Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

PURPOSE: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. RESULTS: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). CONCLUSIONS: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

Outcomes of Prophylactic Peritoneal Dialysis Catheter Insertion in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: The objective of this Prospective Register of Systematic Reviews (CRD42022384192) registered systematic review and meta-analysis was to determine whether prophylactic peritoneal dialysis (PD) catheter insertion at the time of pediatric cardiac surgery is associated with improved short-term outcomes. DATA SOURCES: Databases search of the MEDLINE, EMBASE, CINAHL, and Cochrane Library completed in April 2021 and updated October 2023. STUDY SELECTION: Two reviewers independently completed study selection, data extraction, and bias assessment. Inclusion criteria were randomized controlled trials (RCTs) and observational studies of children (≤ 18 yr) undergoing cardiac surgery with cardiopulmonary bypass. We evaluated use of prophylactic PD catheter versus not. DATA EXTRACTION: The primary outcome was in-hospital mortality, as well as secondary short-term outcomes. Pooled random-effect meta-analysis odds ratio with 95% CI are reported. DATA SYNTHESIS: Seventeen studies met inclusion criteria, including four RCTs. The non-PD catheter group received supportive care that included diuretics and late placement of PD catheters in the ICU. Most study populations included children younger than 1 year and weight less than 10 kg. Cardiac surgery was most commonly used for arterial switch operation. In-hospital mortality was reported in 13 studies; pooled analysis showed no association between prophylactic PD catheter placement and in-hospital mortality. There were mixed results for ICU length of stay and time to negative fluid balance, with some studies showing shortened duration associated with use of prophylactic PD catheter insertion and others showing no difference. Overall, the studies had high risk for bias, mainly due to small sample size and lack of generalizability. CONCLUSIONS: In this meta-analysis, we have failed to demonstrate an association between prophylactic PD catheter insertion in children and infants undergoing cardiac surgery and reduced in-hospital mortality. Other relevant short-term outcomes, including markers of fluid overload, require further study.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Epidemiology of acute kidney injury in children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Acute Kidney Injury in Critically Ill Children Is Not all Acute: Lessons Over the Last 5 Years.

Acute kidney injury (AKI) in the pediatric intensive care unit (PICU) is an important risk factor for increased morbidity and mortality during hospitalization. Over the past decade, accumulated data on children and young people indicates that acute episodes of kidney dysfunction can have lasting consequences on multiple organ systems and health outcomes. To date, there are no guidelines for follow-up of surviving children that may be at risk of long-term sequelae following AKI in the PICU. This narrative review aims to describe literature from the last 5 years on the risk of medium and long-term kidney and non-kidney outcomes after AKI in the PICU. More specifically, we will focus on outcomes in children and young people following AKI in the general PICU population and children undergoing cardiac surgery. These outcomes include mortality, hypertension, proteinuria, chronic kidney disease, and healthcare utilization. We also aim to highlight current gaps in knowledge in medium and long-term outcomes in this pediatric population. We suggest a framework for future research to develop evidence-based guidelines for follow-up of children surviving an episode of critical illness and AKI.

Association Between Acute Kidney Injury Duration and Outcomes in Critically Ill Children.

OBJECTIVES: Acute kidney injury occurs frequently in children during critical illness and is associated with increased morbidity, mortality, and health resource utilization. We aimed to examine the association between acute kidney injury duration and these outcomes. DESIGN: Retrospective cohort study. SETTINGS: PICUs in Alberta, Canada. PATIENTS: All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 1,017 children were included, and 308 (30.3%) developed acute kidney injury during PICU stay. Acute kidney injury was categorized based on duration to transient (48 hr or less) or persistent (more than 48 hr). Transient acute kidney injury occurred in 240 children (77.9%), whereas 68 children (22.1%) had persistent acute kidney injury. Persistent acute kidney injury had a higher proportion of stage 2 and stage 3 acute kidney injury compared with transient acute kidney injury and was more likely to start within 24 hours from PICU admission. Persistent acute kidney injury occurred more frequently in those with higher illness severity and in those admitted with shock, sepsis, or with a history of transplant. Mortality varied significantly according to acute kidney injury status: 1.8% of children with no acute kidney injury, 5.4% with transient acute kidney injury, and 17.6% with persistent acute kidney injury died during hospital stay (p < 0.001). On multivariable analysis adjusting for illness and acute kidney injury severity, transient and persistent acute kidney injury were both associated with fewer ventilation-free days at 28 days (-1.28 d; 95% CI, -2.29 to -0.26 and -4.85 d; 95% CI, -6.82 to -2.88), vasoactive support-free days (-1.07 d; 95% CI, -2.00 to -0.15 and -4.24 d; 95% CI, -6.03 to -2.45), and hospital-free days (-1.93 d; 95% CI, -3.36 to -0.49 and -5.25 d; 95% CI, -8.03 to -2.47), respectively. CONCLUSIONS: In critically ill children, persistent and transient acute kidney injury have different clinical characteristics and association with outcomes. Acute kidney injury, even when its duration is short, carries significant association with worse outcomes. This risk increases further if acute kidney injury persists longer independent of the degree of its severity.

Clinical phenotypes of acute kidney injury are associated with unique outcomes in critically ill septic children.

BACKGROUND: Assessment of acute kidney injury (AKI) in septic patients remains imprecise. In adults, the classification of septic patients by clinical AKI phenotypes (severity and timing) demonstrates unique associations with patient outcome vs. broadly defined AKI. METHODS: In a multinational prospective observational study, AKI diagnosis in critically ill septic children was stratified by duration (transient vs. persistent) and severity (mild vs. severe by creatinine change and urine output). The outcomes of interest were mortality and intensive care unit resource complexity at 28 days. RESULTS: Seven hundred and fifty-seven septic children were studied (male 52.7%, age 4.6 years (1.5-11.9)). Mortality (overall 12.1%) was different between severe AKI and mild AKI (18.3 vs. 4.4%, p < 0.001) as well as intensive care unit (ICU) complexity (overall 34.5%, 45 vs. 21.7%, p < 0.001). Patients with Persistent AKI had fewer ICU-free days (17 (7, 21) vs. 24 (17, 26), p < 0.001) and higher ICU complexity (52.8 vs. 22.9%, p = 0.002) than transient AKI, even after exclusion of patients with early mortality. AKI phenotypes incorporating temporal and severity data correlate with unique survival (range 4.4-21.6%) and ICU-free days (range of 15-25 days) CONCLUSIONS: The outcome of septic children with AKI changes by clinical phenotype. Our findings underscore the importance of prognostic enrichment in sepsis and AKI for the purpose of trial design and patient management. IMPACT: Although AKI occurs commonly in patients with sepsis (S-AKI), outcomes for children with S-AKI varies based on the severity and timing of the AKI. Existing S-AKI pediatric data utilize a broad singular definition of kidney injury. Increasing the precision of AKI classification results in a new understanding of how S-AKI associates with patient outcome. A refined classification of S-AKI identifies subgroups of children, making possible a targeted and a personalized medicine approach to S-AKI study and management.

Fluid Accumulation in Critically Ill Children.

OBJECTIVES: To describe the characteristics of fluid accumulation in critically ill children and evaluate the association between the degree, timing, duration, and rate of fluid accumulation and patient outcomes. DESIGN: Retrospective cohort study. SETTING: PICUs in Alberta, Canada. PATIENTS: All children admitted to PICU in Alberta, Canada, between January 1, 2015, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,017 patients were included. Fluid overload % increased from median (interquartile range) 1.58% (0.23-3.56%; n = 1,017) on day 1 to 16.42% (7.53-27.34%; n = 111) on day 10 among those remaining in PICU. The proportion of patients (95% CI) with peak fluid overload % greater than 10% and greater than 20% was 32.7% (29.8-35.7%) and 9.1% (7.4-11.1%), respectively. Thirty-two children died (3.1%) in PICU. Peak fluid overload % was associated with greater PICU mortality (odds ratio, 1.05; 95% CI, 1.02-1.09; p = 0.001). Greater peak fluid overload % was associated with Major Adverse Kidney Events within 30 days (odds ratio, 1.05; 95% CI, 1.02-1.08; p = 0.001), length of mechanical ventilation (B coefficient, 0.66; 95% CI, 0.54-0.77; p < 0.001), and length of PICU stay (B coefficient, 0.52; 95% CI, 0.46-0.58; p < 0.001). The rate of fluid accumulation was associated with PICU mortality (odds ratio, 1.15; 95% CI, 1.01-1.31; p = 0.04), Major Adverse Kidney Events within 30 days (odds ratio, 1.16; 95% CI, 1.03-1.30; p = 0.02), length of mechanical ventilation (B coefficient, 0.80; 95% CI, 0.24-1.36; p = 0.005), and length of PICU stay (B coefficient, 0.38; 95% CI, 0.11-0.66; p = 0.007). CONCLUSIONS: Fluid accumulation occurs commonly during PICU course and is associated with considerable mortality and morbidity. These findings highlight the need for the development and evaluation of interventional strategies to mitigate the potential harm associated with fluid accumulation.

Population-Based Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Children.

OBJECTIVES: We describe the epidemiology, characteristics, risk factors, and incremental risks associated with acute kidney injury in critically ill children at a population-level. DESIGN: Population-based retrospective cohort study. SETTING: PICUs in Alberta, Canada. PATIENTS: All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,017 patients were included. Acute kidney injury developed in 308 patients (30.3%; 95% CI, 28.1-33.8%) and severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3-14.4%). Incidence rates for critical illness-associated acute kidney injury and severe acute kidney injury were 34 (95% CI, 30.3-38.0) and 14 (95% CI, 11.38-16.38) per 100,000 children-year, respectively. Severe acute kidney injury incidence rates were greater in males (incidence rate ratio, 1.55; 95% CI, 1.08-2.33) and infants younger than 1 year old (incidence rate ratio, 14.77; 95% CI, 10.36-21.07). Thirty-two patients (3.1%) did not survive to PICU discharge. The acute kidney injury-associated PICU mortality rate was 2.3 (95% CI, 1.4-3.5) per 100,000 children-year. In multivariate analysis, severe acute kidney injury was associated with greater PICU mortality (odds ratio, 11.93; 95% CI, 4.68-30.42) and 1-year mortality (odds ratio, 5.50; 95% CI, 2.76-10.96). Severe acute kidney injury was further associated with greater duration of mechanical ventilation, duration of vasoactive support, and lengths of PICU and hospital stay. CONCLUSIONS: The population-level burden of acute kidney injury and its attributable risks are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for acute kidney injury, identification of modifiable risks, and evaluation of interventional strategies.

Doppler ultrasound values after liver transplantation in children and their association with graft outcomes: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Liver graft and patient survival in children have improved substantially over the years; nevertheless, graft-related complications persist as the most important risk factor for mortality and graft loss. Doppler ultrasound evaluation is routinely used after liver transplantation; however, there is no consensus defining normal values, timing or frequency of Doppler ultrasound postoperative evaluation. Identification of patients who require an intervention or change in postoperative management is therefore challenging. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis to appraise and synthesise evidence describing Doppler ultrasound measurements and their association with graft complications in children who have received a liver transplant. We will search multiple databases: Ovid Medline, Embase, Wiley Cochrane Library, Web of Science-Science Citation Index Expanded, trial registry records and meeting abstracts using a combination of subject headings and keywords for liver transplantation, Doppler ultrasound and paediatric patients. All identified titles and abstracts of studies will be assessed for potential relevance. Selected studies will be retrieved and subjected to a second phase of screening, both selection phases will be done in duplicate by two independent reviewers, and discrepancies will be documented and resolved by a third reviewer. Data extraction will be done independently by two reviewers using a standardised data extraction form. Quality of evidence and risk of bias will be assessed, synthesised and pooled for meta-analysis if possible. We will perform a subgroup analysis if enough data are available. ETHICS AND DISSEMINATION: Strategies to disseminate our review include presenting in liver transplant review sessions, publishing in high-impact peer-reviewed medical journals, and presenting at national and international paediatric radiology and liver transplant meetings, conference presentations, events, courses and plain-language summaries. This knowledge will allow easier identification of patients with a higher risk of developing graft-related complications and could potentially improve patient and graft outcomes. We wish to disseminate our results to discover potential areas for future research and drive improved future practices and policies. Our target audience includes researchers, institutions, healthcare professionals, health system decision-makers, policy-makers and research funders community. TRIAL REGISTRATION NUMBER: CRD42019119986.

Predicting early outcomes of liver transplantation in young children: The EARLY study.

AIM: To determine potentially modifiable predictors of early outcomes after liver transplantation in children of age < 3 years. METHODS: This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015. Pre-specified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic [odds ratio (OR); 95%CI] or linear (effect size, ES; 95%CI) regressions. RESULTS: There were 65 children, of mean age 11.9 (SD 7.1) mo and weight 8.5 (2.1) kg, with biliary-atresia in 40 (62%), who had a living related donor [LRD; 29 (45%)], split/reduced [21 (32%)] or whole liver graft [15 (23%)]. Outcomes after liver transplant included: ventilator-days of 12.5 (14.1); pediatric intensive care unit mortality of 5 (8%); re-operation in 33 (51%), hepatic artery thrombosis (HAT) in 12 (19%), portal vein thrombosis (PVT) in 11 (17%), and any severe complication (HAT, PVT, bile leak, bowel perforation, intraabdominal infection, retransplant, or death) in 32 (49%) patients. Predictors of the prespecified primary outcomes on multiple regression were: (1) HAT: split/reduced (OR 0.06; 0.01, 0.76; P = 0.030) or LRD (OR 0.16; 0.03, 0.95; P = 0.044) vs whole liver graft; and (2) ventilator-days: surgeon (P < 0.05), lowest antithrombin (AT) postoperative day 2-5 (ES -0.24; -0.47, -0.02; P = 0.034), and split/reduced (ES -12.5; -21.8, -3.2; P = 0.009) vs whole-liver graft. Predictors of the pre-specified secondary outcomes on multiple regression were: (1) any thrombosis: LRD (OR 0.10; 0.01, 0.71; P = 0.021) or split/reduced (OR 0.10; 0.01, 0.85; P = 0.034) vs whole liver graft, and lowest AT postoperative day 2-5 (OR 0.93; 0.87, 0.99; P = 0.038); and (2) any severe complication: surgeon (P < 0.05), lowest AT postoperative day 2-5 (OR 0.92; 0.86-0.98; P = 0.016), and split/reduced (OR 0.06; 0.01, 0.78; P = 0.032) vs whole-liver graft. CONCLUSION: In young children, whole liver graft and surgeon was associated with more complications, and higher AT postoperative day 2-5 was associated with fewer complications early after liver transplantation.

Association Between Fluid Balance and Outcomes in Critically Ill Children: A Systematic Review and Meta-analysis.

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.

Associations Between Fluid Balance and Outcomes in Critically Ill Children: A Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Fluid therapy is a mainstay during the resuscitation of critically ill children. After initial stabilization, excessive fluid accumulation may lead to complications of fluid overload, which has been independently associated with increased risk for mortality and major morbidity in critically ill children. OBJECTIVES: Perform an evidence synthesis to describe the methods used to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. DESIGN: Systematic review and meta-analysis. MEASUREMENTS: Fluid balance, fluid accumulation, and fluid overload as defined by authors. METHODS: We will search Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and ProQuest, Dissertations and Theses. In addition, we will search www.clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and the proceedings of selected key conferences for ongoing and completed studies. Search strategy will be done in consultation with a research librarian. Clinical trials and observational studies (from database inception to present) in patients (<25 years) admitted to pediatric intensive care units (PICUs) reporting fluid balance, fluid accumulation, or fluid overload, and associated outcomes will be included. Language will not be restricted. Two reviewers will independently screen studies and extract data. Primary outcome is mortality, and secondary outcomes encompass critical care resource utilization. Quality of evidence and risk of bias will be assessed using the Newcastle-Ottawa Scale (NOS). Results will be synthesized qualitatively and pooled for meta-analysis if possible. LIMITATIONS: Quality of the included studies; lack of randomized trials; high degrees of expected heterogeneity; and variations in definitions of fluid balance and fluid overload between studies. CONCLUSION: We will comprehensively appraise and summarize the evidence of the association between fluid balance and outcomes in critically ill children, and in doing so attempt to harmonize definitions related to fluid balance, accumulation, and overload. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42016036209.

MISE EN CONTEXTE: Une saine gestion des fluides est cruciale lors de la réanimation des enfants gravement malades puisqu'à la suite de la stabilisation du patient, l'accumulation excessive de liquides est susceptible de conduire à des complications. La surcharge liquidienne chez les enfants gravement malades a été associée de façon indépendante avec un risque accru de mortalité et à une morbidité plus importante. OBJECTIFS DE L'ÉTUDE: Cette étude vise à faire la synthèse des données probantes utilisées pour décrire les méthodes de mesure de l'équilibre hydrique, à mieux définir la surcharge liquidienne et à évaluer le rapport entre l'équilibre hydrique et les résultats observés chez les enfants gravement malades. TYPE D'ÉTUDE: L'étude s'effectuera sous la forme d'une revue systématique de la littérature suivie d'une méta-analyse. MESURES: L'étude tiendra compte de l'équilibre hydrique, de l'accumulation de fluides et de la surcharge hydrique tels que ces termes sont définis par les auteurs. MÉTHODOLOGIE: Les bases de données Ovid MEDLINE et Ovid EMBASE, de même que ProQuest, la Cochrane Library et les mémoires et thèses sur le sujet seront fouillés. Nous chercherons également sur le site internet www.clinicaltrials.gov, la plateforme WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) et les comptes rendus d'une sélection de conférences traitant d'études complétées ou en cours sur le sujet. La stratégie de recherche sera établie en collaboration avec un bibliothécaire de recherche. La revue colligera les essais cliniques et les études observationnelles répertoriés dans les bases de données qui font mention de l'équilibre hydrique, de l'accumulation de fluides, de surcharge liquidienne et des issues sur la santé associées à ceux-ci chez les patients de moins de 25 ans admis dans les unités de soins intensifs pédiatriques. La recherche ne sera pas restreinte à une langue en particulier. La sélection des études et l'extraction des données seront effectuées de manière indépendante par deux réviseurs. Le principal résultat observé sera la mortalité du patient, le second concernera l'utilisation des ressources en matière de soins critiques. La qualité des données retenues et le risque de biais seront évalués par la méthode de l'échelle de Newcastle-Ottawa. Les résultats seront synthétisés de façon qualitative et, si possible, regroupés en vue d'une méta-analyse. LIMITES DE L'ÉTUDE: Les conclusions pourraient être limitées par la qualité inégale des études répertoriées, le manque d'essais cliniques randomisés, un fort degré d'hétérogénéité des données recueillies, et en raison de variations entre les études sélectionnées dans leur définition des termes équilibre hydrique et surcharge liquidienne. CONCLUSIONS: Nous proposons de résumer et d'évaluer de manière globale les preuves rapportées dans la littérature d'une association entre l'équilibre hydrique et les issues sur la santé des enfants gravement malades. Parallèlement, nous souhaitons contribuer à harmoniser les définitions des termes équilibre hydrique, accumulation de fluides et surcharge liquidienne.

Sepsis-associated acute kidney injury.

Acute kidney injury (AKI) is an epidemic problem. Sepsis has long been recognized as a foremost precipitant of AKI. Sepsis-associated AKI (SA-AKI) portends a high burden of morbidity and mortality in both children and adults with critical illness. Although our understanding of its pathophysiology is incomplete, SA-AKI likely represents a distinct subset of AKI contributed to by a unique constellation of hemodynamic, inflammatory, and immune mechanisms. SA-AKI poses significant clinical challenges for clinicians. To date, no singular effective therapy has been developed to alter the natural history of SA-AKI. Rather, current strategies to alleviate poor outcomes focus on clinical risk identification, early detection of injury, modifying clinician behavior to avoid harm, early appropriate antimicrobial therapy, and surveillance among survivors for the longer-term sequelae of kidney damage. Recent evidence has confirmed that patients no longer die with AKI, but from AKI. To improve the care and outcomes for sufferers of SA-AKI, clinicians need a robust appreciation for its epidemiology and current best-evidence strategies for prevention and treatment.