Cause Of Critical Illness Research Articles

Comorbid burden at ICU admission in COVID-19 compared to sepsis and acute respiratory distress syndrome.

Comorbidities are similarly associated with short-term mortality for COVID-19, acute respiratory distress syndrome (ARDS) and sepsis in intensive care unit (ICU) patients, but their adjusted frequencies at admission are unknown. Thus, we aimed to evaluate the adjusted distribution, reported as odds ratios, of known risk factors (i.e., age, sex and comorbidities) for ICU admission between COVID-19, sepsis and ARDS patients in this nationwide registry-based study. In this cohort study, we included adult patients admitted to Swedish ICUs with COVID-19 (n = 7382) during the pandemic and compared them to patients admitted to ICU with sepsis (n = 22,354) or ARDS (n = 2776) during a pre-COVID-19 period. The main outcomes were the adjusted odds for comorbidities, sex, and age in multivariable logistic regression on diagnostic categories in patients admitted to ICU, COVID-19 or sepsis and COVID-19 or ARDS. We found that most comorbidities, as well as age, had a stronger association with sepsis admission than COVID-19 admission with the exception of male sex, type 2 diabetes mellitus, and asthma that were more strongly associated with COVID-19 admission, while no difference was seen for chronic renal failure and obesity. For COVID-19 and ARDS admission most risk factors were more strongly associated with ARDS admission except for male sex, type 2 diabetes mellitus, chronic renal failure, and obesity which were more strongly associated with COVID-19 admission, whereas hypertension, chronic obstructive pulmonary disease and asthma were not different. Patients admitted to ICU with sepsis or ARDS carry a heavier burden of comorbidity and high age than patients admitted with COVID-19. This is likely caused by a combination of: (1) respiratory failure in COVID-19 being less dependent on comorbidities than in other forms of ARDS, and the cause of critical illness in other infections causing sepsis and (2) COVID-19 patients being deferred admission in situations where patients with the other syndromes were admitted.

Implications of frailty before and after intensive care unit admission.

In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19. A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons. Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.

Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.

Semaphorin 4D (Sema4D), also known as CD100, is a multifunctional transmembrane protein with immunoregulatory functions. Upon the activation of immune cells, soluble Semaphorin 4D (sSema4D) is proteolytically cleaved from the membrane by metalloproteinases. sSema4D levels are elevated in various (auto-)inflammatory diseases. Our aim was to investigate sSema4D levels in association with sepsis and critical illnesses and to evaluate sSema4D's potential as a prognostic biomarker. We measured sSema4D levels in 192 patients upon admission to our medical intensive care unit. We found similar levels of sSema4D in 125 patients with sepsis compared to 67 non-septic patients. sSema4D levels correlated with leukocytes but not with other markers of systemic inflammation such as C-reactive protein or procalcitonin. Most interestingly, in a subgroup of patients suffering from pre-existing liver cirrhosis, we observed significantly higher levels of sSema4D. Consistently, sSema4D was also positively correlated with markers of hepatic and cholestatic injury. Our study suggests that sSema4D is not regulated in sepsis compared to other causes of critical illness. However, sSema4D seems to be associated with hepatic injury and inflammation.

A retrospective analysis of 20,178 adult neurological infection admissions to United Kingdom critical care units from 2001 to 2020

BackgroundNeurological infection is an important cause of critical illness, yet little is known on the epidemiology of neurological infections requiring critical care.MethodsWe analysed data on all adults with proven or probable neurological infection admitted to UK (NHS) critical care units between 2001 and 2020 reported to the Intensive Care National Audit and Research Centre. Diagnoses, physiological variables, organ support and clinical outcomes were analysed over the whole period, and for consecutive 5-year intervals within it. Predictors of in-hospital mortality were identified using a backward stepwise regression model.ResultsWe identified 20,178 critical care admissions for neurological infection. Encephalitis was the most frequent presentation to critical care, comprising 6725 (33.3%) of 20,178 cases. Meningitis– bacterial, viral or unspecified cases - accounted for 10,056 (49.8%) of cases. In-hospital mortality was high, at 3945/19,765 (20.0%) overall. Over the four consecutive 5-year periods, there were trends towards higher Glasgow Coma Scale scores on admission, longer critical care admissions (from median 4 [IQR 2–8] to 5 days [IQR 2–10]), and reduced in-hospital mortality (from 24.9 to 18.1%). We identified 12 independent predictors of in-hospital death which when used together showed good discrimination between patients who die and those who survive (AUC = 0.79).ConclusionsAdmissions with neurological infection to UK critical care services are increasing and the mortality, although improving, remains high. To further improve outcomes from severe neurological infection, novel approaches to the evaluation of risk stratification, monitoring and management strategies are required.

Critical illness at the emergency department of a Tanzanian national hospital in a three-year period 2019–2021

BackgroundCritically ill patients have life-threatening conditions requiring immediate vital organ function intervention. But, critical illness in the emergency department (ED) has not been comprehensively described in resource-limited settings. Understanding the characteristics and dynamics of critical illness can help hospitals prepare for and ensure the continuum of care for critically ill patients. This study aimed to describe the pattern and outcomes of critically ill patients at the ED of the National Hospital in Tanzania from 2019 to 2021.MethodologyThis hospital-records-based retrospective cohort study analyzed records of all patients who attended the ED of Muhimbili National Hospital between January 2019 and December 2021. Data extracted from the ED electronic database included clinical and demographic information, diagnoses, and outcome status at the ED. Critical illness in this study was defined as either a severe derangement of one or more vital signs measured at triage or the provision of critical care intervention. Data were analyzed using Stata 17 to examine critical illnesses’ burden, characteristics, first-listed diagnosis, and outcomes at the ED.ResultsAmong the 158,445 patients who visited the ED in the study period, 16,893 (10.7%) were critically ill. The burden of critical illness was 6,346 (10.3%) in 2019, 5,148 (10.9%) in 2020, and 5,400 (11.0%) in 2021. Respiratory (18.8%), cardiovascular (12.6%), infectious diseases (10.2%), and trauma (10.2%) were the leading causes of critical illness. Most (81.6%) of the critically ill patients presenting at the ED were admitted or transferred, of which 11% were admitted to the ICUs and 89% to general wards. Of the critically ill, 4.8% died at the ED.ConclusionMore than one in ten patients attending the Tanzanian National Hospital emergency department was critically ill. The number of critically ill patients did not increase during the pandemic. The majority were admitted to general hospital wards, and about one in twenty died at the ED. This study highlights the burden of critical illness faced by hospitals and the need to ensure the availability and quality of emergency and critical care throughout hospitals.

Brief Report: Detection of Urine Lipoarabinomannan Is Associated With Proinflammatory Innate Immune Activation, Impaired Host Defense, and Organ Dysfunction in Adults With Severe HIV-Associated Tuberculosis in Uganda.

The immunopathology of disseminated HIV-associated tuberculosis (HIV/TB), a leading cause of critical illness and death among persons living with HIV in sub-Saharan Africa, is incompletely understood. Reflective of hematogenously disseminated TB, detection of lipoarabinomannan (LAM) in urine is associated with greater bacillary burden and poor outcomes in adults with HIV/TB. We determined the relationship between detection of urine TB-LAM, organ dysfunction, and host immune responses in a prospective cohort of adults hospitalized with severe HIV/TB in Uganda. Generalized additive models were used to analyze the association between urine TB-LAM grade and concentrations of 14 soluble immune mediators. Whole-blood RNA-sequencing data were used to compare transcriptional profiles between patients with high- vs. low-grade TB-LAM results. Among 157 hospitalized persons living with HIV, 40 (25.5%) had positive urine TB-LAM testing. Higher TB-LAM grade was associated with more severe physiologic derangement, organ dysfunction, and shock. Adjusted generalized additive models showed that higher TB-LAM grade was significantly associated with higher concentrations of mediators reflecting proinflammatory innate and T-cell activation and chemotaxis (IL-8, MIF, MIP-1β/CCL4, and sIL-2Ra/sCD25). Transcriptionally, patients with higher TB-LAM grades demonstrated multifaceted impairment of antibacterial defense including reduced expression of genes encoding cytotoxic and autophagy-related proteins and impaired cross-talk between innate and cell-mediated immune effectors. Our findings add to emerging data suggesting pathobiological relationships between LAM, TB dissemination, innate cell activation, and evasion of host immunity in severe HIV/TB. Further translational studies are needed to elucidate the role for immunomodulatory therapies, in addition to optimized anti-TB treatment, in this often critically ill population.

Can Neutrophils Prevent Nosocomial Pneumonia after Serious Injury?

Nosocomial pneumonia is a leading cause of critical illness and mortality among seriously injured trauma patients. However, the link between injury and the development of nosocomial pneumonia is still not well recognized. Our work strongly suggests that mitochondrial damage-associated molecular patterns (mtDAMPs), especially mitochondrial formyl peptides (mtFPs) released by tissue injury, play a significant role in developing nosocomial pneumonia after a serious injury. Polymorphonuclear leukocytes (neutrophils, PMN) migrate toward the injury site by detecting mtFPs through formyl peptide receptor 1 (FPR1) to fight/contain bacterial infection and clean up debris. Activation of FPR1 by mtFPs enables PMN to reach the injury site; however, at the same time it leads to homo- and heterologous desensitization/internalization of chemokine receptors. Thus, PMN are not responsive to secondary infections, including those from bacteria-infected lungs. This may enable a progression of bacterial growth in the lungs and nosocomial pneumonia. We propose that the intratracheal application of exogenously isolated PMN may prevent pneumonia coupled with a serious injury.

COVID-19 and the Genetics of Inflammation.

Interindividual variability in the clinical progression of COVID-19 may be explained by host genetics. Emerging literature supports a potential inherited predisposition to severe forms of COVID-19. Demographic and inflammatory characteristics of COVID-19 suggest that acquired hematologic mutations leading to clonal hematopoiesis (CH) may further increase vulnerability to adverse sequelae. This review summarizes the available literature examining genetic predispositions to severe COVID-19 and describes how these findings could eventually be used to improve its clinical management. A PubMed literature search was performed. Studies examining the significance of inherited genetic variation or acquired CH mutations in severe COVID-19 were selected for inclusion. Relevant genetic association data and aspects of study design were qualitatively assessed and narratively synthesized. Genetic variants affecting inflammatory responses may increase susceptibility to severe COVID-19. Genome-wide association studies and candidate gene approaches have identified a list of inherited mutations, which likely alter cytokine and interferon secretion, and lung-specific mechanisms of immunity in COVID-19. The potential role of CH in COVID-19 is more uncertain at present; however, the available evidence suggests that the various types of acquired mutations and their differential influence on immune cell function must be carefully considered. The current literature supports the hypothesis that host genetic factors affect vulnerability to severe COVID-19. Further research is required to confirm the full scope of relevant variants and the causal mechanisms underlying these associations. Clinical approaches, which consider the genetic basis of interindividual variability in COVID-19 and potentially other causes of critical illness, could optimize hospital resource allocation, predict responsiveness to treatment, identify more efficacious drug targets, and ultimately improve outcomes.

Focus on host/organ unregulated response: a common cause of critical illness.

Focus on host/organ unregulated response: a common cause of critical illness.

Dead space fraction for treatment guidance and prognosis evaluation of acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common cause of critical illness and high mortality from respiratory failure. Increased dead space fraction (VD/VT) was independently associated with lung injury and mortality of ARDS. VD/VT is readily obtained by bedside measurements of arterial blood gas and end-tidal carbon dioxide. Early attention and application of VD/VT as an indicator will help to better understand the pathophysiological of ARDS, guide clinical treatment, and better assess the severity and clinical prognosis of the disease.

C-Reactive Protein (CRP) Medium and Severe Symptoms Levels of COVID-19

Coronavirus Disease 2019 (COVID-19) is a disease caused by SARS-CoV-2 and has caused a global pandemic. Patients with COVID-19 can experience symptoms such as fever, dry cough, headache, and shortness of breath which can lead to pneumonia. Excessive inflammation is considered a leading cause of critical illness and death in COVID-19 patients. C-Reactive Protein is a sensitive indicator as an early marker of infection and inflammation. This study presents an overview of the difference in the average CRP levels between patients with moderate and severe confirmed COVID-19 symptoms at UKI Hospital for June-September 2021. The study design was cross-sectional with descriptive and analytical data presentation obtained from medical record documents at UKI Hospital. The average CRP level of COVID-19 patients with moderate symptoms is 63,705 mg/L, totaling 139 patients. The average CRP level of COVID-19 patients with severe symptoms is 132,050 mg/L, totaling 57 patients. The results obtained from the Mann-Whitney test between groups of patients with moderate and severe COVID-19 showed a significant difference between CRP levels with moderate and severe symptoms with p <0.05.
 Keywords: COVID-19, CRP levels, SARS-CoV-2

Lipidomic signatures align with inflammatory patterns and outcomes in critical illness

Alterations in lipid metabolism have the potential to be markers as well as drivers of pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. The previously reported survival benefit of early thawed plasma administration was associated with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers in causal modelling. Phosphatidylethanolamines (PE) were elevated in patients with persistent critical illness and PE levels were prognostic for worse outcomes not only in trauma but also severe COVID-19 patients. Here we show selective rise in systemic PE as a common prognostic feature of critical illness.

Novel insights in endocrine and metabolic pathways in sepsis and gaps for future research.

Sepsis is defined as any life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains an important cause of critical illness and has considerable short- and long-term morbidity and mortality. In the last decades, preclinical and clinical research has revealed a biphasic pattern in the (neuro-)endocrine responses to sepsis as to other forms of critical illness, contributing to development of severe metabolic alterations. Immediately after the critical illness-inducing insult, fasting- and stress-induced neuroendocrine and cellular responses evoke a catabolic state in order to provide energy substrates for vital tissues, and to concomitantly activate cellular repair pathways while energy-consuming anabolism is postponed. Large randomized controlled trials have shown that providing early full feeding in this acute phase induced harm and reversed some of the neuro-endocrine alterations, which suggested that the acute fasting- and stress-induced responses to critical illness are likely interlinked and benefical. However, it remains unclear whether, in the context of accepting virtual fasting in the acute phase of illness, metabolic alterations such as hyperglycemia are harmful or beneficial. When patients enter a prolonged phase of critical illness, a central suppression of most neuroendocrine axes follows. Prolonged fasting and central neuroendocrine suppression may no longer be beneficial. Although pilot studies have suggested benefit of fasting-mimicking diets and interventions that reactivate the central neuroendocrine suppression selectively in the prolonged phase of illness, further study is needed to investigate patient-oriented outcomes in larger randomized trials.

Antibiotic resistance of biofilm-producing bacteria from sepsis patients in Prof. Dr. Margono Soekarjo Hospital, Purwokerto, Central Java

Sepsis is a life-threatening organ dysfunction induced by the body's response to infection and is a significant cause of critical illness and death in hospitals. Bacteria are the most common pathogens that cause sepsis, and their ability to form biofilms increases their resistance to antibiotics. As a result of the failure of antibiotic administration therapy, the severity and pain of sepsis worsen. The study used a descriptive research design to determine the antibiotic resistance pattern of biofilm-producing bacteria from clinical isolates of sepsis patients. Using the BacT/Blood Culture System Alert, all patients suspected of sepsis in the intensive care unit of Prof. Dr. Margono Soekarjo General Hospital Purwokerto were examined for blood cultures between March and July 2018. These were then identified and tested for antibiotic resistance with the Vitek 2 Compact. Biofilm formation was detected utilizing the microtiter plate assay method, and the data were analyzed using a frequency distribution table. The results obtained 12 bacterial isolates, with Escherichia coli (41.67%), Staphylococcus haemolyticus (33.33%), Klebsiella pneumoniae ssp pneumoniae, Enterobacter cloacae complex, and Acinetobacter baumannii complex (8.33%) as the most common bacteria. All gram-negative bacteria (more than 80%) were resistant to ampicillin, cefoxitin, ceftazidime, ceftriaxone, aztreonam, and trimethoprim but were sensitive to meropenem (100%). Gram-positive bacteria were resistant to cefoxitin, benzylpenicillin, oxacillin, ciprofloxacin, erythromycin, and clindamycin (100% each). However, they were sensitive to tigecycline, nitrofuran, quinupristin, linezolid, vancomycin, and tetracycline (100% each). Gram-negative bacteria formed 50% biofilms, and 50% did not, whereas gram-positive bacteria produced 100% biofilms. In conclusion, bacteria clinical isolates of septic patients from Prof. Dr. Margono Soekarjo General Hospital Purwokerto are multiresistant to more than six types of antibiotics and produce weak to moderate biofilms, which can promote antibiotic resistance.

Outcomes and Predictors of Mortality Among Cardiac Intensive Care Unit Patients With Heart Failure

BackgroundLittle is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU. Methods and ResultsRetrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan–Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year. ConclusionsCICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort. Lay summaryPatients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients’ left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.

Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics

SummaryBackgroundLower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.MethodsWe conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.FindingsBetween Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.InterpretationThese findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.FundingUS National Institutes of Health and CZ Biohub

Recommendations for antibiotic selection for severe nosocomial infections.

ABSTRACTSevere infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.

Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study

BackgroundAnalyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19.MethodsWe prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission.ResultsIn critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients.ConclusionsThese studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

Role of an anti-aging molecule in a toxic lifestyle: Relevance for alcohol effects on sepsis.

Sepsis is a clinical syndrome associated with life-threatening multiple organ dysfunction induced by an excessive host defense response to infectious agents (Hotchkiss et al., 2016). Sepsis is also a leading cause of critical illness and mortality worldwide (Lonsdale et al., 2020, Hotchkiss et al., 2016). The global incidence of sepsis in 2017 alone was estimated at 48.9 million cases with 11 million resulting in mortality (Rudd et al., 2020).

P0230 / #833: A DIFFERENT USE OF EXCHANGE TRANSFUSION

Aims & Objectives:Bordetella pertussis is a common, under-recognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Severe pertussis is characterized by refractory hypoxemia, pneumonia, cardiogenic shock and requires intensive care. When pertussis is associated with hyperleukocytosis, mortality rate approaches to 80% with the degree of leukocytosis consisting an independent predictor of death. It is proposed that severe leukocytosis may contribute to pulmonary hypertension by blocking pulmonary capillaries and restricting blood flow. Aims:To describe the use of exchange transfusion in pertussis as a safe and useful technique for reducing leukocyte mass. Methods: A 2.5 month-old girl admitted to PICU due to an apnoeic cyanotic episode. She had presented cough, rhinitis and poor feeding for 10 days and B. pertussis had been detected by PCR on nasal secretions. She presented a second apnoeic cyanotic episode with bradycardia and was intubated. Due to severe and persistent hypercapnoea, she was ventilated in high frequency oscillatory ventilation with no amelioration. As she presented leukocytosis and hemodynamic instability with tachycardia, she underwent a double volume exchange transfusion through a central line, and white blood cells reduced from 72,000/μL to 19,000/μL. The benefits of the procedure were clear and immediate, as the respiratory parameters improved and the heart rate stabilized in normal range in less than 24 hours. Although the course was prolonged, the outcome was favorable. Results: She was discharged without any neurological sequelae. Conclusions: Exchange transfusion should be considered as useful therapeutic tool in children with severe pertussis and severe leukocytosis before shock has occurred.