scholarly journals Sars-Cov-2 Induced Endotheliopathy and the Impact on Clinical Outcomes in Critically Ill Pediatric Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3145-3145
Author(s):  
Shreya Agarwal ◽  
Mark Zobeck ◽  
Clay T Cohen ◽  
Sarah E Sartain
Keyword(s):  
Mechanical Ventilation ◽  
Statistical Analysis ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Pediatric Patients ◽  
Endothelial Injury ◽  
Negative Regulator ◽  
Plasma Samples ◽  
Positive Correlation

Abstract Background: Coronavirus disease-19 (COVID-19) is an acute respiratory illness caused by the SARS-COV-2 virus. Patients with COVID-19 infection can present with thrombosis in the setting of inflammation (thromboinflammation), presumably from endothelial dysfunction, or "endotheliopathy". Yu et al demonstrated in vitro that the spike protein subunit of SARS-COV2 acts as a potent activator of the alternative complement pathway (AP), one of three complement pathways within the innate immune system. Satyam et alreported the deposition of complement components on lung tissue of patients who succumbed to COVID-19, consistent with activation of classical and alternate pathways. These studies suggest complement dysregulation potentially causing endotheliopathy in COVID-19 patients. Thrombomodulin (TM) is an endothelial glycoprotein that plays two crucial roles in maintaining a healthy endothelium - as a natural anticoagulant and a negative regulator of complement. TM shed into the circulation due to endothelial injury can be measured in the plasma as soluble TM (sTM). Goshua et al showed elevated sTM in an adult cohort of patients with COVID-19. However, it is yet to be demonstrated if there is any correlation between endothelial injury and AP activation in COVID-19, or if either play a role in clinical outcome in the pediatric population. Objective: To 1) assess endothelial injury and AP activation in a cohort of critically ill pediatric patients with COVID-19 by measuring sTM and Ba (an AP activation product); 2) determine the correlation between endothelial injury and AP activation; and 3) analyze the utility of sTM and Ba in predicting pediatric clinical outcomes. Methods: We collected plasma samples of patients admitted to the Pediatric Intensive Care Unit and found to be positive for SARS-CoV-2 between Dec 2, 2020 and Jan 22, 2021 at Texas Children's Hospital. For controls, we collected plasma samples from pediatric patients undergoing preoperative clearance, all at their baseline state of health. sTM levels and Ba levels were measured in plasma samples using commercially available TM and Ba ELISA kits. sTM greater than 7.6 ng/ml (based on the assay range in adults) and Ba greater than 1080 ng/ml (based on data from adult healthy controls) were considered elevated. Data regarding demographics, length of ICU stay, clinical indicators of end organ damage- mechanical ventilation, dialysis, use of vasopressors, ECMO, mortality were obtained retrospectively via chart review. Inclusion criteria included all patients with a positive SARS-COV2 PCR admitted to the ICU. Exclusion criteria was age greater than 21 years, pregnant female, patients with known inflammatory or complement-mediated disorders. Statistical analysis: For sTM and Ba levels between control and COVID-19 patients, mean +/- standard deviation was calculated and significance determined with an unpaired t-test. Fischer exact test, Wilcoxon rank sum and Pearson product-moment correlation tests were used for statistical analysis of clinical outcomes as appropriate. A p-value <0.05 was considered statistically significant. Results: A total of 38 control patients and 33 COVID-19 patients were enrolled. Ba and sTM levels were both significantly higher in the COVID-19 pediatric patients compared to the controls (Fig. 1). Within the COVID-19 patient cohort, 61% (n=20) had elevated sTM and 42% (n=14) had elevated Ba levels. There was a moderately positive correlation between sTM and plasma Ba levels in the COVID-19 cohort (Fig. 2). Within the COVID-19 patients' cohort, though higher Ba levels were not associated with an increased rate of intubation, they were associated with an increased duration of mechanical ventilation (p=.039) for those intubated (Table 1). Elevated sTM was associated with increased vasopressor use (p=.011). Although other clinical outcome variables did not reach statistical significance likely owing to small numbers, overall trend indicated worse outcomes in patients with elevated sTM. Conclusions: Our findings are consistent with the hypothesis that SARS-COV-2 activates AP and causes endothelial injury in children. The positive correlation between sTM and Ba suggest interplay between inflammation, coagulation and endotheliopathy supporting thromboinflammation in COVID-19. Higher sTM and Ba levels indicated worse clinical outcomes in children, but larger studies are needed to confirm our findings. Figure 1 Figure 1. Disclosures Sartain: Alexon Pharamaceuticals: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Eleni Papoutsi ◽  
Vassilis G. Giannakoulis ◽  
Eleni Xourgia ◽  
Christina Routsi ◽  
Anastasia Kotanidou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Meta Analysis ◽  
Mortality And Morbidity ◽  
Icu Admission ◽  
All Cause Mortality ◽  
Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

scholarly journals 688 Pediatric Obstructive Sleep Apnea (OSA) and COVID-19-Related Adverse Clinical Outcomes

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A269-A269
Author(s):  
Vaishal Shah ◽  
Nancy Foldvary-Schaefer ◽  
Lu Wang ◽  
Lara Jehi ◽  
Cynthia Pena Obrea ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Pediatric Patients ◽  
Control Design ◽  
Supplemental Oxygen ◽  
Case Control ◽  
World Health ◽  
Invasive Ventilation ◽  
High Flow Oxygen

Abstract Introduction The relationship of OSA and human coronavirus (COVID-19) in the pediatric population is unknown. We postulate that OSA is associated with SARS-CoV-2 positivity and with adverse COVID-19 outcomes in children. Methods A retrospective review of 120 consecutive patients (<18 years) with prior polysomnogram (PSG) and COVID-19 testing from the Cleveland Clinic COVID-19 registry was conducted. Using a case control design of SARS-CoV-2 positive and negative pediatric patients, we examined COVID-19 and pre-existing OSA (dichotomized AHI≥1) using logistic (OR,95%CI) regression and as continuous measures: AHI, oxygen(SpO2) nadir, %time SpO2<90%) using linear regression(beta+/-SE). In those positive for SARS-CoV-2(cases only), we assessed the association of OSA and World Health Organization(WHO) COVID-19 clinical outcome composite score (hospitalization, requiring supplemental oxygen, non-invasive ventilation/high-flow oxygen, invasive ventilation/ECMO or death) using Wilcoxon rank sum test for ordinal data. Results Cases (n=36) were 11.8±4.4 years, 61% male, 27.8% black and 88.9% with OSA, while 85.7% of controls (n=84) had OSA. OSA was not associated with increased SARS-CoV-2 positivity: OR=1.33(0.40, 4.45,p=0.64). No significant difference between cases and controls for mean AHI 3.7(1.5,6.0) vs 3.5(1.5,7.1),p=0.91,SpO2 nadir 88.6±5.4 vs 89.1±4.4,p=0.58,%time SpO2<90% 0.05[0.00,1.00) vs 0.10 (0.00,1.00, p=0.65) respectively was noted. WHO-7 COVID-19 clinical outcome did not meet statistical significance in relation to OSA due to the low event frequency (p=0.49). Of note, those with OSA vs without OSA had a higher WHO-7 outcome score of 2 vs 0 and prevalence of hospitalization: 12.5 vs 0% respectively. Of hospitalized patients, the following was observed: 23% had moderate/severe OSA vs 4.3% mild OSA, 50% required supplemental oxygen and 25% required intubation/invasive ventilation. No deaths or readmissions were reported. High risk conditions included: 75% obesity, 50% asthma, 25% sickle cell disease and 25% hypoplastic left heart. Conclusion In this first report of which we are aware focused on COVID-19 in pediatric OSA, we use a case control design leveraging COVID-19 and sleep laboratory registries. Albeit not statistically significant, pediatric patients with OSA had a higher percentage of worse clinical outcomes. Larger network studies are needed to clarify whether poorer COVID-19 outcomes may be attributable to OSA or modulated via high risk health conditions. Support (if any):

Effect of Red Blood Cell Transfusions on Clinical Outcomes in Critically Ill Children

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3851-3851
Author(s):  
Irina B. Pateva ◽  
Steven L Shein ◽  
MaryAnn O'Riordan ◽  
Sanjay P Ahuja
Keyword(s):  
Mechanical Ventilation ◽  
Length Of Stay ◽  
Blood Cell ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Age Groups ◽  
Critically Ill Children ◽  
Age Group ◽  
Vasoactive Agents ◽  
The Impact

Abstract Introduction: The association of packed Red Blood Cell (pRBC) transfusions with worse outcomes in critically ill adults is well documented. The impact of pRBC transfusions on clinical outcomes in critically ill children, however, has not been well studied. Associations of pRBCs with outcomes such as mortality and length of stay need to be studied in large clinical databases. This will lead to improvement of our knowledge and generation of guidelines for transfusions in children hospitalized in the Pediatric Intensive Care Units (PICU). Methods: With IRB approval, the Pediatric Health Information System (PHIS) database was queried for children ≤ 18 years admitted to the PICU, receiving pRBC transfusions between January 2011 and December 2015. The PHIS is a database that captures de-identified patient information from 45 pediatric hospitals in the US. The patients of this study were stratified by age groups: less than 1 month of age; 1 month to < 3years; 3 to <10 years; 10 to < 15 years and 15 to 18 years. Patients with underlying hematological or oncological diagnoses and who had undergone HSCT were excluded from the study. Information regarding major comorbidities such as mechanical ventilation, sepsis, use of vasoactive agents, acute kidney injury (AKI) and post-operative state were extracted. Patients who received pRBCs and who did not receive pRBCs were included in the analyses. The primary outcomes were Length of Stay (LOS) and mortality. Multiple linear and logistic regression analyses were performed to define the association between pRBC transfusions and outcomes and to control for sepsis, mechanical ventilation, vasoactive medications, post-operative state and AKI. Data are shown as median (IQR). Results: Of the 393,384 patients who met the inclusion criteria, 43,569 (11%) had transfusions, with 97.2% of the patients receiving only 1 transfusion. The median (IQR) overall length of stay was 5.0 days (2, 10) and the overall mortality was 3.1%. The median (IQR) LOS for those who received pRBCs was 13 days (6, 29) compared to 4.0 days (2, 8) for those who did not. Mortality for those who received pRBCs was 10.1% compared to 2.2% for those who did not. The highest rate of pRBC transfusion was noted in the patients less than 1 month old (22%). The highest unadjusted mortality for patients who received pRBCs was also in the same age group- 7%. The associations between transfusion of pRBCs and outcomes are summarized in Table 1. Of the 393,384 patients, 19,686 (5.0 %) had sepsis; 143,085 (36.4%) were on mechanical ventilation; 141,123 (35.9%) were on vasoactive agents and 14,243 (3.6%) had AKI. After adjusting for sepsis, mechanical ventilation, use of vasoactive agents, post-op state and AKI, pRBC transfusions were associated with significantly increased LOS for all age groups. The highest increase in LOS was noted for the infants younger than 1 month of age - by 11.6 days (p<0.001). The mortality was also increased in patients who received PRBCs, when adjusted for other comorbidites, the highest risk was for patients in the age group of 15 to 18 years old: OR 2.50 (95% CI 2.14- 2.93). Conclusions: In this large, multicenter database study, we identified an association of increased mortality and LOS in critically ill children who received pRBC transfusions. More studies are needed to further investigate the impact of blood transfusions on clinical outcomes in the pediatric population. Disclosures No relevant conflicts of interest to declare.

Effect of early vs. late tracheostomy on clinical outcomes in critically ill pediatric patients

2016 ◽  
Vol 60 (9) ◽  
pp. 1281-1288 ◽  
Author(s):  
J.-H. Lee ◽  
C.-H. Koo ◽  
S.-Y. Lee ◽  
E.-H. Kim ◽  
I.-K. Song ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Critically Ill ◽  
Pediatric Patients

Intensive plasma exchange in small and critically ill pediatric patients: Techniques and clinical outcome

1983 ◽  
Vol 1 (4) ◽  
pp. 215-224 ◽  
Author(s):  
Martin Fosburg ◽  
Mary Dolan ◽  
Richard Propper ◽  
Lawrence Wolfe ◽  
Sherwin Kevy
Keyword(s):  
Clinical Outcome ◽  
Plasma Exchange ◽  
Critically Ill ◽  
Pediatric Patients

scholarly journals Nutritional Management of Critically Ill Patients Infected with SARS-CoV-2

2021 ◽  
Vol 14 (01) ◽  
pp. 002-005
Author(s):  
Sérgio dos Anjos Garnes ◽  
Fernanda Lasakosvitsch ◽  
Adriana Bottoni ◽  
Andrea Bottoni
Keyword(s):  
Mechanical Ventilation ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcome ◽  
Critically Ill ◽  
Prone Position ◽  
Critically Ill Patients ◽  
Protein Intake ◽  
Nutritional Therapy ◽  
Nutritional Management

AbstractEarly nutritional therapy is essential to ensure the maintenance of adequate energy/protein intake for critically ill patients infected with severe acute respiratory syndrome caused by COVID-19 (SARS-CoV-2) infection. However, this poses a major challenge when it comes to individuals on mechanical ventilation in prone position. Therefore, the present work presents a nutritional therapy flowchart developed for patients with SARS-CoV-2 infection to guide nutritional management and ensure that energy/protein intake goals are met, thus favoring a positive clinical outcome.

scholarly journals Five novel clinical phenotypes for critically ill patients with mechanical ventilation in intensive care units: a retrospective and multi database study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Longxiang Su ◽  
Zhongheng Zhang ◽  
Fanglan Zheng ◽  
Pan Pan ◽  
Na Hong ◽  
...  
Keyword(s):  
Machine Learning ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Mortality Rate ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
The Other ◽  
Clinical Phenotypes ◽  
Mimic Iii

Abstract Background Although protective mechanical ventilation (MV) has been used in a variety of applications, lung injury may occur in both patients with and without acute respiratory distress syndrome (ARDS). The purpose of this study is to use machine learning to identify clinical phenotypes for critically ill patients with MV in intensive care units (ICUs). Methods A retrospective cohort study was conducted with 5013 patients who had undergone MV and treatment in the Department of Critical Care Medicine, Peking Union Medical College Hospital. Statistical and machine learning methods were used. All the data used in this study, including demographics, vital signs, circulation parameters and mechanical ventilator parameters, etc., were automatically extracted from the electronic health record (EHR) system. An external database, Medical Information Mart for Intensive Care III (MIMIC III), was used for validation. Results Phenotypes were derived from a total of 4009 patients who underwent MV using a latent profile analysis of 22 variables. The associations between the phenotypes and disease severity and clinical outcomes were assessed. Another 1004 patients in the database were enrolled for validation. Of the five derived phenotypes, phenotype I was the most common subgroup (n = 2174; 54.2%) and was mostly composed of the postoperative population. Phenotype II (n = 480; 12.0%) led to the most severe conditions. Phenotype III (n = 241; 6.01%) was associated with high positive end-expiratory pressure (PEEP) and low mean airway pressure. Phenotype IV (n = 368; 9.18%) was associated with high driving pressure, and younger patients comprised a large proportion of the phenotype V group (n = 746; 18.6%). In addition, we found that the mortality rate of Phenotype IV was significantly higher than that of the other phenotypes. In this subgroup, the number of patients in the sequential organ failure assessment (SOFA) score segment (9,22] was 198, the number of deaths was 88, and the mortality rate was higher than 44%. However, the cumulative 28-day mortality of Phenotypes IV and II, which were 101 of 368 (27.4%) and 87 of 480 (18.1%) unique patients, respectively, was significantly higher than those of the other phenotypes. There were consistent phenotype distributions and differences in biomarker patterns by phenotype in the validation cohort, and external verification with MIMIC III further generated supportive results. Conclusions Five clinical phenotypes were correlated with different disease severities and clinical outcomes, which suggested that these phenotypes may help in understanding heterogeneity in MV treatment effects.

scholarly journals Early mannitol administration improves clinical outcomes of pediatric patients with brain edema

2018 ◽  
Vol 27 (4) ◽  
pp. 244-9 ◽  
Author(s):  
Putu A. Sekarningrum ◽  
Dyah K. Wati ◽  
IGN Made Suwarba ◽  
I Nyoman B. Hartawan ◽  
Dewi S. Mahalini ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Outcome ◽  
Brain Edema ◽  
Clinical Outcomes ◽  
Pediatric Patients ◽  
Pediatric Intensive Care ◽  
Outcome Variable ◽  
Chi Square ◽  
Primary Outcome Variable ◽  
Chi Square Test

Background: Mannitol 20% is used to treat patients with decreased consciousness and as the first line of treatment to reduce intracranial pressure (ICP). However, its application in pediatric patients is still based on minimal evidence. This study was performed to determine the predictive factors of clinical outcomes in pediatric patients with brain edema in the pediatric intensive care unit (PICU).Methods: This prospective cohort study was conducted in the PICU, Sanglah Hospital Denpasar, Bali, Indonesia. The subjects were chosen by consecutive sampling from July 2016 to July 2017. The primary outcome variable was the patient’s clinical outcome. A chi-square test was used to evaluate the association between the timing of mannitol administration and the patient’s clinical outcome. Multivariate analysis was performed on all variables with p≤0.25.Results: Forty-one patients were included in the study, 65% of them were male, 65% had good nutritional status, 90% had non-traumatic brain injury, and 73% had confirmed intracranial infection. The risk of sequelae or death for patients in a coma was 1.8 times greater than that of non-comatose patients (p=0.018; CI 95% 1.119–3.047). Based on the timing of mannitol administration from the onset of decreased consciousness, the risk of sequelae or death in patients who received mannitol after 24 hours was 2.1 times higher than that in patients who received mannitol within 24 hours (p=0.006; CI 95% 1.167–3.779). Based on multivariate analysis, only two variables were associated with the patient’s clinical outcome: pediatric Glasgow coma scale (PGCS) ≤3 (p=0.03) and timing of mannitol administration >24 hours (p=0.01).Conclusion: Early administration (<24 hours) of mannitol and high PGCS are related to favorable outcomes in patients with brain edema in the PICU.

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