Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Bline KE
PROVIDER: S-EPMC7650515 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis.
Bline Katherine E KE Moore-Clingenpeel Melissa M Hensley Josey J Steele Lisa L Greathouse Kristin K Anglim Larissa L Hanson-Huber Lisa L Nateri Jyotsna J Muszynski Jennifer A JA Ramilo Octavio O Hall Mark W MW
Critical care (London, England) 20200904 1
<h4>Background</h4>Severe critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test ...[more]
Similar Datasets
Project description:To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis.Retrospective cohort study.Tertiary care children's hospital from January 1, 2012, to March 31, 2014.Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included.The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4).Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.
| S-EPMC5008999 | biostudies-literature
Project description:ObjectivesInfants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown.InterventionsOne hundred and twenty-eight consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed versus standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1-2 units on the day of surgery was performed.Measurements and main resultsMortality was low (4.9%) with no association between RBC storage duration and survival. The postoperative infection rate was significantly higher in children receiving the oldest blood (25-38 d) compared with those receiving the freshest RBCs (7-15 d) (34% vs 7%; p = 0.004). Subgroup analysis of subjects receiving only 1-2 RBC transfusions on the day of surgery (n = 74) also demonstrates a greater prevalence of infections in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage; 1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage; p = 0.01). In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of postoperative infection. Washing the oldest RBCs (> 27 d) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs.DiscussionLonger RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single-donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on postoperative infection rate in pediatric cardiac surgery are warranted.
| S-EPMC4351137 | biostudies-literature
Project description:Although many forms of critical illness are initiated by a proinflammatory stimulus, a compensatory anti-inflammatory response can occur with systemic inflammation. Immunoparalysis, an important form of acquired immunodeficiency, affects the innate and adaptive arms of the immune system. Immunoparalysis has been associated with increased risks for nosocomial infection and death in a variety of pediatric critical illnesses. Evidence suggests that immunoparalysis is reversible with immunostimulants. Highly standardized, prospective immune monitoring regimens are needed to better understand the immunologic effects of critical care treatment regimens and to enrich clinical trials with subjects most likely to benefit from immunostimulatory therapies.
| S-EPMC5724958 | biostudies-literature
Project description: Not available
| S-EPMC6900703 | biostudies-literature
Project description:Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS.In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28.Over the course of 4 years, 197 patients were randomized to either hydrocortisone (n?=?98) or placebo (n?=?99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p?=?0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51-1.07; p?=?0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46-1.41; p?=?0.44) and for the larger subgroup (n?=?126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24-1.36; p?=?0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p?=?0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome.In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit.ClinicalTrials.gov identifier NCT01284452 . Registered on 18 January 2011.
| S-EPMC5065699 | biostudies-literature
Project description:IntroductionThe aim of this study was to assess the effect of low-dose corticosteroid therapy in reducing shock duration after severe burn.MethodsA placebo-controlled, double-blind, randomized clinical trial (RCT) was performed on two parallel groups in the burn intensive care unit (ICU). Patients were randomized to receive either low-dose corticosteroid therapy or placebo for seven days. A corticotropin test was performed at the time of randomization, before the administration of the treatment dose. Thirty-two severely burned patients with refractory shock (>0.5 μg/kg/min of norepinephrine) were prospectively included in the study.ResultsWe included 12 patients in the hydrocortisone-treated group and 15 patients in the placebo group in the final analysis. Among these patients, 21 were nonresponders to the corticotropin test. Median norepinephrine treatment duration (primary objective) was significantly lower in the corticosteroid-treated versus the placebo group (57 hours versus 120 hours, P = 0.035). The number of patients without norepinephrine 72 hours after inclusion was significantly lower in the treated group (P = 0.003, log-rank test analysis). The total quantities of norepinephrine administered to patients were lower in the hydrocortisone-treated versus the placebo group (1,205 μg/kg (1,079 to 2,167) versus 1,971 μg/kg (1,535 to 3,893), P = 0.067). There was no difference in terms of ICU or hospital length of stay, sepsis incidence, cicatrization or mortality.ConclusionsIn this placebo-controlled, randomized, double-blind clinical trial, we show for the first time that the administration of low-dose hydrocortisone in burn patients with severe shock reduces vasopressor administration.Trial registrationClinicaltrial.gov NCT00149123 . Registered 6 September 2005.
| S-EPMC4347659 | biostudies-literature
Project description:To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies.Observational cohort study from 2004 to 2012.Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database.Children 18 years old or younger.We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort.Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to seven-fold depending on the strategy used for case ascertainment.
| S-EPMC4221502 | biostudies-literature
Project description:Background: Early detection of pediatric severe sepsis is necessary in order to optimize effective treatment, and new methods are needed to facilitate this early detection. Objective: Can a machine-learning based prediction algorithm using electronic healthcare record (EHR) data predict severe sepsis onset in pediatric populations? Methods: EHR data were collected from a retrospective set of de-identified pediatric inpatient and emergency encounters for patients between 2-17 years of age, drawn from the University of California San Francisco (UCSF) Medical Center, with encounter dates between June 2011 and March 2016. Results: Pediatric patients (n = 9,486) were identified and 101 (1.06%) were labeled with severe sepsis following the pediatric severe sepsis definition of Goldstein et al. (1). In 4-fold cross-validation evaluations, the machine learning algorithm achieved an AUROC of 0.916 for discrimination between severe sepsis and control pediatric patients at the time of onset and AUROC of 0.718 at 4 h before onset. The prediction algorithm significantly outperformed the Pediatric Logistic Organ Dysfunction score (PELOD-2) (p < 0.05) and pediatric Systemic Inflammatory Response Syndrome (SIRS) (p < 0.05) in the prediction of severe sepsis 4 h before onset using cross-validation and pairwise t-tests. Conclusion: This machine learning algorithm has the potential to deliver high-performance severe sepsis detection and prediction through automated monitoring of EHR data for pediatric inpatients, which may enable earlier sepsis recognition and treatment initiation.
| S-EPMC6798083 | biostudies-literature
Project description:ObjectivesSevere sepsis is a significant cause of healthcare use and morbidity among pediatric patients, but little is known about readmission diagnoses. We sought to determine the most common readmission diagnoses after pediatric severe sepsis, the extent to which post-sepsis readmissions may be potentially preventable, and whether patterns of readmission diagnoses differ compared with readmissions after other common acute medical hospitalizations.DesignObservational cohort study.SettingNational Readmission Database (2013-2014), including all-payer hospitalizations from 22 states.PatientsFour-thousand five-hundred twenty-eight pediatric severe sepsis hospitalizations, matched by age, gender, comorbidities, and length of stay to 4,528 pediatric hospitalizations for other common acute medical conditions.InterventionsNone.Measurements and main resultsWe compared rates of 30-day all cause, diagnosis-specific, and potentially preventable hospital readmissions using McNemar's chi-square tests for paired data. Among 5,841 eligible pediatric severe sepsis hospitalizations with live discharge, 4,528 (77.5%) were matched 1:1 to 4,528 pediatric hospitalizations for other acute medical conditions. Of 4,528 matched sepsis hospitalizations, 851 (18.8% [95% CI, 16.0-18.2]) were rehospitalized within 30 days, compared with 775 (17.1% [95% CI, 17.1-20.0]) of matched hospitalizations for other causes (p = 0.02). The most common readmission diagnoses were chemotherapy, device complications, and sepsis, all of which were several-fold higher after sepsis versus after matched nonsepsis hospitalization. Only 11.5% of readmissions were for ambulatory care sensitive conditions compared with 23% of rehospitalizations after common acute medical conditions.ConclusionsMore than one in six children surviving severe sepsis were rehospitalized within 30 days, most commonly for maintenance chemotherapy, medical device complications, or recurrent sepsis. Only a small proportion of readmissions were for ambulatory care sensitive conditions.
| S-EPMC6535212 | biostudies-literature
Project description:ImportanceSepsis is a leading cause of morbidity and mortality in the United States and disparate outcomes exist between racial/ethnic groups despite improvements in sepsis management. These observed differences are often related to social determinants of health (SDoH). Little is known about the role of SDoH on outcomes in pediatric sepsis.ObjectiveThis study examined the differences in care delivery and outcomes in children with severe sepsis based on race/ethnicity and neighborhood context (as measured by the social vulnerability index).Design setting and participantsThis retrospective, cross-sectional study was completed in a quaternary care children's hospital. Patients 18 years old or younger who were admitted between May 1, 2018, and February 28, 2022, met the improving pediatric sepsis outcomes (IPSO) collaborative definition for severe sepsis. Composite measures of social vulnerability, care delivery, and clinical outcomes were stratified by race/ethnicity.Main outcomes and measuresThe primary outcome of interest was admission to the PICU. Secondary outcomes were sepsis recognition and early goal-directed therapy (EGDT).ResultsA total of 967 children met the criteria for IPSO-defined severe sepsis, of whom 53.4% were White/non-Hispanic. Nearly half of the cohort (48.7%) required PICU admission. There was no difference in illness severity at PICU admission by race (1.01 vs. 1.1, p = 0.18). Non-White race/Hispanic ethnicity was independently associated with PICU admission (odds ratio [OR] 1.35 [1.01-1.8], p = 0.04). Although social vulnerability was not independently associated with PICU admission (OR 0.95 [0.59-1.53], p = 0.83), non-White children were significantly more likely to reside in vulnerable neighborhoods (0.66 vs. 0.38, p < 0.001). Non-White race was associated with lower sepsis recognition (87.8% vs. 93.6%, p = 0.002) and less EGDT compliance (35.7% vs. 42.8%, p = 0.024).Conclusions and relevanceNon-White race/ethnicity was independently associated with PICU admission. Differences in care delivery were also identified. Prospective studies are needed to further investigate these findings.
| S-EPMC10896474 | biostudies-literature