Unbalanced Solutions Research Articles

A brief history of crystalloids: the origin of the controversy.

Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term "physiological solution" referred to fluids which did not cause red blood cell hemolysis in amphibians in in vitro studies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer's lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.

A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis.

The Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer's (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer's lactate in a cohort of sepsis patients. We performed a retrospective cohort analysis of patients visiting the ED of 19 different Mayo Clinic sites between August 2018 to November 2020 with sepsis and receiving at least 30 mL/kg fluid in the first 6 h. Patients were divided into two cohorts based on the type of resuscitation fluid (LR vs. NS) and propensity-matching was done based on clinical characteristics as well as fluid amount (with 5 ml/kg). Single variable logistic regression (categorical outcomes) and Cox proportional hazards regression models were used to compare the primary and secondary outcomes between the 2 groups. Out of 2022 patients meeting our inclusion criteria; 1,428 (70.6%) received NS, and 594 (29.4%) received LR as the predominant fluid (>30 mL/kg). Patients receiving predominantly NS were more likely to be male and older in age. The LR cohort had a higher BMI, lactate level and incidence of septic shock. Propensity-matched analysis did not show a difference in 30-day and in-hospital mortality rate, mechanical ventilation, oxygen therapy, or CRRT requirement. We did observe longer hospital LOS in the LR group (median 5 vs. 4 days, p = 0.047 and higher requirement for ICU post-admission (OR: 0.70; 95% CI: 0.51-0.96; p = 0.026) in the NS group. However, these did not remain statistically significant after adjustment for multiple testing. In our matched cohort, we did not show any statistically significant difference in mortality rates, hospital LOS, ICU admission after diagnosis, mechanical ventilation, oxygen therapy and RRT between sepsis patients receiving lactated ringers and normal saline as predominant resuscitation fluid. Further large-scale prospective studies are needed to solidify the current guidelines on the use of balanced crystalloids.

Does Extended Sawyer–Eliassen Equation Effectively Capture the Secondary Circulation of a Simulated Tropical Cyclone?

Abstract The validity of the gradient wind balance in a tropical cyclone (TC) remains controversial, especially for the boundary layer and the upper outflow layer, even though this balance is assumed in the derivation of the Sawyer–Eliassen (SE) equation. This study derives an extended SE equation with the relaxation of the gradient wind and hydrostatic balance in cylindrical r–z coordinates, and then we diagnose the secondary circulation using this unbalanced SE equation and the azimuthally averaged tangential wind and thermodynamical fields from a three-dimensional numerical simulation of an intensifying TC. The gradient wind and hydrostatic imbalance produce two additional time-dependent forcing terms on the right-hand side (rhs) of SE equation, which are proved to be negligible for diagnosing the secondary circulation, even as the storm evolves rapidly. The use of the unbalanced basic state deforms the fields of coefficients that appear in the SE equation, and thus the forced secondary flows. The results indicate that the unbalanced solution captures the boundary layer inflow better than the balanced solution described by Bui et al. and the pseudobalanced solution described by Heng et al. The unbalanced solution is closer to the simulation because more unbalanced components are included. Many previous studies always employ the thermal wind balance relation to simplify the SE equation, which is invalid in an unbalanced vortex and result in an overestimation of the boundary layer inflow. These unbalanced dynamics could provide a reliable diagnosis of the secondary flow near the boundary layer.

Solving Tea Blending Problems Using Interactive Fuzzy Multi-Objective Linear Programming

Blending is a classical and well-known optimization problem that has been applied in the food, steel, and composite material industries. However, tea blending is more complicated than general problems due to the variety of products, processes, and sources of raw materials and semi-products. So, in this research, a fuzzy multi-objective model for the tea blending problem was proposed to minimize the total production cost and the deviation of quality target score; it provides a more robust and flexible method than existing models for complex real-world problems. Existing research works of a blending problem consider only raw material cost, but semi-product cost and processing cost are included in the proposed model that matches the actual case. Losses that occur during production are also incorporated. The selection of appropriate raw materials and semi-product sources can be obtained with the preferred levels of cost and quality by the proposed algorithm. The interactive fuzzy multi-objective programming to solve the problem has advantages over existing interactive programming methods. It is easy to manipulate interactively to obtain more efficient solutions than existing methods and both balanced and unbalanced solutions can be selected. The comparison of the results of an existing approach and the interactive fuzzy multi-objective programming algorithm for the tea industry is illustrated.

Patient allocation method in major epidemics under the situation of hierarchical diagnosis and treatment

ObjectivesPatients are classified according to the severity of their condition and graded according to the diagnosis and treatment capacity of medical institutions. This study aims to correctly assign patients to medical institutions for treatment and develop patient allocation and medical resource expansion schemes among hospitals in the medical network.MethodsIllness severity, hospital level, allocation matching benefit, distance traveled, and emergency medical resource fairness were considered. A multi-objective planning method was used to construct a patient allocation model during major epidemics. A simulation study was carried out in two scenarios to test the proposed method.Results(1) The single-objective model obtains an unbalanced solution in contrast to the multi-objective model. The proposed model considers multi-objective problems and balances the degree of patient allocation matching, distance traveled, and fairness. (2) The non-hierarchical model has crowded resources, and the hierarchical model assigns patients to matched medical institutions. (3) In the “demand exceeds supply” situation, the patient allocation model identified additional resources needed by each hospital.ConclusionResults verify the maneuverability and effectiveness of the proposed model. It can generate schemes for specific patient allocation and medical resource amplification and can serve as a quantitative decision-making tool in the context of major epidemics.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Базові основи та принципи керованої інфузійної терапії у хворих із невідкладною хірургічною патологією органів черевної порожнини

За останні п’ятнадцять років кількість ургентних лапаратомій становила 36–58 % з летальністю 30–80 %. Однією з головних причин такої високої смертності є гіповолемія, що формує гемодинамічні порушення, тканинну гіпоксію і розвиток поліорганної недостатності. Основним методом її лікування є поповнен­ня дефіциту об’єму циркулюючої крові. Препаратами вибору вважаються кристалоїди. Прогнозування ефектів кристалоїдних розчинів легко провести за допомогою фізико-хімічної моделі кислотно-лужної рівноваги Стюарта. Згідно теорії, характеристиками збалансованого кристалоїдного розчину є: SIDinf = 24 мEqL–1; відповідність вмісту електролітів до їх концентрації в плазмі; наявність у складі органічних іонів, що запобігають підвищенню концентрації Cl– в інфузійному розчині і є донаторами резервної лужності. Виходячи з цього ми виділяємо серед кристалоїдних розчинів незбалансовані (0,9% розчин NaCl); частково збалансовані (розчини Рінгера лактат і Хартмана); повністю збалансовані розчини (плазмаліт, плазмаліт А, стерофундін, стерофундін ISO). Використання незбалансованих розчинів небезпечно у зв’язку з розвитком гіперхлоремічного ацидозу. Використання частково збалансованих кристалоїдних розчинів може формувати або посилювати лактатацидоз в умовах тканинної гіпоксії і/або дисфункції печінки. Інфузія збалансованих розчинів дозволяє швидко коригувати метаболічний ацидоз.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

Obstetric blood loss: priorities in the choice of infusion solutions

Background. Bleeding accounts for 34 % of maternal mortality. Every 7 minutes 1 woman dies from bleeding during the labour. Retrospective analysis of medical records shows that in 60-80 % of cases, fatal consequences can be avoided. Criteria for defining the concept of “massive blood loss” are the loss of 100 % of circulating blood volume (CBV) within 24 hours or 50 % of CBV within 3 hours, loss of 150 ml/min, of 2 % of body weight within 3 hours, reduction of hematocrit by 10 % in combination with hemodynamic disturbances, one-time blood loss more than 1500-2000 ml or 25-35 % CBV, the need for transfusion of &gt;10 doses of erythromass for 24 hours. The main causes of bleeding in obstetrics include uterine atony, premature placental abruption, uterine rupture, placental abruption, hereditary blood diseases, coagulopathy, sepsis, amniotic fluid embolism.&#x0D; Objective. To describe infusion therapy (IT) for obstetric bleeding.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. Strategies for the treatment of obstetric hemorrhage include restriction of the traditional massive crystalloid-based IT, applying the principle of antihypertensive resuscitation, using of adequate doses of tranexamic acid, fibrinogen concentrate and prothrombin complex concentrate, early informed use of blood components, and low-volume IT. Routine use of unbalanced crystalloid solutions in critically severe patients is dangerous. Infusion of large amounts of 0.9 % NaCl may cause metabolic hyperchloremic acidosis. Therefore, except in cases of hypochloremia, it is advisable to replace saline with balanced solutions. Reosorbilact (“Yuria-Pharm”) is the most suitable solution for this purpose. It mobilizes the own fluid of the organism, helping it to move from the intercellular space into the vessels. Hypotensive resuscitation involves the introduction of limited amounts of fluid in the early stages of treatment of hemorrhagic shock (until the bleeding stops). Low-volume IT program is a part of hypotensive resuscitation. In this case, the following solutions can be used: Reosorbilact, Sorbilact, Gekoton (“Yuria-Pharm”), 130/0.4 hydroxyethyl starch (HES), hypertonic NaCl solutions (including combined solutions with colloids), polyhydric alcohols. It should be noted that the new generation of HEC has less effect on coagulation than older drugs. Due to the risk of kidney damage, HEC solutions should be used in the lowest effective dose for as shortest period of time as possible. HEC infusion should be stopped as soon as hemodynamic targets are reached. Solutions containing polyhydric alcohols (Reosorbilact, Sorbilact, Xylate) occupy an important position in IT of critically ill patients. Due to their high osmolarity, Reosorbilact and Sorbilact cause fluid to move from the intercellular space into the vascular bed, improving microcirculation and tissue perfusion. The polyhydric alcohol sorbitol contained in these solutions creates increased osmotic pressure in the renal tubules, which provides a diuretic effect. In case of the blood loss volume of I-II functional class up to 1500 ml and stopped bleeding, IT is performed in a limited mode. The volume of intravenous infusion together with blood components should not exceed 200 % of the blood loss volume. Reosorbilact (10-15 ml/kg) is an initial solution in combination with 0.9 % NaCl (20-30 ml/kg). In case of unstable hemodynamics HEC may be added (up to 1,5 L). Blood components are used only in case of confirmed coagulopathy and continued bleeding. In case of massive critical blood loss &gt;1500-2000 ml, it is advisable to use the protocol of massive blood transfusion 1:1:1:1. In order to reduce the pathological response of the endothelium to IT, it is advisable to use a substrate for the nitric oxide synthesis, namely, Tivortin (“Yuria-Pharm”). To stop life-threatening obstetric bleeding, CBV must be refilled using the protocol of massive blood transfusion and automatic blood reinfusion, oxytocin and prostaglandin analogues for the correction of uterine tone, uterine massage, correction of coagulopathy, balloon tamponade of the uterus.&#x0D; Conclusions. 1. Emergency care for massive bleeding in obstetrics is one of the priorities in reducing maternal morbidity and mortality. 2. Intensive therapy of blood loss should be based on modern recommendations and the use of modern drugs. 3. The indications for transfusion of blood components should be clearly applied.

The role of hyperosmolar solutions in the physician’s practice

Background. The goal of infusion therapy (IT) is to maintain central euvolemia without excess sodium and water. The term “restrictive IT”, which allows hypovolemia, should be replaced by the term “IT with a zero balance”. Individualized targeted IT involves monitoring cardiac output, optimizing stroke volume, and preventing episodes of hypovolemia. Less stringent restrictions on preoperative nutrition contribute to better control of hemodynamic parameters.&#x0D; Objective. To describe the role of hyperosmolar solutions in the physician’s practice.&#x0D; Materials and methods. Analysis of literature sources on this issue.&#x0D; Results and discussion. Support of perioperative euvolemia is the basis of the concept of enhanced recovery and improvement of the surgery outcomes. Clinical indices of tissue perfusion adequacy include mean blood pressure, central and abdominal perfusion pressure, diuresis, consciousness level, skin perfusion, lactate and blood pH, etc. Each patient with suspected hypovolemia should be physically examined with an emphasis on searching for bleeding, dehydration, and other causes of hypovolemia. Fluid deficiency should be compensated before surgery. Hyperhydration must also be detected and eliminated timely, as the diagnosis and prediction of pulmonary edema are difficult. There are 4 phases in IT of shock: rescue (achieving blood pressure and cardiac output required for survival), optimization (ensuring sufficient oxygen delivery and lactate control), stabilization (preventing organ dysfunction after achieving hemodynamic stability), and de-escalation (ensuring negative fluid balance). In resuscitation of patients with sepsis and septic shock, the use of hydroxyethyl starch (HES) is not recommended; crystalloids should be preferred over gelatin. If HES were still prescribed, their introduction should be stopped if there are signs of kidney damage or signs of coagulopathy. It is also proposed not to administer hyperoncotic solutions to critically ill patients outside of clinical trials. New colloidal solutions should be introduced into clinical practice only after the establishment of safety for the patient. Following an appeal by HES-manufacturing companies, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency stated that HES could be used for massive bleeding at the discretion of the chief physician. Continued use of HES in the postoperative period should be further investigated, including monitoring of renal function for 90 days. In general, the use of HES in clinical practice remains relevant in conditions such as massive bleeding or penetrating trauma, as well as for preloading before regional anesthesia and IT of critical conditions without the risk of bleeding. Modern HES should be used and the dose should not exceed 30 ml/kg. The benefits of preoperative targeted preload optimization using HES are beyond doubt, while recommendations for the overall hazard of these solutions are debatable and inconclusive. The volume of injected solutions should be monitored during IT, as infusion of large volumes of crystalloids may cause pulmonary edema and large volumes of 0.9 % NaCl may lead to the development of hyperchloremic metabolic acidosis. Hypertonic solutions have been shown to be effective in reducing the number of abdominal complications of pancreatoduodenectomy, reducing the length of stay on mechanical ventilation in patients with hemorrhagic shock, and in a number of other interventions. Fluid resuscitation with a small volume of hypertonic saline after damage control operations significantly reduces the length of stay in the intensive care unit, decreases the likelihood of acute respiratory distress syndrome, sepsis and multiple organ failure, reduces 30-day mortality. In patients with brain injuries, hypertonic solutions reduce intracranial pressure and help to balance the fibrinolysis system by reducing secondary brain damage. Unfortunately, most (60 %) of the solutions on the market are unbalanced (Hohn R., 2014). The reasons for this include lower cost of the latter, the lack of understanding of the benefits of alternatives by doctors, the lack of awareness of the seriousness of these solutions’ disadvantages. Due to the risk of acidosis on the background of unbalanced solutions, chloride-restrictive IT should be followed. Hyperosmolar balanced solution Reosorbilact (“Yuria-Pharm”) helps to activate the sympathetic nervous system, which leads to increased blood pressure, decreased diuresis, adrenaline release and increase of circulating blood volume by contracting the spleen. Reosorbilact quickly normalizes hemodynamic parameters, microcirculation, laboratory and biochemical parameters, stabilizes and normalizes the function of external respiration and blood circulation. The use of osmotic drugs Reosorbilact and Xylate (“Yuria-Pharm”) is indicated for plasma volume replacement in hypovolemia of various origins.&#x0D; Conclusions. 1. Perioperative euvolemia is the main principle of perioperative IT. 2. It is not recommended to use HES in intensive care. 3. HES remain relevant in acute hypovolemia and blood loss. 4. Balanced hyperosmolar solutions (Reosorbilact) are an alternative to HES in the treatment of patients with multiple organ failure in intensive care units.

Infusion therapy of an oncologic patient: pros and cons

Background. The goals of infusion therapy (IT) include the restoration of adequate tissue perfusion, maintaining the quantity and quality of the body fluid sectors, correction of homeostasis parameters. In addition, IT can be used for parenteral nutrition, reducing the risk of thrombosis and urinary tract infections.&#x0D; Objective. To identify key IT parameters of a cancer patient.&#x0D; Materials and methods. Analysis of the available literature on this topic.&#x0D; Results and discussion. Indications for IT include hypovolemia, cellular and protein deficiency of blood, nutrition disorders, intoxication, disorders of hemostasis, hemorheological properties, fluid and electrolyte balance, acid-base status. Cancer patients often have the listed syndromes. The appropriate infusion volume should not be exceeded, as the hypervolemia is accompanied by edema, multiorgan dysfunction and worsening of the prognosis. On the other hand, dehydration is the most common fluid and electrolyte balance disorder in the elderly. It is an independent predictor of mortality and high healthcare costs. At any IT administration it is necessary to assess the volemia condition, to determine the cause of the deficiency, to choose the optimal solution and infusion rate, to set and to monitor target values. Capillary filling time, heart rate, blood pressure, jugular veins’ condition, skin turgor, pulmonary and cardiac auscultation data, edema control, diuresis rate, and weight changes are used to assess volemia. Peculiarities of the elderly and debilitated patients, which should be taken into account when prescribing IT, include the loss of thirst feeling, deterioration of renal function and worsening of hormonal regulation of fluid and electrolyte balance. Anticancer therapy has a number of side effects, and some of them can be eliminated with the help of IT. The amount of fluid required should be calculated based on physiological needs (30-40 ml/kg/day), deficiency severity and pathological losses (fever, blood loss, polyuria, perspiration, drainage losses). Plasma replacement solutions can be divided into crystalloids (iso- and hypertonic saline, Ringera lactate) and colloids (albumin, solutions of gelatin, dextranes, hydroxyethyl starch). Crystalloids are recommended for short-term interventions, while long-term therapy requires colloids or balanced solutions, as the introduction of unbalanced solutions is accompanied by such risks as hyperchloremia, dilutive acidosis, acute kidney damage, and systemic vasoconstriction. In settings of the chronic inflammation, which often accompanies oncological diseases, the role of thirst as a means of controlling osmolarity changes. Hyperosmolarity may also accompany central diabetes mellitus and tumor metastases to the hypothalamus. Hyperosmolarity leads to the microcirculatory disorders, increased inflammation, cachexia development and multiple organ failure. Another feature of IT in oncology settings is the disruption of tissue energy supply due to nutritional deficiencies and changes in metabolism. Xylitol (Xylate, “Yuria-Pharm”) can be used to eliminate this problem. Xylitol is a five-atom alcohol, which is directly included into the pentose phosphate cycle. The benefits of xylitol include metabolism stabilization in people with diabetes, promotion of slow but stable energy production, antiketogenic properties, improved metabolism of B vitamins, cholekinetic action, and high safety. Xylitol is not used by the tumor cells as an energy substrate. The role of xylitol (Xylate) in IT is to increase the volume of circulating plasma, to reduce the interstitial edema, to decrease the production of ketone bodies, to activate the antioxidant systems, and to increase alkaline blood reserve. It has been reported that xylitol infusion has an oncosuppressive effect due to its antioxidant effect and inhibition of glucose utilization by tumor cells.&#x0D; Conclusions. 1. IT is an important component of cancer treatment; it should be based on the individual features of the patient. 2. Rational IT eliminates chronic inflammation, endothelial dysfunction and microcirculatory disorders. 3. Rational IT is based on the correct choice of solution, its timely introduction and frequent evaluation of the infusion response. 4. Xylate (“Yuria-Pharm”) has a multifunctional effect in oncology: eliminates dehydration, corrects energy deficiency, and has a direct oncosuppressive effect.

Novel Node-Ranking Approach for SDN-Based Virtual Network Embedding

Network virtualization is considered as a key technology for the future network. The emergence of software-defined network (SDN) provides a platform for the research and development of network virtualization. One of the key challenges in network virtualization is virtual network embedding (VNE). Some of the previous VNE algorithms perform virtual node embedding, which combines the nodes’ resource attributes and local topology attributes by arithmetic operations. On the one hand, it is not easy to distinguish the topological differences between SN and VN only by simple topology metrics. On the other hand, it is easy to ignore the different weight impacts of different metrics using only arithmetic operations, which will lead to an unbalanced embedding solution. To deal with these issues, we propose a novel node-ranking approach based on topology-differentiating (VNE-NRTD) for SDN-based virtual network embedding. Owing to the topological difference between SN and VN, different node metrics are used to quantify the substrate nodes and virtual nodes, respectively. Then, the nodes are ranked using the modified set pair analysis (SPA) method to avoid the unbalanced embedding solution. On this basis, we introduce the global bandwidth of the network topology into node-ranking to further improve the efficiency of node embedding. The simulation results show that the VNE-NRTD algorithm proposed in this paper outperforms other latest heuristic algorithms in terms of the VNR acceptance ratio, long-term average R/C ratio, substrate node utilization, and substrate link utilization.

Effect of Small Tidal Fluctuations on the Stability and Equilibrium Configurations of Bifurcations

Deltas are fascinating landforms subject to fluvial and marine forcing. Bifurcations are common features in deltas, governing the distribution of water and sediment fluxes among the distributary channel network. Recently, it has been observed that tide‐influenced deltas tend to display less numerous but more stable branches in comparison to their riverine counterparts. River bifurcations subject to unidirectional flow have been widely studied in the last decades. In contrast, the acting physical mechanisms and factors controlling the stability of bifurcations in tide‐influenced deltas are still not well understood, and a theoretical framework is still lacking. In order to fill this gap and understand how the stability and evolution of bifurcations in distributary deltaic systems could be affected by the tides, we investigate, through an analytical model, the equilibrium configurations and stability of tidal bifurcations under the hypothesis of small monochromatic tidal oscillations. In particular, we build on previous works on river bifurcations, incorporating the solution for the equilibrium of a single‐river‐dominated estuary. We find that higher tidal amplitudes and a closer proximity of the junction node to the sea tend to hamper the development of unbalanced solutions, reducing the asymmetries in water and sediment fluxes between branches. This stabilizing effect exerted by the tidal action is associated with the erosive character of the tidal currents that promotes channel deepening and increases the capacity of the system to keep morphodynamically active both bifurcates in comparison with the purely fluvial case. Preliminary field observations of natural deltas corroborate our findings.

Intravenous Fluid Prescription Practices in Critically Ill Children: A Shift in Focus from Natremia to Chloremia?

Our objective is to evaluate intravenous (IV) fluid prescription practice patterns in critically ill children in the first 72 hours of pediatric intensive care unit (PICU) admission and to evaluate the incidence and predictors of hyperchloremic metabolic acidemia (HCMA) and the association between HCMA and adverse outcomes. This retrospective cohort study was conducted in two tertiary-care Canadian PICUs. Children aged 0 to 18 years admitted to the PICU between January 2015 and January 2016 who received at least 50% of their calculated maintenance fluid requirements parenterally during the first 24 hours of admission were included. Children with known preexisting conditions associated with HCMA, such as renal tubular acidosis and gastrointestinal bicarbonate losses, were excluded. Of the 771 children screened, 543 met eligibility criteria and were included. The commonest prescribed maintenance fluid was 0.9% NaCl (72.9%) followed by lactated Ringer's solution (19.6%) and hypotonic solutions (4.6%). Balanced salt solutions (i.e., lactated Ringer's and Plasma-Lyte) were as commonly administered as unbalanced solutions (0.9% NaCl) for volume expansion (49.6 vs. 48.5%, respectively). Medications contributed to a significant proportion of total daily intake, in excess of bolus fluids. The incidence of hyperchloremia and HCMA was 94.9% (95% confidence interval [CI]: 93.2-96.9; 470/495) and 38.9% (95% CI: 34.6-43.2; 196/504), respectively. Predictors of HCMA were increasing combined bolus and maintenance 0.9% NaCl intake (odds ratio: 1.13; 95% CI: 1.04-1.23) and increasing severity of illness. HCMA was not associated with an increased risk of acute kidney injury, feeding intolerance, or PICU-acquired weakness. Isotonic fluids, specifically 0.9% NaCl, were the most commonly administered maintenance IV fluid in critically ill children. Sources of chloride load are not isolated to resuscitation fluids as previously suggested. Maintenance fluids and fluids administered with medications and IV flushes (fluid creep) are under-recognized significant sources of fluid and electrolyte intake in critically ill children. HCMA is common, and further prospective research is required to determine whether HCMA is indeed harmful in children. However, all significant sources of fluid should be accounted for in the design of future trials comparing balanced and unbalanced salt solutions.

Goal-directed use of balanced solutions for laparoscopic surgery in obese patients

Modern guidelines for infusion therapy in laparoscopic surgery of patients with obesity are ambiguous due to insufficient number of clinical researches. The aim of our work was to evaluate the effect of goal-directed infusion therapy with balanced solutions on hemodynamics, electrolyte balance, renal function and incidence of perioperative complications of laparoscopic surgery in obese patients. Materials and methods. The study included 54 obese patients (BMI >30 kg/m 2 ) who were performed laparoscopic surgery in case of the diaphragmatic hernia, colon tumors, postoperative ventral hernia and morbid obesity. In the group A (n = 26) goal-directed infusion therapy by balanced solutions Gelaspan and Sterofundin (B. Braun, Germany) was used. Impedance measuring technology using the monitor Utas 300 (Ukraine) was used to determine the target stroke volume (SV). In the group B (n = 28) infusion therapy was performed by unbalanced solutions (6 % HES and 0.9 % NaCl), focusing on fluid deficiency according to changes in blood pressure (BP), heart rate (HR), and diuresis. The incidence of hypotension and total volume of infusion therapy (TVIT) were evaluated intraoperatively, changes in BP and HR were compared. After surgery diuresis, blood Na + , K + , Cl – and creatinine concentrations, diuretic use frequency and incidence of cardiac, respiratory, hemorrhagic and infectious complications were controlled. Statistical analysis was performed using the Statistica for Windows software version 6.0. Results. The incidence of hypotension in the group B was almost 2 times more than in the group A (P 0.05). Intraoperative TVIT in the group B was 23 % higher due to crystalloid, and diuresis intensity was twice less than in the group A (P < 0.05). Concentrations of electrolytes and creatinine blood level did not change significantly in the study groups. After surgery in the group B 25 % of patients were prescribed diuretic and in the group A diuretic was not prescribed in any case (P < 0.05). In-hospital mortality in both groups was zero, no serious complications were observed. Conclusions. Goal-directed infusion therapy with balanced solutions in laparoscopic surgery in obese patients halved the incidence of intraoperative hemodynamic instability, reduces the volume loading of crystalloids by 23 % during surgery and provides adequate perioperative diuresis without additional stimulation.

Optimal packings of three-arm star polyphiles: from tricontinuous to quasi-uniformly striped bicontinuous forms.

Star-shaped molecules with three mutually immiscible arms self-assemble to form a variety of novel structures, with conformations that attempt to minimize interfacial area between the domains composed of the different arms. The geometric frustration caused by the joining of these arms at a common centre limits the size and shape of each domain, encouraging the creation of complex and interesting solutions. Some solutions are tricontinuous, and these solutions (and others) share aspects of bicontinuous structures with amphiphilic assemblies as similar molecular segregation factors are at work. We describe both highly symmetric and balanced structures, as well as unbalanced solutions that take the form of intricately striped amphiphilic membranes. All these patterns can result in chiral assemblies with multiple networks.

Fluid composition and acute kidney injury.

To describe recent advances in the understanding of the role of fluid composition in renal outcomes in critically ill patients. The debate on fluid composition is now focused in a pragmatic discussion on fluid electrolyte composition. The resurgence of this debate was propelled by several observational studies that suggested that balanced (i.e., low chloride) solutions were associated with less acute kidney injury in critically ill patients. Nevertheless, a cluster randomized trial failed to show any benefit of balanced solutions. This trial, however, may have failed to detect an effect because of low global illness severity and little fluid infused. If balanced solutions are to be associated with less acute kidney injury, it will probably be in high risk, aggressively resuscitated patients. Additionally, the causal loop involving unbalanced solution infusion, induction of hyperchloremia and acute kidney injury is yet to be closed. Other factors, such as buffer type, speed of infusion and temperature, among others, may also be important. Recent evidence suggests that crystalloid fluid composition matters and can influence renal outcomes in critically ill patients. Further studies should assess the impact and cost-efficiency of balanced solutions in the context of high-risk scenarios.

The role of bicarbonate precursors in balanced fluids during haemorrhagic shock with and without compromised liver function

BackgroundLactate, acetate, and gluconate are anions used in balanced resuscitation fluids, of which lactate and acetate are considered bicarbonate precursors. This study investigated the role of the liver in the ability of balanced and unbalanced solutions to correct acid–base alterations and renal haemodynamics and microvascular oxygenation in a rat model of resuscitated haemorrhagic shock. MethodsRinger’s lactate, Ringer’s acetate, PlasmaLyte, or normal saline were administered following haemorrhagic shock in the presence or absence of a 70% partial liver resection. Renal haemodynamics and microvascular oxygenation (by oxygen-dependent quenching of phosphorescence) were measured as well as concentrations of lactate, gluconate, and acetate in plasma and urine. Kidney wet and dry weight was also assessed. ResultsPartial liver resection resulted in increased liver enzymes compared with control and shock groups (P< 0.01). Haemorrhagic shock decreased systemic and renal perfusion and reduced microvascular kidney oxygenation with lactic acidosis (P< 0.01). Resuscitation with balanced fluids did not fully restore renal oxygenation (P< 0.01). Ringer’s acetate and PlasmaLyte increased bicarbonate content and restored pH better than Ringer’s lactate or saline after partial liver resection (P< 0.01). Liver resection caused an increase in plasma gluconate after PlasmaLyte resuscitation (P< 0.05). ConclusionsAcetate-buffered balanced fluids show superior buffering effects compared with Ringer’s lactate or saline. Gluconate is partially metabolized by the liver, although it does not contribute to acid–base control because of its excretion in urine. Acetate is metabolized regardless of liver function and may be the most efficient bicarbonate precursor. Lactate infusion tends to overwhelm the metabolism capacity of the residual liver.

Balanced crystalloids for septic shock resuscitation.

Timely fluid administration is crucial to maintain tissue perfusion in septic shock patients. However, the question concerning which fluid should be used for septic shock resuscitation remains a matter of debate. A growing body of evidence suggests that the type, amount and timing of fluid administration during the course of sepsis may affect patient outcomes. Crystalloids have been recommended as the first-line fluids for septic shock resuscitation. Nevertheless, given the inconclusive nature of the available literature, no definitive recommendations about the most appropriate crystalloid solution can be made. Resuscitation of septic and non-septic critically ill patients with unbalanced crystalloids, mainly 0.9% saline, has been associated with a higher incidence of acid-base balance and electrolyte disorders and might be associated with a higher incidence of acute kidney injury. This can result in greater demand for renal replacement therapy and increased mortality. Balanced crystalloids have been proposed as an alternative to unbalanced solutions in order to mitigate their detrimental effects. Nevertheless, the safety and effectiveness of balanced crystalloids for septic shock resuscitation need to be further addressed in a well-designed, multicenter, pragmatic, randomized controlled trial.

Intravenous balanced solutions: from physiology to clinical evidence.

"Balanced" solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. Recently, the term "balanced" solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered and supra-physiologic in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental effect on renal function associated with hyperchloremia. Despite efforts for its identification, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available. After the accumulation of pre-clinical and clinical physiologic data, in the last three years, several clinical trials, mostly observational and retrospective, have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival. Nonetheless, the first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solution on renal function in critically-ill patients (SPLIT trial, the 0.9% Saline vs Plasma-Lyte 148 for Intensive Cate Unit Fluid Therapy), just recently published, showed identical equipoise between the two treatments. In the present review, we offer a comprehensive and updated summary on this issue, firstly, by providing a full physiological background of balanced solutions, secondly, by summarizing their potential pathophysiologic effects, and lastly, by presenting the clinical evidence available to support, at the moment, their use.