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Background: Critically ill patients are at increased risk for fluid overload, but objective prediction tools to guide clinical decision-making are lacking. The MRC-ICU scoring tool is an objective tool for measuring medication regimen complexity. Objective: To evaluate the relationship between MRC-ICU score and fluid overload in critically ill patients. Methods: In this multi-center, retrospective, observational study, the relationship between MRC-ICU and the risk of fluid overload was examined. Patient demographics, fluid balance at day 3 of ICU admission, MRC-ICU score at 24 hours, and clinical outcomes were collected from the medical record. The primary outcome was relationship between MRC-ICU and fluid overload. To analyze this, MRC-ICU scores were divided into tertiles (low, moderate, high), and binary logistic regression was performed. Linear regression was performed to determine variables associated with positive fluid balance. Results: A total of 125 patients were included. The median MRC-ICU score at 24 hours of ICU admission for low, moderate, and high tertiles were 9, 15, and 21, respectively. For each point increase in MRC-ICU, a 13% increase in the likelihood of fluid overload was observed (OR 1.128, 95% CI 1.028-1.238, p = 0.011). The MRC-ICU score was positively associated with fluid balance at day 3 (β-coefficient 218.455, 95% CI 94.693-342.217, p = 0.001) when controlling for age, gender, and SOFA score. Conclusions: Medication regimen complexity demonstrated a weakly positive correlation with fluid overload in critically ill patients. Future studies are necessary to establish the MRC-ICU as a predictor to identify patients at risk of fluid overload.

The perinatal environment interacts with the genotype of the developing organism resulting in a unique phenotype through a developmental or perinatal programming phenomenon. However, it remains unclear how this phenomenon differentially affects particular targets expressing specific drinking responses depending on the perinatal conditions. The main goal of the present study was to compare the dipsogenic responses induced by different thirst models as a function of two perinatal manipulation models, defined by the maternal free access to hypertonic sodium solution and a partial aortic ligation (PAL-W/Na) or a sham-ligation (Sham-W/Na). The programmed adult offspring of both perinatal manipulated models responded similarly when was challenged by overnight water dehydration or after a sodium depletion showing a reduced water intake in comparison to the non-programmed animals. However, when animals were evaluated after a body sodium overload, only adult Sham-W/Na offspring showed drinking differences compared to PAL and control offspring. By analyzing the central neurobiological substrates involved, a significant increase in the number of Fos + cells was found after sodium depletion in the subfornical organ of both programmed groups and an increase in the number of Fos + cells in the dorsal raphe nucleus was only observed in adult depleted PAL-W/Na. Our results suggest that perinatal programming is a phenomenon that differentially affects particular targets which induce specific dipsogenic responses depending on matching between perinatal programming conditions and the osmotic challenge in the latter environment. Probably, each programmed-drinking phenotype has a particular set point to elicit specific repertoires of mechanisms to reestablish fluid balance.

The issues of fluid balance and fluid overload are currently considered crucial aspects of pediatric critically ill patients' care.This review describes current understanding of fluid management in critically ill children in terms of fluid balance and fluid overload and its effects on patients' outcomes. The review describes current evidence surrounding definitions, monitoring, and treatment of positive fluid balance. In particular, the review focuses on specific patient conditions, including perioperative cardiac surgery, severe acute respiratory failure, and extracorporeal membrane oxygenation therapy, as the ones at highest risk of developing fluid overload and poor clinical outcomes. Gaps in understanding include specific thresholds at which fluid overload occurs in all critically ill children or specific populations and optimal timing of decongestion of positive fluid balance.Current evidence on fluid balance in critically ill children is mainly based on retrospective and observational studies, and intense research should be recommended in this important field. In theory, active decongestion of patients with fluid overload could improve mortality and other clinical outcomes, but randomized trials or advanced pragmatic studies are needed to better understand the optimal timing, patient characteristics, and tools to achieve this.

This study sought to (a) estimate how the duration of running influences sweat losses and contributes to the daily fluid requirement, and (b) empirically estimate the drinking rates required to prevent significant dehydration (≥2% body weight as body water). Individual sweating data and running duration were obtained from male (n = 83) and female (n = 36) runners (n = 146 total observations) performing under highly heterogeneous conditions and over a range of exercise durations (33–280 min). Running 60 min/day increased the daily fluid need by a factor of 1.9–2.3. Running 60 min/day required more than 50% replacement of sweating rates to prevent the same (65/111 runners). Overall sweat losses ranged from ∼0.2 to ∼5.0 L/day, whereas the drinking rates required to prevent significant dehydration ranged from 0 to 1.4 L/hr. The characterization of sweat losses, sweat rate, and required drinking among runners in this study indicate wide individual variability that warrants personalized hydration practices, particularly when running is prolonged (>60 min) and performance is important. This study may serve as a useful guidepost for sports dietitians when planning and communicating fluid needs to athletes, as well as complement guidance related to both personalized programmed and thirst-driven drinking strategies.

Determining the optimal dialysate sodium remains one of the challenges of hemodialysis prescription. Several arguments suggest that the dialysate sodium should be individually adjusted according to the patient's natremia. This strategy is greatly facilitated by using an algorithm. Only three such algorithms have been embedded in hemodialysis machines for the widespread generalization of this strategy in clinical routine: the Diacontrol (Hospal-Baxter Healthcare Corp., Deerfield, IL, USA), the HFR-Aequilibrium (Bellco-Medtronic, Dublin, Ireland), and the Na-control (Fresenius Medical Care, Bad-Homburg, Germany).Model the solute mass-transfer across the dialyzer membrane in online hemodiafiltration and adapt the Diacontrol algorithm based on a single-pool kinetic model of sodium balance for quantifying ionic balance and managing tonicity.(1) Substituting sodium measurements with conductivity measurements allows the control of tonicity which is a more physiological parameter than natremia. (2) Consideration of all ion exchanges as a whole and not just sodium exchange avoids some of the assumptions required by kinetic modeling of sodium balance. (3) Equations provided by the model are applicable to both hemodialysis and online hemodiafiltration. (4) The differences between this model used by Diacontrol and the models on which the other two software's (HFR-Aequilibrium and Na-control) are based are highlighted.The single-pool kinetic model developed for the management of natremia in hemodialysis is also valid for the management of tonicity for both conventional hemodialysis and all online hemodiafiltration procedures.

Synopsis Early marine invertebrates like the Branchiopoda began their sojourn into dilute media some 500 million years ago in the Middle Cambrian. Others like the Mollusca, Annelida, and many crustacean taxa have followed, accompanying major marine transgressions and regressions, shifting landmasses, orogenies, and glaciations. In adapting to these events and new habitats, such invertebrates acquired novel physiological abilities that attenuate the ion loss and water gain that constitute severe challenges to life in dilute media. Among these taxon-specific adaptations, selected from the subcellular to organismal levels of organization, and constituting a feasible evolutionary blueprint for invading freshwater, are reduced body permeability and surface (S) to volume (V) ratios, lowered osmotic concentrations, increased osmotic gradients, increased surface areas of interface epithelia, relocation of membrane proteins in ion-transporting cells, and augmented transport enzyme abundance, activity, and affinity. We examine these adaptations in taxa that have penetrated into freshwater, revealing diversified modifications, a consequence of distinct body plans, morpho-physiological resources, and occupation routes. Contingent on life history and reproductive strategy, numerous patterns of osmotic regulation have emerged, including intracellular isosmotic regulation in weak hyper-regulators and well-developed anisosmotic extracellular regulation in strong hyper-regulators, likely reflecting inertial adaptations to early life in an estuarine environment. In this review, we address osmoregulation in those freshwater invertebrate lineages that have successfully invaded this biotope. Our analyses show that across 66 freshwater invertebrate species from six phyla/classes that have transmuted into freshwater from the sea, hemolymph osmolalities decrease logarithmically with increasing S:V ratios. The arthropods have the highest osmolalities, from 300 to 650 mOsmoles/kg H2O in the Decapoda with 220–320 mOsmoles/kg H2O in the Insecta; osmolalities in the Annelida range from 150 to 200 mOsmoles/kg H2O, and the Mollusca showing the lowest osmolalities at 40–120 mOsmoles/kg H2O. Overall, osmolalities reach a cut-off at ∼200 mOsmoles/kg H2O, independently of increasing S:V ratio. The ability of species with small S:V ratios to maintain large osmotic gradients is mirrored in their putatively higher Na+/K+-ATPase activities that drive ion uptake processes. Selection pressures on these morpho-physiological characteristics have led to differential osmoregulatory abilities, rendering possible the conquest of freshwater while retaining some tolerance of the ancestral medium.

Increasing trends in environmental temperatures and changes in the hydrological cycle caused by climate change are affecting organisms around the world. Water balance is an important feature of organisms as warmer and drier environments increase water vapour pressure deficit and cutaneous water loss. The aim of our study was to understand the hourly kinetics of losses under water-restricted conditions. In general, these kinetics are thought to be negligible, and values from water loss studies have often been summed or averaged for population and species comparisons. We compiled a cross-species data set of instantaneous water loss (EWL

Purpose: We aimed to provide an extended analysis of the physiological handling of of the sodium burden induced by maintenance fluids. Materials and methods: We revisited two studies that demonstrated, in healthy volunteers and in surgical patients, that maintenance fluids with 154 mmol/L of sodium lead to a more positive fluid balance than a regimen containing 54 mmol/L. We report different unpublished data on the renal handling of the imposed sodium bur -dens with specific attention to the resulting fluid and sodium balances. Results: The kidneys adapt to the sodium-rich fluids not only by altering sodium excretion, but also by retaining extra free water by concentrating urine. Realigning urinary sodium excretion with an increased administration takes around one day in health and much longer in the clinical setting. This difference may be explained by the presence of hypovolemia-induced aldosterone secretion in the latter group. Non-osmotic storage of sodium limits an unrestrained fluid retention even when very high amounts of sodium are administered but fluid accu-mulation will inevitably be further prolonged. Conclusions: Sodium administration induced by sodium-rich maintenance fluids leads, especially in the clinical setting, to prolonged fluid retention when compared with a regimen that resembles a healthy dietary sodium in-take, even when kidney function is normal. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction. METHODS AND RESULTS EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (P = .127) and +0.40 L (P = .001) in ECW (P = .001) and -0.23 L (P = .264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25. CONCLUSIONS Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.

Fluid overload in acute respiratory distress syndrome is associated with increased mortality. The purpose of this study was to investigate the association of cumulative fluid balance (CFB) during the first 7 days of veno-venous extracorporeal membrane oxygenation (VV ECMO) and mortality. Adult patients on VV ECMO for greater than 168 hours, between November 2015 and October 2019, were included. CFB during the first 7 ECMO days was compared between survivors and nonsurvivors, and survival was analyzed using Kaplan-Meier analysis and cox proportional hazards modeling. One hundred forty-six patients were included. Median age was 45 years [32, 55], respiratory ECMO survival prediction score was 3 [0, 5], and P/F ratio was 70 [55, 85]. CFB for ECMO days 1-3 was +2,350 cc [-540, 5,941], days 4-7 -3,070 cc [-6,545, 437], and days 1-7 -341 cc [-4,579, 5,290]. One hundred seventeen patients (80%) survived to hospital discharge. Survivors were younger (41 years [31, 53] vs. 53 years [45, 60], plt; 0.001) and had a higher respiratory ECMO survival prediction score, (3 [1, 5] vs. 1.5 [-1, 3], p = 0.002). VV ECMO survivors had a significantly more negative CFB during the first 7 days of VV ECMO (-1,311 cc [-4,755, 4,217] vs. 3,617 cc [-2,764, 9,413], p = 0.02), and CFB was an independent predictor of 90 day mortality (HR = 1.07 [1.01, 1.14], p = 0.02). Further studies are needed to determine the causal relationship between fluid balance and survival during VV ECMO.

PURPOSE: Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness.METHODS: Open-label, parallel-group, allocation-concealed randomised clinical feasibility trial. Mechanically ventilated adult patients expected to require critical care beyond the next calendar day were enrolled between 24 and 48 h following admission to the intensive care unit (ICU). Patients were randomised to either a 2-stage fluid strategy comprising conservative fluid administration and, if fluid overload was present, active deresuscitation, or usual care. The primary endpoint was fluid balance in the 24 h up to the start of study day 3. Secondary endpoints included cumulative fluid balance, mortality, and duration of mechanical ventilation.RESULTS: One hundred and eighty patients were randomised. After withdrawal of 1 patient, 89 patients assigned to the intervention were compared with 90 patients assigned to the usual care group. The mean plus standard deviation (SD) 24-h fluid balance up to study day 3 was lower in the intervention group (- 840 ± 1746 mL) than the usual care group (+ 130 ± 1401 mL; P CONCLUSIONS: A strategy of conservative fluid administration and active deresuscitation is feasible, reduces fluid balance compared with usual care, and may cause benefit or harm. In view of wide variations in contemporary clinical practice, large, adequately powered trials investigating the clinical effectiveness of conservative fluid strategies in critically ill patients are warranted.

Fluid overload (FO) is associated with higher rates of mortality and morbidity in pediatric and adult populations. The aim of this systematic review and meta-analysis was to investigate the association between FO and mortality in critically ill neonates. Systematic search of Ovid MEDLINE, EMBASE, Cochrane Library, trial registries, and gray literature from inception to January 2021. We included all studies that examined neonates admitted to neonatal intensive care units and described FO and outcomes of interest. We identified 17 observational studies with a total of 4772 critically ill neonates who met the inclusion criteria. FO was associated with higher mortality (OR, 4.95 [95% CI, 2.26-10.87]), and survivors had a lower percentage of FO compared with nonsurvivors (WMD, - 4.33 [95% CI, - 8.34 to - 0.32]). Neonates who did not develop acute kidney injury (AKI) had lower FO compared with AKI patients (WMD, - 2.29 [95% CI, - 4.47 to - 0.10]). Neonates who did not require mechanical ventilation on postnatal day 7 had lower fluid balance (WMD, - 1.54 [95% CI, - 2.21 to - 0.88]). FO is associated with higher mortality, AKI, and need for mechanical ventilation in critically ill neonates in the intensive care unit. Strict control of fluid balance to prevent FO is essential. A higher resolution version of the Graphical abstract is available as Supplementary information.

Kidneys continuously filter an enormous amount of sodium and adapt kidney Na+ reabsorption to match Na+ intake to maintain circulatory volume and electrolyte homeostasis. Males (M) respond to high-salt (HS) diet by translocating proximal tubule Na+/H+ exchanger isoform 3 (NHE3) to the base of the microvilli, reducing activated forms of the distal NaCl cotransporter (NCC) and epithelial Na+ channel (ENaC). Males (M) and females (F) on normal-salt (NS) diet present sex-specific profiles of “transporters” (cotransporters, channels, pumps, and claudins) along the nephron, e.g., F exhibit 40% lower NHE3 and 200% higher NCC abundance than M. We tested the hypothesis that adaptations to HS diet along the nephron will, likewise, exhibit sexual dimorphisms. C57BL/6J mice were fed for 15 days with 4% NaCl diet (HS) versus 0.26% NaCl diet (NS). On HS, M and F exhibited normal plasma [Na+] and [K+], similar urine volume, Na+, K+, and osmolal excretion rates normalized to body weight. In F, like M, HS lowered abundance of distal NCC, phosphorylated NCC, and cleaved (activated) forms of ENaC. The adaptations associated with achieving electrolyte homeostasis exhibit sex-dependent and independent mechanisms. Sex differences in baseline “transporters” abundance persist during HS diet, yet the fold changes during HS diet (normalized to NS) are similar along the distal nephron and collecting duct. Sex-dependent differences observed along the proximal tubule during HS show that female kidneys adapt differently from patterns reported in males, yet achieve and maintain fluid and electrolyte homeostasis.

In thoracic aortic surgery, fluid replacement and blood transfusion during extracorporeal circulation (ECC) are associated with increased coagulopathy, elevated inflammatory response, and end-organ dysfunction. The optimal strategy has not been established in this regard. The aim of this study was to evaluate the effect of the fluid balance during ECC in thoracic aortic dissection surgery on outcome.Between 2009 and 2020, 358 patients suffering from acute type A aortic dissection (ATAAD) underwent aortic surgery at our heart center. In-hospital mortality, major complications (postoperative stroke, respiratory failure, heart failure, acute renal failure), and follow-up mortality were assessed. Logistic regression analysis was used to identify whether fluid balance and blood transfusion during ECC were risk factors for occurring adverse events.The in-hospital mortality amounted to 20.4%. Major complications included temporary neurologic deficit in 13.4%, permanent neurologic deficit in 6.1%, acute renal failure in 32.7%, prolonged ventilation for respiratory failure in 17.9%, and acute heart failure in 10.9% of cases. At a mean of 42 months after discharge of 285 survivors, follow-up mortality was 13.3%. Multivariate analysis revealed major complications as well as the risk of in-hospital and follow-up mortality to increase with fluid balance and blood transfusion during ECC.Fluid balance and blood transfusion during ECC present with predictive potential concerning the risk of postoperative adverse events.

Volume overload is a common complication of a multitude of disease states, as well as a complication of many medical therapies. For the critically ill patient in the intensive care unit, volume overload is especially concerning when persistent past the first few days of admission. In the setting of chronic kidney disease, the maintenance of fluid balance presents additional challenges. This article focuses on the causes of volume overload as well as treatment options of the critically ill patient, including the nuances of the kidney patient, and ends with outpatient guidelines and recommendations to avoid recurrence.

The renin-angiotensin system (RAS) is a hormonal system that plays an important role in the regulation of blood pressure and cardiovascular homeostasis in mammals. In fishes, the RAS pathway participates in osmoregulation and salinity adaptation. However, the role of the RAS pathway in invertebrates, particularly in crustaceans, remains unknown. In this study, four key genes of the RAS pathway (

Background More than 50% of patients have a major complication after emergency gastrointestinal surgery. Intravenous (i.v.) fluid therapy is a life-saving part of treatment, but evidence to guide what i.v. fluid strategy results in the best outcome is lacking. We hypothesised that goal-directed fluid therapy during surgery (GDT group) reduces the risk of major complications or death in patients undergoing major emergency gastrointestinal surgery compared with standard i.v. fluid therapy (STD group). Methods In a randomised, assessor-blinded, two-arm, multicentre trial, we included 312 adult patients with gastrointestinal obstruction or perforation. Patients in the GDT group received i.v. fluid to near-maximal stroke volume. Patients in the STD group received i.v. fluid following best clinical practice. Postoperative target was 0–2 L fluid balance. The primary outcome was a composite of major complications or death within 90 days. Secondary outcomes were time in intensive care, time on ventilator, time in dialysis, hospital stay, and minor complications. Results In a modified intention-to-treat analysis, we found no difference in the primary outcome between groups: 45 (30%) (GDT group) vs 39 (25%) (STD group) (odds ratio=1.24; 95% confidence interval, 0.75–2.05; P=0.40). Hospital stay was longer in the GDT group: median (inter-quartile range), 7 (4–12) vs 6 days (4–8.5) (P=0.04); no other differences were found. Conclusion Compared with pressure-guided i.v. fluid therapy (STD group), flow-guided fluid therapy to near-maximal stroke volume (GDT group) did not improve the outcome after surgery for bowel obstruction or gastrointestinal perforation but may have prolonged hospital stay. Clinical trial registration EudraCT number 2015-000563-14; the Danish Scientific Ethics Committee and the Danish Data Protection Agency (REG-18-2015).

Background Fluid overload is associated with poor outcomes. Clinicians might be reluctant to initiate diuretic therapy for patients with recent vasopressor use. We estimated the effect on 30-day mortality of withholding or delaying diuretics after vasopressor use in patients with probable fluid overload. Methods This was a retrospective cohort study of adults admitted to ICUs of an academic medical centre between 2008 and 2012. Using a database of time-stamped patient records, we followed individuals from the time they first required vasopressor support and had >5 L cumulative positive fluid balance (plus additional inclusion/exclusion criteria). We compared mortality under usual care (the mix of care actually delivered in the cohort) and treatment strategies restricting diuretic initiation during and for various durations after vasopressor use. We adjusted for baseline and time-varying confounding via inverse probability weighting. Results The study included 1501 patients, and the observed 30-day mortality rate was 11%. After adjusting for observed confounders, withholding diuretics for at least 24 h after stopping most recent vasopressor use was estimated to increase 30-day mortality rate by 2.2% (95% confidence interval [CI], 0.9–3.6%) compared with usual care. Data were consistent with moderate harm or slight benefit from withholding diuretic initiation only during concomitant vasopressor use; the estimated mortality rate increased by 0.5% (95% CI, –0.2% to 1.1%). Conclusions Withholding diuretic initiation after vasopressor use in patients with high cumulative positive balance (>5 L) was estimated to increase 30-day mortality. These findings are hypothesis generating and should be tested in a clinical trial.

Introduction: Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. Methods: We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. Results: After 72 h, the treatment group had a fluid balance of −3840 mL versus + 425 mL (p ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10–5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, p ≤ 0.05). We did not observe any significant difference in renal outcomes. Conclusions: The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction.

The purpose of the current study was to assess effects of a hydration management program on the fluid consumption and dehydration parameters (i.e., dehydration risk scores, urine specific gravity, and urine color) of older adults. The study was conducted as a pre-/post-test quasi-experimental study with a control group (intervention group: n = 42, control group: n = 37). The hydration management program applied to the intervention group was completed in 1 week. After the intervention, the knowledge and awareness of the intervention group regarding fluid consumption increased (p = 0.001). The dehydration risk score of the intervention group was significantly lower than that of the control group (p = 0.0001). There was a significant change in average 3-day water intake (p = 0.0001), urine specific gravity value (p = 0.01), and urine color scale score (p = 0.0001) in the intervention group between pre- and post-test. The hydration management program provided a significant improvement in daily water intake and dehydration risk score and increased knowledge and awareness among older adults concerning the importance of fluid intake., Ege University Scientific Research Coordination Unit [17-HEF-003], This study was funded by the Ege University Scientific Research Coordination Unit (project number 17-HEF-003).

Background: Thiazide diuretics are a mainstay in the management of hypertension and often associated with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia and hypokalemia in thiazide users, substance-specific differences, and the association of thiazides with syncope and falls. Methods: In this cross-sectional analysis all patients admitted to an interdisciplinary emergency department in Switzerland between January 1, 2017, and December 31, 2018, with measurements of serum sodium and potassium were included. Data regarding serum electrolytes and creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney injury. Chart reviews were performed to screen for syncope or falls. Results: A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent effect was found for electrolyte disorders, and there was a variance in risk between the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk. Patients taking thiazide diuretics had significantly more episodes of syncope and falls. Conclusions: Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears to be dose-dependent and highly variable depending on the substance. Syncope and falls seem to be causally related to thiazide use. Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned.

Beer is used to socialize postexercise, celebrate sport victory, and commiserate postdefeat. Rich in polyphenols, beer has antioxidant effects when consumed in moderation, but its alcohol content may confer some negative effects. Despite beer’s popularity, no review has explored its effects on exercise performance, recovery, and adaptation. Thus, a systematic literature search of three databases (PubMed, SPORTDiscus, and Web of Science) was conducted by two reviewers. The search resulted in 16 studies that were appraised and reviewed. The mean PEDro score was 5.1. When individuals are looking to rehydrate postexercise, a low-alcohol beer (4%), it is advised to pair this with a nonalcoholic option to limit diuresis, particularly when relatively large volumes of fluid (>700 ml) are consumed. Adding Na+ to alcoholic beer may improve rehydration by decreasing fluid losses, but palatability may decrease. These conclusions are largely based on studies that standardized beverage volume, and the results may not apply equally to situations where people ingest fluids and food ad libitum. Ingesting nonalcoholic, polyphenol-rich beer could be an effective strategy for preventing respiratory infections during heavy training. If consumed in moderation, body composition and strength qualities seem largely unaffected by beer. Mixed results that limit sweeping conclusions are owed to variations in study design (i.e., hydration and exercise protocols). Future research should incorporate exercise protocols with higher ecological validity, recruit more women, prioritize chronic study designs, and use ad libitum fluid replacement protocols for more robust conclusions.

OBJECTIVES In addition to the association between positive fluid balance (FB) and acute kidney injury (AKI) after cardiac surgery reported by former studies, this study examined the relationship between FB and progressive AKI. DESIGN A retrospective, observational study. SETTING University teaching, grade A tertiary hospital in Shanghai, China. PARTICIPANTS Adult patients after cardiac surgery from July-December 2016. INTERVENTIONS Perioperative data relating to postoperative fluid intake and output were collected. AKI progression was defined as a worsening of AKI stage. FB was calculated as (fluid intake [L] - fluid output [L]/body weight [kg] × 100%). MEASUREMENTS AND MAIN RESULTS The study comprised 1,522 patients. The incidences of AKI and progressive AKI were 33.1% (n = 504) and 18.1% (n = 91), respectively. There was an exponential increase between 24-hour FB and AKI occurrence, and an approximate "U"-shape association between 48-hour FB and AKI progression. Multivariate logistic regression showed that 24-hour FB ≥5% was an independent risk factor for AKI incidence (odds ratio [OR] 3.976; p < 0.001) and 48-hour FB

Supplemental Digital Content is available in the text., OBJECTIVES: Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events. DESIGN: Nested case-control study. SETTING: The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China). PATIENTS: A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between –1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (–5 L: 1.34; –3 L: 1.14; –1 L: 0.98). CONCLUSIONS: There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between –1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

The ability of perioperative fluid management to prevent postoperative recurrence of atrial tachyarrhythmia remains controversial. The aim of the present study was to assess if intraoperative net fluid balance was associated with atrial tachyarrhythmia recurrence after the Cryo-Maze procedure.An observational cohort study.A tertiary care hospital from April 2007 to May 2019.Four hundred forty-four patients undergoing the Cryo-Maze procedure in conjunction with other cardiac surgeries.The Cryo-Maze procedure in conjunction with other cardiac surgeries.The main outcome was early atrial tachyarrhythmia recurrence, consisting of atrial fibrillation, atrial flutter, or atrial tachycardia, within the first three months after surgery. Complete follow-up was achieved in 443 patients (99.8%), of them 127 (28.6%) developed early atrial tachyarrhythmia recurrence. The median intraoperative net fluid balance was 1,627 mL (interquartile range, -215 to 3,557 mL). Multivariate logistic regression showed that intraoperative net fluid balance (p = 0.001), preoperative AF duration (adjusted odds ratio, 1.40; 95% CI, 1.17-1.68; p0.001) and left atrial volume index (aOR, 1.61; 95% CI, 1.06-2.45; p = 0.025) were independent predictors of early atrial tachyarrhythmia recurrence. The adjusted log odds were lowest (-1.52) when net fluid balance was 1,557 mL.There is a significant U-shaped association between intraoperative net fluid balance and early atrial tachyarrhythmia recurrence among patients undergoing the Cryo-Maze procedure.

Background Fluid resuscitation is necessary to correct the sepsis-induced hypoperfusion, which is contradictory to the treatment of heart failure. This study explored the association between fluid balance (FB) of the first 24 h after ICU admission and mortality in critically ill patients with heart failure and sepsis. Methods Data were extracted from the Medical Information Mart for Intensive Care database. The locally weighted scatterplot smoothing (Lowess) method was used to demonstrate the relationship between FB and in-hospital mortality. Groups were divided into high FB (≥ 55.85 ml/kg) and low FB ( Results A total of 936 patients were included. The Lowess curve showed an approximate positive linear relationship for FB and in-hospital mortality. In the multivariable logistic regression adjusted model, high FB showed strong associations with in-hospital mortality (OR 2.53, 95% CI 1.60–3.99, p Conclusion For critically ill patients with heart failure and sepsis, high FB within the first 24 h after ICU admission could serve as an independent risk factor for in-hospital mortality and 30-day mortality. The avoidance of fluid overload exerts important effects on reducing mortality in such patients.

Background Fluid overload is associated with worse outcome in critically ill patients requiring continuous renal replacement therapy (CRRT). Net ultrafiltration (UFNET) allows precise control of the fluid removal but is frequently ceased due to hemodynamic instability episodes. However, approximately 50% of the hemodynamic instability episodes in ICU patients treated with CRRT are not associated with preload dependence (i.e., are not related to a decrease in cardiac preload), suggesting that volume removal is not responsible for these episodes of hemodynamic impairment. The use of advanced hemodynamic monitoring, comprising continuous cardiac output monitoring to repeatedly assess preload dependency, could allow securing UFNET to allow fluid balance control and prevent fluid overload. Methods The GO NEUTRAL trial is a multicenter, open-labeled, randomized, controlled, superiority trial with parallel groups and balanced randomization with a 1:1 ratio. The trial will enroll adult patients with acute circulatory failure treated with vasopressors and severe acute kidney injury requiring CRRT who already have been equipped with a continuous cardiac output monitoring device. After informed consent, patients will be randomized into two groups. The control group will receive protocolized fluid removal with an UFNET rate set to 0–25 ml h−1 between inclusion and H72 of inclusion. The intervention group will be treated with an UFNET rate set on the CRRT of at least 100 ml h−1 between inclusion and H72 of inclusion if hemodynamically tolerated based on a protocolized hemodynamic protocol aiming to adjust UFNET based on cardiac output, arterial lactate concentration, and preload dependence assessment by postural maneuvers, performed regularly during nursing rounds, and in case of a hemodynamic instability episode. The primary outcome of the study will be the cumulative fluid balance between inclusion and H72 of inclusion. Randomization will be generated using random block sizes and stratified based on fluid overload status at inclusion. The main outcome will be analyzed in the modified intention-to-treat population, defined as all alive patients at H72 of inclusion, based on their initial allocation group. Discussion We present in the present protocol all study procedures in regard to the achievement of the GO NEUTRAL trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial result report. Enrollment of patients in the GO NEUTRAL trial has started on June 31, 2021, and is ongoing. Trial registration ClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.

Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol.We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3–5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid’s oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.

Positive fluid balance (FB) in the intensive care unit (ICU) may be a marker for increased venous thromboembolism (VTE) risk. We hypothesized that an early positive fluid balance (FB) would be associated with increased VTE occurrence.A single-center retrospective review of surgical ICU patients was conducted from May 2011 to December 2014. Patients with a VTE were compared to those who did not develop a VTE (NVTE).There were 619 patients analyzed with 77 (12.4%) diagnosed with a VTE; these patients had longer ventilator days (12.3 vs. 5.0 days, p 0.01) and ICU stays (10.3 vs. 6.4 days, p 0.01), and were more likely to have a net FB ≥ 4L over the first three days (62% vs. 44%, p 0.01). A FB ≥ 4L over the first three ICU days was an independent predictor of VTE (AOR 1.74, p = 0.04).Patients with an early positive FB are more likely to develop a VTE.

This review explores the effects of oestrogen and progesterone fluctuations across the menstrual cycle on fluid and electrolyte balance. The review aims to provide information on this topic for the exercising female but also for researchers working in this field. Beginning with a basic introduction to fluid and electrolyte balance, the review goes on to describe how oestrogen and progesterone have independent and integrated roles to play in the regulation of fluid and electrolyte balance. Despite evidence that oestrogen can influence the osmotic threshold for arginine vasopressin release, and that progesterone can influence aldosterone production, these actions do not appear to influence fluid retention, plasma volume changes at rest and during exercise, or electrolyte losses. However, the large inter-individual variations in hormonal fluctuations throughout the menstrual cycle may mean that specific individuals with high fluctuations could experience disturbances in their fluid and electrolyte balance. During phases of oestrogen dominance (e.g. late-follicular phase) heat dissipation is promoted, while progesterone dominance (e.g. mid-luteal phase) promotes heat conservation with overall higher basal body temperature. However, these responses do not consistently lead to any change in observed sweat rates, heat-stress, or dehydration during exercise. Finally, the literature does not support any difference in fluid retention during post-exercise rehydration periods conducted at different menstrual cycle phases. Although these mean responses largely reveal no effects on fluid and electrolyte balance, further research is required particularly in those individuals who experience high hormonal fluctuations, and greater exploration of oestrogen to progesterone interactions is warranted.

Background: The current practice of fluid intake and output monitoring for hospitalised patients in one local acute care tertiary hospital was unclear and inconsistent. Inaccurate fluid balance monitoring and poor documentation can result in poor clinical outcomes. Aim: To provide an overview of the current practice of ordering, monitoring and documentation of patient fluid intake and output during hospitalisation. Methods: Electronic charts of 2199 adults were reviewed for appropriateness and accuracy of monitoring and documentation of the fluid balance records. Data retrieved for each patient included: (1) Was daily fluid balance monitoring clinically indicated? (2) Was daily fluid balance monitoring prescribed by the doctors or initiated by the nurses? (3) Was the daily fluid balance documentation accurate for the entire admission? Findings: Of the reviewed patients, 68% were on fluid balance monitoring, of whom 31% were prescribed by medical teams and 69% were nurse-initiated. Among patients who were receiving fluid balance monitoring, 78% were clinically indicated (35% prescribed by doctors), and 22% had no clinical indications (18% prescribed by doctors). Overall, documentation accuracy of the intake and output charts was 77%, with 100% accuracy in the oral and intravenous fluid intake, and 21% accuracy in the output documentation. Among the inaccurate documentation of monitoring with no quantifiable amount, ‘void in toilet’ was the most inaccurately documented (93.3%). Conclusions: It is vital to address the current disparities in hospital practice, which include prescribing fluid balance monitoring for patients without a clinical indication and documenting incomplete or poor quality information in patients' intake and output charts. Future quality improvement and research work is needed to improve patient safety and outcomes.

To study the association of cumulative fluid balance and clinical outcomes in a pediatric intensive care unit (PICU) practicing restrictive fluid protocol. In this prospective cohort study, children aged less than 13 y admitted for more than 48 h were screened. Children with unstable hemodynamics throughout the stay were excluded. Fluid balance was calculated by percentage fluid overload (%FO) for the first 7 d. Patients were divided into positive fluid and negative fluid balance groups. The primary outcome was all-cause 28-d mortality. A total of 888 patients (positive fluid balance group = 531, negative fluid balance group = 357) were analyzed. Mean (SD) cumulative %FO was 1.52 (0.67) vs. −1.18 (0.71), p = < 0.001, and minimum and maximum cumulative %FO were −3.0% and 3.1%, respectively. There was no significant difference in all-cause 28-d mortality between the two groups (n = 104/531, 19.6% vs. n = 60/357, 16.8%, RR = 1.17, 95% CI 0.87 to 1.55; p = 0.29). There was no difference in organ dysfunction [mean (SD) sequential organ failure assessment (SOFA) score 3.3 (0.7) vs. 3.3 (0.6)], acute kidney injury (65% vs. 63.6%), need for renal replacement therapy (14% vs. 13%), and duration of ventilation (median, IQR 4, 2–6 vs. 4, 2–6 d). Longer stay in PICU (5, 3–9 vs. 4, 3–7 d; p = 0.014) and in hospital (8, 5–11 vs. 7, 4–10 d; p = 0.007) were noted in the positive fluid balance group. Cumulative fluid balance within 3% using restrictive fluid protocol was not associated with a significant difference in PICU mortality and morbidity.

Newborns with gastroschisis require appropriate fluid resuscitation but are also at risk for hyponatremia that may lead to adverse outcomes. The etiology of hyponatremia in gastroschisis has not been defined.Over a 24-month period, all newborns with gastroschisis in a free-standing pediatric hospital had sodium levels measured from serum, urine, gastric output, and the bowel bag around the eviscerated contents for the first 48 h of life. Total fluid intake and output were measured. Maintenance fluids were standardized at 120 mL/kg/day. Hyponatremia was defined as a serum sodium132 mEq/L. A logistic regression model was created to determine independent predictors of hyponatremia.28 infants were studied, and 14 patients underwent primary closure. While serum sodium was normal in all patients at birth, 9 (32%) infants developed hyponatremia at a median of 17.4 h of life. On univariate analysis, hyponatremic babies had a greater net positive fluid balance (74.9 vs 114.7 mL/kg, p = 0.001) primarily due to a decrease in total fluid output (p = 0.05). On multivariable regression, a 10 mL/kg increase in overall fluid balance was associated with an increased risk of developing hyponatremia (OR 1.84 [1.23, 3.45], p = 0.016). No differences in the sodium content of urine, gastric, or bowel bag fluid were observed, and sodium balance was equivalent between cohorts.Hyponatremia in babies with gastroschisis in the early postnatal period was associated with positive fluid balance and decreased fluid output. Prospective studies to determine the appropriate fluid resuscitation strategy in this population are warranted.

Osmoregulatory abilities and mechanisms of adults and larvae of decapod crustaceans have been extensively investigated. However, how embryos carried by their mothers can deal with changing or extreme salinities is less understood. The egg membranes are believed to isolate embryos from a challenging environment, although osmoregulatory ability has been demonstrated in early developing embryos (naupliar stage) of two crabs. To establish whether embryos are isolated by their membranes and/or are able to osmoregulate, we measured the survival and volume change over 48 h of oocytes and embryos in different stages of three carideans (Betaeus lilianae, Palaemon macrodactylus and P. argentinus) and the brachyuran Neohelice granulata, subjected to different salinities. In addition, we recorded osmolality changes in homogenates of the same stages in P. argentinus and N. granulata after 2 h of exposure and mapped the presence of putative sites of ions exchange in the membrane of all species. High mortality, when it occurred, was associated with low salinity and mortality variation with the stage of development depended on the species. All species precipitated silver salts in or under the egg envelope, with a different pattern between carideans and the brachyuran. Changes in osmolality and egg volume after hypo- or hyper-osmotic salinity challenges indicate that eggs are not fully isolated by their membranes, and that some osmoregulatory mechanisms are in play to maintain developmental homeostasis. We suggest that egg membranes can participate in osmoregulation by selectively transporting ions to an intramembrane space, with differences between carideans and brachyurans.

Urine specific gravity reflects hydration status and correlates well with urine osmolality.To compare intravenous fluid therapy guided with and without inclusion of urine specific gravity to the standard parameters for maintaining postnatal weight loss within permissible limits in neonates admitted to the intensive care unit.An open-label randomized controlled trial was conducted, including neonates requiring intravenous fluids for ≥72 hours, randomized into the study (urine specific gravity guided fluids) and control arms. The outcomes of the study were to determine proportion of neonates with weight loss within permissible limits, mean percentage weight loss and number of days to reach maximum weight loss.80 preterm and term neonates (40 in each arm) were enrolled. A comparable proportion of neonates had weight loss within permissible limits in study arm and in control arms [39 (97.5%) vs 36 (90%); P=0.165]. The (mean (SD) percentage weight loss was significantly less in the study arm compared to control arm [All neonates: 7.2(2.6) vs 9.3(3.5); P=0.004); preterm neonates: 7.7 (2.8) vs 11 (3.9); P=0.008)]. Preterm neonates in the study arm attained nadir weight significantly earlier than in the controls (P=0.03) and attained complete enteral feeding earlier. Urine specific gravity showed a moderate negative correlation with the percentage weight loss.Using urine specific gravity to regulate intravenous fluids in neonates resulted in a significant reduction in postnatal weight loss, especially in preterm neonates.

Prostaglandin E2 (PGE2) is an important prostanoid expressing throughout the kidney and cardiovascular system. Despite the diverse effects on fluid metabolism and blood pressure, PGE2 is implicated in sustaining volume and hemodynamics homeostasis. PGE2 works through four distinct E-prostanoid (EP) receptors which are G protein-coupled receptors. To date, pharmacological specific antagonists and agonists of all four subtypes of EP receptors and genetic targeting knockout mice for each subtype have helped in uncoupling the diverse functions of PGE2 and discriminating the respective characteristics of each receptor. In this review, we summarized the functions of individual EP receptor subtypes in the renal and blood vessels and the molecular mechanism of PGE2-induced fluid metabolism and blood pressure homeostasis.

Autosomal dominant mutations in FAM111A are causative for Kenny-Caffey syndrome type 2. Patients with Kenny-Caffey syndrome suffer from severe growth retardation, skeletal dysplasia, hypoparathyroidism, hypocalcaemia, hyperphosphataemia and hypomagnesaemia. While recent studies have reported FAM111A to function in antiviral response and DNA replication, its role in regulating electrolyte homeostasis remains unknown. In this study, we assessed the role of FAM111A in the regulation of serum electrolyte balance using a Fam111a knockout (Fam111a−/−) C57BL/6 N mouse model. Fam111a−/− mice displayed normal weight and serum parathyroid hormone (PTH) concentration and exhibited unaltered magnesium, calcium and phosphate levels in serum and 24-hour urine. Expression of calciotropic (including Cabp28k, Trpv5, Klotho and Cyp24a1), magnesiotropic (including Trpm6, Trpm7, Cnnm2 and Cnnm4) and phosphotropic (Slc20a1, Slc20a2, Slc34a1 and Slc34a3) genes in the kidneys, duodenum and colon were not affected by Fam111a depletion. Only Slc34a2 expression was significantly upregulated in the duodenum, but not in the colon. Analysis of femurs showed unaffected bone morphology and density in Fam111a−/− mice. Kidney and parathyroid histology were also normal in Fam111a−/− mice. In conclusion, our study is the first to characterise the function of FAM111A in vivo and we report that mice lacking FAM111A exhibit normal electrolyte homeostasis on a standard diet.

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.

Diagnosis of fluid overload (FO) in early stage is essential to manage fluid balance of patients with chronic kidney disease (CKD) and to prevent cardiovascular disease (CVD). However, the identification of fluid status in patients with CKD is largely dependent on the physician's clinical acumen. The ratio of fluid overload to extracellular volume (FO/ECV) has been used as a reference to assess fluid status. The primary aim of this study was to compare FO/ECV with other bioimpedance methods and clinical assessments in patients with CKD. Whole body ECV, intracellular volume (ICV), total body water (TBW), and calf normalized resistivity (CNR) were measured (Hydra 4200). Thresholds of FO utilizing CNR and ECV/TBW were derived by receiver operator characteristic (ROC) analysis based on data from pooled patients with CKD and healthy subjects (HSs). Clinical assessments of FO in patients with CKD were performed by nephrologists. Patients with CKD (stage 3 and stage 4) (

Maintenance of electrolyte balance in the neonate is a challenge in the context of illness or prematurity. Neonatal providers’ approach to fluid management changes and adapts based on the newborn’s age, maintenance needs, deficits, and ongoing losses. Understanding the total body water content of the fetus and newborn is foundational to management of electrolyte disturbances. This article reviews common imbalances of sodium and chloride, identifies causes of imbalances, and discusses current evidence-based treatment options.

Background Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods We analyzed data from the multicenter observational ‘PRactice of VENTilation in COVID-19 patients’ study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. Results Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27–7.72 L), 0.78 L (0.26–1.27 L), and − 0.35 L (− 6.52–0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77–0.95, P = 0.0047). Sensitivity analyses showed similar results. Conclusions In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov (NCT04346342); Date of registration: April 15, 2020. Graphical abstract

Background Hyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions. Results The initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P . Conclusions The hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap. Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092

Background Intra-abdominal hypertension (IAH) is frequently encountered in critically ill surgical patients. We aimed to evaluate the incidence of IAH after orthotopic liver transplant (OLT) and its impact on organ function, hospital length-of-stay (LOS), and death. Methods This prospective, observational, cohort study evaluated consecutive adult patients admitted in the ICU after undergoing OLT. Intra-abdominal pressure (IAP) was measured every 4–6 h for 3 days. Worsening IAP was defined as a gradual increase in IAP over a period of time. Daily fluid balance was the daily sum of all intakes minus the output. Results IAH was observed in 48% of the patients within the first 3 days after ICU admission, while ACS was diagnosed in 15%. Patients with IAH had a higher positive fluid balance at day 1 (1764 mL [812–2733 mL] vs. 1301 mL [241–1904 mL], p = 0.025). Worsening IAH was associated with fewer days free of organ dysfunction. IAH within 72 h after ICU admission was independently associated with a composite outcome of death or a longer ICU LOS (odds ratio 2.9; CI 95% 1.02–8.25, p = 0.043). Conclusion After OLT, nearly half of the patients presented IAH, that was associated with unfavorable outcomes.

Postnatal growth failure is a common morbidity for preterm infants and is associated with adverse neurodevelopmental outcomes. Although sodium (Na) deficiency early in life impairs somatic growth, its impact on neurocognitive functions has not been extensively studied. We hypothesized that Na deficiency during early life is sufficient to cause growth failure and program neurobehavioral impairments in later life. C57BL/6J mice were placed on low- (0.4), normal- (1.5), or high- (3 g/kg) Na chow at weaning ( PD22) and continued on the diet for 3 wk (to PD40). Body composition and fluid distribution were determined serially by time-domain NMR and bioimpedance spectroscopy, and anxiety, learning, and memory were assessed using the elevated plus maze and Morris water maze paradigms in later adulthood ( PD63– PD69). During the diet intervention, body mass gains were suppressed in the low- compared with normal- and high-Na groups despite similar caloric uptake rates across groups. Fat mass was reduced in males but not in females fed low-Na diet. Fat-free mass and hydration were significantly reduced in both males and females fed the low-Na diet, although rapidly corrected after return to normal diet. Measures of anxiety-like behavior and learning in adulthood were not affected by diet in either sex, yet memory performance was modified by a complex interaction between sex and early life Na intake. These data support the concepts that Na deficiency impairs growth and that the amount of Na intake which supports optimal somatic growth during early life may be insufficient to fully support neurocognitive development.