Rashid Alobaidi1, Catherine Morgan2, Rajit K Basu3, Erin Stenson4, Robin Featherstone5, Sumit R Majumdar6, Sean M Bagshaw7. 1. Division of Pediatric Critical Care, Department of Pediatrics, Stollery Children's Hospital, Edmonton, Alberta, Canada. 2. Division of Nephrology, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. 3. Division of Critical Care Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia. 4. Division of Critical Care Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 5. Alberta Strategy for Patient-Oriented Research (SPOR) SUPPORT Unit Knowledge Translation Platform, Alberta Research Center for Health Evidence (ARCHE), Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. 6. Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. 7. Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Abstract
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.
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.
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