Control Of Fluid Balance Research Articles

The path to individualization of infusion therapy for emergency conditions according to the ROSE concept

The article is devoted to the role of intravenous fluid therapy in conditions of impaired fluid homeostasis, which often occur during major surgical interventions and critical conditions, such as sepsis and trauma. The importance of adequate fluid administration to maintain cellular homeostasis, as well as the management of conditions associated with hypovolemia and hemodynamic disturbances, is described. It is noted that, despite numerous studies, the topic of optimal fluid management strategies remains controversial, with potential risks of adverse effects of excessive fluid administration on clinical outcomes. The concept of liquid resuscitation ROSE is presented, which includes four stages: resuscitation, optimization, stabilization and evacuation. This concept will assist physicians in making decisions about fluid therapy management. Different types of fluids are reviewed, including balanced solutions and the multifunctional hyperosmolar solution Reosorbilact, and the importance of individualizing therapy based on the needs of each patient is emphasized. The importance of the need for careful monitoring and control of fluid balance is emphasized to avoid complications and ensure improved clinical outcomes

Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial.

Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care. In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72h a UFNET ≥ 100ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population. Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms. In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Simultaneous removal of endotoxins, inflammatory mediators and uremic toxins in ICU patients with septic shock: a retrospective cohort study

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48–1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17–1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18–0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Implementation of a fluid balance control strategy in critically ill patients: POINCARE-2 trial process evaluation

BackgroundPOINCARE-2 trial aimed to assess the effectiveness of a strategy designed to tackle fluid overload through daily weighing and subsequent administration of treatments in critically ill patients. Even in highly standardized care settings, such as intensive care units, effectiveness of such a complex intervention depends on its actual efficacy but also on the extent of its implementation. Using a process evaluation, we aimed to provide understanding of the implementation, context, and mechanisms of change of POINCARE-2 strategy during the trial, to gain insight on its effectiveness and inform the decision regarding the dissemination of the intervention.MethodsWe conducted a mixed-method process evaluation following the Medical Research Council guideline. Both quantitative data derived from the trial, and qualitative data from semi-structured interviews with professionals were used to explain implementation, mechanisms of change of the POINCARE-2 strategy, as well as contextual factors potentially influencing implementation of the strategy.ResultsScore of actual exposure to the strategy ranged from 29.1 to 68.2% during the control period, and from 61.9 to 92.3% during the intervention period, suggesting both potential contamination and suboptimal fidelity to the strategy. Lack of appropriate weighing devices, lack of human resources dedicated to research, pre-trial rooted prescription habits, and anticipated knowledge of the strategy have been identified as the main barriers to optimal implementation of the strategy in the trial context.ConclusionsBoth contamination and suboptimal fidelity to POINCARE-2 strategy raised concerns about a potential bias towards the null of intention-to-treat (ITT) analyses. However, optimal fidelity seemed reachable. Consequently, a clinical strategy should not be rejected solely on the basis of the negativity of ITT analyses’ results. Our findings showed that, even in highly standardized care conditions, the implementation of clinical strategies may be hindered by numerous contextual factors, which demonstrates the critical importance of assessing the viability of an intervention, prior to any evaluation of its effectiveness.Trial registrationNumber NCT02765009

Renal replacement therapy in critical ill patients

Acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression of chronic kidney disease (CKD), financial burden on the health care system, and increases mortality in various entities. Extended renal replacement therapy (CRRT) is the predominant form of renal replacement therapy (RRT) in intensive care units (ICU) by providing hemodynamic stability in critically ill patients, more precise control of fluid balance, correction of acid-base imbalances, electrolyte disorders and achieving a stable level of osmolarity correction, including in multimorbid patients. This article examines the various aspects of CRRT in critically ill patients with severe AKI with high comorbidity, as well as in patients with sepsis and multiple organ failure. An analytical evaluation of the choice of CRRT over intermittent/intermittent hemodialysis (IHD) in selected clinical settings is being conducted. Filter/dialyzer life is assessed, including assessment of filtration fraction, use of anticoagulation options including regional citrate anticoagulation (RCA), dose of CRRT prescribed and delivered, vascular access management, general criteria, timing of initiation and cessation of CRRT, and initiation of renal replacement therapy for nonrenal indications. with AKI and/or sepsis.

HIGH BLOOD PRESSURE IN HEMODIALYSIS: PREVALENCE AND PROGRESSION

Objective: High blood pressure (hypertension) is frequently found in chronic hemodialysis patients. It affects the prognosis by increasing the morbidity and mortality of patients. The objective of our study was to assess the prevalence of hypertension and to study its evolutionary profile in chronic hemodialysis patients at the University Hospital of Béjaia Design and method: This is a three-year retrospective cross-sectional study of 40 patients who have been chronic hemodialysis patients for at least one year and are over 18 years of age. For each patient, we recorded age, sex, initial nephropathy, date of start of hemodialysis, blood pressure balance, fluid status and different treatments prescribed. Results: We included 40 haemodialysis patients: 24 men and 16 women. The average age of our population was 54.37± 15.33 years. The duration of hemodialysis was 08.17± 7.5 years. High blood pressure was found in 67.5%. All of our patients were on antihypertensive therapy at the start of dialysis. After 3 years of evolution, 55% of patients had reached the blood pressure target, 30% had a correct blood pressure without any therapy and 15% had not reached the blood pressure targets despite triple therapy. Blood pressure balance in dialysis patients; Of course, it depends on adherence to treatment and hygienic and dietary rules, but also on effective dialysis and strict control of fluid balance in order to fight against volo-dependent hypertension. Conclusions: The control of hypertension in dialysis patients is essential and must include, in addition to adherence to treatment and dietary rules, adequate dialysis and strict control of dry weight, which must be assessed and adjusted periodically.

Fluid balance control in critically ill patients: results from as-treated analyses of POINCARE-2 randomized trial

BackgroundIntention-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.MethodsPOINCARE‑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.ResultsA 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).ConclusionActual 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.

Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative (< 0 mL) and positive (> 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT.

The impact of heterogeneity of the air-blood barrier on control of lung extravascular water and alveolar gas exchange.

The architecture of the air-blood barrier is effective in optimizing the gas exchange as long as it retains its specific feature of extreme thinness reflecting, in turn, a strict control on the extravascular water to be kept at minimum. Edemagenic conditions may perturb this equilibrium by increasing microvascular filtration; this characteristically occurs when cardiac output increases to balance the oxygen uptake with the oxygen requirement such as in exercise and hypoxia (either due to low ambient pressure or reflecting a pathological condition). In general, the lung is well equipped to counteract an increase in microvascular filtration rate. The loss of control on fluid balance is the consequence of disruption of the integrity of the macromolecular structure of lung tissue. This review, merging data from experimental approaches and evidence in humans, will explore how the heterogeneity in morphology, mechanical features and perfusion of the terminal respiratory units might impact on lung fluid balance and its control. Evidence is also provided that heterogeneities may be inborn and they could actually get worse as a consequence of a developing pathological process. Further, data are presented how in humans inter-individual heterogeneities in morphology of the terminal respiratory hinder the control of fluid balance and, in turn, hamper the efficiency of the oxygen diffusion-transport function.

Assessment of Volume Status Using Body Composition Monitor for Blood Pressure Control in Patients Undergoing Maintenance Hemodialysis: A Randomized Controlled Trial

Introduction: Optimal fluid balance and blood pressure control have been shown to improve outcomes in hemodialysis population. We investigated the effectiveness of body composition monitor (BCM) to target dry weight in maintenance hemodialysis (MHD) patients for blood pressure (BP) control and intradialytic adverse events. Methods: A total of 61 consenting adults under MHD were randomly allocated into either BCM group or Clinical Method group. Target dry weight was set every 4-weekly based on BCM report or clinical assessment; dry weight was adjusted with 200-500 ml/session reduction or increment of ultrafiltration in addition to interdialytic weight gain. Outcomes were analyzed in terms of BP control, anti-hypertensive medicine score, and intradialytic adverse events. Results: During 12 weeks of study period, systolic blood pressure (p&lt;0.001), diastolic blood pressure (p=0.01) and mean arterial pressure (p&lt;0.001) significantly decreased from baseline in BCM group but there were no significant changes in Clinical Method group. Lower blood pressure was achieved in BCM group as compared to Clinical Method group. There was a significant decrease from baseline in anti-hypertensive medicine score in the BCM group (p&lt;0.001) but not in the clinical method group (p=0.34). There were significantly fewer events of cramps in the BCM group as compared to the Clinical Method group (p=0.04). Conclusion: BCM guided volume management in MHD patients was more effective than volume management based on clinical judgment only in controlling blood pressure and decreasing anti-hypertensive medicine burden and intradialytic cramps.

Fluid balance control in critically ill patients: results from POINCARE-2 stepped wedge cluster-randomized trial

BackgroundIn 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.MethodsPOINCARE-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).ResultsA 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.ConclusionThe 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.

Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in critically ill patients requiring continuous renal replacement therapy: study protocol of the GO NEUTRAL randomized controlled trial

BackgroundFluid 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.MethodsThe 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.DiscussionWe 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 registrationClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

Chronic intracerebroventricular infusion of angiotensin II causes dose- and sex-dependent effects on intake behaviors and energy homeostasis in C57BL/6J mice.

The renin-angiotensin system (RAS) within the brain is implicated in the control of fluid and electrolyte balance, autonomic functions, blood pressure, and energy expenditure. Mouse models are increasingly used to explore these mechanisms; however, sex and dose dependencies of effects elicited by chronic intracerebroventricular (ICV) angiotensin II (ANG II) infusion have not been carefully established in this species. To examine the interactions among sex, body mass, and ICV ANG II on ingestive behaviors and energy balance, young adult C57BL/6J mice of both sexes were studied in a multiplexed metabolic phenotyping system (Promethion) during chronic infusion of ANG II (0, 5, 20, or 50 ng/h). At these infusion rates, ANG II caused accelerating dose-dependent increases in drinking and total energy expenditure in male mice, but female mice exhibited a complex biphasic response with maximum responses at 5 ng/h. Body mass differences did not account for sex-dependent differences in drinking behavior or total energy expenditure. In contrast, resting metabolic rate was similarly increased by ICV ANG II in a dose-dependent manner in both sexes after correction for body mass. We conclude that chronic ICV ANG II stimulates water intake, resting, and total energy expenditure in male C57BL/6J mice following straightforward accelerating dose-dependent kinetics, but female C57BL/6J mice exhibit complex biphasic responses to ICV ANG II. Furthermore, control of resting metabolic rate by ANG II is dissociable from mechanisms controlling fluid intake and total energy expenditure. Future studies of the sex dependency of ANG II within the brain of mice must be designed to carefully consider the biphasic responses that occur in females.

Ibuprofen-Induced Toxic Epidermal Necrolysis: A Case Report

Introduction: Toxic epidermal necrolysis (TEN) is a medical emergency that most commonly occurs as an adverse effect of certain drugs. Here, we describe a case of a 41-year-old man with no comorbid illness who developed TEN. Case Presentation: The patient had been prescribed ibuprofen for myalgia and developed skin lesions after the single dose. The lesions were erythematous papules and macules distributed all over the body after ibuprofen intake. TEN was diagnosed based on the patient’s clinical presentation and laboratory findings. He was treated with intravenous dexamethasone, intravenous immunoglobulin, and cyclosporine. Daily dressing changes and skin care was done with saline, chlorhexidine, and liquid paraffin. The patient was intubated and tracheostomized, and he gradually improved and survived. Later, he developed septicemia in the intensive care unit and was treated successfully. Discussion: The management of TEN includes cessation of the causative cause, multidisciplinary ICU care, prevention and early detection of sepsis, fluid and electrolyte balance, adequate analgesia and temperature control, proper organ support, aggressive nutritional management, and good psychological support. The pharmacological therapy for TEN includes corticosteroids, intravenous immunoglobulin, and cyclosporine. The key elements of management are aseptic care and proper dressing of the skin. Conclusion: TEN is associated with high mortality if not managed in a systemic and protocolized way.

Sex Modulates Cardiovascular Effects of Icodextrin-Based Peritoneal Dialysis Solutions.

Background/Aims: Some previous observations have noted that after six months of peritoneal dialysis (PD) treatment with icodextrin solutions, blood pressure (BP) and NT-proBNP tend to return to baseline values. This may be due to accumulation of icodextrin products that exert a colloid osmotic effect, which drives water into the bloodstream, causing the rise in blood pressure. Since icodextrin is metabolized by α-Amylase and its gene copies are lower in females than in males, we hypothesized icodextrin metabolites reach higher concentrations in females and that cardiovascular effects of icodextrin are influenced by sex. Methods: Secondary analysis of a RCT comparing factors influencing fluid balance control in diabetic PD patients with high or high average peritoneal transport receiving icodextrin (n = 30) or glucose (n = 29) PD solutions. Serum icodextrin metabolites, osmolality, body composition and Inferior Vena Cava (IVC) diameter were measured at baseline, and at 6 and 12 months of follow-up. Results: After six months of treatment, icodextrin metabolites showed higher levels in females than in males, particularly G5-7 and >G7, serum osmolality was lower in females. In spite of reduction in total and extracellular body water, ultrafiltration (UF) was lower and IVC diameter and BP increased in females, suggesting increment of blood volume. Conclusion: Females undergoing PD present with higher levels of icodextrin metabolites in serum that may exert an increased colloid-osmotic pressure followed by less UF volumes and increment in blood volume and blood pressure. Whether this could be due to the lesser number of α-Amylase gene copies described in diabetic females deserves further investigation.

Vasopressin, Cortisol, and Osmotic Regulation in Non‐hospitalized SARS‐CoV‐2 Infected Patients

Vasopressin (AVP) has been implicated in the inflammatory response to SARS‐CoV‐2 infection as increased disease severity has been reported to be associated with elevated levels of copeptin. Elevated AVP and cortisol levels seen in systemic inflammatory responses may be associated with severe pulmonary edema and dilutional hyponatremia caused be dysregulation of neurohormonal control of fluid and electrolyte balance. Early and effective regulation of fluid balance before acute respiratory failure spirals into hypoxemia‐induced septic shock and multisystem organ failure, may be needed to prevent progression to severe disease.We hypothesized that control of osmotic homeostasis in non‐severe cases of COVID‐19 is an outcome of cortisol and AVP stimulation arising from an appropriate stress response. In an observational study of asymptomatic to moderately symptomatic non‐hospitalized individuals (n = 45; 14 to 71 years of age) positive for SARS‐CoV‐2 (confirmed by PCR test), we assessed osmotic regulation by measuring circulating AVP (by radioimmunoassay), cortisol (by enzyme linked immunoassay), plasma osmolality (pOsm), plasma sodium (pNa) and plasma potassium (pK). Two plasma specimens from each person were collected between 2 and 32 days from onset of symptoms or confirmed positive test. Inflammatory stimulation of the immune response was verified by quantitative measurement of IgG targeted to the SARS‐Cov‐2 spike protein (Epitope Diagnostics, Dynex Agility).Plasma osmolality (293+1 mOsm/L) remained stable even at the peak of IgG immune response. Multiple regression analyses showed pOsm was directly related to AVP and inversely related to cortisol (p<0.001). Examination of electrolyte levels over time from positive SARS‐CoV‐2 test week 1 vs week 3 (7+1 vs 18+1 days) revealed a slight decrease in pNa (139.7+0.8 to 136.9+0.5 mEq/l p<0.05, but there was no evidence of hyponatremia or inappropriate levels of AVP (SIADH) which was 1.9+0.2 uU/ml at week 1 and 2.2+0.3 uU/ml at week 3. Vasopressin regulation was appropriately positively correlated with pOsm and cortisol and negatively related to pK (p<0.001). Cortisol levels increased from week 1 to 3 (14.7+1.2 to 22.2+2.2 ug/dL), and positively correlated with AVP and negatively correlated with pNa.Results demonstrated that the stimulated immune response to SARS‐CoV‐2 infection in mild to moderate cases of COVID‐19 does not disrupt osmotic regulation by AVP. Thus, reports of dysregulation of osmotic homeostasis and SIADH observed in severe pneumonia and coronavirus sepsis in hospitalized patients is likely due to the dominating non‐osmotic stimulation of AVP to pathophysiological levels needed to maintain blood pressure and renal perfusion. In mild to moderate COVID‐19 cases, control of fluid and electrolyte balance at physiological levels of AVP appears to be maintained.

Non-anticoagulation pediatric continuous renal replacement therapy methods to increase circuit life.

Acute kidney injury (AKI) is a clinical condition characterized by an abrupt increase in serum creatinine levels due to functional changes in the kidneys from a newfound insult or injury. For supportive treatment, continuous renal replacement therapy (CRRT) is one of the most widely used modalities due to its precise control of fluid balance over extended periods of time. However, its complications include circuit clotting, the most frequent cause for CRRT interruption. Vascular access and circuit management were found to be major determinants of performance efficiency. Anticoagulation required to prevent clotting has the downside of increasing the risk of bleeding, especially in the setting of overdosage. Hence, a delicate balance needs to be maintained consistently. This study explores the adequacy of non-anticoagulation measures in the prevention of circuit clotting. A comprehensive literature search was conducted using PubMed/Medline and Embase databases to include all relevant studies. The most-effective CRRT catheter would be made of nonthrombogenic material, noncuffed and nontunneled with separate lumens for arterial and venous blood. Further, studies show that blood flow during the process is optimized at 200 ml/min, which can be lowered in the pediatric population due to more narrow catheters. Platelet count and hematocrit need to be closely monitored as levels above 450,000 × 106 /L and 0.40, respectively, increase risk of clotting. Predilution is a non-anticoagulation technique to reduce the risk of clotting by returning replacement solution to the blood before it reaches the filter. Also, biocompatible membranes such as polyacrylonitrile or polysulfone activate the coagulation cascade significantly less than the conventional cellulose-based membranes, thereby reducing clotting chances. With the advent of such techniques and maneuvers, anticoagulation can be efficiently maintained in patients undergoing CRRT without increasing the risk of bleeding.

Disrupted Circadian Control of Hormonal Rhythms and Anticipatory Thirst by Dim Light at Night.

Our study addresses underlying mechanisms of disruption of the circadian timing system by low-intensity artificial light at night (ALAN), which is a growing global problem, associated with serious health consequences. Rats were exposed to low-intensity (∼2 lx) ALAN for 2 weeks. Using in situ hybridization, we assessed 24-h profiles of clock and clock-controlled genes in the suprachiasmatic nuclei (SCN) and other hypothalamic regions, which receive input from the master clock. Moreover, we measured the daily rhythms of hormones within the main neuroendocrine axes as well as the detailed daily pattern of feeding and drinking behavior in metabolic cages. ALAN strongly suppressed the molecular clockwork in the SCN, as indicated by the suppressed rhythmicity in the clock (Per1, Per2, and Nr1d1) and clock output (arginine vasopressin) genes. ALAN disturbed rhythmic Per1 expression in the paraventricular and dorsomedial hypothalamic nuclei, which convey the circadian signals from the master clock to endocrine and behavioral rhythms. Disruption of hormonal output pathways was manifested by the suppressed and phase-advanced corticosterone rhythm and lost daily variations in plasma melatonin, testosterone, and vasopressin. Importantly, ALAN altered the daily profile in food and water intake and eliminated the clock-controlled surge of drinking 2 h prior to the onset of the rest period, indicating disturbed circadian control of anticipatory thirst and fluid balance during sleep. Our findings highlight compromised time-keeping function of the central clock and multiple circadian outputs, through which ALAN disturbs the temporal organization of physiology and behavior.

Association between fluid overload and mortality in newborns: a systematic review and meta-analysis.

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.