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      Associations of resuscitation fluid load, colloid-to-crystalloid infusion ratio and clinical outcomes in children with dengue shock syndrome

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          Abstract

          Background

          Severe respiratory distress and acute kidney injury (AKI) are key factors leading to poor outcomes in patients with dengue shock syndrome (DSS). There is still limited data on how much resuscitated fluid and the specific ratios of intravenous fluid types contribute to the development of severe respiratory distress necessitating mechanical ventilation (MV) and AKI in children with DSS.

          Methodology/principal findings

          This retrospective study was conducted at a tertiary pediatric hospital in Vietnam between 2013 and 2022. The primary outcomes were the need for MV and renal function within 48 h post-admission. A predictive model for MV was developed based on covariates from the first 24 h of PICU admission. Changes in renal function within 48 h were analyzed using a linear mixed-effects model. A total of 1,278 DSS children with complete clinical and fluid data were included. The predictive performance of MV based on the total intravenous fluid volume administered yielded an AUC of 0.871 (95% CI, 0.836–0.905), while the colloid-to-crystalloid ratio showed an AUC of 0.781 (95% CI, 0.743–0.819) (both P < 0.001). The optimal cut-off point of the cumulative fluid infusion was 181 mL/kg, whereas that of the colloid-to-crystalloid ratio was 1.6. Multivariable analysis identified female patients, severe bleeding, severe transaminitis, excessive fluid resuscitation, and a higher proportion of colloid solutions in the first 24 h as significant predictors of MV in DSS patients. The predictive model for MV demonstrated high accuracy, with a C-statistic of 89%, strong calibration, and low Brier score (0.04). Importantly, a more pronounced decline in glomerular filtration rate was observed in DSS patients who required MV than in those who did not.

          Conclusions/significance

          This study provides insights into optimizing fluid management protocols, highlighting the importance of monitoring fluid volume and the colloid-to-crystalloid ratio during early resuscitation to improve the clinical outcomes of DSS patients.

          Author summary

          Dengue shock syndrome (DSS) in children admitted to the pediatric intensive care unit (PICU) has mortality rates ranging from 5% to > 20%, particularly in those with prolonged shock, severe respiratory distress requiring mechanical ventilation (MV), and acute kidney injury (AKI). Although colloidal solutions are commonly used in severe DSS management, excessive use can lead to respiratory failure and AKI, raising concerns regarding optimal fluid strategies. This study analyzed 1,278 children with DSS and found that 13.3% required MV, with a significantly higher mortality rate in the MV group (22.4%) than in the non-MV group (0.1%). Both the total intravenous fluid volume and colloid-to-crystalloid ratio were strong predictors of MV, with optimal cut-offs of 181 mL/kg for fluid volume and a ratio of 1.6. In practice, a cut-off of colloid-to-crystalloid ratio ≥ 1.6 may indicate the need to transition to alternative fluids such as albumin or fresh frozen plasma. Moreover, a marked reduction in the estimated glomerular filtration rate (eGFR) was observed in the MV group, indicating a link between fluid management and renal function. These findings underscore the importance of fluid management in DSS, providing key predictors of MV and AKI to guide treatment and improve the clinical outcomes.

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          Most cited references31

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          Assessing the performance of prediction models: a framework for traditional and novel measures.

          The performance of prediction models can be assessed using a variety of methods and metrics. Traditional measures for binary and survival outcomes include the Brier score to indicate overall model performance, the concordance (or c) statistic for discriminative ability (or area under the receiver operating characteristic [ROC] curve), and goodness-of-fit statistics for calibration.Several new measures have recently been proposed that can be seen as refinements of discrimination measures, including variants of the c statistic for survival, reclassification tables, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Moreover, decision-analytic measures have been proposed, including decision curves to plot the net benefit achieved by making decisions based on model predictions.We aimed to define the role of these relatively novel approaches in the evaluation of the performance of prediction models. For illustration, we present a case study of predicting the presence of residual tumor versus benign tissue in patients with testicular cancer (n = 544 for model development, n = 273 for external validation).We suggest that reporting discrimination and calibration will always be important for a prediction model. Decision-analytic measures should be reported if the predictive model is to be used for clinical decisions. Other measures of performance may be warranted in specific applications, such as reclassification metrics to gain insight into the value of adding a novel predictor to an established model.
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            Association Between Fluid Balance and Outcomes in Critically Ill Children

            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.
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              Comparison of three fluid solutions for resuscitation in dengue shock syndrome.

              Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based. We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with dengue shock syndrome. We randomly assigned 383 children with moderately severe shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid. Only one patient died (<0.2 percent mortality). The primary outcome measure--requirement for rescue colloid--was similar for the different fluids in the two severity groups. The relative risk of requirement for rescue colloid was 1.08 (95 percent confidence interval, 0.78 to 1.47; P=0.65) among children with moderate shock who received Ringer's lactate as compared with either of the colloid solutions, 1.13 (95 percent confidence interval, 0.74 to 1.74; P=0.59) among children who received dextran as compared with starch in the group with severe shock, and 0.88 (95 percent confidence interval, 0.66 to 1.17; P=0.38) among children who received dextran as compared with starch in the combined analysis. Although treatment with Ringer's lactate resulted in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions, there were no differences in all other measures of treatment response. Only minor differences in efficacy were detected between the two colloids, but significantly more recipients of dextran than of starch had adverse reactions. Bleeding manifestations, coagulation derangements, and severity of fluid overload were similar for all fluid-treatment groups. Initial resuscitation with Ringer's lactate is indicated for children with moderately severe dengue shock syndrome. Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock, but given the adverse reactions associated with the use of dextran, starch may be preferable for this group. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLOS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                10 January 2025
                January 2025
                : 19
                : 1
                : e0012786
                Affiliations
                [1 ] Department of Infectious Diseases, Children’s Hospital 2, Ho Chi Minh City, Vietnam
                [2 ] Department of Family Medicine, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
                [3 ] Department of Pediatric Cardiology, Children’s Hospital 2, Ho Chi Minh City, Vietnam
                [4 ] Department of Tuberculosis, Woolcock Institute of Medical Research, Ho Chi Minh City, Vietnam
                Zhejiang Wanli University, CHINA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-7600-6757
                Article
                PNTD-D-24-01370
                10.1371/journal.pntd.0012786
                11756768
                39792932
                32a5100c-4f83-41ec-bac0-f31d790ed932
                © 2025 Luan et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 September 2024
                : 16 December 2024
                Page count
                Figures: 4, Tables: 4, Pages: 17
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Dengue Fever
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Dengue Fever
                Physical Sciences
                Materials Science
                Materials
                Mixtures
                Colloids
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Resuscitation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Vascular Medicine
                Hemorrhage
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
                Physiology
                Renal Physiology
                Glomerular Filtration Rate
                Custom metadata
                vor-update-to-uncorrected-proof
                2025-01-23
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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