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Efficacy of Furosemide, Oral Sodium Chloride, and Fluid Restriction for Treatment of Syndrome of Inappropriate Antidiuresis (SIAD): An Open-label Randomized Controlled Study (The EFFUSE-FLUID Trial).
Krisanapan, P, Vongsanim, S, Pin-On, P, Ruengorn, C, Noppakun, K
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(2):203-212
Abstract
RATIONALE & OBJECTIVE First-line therapy for syndrome of inappropriate antidiuresis (SIAD) is fluid restriction. Additional treatment for patients who do not respond to fluid restriction are water restriction with furosemide or water restriction with furosemide and salt supplementation. However, the efficacy of these treatments has never been tested in a randomized controlled study. The objective of this study was to investigate whether, combined with fluid restriction, furosemide with or without sodium chloride (NaCl) supplementation was more effective than fluid restriction alone in the treatment of hyponatremia in SIAD. STUDY DESIGN Open-label randomized controlled study. SETTING & PARTICIPANTS Patients with serum sodium concentrations ([Na+]) ≤ 130mmol/L due to SIAD. INTERVENTION(S): Random assignment to 1 of 3 groups: fluid restriction alone (FR), fluid restriction and furosemide (FR+FM), or fluid restriction, furosemide, and NaCl (FR+FM+NaCl). Strictness of fluid restriction (<1,000 or<500mL/d) was guided by the urine to serum electrolyte ratio. Furosemide dosage was 20 to 40mg/d. NaCl supplements were 3g/d. All treatments were continued for 28 days. OUTCOMES The primary outcome was change in [Na+] at days 4, 7, 14, and 28 after randomization. RESULTS 92 patients were recruited (FR, n=31; FR+FM, n=30; FR+FM+NaCl, n=31). Baseline [Na+] was 125±4mmol/L, and there were no significant differences between groups. Mean [Na+] on day 4 in all treatment groups was significantly increased from baseline by 5mmol/L (P<0.001); however, the change in [Na+] was not significantly different across groups (P=0.7). There was no significant difference in percentage of patients or time to reach [Na+] ≥ 130 or≥135mmol/L across the 3 groups. Acute kidney injury and hypokalemia (potassium≤3.0mmol/L) were more common in patients receiving furosemide. LIMITATIONS Open-label treatment. CONCLUSIONS In patients with SIAD, furosemide with NaCl supplement in combination with fluid restriction did not show benefits in correction of [Na+] compared with treatment with fluid restriction alone. Incidences of acute kidney injury and hypokalemia were increased in patients receiving furosemide. FUNDING None. TRIAL REGISTRATION Registered at the Thai Clinical Trial Registry with study number TCTR20170629004.
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Lactate versus acetate buffered intravenous crystalloid solutions: a scoping review.
Ellekjaer, KL, Perner, A, Jensen, MM, Møller, MH
British journal of anaesthesia. 2020;(5):693-703
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Abstract
BACKGROUND Buffered crystalloid solutions are increasingly recommended as first-line intravenous resuscitation fluids. However, guidelines do not distinguish between the different types of buffered solutions. The aim of this scoping review was to assess the evidence on the use of lactate- vs acetate-buffered crystalloid solutions and their potential benefits and harms. METHODS We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We searched PubMed, Embase, Epistemonikos, and the Cochrane Library for studies assessing the effect of lactate- vs acetate-buffered crystalloid solutions on any outcome in adult hospitalised patients. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS We included a total of 29 studies, 25 of which were clinical trials and four were observational studies. Most studies were conducted in surgical settings and indications for use were poorly described. The most commonly administered solutions were Ringer's lactate vs Ringer's acetate or Plasma-Lyte™. Outcomes included acid/base and electrolyte status; haemodynamic variables; and markers of renal and liver function, metabolism, and coagulation. Only a few studies reported patient-centred outcomes. Overall, the data provided no firm evidence for benefit or harm of either solution, and the quantity and quality of evidence were low. CONCLUSIONS The quantity and quality of evidence on the use of different buffered crystalloid intravenous solutions were low, data were derived primarily from surgical settings, and patient-important outcomes were rarely reported; thus, the balance between benefits and harms between these solutions is largely unknown.
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Impact of Nuun Electrolyte Tablets on Fluid Balance in Active Men and Women.
Pence, J, Bloomer, RJ
Nutrients. 2020;(10)
Abstract
BACKGROUND Maintaining adequate hydration is important for overall health and has major implications for athletes involved in physically demanding tasks. While water is viewed as an effective means to rehydrate, and is inexpensive and readily available, electrolyte beverages appear to be more beneficial, in particular for athletes who routinely lose electrolytes through sweating. Nuun tablets contain a mix of electrolytes and are quickly dissolved in water to create an electrolyte-rich beverage. We determined the impact of Nuun tablets on the fluid balance of healthy, exercise-trained men and women at rest. METHODS Eight men (25.9 ± 4.5 yrs) and 10 women (28.2 ± 9.4 yrs) ingested either water only or water with Nuun electrolyte tablets, at both a single and double strength concentration, in random order, on three separate occasions separated by approximately one week, in a fasted and euhydrated state. A total of 1 liter of fluid was ingested at each visit over a 30 minute period. Urine was collected from each subject at 0, 1, 2, 3, and 4 hours post-ingestion. Urine mass values were used to calculate fluid balance and the beverage hydration index (BHI; i.e., the volume of urine produced after drinking the Nuun beverages, relative to that of water only-control condition). Heart rate and blood pressure were measured throughout the four-hour period, while body weight was measured at the start and end of the experiment. RESULTS Neither heart rate nor blood pressure were impacted by beverage consumption. Nuun tablets resulted in a lower urine output compared to water, with fluid balances for both concentrations more favorable compared to water (p < 0.05), beginning at 2 h post-ingestion and continuing at the 3 h and 4 h times. Body weight loss was less with Nuun at the single dose (0.38 kg; p = 0.02) and double dose (0.43 kg; p = 0.08), compared to water (0.57 kg). The BHI was higher for Nuun (single dose in particular) compared to water at both 2 h (p = 0.05) and 4 h (p = 0.02). CONCLUSION The addition of Nuun electrolyte tablets to water improves the fluid balance and BHI in healthy men and women. Results were similar for both concentrations, suggesting that additional electrolytes are not necessary when in a rested state. Future studies should determine the impact of various concentrations of the Nuun beverage during physical exercise-in particular, exercise in the heat, when sweat loss may be highest.
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Efficacy of "optimal hydration" during labor: HYDRATA study protocol for a randomized clinical trial.
Hernández López, AB, Muriel Miguel, C, Fernández-Cañadas Morillo, A, López Lapeyrere, C, Pérez Medina, T, Salcedo Mariña, Á, Fornet Ruiz, I, Rubio González, E, Solís Muñoz, M
Research in nursing & health. 2020;(1):8-16
Abstract
There is a lack of consensus in the international scientific community with respect to the most suitable hydration strategies when attending nulliparous women during low-risk births. This paper describes the protocol for a randomized controlled trial to compare two hydration strategies and their influence on maternal and neonatal morbidity. The study population consists of nulliparous women admitted to the obstetrics department of a University Hospital. The women are being randomized into two groups: the "optimal hydration" group, which will be guaranteed 300 ml/hr liquids (crystalloids and bottled mineral water) with a minimum diuresis of 35 ml/hr; and the "variability in hydration" group, which will receive intravenous (alternating normal saline, Ringer's lactate solution, glucose, or Voluven®) and clear (bottled mineral water or isotonic drinks [Aquarius®]) liquids, without any established perfusion rate, and without established minimum diuresis. Outcomes for mothers include duration of labor, cesarean section, fever, and dehydration. Outcomes for newborns are respiratory distress, hypoglycemia, hyponatremia, jaundice, weight loss over 48 hr, and breastfeeding difficulties. Analysis will be per-protocol. Administering optimal hydration may improve health and safety for mothers and their newborn and reduce maternal and neonatal morbidity. The study is registered at www.clinicaltrials.gov. The project received funding by the Ministry of Health of Spain and is approved by the Research Ethics Committee.
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Hydration may reverse most symptoms of lower extremity intermittent claudication or rest pain.
Parodi, JC, Fernandez, S, Moscovich, F, Pulmaria, C
Journal of vascular surgery. 2020;(4):1459-1463
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BACKGROUND Medical treatment of severe intermittent claudication or critical limb-threatening ischemia causing rest pain frequently achieves only partial relief or is not effective at all. METHODS Patients with severe intermittent claudication or rest pain of the lower extremities who did not improve after control of risk factors, supervised exercises, and cilostazol medication were included in this study. All patients were treated with hydration. They were asked to drink 2500 mL of fluids (water, soup, milk) during a 24-hour period and to ingest 0.6 g/kg of albumin a day, as egg white or albumin powder. Total salt administered daily was 3.5 g. Symptoms, skin temperature, ankle-brachial index, albumin concentration in serum, and time and distance to claudication were recorded before treatment, at 6 weeks, and at 6 months. Electrolytes were measured monthly. No additional treatment was used during the study. Walking was encouraged but not supervised. The trial has continued indefinitely. For statistical analysis, SPSS software (IBM Corp, Armonk, NY) was used. The Ethical Committee approved the protocol, and an informed consent was signed by all patients. RESULTS There were 132 patients (94 male, 38 female) included in the study. Median age was 72.5 years (range, 67-77 years); all had severe claudication of a mean of 100 meters or rest pain. Symptoms had been present for >5 months in all patients; 22 (16.8%) had rest pain. Proper hydration, determined as drinking at least 2000 mL of water during 24 hours for a period of 6 months, was achieved in 131 compliant patients. Only one patient failed to drink 2000 mL of water or more. Ankle-brachial index in 131 compliant patients improved from 0.6 to 0.75 (P < .0001) after 6 months. Skin temperature of the feet increased from 29.4°C to 31.7°C (P = .009). Distance to claudication using the treadmill improved from 100 meters to 535 meters (P < .0001) at 6 weeks and remained stable at 6 month in 65.83% of the patients; in 34.17% of them, distance to claudication increased further by 200 (100-500) meters and time to claudication improved from 1.3 to 6.3 minutes (P < .0001) at 6 weeks, but the same group of patients (34.17%) that increased the distance to claudication further prolonged the time to claudication by 2.49 (1.24-6.23) minutes. All 131 compliant patients improved their status related to lower extremity ischemia; the noncompliant patient did not have any variation of symptoms, skin temperature, ankle-brachial index, or time and distance to claudication. All patients survived the initial 6 months of treatment; afterward, three patients abandoned the treatment and four died of unrelated causes. After the 6-month control, 49% of the patients continued to improve the time and distance to claudication as well as the ankle-brachial index. The rest of the patients conserved the initial improvement. Five patients who had significantly improved the time and distance to claudication were asked to decrease water intake for 3 days. No changes in time and distance to claudication were detected. Hydration was reinitiated. CONCLUSIONS This study suggests that proper hydration by drinking ≥2000 mL of water daily and albumin complement orally to reach 4 g/dL in serum could be included in the armamentarium of physicians treating patients with disabling claudication or rest pain caused by peripheral artery disease. Further comparative studies to assess the benefit of hydration and increasing the serum oncotic pressure are warranted.
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Hypertension during Diabetic Ketoacidosis in Children.
DePiero, A, Kuppermann, N, Brown, KM, Schunk, JE, McManemy, JK, Rewers, A, Stoner, MJ, Tzimenatos, L, Garro, A, Myers, SR, et al
The Journal of pediatrics. 2020;:156-163.e5
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OBJECTIVES To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. STUDY DESIGN This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension. RESULTS Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment. CONCLUSIONS Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.
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Subcutaneous hydration and medications infusions (effectiveness, safety, acceptability): A systematic review of systematic reviews.
Broadhurst, D, Cooke, M, Sriram, D, Gray, B
PloS one. 2020;(8):e0237572
Abstract
OBJECTIVE To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality. INTRODUCTION Peripheral intravascular cannula/catheter insertion is a common invasive procedure for administering fluids and medications. Venous depletion is a growing concern for several patient populations. Subcutaneous access for the administration of isotonic solutions and medications is an alternative; however, vascular access assessment and planning guidelines rarely consider this route. METHODS Systematic review of systematic reviews (PROSPERO CRD42018046504). We searched 6 databases published in English language from 1990 to June 2020, identifying subcutaneous infusions an alternate route for fluids or medication. Methodological quality was evaluated using AMSTAR 2 criteria and data for mechanisms of infusion and outcomes related to effectiveness, safety, efficiency and acceptability extracted. The Johanna Briggs Institute's grades of recommendation informed the strength of recommendation. RESULTS The search yielded 1042 potential systematic reviews; 922 were excluded through abstract and duplicate screen. Of the remaining articles, 94 were excluded, and 26 were included. Overall, evidence is strong for recommending subcutaneous hydration infusions for older adults, weak for pediatric patients and inconclusive for palliative patients. There is strong evidence for 10 medications; weak evidence supporting 28 medications; however, there are eight medications with inconclusive evidence to make a recommendation and four medications not appropriate for subcutaneous delivery. CONCLUSION Subcutaneous access should be considered alongside intravenous therapy for hydration in older adults, and several medications. There are additional benefits in terms of ease of use and cost-effectiveness of this mode. Inclusion of subcutaneous access in clinical guidelines may promote uptake of this route to help preserve vessel health of vulnerable patients. Further high-quality research is needed to inform subcutaneous infusion therapy in a variety of populations (including pediatrics and palliative care) and medications and clarifying the mechanism of delivery.
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Weight-Based Assessment of Fluid Overload in Patients with Acute Kidney Injury.
Chow, BL, Poh, CB, Chionh, CY
Nephron. 2020;(6):281-289
Abstract
INTRODUCTION Acute kidney injury (AKI) with fluid overload is associated with poor outcomes. While percentage fluid overload (PFO) using intake/output charts (PFOi/o) has been validated as a marker of overload, accurate PFOi/o measurements may not be possible in a general ward. We propose an alternative weight-based PFO calculation: PFOw = [(maximum weight - baseline weight) ÷ baseline weight] × 100%. METHODS This is a prospective, observational pilot study on general ward inpatients with AKI who were referred for nephrology consult. PFOw was compared with PFOi/o, and both were evaluated for associations with dialysis requirement, AKI stage 2 or 3, and 90-day mortality. RESULTS Fifty-eight patients with a median age of 67.5 years (interquartile range 18.0) were recruited. Of which, 33 (56.9%) were males and 41 (70.7%) had preexisting CKD 3 or higher. We found no correlation between PFOi/o and PFOw (R2 = 0.015, p = 0.531). A higher PFOw was observed in AKI stage 2 or 3 (p = 0.005) and in patients requiring dialysis (p = 0.001). On multivariate analysis, each percentage increase in PFOw was associated with increased odds of AKI stage 2 or 3 (odds ratio 1.37 [95% CI 1.05-1.78], p = 0.020) and dialysis need (odds ratio 1.69 [95% CI 1.20-2.39], p = 0.003). Twenty-nine patients had complete quantitative data to calculate PFOi/o. Multivariate analysis of these 29 patients showed that PFOw correlated with AKI stage 2 or 3 and dialysis requirement, while PFOi/o had no correlation with these events. The area under the curve receiver operating characteristics of PFOw was 0.706 for AKI stage 2 or 3 and 0.819 for AKI requiring dialysis. The optimal PFOw cutoff was determined at ≥1%. Three deaths occurred within 90 days, and all had PFOw ≥ 1%, although the log-rank test did not achieve statistical significance (p = 0.050). CONCLUSION The proposed PFOw is a potential prognostic indicator for general ward patients with AKI. PFOw ≥ 1% is associated with poor renal outcomes.
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Fluid Balance and Hydration Considerations for Women: Review and Future Directions.
Giersch, GEW, Charkoudian, N, Stearns, RL, Casa, DJ
Sports medicine (Auckland, N.Z.). 2020;(2):253-261
Abstract
Although it is well understood that dehydration can have a major impact on exercise performance and thermoregulatory physiology, the potential for interactions between female sex hormone influences and the impact of dehydration on these variables is poorly understood. Female reproductive hormonal profiles over the course of the menstrual cycle have significant influences on thermoregulatory and volume regulatory physiology. Increased insight into the interactions among dehydration and menstrual cycle hormonal influences may have important implications for safety, nutritional recommendations, as well as optimal mental and physical performance. The purpose of this review is to summarize what is known in this area and highlight the areas that will be important for future work.
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Phases of fluid management and the roles of human albumin solution in perioperative and critically ill patients.
Wiedermann, CJ
Current medical research and opinion. 2020;(12):1961-1973
Abstract
OBJECTIVE Positive fluid balance is common among critically ill patients and leads to worse outcomes, particularly in sepsis, acute respiratory distress syndrome, and acute kidney injury. Restrictive fluid infusion and active removal of accumulated fluid are being studied as approaches to prevent and treat fluid overload. Use of human albumin solutions has been investigated in different phases of restrictive fluid resuscitation, and this narrative literature review was undertaken to evaluate hypoalbuminemia and the roles of human serum albumin with respect to hypovolemia and its management. METHODS PubMed/EMBASE search terms were: "resuscitation," "fluids," "fluid therapy," "fluid balance," "plasma volume," "colloids," "crystalloids," "albumin," "hypoalbuminemia," "starch," "saline," "balanced salt solution," "gelatin," "goal-directed therapy" (English-language, pre-January 2020). Additional papers were identified by manual searching of reference lists. RESULTS Restrictive fluid administration, plus early vasopressor use, may reduce fluid balance, but in some cases fluid overload cannot be entirely avoided. Deresuscitation, with fluid actively removed through diuretics or ultrafiltration, reduces duration of mechanical ventilation and intensive care unit stay. Combining hyperoncotic human albumin solution with diuretics increases hemodynamic stability and diuresis. Hyperoncotic albumin corrects hypoalbuminemia and raises colloid osmotic pressure, limiting edema formation and potentially improving endothelial function. Serum levels of albumin relative to C-reactive protein and lactate may predict which patients will benefit most from albumin therapy. CONCLUSIONS Hyperoncotic human albumin solution facilitates restrictive fluid therapy and the effectiveness of deresuscitative measures. Current evidence is mostly from observational studies, and more randomized trials are needed to better establish a personalized approach to fluid management.