm propagated through the device blood compartment (4 mm), while light at 460 and 523 nm only penetrated 48% to 50% (~2 mm). The blood flow velocity in the blood compartment varied with regions of high (5 mm/s) and low (1 mm/s) velocity, including stagnant flow. The blood temperatures at the device outlet for 460, 523, and 620 nm wavelengths were approximately 26.7°C, 27.4°C, and 20°C, respectively. However, the maximum temperatures within the blood treatment compartment rose to approximately 71°C, 77°C, and 21°C, respectively. CONCLUSIONS: As the extent of light propagation correlates with efficiency in photodissociation, the light at 620 nm is the optimal wavelength for removing CO from Hb while maintaining blood temperatures below thermal damage. Measuring the inlet and outlet blood temperatures is not enough to avoid unintentional thermal damage by light irradiation. Computational models can help eliminate risks of excessive heating and improve device development by analyzing design modifications that improve blood flow, like suppressing stagnant flow, further increasing the rate of CO elimination.

Alveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.

OBJECTIVES: We sought to determine whether hyperinflammatory acute respiratory distress syndrome (ARDS) and hypoinflammatory ARDS, which have been associated with differences in plasma biomarkers and mortality risk, also display differences in bronchoalveolar lavage (BALF) biomarker profiles. We then described the relationship between hyperinflammatory ARDS and hypoinflammatory ARDS to novel subphenotypes derived using BALF biomarkers. DESIGN: Secondary analysis of a randomized control trial testing omega-3 fatty acids for the treatment of ARDS. SETTING: Five North American intensive care units. PATIENTS: Adults (n = 88) on invasive mechanical ventilation within 48 hours of ARDS onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We classified 57 patients as hypoinflammatory and 31 patients as hyperinflammatory using a previously validated logistic regression model. Of 14 BALF biomarkers analyzed, interleukin-6 and granulocyte colony stimulating factor were higher among patients with hyperinflammatory ARDS compared with hypoinflammatory ARDS, though the differences were not robust to multiple hypothesis testing. We then performed a de novo latent class analysis of the 14 BALF biomarkers to identify two classes well separated by alveolar profiles. Class 2 (n = 63) displayed significantly higher interleukin-6, von Willebrand factor, soluble programmed cell death receptor-1, % neutrophils, and other biomarkers of inflammation compared with class 1 (n = 25). These BALF-derived classes had minimal overlap with the plasma-derived hyperinflammatory and hypoinflammatory classes, and the majority of both plasma-derived classes were in BALF-derived class 2 and characterized by high BALF biomarkers. Additionally, the BALF-derived classes were associated with clinical severity of pulmonary disease, with class 2 exhibiting lower Pao2 to Fio2 and distinct ventilatory parameters, unlike the plasma-derived classes, which were only related to nonpulmonary organ dysfunction. CONCLUSIONS: Hyperinflammatory and hypoinflammatory ARDS subphenotypes did not display significant differences in alveolar biologic profiles. Identifying ARDS subgroups using BALF measurements is a unique approach that complements information obtained from plasma, with potential to inform enrichment strategies in trials of lung-targeted therapies.

[Clinical observation of electroacupuncture combined with Qingyi Xianxiong Decoction in the treatment of acute respiratory distress syndrome due to severe acute pancreatitis].

OBJECTIVE: To observe the clinical effect of electroacupuncture combined with Qingyi Xianxiong Decoction on the treatment of acute respiratory distress syndrome (ARDS) caused by severe acute pancreatitis (SAP). METHODS: From February 2021 to April 2022, 120 patients with ARDS caused by SAP who were admitted to the department of critical care medicine of Tianjin Nankai Hospital and whose syndrome differentiation belonged to the syndrome of knot chest were selected. They were randomly divided into pure traditional Chinese medicine group and acupuncture medicine group, with 60 cases in each group. The pure traditional Chinese medicine group was received Qingyi Xianxiong Decoction on the basis of conventional western medicine treatment, and the acupuncture medicine group was received electric acupuncture treatment on the basis of the pure traditional Chinese medicine group. The two groups continued to be treated for 7 days. The primary outcome was the ventilator-free days within 28 days after admission to the intensive care unit (ICU), and the secondary outcome measures were mechanical ventilation time, the length of ICU stay, total lenth of hospital stay, time of intra-abdominal pressure recovery, scores of organ function, oxygenation index (PaO2/FiO2), serum inflammatory factors, blood amylase, urine amylase, etc. RESULTS: Compared with the pure traditional Chinese medicine group, the ventilator-free days in the acupuncture medicine group within 28 days after admission to the ICU were significantly longer [day: 22.10±2.29 vs. 20.97±2.31, P < 0.05, odds ratio (OR) = 1.24, 95% confidence interval (95%CI) was 1.053-1.460, P < 0.05]. The time of mechanical ventilation, the length of ICU stay, total length of hospital stay, and recovery time of intra-abdominal pressure were significantly shortened [mechanical ventilation time (days): 5.90±2.29 vs. 7.03±2.31, the length of ICU stay (days): 8.07±1.89 vs. 12.08±2.23, total length of hospital stay (days): 19.55±6.82 vs. 22.28±5.19, recovery time of intra-abdominal pressure (days): 6.05±1.81 vs. 8.45±1.76, all P < 0.05]. The Murray score and bedside index for severity in acute pancreatitis (BISAP) score of the two groups after 7 days of treatment were significantly lower than those before treatment, while PaO2/FiO2 was significantly higher than those before treatment, and the Murray score of the acupuncture medicine group after 7 days of treatment was significantly lower than that of the pure traditional Chinese medicine group [score: 0.50 (0.33, 0.75) vs. 1.00 (1.00, 1.33), P < 0.05], PaO2/FiO2 was significantly higher than that in the pure traditional Chinese medicine group [mmHg (1 mmHg ≈ 0.133 kPa): 390.75±27.73 vs. 330.02±42.34, P < 0.05]. With the prolongation of treatment time, the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), serum amylase and urine amylase in both groups after treatment continued to decrease, and the levels of the inflammatory factors in the acupuncture medicine group after 7 days of treatment were significantly lower than those in the pure traditional Chinese medicine group [TNF-α (ng/L): 38.20±10.00 vs. 45.35±5.09, IL-6 (ng/L): 0.95±0.44 vs. 7.42±1.39, CRP (mg/L): 8.55±2.79 vs. 36.20±13.97, all P < 0.05]. Subgroup analysis showed that biliary system disease was a risk factor for the duration of mechanical ventilation ≥ 7 days in the treatment of ARDS with acupuncture and medicine (OR = 2.728, 95%CI was 1.293-5.754). CONCLUSIONS: Compared with the pure traditional Chinese medicine, acupuncture combined can better reduce the clinical symptoms of patients with ARDS caused by SAP, promote the recovery of patients, and reduce systemic inflammatory reaction, which is worthy of clinical promotion.

Integrated therapeutic plasma exchange and traditional Chinese medicine treatment in a patient with severe COVID-19: A case report.

This report presents the case of a 59-year-old man with severe COVID-19 that gradually progressed to cytokine release syndrome and then acute respiratory distress syndrome; he was successfully treated via integration of therapeutic plasma exchange and traditional Chinese medicine. The patient initially presented with a sore throat, severe muscle aches, productive cough and fever. On the worsening of symptoms, remdesivir was administered. However, as the symptoms continued to worsen and a cytokine release syndrome was suspected, oxygen was provided through a high-flow nasal cannula (50 L/min) and therapeutic plasma exchange was performed to prevent worsening of the acute respiratory distress syndrome. On the same day, a course of traditional Chinese medicine was introduced in consultation with the infectious house staff. The patient's symptoms gradually improved; the levels of C-reactive protein and D-dimers reduced, and the patient was weaned to a simple oxygen mask and eventually to room air. This is the first reported case of the integration of these treatments. Together, they prevented the patient from requiring intubation, played a role in cytokine management, and also improved the clinical symptoms, including productive purulent sputum, cough, frequent stool passage and intermittent fever, with no adverse effects. As a result, the patient was discharged within two weeks of the integration of these treatments. Therefore, the integration of therapeutic plasma exchange and traditional Chinese medicine is an effective therapy for patients with severe COVID-19.

Warm Cupping of the Posterior Thorax in Combination with Standard Conventional Therapy for ARDS in COVID-19 Patients in ICU: a Case Series.

Acute respiratory distress syndrome (ARDS) is commonly found in critically ill patients with coronavirus disease 2019 (COVID-19). As a non-pharmacological treatment of complementary and alternative medicine (CAM), cupping has been clinically used for respiratory symptoms. We sequentially identified a series of patients with COVID-19 with ARDS who were admitted to the intensive care unit (ICU). Warm cupping of the posterior thorax was performed for seven days. We collected longitudinal severity scores on cough, breathlessness, chest tightness, type of oxygen therapy, and oxygen saturation (SpO2). We hereby report the changes in the severity scores in a series of eight patients who received 21 sessions of cupping in addition to conventional treatments. All patients reported improvement in symptom scores that was matched by an increase in SpO2 by as much as 3.16%. All patients were discharged and did not require the use of a mechanical ventilator. The results suggest that combining cupping with conventional treatment may provide a good prognosis for patients with COVID-19 with ARDS.

Prognostic Prediction Using the Clinical Data and Ultrasomics-Based Model in Acute Respiratory Distress Syndrome (ARDS) Combined with Acute Kidney Injury (AKI).

Objective: A model was constructed based on clinical and ultrasomics features to predict the prognosis of patients in the respiratory intensive unit (RICU) who had acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI). AKI ensues after ARDS in RICU ordinarily. The prognostic prediction tool was further developed on this basis. Methods: We collected clinical and ultrasonic data from 145 patients who had ARDS combined with AKI and received continuous renal replacement therapy (CRRT) in the RICU of Xiangyang Hospital of Traditional Chinese Medicine from March 2016 to November 2019. The patients were divided into the survival group (n = 51) and the death group (n = 94), depending on the treatment outcome. The training set (n = 102) and the testing set (n = 43) were established based on patient data. The clinical and ultrasomics features and the CRRT parameters were compared between the two groups. The influence factors of death were analyzed by logistic regression, and four predictive models were established. The predictive performance of 4 models was compared using the R Software 4.1.3. The decision curve analysis graphs were drawn using the R language to determine the net benefit of each. Result: Univariate analysis was conducted in the training set. The following risk factors for poor prognosis were identified: age, concurrent cancers, sequential organ failure assessment score (SOFA), number of organ dysfunctions, positive cumulative fluid balance at 72 h, time from ICU admission to CRRT, mean arterial pressure, oxygenation index, and gray-level size zone matrix, GLSZM (SumEntropy.239/SmallDependenceHighGrayLevelEmphasis.314/Maximum.327/Variance.338) (P < 0.05). Four models were built based on the above factors: clinical model, CRRT model, ultrasomics-based model, and combination model. Comparison using the MedCalc software indicated that the best predictive performance achieved with the combination model. The decision curve analysis also suggested that the combination model had the highest net benefit. Similar results were reported after validation on the testing set. Conclusion: The prognosis of ARDS patients combined with AKI is usually poor. The combination model based on clinical and ultrasomics features had the highest predictive performance. This model can be used to improve the clinical outcome and prognosis.

Respiratory Distress in Hospitalized Non-Mechanically Ventilated COVID-19 Adults: A Retrospective Multicenter Cohort Study.

BACKGROUND: COVID-19 typically presents with respiratory symptoms which may progress with severe disease. There are standard guidelines for managing respiratory distress (e.g. opioids, anxiolytics) and palliative care teams are well versed in managing these symptoms. AIM: Determine the extent to which hospitalized COVID-19 patients with moderate respiratory distress received medications or palliative consultation for symptom management and if these interventions had any association with outcomes. DESIGN: Retrospective chart review for hospitalized COVID-19+ patients from March 2-April 30, 2020. SETTING: Large integrated health system in the New York Metropolitan area. PATIENTS: 312 adult patients hospitalized with COVID-19 with an order for a non-rebreather mask and meeting criteria for moderate respiratory distress on the Respiratory Distress Observation Scale: concurrent respiratory rate ≥30 and heart rate ≥110 at any point during hospitalization. Patients receiving mechanical ventilation or intensive care were excluded. RESULTS: Most COVID-19 patients experiencing moderate respiratory distress did not receive medications or palliative consultation for symptom management. Patients who received medications were predominantly white, older, and had a Do-Not-Resuscitate order. Patients who received a palliative consultation were more likely to be older, female, and white, with a Do-Not-Resuscitate order. Mortality was similar between those receiving medication and those who did not. CONCLUSION: Medications and palliative expertise for symptom management were underused for patients with moderate respiratory distress due to COVID-19. Education and triggers may help providers to identify moderate respiratory distress and consider symptomatic treatment and palliative consultation when appropriate.

Hypoxic respiratory distress potentially secondary to phosphorus trifluoride gas exposure.

We herein report a rare, probable exposure of a patient to phosphorus trifluoride gas. The objective of this case report is to highlight the potential exposure to phosphorus trifluoride gas and discuss the best management of it. A 48-year-old worker at a specialty gases laboratory was transported to the community Emergency Department (ED) in respiratory distress, presenting with peripheral cyanosis, an unobtainable oxygen saturation, chocolate-colored blood, and a Glasgow coma scale of 15. A non-rebreather was placed, poison control was contacted, and the patient was administered empiric methylene blue intravenously due to worsening cyanosis and respiratory distress. Upon arrival at the academic facility, the patient was no longer cyanotic and reported improvement of his symptoms. The patient's employer informed staff that a canister of phosphorus trifluoride gas in his workstation was found to be empty but should have been full. It was also discovered that a coworker left work early the same day with similar but milder symptoms. Hyperbaric oxygen therapy was considered; however, the patient was improving on oxygen via non-rebreather, and he had no other indications. Because the patient continued to require supplemental oxygen to maintain their oxygen saturation above 92%, he was admitted to the ICU and treated with prednisone daily for chemical pneumonitis. After 4 days, he successfully transitioned to room air without hypoxia. While exposures such as this do not occur frequently, it is important to maintain a broad differential and treatment plan as we continue to investigate the etiology and best treatment option.

Effect of enteral immunomodulatory nutrition formula on mortality and critical care parameters in critically ill patients: A systematic review with meta-analysis.

BACKGROUND: Enteral immunomodulatory nutrition is recommended as an adjuvant therapy for patients in intensive care units (ICU), but its effectiveness is incompletely understood. AIM: The aim of this review was to examine the effect of a commonly used immunomodulatory formula-omega-3 fatty acids, γ-linolenic acid, and antioxidants-on clinical outcomes and mortality risk in critically ill patients. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHOD: PubMed, Scopus, and Institute for Scientific Information (ISI) Web of Knowledge databases were searched until 18 February 2021. RCTs that used the immunomodulatory formula in the ICU were included. RESULTS: Ten RCTs (1166 participants) were included in the meta-analysis. The immunomodulatory formula reduced the duration of ICU stay weighted mean difference [(WMD): -2.97 days; 95%CI: -5.59, -0.35)], mechanical ventilation (WMD = -2.20 days, 95%CI: -4.29, -0.10), sequential organ failure assessment and multiple organ dysfunction scores (Hedge's g: -0.42 U/L; 95% CI: -0.74, -0.11), decreased 8-day overall mortality risk (RR = 0.74, 95% CI: 0.58, 0.91), and extended the ICU-free days (WMD: 4.06 days, 95% CI: 0.02, 8.09). The improvement in respiratory function and reduction in mortality risk was more in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Furthermore, the reduction in mechanical ventilation and mortality risk was more evident in older (>60 years) vs young adults. CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Taken together, the immunomodulatory formula may enhance clinical practice for critical care nurses, such that the prevalence and/or susceptibility to secondary conditions commonly encountered in the ICU (ie, ALI and ARDS) could be attenuated, ultimately allowing critical care nurses to focus their care on the primary reason for which a patient is in the ICU. The study protocol was registered in PROSPERO.

Vitamin D Status and Clinical Outcomes in Acute Respiratory Distress Syndrome: A Secondary Analysis From the Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury (ALVEOLI) Trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a highly morbid condition that has limited therapeutic options. Optimal vitamin D status has been linked to immunological effects that may benefit critically ill patients. Therefore, we investigated whether admission 25-hydroxyvitamin D levels (25OHD) are associated with clinical outcomes in ARDS patients. METHODS: We performed a secondary analysis of data from a randomized, controlled trial comparing oxygenation strategies in 549 patients with ARDS (NCT00000579). Baseline 25OHD was measured in stored plasma samples. We investigated the relationship between vitamin D status and ventilator-free days (VFD) as well as 90-day survival, using linear regression and Cox proportional hazard models, respectively. Analyses were adjusted for age, race, and Acute Physiology and Chronic Health Evaluation III score. RESULTS: Baseline 25OHD was measured in 476 patients. 90% of these individuals had 25OHD <20 ng/ml and 40% had 25OHD <10 ng/ml. Patients with 25OHD <20 ng/ml were likely to be ventilated for 3 days longer than patients with levels ≥20 ng/ml (ß 3.41; 95%CI 0.42-6.39: P = 0.02). Patients with 25OHD <10 ng/ml were likely to be ventilated for 9 days longer (ß 9.27; 95%CI 7.24-11.02: P < 0.001) and to have a 34% higher risk of 90-day mortality (HR 1.34; 95% CI 1.06-1.71: P = 0.02) compared to patients with levels >10 ng/ml. CONCLUSIONS: In patients with ARDS, vitamin D status is associated with duration of mechanical ventilation and 90-day mortality. Randomized, controlled trials are warranted to determine whether vitamin D supplementation improves clinical outcomes in ARDS patients.

Vitamin D deficiency in critically ill COVID-19 ARDS patients.

BACKGROUND & AIMS: Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS: A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION: The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.

Energy Achievement Rate Is an Independent Factor Associated with Intensive Care Unit Mortality in High-Nutritional-Risk Patients with Acute Respiratory Distress Syndrome Requiring Prolonged Prone Positioning Therapy.

Early enteral nutrition (EN) and a nutrition target >60% are recommended for patients in the intensive care unit (ICU), even for those with acute respiratory distress syndrome (ARDS). Prolonged prone positioning (PP) therapy (>48 h) is the rescue therapy of ARDS, but it may worsen the feeding status because it requires the heavy sedation and total paralysis of patients. Our previous studies demonstrated that energy achievement rate (EAR) >65% was a good prognostic factor in ICU. However, its impact on the mortality of patients with ARDS requiring prolonged PP therapy remains unclear. We retrospectively analyzed 79 patients with high nutritional risk (modified nutrition risk in the critically ill; mNUTRIC score ≥5); and identified factors associated with ICU mortality by using a Cox regression model. Through univariate analysis, mNUTRIC score, comorbid with malignancy, actual energy intake, and EAR (%) were associated with ICU mortality. By multivariate analysis, EAR (%) was a strong predictive factor of ICU mortality (HR: 0.19, 95% CI: 0.07-0.56). EAR >65% was associated with lower 14-day, 28-day, and ICU mortality after adjustment for confounding factors. We suggest early EN and increase EAR >65% may benefit patients with ARDS who required prolonged PP therapy.

Caloric Intake with High Ratio of Enteral Nutrition Associated with Lower Hospital Mortality for Patients with Acute Respiratory Distress Syndrome Using Prone Position Therapy.

Positioning patients in the prone position leads to reduced hospital mortality rates for those with severe acute respiratory distress syndrome (ARDS). What constitutes the optimal feeding strategy for prone patients with ARDS is controversial. We conducted a retrospective study that enrolled 110 prone patients with ARDS in two medical intensive care units (ICUs) from September 2015 to November 2018. Inclusion criteria were as follows: age ≥20 years, diagnosis of respiratory failure requiring mechanical ventilation, diagnosis of ARDS within 72 h of ICU admission, placement in a prone position within the first 7 days of ICU admission, and ICU stay of more than 7 days. Exclusion criteria were as follows: nil per os orders because of gastrointestinal bleeding or hemodynamic instability, and ventilator dependency because of chronic respiratory failure. The consecutive daily enteral nutrition(EN)/EN + parenteral nutrition(PN) ratio could predict hospital mortality rates within the first 7 days of admission when using generalized estimating equations (p = 0.013). A higher average EN/EN + PN ratio within the first 7 days predicted (hazard ratio: 0.97, confidence interval: 0.96-0.99) lower hospital mortality rates. To reduce hospital mortality rates, caloric intake with a higher EN ratio may be considered for patients in prone positions with ARDS.

Effect of Esophageal Pressure-guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-based and Mechanistic Reanalysis of the EPVent-2 Trial.

Rationale: In acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension. Objectives: To evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect in the EPVent-2 (Esophageal Pressure-guided Ventilation 2) trial, a multicenter trial of esophageal pressure (Pes)-guided PEEP versus empirical high PEEP in moderate to severe ARDS. Methods: This post hoc reanalysis of the EPVent-2 trial evaluated for heterogeneity of treatment effect on mortality by baseline multiorgan dysfunction, determined via Acute Physiology and Chronic Health Evaluation II (APACHE-II). It also evaluated whether PEEP titrated to end-expiratory transpulmonary pressure near 0 cm H2O was associated with survival. Measurements and Main Results: All 200 trial participants were included. Treatment effect on 60-day mortality differed by multiorgan dysfunction severity (P = 0.03 for interaction). Pes-guided PEEP was associated with lower mortality among patients with APACHE-II less than the median value (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92) and may have had the opposite effect in patients with higher APACHE-II (hazard ratio, 1.69; 95% confidence interval, 0.93-3.05). Independent of treatment group or multiorgan dysfunction severity, mortality was lowest when PEEP titration achieved end-expiratory transpulmonary pressure near 0 cm H2O. Conclusions: The effect on survival of Pes-guided PEEP, compared with empirical high PEEP, differed by multiorgan dysfunction severity. Independent of multiorgan dysfunction, PEEP titrated to end-expiratory transpulmonary pressure closer to 0 cm H2O was associated with greater survival than more positive or negative values. These findings warrant prospective testing in a future trial.

A systematic review and meta-analysis of effect evaluation of traditional Chinese medicine in treating acute respiratory distress syndrome.

BACKGROUND: It was to systematically evaluate the effects of traditional Chinese medicine (TCM) in the treatment of acute respiratory distress syndrome (ARDS), and provide a theoretical basis for the clinical treatment of ARDS. METHODS: English databases of PubMed, Embase, Medline, Spring, Cochrane Library, and Web of Science were searched, and the randomized controlled trial literatures on the treatment of ARDS patients with TCM published from January 1, 2001 to December 31, 2020 were screened. Then, Cochrane Handbook 5.0.2 was employed to evaluate the risk of bias in the included literatures, and Review Manager 5.3 was utilized for meta-analysis. RESULTS: A total of 16 studies met the requirements and were included, with a total of 1,460 participants. The meta-analysis results showed that the mortality rate of patients in the observation group was remarkably reduced after treatment with TCM [mean deviation (MD) =0.51; 95% confidence interval (CI): 0.32-0.84; Z=2.69; P=0.007]. The effective rate of clinical treatment was improved (MD =2.64; 95% CI: 1.79-3.90; Z=4.90; P<0.00001). Arterial partial pressure of oxygen (PaO2) increased remarkably (MD =12.29; 95% CI: 8.88-15.71; Z=7.05; P<0.00001). The oxygenation index (PaO2/FiO2) increased remarkably (MD =50.70; 95% CI: 32.78-68.63; Z=5.54; P<0.00001). Interleukin-6 (IL-6) levels were remarkably reduced (MD =-8.32; 95% CI: -11.48 to -5.17; Z=5.17; P<0.00001). The level of C-reactive protein (CRP) decreased remarkably (MD =-9.23; 95% CI: -14.23 to -4.24; Z=3.62; P=0.0003). Compared with the control group, the above 8 analysis indicators showed statistically considerable differences. However, difference of partial pressure of carbon dioxide (PaCO2) level (MD =-0.16; 95% CI: -2.97-2.65; Z=0.11; P=0.91) was not obvious between groups. DISCUSSION: The treatment of ARDS with TCM can reduce the mortality rate of patients, improves the effective rate of clinical treatment, reduces the average mechanical ventilation time, increases the levels of PaO2, PaO2/FiO2, and reduces the levels of IL-6, tumor necrosis factor α (TNF-α), and CRP. The use of TCM has a significant treatment effect on ARDS.

Linopirdine-supplemented resuscitation fluids reduce mortality in a model of ischemia-reperfusion injury induced acute respiratory distress syndrome.

Previously, we demonstrated that supplementation of resuscitation fluids with the Kv7 voltage-activated potassium channel inhibitor linopirdine reduces fluid resuscitation requirements and stabilizes hemodynamics in various rat models of hemorrhagic shock. To further evaluate the therapeutic potential of linopirdine, we tested the effects of linopirdine-supplemented resuscitation fluids in a rat model of ischemia-reperfusion injury-induced acute respiratory distress syndrome (ARDS). Ventilated rats underwent unilateral lung ischemia from t=0-75 min, followed by lung reperfusion and fluid resuscitation to a mean arterial blood pressure of 60 mmHg with normal saline (NS, n=9) or NS supplemented with 50 µg/ml linopridine (NS-L), n=7) until t=360 min. As compared with NS, fluid resuscitation with NS-L stabilized blood pressure and reduced fluid requirements by 40% (p<0.05 vs. NS at t=240-360 min). While NS-L did not affect ARDS development, it reduced mortality from 66% with NS to 14% with NS-L (p=0.03, hazard ratio 0.14; 95% confidence interval of the hazard ratio: 0.03-0.65). Median survival time was 240 min with NS and >360 min with NS-L. As compared with NS treated animals that survived the observation period (n=3), however, plasma lactate and creatinine concentrations at t=360 min were higher with NS-L (n=6; p<0.05). Our findings extend therapeutic potential of NS-L from hypovolemic/hemorrhagic shock to hemodynamic instability under normovolemic conditions during organ ischemia-reperfusion injury. Possible adverse effects of NS-L, such as impairment of renal function and/or organ hypoperfusion, require further evaluation in long-term pre-clinical models.

Risk Factors of Coronavirus Disease 2019-Related Mortality and Optimal Treatment Regimens: A Retrospective Study.

BACKGROUND Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide, and scientists are trying to find a way to overcome the disease. We explored the risk factors that influence patient outcomes, including treatment regimens, which can provide a reference for further treatment. MATERIAL AND METHODS A retrospective cohort study analysis was performed using data from 97 patients with COVID-19 who visited Wuhan Union Hospital from February 2020 to March 2020. We collected data on demographics, comorbidities, clinical manifestations, laboratory tests, treatment methods, outcomes, and complications. Patients were divided into a recovered group and a deceased group. We compared the differences between the 2 groups and analyzed risk factors influencing the treatment effect. RESULTS Seventy-six patients recovered and 21 died. The average age and body mass index (BMI) of the deceased group were significantly higher than those of the recovered group (69.81±6.80 years vs 60.79±11.28 years, P<0.001 and 24.95±3.14 kg/m² vs 23.09±2.97 kg/m², P=0.014, respectively). The combination of antiviral drugs and supportive therapy appears to be associated with the lowest mortality (P<0.05). Multivariate Cox regression analysis revealed that age, BMI, H-CRP, shock, and acute respiratory distress syndrome (ARDS) were independent risk factors for patients with COVID-19 (P<0.05). CONCLUSIONS Elderly patients and those with a high BMI, as well as patients who experience shock and ARDS, may have a higher risk of death from COVID-19. The combination of antiviral drugs and supportive therapy appears to be associated with lower mortality, although further research is needed.

Case Report: Refractory Acute Respiratory Distress Syndrome Supported by Extracorporeal Membrane Oxygenation due to Coinfection with Chlamydia pneumoniae and Leptospirosis in Reunion Island.

Infection with Leptospira spp. is common in Réunion, a tropical island in the Indian Ocean. However, respiratory coinfections between strains of Leptospira spp. and other microorganisms are rarely described. Here, we describe the first reported case of coinfection between Leptospira spp. and Chlamydia pneumoniae, responsible for refractory acute respiratory distress syndrome requiring extracorporeal membrane oxygenation with a favorable outcome. In a case of leptospirosis with severe respiratory illness, testing for respiratory coinfection, especially with atypical pathogens, could explain the seriousness of the clinical condition and lead to specific treatment.