Comparative Efficacy of Tegoprazan vs Esomeprazole/Sodium Bicarbonate for the Treatment of Helicobacter pylori Infection.

INTRODUCTION: Potassium-competitive acid blockers and proton pump inhibitors/sodium bicarbonate can rapidly increase intragastric pH. In this study, we aimed to compare the clinical outcomes of tegoprazan-based and esomeprazole/sodium bicarbonate-based triple therapies in the treatment of Helicobacter pylori infection. METHODS: We retrospectively reviewed the data of patients with H. pylori infection treated with a 14-day tegoprazan-based triple therapy or 14-day esomeprazole/sodium bicarbonate-based triple therapy. The primary end point was the H. pylori eradication rate with first-line treatment in an intention-to-treat analysis. Secondary end points included the eradication rate with first-line therapy in the per-protocol analysis and adverse events associated with eradication therapy. RESULTS: Of the 854 included patients, 435 were treated with tegoprazan-based therapy, and 419 received esomeprazole/sodium bicarbonate-based therapy. In the intention-to-treat population, no significant difference in eradication rate was detected between the tegoprazan-treated and esomeprazole/sodium bicarbonate-treated groups (78.6% [95% confidence interval (CI), 74.6-82.3%] vs 81.4% [95% CI, 77.4-84.9%], P = 0.313). The per-protocol analysis also revealed a similar eradication rate between groups (tegoprazan vs esomeprazole/sodium bicarbonate: 85.5% [95% CI, 81.8-87.5%] vs 87.8% [95% CI, 84.1-90.7%], P = 0.339). However, abdominal discomfort and diarrhea were more common in the esomeprazole/sodium bicarbonate-treated group than in the tegoprazan-treated group (abdominal discomfort: 1.1% vs 3.8%, P = 0.012; diarrhea: 9.9% vs 21.2%, P < 0.001). DISCUSSION: The efficacy of the esomeprazole/sodium bicarbonate-based triple therapy for H. pylori eradication was comparable with that of the tegoprazan-based triple therapy. However, esomeprazole/sodium bicarbonate-based therapy exhibited a higher risk of abdominal discomfort and diarrhea than tegoprazan-based therapy.

Pharmacokinetics and Pharmacodynamics of Lansoprazole/Sodium Bicarbonate Immediate-release Capsules in Healthy Chinese Subjects: An Open, Randomized, Controlled, Crossover, Single-, and Multiple-dose Trial.

Proton pump inhibitors (PPIs) differ in onset of action and bioavailability. This trial was conducted to investigate the pharmacokinetics and pharmacodynamics of an immediate-release capsule formulation containing lansoprazole 30 mg and sodium bicarbonate 1100 mg (T preparation) in healthy Chinese subjects. This was an open, single-center, randomized, single and multiple oral doses, and two-period crossover study in 30 healthy subjects. After single- and multiple-dose oral administration, blood samples were obtained and lansoprazole concentration in serum was measured for pharmacokinetic analysis. Meanwhile, the intragastric pH was monitored continuously to evaluate the pharmacodynamics of the investigational drugs. The Tmax of the T preparation was 0.5 hours, while the Tmax of the R preparation was 1.5 hours after multiple doses, which indicated that the absorption speed of the T preparation was significantly faster than that of the R preparation. The same characteristics also existed after single-dose administration. The area under the curve (AUC)ss of the T preparation was bio-equivalent to that of the R preparation under steady state. The time percentage of intragastric pH > 4.0 for the T preparation was higher than that of the R preparation after 1 hour for both single- and multiple-dose. It suggested compared with R preparation, the time percentage of intragastric pH > 4.0 met the criteria for superiority after 1 hour administration for the T preparation. In addition, no serious adverse events occurred in this study. Across this study, the T preparation was better than the R preparation at improving drug absorption and increasing intragastric pH, and had a favorable safety profile.

[The effect of natural mineral bicarbonate sodium-calcium water «Tib-1¼ on the antioxidant status of rats with adjuvant rheumatoid arthritis]. / Vliyanie prirodnoi mineral'noi gidrokarbonatnoi natrievo-kal'tsievoi vody «Tib-1¼ na antioksidantnyi status krys s ad"yuvantnym revmatoidnym artritom.

The combination of traditional basic pharmacotherapy for rheumatoid arthritis (RA) and physiotherapeutic methods can reduce the activity of the disease and accelerate the onset of remission, and therefore the development of new non-drug methods for the treatment of RA is relevant. PURPOSE OF THE STUDY: Study of the effect of natural mineral water « Tib-1¼ on the lipid peroxidation system in an experiment with a model adjuvant-induced RA in rats. MATERIAL AND METHODS: The object of the study were Wistar rats, divided into three groups: negative control (solvents), positive control (model of adjuvant-induced RA by subcutaneous injection of complete Freund's adjuvant) and experimental (correction of RA with mineral water « Tib-1¼, diluted in a ratio of 1:3 during the first 2 weeks from the moment the model was formed in the ad libitum mode). On the 3rd and 7th weeks in the blood of the animals were determined: the total number of leukocytes, the content of hydroperoxides according to Gavrilov, the level of malondialdehyde (MDA), catalase activity. Pathological changes in the hip and knee joints were recorded using radiography. RESULTS: The inflammatory process in the positive control group by the 3rd week was characterized by an increase in the number of leukocytes by 66% (p<0.01) and was accompanied by an increase in MDA by 60% (p<0.001). By the 7th week, despite a relative increase in catalase activity (16%), the MDA level continued to be elevated compared to the negative control by 67% (p<0.001). Against the background of exposure to mineral water, inflammation decreased (the number of leukocytes in the "model/experiment" groups turned out to be reduced by 41%; p<0.01) and an increase in compensatory-adaptive reactions in the form of catalase activation was noted (by 8%; p<0.01), which was accompanied by a persistent (weeks 3 and 7) decrease in MDA output (by 20%; p<0.01). Using the method of radiation diagnostics, positive changes in the articular apparatus of experimental animals were revealed, consisting in the relief of signs of subchondral sclerosis of the bone heads, which were noted for animals of the model group. CONCLUSION: The use of natural mineral water «Tib-1¼ helps to reduce the acute inflammatory response during the formation of adjuvant-induced RA in Wistar rats, initiates the normalization of the balance of pro- and antioxidant processes in the body, and minimizes the intensity of degenerative-inflammatory joint lesions.

Fludrocortisone Among Adult Renal Transplant Recipients With Persistent Hyperkalemia: Single-Center Experience.

OBJECTIVES: Calcineurin inhibitors are the cornerstone of immunosuppression following solid-organ transplant. However, hyperkalemia may occur by multiple mechanisms affecting potassium in the distal tubule. Hyperkalemia is commonly observed in renal transplant recipients, and it is dose-dependent. Here, we evaluated the impact of fludrocortisone in the management of calcineurin inhibitor-induced hyperkalemia after renal transplant. MATERIALS AND METHODS: We evaluated newly transplanted patients who developed hyperkalemia or those with hyperkalemia who attended our outpatient renal transplant clinic (Hamed Al-Essa Organ Transplant Center, Kuwait). Clinical and laboratory parameters were collected before starting fludrocortisone (baseline values) and then at 1, 2, 4, and 8 weeks. Drug history was assessed, with any drugs that could induce hyperkalemia being discontinued (such as spironolactone); otherwise, essential drugs like prophylactic agents (sulfamethoxazole-trimethoprim) were maintained. Oral anti-hyperkalemic doses (bicarbonate, resonium calcium, fludrocortisone) were noted. RESULTS: Our study included 29 patients; most were men (aged 45.8 ± 15 years). Body weight did not significantly change after introduction of fludrocortisone (79.53 ± 24.31, 79.82 ± 23.85, 80.62 ± 24.24, 77.03 ± 20.7, and 79.21 ± 27.93 kg at baseline and at postdose week 1, 2, 4, and 8, respectively). Systolic and diastolic blood pressure levels were also similar at baseline versus postdose. Steroid doses (prednisolone) were significantly reduced over 1 month (15.7 ± 12.4, 14.1 ± 10.19, 12.6 ± 8.7, 9.5 ± 5.2, and 9.5 ± 5.2 mg/ day). Serum potassium levels significantly improved (5.18 ± 0.58, 4.9 ± 0.49, 4.8 ± 0.54, 4.8 ± 0.65, and 4.4 ± 0.72 mmol/L). Serum creatinine levels significantly improved by postdose week 8 (129.28 ± 48.9, 130.92 ± 52.2, 127.66 ± 50.9, 121.42 ± 41.7, and 124.1 ± 51.27 µmol/L). Serum bicarbonate levels remained similar. CONCLUSIONS: Fludrocortisone was a safe and effective option in management of calcineurin inhibitor-induced hyperkalemia among renal transplant recipients.

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis.

BACKGROUND: A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months. METHODS: Thirty pediatric and adult patients were included in an open-label extension study after a phase II/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored. RESULTS: There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69-86% and 83-93% of patients. Overall adherence rates were ≥ 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study. CONCLUSIONS: Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable. TRIAL REGISTRATION NUMBER: Registered as EudraCT 2013-003828-36 on the 3rd of September 2013.

Effect of Del Nido cardioplegia on ventricular arrhythmias after cardiovascular surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients. METHODS: This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups. RESULTS: In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries. CONCLUSIONS: Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.

Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise.

PURPOSE: We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a 3 h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise. METHODS: Nine well-trained male cyclists participated in a similar RACE consisting of 3 h submaximal intermittent cycling (IMT180') followed by a 15-min time trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized crossover design, participants received (i) 65 g KE, (ii) 300 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON), together with consistent 60 g·h-1 carbohydrate intake. RESULTS: KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 h of RACE (P < 0.001 vs CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whereas bicarbonate decreased from 25.5 to 20.5 mM (both P < 0.001 vs CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (P < 0.05 vs KE) and increased blood bicarbonate to 31.1 ± 1.8 mM and blood pH to 7.51 ± 0.03 by the end of IMT180' (P < 0.001 vs KE). Mean power output during TT15' was similar between KE, BIC, and CON at ~255 W but was 5% higher in KE + BIC (P = 0.02 vs CON). Time to exhaustion in the sprint was similar between all conditions at ~60 s (P = 0.88). Gastrointestinal symptoms were similar between groups. DISCUSSION: The coingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress.

Effect of high bicarbonate hemodialysis solution on biochemical parameters and anthropometric indices.

INTRODUCTION: Protein energy wasting is an adverse consequence of renal failure, which is correlated with increased mortality and morbidity. Metabolic acidosis has a major role in the development of protein energy wasting in hemodialysis patients. Every effort that could ameliorate this catabolic state would be beneficial to stabilize body composition. The aim of this study was to investigate the possible beneficial effects of high bicarbonate dialysis on anthropometric indices and biochemical parameters of nutrition. METHODS: Fifty-six hemodialysis patients were randomly enrolled in two groups: an intervention group that underwent hemodialysis for 6 months with high bicarbonate dialysate concentration (36 mmol/L, N = 26) and a control group that underwent hemodialysis using a bicarbonate dialysate concentration of 30 mmol/L (N = 30). Biochemical parameters of nutrition and weight, body mass index (BMI), total body water, percent body fat, and other anthropometric indices were measured at the beginning and the end of the trial. FINDINGS: At the end of the 6 month evaluation period, plasma levels of albumin, phosphorus, K, calcium, and bicarbonate showed no significant changes. Body weight and BMI increased significantly in high bicarbonate arm but did not change significantly in the control group. Percent body fat in the arms and legs did not change in intervention arm, but decreased significantly in the controls. DISCUSSION: The results suggest that higher bicarbonate dialysis can have beneficial effects on nutritional status and might protect against loss of fat mass.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Hypersensitivity reactions to bicarbonate dialysate containing acetate: a case report with literature review.

Although hemodialysis-hypersensitivity reactions have various causes, only a few cases of hypersensitivity to acetate dialysate accompanied by fever have been reported. We present the case of a 69-year-old hemodialysis patient who was admitted due to fever after dialysis. He had undergone online hemodiafiltration using acetate-free citrate-containing dialysate. After admission, we switched to acetate-containing bicarbonate dialysate. He was diagnosed with pneumonia and treated with ceftriaxone. However, fever that occurred post dialysis persisted, displaying a gradual elevation in CRP level and eosinophils (up to 9.7 mg/dL and 3774 cells/µL, respectively). After a series of negative workups for infection and dialysis membrane allergy, we suspected that acetate-containing bicarbonate dialysate to be the cause of the allergic reaction and switched to acetate-free bicarbonate dialysate. Consequently, eosinophil count decreased and the fever abated. The drug-induced lymphocyte stimulation test finding (for acetate dialysate) was positive, and he was diagnosed with acetate dialysate-induced hypersensitivity reactions. The condition was not detected earlier due to the complications associated with pneumonia.

Half Saline-Bicarbonate Solution as Intraoperative Fluid Replacement Therapy Leads to Less Acidosis and Better Early Renal Function During Deceased-Donor Transplant.

OBJECTIVES: Normal saline is the most common crystalloid solution that is used in renal transplant surgery. In this study, our aim was to determine the effects of a combination of half saline and bicarbonate versus normal saline as a routine solution. MATERIALS AND METHODS: For this double-blind random-ized clinical trial, we enrolled 100 adult patients undergoing kidney transplant. Patients were divided into 2 groups: those who received normal saline and those who received half saline and bicarbonate infusion as fluid replacement therapy during renal transplant. All patients received about 40 mL/kg of crystalloids during surgery. Serial creatinine con-centrations (primary outcomes) were compared between groups at 1, 2, 3, and 7 days after surgery. Urine output (secondary outcome) was compared between groups at recovery and at 6 and 24 hours after surgery. In addition, base excess, chloride, and sodium levels were measured before and 6 hours after surgery. Each liter of half saline-bircarbonate, which is relatively isoosmotic to human plasma, was composed of 70 mEq bicarbonate, 77 mEq chloride, and 147 mEq sodium. RESULTS: Patients who received half saline-bicarbonate had significantly lower postoperative creatinine levels at all time points than patients who received normal saline (P = .019). Serum chloride and sodium levels (P = .001) were significantly higher and base excess (P = .007) was significantly lower in the normal saline group at 6 hours after transplant. At all time points, urine output levels were significantly higher in the half saline-bicarbonate group (P = .001). CONCLUSIONS: The use of half saline-bicarbonate was associated with better early graft function compared with normal saline in the first 7 days after transplant.

Managing Chloride and Bicarbonate in the Prevention and Treatment of Acute Kidney Injury.

Intravenous crystalloid therapy is one of the most ubiquitous aspects of hospital and critical care medicine. In recent years, there has been increasing focus on the electrolyte composition, and particularly chloride content, of crystalloid solutions. This has led to increasing clinical adoption of balanced solutions, containing substrates for bicarbonate generation and consequently a lower chloride content, in place of 0.9% saline. In this article we review the physiochemical rationale for avoidance of 0.9% saline and the effects of hyperchloremic acidosis on renal physiology. Finally, we review the current evidence and rationale for use of balanced solutions greater than 0.9% saline in acutely ill patients in a variety of clinical settings, as well as considering the role for sodium bicarbonate in preventing or correcting metabolic acidosis. In conclusion, there is a strong physiological rationale for avoidance of iatrogenic hyperchloremic acidosis from 0.9% saline administration in acutely unwell patients and an association with adverse renal outcomes in several studies. However, evidence from large definitive multicenter randomized trials is not yet available to establish the dose-relationship between 0.9% saline administration and potential harm and inform us if some 0.9% saline use is acceptable or if any exposure confers harm.

Cambios estructurales de la superficie dental erosionada pre y post tratamiento con bicarbonato de arginina y monofluorofosfato de sodio: estudio piloto / Structural changes of the eroded tooth surface before and after treatment with arginine bicarbonate and sodium monofluorophosphate: pilot study

La erosión dental se define como la pérdida patológica, crónica e indolora de los tejidos dentales, por la acción química de ácidos no producidos por la microflora bacteriana bucal. Los estadíos más avanzados pueden generar diferentes niveles de desgaste y producir hipersensibilidad destinaria. Objetivo: evaluar y describir los cambios estructurales de la superficie dental erosionada pre y post tratamiento con bicarbonato de arginina y monofluorofosfato de sodio, observados mediante microscopia electrónica de barrido (MEB). Materiales y Métodos: Se realizó un estudio piloto de tipo descriptivo, transversal y cuasi-experimental. Se seleccionó una muestra de cuatro pacientes, previo consentimiento informado; de manera aleatoria se le asignó el tratamiento luego de la primera cirugía, grupo 1 (bicarbonato de arginina) y grupo 2 (monofluorofosfato de sodio). Las exodoncias se realizaron en dos tiempos (tiempo 0 y post-tratamiento) para obtener los especímenes y ser evaluados con MEB. Resultados: Tras la evaluación realizada por MEB se observó que los segmentos de esmalte dental diagnosticados clínicamente con grado 1 de erosión, ya presentaban exposición de algunos túbulos dentinarios en la superficie evaluada. Luego de 14 días de tratamiento, se observó que ambas cremas dentales fueron capaces de sellar la entrada de los canalículos dentinarios; sin embargo, la crema dental con bicarbonato de arginina, formó una estructura mineralizada que se depositó sobre la superficie dental. Conclusión: ambos tratamientos fueron capaces de producir cambios estructurales en la superficie dental erosionada sellando la entrada de los túbulos dentinarios(AU)

Dental erosion is defined as the pathological, chronic and painless loss of dental tissues due to the chemical action of acids not produced by the oral bacterial microflora. The more advanced stages can generate different levels of wear and produce dentine hypersensitivity. Objective: to evaluate and describe the structural changes of the eroded dental surface before and after treatment with arginine bicarbonate and sodium monofluorophosphate, observed by scanning electron microscopy (SEM). Materials and Methods: A pilot study of descriptive, transversal and quasi-experimental type was carried out. A sample of four patients was selected, with prior informed consent; Randomly, he was assigned to the treatment after the first surgery, group 1 (arginine bicarbonate) and group 2 (sodium monofluorophosphate). Extractions were performed in two stages (time 0 and post-treatment) to obtain the specimens and be evaluated with SEM. Results: After the evaluation made by SEM, it was observed that dental enamel segments clinically diagnosed with erosion grade 1, already had exposure of some dentinal tubules in the evaluated surface. After 14 days of treatment, it was observed that both dental creams were able to seal the entrance of the dentinal canaliculi; however, the toothpaste with arginine bicarbonate, formed a mineralized structure that was deposited on the tooth surface. Conclusion: both treatments were able to produce structural changes in the eroded dental surface sealing the entrance of the dentinal tubules(AU)

Effect of Bicarbonate-Buffered Dialysate on Ventricular Arrhythmias in Hemodialysis Patients.

BACKGROUND: The etiology of sudden cardiac death in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is largely unknown, though there is evidence to suggest that metabolic alkalosis induced by HD with a high-bicarbonate dialysate/prescription may play a role. METHODS: We investigated the effects of metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate on frequency of ventricular arrhythmia in 47 patients with ESRD on chronic HD using 48-h Holter monitoring in 3 phases: intra-HD, post-HD day 1, and post-HD day 2. Serum levels of bicarbonate, calcium, and potassium along with hemodynamics were measured pre-HD, post-HD, 20-h post-HD, and 44-h post-HD. Correlations were performed to verify the association between bicarbonate prescription and change in serum bicarbonate levels post-HD and to determine if the HD-induced change in serum bicarbonate level (metabolic alkalosis) had any direct association with ambient ventricular arrhythmia (premature ventricular contractions per hour) or indirect associations with ambient ventricular arrhythmia by affecting electrolytes or hemodynamics that are known to increase the risk of ventricular arrhythmia. RESULTS: Mean pre-HD serum bicarbonate level was 21.3 mEq/L. Dialysate bicarbonate prescription (mean of 36.4 mEq/L) correlated with changes in serum bicarbonate levels immediately post-HD 26.7 mEq/L (r = 0.46, p < 0.01), 20-h post-HD 25.2 mEq/L (r = 0.38), and 44-h post-HD 23.2 mEq/L (r = 0.35, p = 0.01). No statistically significant correlations were found between the post-HD change in serum bicarbonate levels (metabolic alkalosis) with ambient ventricular arrhythmia, changes in serum calcium, potassium, or hemodynamics in any phase. CONCLUSIONS: High-bicarbonate dialysate prescription is associated with metabolic alkalosis following the HD procedure. A mild metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate solution had no direct association with ambient ventricular arrhythmia on Holter monitoring and was not associated with changes in hemodynamics or changes in serum total calcium or potassium levels. This study helps to provide guidance for the safe use of high bicarbonate dialysate/prescription in patients with ESRD on HD.

Bicarbonate refractory QRS prolongation and left bundle-branch block following escitalopram and lamotrigine overdose: A case report and literature review of toxic left bundle-branch block.

WHAT IS KNOWN AND OBJECTIVE: Toxic prolongation of the QRS interval most often results from blockade of cardiac voltage-gated sodium channels and manifests on electrocardiogram with a right bundle-branch block-like morphology. Rarely, a left bundle-branch block (LBBB) morphology has been reported. CASE REPORT: We report a case of transient LBBB resultant from ingestion of lamotrigine and citalopram which was refractory to sodium bicarbonate therapy and eventually resolved spontaneously. WHAT IS NEW AND CONCLUSION: Cases of toxic LBBB are less likely to respond to bicarbonate therapy, suggesting that this finding is due to a mechanism other than sodium channel blockade.

Normokalemic nondepolarizing long-acting blood cardioplegia.

Objective Blood cardioplegia, the gold-standard cardioprotective strategy, requires frequent dosing, resulting in hyperkalemia-induced myocardial edema. The aim of our study was to compare the efficacy and safety of a long-acting blood-based cardioplegia with physiological potassium levels versus the well-established cold blood St. Thomas' Hospital no. 1 cardioplegia solution in multivalve surgeries. Methods One hundred patients undergoing simultaneous elective aortic and mitral valve replacement ± tricuspid valve repair were randomized in two groups. In group 1, adenosine 12 mg was given via the aortic root after crossclamping, followed by a single dose of long-acting solution at 14℃ (30 mLckg-1); in group 2, an initial 30 mLckg-1 of St. Thomas' cardioplegia at 14℃ was administered, followed by 15 mLckg-1 every 20 min. Duration of cardiopulmonary bypass, inotropic score, arrhythmias, ventilation time, and the levels of interleukin-6, creatinine kinase-MB, and troponin I were compared. Results Mean cardiopulmonary bypass and crossclamp times were 134.04 ± 36.12 vs. 154.34 ± 34.26 ( p = 0.004) and 110.37 ± 24.80 vs. 132.48 ± 31.68 min ( p = 0.002), respectively, in the long-acting and St. Thomas' groups. Cardiac index, creatinine kinase-MB and troponin I levels were comparable. Interleukin-6 levels post-bypass were 61.72 ± 15.33 and 75.44 ± 31.78 pgcmL-1 ( p = 0.007) in the long-acting and St. Thomas' cardioplegia groups, respectively. Conclusions Single-dose long-acting cardioplegia gives a cardioprotective effect comparable to repeated doses of the well-established St. Thomas' Hospital no. 1 cold blood cardioplegia.

Long term variation of serum levels of uremic toxins in patients treated by post-dilution high volume on-line hemodiafiltration in comparison to standard low-flux bicarbonate dialysis: results from the REDERT study.

PURPOSE OF THE STUDY: Little information have been provided till now regarding the effect of high volume HDF (hv-OL-HDF) in respect to standard bicarbonate dialysis (BHD) in medium-long term protein-bound toxins removal. PROCEDURES: A randomised cross-over multicentre study (REDERT study) was designed to compare the effects of hv-OL-HDF and low-flux BHD on uremic toxins serum levels in 36 chronic dialysis patients followed for 13 months. Group 1 patients were treated with BHD (Treatment A) for 6 months, and afterwards, they were transferred to hv-OL-HDF for a further 6 months (Treatment B). Group 2 patients were treated with Treatment B for 6 months, and afterwards, they were transferred to Treatment A for a further 6 months. Total and free pre-dialysis indoxyl-sulfate (IS) and p-cresyl-sulfate (pCS) were determined starting a midweek dialysis session at baseline and after six months of hv-OL-HDF or BHD. IS and pCS, were simultaneously measured, by liquid chromatography/electrospray ionization-tandem mass spectrometry, Kt/v and pre and post-dialysis b-2microglobulin (b2MG) levels were measured every three months. RESULTS: Kt/V was significantly increased in hv-OL-HDF (from 1.47 ± 0.24 to 1.49 ± 0.16; p < 0.01) and was reduced in BHD (from 1.51 ± 0.2 to 1.36 ± 0.21; p < 0.001). The mean infusion volume in HDF was 20.9 ± 2.1 L with a mean total convective volume of 23.8 ± 2.3 L and a significant removal of b2MG was obtained in hv-OL-HDF at month 3 and month 6. Both free and total levels of IS and pCS were significantly reduced in hv-OL-HDF at month 6 in respect to BHD. CONCLUSIONS: In the present study we confirm the assumption that post-HDF is an effective technique in small and protein-bound uremic toxins removal.

A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy.

BACKGROUND: We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance. METHODS: We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively. RESULTS: 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline. CONCLUSIONS: We demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

The Effects of Elevated Specific Conductivity on the Chronic Toxicity of Mining Influenced Streams Using Ceriodaphnia dubia.

Salinization of freshwater ecosystems as a result of human activities has markedly increased in recent years. Much attention is currently directed at evaluating the effects of increased salinity on freshwater biota. In the Central Appalachian region of the eastern United States, specific conductance from alkaline discharges associated with mountain top mining practices has been implicated in macroinvertebrate community declines in streams receiving coal mining discharges. Whole effluent toxicity testing of receiving stream water was used to test the hypothesis that mine discharges are toxic to laboratory test organisms and further, that toxicity is related to ionic concentrations as indicated by conductivity. Chronic toxicity testing using Ceriodaphnia dubia was conducted by contract laboratories at 72 sites with a total of 129 tests over a 3.5 year period. The database was evaluated to determine the ionic composition of mine effluent dominated streams and whether discharge constituents were related to toxicity in C. dubia. As expected, sulfate was found to be the dominant anion in streams receiving mining discharges with bicarbonate variable and sometimes a substantial component of the dissolved solids. Overall, the temporal variability in conductance was low at each site which would indicate fairly stable water quality conditions. Results of the toxicity tests show no relationship between conductance and survival of C. dubia in the mining influenced streams with the traditional toxicity test endpoints. However, consideration of the entire dataset revealed a significant inverse relationship between conductivity and neonate production. While conductivity explained very little of the high variability in the offspring production (r2 = 0.1304), the average numbers of offspring were consistently less than 20 neonates at the highest conductivities.