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Background Intravenous administration of fluids is an essential part of critical care. While some fluid administration is likely beneficial, there is increasing observational evidence that the development of fluid overload is associated with increased mortality. There are no randomised trials to confirm this association in patients with acute kidney injury. We aim to perform a pilot trial to test the feasibility of forced fluid removal compared to standard care in patients with acute kidney injury and severe fluid overload, the FFAKI trial. Methods Then FFAKI trial is a pilot, multicentre, randomised clinical trial recruiting adult intensive care patients with acute kidney injury and fluid overload, defined as more than 10% of ideal bodyweight. Patients are randomised with concealed allocation to either standard care or forced fluid removal with a therapeutic target of negative net fluid balance ≥1 mL/kg/h. The safety of fluid removal is continually evaluated according to predefined criteria of hypoperfusion: lactate ≥4 mmol/L, mean arterial pressure <50 mmHg or mottling beyond the edge of the kneecaps. If patients fulfil one of these criteria, fluid removal is suspended until hypoperfusion has resolved. The primary outcome measure is fluid balance at 5 days after randomisation and secondary outcomes include mean daily fluid balance, fluid balance at discharge from the intensive care unit, time to neutral fluid balance, number of serious adverse reactions and number of protocol violations. All patients are followed for 90 days. Discussion The FFAKI trial started in October 2015 and, when completed, will provide data to evaluate whether a large trial of forced fluid removal in critically ill patients is feasible. Our primary outcome will show if the experimental intervention leads to a clinically relevant difference in fluid balance, which could prove beneficial in intensive care patients with acute kidney injury. Trial registration EudraCT, identifier: 2015-001701-13. Registered on 19 September 2015; ClinicalTrials.gov, identifier: NCT02458157 . Registered on 21 May 2015; Danish Ethics Committee, identifier: H-15009589H. Registered on 22 September 2015; Danish Health and Medicines Authority, identifier: 2015070013. Registered on 11 August 2015.

Background Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Discussion Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. Trial registration ClinicalTrials.gov, NCT01416753

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.

BackgroundIn 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.MethodsThis 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.ResultsThe 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.ConclusionsWe 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.

Excess mortality and hospitalization have been identified after the 2-day gap in thrice-weekly hemodialysis patients compared with 1-day intervals, although findings vary internationally. Here we aimed to identify factors associated with mortality and hospitalization events in England using an incident cohort of 5864 hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry linked to hospitalization data. Higher admission rates were seen after the 2-day gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday or Tuesday (2.4 per year after the 2-day gap vs. 1.4 for the rest of the week, rate ratio 1.7). The greatest differences in admission rates were seen in patients admitted with fluid overload or with conditions associated with a high risk of fluid overload. Increased mortality following the 2-day gap was similarly independent of session pattern (20.5 vs. 16.7 per 100 patient years, rate ratio 1.22), with these increases being driven by out-of-hospital death (rate ratio 1.59 vs. 1.06 for in-hospital death). Non-white patients had an overall survival advantage, with the increased mortality after the 2-day gap being found only in whites. Thus, fluid overload may increase the risk of hospital admission after the 2-day gap and that the increased out-of-hospital mortality may relate to a higher incidence of sudden death. Future work should focus on exploring interventions in these subgroups.

Both overhydration and comorbidity predict mortality in end-stage kidney failure (ESKF) but it is not clear whether these are independent of one another. We undertook a systematic review of studies reporting outcomes in adult dialysis patients in which comorbidity and overhydration, quantified by whole body bioimpedance (BI), were reported. PubMed, EMBASE, PsychInfo and the Cochrane trial database were searched (1990–2017). Independent reviewers appraised studies including methodological quality (assessed using QUIPS). Primary outcome was mortality, with secondary outcomes including hospitalisation and cardiovascular events. Of 4028 citations identified, 46 matched inclusion criteria (42 cohorts; 60790 patients; 8187 deaths; 95% haemodialysis/5% peritoneal dialysis). BI measures included phase angle/BI vector (41%), overhydration index (39%) and extra:intracellular water ratio (20%). 38 of 42 cohorts had multivariable survival analyses (MVSA) adjusting for age (92%), gender (66%), diabetes (63%), albumin (58%), inflammation (CRP/IL6–37%), non-BI nutritional markers (24%) and echocardiographic data (8%). BI-defined overhydration (BI-OH) independently predicted mortality in 32 observational cohorts. Meta-analysis revealed overhydration >15% (HR 2.28, 95% CI 1.56–3.34, P < 0.001) and a 1-degree decrease in phase angle (HR 1.74, 95% CI 1.37–2.21, P < 0.001) predicted mortality. BI-OH predicts mortality in dialysis patients independent of the influence of comorbidity.

Background Electrolyte imbalances are commonly observed in individuals diagnosed with myocardial infarction (MI). The levels of serum sodium have been linked to unfavorable outcomes in relation to MI. Additionally, there exists a correlation between serum sodium and serum chloride, although the combined influence of these electrolytes on the prognosis of MI patients has not been extensively studied. Consequently, our study aimed to examine whether an autonomous association exists between the sodium-to-chloride (Na/Cl) ratio and mortality rates during hospitalization among patients admitted to intensive care unit (ICU) with MI. Methods A retrospective cohort study analysis was conducted on the Na/Cl ratio within the ICU from 2008 to 2019. Patients diagnosed with MI were divided into two groups based on a predetermined cutoff value for the Na/Cl ratio. Various statistical models, including the Cox proportional hazard model, generalized additive model, and two-piecewise linear regression model, were employed to assess the relationship between the initial Na/Cl ratio upon admission and the likelihood of in-hospital mortality while accounting for other relevant covariates. Results After adjusting for all other factors, the study revealed that the Na/Cl ratio exhibited an independent association with in-hospital mortality (HR = 1.28; 95% CI: 1.11–1.47, P  < 0.001). Further analysis indicated a nonlinear relationship between the Na/Cl ratio and in-hospital mortality among patients with MI, with a threshold at approximately 1.37. Specifically, if the Na/Cl ratio exceeded 1.37, there was a significant and progressively increasing likelihood of mortality during hospitalization (HR = 1.46; 95% CI: 1.20–1.77). Conclusion The in-hospital mortality of patients admitted to ICU with MI is predicted independently by the ratio of sodium to chloride (Na/Cl). A curvilinear correlation was observed between the Na/Cl ratio and in-hospital mortality, with a statistically significant threshold identified at 1.37.

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.

Purpose The purpose of this study was to evaluate the association between early fluid accumulation and mortality in children with shock states. Methods We retrospectively reviewed children admitted in shock states to the pediatric intensive care unit (ICU) at a tertiary level children’s hospital over a 7-month period. The study was designed as a matched case–control study. Children with early fluid overload, defined as fluid accumulation of ≥10 % of admission body weight during the initial 3 days, were designated as the cases. They were compared with matched controls without early fluid accumulation. Cases and controls were matched for age, severity of illness at ICU admission and need for organ support. They were compared with respect to all-cause ICU mortality and other secondary outcomes. Results A total of 114 children (age range 0–17.4 years; N = 42 cases and 72 matched controls) met the study criteria. Mortality rate was 13 % (15/114) in this cohort. Multivariable logistic regression analysis identified the presence of early fluid overload [adjusted odds ratio (OR) 9.17, 95 % confidence interval (CI) 2.22–55.57], its severity (adjusted OR 1.11, 95 % CI 1.05–1.19) and its duration (adjusted OR 1.61, 95 % CI 1.21–2.28) as independent predictors of mortality. Cases had higher mortality than the controls (26 vs. 6 %; p 0.003), and this difference remained significant in the matched analysis (37 vs. 3 %; p 0.002). Conclusion The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states.

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. 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. 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). In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality. •Low strength and abnormal fluid distribution were associated with mortality in men.•Patients with heart failure should be evaluated for fluid and handgrip strength.•An impedance index can detect fluid shifts from intracellular water to extracellular water.