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.

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.

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.

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.

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.

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.

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.

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.

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness.

OBJECTIVES: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. DESIGN: Retrospective cohort study. SETTING: Ten ICUs in the United Kingdom and Canada. PATIENTS: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site. CONCLUSIONS: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

Greater fluid overload and lower interdialytic weight gain are independently associated with mortality in a large international hemodialysis population.

Background: Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. Methods: We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. Results: In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21-3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. Conclusions: FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

Overhydration, underhydration, and total body sodium: A tricky "ménage a trois" in dialysis patients.

Overhydration is a frequent complication in dialysis patients. It has been linked with hypertension, left ventricular hypertrophy, arterial stiffness, atherosclerosis uremic cardiomyopathy, and all-cause mortality or cardiovascular morbidity. In addition, predialysis underhydration is also associated with increased risk of death in ESRD patients. In this context, the optimal evaluation of hydration status is a must. However, this mission is not easy or accurate. In the last 10 years, several new methods have been tested in dialysis patients, particularly bioimpedance and lung ultrasonography. The precise clinical value of these techniques in the daily care of hemodialysis patients is not obvious yet. Sodium is also an important piece of this puzzle. Salt intake and/or removal of sodium during dialysis are essential determinants of optimal hydration status. Recent studies have revealed that salt and water homeostasis is also dependent of tissue sodium storage-increased in hemodialysis patients. However, the significance of increased sodium tissue storage as a cardiovascular risk factor and the relationship between tissue sodium content and hard CV endpoint have not yet been elucidated yet.

Hyperchloremia is independently associated with mortality in critically ill children who ultimately require continuous renal replacement therapy.

BACKGROUND: The optimal fluid management in critically ill children is currently under investigation with several studies suggesting that hyperchloremia, chloride load, and the use of chloride-rich fluids contribute to worse outcomes. METHODS: This is a single-center retrospective cohort study of Pediatric Intensive Care Unit patients from 2008 to 2016 requiring continuous renal replacement therapy (CRRT). Patients were excluded if they had end-stage renal disease, a disorder of chloride transport, or concurrent provision of extracorporeal membrane oxygenation therapy. RESULTS: Patients (n = 66) were dichotomized into two groups (peak chloride (Cl) ≥ 110 mmol/L vs. peak Cl < 110 mmol/L prior to CRRT initiation). Hyperchloremia was present in 39 (59%) children. Baseline characteristics were similar between groups. Fluid overload at CRRT initiation was more common in patients with hyperchloremia (11.5% IQR 3.8-22.4) compared to those without (5.5% IQR 0.9-13.9) (p = 0.04). Mortality was significantly higher in patients with hyperchloremia (n = 26, 67%) compared to those without (n = 8, 29%) (p = 0.006). Patients with hyperchloremia had 10.9 times greater odds of death compared to those without hyperchloremia, after adjusting for percent fluid overload, PRISM III score, time to initiation of CRRT, height, and weight (95% CI 2.4 to 49.5, p = 0.002). CONCLUSIONS: Hyperchloremia is common among critically ill children prior to CRRT initiation. In this population, hyperchloremia is independently associated with mortality. Further studies are needed to determine the impact of hyperchloremia on all critically ill children and the impact of chloride load on outcomes.

Risk of overhydration and low lean tissue index as measured using a body composition monitor in patients on hemodialysis: a systemic review and meta-analysis.

Overhydration and sarcopenia, related to an individual's nutritional status, have been associated with increased cardiovascular mortality and poor prognosis in patients on hemodialysis. The purpose of this study was to investigate the prediction of overhydration and sarcopenia on mortality in patients on hemodialysis using a body composition monitor. We conducted a systematic review and meta-analysis using a random-effects model. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published prior to December 9, 2016 and reviewed the reference lists of relevant reviews, registered trials and relevant conference proceedings. The overhydration group (fluid excess, >15% vs. the normohydration group) and the low lean tissue index group ( <10%) were compared with a reference group. Six trials, consisting of 29,469 patients, were included in the pooled analysis. The pooled hazard ratio for overall survival of the overhydration group, compared with the reference normohydration group was 1.798 (95% confidence interval [CI]: 1.53-2.804, p = .001). The hazard ratio for mortality in the low lean tissue index group was 1.533 (95% CI, 1.411-1.644; p = .001) in the random-effects model. The results from the most recent study showed the greatest heterogeneity in the sensitivity analysis. Low lean tissue index and overhydration, measured using a body composition monitor, were associated with a high mortality rate in patients on hemodialysis.

Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

A Case-Control Analysis of Postoperative Fluid Balance and Mortality After Pediatric Cardiac Surgery.

OBJECTIVES: A positive fluid balance after cardiac surgery may be associated with poor outcomes; however, previous studies looking at this association have been limited by the number of deaths in the study population. Our primary aim was to determine the relationship between postoperative cumulative fluid balance and mortality in cardiac surgical patients. Secondary aims were to study the association between fluid balance and duration of mechanical ventilation, intensive care and hospital length of stay. DESIGN: Case-control study. SETTING: A 30-bed multidisciplinary PICU. PATIENTS: All patients admitted to the PICU following cardiac surgery from 2010 to 2014. INTERVENTIONS: Deaths during PICU admission following cardiac surgery (cases) were matched 1:3 with children who survived to PICU discharge (controls) using the following criteria: age at surgery (within a 20% age range), Risk Adjusted Congenital Heart Surgery (RACHS-1) category, and year of admission. MEASUREMENTS AND MAIN RESULTS: Of 1,996 eligible children, 46 died (2.3%) of whom 45 (98%) were successfully matched. Cumulative fluid balance on days 2 and 7 was not associated with PICU mortality. On multivariable analysis, factors associated with mortality were cardiopulmonary bypass time (per 10-min increase, odds ratio [95% CI], 1.06 [1.00-1.12]; p = 0.03), extracorporeal membrane oxygenation requirement within 3 days (46.6 [9.47-230.11]; p < 0.001), peak serum chloride (mmol/L) in the first 48 hours (1.12 [1.01-1.23]), and time to start peritoneal dialysis after surgery (in comparison to no peritoneal dialysis, odds ratio [95% CI] in those started on early peritoneal dialysis was 1.07 [0.33-3.41]; p = 0.90 and in late peritoneal dialysis 3.65 [1.21-10.99]; p = 0.02). Children with cumulative fluid balance greater than or equal to 5% by day 2 spent longer on mechanical ventilation (median [interquartile range], 211 hr [97-539] vs 93 hr [34-225]; p <0.001), in PICU (11 d [8-26] vs 6 [3-13]; p < 0.001) and in hospital (22 d [13-39] vs 14 d [8-30]; p = 0.001). CONCLUSIONS: Early fluid overload is not associated with mortality. However, it is associated with increased duration of mechanical ventilation and PICU length of stay. Early peritoneal dialysis commencement (compared with late peritoneal dialysis) after surgery was associated with decreased mortality.

Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study.

BACKGROUND: Acute Kidney injury (AKI) is common and increases mortality in the intensive care unit (ICU). We carried out this study to explore whether fluid overload is an independent risk factor for AKI. METHODS: Single-center prospective, observational study. Consecutively admitted, ICU patients were followed for development of AKI. Intravenous fluid volumes, daily fluid balances were measured, hourly urine volumes, daily creatinine levels were recorded. RESULTS: Three hundred thirty nine patients were included; AKI developed in 141 (41.6%) patients; RISK in 27 (8%) patients; INJURY in 25 (7%); FAILURE in 89 (26%) by the RIFLE criteria. Fluid balance was significantly higher in patients with AKI; 1755 ± 2189 v/s 924 ± 1846 ml, p < 0.001 on ICU day 1. On multivariate regression analysis, a net fluid balance in first 24 h of ICU admission, OR 1.02 (95% CI 1.01,1.03 p = 0.003), percentage of fluid accumulation adjusted for body weight OR1.009 (95% CI 1.001,1.017, p = 0.02), fluid balance in first 24 h of ICU admission with serum creatinine adjusted for fluid balance, OR 1.024 (95% CI 1.012,1,035, p = 0.005), Age, OR 1.02 95% CI 1.01,1.03, p < 0.001, CHF, OR 3.1 (95% CI 1.16,8.32, p = 0.023), vasopressor requirement on ICU day one, OR 1.9 (95% CI 1.13,3.19, p = 0.014) and Colistin OR 2.3 (95% CI 1.3, 4.02, p < 0.001) were significant predictors of AKI. There was no significant association between fluid type; Chloride-liberal, Chloride-restrictive, and AKI. CONCLUSIONS: Fluid overload is an independent risk factor for AKI.