Berlin Criteria Research Articles

887: INFLUENCE OF INFLAMMATORY MARKERS AND ACUTE PHASE REACTANTS ON PULMONARY DEAD SPACE IN COVID-19 ARDS

Introduction: Ventilatory ratio (VR) is a bedside index of impaired ventilation that can be used as a surrogate marker for pulmonary dead space fraction (VD/VT). Vasculopathy is hypothesized to increase VD/VT in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. The purpose of this study was to investigate associations between VR and markers of inflammation in critically ill COVID-ARDS patients. Methods: We conducted a retrospective study of patients admitted to an intensive care unit due to SARS-CoV-2 infection. All subjects required invasive mechanical ventilation and met the Berlin criteria for ARDS. Clinical lab values were collected at two timepoints: 2-8 hours after intubation (T1) and 2-24 hours before tracheostomy (T2). VR was split into high (VR>2) and low (VR< 2) groups. Comparisons were performed using student’s t, Mann-Whitney, and z tests for difference in proportions with ⍺=0.05. Results: Of the 139 subjects enrolled at T1, 67 (48%) had high VR (>2), with an overall mean VR of 2.08. High VR was significantly associated with leukocyte count (WBC) (13.3 vs. 10.6 x10^9/L, p=0.004), and platelet count (284 vs 248 x10^9/L, p=0.003). There was no association between VR status and procalcitonin (p=0.08), d-dimer (p=0.73), fibrinogen (p=0.38), CRP (p=0.22), and ferritin (p=0.33). Since certain markers had non-Gaussian distributions, we determined threshold values. D-dimer over 500 ng/mL was associated with higher VR (2.3 vs. 1.8, p=0.004) and procalcitonin over 0.5 ng/mL was moderately associated with higher VR (2.2 vs 1.9, p=0.052). CRP >181 μg/mL (the median) and ferritin values >1.5x the upper limit of normal were not associated with VR (p=0.30 and p=0.26, respectively). To enrich the dataset, we pooled data from T1 and T2 and treated each as an independent sample. In this pooled analysis, high VR was associated with higher platelet count (282 vs. 253, p=0.046), and higher procalcitonin (3.464 vs. 0.964, p=0.032). There were no significant associations with VR and d-dimer (p=0.88), fibrinogen (p=0.54), CRP (p=0.20), and ferritin (p=0.76) in the pooled data. Conclusions: Ventilatory ratio appears to be associated with higher levels of some inflammatory markers including WBC, platelets, d-dimer, and procalcitonin in COVID-ARDS patients.

Prospective Study of Immune Phenotype and Associated Outcomes in Patients with Leukemia and Acute Respiratory Distress Syndrome

Background: Patients with active malignancy are frequently admitted to intensive care units (ICUs) and experience organ failure including acute respiratory distress syndrome (ARDS). In ARDS clinical trial populations, two immune phenotypes have been identified which seem to differ based on plasma protein expression, predicted mortality, and response to several randomized therapies. It is unknown if similar patters exist among ICU patients with hematologic malignancies as these patients are often excluded from clinical trials in critical care. We therefore sought to classify patients with leukemia who develop ARDS secondary to septic insult according to validated immune phenotyping algorithms and describe their characteristics and outcomes. Methods: We conducted a prospective cohort study of sepsis subjects admitted to the ICU. Eligible patients had suspected infection and organ injury upon ICU admission; exclusion criteria included non-infectious causes of organ failure, a desire for comfort measures only, or lack of informed consent. Plasma collected on day 0 of ICU admission was profiled for proteins including IL8 and sTNFR1 by electrochemiluminescence. We limited our investigation to subjects with a diagnosis of active leukemia (acute or chronic) who developed ARDS (by Berlin criteria) within 6 days of ICU admission. Using a published parsimonious algorithm incorporating plasma IL8, sTNFR1, and bicarbonate, we assigned either a hyper- or hypo-inflammatory ARDS immune phenotype. We then constructed a multivariable Cox proportional hazards model controlling for APACHE III, history of BMT, sex, acute vs. chronic leukemia, and site of infection to assess the independent effect of phenotype assignment on mortality. Univariate comparisons between patients assigned to either phenotype were made as appropriate with T or Chi-Square tests. Results: 86 subjects diagnosed with leukemia and ARDS between 2008 and 2017 were identified. In-hospital mortality was 76%. 64 (74.4%) were assigned a hyper-inflammatory phenotype using the 3-marker algorithm. Male sex, higher APACHE III, and non-pulmonary infectious source appeared to be associated with hyper-inflammatory assignment in univariate comparison, while tumor-specific characteristics such as leukemia type and cytogenetic features were not (table 1). Median survival in the hyper-inflammatory group was 6 days vs. 20 in the hypo-inflammatory group (log-rank p = 0.04, figure 1). However in our Cox proportional hazards model ARDS immune phenotype was not significantly associated with mortality (HR 1.63, 95% CI 0.87 - 3.08, p = 0.12). A sub-analysis of patients diagnosed with AML did not reveal any association between European LeukemiaNet cytogenetic risk category and mortality, controlling for the same baseline covariates and immune phenotype. Interpretation: We identified previously described ARDS immune phenotypes among leukemic ARDS patients, though we did not observe an independent association between immune phenotype and mortality when controlling for relevant baseline covariates. At 76%, overall mortality was consistent with prior estimates in oncologic ICU patients and higher than the general population (~40%). A higher proportion of leukemia subjects were assigned to the hyper-inflammatory phenotype (74.4%) than described in non-oncologic trial populations (30-35% in 5 prior ARDS trials). Limitations include small sample size and knowledge that both malignancy and immunosuppression may affect cytokine expression such that phenotypic assignment is unreliable. Future efforts might focus on re-deriving ARDS phenotypes from a larger cohort of patients with hematologic malignancies in order to better understand how tumor interacts with the immunopathology of their critical illness. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Awareness and knowledge of the common features of inflammatory back pain among primary care physicians in the western region of Saudi Arabia.

Often, there is a delay in the diagnosis of inflammatory back pain (IBP) in the primary care setting. This may be attributed to the inability of healthcare providers to distinguish between inflammatory and mechanical back pain. This study aimed to evaluate primary care physicians' current practices for assessing patients with IBP using clinical, radiographic, and laboratory tests. A questionnaire-based survey was emailed to all primary care physicians in the western region of Saudi Arabia by the Saudi Commission of Health Specialists from February to May 2021. The questionnaire included data about axial spondyloarthropathy based on the Calin, Berlin, and European Spondyloarthropathy Study Group criteria. A total of 103 primary care physicians responded who represented around 24% of primary care physicians at primary healthcare. The most often perceived IBP symptoms include a response to NSAIDs, morning stiffness lasting >30 minutes, age of onset <45 years old, duration of back pain >3 months, and improvement with exercise. The most frequently questioned patient or family history conditions were peripheral arthritis (92.2%), family history of spondyloarthritis (83.5%), and inflammatory bowel disease (97.6%). The most-reported investigations were CRP/ESR (86.4%) and spinal radiography (66%). For treatment of IBP, NSAIDs were most prescribed (48.6%), followed by physiotherapy (45.6%) and disease-modifying anti-rheumatic drugs (41.7%). Primary care physicians were more confident in management of mechanical back pain than IBP (P < .001). Primary care physicians have good knowledge of IBP symptoms but not of disease-specific features and modest confidence in evaluating patients with IBP, indicating the need for educational programs and a more effective, feasible referral strategy.

POSITIVE END-EXPIRATORY PRESSURE (PEEP) INDEX: A NOVEL, BETTER DISCRIMINATION MARKER THAN PAO2/FIO2 FOR RESCUE MEASURES IN COVID-RELATED ARDS

POSITIVE END-EXPIRATORY PRESSURE (PEEP) INDEX: A NOVEL, BETTER DISCRIMINATION MARKER THAN PAO2/FIO2 FOR RESCUE MEASURES IN COVID-RELATED ARDS

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

METABOLOMIC PROFILING AND PROGNOSTICATION IN COVID-19-RELATED ARDS

METABOLOMIC PROFILING AND PROGNOSTICATION IN COVID-19-RELATED ARDS

Delirium in Adults With COVID-19-Related Acute Respiratory Distress Syndrome: Comparison With Other Etiologies.

Neurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. We conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality. Three hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%, p = 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35-2.1]). Similarly, COVID-19-related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39-1.92]) and 180 days (adjusted OR: 0.67 [0.33-1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25-5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97-9.1]) were not higher in the COVID-19 group. Compared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19-associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.

An expanded definition of acute respiratory distress syndrome: Challenging the status quo

Although the Berlin definition of acute respiratory distress syndrome (ARDS), 2012 has been widely used in clinical practice, issues have occasionally been raised regarding various criteria since it was proposed. High-flow nasal oxygen (HFNO) is widely used for effective respiratory support in acute respiratory failure. As patients who do not require ventilation but meet the Berlin criteria have similar characteristics to those with ARDS, the definition of ARDS may be broadened to include patients receiving HFNO. As the PaO2/FiO2 under-recognizes the diagnosis of ARDS, a SpO2/FiO2 value of ≤315 may be considered instead of a PaO2/FiO2 value of ≤300 for diagnosing the condition in resource-constrained settings. In this context, patients with severe COVID-19 always meet other criteria for ARDS except for 7-day acute onset. Therefore, the timeframe for the onset of ARDS may be extended to up to 14 days. An expanded definition of ARDS may allow early identification of patients with less severe diseases and facilitate testing and application of new therapies in patients with a high risk of poor outcomes. Here, we discuss the major controversies regarding the extension of the ARDS definition with a view to improving clinical implementation and patient outcomes.

Titration of Ventilator Settings to Target Driving Pressure and Mechanical Power.

Driving pressure (ΔP) and mechanical power (MP) may be important mediators of lung injury in acute respiratory distress syndrome (ARDS) however there is little evidence for strategies directed at lowering these parameters. We applied predictive modeling to estimate the effects of modifying ventilator parameters on ΔP and MP. 2,622 ARDS patients (Berlin criteria) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version1.0) admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2019 were included. Flexible confounding-adjusted regression models for time varying data were fit to estimate the effects of adjusting PEEP and tidal volume (VT) on ΔP, and adjusting VT and respiratory rate (f) on MP. Reduction in VT reduced ΔP and MP, with more pronounced effect on MP with lower compliance. Strategies reducing f, consistently increased MP (when VT was adjusted to maintain consistent minute ventilation). Adjustment of PEEP yielded a U-shaped effect on ΔP. This novel conditional modeling confirmed expected response patterns for ΔP, with the response to adjustments depending on patients' lung mechanics. Furthermore a VT -driven approach should be favored over a f -driven approach when aiming to reduce MP.

Correlación entre el aumento del dímero D en sangre con el espacio muerto en pacientes con COVID-19 y síndrome de dificultad respiratoria aguda

IntroductionSince December 2019, a number of cases of CoV2/COVID-19 severe acute respiratory syndrome (SARS) pneumonia in Wuhan China have been identified as a cause of acute respiratory failure and have spread around the world at high speed. Due to the large number of cases and the need to better understand this condition, tools are required to grade the intensity and vital prognosis of patients. The objective of this study is to determine the relationship between the dead space measured by volumetric capnography or ventilatory ratio and the increase in D-dimer levels in patients diagnosed with COVID-19 pneumonia and who meet the Berlin criteria for Acute Respiratory Distress Syndrome (ARDS). Materials and methodsA single-centre observational study of a prospective cohort on the use of D-dimer and the correlation with dead space. Adults older than 18 years with a diagnosis of pneumonia due to COVID-19 and ARDS hospitalized in the intensive care units of Hospital Santa Clara in Bogotá, Colombia, from August 2020 to July 2021 were included. ResultsThe study included 67 patients, all with a confirmed SARS-CoV-2 diagnosis, no association was found between D-dimer and dead space on day 1 and 3 of hospitalization in the ICU. ConclusionsD-dimer was not correlated with increased dead space in our study and was not associated with relevant outcomes in patients with ARDS.

Is obesity paradox valid for critically-ill COVID-19 patients with respiratory failure?

OBJECTIVE:We aimed to analyze the association between body mass index and mortality in patients with coronavirus disease 2019 induced acute respiratory distress syndrome.MATERIAL AND METHODS:In this retrospective cohort study, we analyzed 108 consecutive patients admitted in the intensive care unit for coronavirus disease 2019-induced lung disease in a single center between March 2020 and February 2021. Coronavirus disease 2019 infection was confirmed by real-time reverse transcription-polymerase chain reaction assay of nasal swabs or lower respiratory tract samples. Acute respiratory distress syndrome was defined using Berlin criteria. Acute respiratory distress syndrome severity was assessed with partial pressure of arterial oxygen/fraction of inspired oxygen ratio. We categorized patients according to the body mass index as underweight, <18.5 kg/m2; normal weight, from 18.5 kg/m2 to <25 kg/m2; overweight, from 25 kg/m2 to <30 kg/m2; obese, ≥30 kg/m2. Clinical characteristics and mortality were compared among groups. Demographic and clinical data were collected from electronic medical records of the hospital system.Results:The mean age was 67.3 ± 13.3 years. Study participants were predominantly males (66.7%). The mean BMI was 28.2 ± 5.6 kg/m2. There were 2 patients (2%), 28 (26%), 42 (39%), and 36 patients (33%) in the underweight, normal-weight, overweight, and obese groups, respectively. The hospital mortality was 40.7%. There was no association between body mass index and mortality (P = .09). In multivariate analysis, mortality was associated with the presence of cancer [odds ratio = 7.338 (1.636-32.914), P = .009], and time between diagnosis and intubation [odds ratio = 1.318 (1.150-1.509), P ≤ .001].Conclusion:Neither acute respiratory distress syndrome severity nor mortality was higher in patients with higher body mass index compared to the ones with normal body mass index.

Factores asociados a mortalidad en pacientes con síndrome de dificultad respiratoria aguda en una unidad de cuidados intensivos de Medellín durante el período 2012-2019

IntroductionDespite all the advances, acute respiratory distress syndrome continues to be one of the main causes of mortality in Intensive Care Units. Little is known about the factors that predispose patients to death. ObjectiveTo identify the demographic, clinical and treatment factors associated with mortality in patients treated with acute respiratory distress syndrome in the Intensive Care Units. Materials and methodsRetrospective observational follow-up study was carried out on a cohort of patients diagnosed with acute respiratory distress syndrome according to the Berlin criteria and treated in the Intensive Care Units of an institution in the city of Medellín (Colombia) between January 2012 and December 2019. Results175 patients with acute respiratory distress syndrome treated in the Intensive Care Units were included. The median age was 56 years (IQR 66-40), and most of the patients were men (59.4%). The aetiology of acute respiratory distress syndrome was predominantly sepsis (90.3%). A mortality of 38.3% was observed.No significant differences were found between the groups regarding ventilatory parameters upon admission. The performance of a tracheostomy showed a negative correlation with mortality (HR.14 [95% CI: .07 -.29] P≤.001); while vasopressor support stood out as a risk factor (HR 4.43 [95% CI 1.66 - 11.84] P=.003). A history of oncological pathology and chronic lung disease are associated with an unfavourable outcome in Intensive Care Units (HR 2.18 [95% CI: 1.01 - 4.68] P=.040 and HR 2.27 [95% CI: 1.13 - 4.55] P=.021). ConclusionsMortality from Acute Respiratory Distress Syndrome in Intensive Care Units continues to be high. The presence of oncological pathology, chronic lung disease, and the use of vasopressor support are associated with adverse outcomes due to this aetiology.

Acute respiratory distress syndrome after in-hospital cardiac arrest

ObjectiveAcute respiratory distress syndrome (ARDS) after out-of-hospital cardiac arrest is common and associated with worse outcomes. In the hospital setting, there are many potential risk factors for post-arrest ARDS, such as aspiration, sepsis, and shock. ARDS after in-hospital cardiac arrest (IHCA) has not been characterized. MethodsWe performed a single-center retrospective study of adult patients admitted to the hospital between 2014–2018 who suffered an IHCA, achieved return of spontaneous circulation (ROSC), and were either already intubated at the time of arrest or within 2 hours of ROSC. Post-IHCA ARDS was defined as meeting the Berlin criteria in the first 3 days following ROSC. Outcomes included alive-and-ventilator free days across 28 days, hospital length-of-stay, hospital mortality, and hospital disposition. ResultsOf 203 patients included, 146 (71.9%) developed ARDS. In unadjusted analysis, patients with ARDS had fewer alive-and-ventilator-free days over 28 days with a median of 1 (IQR: 0, 21) day, compared to 18 (IQR: 0, 25) days in patients without ARDS (p = 0.03). However, this association was not significant after multivariate adjustment. There was also a non-significant longer hospital length-of-stay (15 [IQR: 7, 26] vs 10 [IQR: 7, 22] days, p = 0.25; median adjusted increase in ARDS patients: 3 [95% CI: −2 to 8] days, p = 0.27) and higher hospital mortality (53% vs 44%, p = 0.26; aOR 1.6 [95% CI: 0.8–2.9], p = 0.17) in the ARDS group. ConclusionAmong IHCA patients, almost three-quarters developed ARDS within 3 days of ROSC. As in out of hospital cardiac arrest, post-IHCA ARDS is common.

Diagnostic Accuracy of Chest Digital Tomosynthesis in Patients Recovering after COVID-19 Pneumonia.

Purpose: To assess the diagnostic accuracy of traditional chest X-ray (CXR) and digital tomosynthesis (DTS) compared to computed tomography (CT) in detecting pulmonary interstitial changes in patients having recovered from severe COVID-19. Materials and Methods: This was a retrospective observational study, and received local ethics committee approval. Patients suspected of having COVID-19 pneumonia upon emergency department admission between 1 March and 31 August 2020, and who underwent CXR followed by DTS and CT, were considered. Inclusion criteria were as follows: (1) patients with previous SARS-CoV-2 infection proven by a positive RT-PCR on nasopharyngeal swabs performed upon admission to the hospital, and with complete clinical recovery; (2) a diagnosis of SARS-CoV-2-related ARDS, according to the Berlin criteria, during hospitalization; (3) no recent history of other lung disease; and (4) complete imaging follow-up by CXR, DTS, and CT for at least 6 months and up to one year. Analysis of DTS images was carried out independently by two radiologists with 16 and 10 years of experience in chest imaging, respectively. The following findings were evaluated: (1) ground-glass opacities (GGOs); (2) air-space consolidations with or without air bronchogram; (3) reticulations; and (4) linear consolidation. Indicators of diagnostic performance of RX and digital tomosynthesis were calculated using CT as a reference. All data were analyzed using R statistical software (version 4.0.2, 2020). Results: Out of 44 patients initially included, 25 patients (17 M/8 F), with a mean age of 64 years (standard deviation (SD): 12), met the criteria and were included. The overall average numbers of findings confirmed by CT were GGOs in 11 patients, lung consolidations in 8 patients, 7 lung interstitial reticulations, and linear consolidation in 20 patients. DTS showed a significantly higher diagnostic accuracy compared to CXR in recognizing interstitial lung abnormalities—especially GGOs (p = 0.0412) and linear consolidations (p = 0.0009). The average dose for chest X-ray was 0.10 mSv (0.07–0.32), for DTS was 1.03 mSv (0.74–2.00), and for CT scan was 3 mSv. Conclusions: According to our results, DTS possesses a high diagnostic accuracy, compared with CXR, in revealing lung fibrotic changes in patients who have recovered from COVID-19 pneumonia.

P270 ‘Act on Axial SpA': a gold standard time to diagnosis

Abstract Background/Aims A lack of public understanding of the symptoms of axial spondyloathritis (axial SpA) is a significant factor in diagnostic delay. Research commissioned by The National Axial Spondyloarthritis Society (NASS) found that 91% of the UK population had never heard of axial SpA, despite more people living with the condition than MS and Parkinson’s combined. Additionally, 8 in 10 people could not identify the symptoms of axial SpA when prompted. As part of a 5-year programme called ‘Act on Axial SpA’, NASS created the first phase of a campaign to increase public awareness, help people recognise symptoms, and encourage them to visit their GP if concerned. Aims: 1) Ensure people have heard of axial SpA. 2) Help people understand that it’s a condition that affects young people. 3) Ensure people recognise the signs and symptoms of the condition. 4) Get people to visit actonaxialspa.com to use the symptom checker and visit their GP if concerned. Methods 1) Raise awareness about the condition: to make an emotional connection with a cold audience, who are unlikely to have heard of axial SpA (AS) and show them why the campaign is relevant to them. We told stories about people with the condition and their families, so people can see that the condition could affect someone like ‘them’. We ensured our campaign key messages are highly visible in the places, publications and online media people in our target audiences are likely to see every day. 2) Identify a core set of symptoms using a newly developed acronym (SPINE). 3) Direct people to an online symptom checker which combines the ASAS, Berlin and Calin inflammatory back pain criteria. 4) Provide information for the patient and primary care professional on the results of the symptom checker and next steps as per the NICE guidelines 5) Provide information for the patient on preparing for their GP and rheumatologist appointments. Results We report results from June 23 - October 13 2021. 1) Case studies have featured in 11 national media publications with a combined reach of over 101 million. 2) Social media activity has a reach of 440,000. 3) Video content has been viewed 375,000 times. 4) 1,264 people have used the symptom checker. 5) We are reaching new audiences, in particular those aged 18-45 and a larger proportion of women. Conclusion The first phase of the campaign has demonstrated cut through to new audiences. People are interested, engaged and eager to learn more about axial SpA. When people are aware of the condition and its symptoms, they are more likely to act. We are confident that, with time, the ‘Act on Axial SpA’ public awareness campaign will play a huge part in reducing diagnosis times for people with axial SpA. Disclosure L. Marshall: None. D. Webb: None. F. MacAulay: None. K. Gaffney: Consultancies; Novartis, AbbVie, UCB, Lilly, Pfizer. Shareholder/stock ownership; SpA Academy www.spaacademy.org. Honoraria; Novartis, AbbVie, UCB, Lilly, Pfizer. Member of speakers’ bureau; Novartis, UCB, AbbVie, Lilly. Grants/research support; NASS, AbbVie, Pfizer, UCB, Novartis, Lilly, Cellgene, Celltrion, Janssen, Gilead, Biogen. Other; Expenses: Abbvie, Lilly, Roche, Novartis, Pfizer and UCB. R. Sengupta: Consultancies; Abbvie, Biogen, Celgene, Chugai, Lilly, MSD, Novartis, UCB. Honoraria; Abbvie, Biogen, Celgene, Chugai, Lilly, MSD, Novartis, UCB. Grants/research support; Abbvie, Celgene, Novartis, UCB. Other; Advisory boards:, Abbvie, Biogen, Chugai, Lilly, Novartis, UCB.

Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.

Driving pressure versus right ventricular echocardiography parameters as a predictive for acute respiratory distress syndrome outcome

Background: Acute respiratory distress syndrome (ARDS) is an inflammatory disease that affects the lung in a heterogeneous manner , so that ,even ideal body weight (IBW) based tidal volume may apply different lung stress and strain according to the available aerated lung areas. Airway driving pressure (DP) is the difference between airway plateau pressure (P plat) and positive endexpiratory pressure (PEEP), it can be used as a bedside surrogate for lung stress in several previous studies. Acute corpulmonale manifested by pulmonary hypertension and right ventricular dysfunction occurs as a consequence for ARDS with a prevalence ( 25% to 61%) in different studies. Objectives : This study was designed to show he clinical value of airway driving pressure and right heart echocardiography parameters in predicting ARDS outcome , and to correlate between airway pressures and right ventricle parameters. Methodology : fifty ARDS patients were diagnosed by Berlin criteria and monitored for airway pressures including DP and Pplat on day 0, day 3 and day 7. transthoracic echocardiography was used to assess RV parameters on day 0 and day 7 . According the ICU mortality patients are divided into survivors and nonsurvivors.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study

IntroductionPrognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a...

520 Efficacy of high volume hemofiltration (HVHF) with step-down approach in critically ill burn patients

IntroductionContinuous renal replacement therapy (CRRT) is the standard of care for critically ill burn patients with acute kidney injury. Historical mortality rates for burn patients requiring CRRT is over 50%. High volume hemofiltration (HVHF) is a purification method that may have superior outcomes in the critically ill but has not been well studied in burn patients. We report results of utilizing HVHF with a step-down approach in our burn center.MethodsRetrospective review of all adult burn patients at a verified adult and pediatric burn center requiring continuous veno-venous hemodiafiltration (CVVHDF) from 2018 to 2021 when HVHF (50ml/kg/hr) for 18-24 hours with a step-down approach (25-30ml/kg/hr) was started. A normocarbia bicarbonate based dialysate was used with blood flow rates of 200ml/hr along with citrate anticoagulation. Demographics, indications and duration of CVVHDF, duration of vasopressor requirements, days on mechanical ventilation, length of stay, correction of acidosis and mortality were recorded.ResultsThirteen patients were identified, of which four were excluded as they had an exfoliative skin disease (two patients) or were treated with conventional CVVHDF (two patients). Of the remaining nine patients (six male and three female) the average age was 58.7 years (range: 42-75) and average total body surface area burn (%TBSA) was 46% (range: 20-92). All patients were diagnosed with AKI (Acute Kidney Injury Network [AKIN] Class III) with the indication for CRRT being diuretic resistant fluid overload in three patients and sepsis in the remaining six patients. Of the three patients with fluid overload, two developed sepsis while on CRRT. Acute respiratory distress syndrome (ARDS) as defined by the Berlin criteria was noted in six patients (66%). Three patients died (33% mortality) with the remaining six being eventually converted to intermittent hemodialysis and progressing to renal recovery. Amongst survivors, the duration of CRRT ranged between 7-33 days (average 13.8 days) and duration of vasopressor support from 1-30 (average 17 days). Metabolic acidosis resolved in all survivors within 48 hours. No hemorrhagic events were noted and all patients tolerated regional citrate anticoagulation well. Reduction in serum creatinine was noted to be significant.ConclusionsHigh volume hemofiltration resulted in improved mortality rates compared to what is reported in the literature. Further research and comparative studies are required to determine if HVHF with a step-down approach is superior.

Clinical impact of ventilator-associated pneumonia in patients with the acute respiratory distress syndrome: a retrospective cohort study

BackgroundThe clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS).MethodsPatients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO2/FiO2 ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes.ResultsAmong the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO2/FiO2 ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, − 19 [− 20; − 13.5] days) and vasopressor-free days (− 5 [− 9; − 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04–4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11–5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32–4.49, P = 0.80).ConclusionsVAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.