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Introduction: Insufficient knowledge of intravenous fluid therapy is a significant challenge contributing to morbidity and mortality in hospitalized patients. Nurses play a critical role in evaluating patients' fluid and electrolyte balance as well as in restoring fluid levels. Various studies have indicated a deficiency in nurses' knowledge of intravenous therapy, yet this remains understudied in many settings, including Namibia. Objectives: To assess nurses' knowledge of intravenous fluid therapy and to describe the variables associated with knowledge of intravenous fluid therapy at a teaching hospital in Namibia. Methods: A cross-sectional online survey involving 164 nurses who were recruited using total population sampling. Data were collected between September and November 2021, using a self-administered 14-item validated tool (α = 0.8). Data analysis was conducted using SPSSv28.0 software. Results: The majority of nurses (84%) in this study exhibited an insufficient level of knowledge regarding intravenous therapy, with only a minority (16%) demonstrating a moderately adequate understanding of intravenous fluid therapy. A significant positive correlation was found between educational qualification and knowledge of intravenous therapy (r = 0.21; p =.01). Conclusion: The study's results indicate a worrying trajectory in nurses' knowledge of intravenous therapy. These findings underscore the need for hospitals to establish comprehensive training programs for nurses to guarantee the provision of secure and efficient intravenous therapy. Additional research is needed to investigate how educational qualifications impact patient outcomes related to intravenous therapy. [ABSTRACT FROM AUTHOR]

Introduction: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high‐volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low‐volume IV fluids during labor (<2500 mL). Material and Methods: A retrospective cohort study was conducted at a tertiary referral hospital in Sydney, Australia between 1st September 2021 and 31st October 2022. Inclusion criteria were: women with a live singleton fetus in a cephalic presentation; planning a vaginal birth; and admitted for labor and birth care between 37 and 42 week gestation. The study factor was IV fluids during labor and the primary outcome was primary PPH ≥500 mL. Secondary outcomes included cesarean section and major perineal injury. Pregnancy, birth, and postnatal data were obtained from the hospital's electronic clinical database, electronic medical records, and paper fluid order documentation. Multivariable logistic regression and multiple imputation were used to explore the relationship between volume of IV fluids in labor and PPH. Results: A total of 1023 participants were included of which 339 had a primary PPH (33.1%). There was no association between high‐volume IV fluids and PPH after adjusting for demographic and clinical factors (adjusted odds ratio [ORadj]1.02 95% confidence interval [95%CI] 0.72, 1.44). However, there was a positive association between high‐volume IV fluids and cesarean section (ORadj 1.99; 95%CI 1.4, 2.8). Conclusions: The findings of this research are important to further knowledge relating to the administration of IV fluids during labor. The findings emphasize the importance of accurately documenting IV fluids administration and identifies research priorities to enable us to better understand the broader implications of IV fluids administration on pregnancy and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Aim: To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very‐low‐birthweight (VLBW, <1500 g) infants during the first week of life. Methods: This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23–26 (n = 275), 27–29 (n = 433) and 30–31 (n = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. Results: The median sodium intake was highest in the 23–26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23–26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23–26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. Conclusion: Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load. [ABSTRACT FROM AUTHOR]

Innovations in healthcare technologies have the potential to address challenges, including the monitoring of fluid balance. This study aims to evaluate the functionality and accuracy of a digital technology compared to standard manual documentation in a real-life setting. The digital technology, LICENSE, was designed to calculate fluid balance using data collected from devices measuring urine, oral and intravenous fluids. Participating patients were connected to the LICENSE system, which transmitted data wirelessly to a database. These data were compared to the nursing staff’s manual measurements documented in the electronic patient record according to their usual practice. We included 55 patients in the Urology Department needing fluid balance charting and observed them for an average of 22.9 hours. We found a mean difference of -44.2 ml in total fluid balance between the two methods. Differences ranged from -2230 ml to 2695 ml, with a divergence exceeding 500 ml in 57.4% of cases. The primary source of error was inaccurate or omitted manual documentation. However, errors were also identified in the oral LICENSE device. When used correctly, the LICENSE system performs satisfactorily in measuring urine and intravenous fluids, although the oral device requires revision due to identified errors. [ABSTRACT FROM AUTHOR]

IntroductionThe interstitial space harbours two fluid compartments linked serially to the plasma. This study explores conditions that lead to fluid accumulation in the most secluded compartment, termed the “third space”.MethodsRetrospective data was collected from 326 experiments in which intravenous crystalloid fluid was administered to conscious volunteers as well as a small group of anaesthetized patients. The urinary excretion and plasma dilution derived from haemoglobin served as input variables in nine population volume kinetic analyses representing subtly different settings.ResultsAn infusion of 250–500 mL of Ringer’s solution expanded only the central fluid space (plasma), whereas the infusion of 500–1,000 mL extended into a rapidly exchanging interstitial fluid space. When more than 1 L was infused over 30 min, it was distributed across plasma and both interstitial fluid compartments. The remote space, characterized by slow turnover, abruptly accommodated fluid upon accumulation of 700–800 mL in the rapidly exchanging space, equivalent to an 11%–13% volume increase. However, larger expansion was necessary to trigger this event in a perioperative setting. The plasma half-life of crystalloid fluid was 25 times longer when 2,000–2,700 mL expanded all three fluid compartments compared to when only 250–500 mL expanded the central space (14 h versus 30 min).ConclusionAs the volume of crystalloid fluid increases, it apparently occupies a larger proportion of the interstitial space. When more than 1 L is administered at a high rate, there is expansion of a remote “third space”, which considerably extends the intravascular half-life.

BACKGROUND: Precise fluid balance monitoring is essential for patient treatment, as incorrect fluid balance can lead to disorders. OBJECTIVE: This study aimed to assess the accuracy of the digital technology LICENSE (LIquid balanCE moNitoring SystEm) for fluid balance charting and compare it to the standard method (SM) to determine its usability in clinical practice. METHODS: This prospective study included 20 patients. The results from LICENSE were compared to those from SM and a reference measurement (manual weight of fluids, RM). Three LICENSE devices were used for urine output, intravenous fluids, and oral fluid intake. The accuracy of methods was evaluated using Bland Altman plots. RESULTS: The mean difference between LICENSE and RM was less than 2 millilitres (p = 0.031 and p = 0.047), whereas the mean difference between SM and RM was 6.6 ml and 10.8 ml (p < 0.0001). The range between the upper and lower limits of agreement was between 16.4 and 27.8 ml for LICENSE measurements and 25.2 and 52 ml for SM. CONCLUSION: LICENSE is comparable to or more accurate than the standard method for fluid balance monitoring. The use of LICENSE may improve the accuracy of fluid balance measurements. Further research is needed to evaluate its feasibility in daily clinical practice. [ABSTRACT FROM AUTHOR]

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.

Stroke clinical guidelines recommend care processes that optimize patient outcomes and minimize hospital‐acquired complications. However, audits and surveys illustrate that recommended care is not always consistently or thoroughly implemented. This paper outlines the methods for implementing and evaluating a new bundle of care. Screen‐Clean‐Hydrate bundles together recommendations from the Australian Clinical Guidelines for Stroke Management and supplements these with evidence‐informed best practice from the literature for: swallow screening within 4 h of presentation to hospital (Screen); oral health assessment and delivery of oral care (Clean); and hydration assessment and management (Hydrate). The study is a pre−post Type 2 hybrid effectiveness/implementation design with an embedded process evaluation, which will be conducted in two acute stroke units in a capital city of Australia. The integrated‐Promoting Action on Research Implementation in Health Services (iPARIHS) framework will be used to guide study design, conduct, and evaluation. Clinical effectiveness will be measured by rates of hospital‐acquired complications and proxy measures of cost (length of stay, procedure costs) for 60 patient participants pre‐ and postimplementation. Implementation outcomes will focus on acceptability, feasibility, uptake and fidelity, and identification of barriers and enablers to implementation through staff interviews, medical record audits, and researcher field notes. Due to its design as a hybrid effectiveness/implementation study, once completed, the study will provide information on both intervention and implementation effectiveness, including details of successful and unsuccessful multidisciplinary implementation strategies. This will inform a larger multisite effectiveness/implementation trial for future upscale, leading to improved compliance with stroke guidelines and therefore stroke outcomes. [ABSTRACT FROM AUTHOR]

Background: Intention-to-treat analyses of POINCARE-2 trial led to inconclusive results regarding the effect of a conservative fluid balance strategy on mortality in critically ill patients. The present as-treated analysis aimed to assess the effectiveness of actual exposure to POINCARE-2 strategy on 60-day mortality in critically ill patients. Methods: POINCARE‑2 was a stepped wedge randomized controlled trial. Eligible patients were ≥ 18 years old, under mechanical ventilation and had an expected length of stay in ICU > 24 h. POINCARE-2 strategy consisted of daily weighing over 14 days, and subsequent restriction of fluid intake, administration of diuretics, and/or ultrafiltration. We computed a score of exposure to the strategy based on deviations from the strategy algorithm. We considered patients with a score ≥ 75 as exposed to the strategy. We used logistic regression adjusted for confounders (ALR) or for an instrumental variable (IVLR). We handled missing data using multiple imputations. Results: A total of 1361 patients were included. Overall, 24.8% of patients in the control group and 69.4% of patients in the strategy group had a score of exposure ≥ 75. Exposure to the POINCARE-2 strategy was not associated with 60-day all-cause mortality (ALR: OR 1.2, 95% CI 0.85–1.55; IVLR: OR 1.0, 95% CI 0.76–1.33). Conclusion: Actual exposure to POINCARE-2 conservative strategy was not associated with reduced mortality in critically ill patients. Trial registration POINCARE-2 trial is registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016. [ABSTRACT FROM AUTHOR]

BackgroundAmong critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization.MethodsWe conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables.ResultsAmong 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (- 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08).ConclusionsEarlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality.Trial registrationClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722 , registered October 6, 2015.

Rapid weight loss or "weight cutting" is a common but potentially harmful practice used in mixed martial arts competition. Following the official weigh-in, competitors refeed and rehydrate themselves in a process known as rapid weight gain (RWG) to realize a potential competitive advantage. While data from surveys and small series have indicated the majority of mixed martial arts athletes engage in rapid weight loss, there is a lack of officially collected data from sanctioning organizations describing its prevalence. The present investigation represents a summary of the data collected between December 2015 and January 2018 by the California State Athletic Commission. In total, 512 professional mixed martial artists (455 males and 57 females) were included. Of these, 503 (98%) athletes gained body mass between weigh-in and their bouts. Total RWG between weigh-in and competition was 5.5 ± 2.5 kg, corresponding to an 8.1% ± 3.6% body mass increase. Total RWG was 5.6 ± 2.5 kg (8.1% ± 3.6%) for males and 4.5 ± 2.3 kg (8.0% ± 3.8%) for females. More than one quarter of men and one third of women gained >10% body mass between weigh-in and competition. Athletes from leading international promotions gained more absolute, but not relative, body mass than those from regional promotions. Our findings indicate RWG is nearly ubiquitous in professional , with a similar prevalence in male and female athletes. Trends based on promotion suggest a larger magnitude of RWG in presumably more experienced and/or successful mixed martial artists from leading international promotions. [ABSTRACT FROM AUTHOR]

Abstract Background In critically ill patients, positive fluid balance is associated with excessive mortality. The POINCARE-2 trial aimed to assess the effectiveness of a fluid balance control strategy on mortality in critically ill patients. Methods POINCARE-2 was a stepped wedge cluster open-label randomized controlled trial. We recruited critically ill patients in twelve volunteering intensive care units from nine French hospitals. Eligible patients were ≥ 18 years old, under mechanical ventilation, admitted to one of the 12 recruiting units for > 48 and ≤ 72 h, and had an expected length of stay after inclusion > 24 h. Recruitment started on May 2016 and ended on May 2019. Of 10,272 patients screened, 1361 met the inclusion criteria and 1353 completed follow-up. The POINCARE-2 strategy consisted of a daily weight-driven restriction of fluid intake, diuretics administration, and ultrafiltration in case of renal replacement therapy between Day 2 and Day 14 after admission. The primary outcome was 60-day all-cause mortality. We considered intention-to-treat analyses in cluster-randomized analyses (CRA) and in randomized before-and-after analyses (RBAA). Results A total of 433 (643) patients in the strategy group and 472 (718) in the control group were included in the CRA (RBAA). In the CRA, mean (SD) age was 63.7 (14.1) versus 65.7 (14.3) years, and mean (SD) weight at admission was 78.5 (20.0) versus 79.4 (23.5) kg. A total of 129 (160) patients died in the strategy (control) group. Sixty-day mortality did not differ between groups [30.5%, 95% confidence interval (CI) 26.2–34.8 vs. 33.9%, 95% CI 29.6–38.2, p = 0.26]. Among safety outcomes, only hypernatremia was more frequent in the strategy group (5.3% vs. 2.3%, p = 0.01). The RBAA led to similar results. Conclusion The POINCARE-2 conservative strategy did not reduce mortality in critically ill patients. However, due to open-label and stepped wedge design, intention-to-treat analyses might not reflect actual exposure to this strategy, and further analyses might be required before completely discarding it. Trial registration POINCARE-2 trial was registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016.

BackgroundHemodialysis sessions frequently become unstable from complications such as intradialytic hypotension and untoward symptoms. Previous patient safety initiatives promote prevention of treatment complications; yet, they have placed little specific focus on avoidable session instability. A patient-centered definition of session instability grounded in patient experiences, and an understanding of patient perceptions of causes and solutions to instability, may enable such efforts.MethodsTwenty-five participants participated in three focus groups and/or a survey. They were purposively sampled for variation in region of residence, and sensitivity to patient well-being. Focus group recordings were analyzed using descriptive coding, in vivo coding, and thematic analysis.ResultsPatients define unstable sessions ("bad runs") as those in which they experience severe discomfort or unanticipated events that interfere with their ability to receive therapy. Bad runs were characterized primarily by cramping, low blood pressure ("crashing"), cannulation-related difficulties ("bad sticks"), and clotting of the dialysis circuit or vascular access. Patients believed that cramping and crashing could be explained by both patient and clinician behavior: patient fluid consumption and providers' fluid removal goals. Patients felt that the responsibility for cannulation-related problems lay with dialysis staff, and they asked for different staff or self-cannulated as solutions. Clotting was viewed as an idiosyncratic issue with one's body, and perceived solutions were clinician-driven. Patients expressed concern about "bad runs" on their ability to achieve fluid balance.ConclusionsFindings point to novel priorities for efforts to enhance hemodialysis session stability, and areas in which patients can be supported to become involved in such efforts.

It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to sulfate, and therefore the mEq sulfate excreted in the urine is counted as acid retained in the body. In this study we show that pH in fluids with constant [Na] and [HEPES] declines as sulfate ions are added, and we show that titratable acidity increases exactly with the equivalents of sulfate. Therefore, sulfate excretion in urine is also acid excretion per se. This is in accordance with the down-regulation of proximal sulfate reabsorption under acidosis and the observation that children with distal renal tubular acidosis may be sulfate depleted. These results are well explained using charge-balance modeling, which is based only on the three fundamental principles of electroneutrality, conservation of mass, and rules of dissociation as devised from physical chemistry. In contrast, the findings are in contrast to expectations from conventional narratives. These are unable to understand the decreasing pH as sulfate is added since no conventional acid is present. The results may undermine the traditional notion of endogenous acid production since in the case of sulfur balance, S oxidation and its excretion as sulfate exactly balance each other. Possible clinical correlates with these findings are discussed. [ABSTRACT FROM AUTHOR]

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

It has been shown that the ability to predict the pH in any chemically characterized fluid, together with its buffer-capacity and acid content can be based on the requirement of electroneutrality, conservation of mass, and rules of dissociation as provided by physical chemistry. More is not required, and less is not enough. The charge in most biological fluids is dominated by the constant charge on the completely dissociated strong ions but, nonetheless, a persistent narrative in physiology has problematized the notion that these have any role at all in acid-base homeostasis. While skepticism is always to be welcomed, some common arguments against the importance of strong ions are examined and refuted here. We find that the rejection of the importance of strong ions comes with the prize that even very simple systems such as fluids containing nothing else, or solutions of sodium bicarbonate in equilibrium with known tensions of CO2 become incomprehensible. Importantly, there is nothing fundamentally wrong with the Henderson–Hasselbalch equation but the idea that it is sufficient to understand even simple systems is unfounded. What it lacks for a complete description is a statement of charge-balance including strong ions, total buffer concentrations, and water dissociation. [ABSTRACT FROM AUTHOR]

Objectives: To explain the high mortality of septic shock in children with cancer. Methods: A retrospective cohort from 2016 to 2020, of children aged 0 to 18 years, and septic shock. Results: The authors included 139 patients. Acute lymphocytic leukemia was the most frequent diagnosis (16.5%), and Gram-negative bacteria were the most frequent blood culture isolates (22.3%). There were 57 deaths in ICU (41%), 10 in the first 24 hours of shock (early death). A LASSO model with variables: neutropenia (coefficient 0.215), respiratory (0.81), hematological (1.41), and neurological (0.72) dysfunctions, age (-0.002) and solid tumor recurrence (0.34) generated AUC = 0.79 for the early death outcome. Survivors had significant differences in the PRISM-IV score (mean ± SD 10.9 ± 6.2 in the survivors, 14.1 ± 6.5 in the deceased, p = 0.004), and in the mean number of organ dysfunctions (3.2 ± 1.1 in the survivors, 3.8 ± 6.5 in the deceased, p < 0.001). A positive fluid balance in the first 24 hours of sepsis between 2% and 6% of body weight showed a reduction effect on the probability of death in ICU (hazard ratio 0.47, 95% CI 0.24-0.92, p = 0.027). The recurrence of any cancer was a predictor of in-hospital death, regardless of severity. Conclusions: Recurrence of any cancer is an important risk of sepsis-related death. A positive fluid balance between 20 and 60 mL/kg or 2% and 6% of body weight in the first 24 hours after the onset of sepsis is related to lower mortality. [ABSTRACT FROM AUTHOR]

Background: In critically ill patients, positive fluid balance is associated with excessive mortality. The POINCARE-2 trial aimed to assess the effectiveness of a fluid balance control strategy on mortality in critically ill patients. Methods: POINCARE-2 was a stepped wedge cluster open-label randomized controlled trial. We recruited critically ill patients in twelve volunteering intensive care units from nine French hospitals. Eligible patients were ≥ 18 years old, under mechanical ventilation, admitted to one of the 12 recruiting units for > 48 and ≤ 72 h, and had an expected length of stay after inclusion > 24 h. Recruitment started on May 2016 and ended on May 2019. Of 10,272 patients screened, 1361 met the inclusion criteria and 1353 completed follow-up. The POINCARE-2 strategy consisted of a daily weight-driven restriction of fluid intake, diuretics administration, and ultrafiltration in case of renal replacement therapy between Day 2 and Day 14 after admission. The primary outcome was 60-day all-cause mortality. We considered intention-to-treat analyses in cluster-randomized analyses (CRA) and in randomized before-and-after analyses (RBAA). Results: A total of 433 (643) patients in the strategy group and 472 (718) in the control group were included in the CRA (RBAA). In the CRA, mean (SD) age was 63.7 (14.1) versus 65.7 (14.3) years, and mean (SD) weight at admission was 78.5 (20.0) versus 79.4 (23.5) kg. A total of 129 (160) patients died in the strategy (control) group. Sixty-day mortality did not differ between groups [30.5%, 95% confidence interval (CI) 26.2–34.8 vs. 33.9%, 95% CI 29.6–38.2, p = 0.26]. Among safety outcomes, only hypernatremia was more frequent in the strategy group (5.3% vs. 2.3%, p = 0.01). The RBAA led to similar results. Conclusion: The POINCARE-2 conservative strategy did not reduce mortality in critically ill patients. However, due to open-label and stepped wedge design, intention-to-treat analyses might not reflect actual exposure to this strategy, and further analyses might be required before completely discarding it. Trial registration POINCARE-2 trial was registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016. [ABSTRACT FROM AUTHOR]

ObjectivesAs acute kidney injury and elevated cumulative fluid balance commonly co-occur in pediatric acute respiratory distress syndrome, we aimed to identify risk factors for their development and evaluate their independent relationships with mortality. We hypothesized that acute kidney injury and elevated cumulative fluid balance would be associated with markers of inflammation and that children with elevated cumulative fluid balance and concomitant acute kidney injury would have worse outcomes than other children.DesignProspective observational study using the pediatric Risk, Injury, Failure, Loss, End-Stage acute kidney injury classification.SettingFive academic PICUs.PatientsTwo-hundred sixty patients 1 month to 18 years old meeting the Berlin definition of acute respiratory distress syndrome between 2008 and 2014.InterventionsNone.Measurements and resultsPICU mortality was 13% (34/260). Relative to survivors, nonsurvivors had greater cumulative fluid balance on day 3 of acute respiratory distress syndrome (+90.1 mL/kg; interquartile range 26.6-161.7 vs +44.9 mL/kg; interquartile range 10.0-111.3; p = 0.008) and also had higher prevalence of acute kidney injury on day 3 of acute respiratory distress syndrome (50% vs 23%; p = 0.001). On stratified analysis, greater cumulative fluid balance on day 3 of acute respiratory distress syndrome was associated with mortality among patients with concomitant acute kidney injury (+111.5 mL/kg for nonsurvivors; interquartile range 82.6-236.8 vs +58.5 mL/kg for survivors; interquartile range 0.9-176.2; p = 0.041) but not among patients without acute kidney injury (p = 0.308). The presence of acute kidney injury on acute respiratory distress syndrome day 3 was associated with mortality among patients with positive cumulative fluid balance (29.1% vs 10.4% mortality; p = 0.001) but not among patients with even or negative cumulative fluid balance (p = 0.430). Day 1 plasma interleukin-6 levels were associated with the development of day 3 positive cumulative fluid balance, day 3 acute kidney injury, and PICU mortality and the association between elevated day 1 interleukin-6 and PICU mortality was partially mediated by the interval development of day 3 positive cumulative fluid balance and day 3 acute kidney injury (p < 0.001).ConclusionsIn pediatric acute respiratory distress syndrome, elevated cumulative fluid balance on day 3 of acute respiratory distress syndrome is associated with mortality specifically in patients with concomitant acute kidney injury. Plasma interleukin-6 levels are associated with the development of positive cumulative fluid balance and acute kidney injury, suggesting a potential mechanism by which inflammation might predispose to mortality.

Proton pump inhibitors, PPIs, are widely prescribed and sold globally. Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, PPIs are now commonly used for prolonged durations and are considered safe for over the counter access. Recent studies have raised concern over associations between PPI use and acute kidney injury, chronic kidney disease, end-stage renal disease, and electrolyte abnormalities. The growing concern over potentially serious adverse drug reactions warrants an evaluation of post marketing surveillance data. In this study of over ten million FDA Adverse Event Reporting System records, we provided evidence of kidney injury and electrolyte imbalances in an alarming number of patients taking PPIs. Additionally, we assessed differences between specific PPIs and observed significant electrolyte and renal abnormalities for each individual drug with varying magnitudes.

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk.

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk.

Weight classifications are used in boxing and other combat sports to match opponents of similar size. Professional boxers commonly engage in a potentially harmful practice known as rapid weight loss or 'weight cutting' to make weight the day prior to competition before rehydrating and refueling. This investigation describes the prevalence and magnitude of rapid weight gain in boxers following weigh-in as well as differences in practice with respect to weight class and promotion. This analysis describes official weight data from male professional boxers collected by the California State Athletic Commission between 2015 and 2018. A total of 399 athletes were included in the study. Among included athletes, 389 (97.5%) athletes gained weight between official weigh-in and competition. Total absolute body mass gained was 4.4 ± 2.2 kg corresponding to a total relative body mass gain of 7.2 ± 3.5%. Boxers competing in international promotions gained significantly more body mass than regional competitors (8.0 ± 3.0% vs. 6.6 ± 3.7%; p < 0.001). In total, 82 (20.6%) athletes gained 10% body mass or more before competition. More international competitors reached this 10% threshold than regional competitors (25.3% vs. 17.4%; p = 0.03). These findings indicate high prevalence and magnitude of RWG in professional boxing, particularly in boxers competing in elite international promotions. [ABSTRACT FROM AUTHOR]

Introduction: Even though nearly 20 patients undergo hip replacement every hour just in Italy and the United Kingdom, it is unclear what are the most appropriate oral hydration practices that patients should follow before and after surgery. Improper administration can cause postoperative fluid disturbances or exacerbate pre-existing conditions, which are not an uncommon find in older subjects. Significance: Considering that the number of hip operations is expected to increase in the next years as well as the age of patients, it is important to recall the notions behind water balance, especially in light of modern surgical and anesthetic practices. This technical perspective discusses the perioperative changes in the hydration status that occur during hip replacement and provides the concepts that help clinicians to better manage how much water the patient can drink. Results: The points of view of the surgeon, the anesthetist, and the nurse are offered together with the description of mineral waters intended for human consumption. Before surgery, water should be always preferred over caffeinated, sugar-sweetened, and alcoholic beverages. The drinking requirements on the day of surgery should consider the water output from urine, feces, respiration, exudation, and bleeding along with the water input from metabolic production and intravenous administration of fluids and medications. Healthy eating habits provide water and should be promoted before and after surgery. Conclusions: The judgment on which is the most appropriate approach to oral hydration practices must be the responsibility of the multidisciplinary perioperative team. Nevertheless, it is reasonable to argue that, in the presence of a patient with no relevant illness and who follows a healthy diet, it is more appropriate to stay closer to dehydration than liberalizing water intake both prior to surgery and in the early postoperative hours until the resumption of normal physiological functions. [ABSTRACT FROM AUTHOR]

Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to various aquatic habitats, from oceans to freshwater rivers. We report the sequencing, de novo assembly and analysis of a finless porpoise genome, and the re-sequencing of an additional 48 finless porpoise individuals. We use these data to reconstruct the demographic history of finless porpoises from their origin to the occupation into the Yangtze River. Analyses of selection between marine and freshwater porpoises identify genes associated with renal water homeostasis and urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2, which are likely adaptations associated with the difference in osmotic stress between ocean and rivers. Our results strongly suggest that the critically endangered Yangtze finless porpoises are reproductively isolated from other porpoise populations and harbor unique genetic adaptations, supporting that they should be considered a unique incipient species.

BackgroundDietary sodium and potassium affect the fluctuation in blood pressure (BP) and renal function. Corin, with its enzymatic activity to convert pro-atrial natriuretic peptide (pro-ANP) to biologically active ANP, regulates BP, cardiac, and renal functions. We investigated whether corin expression responds to a high-salt (HS) diet to regulate salt and water balance.MethodsForty-two volunteers followed 3 sequential diets for 7 days each: a low-salt (LS) diet (3.0 g/day NaCl), a HS diet (18.0 g/day NaCl), followed by an HS diet with K+ supplementation (HS + K+) (18.0 g/day NaCl and 4.5 g/day KCl).ResultsCorin level was higher with the HS diet than the LS and HS + K+ diets and was positively correlated with systolic BP (SBP) and 24-hour urinary Na+ and microalbumin (U-mALB) excretion. In rodents, serum and renal levels of corin were transiently increased with the HS diet and were decreased if the HS diet was continued for up to 7 days. HS loading increased SBP, 24-hour urinary Na+, U-mALB excretion, and the expression of proprotein convertase subtilisin/kexin-6 (PCSK6), a corin activator. Knockdown of PCSK6 or corin in high salt-treated M1-cortical collecting duct (M1-CCD) cells increased the expression of aquaporin 2 (AQP2) and β-epithelial Na+ channel (β-ENaC).ConclusionsShort-term HS may induce the PCSK6-corin-ANP-AQP2/β-ENaC pathway in the kidney. Enhanced serum corin level in humans and rodents is positively correlated with HS-induced SBP and 24-hour urinary Na+ and U-mALB excretion, which suggests that corin is involved in the salt-water balance in response to HS intake.Clinical trials registrationPublic Trials Registry Number NCT02915315.

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 < 0.001). On Day 2, most patients had a decreased actual Na–Cl gap (33 ± 5 mmol/L), approaching the corrected value on Day 1. 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 [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to study fluid balance and endothelial glycocalyx degradation, reflected by syndecan-1, and heparan sulfate (HS) levels, in early stages of acute pancreatitis (AP)., Materials and Methods: This study comprised of 210 AP patients (104 mild, 53 moderately severe, 17 severe). Blood was sampled within 72 hours from the onset of symptoms, and plasma syndecan-1 and HS levels were determined using ELISA. Fluid balance up to sampling and up to 4 days was determined retrospectively from medical records., Results: Syndecan-1 levels predicted severe AP (SAP) in receiver operating characteristic analysis [area under curve 0.699, 95% confidence interval (CI) 0.546 to 0.851, P = 0.021]. Increasing AP severity was associated with higher intravenous fluid intake and lower urine output. In multivariate binary logistic regression analysis, positive fluid balance up to sampling [odds ratio (OR) 1.05 per 100 ml, 95% CI 1.02 to 1.11, P = 0.010] and higher Acute Physiology and Chronic Health Evaluation II score at sampling (OR 1.48, 95% CI 1.20 to 1.83, P < 0.001) were independently associated with severe AP, while syndecan-1 level was not., Conclusions: SAP is associated with high positive fluid balance in the early stages of treatment. Although increased in SAP, syndecan-1 was not independently associated with SAP when controlling for fluid balance and Acute Physiology and Chronic Health Evaluation II score., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: The National Institute for Health and Care Excellence's (NICE) Guideline for Maintenance Fluid Therapy in Adults in Hospital is widely used, but the recommendations have not been evaluated properly. In this study, we investigated whether the recommendation of providing 25-30 mL/kg/day of fluid and 1 mmol/kg each of sodium and potassium is sufficient for human needs., Methods: First, we calculated the distribution of fluid between the extracellular fluid volume (ECV) and intracellular fluid volume (ICV) during a cross-over infusion experiment where 12 volunteers received 25 mL/kg/day of either a high-sodium (154 mmol/L) or low-sodium (54 mmol/L) solution over 48 h. Second, urine samples from 719 volunteers and clinical patients were used to quantify their renal water conservation and excretion of sodium and potassium. Third, retrospective analysis of a diet study was used to extrapolate how large the fluid intake and the electrolyte excretion likely had been in the 719 volunteers and hospital patients who delivered urine., Results: The high-sodium fluid maintained the ECV but the ICV had decreased by 1.3 L after 48 h. The low-sodium fluid resulted in a volume deficit of 1.7 L that equally affected the ECV and the ICV. Regression equations based on the diet study suggested that the daily intake of water in the 719 subjects averaged 2.6 L and that 2 mmol/kg of sodium and 1 mmol/kg of potassium was excreted., Conclusion: The NICE guideline recommends too little water and sodium for a human to adequately maintain the ECV and ICV., Clinical Trial Registrations: EudraCT 2016-001846-24 and ISRCTN 12215472., Competing Interests: Declaration of competing interest RGH has received a research grant from Grifols for studies of 20% albumin (2019–2021) and is Member of Baxter's European IV Fluid Therapy Management Advisory Board. NVR has received speaker's fees and resided in a medical advisory board organized by Baxter Healthcare, USA. NVR is co-chairman of the International Fluid Academy (www.fluidacademy.org), a non-profit organization promoting education in fluid management and hemodynamic monitoring that received sponsoring from the industry., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: During continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT., Methods: A retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs., Results: Median age was 60 years (IQR, 48-70), median APACHE III was 94 (IQR, 76-114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (-1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO., Conclusion: A higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the effect of replacing Tifton 85 hay (TH) with Moringa hay (MH) on the intake, apparent digestibility, ingestive behaviour, rumen parameters, serum attributes, nitrogen balance, water balance, and urinary attributes of sheep. Thus, 5 rams, ½ Dorper + ½ Santa Inês, that were 12 ± 4 months of age with an initial body weight of 32.8 ± 2.6 kg were distributed in metabolic cages in a Latin square design. The experiment lasted 85 days and was divided into five 17-day periods. The animals received rations with increasing replacement (0, 100, 200, 300, or 400 g/kg of dry matter in the total diet) of TH for MH. The forage: concentrate ratio of the diets was 40:60. Replacing TH with MH reduced (P < 0.05) the intake of organic matter, crude protein, neutral detergent fibre (NDFap), and total digestible nutrients by sheep. The apparent digestibility of NDFap and the feeding and rumination efficiencies of NDFap were reduced (P < 0.05) when MH replaced TH in the animals' diet. This replacement did not influence (P > 0.05) serum urea, total protein, creatinine, or aspartate aminotransferase in sheep. Replacing TH with MH decreased water intake and excretion (P < 0.05). In addition, nitrogen excretion via urine, urinary creatinine, and nitrogen absorption decreased (P < 0.05) when TH was replaced with MH. However, there was an increase in the sheep's nitrogen retention and urine pH. We recommend replacing 30% TH with MH in the diet of lambs because it does not compromise nutrient metabolism., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Investigations of responses of animals and humans to changes of plasma volume are usually reported as average responses of groups of individuals. This ignores considerable quantitative variation between individuals. We examined the hypothesis that individual responses follow a common temporal pattern with variations reflecting different parameters describing that pattern., Methods: We illustrate this approach using data of Hahn, Lindahl and Drobin (Acta Anaesthesiol Scand.2011, 55:987-94) who measured urine volume and haemoglobin dilution of 10 female subjects during intravenous Ringer infusions for 30 min and subsequent 3.5 h. The published time courses were digitised and analysed to determine if a family of mathematical functions accounted for the variation in individual responses., Results: Urine excretion was characterised by a time delay (Td) before urine flow increased and a time course of cumulative urine excretion described by a logarithmic function. This logarithmic relation forms the theoretical basis of a family of linear relations describing urine excretion as a function of Td. Measurement of Td enables estimation of subsequent values of urine excretion and thereby the fraction of infused fluid retained in the body., Conclusion: The approach might be useful for physiologists and clinical investigators to compare the response to infusion protocols when both test and control responses can be described by linear relations between cumulative urine volume at specific times and Td. The approach may also be useful for clinicians by complementing strategies to guide fluid therapy by enabling the later responses of an individual to be predicted from their earlier response., (© 2024 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

The prostaglandin E 2 (PGE 2 ) receptor EP3 has been detected in the thick ascending limb (TAL) and the collecting duct of the kidney, where its actions are proposed to inhibit water reabsorption. However, EP3 is also expressed in other cell types, including vascular endothelial cells. The aim here was to determine the contribution of EP3 in renal water handling in male and female adult mice by phenotyping a novel mouse model with doxycycline-dependent deletion of EP3 throughout the kidney tubule (EP3 -/- mice). RNAscope demonstrated that EP3 was highly expressed in the cortical and medullary TAL of adult mice. Compared with controls EP3 mRNA expression was reduced by >80% in whole kidney (RT-qPCR) and nondetectable (RNAscope) in renal tubules of EP3 -/- mice. Under basal conditions, there were no significant differences in control and EP3 -/- mice of both sexes in food and water intake, body weight, urinary output, or clinical biochemistries. No differences were detectable between genotypes in handling of an acute water load or in their response to the vasopressin analog 1-deamino-8-d-arginine-vasopressin (dDAVP). No differences in water handling were observed when PGE 2 production was enhanced using 1% NaCl load. Expression of proteins involved in kidney water handling was not different between genotypes. This study demonstrates that renal tubular EP3 is not essential for body fluid homeostasis in males or females, even when PGE 2 levels are high. The mouse model is a novel tool for examining the role of EP3 in kidney function independently of potential developmental abnormalities or systemic effects. NEW & NOTEWORTHY The prostanoid EP3 receptor is proposed to play a key role in the kidney tubule and antagonize the effects of vasopressin on aquaporin-mediated water reabsorption. Here, we phenotyped a kidney tubule-specific inducible knockout mouse model of the EP3 receptor. Our major finding is that, even under physiological stress, tubular EP3 plays no detectable role in renal water or solute handling. This suggests that other EP receptors must be important for renal salt and water handling.

Introduction: The interstitial space harbours two fluid compartments linked serially to the plasma. This study explores conditions that lead to fluid accumulation in the most secluded compartment, termed the "third space"., Methods: Retrospective data was collected from 326 experiments in which intravenous crystalloid fluid was administered to conscious volunteers as well as a small group of anaesthetized patients. The urinary excretion and plasma dilution derived from haemoglobin served as input variables in nine population volume kinetic analyses representing subtly different settings., Results: An infusion of 250-500 mL of Ringer's solution expanded only the central fluid space (plasma), whereas the infusion of 500-1,000 mL extended into a rapidly exchanging interstitial fluid space. When more than 1 L was infused over 30 min, it was distributed across plasma and both interstitial fluid compartments. The remote space, characterized by slow turnover, abruptly accommodated fluid upon accumulation of 700-800 mL in the rapidly exchanging space, equivalent to an 11%-13% volume increase. However, larger expansion was necessary to trigger this event in a perioperative setting. The plasma half-life of crystalloid fluid was 25 times longer when 2,000-2,700 mL expanded all three fluid compartments compared to when only 250-500 mL expanded the central space (14 h versus 30 min)., Conclusion: As the volume of crystalloid fluid increases, it apparently occupies a larger proportion of the interstitial space. When more than 1 L is administered at a high rate, there is expansion of a remote "third space", which considerably extends the intravascular half-life., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hahn.)

Hagfishes are characterized by omo- and iono-conforming nature similar to marine invertebrates. Conventionally, hagfishes had been recognized as the most primitive living vertebrate that retains plesiomorphic features. However, some of the "ancestral" features of hagfishes, such as rudimentary eyes and the lack of vertebrae, have been proven to be deceptive. Similarly, by the principle of maximum parsimony, the unique body fluid regulatory strategy of hagfishes seems to be apomorphic, since the lamprey, another cyclostome, adopts osmo- and iono-regulatory mechanisms as in jawed vertebrates. Although hagfishes are unequivocally important in discussing the origin and evolution of the vertebrate osmoregulatory system, the molecular basis for the body fluid homeostasis in hagfishes has been poorly understood. In the present study, we explored this matter in the inshore hagfish, Eptatretus burgeri , by analyzing the transcriptomes obtained from the gill, kidney, and muscle of the animals acclimated to distinct environmental salinities. Together with the measurement of parameters in the muscular fluid compartment, our data indicate that the hagfish possesses an ability to conduct free amino acid (FAA)-based osmoregulation at a cellular level, which is in coordination with the renal and branchial FAA absorption. We also revealed that the hagfish does possess the orthologs of the known osmoregulatory genes and that the transepithelial movement of inorganic ions in the hagfish gill and kidney is more complex than previously thought. These observations pose a challenge to the conventional view that the physiological features of hagfishes have been inherited from the last common ancestor of the extant vertebrates.

Purpose: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients., Methods: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy., Results: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001)., Conclusion: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB., Key Points: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dehydration and malnutrition are common in infants with severe epidermolysis bullosa (EB), but their nutritional needs have been poorly studied. The principal aim was to assess the nutritional status, fluid and electrolyte balance, and nutritional intake of newborns with EB during the first month of life and estimate their needs during this period. This was a retrospective study over an eight-year period. Inclusion criteria were neonates with confirmed EB admitted to our neonatal referral unit during the first month of life. Exclusion criteria were hospitalisations <7 days. Twenty-seven patients with EB (mean [min-max] gestational age = 39 weeks [33; 41]; birth weight = 2986 g [1982; 4150]), were included. Four patients (15%) had hyponatraemia < 135 mmol/L at admission (age at admission = 4.8 days +/- 2.6 [2; 7]). Sixteen patients (59%) had a sodium deficit -requiring fluid and sodium intake well above recommendations from the World Health Organisation (WHO). The risk of hyponatraemia was significantly higher in infants with the greatest body surface area affected but did not appear to be related to EB subtype. Caloric and protein intake were well above the WHO's recommendations, preventing acquired growth restriction. The rate of sodium deficit in neonates with EB is high and related to the significance of skin exudate. The administration of nutrient intake greater than that recommended helps to prevent acquired growth restriction. We propose recommendations for nutritional intake and monitoring in neonates with EB in the first month of life.

The article presents the discussion on explaining the mechanism of action of commonly used diuretic agents discussing the relationship between diuretic therapy and renal function.

Our bodies are mostly water, and this water is constantly being lost through evaporative and other means. Thus the evolution of robust mechanisms for finding and consuming water has been critical for the survival of most animals. In this Primer, we discuss how the brain monitors the water content of the body and then transforms that physical information into the motivation to drink.

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 < 0.01). Cumulative fluid balance was lower in the intervention group at days 3 and 5. Overall, clinical outcomes did not differ significantly between the two groups, although the point estimate for 30-day mortality favoured the usual care group [intervention arm: 19 of 90 (21.6%) versus usual care: 14 of 89 (15.6%), P = 0.32]. Baseline imbalances between groups and lack of statistical power limit interpretation of clinical outcomes. 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. [ABSTRACT FROM AUTHOR]

This study investigated fluid removal strategies for critically ill patients with fluid overload on mechanical ventilation. Traditionally, a negative fluid balance (FB) is aimed for. However, this approach can have drawbacks. Here, we compared a new approach, namely removing fluids until patients become fluid responsive (FR) to the traditional empiric negative balance approach. Twelve patients were placed in each group (n = 24). FR assessment was performed using passive leg raising (PLR). Both groups maintained stable blood pressure and heart function during fluid management. Notably, the FR group weaned from the ventilator significantly faster than negative FB group (both for a spontaneous breathing trial (14 h vs. 36 h, p = 0.031) and extubation (26 h vs. 57 h, p = 0.007); the difference in total ventilator time wasn't statistically significant (49 h vs. 62 h, p = 0.065). Additionally, FR group avoided metabolic problems like secondary alkalosis and potential hypokalemia seen in the negative FB group. FR-guided fluid-removal in fluid overloaded mechanically ventilated patients was a feasible, safe, and maybe superior strategy in facilitating weaning and disconnection from mechanical ventilation than negative FB-driven fluid removal. FR is a safe endpoint for optimizing cardiac function and preventing adverse consequences during fluid removal., Competing Interests: Declaration of competing interest The authors RC, PB, FM, CG, EK, GH, and JB declare no financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W)., Methods: During visit 1 (V1), participants (10 men and 10 women, 20-35 years old, BMI ≤ 29 kg/m 2 , recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 - 0900) and participants arrived 12-14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants' USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants' USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week., Results: No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements ( p  > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions ( p  < 0.05), and post hoc testing indicated these values were better maintained in the MIDS versus other conditions. Post-exercise cramp prevalence was greater in the CE ( p  < 0.05) and trended higher with W ( p  = 0.083) compared to the MIDS condition. Post-exercise cramp severity was also elevated with the W and CE beverages ( p  < 0.05) but not the MIDS ( p  = 0.211)., Conclusions: The MIDS did not affect 5-km time trial performance but exhibited favorable effects on blood electrolyte and post-exercise self-reporting cramp outcomes compared to the CE and W drinks.

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR−1.9–18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P < .05 and P < .01, respectively), whereas urea's proportion increased (P < .001). The urea's proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea's proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea's proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals. ClinicalTrials.org Identifier: NCT03972475. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Diabetes insipidus (DI) is a clinical syndrome characterized by polyuria and polydipsia that result from a deficiency of antidiuretic hormone (ADH), central DI, or resistance to ADH, nephrogenic DI. In otherwise healthy patients with DI, normal thirst mechanism, and free access to water, the thirst system can maintain plasma osmolality in the near-normal range. However, in cases where DI presents with adipsia, cognitive impairment, or restricted access to water, true hypernatremia may occur, leading to severe morbidity and mortality. Case Report: We report a case of a 2-year-old boy who had global developmental delay and post-brain debulking surgery involving the hypothalamic region, which resulted in central DI and thirst center dysfunction. We describe the clinical presentation, the current understanding of adipsic DI, and a new practical approach for management. The main guidelines of treatment include (1) fixed desmopressin dosing that allows minimal urinary breakthroughs in-between the doses; (2) timely diaper weight-based replacement of water; (3) bodyweight-based fluid correction 2 times a day, and (4) providing the nutritional and water requirements in a way similar to any healthy child but at fixed time intervals. Conclusions: This plan of management showed good effectiveness in controlling plasma sodium level and volume status of a child with adipsic DI without interfering with his average growth. This home treatment method is practical and readily available, provided that the family remains very adherent. [ABSTRACT FROM AUTHOR]

Delays in sepsis diagnosis can increase morbidity and mortality. Previously, we performed a Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) "look-back" analysis to identify symptoms at risk for delayed sepsis diagnosis. We found treat-and-release emergency department (ED) encounters for fluid and electrolyte disorders (FED) and altered mental status (AMS) were associated with downstream sepsis hospitalizations. In this "look-forward" analysis, we measure the potential misdiagnosis-related harm rate for sepsis among patients with these symptoms. Retrospective cohort study using electronic health record and claims data from Kaiser Permanente Mid-Atlantic States (2013–2018). Patients ≥18 years with ≥1 treat-and-release ED encounter for FED or AMS were included. Observed greater than expected sepsis hospitalizations within 30 days of ED treat-and-release encounters were considered potential misdiagnosis-related harms. Temporal analyses were employed to differentiate case and comparison (superficial injury/contusion ED encounters) cohorts. There were 4,549 treat-and-release ED encounters for FED or AMS, 26 associated with a sepsis hospitalization in the next 30 days. The observed (0.57%) minus expected (0.13%) harm rate was 0.44% (absolute) and 4.5-fold increased over expected (relative). There was a spike in sepsis hospitalizations in the week following FED/AMS ED visits. There were fewer sepsis hospitalizations and no spike in admissions in the week following superficial injury/contusion ED visits. Potentially misdiagnosed patients were older and more medically complex. Potential misdiagnosis-related harms from sepsis are infrequent but measurable using SPADE. This look-forward analysis validated our previous look-back study, demonstrating the SPADE approach can be used to study infectious disease syndromes. [ABSTRACT FROM AUTHOR]