A new approach to individualize dialysis fluid sodium concentration using a four-stream, bicarbonate-based fluid delivery system.

We propose a new 45X, four-stream, triple-concentrate, bicarbonate-based dialysis fluid delivery system, allowing a wide range of dialysis fluid sodium concentrations\\ (DFNa ) without affecting the concentrations of other crucial solutes. The four streams consist of product water (W), and concentrates with sodium chloride (S), acid (A), and sodium bicarbonate (B). An adjustment in the DFNa in this new system requires changes only in the W and S concentrate streams. The ingredients in A and B concentrates do not change.

A four-stream method for providing variable dialysis fluid bicarbonate concentrations for bicarbonate-based dialysis fluid delivery systems.

BACKGROUND: Hemodialysis corrects metabolic acidosis by transferring bicarbonate or bicarbonate equivalents across the dialysis membrane from the dialysis fluid to the plasma. With the conventional three-stream bicarbonate-based dialysis fluid delivery system, a change in the bicarbonate concentration results in changes in the other electrolytes. In practice, the dialysis machine draws either a little less or more from the bicarbonate concentrate and a little more or less from the acid concentrate, respectively in a three-stream delivery system. The result not only changes the bicarbonate concentration of the final dialysis fluid but also causes a minor change in the other ingredients. METHODS: We propose a four-stream bicarbonate-based dialysis fluid delivery system consisting of an acid concentrate, a base concentrate, a product water, and a new sodium chloride concentrate. RESULTS: By adjusting the flow rate ratio between the sodium chloride and sodium bicarbonate concentrates, one can achieve the desired bicarbonate concentration in the dialysis fluid without changing the concentration of sodium or ingredients in the acid concentrate. The chloride concentration mirrors the change in bicarbonate but in the opposite direction. CONCLUSION: A four-stream, bicarbonate-based dialysis fluid delivery system allows the bicarbonate concentration to be changed without changing the other constituents of the final dialysis fluid.

Osmotic Pressure in Clinical Medicine with an Emphasis on Dialysis.

Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.

Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.

Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient.

Severe Ethanol Poisoning Among United States College Fraternity Pledges.

Hazing is a longstanding tradition in university and college fraternities. This practice often uses alcohol as a penalty during hazing rituals, resulting in severe ethanol poisoning and even death among pledges. Typically, the serum ethanol levels in these poisoned students are extremely high. Preventing severe ethanol poisoning is crucial, and can be achieved through education about the harms of these hazing activities. Hemodialysis is an effective treatment for severe ethanol poisoning as it removes the excess alcohol in a timely manner.

Hypernatremia in Hyperglycemia: Clinical Features and Relationship to Fractional Changes in Body Water and Monovalent Cations during Its Development.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

Pseudohyponatremia: Mechanism, Diagnosis, Clinical Associations and Management.

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]S, making any inadvertent correction treatment potentially detrimental.

The role of intra- and interdialytic sodium balance and restriction in dialysis therapies.

The relationship between sodium, blood pressure and extracellular volume could not be more pronounced or complex than in a dialysis patient. We review the patients' sources of sodium exposure in the form of dietary salt intake, medication administration, and the dialysis treatment itself. In addition, the roles dialysis modalities, hemodialysis types, and dialysis fluid sodium concentration have on blood pressure, intradialytic symptoms, and interdialytic weight gain affect patient outcomes are discussed. We review whether sodium restriction (reduced salt intake), alteration in dialysis fluid sodium concentration and the different dialysis types have any impact on blood pressure, intradialytic symptoms, and interdialytic weight gain.

Hypervolemic hypernatremia in patients recovering from acute kidney injury in the intensive care unit.

BACKGROUND: A high incidence of hypernatremia is often observed in patients recovering from acute kidney injury (AKI) in intensive care units. METHODS: An unselected cohort of 20 adult patients recovering from AKI in the intensive care unit of a single institution during a 1-year period, were investigated. Serum and urine electrolytes, osmolality, urea nitrogen and creatinine were measured in an attempt to determine the cause of the hypernatremia. RESULTS: Eighty-eight percent of patients who could not drink fluids were found to have hypernatremia (serum Na >145 mEq/L). Even though the hypernatremia was mild in most patients (146-160 mEq/L), the average rise in serum sodium concentration was 17.4 mEq/L. The average urine osmolality was 384 mmol/kg of which 47.6 and 32.8 mmol/kg were contributed by sodium and potassium, respectively. The patients had hypervolemia as evidenced by the presence of edema and an average weight gain of 21.5 kg at the onset of the hypernatremia. The rise in serum sodium level coincided with an increase in urine output. CONCLUSION: The hypernatremia is believed to be due to post-AKI diuresis in the face of inability to maximally concentrate the urine because of renal failure. The diuresis caused a disproportionate loss of water in excess of that of sodium in the absence of replenishment of the water loss. Additionally, the patients were hypervolemic due to the retention of large quantities of sodium and water as a result of infusion of substantial volumes of physiological saline prior to the development of hypernatremia.

Using herbs medically without knowing their composition: are we playing Russian roulette?

Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.

Anticoagulation during haemodialysis using a citrate-enriched dialysate: a feasibility study.

BACKGROUND: The feasibility of anticoagulating the extracorporeal circuit during haemodialysis using a simple citrate-enriched dialysate was evaluated in a prospective, randomised, cross-over study of 24 patients who were at high risk for bleeding. METHODS: A dialysate, with a citrate level of 3 mEq/L (1 mmol/L), was generated by adding citrate to the conventional liquid 'bicarbonate concentrate' of a regular, dual-concentrate, bicarbonate-buffered dialysate delivery system. Each of the 24 patients received two dialysis treatments. For anticoagulation of the extracorporeal circuit, one treatment used the citrate-enriched dialysate (Citrate Group), while the other treatment used conventional saline flushing (Saline Group). The order of the two treatments was randomised. With either method, a heparinized, saline-rinsed dialyser was used, and no heparin was administered during dialysis. RESULTS: Ninety-two per cent (22 out of 24) and 100% of patients tolerated the procedure well in the Citrate Group and the Saline Group, respectively. Eight per cent (two out of 24) of the treatments in each group had to be abandoned because of clotting in the extracorporeal circuit. Significantly less thrombus formation in the venous air traps was detected in the Citrate Group. No patients from either group suffered from hypocalcaemic or bleeding complications, but the immediate post-dialysis and 0.5-h post-dialysis plasma levels of ionised calcium and of magnesium were slightly lower in the Citrate Group than in the Saline Group. CONCLUSIONS: Our findings suggest that it is feasible to use the present simple citrate-enriched dialysate to dialyse patients safely and effectively. Furthermore, the approach is much simpler than a conventional, intermittent, saline-flushing method.

Dysnatremias in Chronic Kidney Disease: Pathophysiology, Manifestations, and Treatment.

The decreased ability of the kidney to regulate water and monovalent cation excretion predisposes patients with chronic kidney disease (CKD) to dysnatremias. In this report, we describe the clinical associations and methods of management of dysnatremias in this patient population by reviewing publications on hyponatremia and hypernatremia in patients with CKD not on dialysis, and those on maintenance hemodialysis or peritoneal dialysis. The prevalence of both hyponatremia and hypernatremia has been reported to be higher in patients with CKD than in the general population. Certain features of the studies analyzed, such as variation in the cut-off values of serum sodium concentration ([Na]) that define hyponatremia or hypernatremia, create comparison difficulties. Dysnatremias in patients with CKD are associated with adverse clinical conditions and mortality. Currently, investigation and treatment of dysnatremias in patients with CKD should follow clinical judgment and the guidelines for the general population. Whether azotemia allows different rates of correction of [Na] in patients with hyponatremic CKD and the methodology and outcomes of treatment of dysnatremias by renal replacement methods require further investigation. In conclusion, dysnatremias occur frequently and are associated with various comorbidities and mortality in patients with CKD. Knowledge gaps in their treatment and prevention call for further studies.

Edelman Revisited: Concepts, Achievements, and Challenges.

The key message from the 1958 Edelman study states that combinations of external gains or losses of sodium, potassium and water leading to an increase of the fraction (total body sodium plus total body potassium) over total body water will raise the serum sodium concentration ([Na]S), while external gains or losses leading to a decrease in this fraction will lower [Na]S. A variety of studies have supported this concept and current quantitative methods for correcting dysnatremias, including formulas calculating the volume of saline needed for a change in [Na]S are based on it. Not accounting for external losses of sodium, potassium and water during treatment and faulty values for body water inserted in the formulas predicting the change in [Na]S affect the accuracy of these formulas. Newly described factors potentially affecting the change in [Na]S during treatment of dysnatremias include the following: (a) exchanges during development or correction of dysnatremias between osmotically inactive sodium stored in tissues and osmotically active sodium in solution in body fluids; (b) chemical binding of part of body water to macromolecules which would decrease the amount of body water available for osmotic exchanges; and (c) genetic influences on the determination of sodium concentration in body fluids. The effects of these newer developments on the methods of treatment of dysnatremias are not well-established and will need extensive studying. Currently, monitoring of serum sodium concentration remains a critical step during treatment of dysnatremias.

The Corrected Serum Sodium Concentration in Hyperglycemic Crises: Computation and Clinical Applications.

In hyperglycemia, hypertonicity results from solute (glucose) gain and loss of water in excess of sodium plus potassium through osmotic diuresis. Patients with stage 5 chronic kidney disease (CKD) and hyperglycemia have minimal or no osmotic diuresis; patients with preserved renal function and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) have often large osmotic diuresis. Hypertonicity from glucose gain is reversed with normalization of serum glucose ([Glu]); hypertonicity due to osmotic diuresis requires infusion of hypotonic solutions. Prediction of the serum sodium after [Glu] normalization (the corrected [Na]) estimates the part of hypertonicity caused by osmotic diuresis. Theoretical methods calculating the corrected [Na] and clinical reports allowing its calculation were reviewed. Corrected [Na] was computed separately in reports of DKA, HHS and hyperglycemia in CKD stage 5. The theoretical prediction of [Na] increase by 1.6 mmol/L per 5.6 mmol/L decrease in [Glu] in most clinical settings, except in extreme hyperglycemia or profound hypervolemia, was supported by studies of hyperglycemia in CKD stage 5 treated only with insulin. Mean corrected [Na] was 139.0 mmol/L in 772 hyperglycemic episodes in CKD stage 5 patients. In patients with preserved renal function, mean corrected [Na] was within the eunatremic range (141.1 mmol/L) in 7,812 DKA cases, and in the range of severe hypernatremia (160.8 mmol/L) in 755 cases of HHS. However, in DKA corrected [Na] was in the hypernatremic range in several reports and rose during treatment with adverse neurological consequences in other reports. The corrected [Na], computed as [Na] increase by 1.6 mmol/L per 5.6 mmol/L decrease in [Glu], provides a reasonable estimate of the degree of hypertonicity due to losses of hypotonic fluids through osmotic diuresis at presentation of DKH or HHS and should guide the tonicity of replacement solutions. However, the corrected [Na] may change during treatment because of ongoing fluid losses and should be monitored during treatment.

Body fluid abnormalities in severe hyperglycemia in patients on chronic dialysis: review of published reports.

Reports of dialysis-associated hyperglycemia (DH) were compared to reports of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH) in patients with preserved renal function. Average serum values in DH (491 observations), DKA (1036 observations), and NKH (403 observations) were as follows, respectively: glucose, 772, 649, and 961 mg/dl; sodium, 127, 134, and 149, mmol/l; and tonicity, 298, 304, and 355 mOsm/kg. Assuming that euglycemic (serum glucose, 90 mg/dl) values were the same (sodium, 140 mmol/l; tonicity, 285 mOsm/kg) for all three states, the hyperglycemic rise in the average serum tonicity value per 100-mg/dl rise in serum glucose concentration was 1.9 mOsm/kg in DH, 3.5 mOsm/kg in DKA, and 8.1 mOsm/kg in NKH. Neurological manifestations in DH patients were caused by coexisting conditions (ketoacidosis, sepsis, and neurological disease) in most instances, and by severe hypertonicity (>320 mOsm/kg), with clearing after insulin administration, in a few instances. In 148 episodes of DH corrected with insulin only, the mean increase in serum sodium per 100-mg/dl decrease in serum glucose (Delta[Na]/Delta[Glu]) was -1.61 mmol/l. In agreement with theoretical predictions, Delta[Na]/Delta[Glu] was numerically smaller in patients with edema than in those with euvolemia. The average hyperglycemic increase in extracellular volume, calculated from changes in serum sodium concentration during correction of DH using insulin alone, was 0.013 l/l per 100-mg/dl increase in serum glucose concentration. A small number of DH patients presented with pulmonary edema rectified by insulin alone. DH causes modest hypertonicity, with few patients having neurological manifestations caused usually by other coexisting conditions. In contrast to DKA or NKH, which usually presents with hypovolemia, DH causes hypervolemia manifested occasionally by pulmonary edema. Insulin is adequate treatment for DH.

Pathophysiology and management of fluid and electrolyte disturbances in patients on chronic dialysis with severe hyperglycemia.

The mechanisms of fluid and solute abnormalities that should be considered in any patient with severe hyperglycemia include changes in the total amount of extracellular solute, osmotic diuresis, intake of water driven by thirst, and influences from associated conditions. The absence of osmotic diuresis distinguishes dialysis-associated hyperglycemia (DH) from hyperglycemia with preserved renal function (HPRF). Mainly because of this absence, comparable degrees of hyperglycemia tend to produce less hypertonicity and less severe intracellular volume contraction in DH than in HPRF, while extracellular volume is expanded in DH but contracted in HPRF. Ketoacidosis can develop in both DH and HPRF. Among DH patients, hyperkalemia appears to be more frequent when ketoacidosis is present than when nonketotic hyperglycemia is present. Among HPRF patients, the frequency of hyperkalemia appears to be similar whether ketoacidosis or nonketotic hyperglycemia is present. Usually patients with severe DH have no symptoms or may exhibit a thirst. Infrequent clinical manifestations of DH include coma and seizures from hypertonicity or ketoacidosis and pulmonary edema from extracellular expansion. Insulin infusion is usually the only treatment required to correct the biochemical abnormalities and reverse the clinical manifestations of DH. Monitoring of the clinical manifestations and biochemical parameters during treatment of DH with insulin is needed to determine whether additional measures, such as administration of saline, free water, or potassium salts, as well as emergency hemodialysis (HD) are needed. Emergency HD carries the risk of excessively rapid decline in tonicity; its benefits in the treatment of DH have not been established.