Dataset Information

Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis.

ABSTRACT: To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis.This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ?5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ?5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission.Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ?10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ?10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08-1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15-25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ?10%: 4 [3-8], 7 [4-11] vs. 10 [6-16] days; P <0.001; n = 154) and in survivors (4 [3-8], 7 [5-11] vs. 10 [5-15] days; P <0.001; n = 121). Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65-0.82; P <0.001; n = 202) for predicting mortality in patients with severe sepsis, with a sensitivity of 67.2% and a specificity of 80.1% at the optimal cut-off value of 2.65%.Both early and acquired daily fluid overload were independently associated with PICU mortality in children with severe sepsis.

SUBMITTER: Chen J

PROVIDER: S-EPMC4965086 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis.

Chen Jiao J Li Xiaozhong X Bai Zhenjiang Z Fang Fang F Hua Jun J Li Ying Y Pan Jian J Wang Jian J Feng Xing X Li Yanhong Y

PloS one 20160728 7

<h4>Objective</h4>To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis.<h4>Methods</h4>This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the ne ...[more]

PMID: 27467522

Similar Datasets

Project description:Importance:After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes. Objective:To describe the methods to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Data Sources:Systematic search of MEDLINE, EMBASE, Cochrane Library, trial registries, and selected gray literature from inception to March 2017. Study Selection:Studies of children admitted to pediatric intensive care units that described fluid balance or fluid overload and reported outcomes of interest were included. No language restrictions were applied. Data Extraction and Synthesis:All stages were conducted independently by 2 reviewers. Data extracted included study characteristics, population, fluid metrics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative description of fluid assessment methods and fluid overload definitions was done. When feasible, pooled analyses were performed using random-effects models. Main Outcomes and Measures:Mortality was the primary outcome. Secondary outcomes included treatment intensity, organ failure, and resource use. Results:A total of 44 studies (7507 children) were included in this systematic review and meta-analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%) was a secondary analysis of a randomized trial. The proportion of children with fluid overload varied by case mix and fluid overload definition (median, 33%; range, 10%-83%). Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n?=?2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2?=?61%). Survivors had lower percentage fluid overload than nonsurvivors (22 studies [n?=?2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2?=?76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n?=?3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2?=?66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n?=?631]; OR, 2.14 [95% CI, 1.25-3.66]; I2?=?0%) and acute kidney injury (7 studies [n?=?1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2?=?78%). Conclusions and Relevance:Fluid overload is common and is associated with substantial morbidity and mortality in critically ill children. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.

Project description:Furosemide is commonly prescribed in critically ill patients to increase the urine output and prevent fluid overload (FO) and acute kidney injury (AKI), but not supported by conclusive evidence. There remain conflicting findings on whether furosemide associates with AKI and adverse outcomes. Information on the impact of furosemide on adverse outcomes in a general population of pediatric intensive care unit (PICU) is limited. The aim of the cohort study was to investigate the associations of furosemide with AKI and clinical outcomes in critically ill children. Study Design: We retrospectively reviewed a cohort of 456 critically ill children consecutively admitted to PICU from January to December 2016. The exposure of interest was the use of furosemide in the first week after admission. FO was defined as ≥5% of daily fluid accumulation, and mean FO was considered significant when mean daily fluid accumulation during the first week was ≥5%. The primary outcomes were AKI in the first week after admission and mortality during PICU stay. AKI diagnosis was based on Kidney Disease: Improving Global Outcomes criteria with both serum creatinine and urine output. Results: Furosemide exposure occurred in 43.4% of all patients (n = 456) and 49.3% of those who developed FO (n = 150) in the first week after admission. Patients who were exposed to furosemide had significantly less degree of mean daily fluid accumulation than those who were not (1.10 [-0.33 to 2.61%] vs. 2.00 [0.54-3.70%], P < 0.001). There was no difference in the occurrence of AKI between patients who did and did not receive furosemide (22 of 198 [11.1%] vs. 36 of 258 [14.0%], P = 0.397). The mortality rate was 15.4% (70 of 456), and death occurred more frequently among patients who received furosemide than among those who did not (21.7 vs. 10.5%, P = 0.002). Furosemide exposure was associated with increased odds for mortality in a multivariate logistic regression model adjusted for body weight, gender, illness severity assessed by PRISM III score, the presence of mean FO, and AKI stage [adjusted odds ratio (AOR) 1.95; 95%CI, 1.08-3.52; P = 0.026]. Conclusion: Exposure to furosemide might be associated with increased risk for mortality, but not AKI, in critically ill children.

Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyteÂ® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyteÂ® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyteÂ® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyteÂ® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyteÂ® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyteÂ® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator

Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.

Project description:BACKGROUND:Data that indicate vitamin A status in critically ill children with sepsis are sparse. The association between serum vitamin A levels and the clinical outcomes of sepsis has not been well assessed. The aim of this study was to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. METHODS:Critically ill children with sepsis admitted to the pediatric intensive care unit were engaged in this prospective study. Sex- and age-matched approximate-health children from the Department of Pediatric Surgery were enrolled as the control group. Blood samples were collected from all patients in the first 24?h of admission for the measurement of serum vitamin A status. We compared vitamin A status between the sepsis group and the control group. In addition, we compared the clinical characteristics of the two subgroups of septic patients with vitamin A deficiency and those without vitamin A deficiency. Univariate and multivariable methods were used to evaluate the association between vitamin A deficiency and septic shock. RESULTS:One hundred sixty septic children and 49 approximate-health children were enrolled in this study. Vitamin A deficiency was found in 94 (58.8%) subjects in the study group and 6 (12.2%) subjects in the control group (P?<?0.001). In septic patients, 28-day mortality and hospital mortality in patients with vitamin A deficiency were not significantly higher than that in patients without vitamin A deficiency (P?>?0.05). However, vitamin A levels were inversely associated with higher PRISM scores in septic children with VAD (r?=?-?0.260, P?=?0.012). Vitamin A deficiency was associated with septic shock with an unadjusted odds ratio (OR) of 3.297 (95% confidence interval (CI), 1.169 to 9.300; P?=?0.024). In a logistic model, vitamin A deficiency (OR, 4.630; 95% CI, 1.027-20.866; P?=?0.046), procalcitonin (OR, 1.029; 95% CI, 1.009-1.048; P?=?0.003), and the Pediatric Risk of Mortality scores (OR, 1.132; 95% CI, 1.009-1.228; P?=?0.003) were independently associated with septic shock. CONCLUSION:The prevalence of vitamin A deficiency was high in children with sepsis. Vitamin A deficiency may be a marker of mortality in critically ill children with sepsis. TRIAL REGISTRATION:Clinicaltrials.gov , NCT03598127.

Project description:In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms.Multicentered retrospective cohort study.Five pediatric intensive care units.Mechanically ventilated children (age?1 month to <18 yrs) with acute lung injury admitted in 2007-2010.None.Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p<.001, each day) and was similar to adults in the liberal arm.Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.

Dataset Information

Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis.

Publications

Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets