Management of Fluid Overload in Patients With Severe Aortic Stenosis (EASE-TAVR): A Randomized Controlled Trial.

BACKGROUND: Fluid overload (FO) subjects patients with severe aortic stenosis (AS) to increased risk for heart failure and death after valve replacement and can be objectively quantified using bioimpedance spectroscopy (BIS). OBJECTIVES: The authors hypothesized that in AS patients with concomitant FO, BIS-guided decongestion could improve prognosis and quality of life following transcatheter aortic valve replacement (TAVR). METHODS: This randomized, controlled trial enrolled 232 patients with severe AS scheduled for TAVR. FO was defined using a portable whole-body BIS device according to previously established cutoffs (≥1.0 L and/or ≥7%). Patients with FO (n = 111) were randomly assigned 1:1 to receive BIS-guided decongestion (n = 55) or decongestion by clinical judgment alone (n = 56) following TAVR. Patients without FO (n = 121) served as a control cohort. The primary endpoint was the composite of hospitalization for heart failure and/or all-cause death at 12 months. The secondary endpoint was the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire. RESULTS: The occurrence of the primary endpoint at 12 months was significantly lower in the BIS-guided vs the non-BIS-guided decongestion group (7/55 [12.7%, all deaths] vs 18/56 [32.1%, 9 hospitalizations for heart failure and 9 deaths]; HR: 0.36; 95% CI: 0.15-0.87; absolute risk reduction = -19.4%). Outcomes in the BIS-guided decongestion group were identical to the euvolemic control group (log-rank test, P = 0.7). BIS-guided decongestion was also associated with a higher increase in the Kansas City Cardiomyopathy Questionnaire score from baseline compared to non-BIS-guided decongestion (P = 0.001). CONCLUSIONS: In patients with severe AS and concomitant FO, quantitatively guided decongestive treatment and associated intensified management post-TAVR was associated with improved outcomes and quality of life compared to decongestion by clinical judgment alone. (Management of Fluid Overload in Patients Scheduled for Transcatheter Aortic Valve Replacement [EASE-TAVR]; NCT04556123).

Prognostic value of hypochloremia on mortality in patients with heart failure: a systematic review and meta-analysis.

AIMS: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure. METHODS: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed. RESULTS: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses. CONCLUSION: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure.

Association of hyperchloremia with all-cause mortality in patients admitted to the surgical intensive care unit: a retrospective cohort study.

BACKGROUND: Serum chloride (Cl-) is one of the most essential extracellular anions. Based on emerging evidence obtained from patients with kidney or heart disease, hypochloremia has been recognized as an independent predictor of mortality. Nevertheless, excessive Cl- can also cause death in severely ill patients. This study aimed to investigate the relationship between hyperchloremia and high mortality rate in patients admitted to the surgical intensive care unit (SICU). METHODS: We enrolled 2131 patients from the Multiparameter Intelligent Monitoring in Intensive Care III database version 1.4 (MIMIC-III v1.4) from 2001 to 2012. Selected SICU patients were more than 18 years old and survived more than 72 h. A serum Cl- level ≥ 108 mEq/L was defined as hyperchloremia. Clinical and laboratory variables were compared between hyperchloremia (n = 664) at 72 h post-ICU admission and no hyperchloremia (n = 1467). The Locally Weighted Scatterplot Smoothing (Lowess) approach was utilized to investigate the correlation between serum Cl- and the thirty-day mortality rate. The Cox proportional-hazards model was employed to investigate whether serum chlorine at 72 h post-ICU admission was independently related to in-hospital, thirty-day and ninety-day mortality from all causes. Kaplan-Meier curve of thirty-day and ninety-day mortality and serum Cl- at 72 h post-ICU admission was further constructed. Furthermore, we performed subgroup analyses to investigate the relationship between serum Cl- at 72 h post-ICU admission and the thirty-day mortality from all causes. RESULTS: A J-shaped correlation was observed, indicating that hyperchloremia was linked to an elevated risk of thirty-day mortality from all causes. In the multivariate analyses, it was established that hyperchloremia remained a valuable predictor of in-hospital, thirty-day and ninety-day mortality from all causes; with adjusted hazard ratios (95% CIs) for hyperchloremia of 1.35 (1.02 ~ 1.77), 1.67 (1.28 ~ 2.19), and 1.39 (1.12 ~ 1.73), respectively. In subgroup analysis, we observed hyperchloremia had a significant interaction with AKI (P for interaction: 0.017), but there were no interactions with coronary heart disease, hypertension, and diabetes mellitus (P for interaction: 0.418, 0.157, 0.103, respectively). CONCLUSION: Hyperchloremia at 72 h post-ICU admission and increasing serum Cl- were associated with elevated mortality risk from all causes in severely ill SICU patients.

Fluid status in the first 10 days of life and death/bronchopulmonary dysplasia among preterm infants.

OBJECTIVE: To investigate the association between fluid and sodium status in the first 10 postnatal days and death/bronchopulmonary dysplasia (BPD) among infants born <29 weeks' gestation. STUDY DESIGN: Single center retrospective cohort study (2015-2018) of infants born 23-28 weeks'. Three exposure variables were evaluated over the first 10 postnatal days: cumulative fluid balance (CFB), median serum sodium concentration, and maximum percentage weight loss. Primary outcome was death and/or BPD. Multivariable logistic regression adjusting for patient covariates was used to assess the association between exposure variables and outcomes. RESULTS: Of 191 infants included, 98 (51%) had death/BPD. Only CFB differed significantly between BPD-free survivors and infants with death/BPD: 4.71 dL/kg (IQR 4.10-5.12) vs 5.11 dL/kg (IQR 4.47-6.07; p < 0.001). In adjusted analyses, we found an association between higher CFB and higher odds of death/BPD (AOR 1.56, 95% CI 1.11-2.25). This was mainly due to the association of CFB with BPD (AOR 1.60, 95% CI 1.12-2.35), rather than with death (AOR 1.08, 95% CI 0.54-2.30). CONCLUSION: Among preterm infants, a higher CFB in the first 10 days after delivery is associated with higher odds of death/BPD. IMPACT: Previous studies suggest that postnatal fluid status influences survival and respiratory function in neonates. Fluid balance, serum sodium concentration, and daily weight changes are commonly used as fluid status indicators in neonates. We found that higher cumulative fluid balance in the first 10 days of life was associated with higher odds of death/bronchopulmonary dysplasia in neonates born <29 weeks. Monitoring of postnatal fluid balance may be an appropriate non-invasive strategy to favor survival without bronchopulmonary dysplasia. We developed a cumulative fluid balance chart with corresponding thresholds on each day to help design future trials and guide clinicians in fluid management.

Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. DATA SOURCES: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. STUDY SELECTION AND DATA EXTRACTION: All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. DATA SYNTHESIS: A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. CONCLUSIONS: This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

Assessment of Hydration Status in Peritoneal Dialysis Patients: Validity, Prognostic Value, Strengths, and Limitations of Available Techniques.

BACKGROUND: The majority of patients undergoing peritoneal dialysis (PD) suffer from volume overload and this overhydration is associated with increased mortality. Thus, optimal assessment of volume status in PD is an issue of paramount importance. Patient symptoms and physical signs are often unreliable indexes of true hydration status. SUMMARY: Over the past decades, a quest for a valid, reproducible, and easily applicable technique to assess hydration status is taking place. Among existing techniques, inferior vena cava diameter measurements with echocardiography and natriuretic peptides such as brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide were not extensively examined in PD populations; while having certain advantages, their interpretation are complicated by the underlying cardiac status and are not widely available. Bioelectrical impedance analysis (BIA) techniques are the most studied tool assessing volume overload in PD. Volume overload assessed with BIA has been associated with technique failure and increased mortality in observational studies, but the results of randomized trials on the value of BIA-based strategies to improve volume-related outcomes are contradictory. Lung ultrasound (US) is a recent technique with the ability to identify volume excess in the critical lung area. Preliminary evidence in PD showed that B-lines from lung US correlate with echocardiographic parameters but not with BIA measurements. This review presents the methods currently used to assess fluid status in PD patients and discusses existing data on their validity, applicability, limitations, and associations with intermediate and hard outcomes in this population. Key Message: No method has proved its value as an intervening tool affecting cardiovascular events, technique, and overall survival in PD patients. As BIA and lung US estimate fluid overload in different compartments of the body, they can be complementary tools for volume status assessment.

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.

Underhydration Is Associated with Obesity, Chronic Diseases, and Death Within 3 to 6 Years in the U.S. Population Aged 51-70 Years.

Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) indicate that over 65% of adults aged 51-70 years in the U.S. do not meet hydration criteria. They have hyponatremia (serum sodium < 135 mmol/L) and/or underhydration (serum sodium >145 mmol/L, spot urine volume <50 mL, and/or spot urine osmolality ≥500 mmol/kg). To explore potential public health implications of not meeting hydration criteria, data from the NHANES 2009-2012 and National Center for Health Statistics Linked Mortality Files for fasting adults aged 51-70 years (sample n = 1200) were used to determine if hyponatremia and/or underhydration were cross-sectionally associated with chronic health conditions and/or longitudinally associated with chronic disease mortality. Underhydration accounted for 97% of the population group not meeting hydration criteria. In weighted multivariable adjusted Poisson models, underhydration was significantly associated with increased prevalence of obesity, high waist circumference, insulin resistance, diabetes, low HDL, hypertension, and metabolic syndrome. Over 3-6 years of follow-up, 33 chronic disease deaths occurred in the sample, representing an estimated 1,084,144 deaths in the U.S. Alongside chronic health conditions, underhydration was a risk factor for an estimated 863,305 deaths. Independent of the chronic health conditions evaluated, underhydration was a risk factor for 128,107 deaths. In weighted multivariable Cox models, underhydration was associated with 4.21 times greater chronic disease mortality (95% CI: 1.29-13.78, p = 0.019). Zero chronic disease deaths were observed for people who met the hydration criteria and did not already have a chronic condition in 2009-2012. Further work should consider effects of underhydration on population health.

Effects of hyperchloremia on renal recovery in critically ill children with acute kidney injury.

BACKGROUND: Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI. METHODS: We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as ≥ 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay. RESULTS: Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders. CONCLUSIONS: Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes. Graphical abstract.

Association of postoperative fluid overload with adverse outcomes after congenital heart surgery: a systematic review and dose-response meta-analysis.

BACKGROUND: Pediatric cardiac surgery is commonly associated with acute kidney injury (AKI) and significant fluid retention, which complicate postoperative management and lead to increased rates of morbidity. This meta-analysis aimed to accumulate current literature evidence and evaluate the correlation of fluid overload degree with adverse outcome in patients undergoing congenital heart surgery. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar were systematically searched from inception. All studies reporting the effects of fluid overload on postoperative clinical outcomes were selected. A dose-response meta-analytic method using restricted cubic splines was implemented in R-3.6.1. RESULTS: Twelve studies were included, with a total of 3111 pediatric patients. Qualitative synthesis indicated that fluid overload was linked to significantly higher risk of mortality, AKI, prolonged hospital, and intensive care unit (ICU) stay, as well as with increased duration of mechanical ventilation, inotrope need, and infection rate. Meta-analysis demonstrated a linear correlation between fluid overload and the risk of mortality (χ2 = 6.22, p value = 0.01) and AKI (χ2 = 35.84, p value < 0.001), while a positive curvilinear relationship was estimated for the outcomes of hospital (χ2 = 18.84, p value = 0.0001) and ICU stay (χ2 = 63.69, p value = 0.0001). CONCLUSIONS: The present meta-analysis supports that postoperative fluid overload is significantly linked to elevated risk of prolonged hospital stay, AKI development, and mortality in pediatric patients undergoing cardiac surgery. These findings warrant replication by future prospective studies, which should define the optimal cutoff values and assess the effectiveness of therapeutic strategies to limit fluid overload in the postoperative setting.

Abnormal fluid distribution and low handgrip strength index as predictors of mortality in Mexican patients with chronic heart failure.

OBJECTIVES: In patients with heart failure, fluid alteration and low muscle strength frequently coexist because of their reduced physical activity and sedentary behavior; however, few studies have evaluated the effects of this coexistence on the prognosis of these patients. The aim of this study was to examine the independent association between fluid alteration and the low handgrip strength (HGS) index with mortality in patients with chronic heart failure. METHODS: This observational study included 546 (53.3% male) stable outpatients with heart failure. The presence of an abnormal fluid distribution was determined with a bioelectrical impedance ratio (200/5 kHz) ≥0.85. Handgrip strength (HGS) was measured with a hand dynamometer, and the HGS index was calculated by dividing the HGS (kg) by the squared height (meters). A low HGS index was defined if men had <10.1 and women <7.95 kg/m2. The primary outcome was all-cause mortality. RESULTS: The mean age of the study population was 60.75 ± 17 y, and 30% were classified with a low HGS index, 9.5% with an abnormal fluid distribution, and 29% with both. During the 36 mo of follow-up, 16.5% of the participants reached the endpoint. In men but not in women, coexistence of a low HGS index and abnormal fluid distribution were independently associated with all-cause mortality with a hazard ratio of 2.8 (95% confidence interval, 1.25-6.4; P = 0.01). CONCLUSIONS: In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality.

Clinical Outcomes Associated with Fluid Overload in Critically Ill Pediatric Patients.

BACKGROUND: Fluid overload (FO) has been accused as being one of the ICU problems affecting morbidity and mortality. The aim of the study was to assess the effect and critical threshold of FO that is related to mortality. METHODS: This prospective observational study was conducted in a pediatric ICU. All patients admitted (n = 203) during 12 months with a length of stay more than 48 h were recruited. RESULTS: FO was found to be related to mortality (p = 0.025) but was not proved to be an independent risk factor of fatal outcome by the logistic regression model. This raises the suspicion about any cause-effect relationship between FO and mortality. Even though, FO was statistically a fair discriminator of death (AUC = 0.655, p = 0.0008) and a cutoff level of FO was set at 7%. Kaplan-Meier curve showed that cumulative of survival differed significantly between groups of patients with FO more and less than 7% (p = 0.002). CONCLUSION: Frequent and accurate monitoring of FO is crucial among critically ill patients. The present study suggested a threshold of 7% FO beyond which a more conservative regimen of fluid administration might improve patients' outcome.

Early Positive Fluid Balance is Associated with Mortality in Patients Treated with Veno-Arterial Extra Corporeal Membrane Oxygenation For Cardiogenic Shock: a Retrospective Cohort Study.

PURPOSE: Veno-arterial Extracoporeal Membrane Oxygenation (VA-ECMO) provides circulatory assistance for patients in cardiogenic shock. Large quantities of fluids are often required, especially during the early stages, but can result in a potentially harmful fluid-overload. The objective was to determine the association of early fluid-balance and mortality. METHODS: Retrospective single-center study in 101 VA-ECMO patients between 2013 and 2016. Daily fluid-balance and weight changes over the 5 first days were observed. Analyses between survivors and non-survivors were conducted using Mann-Whitney tests and logistic regression multivariable and Cox hazard-proportional analyses to determine any association with 28-days mortality. RESULTS: Mortality was 47.5%. The fluid-balance was higher in non-survivors at day-1 (47.3[18.1-71.9] vs. 19.3[1.5-36.2] mL/kg, P < 0.0001) and day-2 (30.6[14.8-71.0] vs. 10.1[-9.8 to 34.7] mL/kg, P = 0.025), as was the cumulative fluid-balance over the first 5 days (107.3[40.5-146.2] vs. 53.0[7.5-74.3] mL/kg, P = 0.04). The administration of unintentional fluids (used for preparation and infusion of drugs) represented an important part of the administrated fluids (15 mL/kg/d-23 mL/kg/d). A significant but moderate correlation was observed between fluid-balance and weight variations over the 5 days (r values ranging from 0.36 to 0.54). Among other parameters, day-1 fluid-balance was independently associated with mortality (OR = 14.34 [1.58-129.79], P = 0.02) and day-1 and day-2 with time to death (HR = 8.26 [1.12-60.98], P = 0.04 and 2.89 [1.26-6.65], P = 0.01). A threshold of 38.8 mL/kg predicted mortality with a sensitivity of 60% and specificity of 83% (area under the curve: 0.749). CONCLUSION: Early positive fluid-balance is associated with mortality in VA-ECMO patients.

Fluid Overload and Risk of Mortality in Critically Ill Patients.

BACKGROUND: Fluid overload (FO) is a condition present in critical care units, and it is associated with clinical complications and worse outcomes for severe patients. OBJECTIVE: The aim of this study was to verify if FO is a risk factor for mortality in critically ill patients. METHODS: Retrospective study performed in a Brazilian intensive care unit, from January to March 2016, with patients older than 18 years and hospitalized for more than 24 hours. Demographic and clinical data, as well as fluid balance and overload, were analyzed to verify the risk factors for mortality. A logistic regression model was elaborated, and significance was set at P < .05. RESULTS: There were 158 patients included, of which only 13 (8.2%) presented FO. Mortality was verified in individuals 30 (18.9%), of whom only 7 (23.3%) developed FO, which was lower in survivors 6 (4.9%), P = .001. In the simple regression model, the FO was significant (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.04-19.53), P = .001. However, in the multiple regression model, there were significant findings only for mechanical ventilation (OR, 5.86; 95% CI, 2.10-18.12, P = .001), acute kidney injury (OR, 4.05; 95% CI, 1.53-11; P = .001), and noradrenaline (OR, 3.85; 95% CI, 1.01-9.51; P = .041); FO was not significant (OR, 3.68; 95% CI, 0.91-15.55; P = .069). CONCLUSION: Fluid overload is higher in patients who died. Therefore, it was not considered a risk factor for mortality.

Long QT and death in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease is not related to electrolyte disorders.

Objectives: COPD is the fourth-leading cause of mortality worldwide. Prolonged QTc has been found to be a long-term negative prognostic factor in ambulatory COPD patients. The aim of this study was to evaluate the extent of prolonged-QTc syndrome in COPD patients upon admission to an internal medicine department, its relationship to hypomagnesemia, hypokalemia, and hypocalcemia, and the effect of COPD treatment on mortality during hospital stay. Methods: This prospective cohort study evaluated COPD patients hospitalized in an internal medicine department. The study evaluated QTc, electrolyte levels, and known risk factors during hospitalization of COPD patients. Results: A total of 67 patients were recruited. The median QTc interval was 0.441 seconds and 0.434 seconds on days 0 and 3, respectively. Prolonged QTc was noted in 35.8% of patients on admission and 37.3% on day 3 of hospitalization. The median QTc in the prolonged-QTc group on admission was 0.471 seconds and in the normal-QTc group 0.430 seconds. There was no significant difference in age, sex, electrolyte levels, renal function tests, or blood gases on admission between the two groups. Mortality during the hospital stay was significantly higher in the prolonged-QTc group (3 deaths, 12%) than in the normal QTc group (no deaths) (P=0.04). A subanalysis was performed, removing known causes for prolonged QTc. We found no differences in age, electrolytes, or renal functions. There was a small but significant difference in bicarbonate levels. Conclusion: Our findings demonstrated that there was no correlation between QTc prolongation in hospitalized COPD patients and electrolyte levels, comorbidities, or relevant medications. A higher rate of mortality was noted in patients with prolonged QTc in comparison to normal QTc. As such, it is suggested that prolonged QTc could serve as a negative prognostic factor for mortality during hospitalization in COPD patients.

Risk Factors for Mortality in Critically Ill Children Requiring Renal Replacement Therapy.

OBJECTIVES: There is an increased mortality risk in critically ill children who require renal replacement therapy for acute kidney injury and fluid overload. Nevertheless, renal replacement therapy is essential in managing these patients. The objective of this study was to identify risk factors for mortality in critically ill children requiring renal replacement therapy. DESIGN: Single-center, retrospective cohort analysis. SETTING: Tertiary care children's hospital. PATIENTS: All patients admitted to an ICU at Boston Children's Hospital from January 2009 to December 2017 who required any form of renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred sixty-three patients required inpatient renal replacement therapy over the study period. Of these, there were 98 patients who had 99 unique encounters for renal replacement therapy that met eligibility criteria for analysis. The most common diagnoses were respiratory failure, stem cell transplant, and sepsis. The overall mortality was 55.6%. Nonsurvivors had a lower ICU admission weight compared with survivors (30.0 kg vs 44.0 kg; p = 0.037) and a higher degree of fluid accumulation at the time of renal replacement therapy initiation (17.1% vs 8.1%; p = 0.021). In multivariable logistic regression analysis, invasive mechanical ventilation (odds ratio, 7.22; 95% CI, 1.88-27.7), a longer duration of stage 3 acute kidney injury (odds ratio, 1.08; 95% CI, 1.02-1.15), and higher fluid balance in the 72 hours after initiating renal replacement therapy (odds ratio, 1.12; 95% CI, 1.05-1.20) were associated with an increased odds of mortality. CONCLUSIONS: Earlier renal replacement therapy initiation with respect to the development of severe acute kidney injury was associated with lower mortality in this cohort of critically ill children. Additionally, invasive mechanical ventilation at the time of renal replacement therapy initiation and a higher degree of fluid accumulation after initiating renal replacement therapy were associated with increased mortality.

A Report of 7-Year Experience on Pediatric Continuous Renal Replacement Therapy.

BACKGROUND: Continuous renal replacement therapies (CRRTs) either as continuous venovenous hemofiltration (CVVH) or hemodiafiltration (CVVHD) are used frequently in critically ill children. Many clinical variables and technical issues are known to affect the result. The factors that could be modified to increase the survival of renal replacement are sought. As a contribution, we present the data on 104 patients who underwent CRRT within a 7-year period. MATERIALS AND METHOD: A total of 104 patients admitted between 2009 and 2016 were included in the study. The demographic information, admittance pediatric risk of mortality (PRISM) scores, indication for CRRT, presence of fluid overload, CRRT modality, durations of CRRT, and pediatric intensive care unit (PICU) stay were compared between survivors and nonsurvivors. RESULTS: The overall rate of survival was 51%. Patients with fluid overload had significantly increased rate of death, CRRT duration, and PICU stay. Multiorgan dysfunction syndrome as the indication for CRRT was significantly related to decreased survival when compared to acute renal failure and acute attacks of metabolic diseases. The CRRT modality was not different between survivors and nonsurvivors. Standardized mortality ratio of the group was calculated to be 0.8. CONCLUSION: The CRRT in critically ill patients is successful in achieving fluid removal and correction of metabolic imbalances caused by organ failures or attacks of inborn errors of metabolism. It has a positive effect on expected mortality in high-risk PICU patients. To affect the outcome, follow-up should be focused on starting therapy in early stages of fluid overload. Prospective studies defining relative importance of risk factors causing mortality can assist in building up guidelines to affect the outcome.

The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group.

BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates. METHODS: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME: mechanical ventilation (MV) on postnatal day 7. RESULTS: The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7. CONCLUSIONS: We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.

Association of Fluid Overload with Mortality in Critically-ill Mechanically Ventilated Children.

OBJECTIVE: To study the association of fluid overload with mortality and morbidity in critically-ill mechanically ventilated children. DESIGN: Prospective observational study. SETTING: Pediatric Intensive Care Unit (PICU) of a tertiary care hospital, New Delhi, India. PARTICIPANTS: 118 children (age 1 mo - 15 y) requiring mechanical ventilation. OUTCOME MEASURES: Primary: Association of fluid overload with mortality. Secondary: Association of fluid overload with oxygenation, organ dysfunction, duration of mechanical ventilation and PICU stay. RESULTS: Cumulative fluid overload of ≥15% was observed in 74 (62.7%) children. About 50% of these children reached cumulative fluid overload of ≥15% within the first 5 days of PICU stay. The mortality was 40.5% in those with ≥15% cumulative fluid compared to 34% in the rest [OR (95% CI): 1.02 (0.97, 1.07)]. On multivariate analysis, after adjusting for confounders, cumulative fluid overload ≥15% was associated with higher maximum PELOD (pediatric logistic organ dysfunction) score (Median: 21 vs. 12; P = 0.03), longer median duration of mechanical ventilation (10 vs. 4 d; P <0.0001) and PICU stay (13.5 vs. 6 d; P <0.0001). There was no significant association of fluid overload with oxygenation index (P=0.32). CONCLUSIONS: There is no association of fluid overload with mortality. However, it is associated with poor organ function, longer duration of mechanical ventilation and PICU stay in critically-ill, mechanically ventilated children.