Development Of Multiple Organ Failure Research Articles

CLINICAL AND PATHOANATOMICAL PARALLELS OF THE HEART DAMAGE DUE TO COVID-19

The aim – to investigate the clinical and pathomorphological features of the heart damagein patients who died due to COVID-19 pneumonia.Materials and methods. A retrospective analysis of the medical records of 556 patients,hospitalized to Lviv Clinical Emergency Care Hospital in January- February 2021, witha diagnosis of COVID-19 pneumonia and 90 reports of pathological examination ofthe causes of death of patients with COVID-19 pneumonia was carried out. Clinicalparameters (demographic data, comorbidities, presence of COVID-19 pneumoniacomplications, complaints, medical history, results of physical examination andadditional laboratory and instrumental investigations, performed during hospitalization,including levels of NT-proBNP and troponin, determined by immunofluorescence method)and results of pathological examination were evaluated.The results. During life, most patients who died due to COVID-19 pneumonia werediagnosed with acute respiratory distress syndrome (ARDS), the development of multipleorgan failure, rarely PE. They showed significantly lower capillary blood oxygensaturation indicators compared to similar indicators of recovered patients, as well asan increase in markers of systemic inflammation (level of leukocytes and interleukin-6),fibrin degradation products (D-dimers) and markers of multiorgan failure (creatinine,NT-proBNP, troponin I). The most frequent pathomorphological signs of heartdamage in patients with COVID-19 were interstitial edema with hyperemia (63.5 %) and fragmentation of cardiomyocytes (34.1 %). Every fourth patient had mononuclear cell infiltration, which was associated with increased level of NTproBNP, oxygen saturationdecrease in capillary blood, and increase in aspartate aminotransferase. Myocardialinfarction, pericarditis, and myocarditis occurred more rarely in patients with COVID-19.Conclusions. The variety of clinical scenarios of heart damage requires a high level ofsuspicion in the early stages of the disease and the use of appropriate investigations toidentify its cause.

Predictive value of plasma biomarkers for mortality and organ failure development in patients with acute respiratory distress syndrome

PurposeTo evaluate the predictive value of 6 different biomarkers in the development of multiple-organ failure (MOF) and mortality in a contemporary prospective cohort of acute respiratory distress syndrome (ARDS). MethodsPatients with ARDS admitted to a tertiary referral center during an 8-month period were included. Plasma sample collection of 6 different biomarkers on days 1, 3, and 5 after ARDS onset was performed (von Willebrand factor, thrombin–antithrombin III complex, plasminogen activator inhibitor 1, interleukin 8, receptor for advanced glycation end-products, and club cell secretory protein). Main outcomes included hospital mortality and development of MOF. Logistic regression models for MOF and mortality prediction were created including biomarkers levels and clinical predictors. ResultsOne hundred patients were included in the study. Do-not-resuscitate status and McCabe score were independently associated with increased mortality. None of the 6 biomarkers measured at the time of ARDS diagnosis predicted hospital mortality. After adjustment for important clinical characteristics, elevated day-1 interleukin 8 levels were associated with the development of MOF. ConclusionsAddition of biomarkers did not improve mortality prediction in this cohort of ARDS. Association between elevated interleukin 8 levels and progression of organ failures suggests an important role of exaggerated inflammatory response in the development of MOF.

Insights into the apoptotic death of immune cells in sepsis.

Sepsis with subsequent multiple-organ dysfunction is a distinct systemic inflammatory response to concealed or obvious infection, and it is a leading cause of death in intensive care units. Thus, one of the key goals in critical care medicine is to develop novel therapeutic strategies that will affect favorably on outcome of septic patients. In addition to systemic response to infection, apoptosis is implicated to be an important mechanism of the death of immune cells, including neutrophils, macrophages, T lymphocytes, and dendritic cells, and it is usually followed by the development of multiple-organ failure in sepsis. The implication of apoptosis of immune cells is now highlighted by multiple studies that demonstrate that prevention of cell apoptosis can improve survival in relevant animal models of severe sepsis. In this review, we focus on major apoptotic death pathways and molecular mechanisms that regulate apoptosis of different immune cells, and advances in these areas that may be translated into more promising therapies for the prevention and treatment of severe sepsis.

Debunking the survival bias myth

Controversy surrounds the optimal ratios of blood (packed red blood cell [PRBC]), plasma (fresh frozen plasma [FFP]) and platelet (PLT) use for patients requiring massive transfusion (MT) owing to possible survival bias in previous studies. We sought to characterize mortality during the first 24 hours while controlling for time varying effects of transfusion to minimize survival bias. Data were obtained from a multicenter prospective cohort study of adults with blunt injury and hemorrhagic shock. MT was defined as 10 U of PRBC or more over 24 hours. High FFP/PRBC (≥1:1.5) and PLT/PRBC (≥1:9) ratios at 6, 12, and 24 hours were compared with low ratio groups. Cox proportional hazards regression was used to determine the independent association of high versus low ratios with mortality at 6, 12, and 24 hours while controlling for important confounders. Cox proportional hazards regression was repeated with FFP/PRBC and PLT/PRBC ratios analyzed as time-dependent covariates to account for fluctuation over time. Mortality for more than 24 hours was treated as survival. In the MT cohort (n = 604), initial base deficit, lactate, and international normalized ratio were similar across high and low ratio groups. High 6-hour FFP/PRBC and PLT/PRBC ratios were independently associated with a reduction in mortality risk at 6, 12, and 24 hours (hazard ratio [HR] range, 0.20-0.41, p < 0.05). These findings were consistent for 12-hour and 24-hour ratios. When analyzed as time-dependent covariates, a high FFP/PRBC ratio was associated with a 68% (HR, 0.32; 95% confidence interval [CI], 0.12-0.87, p = 0.03) reduction in 24-hour mortality, and a high PLT/PRBC ratio was associated with a 96% (HR, 0.04; 95% CI, 0.01-0.94, p = 0.04) reduction in 24-hour mortality. Subgroup analysis revealed that a high 1:1 ratio (≥1:1.5) had a significant 24-hour survival benefit relative to a high 1:2 (1:1.51-1:2.50) ratio group at both 6 hours (HR, 0.19; 95% CI, 0.03-0.86, p = 0.03) and 24 hours (HR, 0.25; 95% CI, 0.06-0.95, p = 0.04), suggesting a dose-response relationship. A high FFP/PRBC or PLT/PRBC ratio was not associated with development of multiple-organ failure, nosocomial infection, or adult respiratory distress syndrome in a 28-day Cox proportional hazards regression. Despite similar degrees of early shock and coagulopathy, high FFP/PRBC and PLT/PRBC ratios are associated with a survival benefit as early as 6 hours and throughout the first 24 hours, even when time-dependent fluctuations of component transfusion are accounted for. This suggests that the observed mortality benefit associated with high component transfusion ratios is unlikely owing to survivor bias and that early attainment of high transfusion ratios may significantly lower the risk of mortality in MT patients.

Synbiotics, Prebiotics, Glutamine, or Peptide in Early Enteral Nutrition: A Randomized Study in Trauma Patients

Since the hepatosplanchnic region plays a central role in development of multiple-organ failure and infections in critically ill trauma patients, this study focuses on the influence of glutamine, peptide, and synbiotics on intestinal permeability and clinical outcome. One hundred thirteen multiple injured patients were prospectively randomized into 4 groups: group A, glutamine; B, fermentable fiber; C, peptide diet; and D, standard enteral formula with fibers combined with Synbiotic 2000 (Synbiotic 2000 Forte; Medifarm, Sweden), a formula containing live lactobacilli and specific bioactive fibers. Intestinal permeability was evaluated by measuring lactulose-mannitol excretion ratio on days 2, 4, and 7. No differences in days of mechanical ventilation, intensive care unit stay, or multiple-organ failure scores were found between the patient groups. A total of 51 infections, including 38 pneumonia, were observed, with only 5 infections and 4 pneumonias in group D, which was significantly less than combined infections (p = .003) and pneumonias (p = .03) in groups A, B, and C. Intestinal permeability decreased only in group D, from 0.148 (0.056-0.240) on day 4 to 0.061 (0.040-0.099) on day 7; (p < .05). In group A, the lactulose-mannitol excretion ratio increased significantly (p < .02) from 0.050 (0.013-0.116) on day 2 to 0.159 (0.088-0.311) on day 7. The total gastric retention volume in 7 days was 1150 (785-2395) mL in group D, which was significantly more than the 410 (382-1062) mL in group A (p < .02), and 620 (337-1190) mL in group C (p < .03). Patients supplemented with synbiotics did better than the others, with lower intestinal permeability and fewer infections.

Multiple-Organ Failure and the Gut

It has been suggested that gut hypoxia is important in the development of multiple-organ failure, by triggering increased mediator release, and through altered gut mucosal permeability leading to incr

Alterations in Regional Blood Flow During Positive End-Expiratory Pressure Ventilation

PEEP improves the gas-exchange abnormalities that accompany adult respiratory distress syndrome (ARDS). However, since PEEP decreases cardiac output, it may also alter regional blood flow and therefore, substrate delivery to specific organs. To test this hypothesis, radiolabeled 15-mu microspheres were used to directly quantify the effects of mechanical ventilation with PEEP on regional blood flow to individual organs in animals. Mechanical ventilation alone produced a -21.2 +/- 3.6% and a -28.1 +/- 5.2% decrease in cardiac output at 30 and 60 min, respectively. The addition of 14 cm H2O PEEP resulted in little further reduction in cardiac output at 30 and 60 min (-28 +/- 2.3% and -36.4 +/- 4.9%, respectively). However, 25 cm H2O PEEP reduced markedly (p less than .01) cardiac output (-59.2 +/- 6.1% at 30 min and -55.1 +/- 4.0% at 60 min). Although blood flows to the kidney and brain were maintained, decreases in cardiac output were invariably accompanied by proportional decreases in blood flow to the heart. Intravascular volume expansion with saline (20 ml/kg) during 14 cm H2O PEEP significantly improved cardiac output (3.23 +/- 0.34 to 4.22 +/- 0.13 L/min; p less than .01) and proportionately increased blood flow to several regional vascular beds, including the heart. These data suggest that PEEP decreases cardiac output to produce reversible alterations in blood flow to a number of regional vascular beds. These PEEP-induced alterations in regional blood flow may have important implications for the development of multiple-organ failure in ARDS patients.