Severity Of ARDS Research Articles

Dose and gender dependence of chlorine inhalation in a conscious ovine model

Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl2 concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl2 premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO2/FiO2 ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO2/FiO2 ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO2/FiO2 ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl2 significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl2 concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl2 concentrations. No significant sex-dependent differences were found in measured endpoint variables.

SIRT1 downregulation in pneumonia is associated with an immature neutrophil response and increased disease severity.

Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD + -dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective. Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa . Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software. Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT. Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury.

Evaluation of the Relationship between Oxygenation Indices and the Extent of Radiographic Findings in Hospitalized COVID-19 Patients: A Cross-Sectional Study

Background: Oxygenation indices are used to assess the condition of patients with pneumonia and ARDS. These indexes determine the status of patients as well as the mortality rate of respiratory diseases and the need for intubation. The aim of this study was to determine and compare oxygenation indices and the extent of radiographic findings in patients with COVID-19 in ICU at Shariati Hospital.&#x0D; Methods: The present study was a cross-sectional study that was performed prospectively in the intensive care units of Shariati Hospital in Tehran. Patients admitted to the intensive care unit were examined if they met the inclusion criteria. Data were analysed by SPSS software version 26.&#x0D; Results: In this study, 39 patients were evaluated. Of these, 35.9% were men and 64.1% were women. The mean age of the population was 62 ±17. On average, SpO2 and PaO2 were not significantly different based on pulmonary involvement, severity of pulmonary involvement and also the pattern of pulmonary involvement (p&gt; 0.05). No significant relationship was found between the severity of ARDS and the parameters of pulmonary involvement severity on CT scan (p&gt; 0.05).&#x0D; Conclusion: It seems that there is no significant relationship between oxygenation indices and the extent of radiographic findings in hospitalized patients with COVID-19. Also, the severity of ARDS has no significant relationship with the extent of radiographic findings (CT scan). Oxygen saturation should be used as an adjunct when considering a CT scan of the lung, but should not be used as the sole means of diagnosis.

Elastic power, a novel predictor of the severity and prognosis of ARDS

PurposeTo explore the predictive value of the new comprehensive respiratory mechanics parameters elastic power (EP) and elastic power normalized to the compliance (Cst-EP) in the evaluation of the severity and 28-day prognosis of ARDS patients. MethodsThe MIMIC-III database was used to identify ARDS patients under invasive mechanical ventilation for at least 48 h. Their baseline data and ventilatory variables were collected. EP, elastic energy, driving pressure and mechanical power were calculated according to the corresponding formulas. Their value in assessing the severity of ARDS was evaluated. The correlation between Cst-EP and 28-day prognosis of ARDS patients was analyzed. ResultsEP was independently associated with the severity of the ARDS and the odds ratio (OR) was 1.301 [95% CI (1.190–1.423), p < 0.001]. It has higher accuracy for the severity of ARDS, with an optimal cut-off value of 14.6 J/min. The Cst-EP was significantly associated with increased risk of death and the hazard ratio (HR) per 100 J/min × cmH2O/ml × 10−3 was 1.169 [95% CI (1.093–1.250), p < 0.001]. In addition, the 28-day cumulative survival rate of the high Cst-EP group was significantly lower than that of the low Cst-EP group. ConclusionEP can be used to predict the severity of ARDS, and Cst-EP is associated with mortality during controlled mechanical ventilation in ARDS.

Evaluating the role of antioxidant therapy in outcome of severe and critical COVID-19 infection requiring high flow oxygen.

To determine the efficacy of antioxidant therapy in the outcome of critical COVID-19-infected patients. At the Patel Hospital, a retrospective cohort analysis was carried out between June 2020 and October 2021. The study included a record of 200 individuals with severe or critical stage COVID-19 who were older than 18 and of either gender. Based on the antioxidant therapy, study participants were placed evenly into two groups. Antioxidant therapy was provided to one group (the exposed group), whereas the other group received simply normal COVID-19 medication (the unexposed group). Outcomes from both groups were evaluated and compared. Patients on antioxidant therapy had lesser mortality and shorter hospital stay than patients on coventional management, but the difference in proportions of mortality and length of hospital stay was statistically insignificant between groups (p > 0.05). Patients on antioxidant therapy had a significantly higher proportion of moderate to severe ARDS and septic shock than unexposed patients. A significantly higher number of patients in the unexposed group had AKI as compared to the exposed group (p = 0.048). Antioxidant therapy seems to have a non-significant positive effect on mortality, hospital stay, and AKI, while it showed a negative effect on the severity of ARDS and septic shock.

Inhaled nitric oxide in patients with acute respiratory distress syndrome caused by COVID-19: treatment modalities, clinical response, and outcomes

BackgroundInhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients.MethodsMulticentre, retrospective cohort study conducted in France.ResultsFrom end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03).ConclusionsOur study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies.

Weaning from prolonged mechanical ventilation on a specialised weaning unit: a retrospective comparison of patients with and without SARS-CoV-2 infection

Available data on patients requiring prolonged mechanical ventilation due to severe COVID-19 are sparse. Here we compare patients with ARDS related or not related to SARS-CoV-2 infection treated in a specialised weaning unit. A retrospective analysis of all patients with prolonged mechanical ventilation associated with an ARDS admitted from the 21st November 2013 to the 23rd July 2021 to the weaning unit of the University Hospital RWTH Aachen was performed. ARDS patients with COVID-19 (cARDS) were compared to patients with ARDS not related to COVID-19 (ncARDS). In total, n=129 patients in prolonged need for mechanical ventilation after ARDS were treated in the weaning unit, of whom n=38 had been suffering from ARDS related to COVID-19. Both patients groups were similar in terms of demographic parameters, underlying chronic illnesses, severity of ARDS and the duration of mechanical ventilation before being admitted to the weaning unit. During ICU stay, prone positioning and therapy with systemic corticosteroids was used more frequently in cARDS patients. Furthermore, therapy with vasoconstrictors was needed more often (cARDS: 42.1% vs. ncARDS 12.1%; p=0.0003) and urinary output was lower (cARDS: 1980 ml vs. ncARDS: 2600 ml; p=0.0037) in this patient group. The clinical course of the weaning process was similar in patients with cARDS and ncARDS, there were no significant differences in the occurrence of complications and the duration of mechanical ventilation. There were n=5 deaths (13.2%) in the cARDS and n=15 deaths (16.5%) in the ncARDS group. After hospital discharge, n=4 patients required non-invasive ventilation whereas out-of-hospital invasive ventilation was only necessary in one patient (all in the ncARDS group). After having survived the acute phase, the disease prognosis of patients with severe COVID-19 is favourable and most patients can be successfully weaned from mechanical ventilation. In addition, there were only minor differences compared to patients with ARDS unrelated to COVID-19.

Association of the C-terminal 42-peptide fragment of alpha-1 antitrypsin with the severity of ARDS: A pilot study

BackgroundAcute respiratory distress syndrome is a life-threatening condition with a hospital mortality rate of up to 40%. Biomarkers related to the pathophysiology of ARDS may not only identify patients at risk but may also serve as potential therapeutic targets. This study examined the association between the proteolytic C-terminal 42-peptide fragment of alpha-1 antitrypsin and ARDS severity. MethodsThe 42-peptide fragment and interleukin-6 levels were measured in 21 patients with mild-to-moderate ARDS and 47 patients with moderate-to-severe ARDS on days 1, 3, and 5 after diagnosis/admission to the intensive care unit. To elucidate the association between both biomarkers and the PaO2/FiO2 ratio, the concentrations of both biomarkers were compared between the two groups, and a multivariate regression analysis was performed. ResultsThe concentrations of both biomarkers were higher in patients with moderate-to-severe ARDS. While the PaO2/FiO2 ratio increased from day 1 to day 3, the concentrations of both biomarkers decreased. Multivariate regression analysis revealed negative associations between the PaO2/FiO2 ratio and both the C-terminal 42-peptide of alpha-1 antitrypsin and interleukin-6 on day 1 (beta: −0.138, p = 0.052; beta: −0.096, p = 0.004) and on day 3 (beta: −0.157, p = 0.045; beta: −0.106, p = 0.043). InterpretationThe C-terminal 42-peptide of alpha-1 antitrypsin is a new biomarker associated with ARDS severity. Its predictive value in identifying patients at risk of developing moderate-to-severe ARDS must be investigated in additional, independent prospective studies.

The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease.

SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients.

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

BackgroundGastrointestinal 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.MethodsWe 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.ResultsMedian 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).ConclusionOur 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.

Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients.

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p<0.05) and d-dimer lower. The 28-day mortality was not statistically significant (1st wave: 42.2% vs 2nd wave: 39.8%). However, when adjusted for key covariates, the hazard ratio for 28-day mortality in those patients with B.1.1.7 was 3.79 (CI 1.04-13.8; p = 0.043) compared to the original strain. During the second surge in the UK, where the COVID-19 variant B.1.1.7 was most prevalent, significantly more patients presented to critical care with severe ARDS. Furthermore, mortality risk was significantly greater in our ICU population during the second wave of the pandemic in those patients with B.1.1.7. As ICUs are experiencing further waves (particularly by the delta (B.1.617.2) variant), we highlight the urgent need for prospective studies describing immunological and pathophysiological differences across novel emerging variants.

Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19

ObjectiveTo compare the efficacy and outcomes with inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO) in patients with refractory hypoxemia due to COVID-19.DesignRetrospective Cohort Study.SettingSingle health system multicenter academic teaching hospitals.Patients OR subjectsAge group of 18–80 years admitted to the medical ICU.InterventionsMechanically ventilated patients with COVID-19 infection, who received either iNO or iEPO between March 1st, 2020, and June 30th, 2020.Measurements and main resultsThe primary outcome was the change in the PaO2/FiO2 (P/F) ratio 1 hour after initiation of pulmonary vasodilator therapy. Secondary outcomes include P/F ratios on days 1–3 after initiation, positive response in P/F ratio (increase of at least 20% in PaO2), total days of treatment, rebound hypoxemia (if there was a drop in oxygen saturation after treatment was stopped), ventilator free days (if any patient was extubated), days in ICU, days to extubation, days to tracheostomy, mortality days after intubation, 30-day survival and mortality. 183 patients were excluded, as they received both iNO and iEPO. Of the remaining 103 patients, 62 received iEPO and 41 received iNO. The severity of ARDS was similar in both groups. Change in P/F ratio at one hour was 116 (70.3) with iNO and 107 (57.6) with iEPO (Mean/SD). Twenty-two (53.7%) patients in the iNO group and 25 (40.3%) in the iEPO group were responders to pulmonary vasodilators n(%)(p = 0.152) (more than 20% increase in partial pressure of oxygen, Pao2), and 18 (43.9%) and 31 (50%) patients in the iNO and iEPO group (p = 0.685), respectively, had rebound hypoxemia. Only 7 patients in the cohort achieved ventilator free days (3 in the iEPO group and 4 in iNO group).ConclusionsWe found no significant difference between iNO and iEPO in terms of change in P/F ratio, duration of mechanical ventilation, ICU, in-hospital mortality in this cohort of mechanically ventilated patients with COVID-19. Larger, prospective studies are necessary to validate these results.

Secondary bacterial infections are a leading factor triggering New Onset Atrial Fibrillation in intubated ICU Covid-19 ARDS patients

BackgroundCardiac arrhythmias, mainly atrial fibrillation (AF), is frequently reported in COVID-19 patients, more often in Intensive Care Unit (ICU) patients, yet causality has not been virtually explored. Moreover, non-Covid ICU patients frequently present AF, sepsis being the major trigger. We aimed to examine whether sepsis or other factors-apart from Covid-19 myocardial involvement-contribute to elicit New Onset AF (NOAF) in intubated ICU patients. MethodsConsecutive intubated, Covid-19ARDS patients, were prospectively studied for factors triggering NOAF. Demographics, data on Covid-19 infection duration, laboratory findings (troponin as well), severity of illness and ARDS were compared between NOAF and control group (no AF) on admission. In NOAF patients, echocardiographic findings, laboratory and secondary infection data on the AF day were compared to the preceding days and/or ICU admission data. ResultsAmong 105 patients screened, 79 were eligible; nineteen presented NOAF (24%). Baseline characteristics did not differ between the NOAF and control groups. Troponin levels were mildly elevated upon ICU admission in both groups. Left ventricular global longitudinal strain was impaired (<16.5%) in 63% vs 78% in the two groups, respectively. The right ventricle was mildly dilated, and pericardial effusion was present in 52 vs 43%, respectively. NOAF occurred on the 18 ± 4.8 days from Covid-19 symptoms’ onset, and the 8.5 ± 2.1 ICUday. A septic secondary infection episode occurred in 89.5% of the patients in the NOAF group ( vs 41.6% in the control group (p < 0.001). In fact, NOAF occurred concurrently with a secondary septic episode in 84.2% of the patients. Sepsis presence was the only factor associated to NOAF occurrence (OR 16.63, p = 0.002). Noradrenaline, lactate and inflammation biomarkers gradually increased in the days before AF (all p < 0.05). Echocardiographic findings did not change on NOAF occurrence. ConclusionSecondary infections seem to be major contributors for NOAF occurrence in Covid-19 patients, probably playing the role of the “second hit” in an affected myocardium from Covid-19.

COVID 19 induced acute pancreatitis in patients with renal impairment: report of five cases

COVID 19 infection is an ongoing pandemic that the world is facing currently. Though SARS-CoV2 infection mainly involves the lungs, it is known to affect other organs like kidneys, brain, heart, endocrine organs and gastrointestinal system. It is hypothesized that the ACE2 and transmembrane serine protease 2 which are expressed in the beta cells of the pancreas are the entry receptors for the SARS-CoV-2 virus, thus causing pancreatitis. A retrospective review of clinical records at our institution during the COVID 19 pandemic from 2019 to 2020 was carried out to find patients with COVID 19 infection presenting with acute pancreatitis. Additionally, a review of literature was conducted about COVID 19 patients presenting with pancreatitis in chronic kidney disease and renal transplantation recipients. Five patients with COVID 19 infection presented with acute pancreatitis during the 2019–2020 pandemic period. All patients were males and mean age of the patients was 48 ± 20 years. Out of 5 patients, 3 were chronic kidney disease patients, 2 were renal transplantation recipients. COVID 19 infection was the cause of acute pancreatitis in all 5 cases. Out of 5, 1 patient had acute necrotizing pancreatitis and the rest had mild to moderate severity pancreatitis. All patients recovered except the patient with acute necrotizing pancreatitis who succumbed to the illness. One patient with chronic kidney disease became dialysis dependent post recovery from pancreatitis. In all 5 patients, there was no correlation between the severity of COVID ARDS and the severity of pancreatitis. There was no correlation between the severity of pancreatitis and the elevation of inflammatory markers. In patients presenting with pancreatitis, we have to keep in mind COVID 19 infection along with other known aetiologies of acute pancreatitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12328-022-01633-5.

Clinical characteristics, physiological features, and outcomes associated with hypercapnia in patients with acute hypoxemic respiratory failure due to COVID-19---insights from the PRoVENT-COVID study.

PurposeWe determined the incidence of hypercapnia and associations with outcome in invasively ventilated COVID–19 patients.MethodsPosthoc analysis of a national, multicenter, observational study in 22 ICUs. Patients were classified as ‘hypercapnic’ or ‘normocapnic’ in the first three days of invasive ventilation. Primary endpoint was prevalence of hypercapnia. Secondary endpoints were ventilator parameters, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, at day 28 and 90.ResultsOf 824 patients, 485 (58.9%) were hypercapnic. Hypercapnic patients had a higher BMI and had COPD, severe ARDS and venous thromboembolic events more often. Hypercapnic patients were ventilated with lower tidal volumes, higher respiratory rates, higher driving pressures, and with more mechanical power of ventilation. Hypercapnic patients had comparable minute volumes but higher ventilatory ratios than normocapnic patients. In hypercapnic patients, ventilation and LOS in ICU and hospital was longer, but mortality was comparable to normocapnic patients.ConclusionHypercapnia occurs often in invasively ventilated COVID–19 patients. Main differences between hypercapnic and normocapnic patients are severity of ARDS, occurrence of venous thromboembolic events, and a higher ventilation ratio. Hypercapnia has an association with duration of ventilation and LOS in ICU and hospital, but not with mortality.

Definition of Acute Respiratory Distress Syndrome on the Plateau of Xining, Qinghai: A Verification of the Berlin Definition Altitude-PaO2/FiO2-Corrected Criteria.

BackgroundAcute respiratory distress syndrome (ARDS) is a common critical respiratory illness. Hypoxia at high altitude is a factor that influences the progression of ARDS. Currently, we lack clear diagnostic criteria for high-altitude ARDS. The purpose of this study was to determine the value of the application of the Berlin Definition altitude-PaO2/FiO2-corrected criteria for ARDS in Xining, Qinghai (2,261 m).MethodsWe retrospectively analyzed the clinical data of patients with ARDS admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity of ARDS was categorized according to the Berlin Definition, Berlin Definition altitude-PaO2/FiO2-corrected criteria, and the diagnostic criteria for acute lung injury (ALI)/ARDS at high altitudes in Western China (Zhang criteria). In addition, the differences between the three criteria were compared.ResultsAmong 1,221 patients, 512 were treated with mechanical ventilation. In addition, 253 met the Berlin Definition, including 49 (19.77%) with mild ARDS, 148 (58.50%) with moderate ARDS, and 56 (22.13%) with severe ARDS. A total of 229 patients met the altitude-PaO2/FiO2-corrected criteria, including 107 with mild ARDS (46.72%), 84 with moderate ARDS (36.68%), and 38 (16.59%) with severe ARDS. Intensive care unit (ICU) mortality increased with the severity of ARDS (mild, 17.76%; moderate, 21.43%; and severe, 47.37%). Twenty-eight-day mortality increased with worsening ARDS (mild 23.36% vs. moderate 44.05% vs. severe 63.16%) (p < 0.001). There were 204 patients who met the Zhang criteria, including 87 (42.65%) with acute lung injury and 117 (57.35%) with ARDS. The area under receiver operating characteristics (AUROCs) of the Berlin Definition, the altitude-P/F-corrected criteria, and the Zhang criteria were 0.6675 (95% CI 0.5866–0.7484), 0.6216 (95% CI 0.5317–0.7116), and 0.6050 (95% CI 0.5084–0.7016), respectively. There were no statistically significant differences between the three diagnostic criteria.ConclusionFor Xining, Qinghai, the altitude-PaO2/FiO2-corrected criteria for ARDS can distinguish the severity of ARDS, but these results need to be confirmed in a larger sample and in multicenter clinical studies.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04199650.

Puntaje radiográfico de evaluación del edema pulmonar (RALE) y su asociación con desenlaces clínicos en el síndrome de dificultad respiratoria aguda en Colombia

IntroductionAcute respiratory distress syndrome (ARDS) is currently the main diagnosis in intensive care units (ICU) and is related to the SARS-CoV-2 pandemic. This syndrome increases hospital stay and costs, and has high mortality. Chest radiography is essential in these patients for diagnosis and clinical follow-up, as it is inexpensive and routinely used in the ICU. The RALE score (Radiographic assessment of lung edema) allows the estimation of the extension and density of alveolar opacities in chest radiography and has been associated with different clinical outcomes such as oxygenation, mortality at 28 days, ventilator-free days, hospital stay, and severity of ARDS. The objective of this work is to establish the association of RALE with clinical outcomes in patients with ARDS in our institution. Materials and methodsAmbispective, monocentric cohort study. Adults older than 18 years with a diagnosis of ARDS hospitalized in the ICUs of Hospital Santa Clara, Bogotá, Colombia, from January to December 2020, were included. ResultsThe study included 100 patients, 93% with a diagnosis of SARS-CoV-2, an association with RALE on the first day was found with oxygenation on the first day of admission, but without finding a statistically significant relationship between RALE and the other outcomes. ConclusionThe RALE score was not associated with relevant clinical outcomes in patients with ARDS. This can be explained by the different mechanisms of hypoxaemia in these patients. Further studies are suggested to confirm these findings.

Factors Associated with 90-Day Mortality in Invasively Ventilated Patients with COVID-19 in Marseille, France.

Objectives: To describe clinical characteristics and management of intensive care units (ICU) patients with laboratory-confirmed COVID-19 and to determine 90-day mortality after ICU admission and associated risk factors. Methods: This observational retrospective study was conducted in six intensive care units (ICUs) in three university hospitals in Marseille, France. Between 10 March and 10 May 2020, all adult patients admitted in ICU with laboratory-confirmed SARS-CoV-2 and respiratory failure were eligible for inclusion. The statistical analysis was focused on the mechanically ventilated patients. The primary outcome was the 90-day mortality after ICU admission. Results: Included in the study were 172 patients with COVID-19 related respiratory failure, 117 of whom (67%) received invasive mechanical ventilation. 90-day mortality of the invasively ventilated patients was 27.4%. Median duration of ventilation and median length of stay in ICU for these patients were 20 (9–33) days and 29 (17–46) days. Mortality increased with the severity of ARDS at ICU admission. After multivariable analysis was carried out, risk factors associated with 90-day mortality were age, elevated Charlson comorbidity index, chronic statins intake and occurrence of an arterial thrombosis. Conclusion: In this cohort, age and number of comorbidities were the main predictors of mortality in invasively ventilated patients. The only modifiable factor associated with mortality in multivariate analysis was arterial thrombosis.

Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units

BackgroundCOVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients.MethodsThis is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio).ResultsHealthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies.ConclusionPatients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial.Trial registration ClinicalTrials.gov NCT04689477. Retrospectively registered 30 December 2020.

Oxygenation and Inflammatory Markers after Early Covid-19 Convalescent Plasma: A Comparison of Survivors and Non-Survivors

BackgroundAcute respiratory distress syndrome (ARDS) is a major complication in patients with severe coronavirus disease in 2019 (COVID-19). COVID-19 convalescent plasma (CCP) has been proposed as a specific therapy for patients with COVID-19. Our goal is to assess changes in oxygenation and inflammatory markers in patients after receiving CCP.MethodsThis is a retrospective, health system-based, a case-control study comparing hospitalized patients with COVID-19 who received CCP and were discharged (survivors) to patients who died after receiving CCP (non-survivors). We analyzed the severity of ARDS, oxygenation, and inflammatory markers of 295 patients, comparing 202 survivors to 93 non-survivors with COVID-19 who received CCP. Demographic information and laboratory data were collected on the day of the admission (initial), the day of the plasma infusion (D1), and post-infusion days 3, 7, 15, and 30 (when available).ResultsSurvivors were younger (52.48 y versus 64.02 y; p<0.001) with no pre-existing conditions (25.2% versus 13.9%; p=0.03) compared to non-survivors. Severe ARDS (PaO2/FiO2 <100) was predictive of increased mortality after CCP in non-survivors (p<0.001). Survivors with mild (20%) or moderate (46%) ARDS on D1 had a 54% resolution of ARDS on D7 after CCP (p<0.001). After 72 hours of transfusion, supplemental oxygen requirements decreased by 63% of the survivors, compared to 33% of non-survivors (p<0.001). Inflammatory markers, including white blood cells, absolute neutrophils, platelets, C-reactive protein (CRP), lactate dehydrogenase (LDH), and creatinine, improved within three days in survivors after CCP (p<0.05). Baseline findings associated with a poor prognosis on D1 include a lower platelet count (219.02 versus 281.64, p<0.001), higher blood urea nitrogen (BUN) (35.41 versus 21.48, p<0.001), higher creatinine (2.24 versus 1.26, p<0.001), higher D-dimer (5.88 versus 2.46, p<0.001) and elevated lactate dehydrogenase (LDH) (698.3 versus 464.51, p<0.001) when comparing non-survivors to survivors, respectively. After 72 hours post-transfusion, the following changes were remarkable: normalization of creatinine with a mean of 1.07 in survivors versus 1.92 in non-survivors (p<0.001), a significant decrease in CRP improving from 129.27 to 84.25 in survivors versus 139.11 to 130.0 in non-survivors (p<0.001), and lower lactate dehydrogenase (LDH) in survivors (459.47) versus non-survivors (674.56, p<0.001).ConclusionIn this retrospective, health system-based, case-control study, we found that the improvement in oxygenation, resolution of ARDS, and reduced inflammatory markers are seen in survivor patients after early COVID-19 convalescent plasma transfusion. These parameters can be used to assess response to COVID-19 convalescent plasma after 72 hours of the transfusion and could help physicians in the decision-making when administering CCP, especially if resources are scarce. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.