Search

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 T max of the T preparation was 0.5 hours, while the T max 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., (© 2023, The American College of Clinical Pharmacology.)

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester ( R )-3-hydroxybutyl ( R )-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT 180' ) followed by a 15-min time-trial (TT 15' ) and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1 ) 75 g of ketone ester (KE), 2 ) 300 mg/kg body mass bicarbonate (BIC), 3 ) KE + BIC, or 4 ) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT 15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

Chronic metabolic acidosis stimulates cell-mediated net Ca 2+ efflux from bone mediated by increased osteoblastic cyclooxygenase 2, leading to prostaglandin E 2 -induced stimulation of receptor activator of NF-κB ligand-induced osteoclastic bone resorption. Ovarian cancer G protein-coupled receptor-1 (OGR1), an osteoblastic H + -sensing G protein-coupled receptor, is activated by acidosis and leads to increased bone resorption. As regulator of G protein signaling (RGS) proteins limit GPCR signaling, we tested whether RGS proteins themselves are regulated by metabolic acidosis. Primary osteoblasts were isolated from neonatal mouse calvariae and incubated in physiological neutral or acidic (MET) medium. Cells were collected, and RNA was extracted for real-time PCR analysis with mRNA levels normalized to ribosomal protein L13a. RGS1 , RGS2 , RGS3 , RGS4 , RGS10 , RGS11 , and RGS18 mRNA did not differ between MET and neutral medium; however, by 30 min, MET decreased RGS16 , which persisted for 60 min and 3 h. Incubation of osteoblasts with the OGR1 inhibitor CuCl 2 inhibited the MET-induced increase in RGS16 mRNA. Gallein, a specific inhibitor of Gβγ signaling, was used to determine if downstream signaling by the βγ-subunit was critical for the response to acidosis. Gallein decreased net Ca 2+ efflux from calvariae and cyclooxygenase 2 and receptor activator of NF-κB ligand gene expression from isolated osteoblasts. These results indicate that regulation of RGS16 plays an important role in modulating the response of the osteoblastic GPCR OGR1 to metabolic acidosis and subsequent stimulation of osteoclastic bone resorption. NEW & NOTEWORTHY The results presented in this study indicate that regulation of regulator of G protein signaling 16 and G protein signaling in the osteoblast plays an important role in modulating the response of osteoblastic ovarian cancer G protein-coupled receptor 1 (OGR1) to metabolic acidosis and the subsequent stimulation of osteoclastic bone resorption. Further characterization of the regulation of OGR1 in metabolic acidosis-induced bone resorption will help in understanding bone loss in acidotic patients with chronic kidney disease.

Rationale & Objective: Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation., Study Design: Randomized order, cross-over study with controlled feeding., Setting & Participants: Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m 2 or 60-70mL/min/1.73m 2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline., Intervention: Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion., Outcomes: Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period., Results: During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed., Limitations: Small sample size and short feeding duration., Conclusions: Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis., Funding: National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research., Trial Registration: Registered at ClinicalTrials.gov with study number NCT02427594., (Copyright © 2021. Published by Elsevier Inc.)

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests were conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet.

Introduction: Oral bicarbonate solution is known to improve both maternal and perinatal outcomes among women with abnormal labour (dystocia). Its effectiveness and safety among women with obstructed labour is not known., Objective: To determine the effect and safety of a single-dose preoperative infusion of sodium bicarbonate on maternal and fetal blood lactate and clinical outcomes among women with obstructed labour (OL) in Mbale hospital., Methods: We conducted a double blind, randomised controlled trial from July 2018 to September 2019. The participants were women with OL at term (≥37 weeks gestation), carrying a singleton pregnancy with no other obstetric emergency, medical comorbidity or laboratory derangements., Intervention: A total of 477 women with OL were randomized to receive 50ml of 8.4% sodium bicarbonate (238 women) or 50 mL of 0.9% sodium chloride (239 women). In both the intervention and controls arms, each participant was preoperatively given a single dose intravenous bolus. Every participant received 1.5 L of normal saline in one hour as part of standard preoperative care., Outcome Measures: Our primary outcome was the mean difference in maternal venous blood lactate at one hour between the two arms. The secondary outcomes were umbilical cord blood lactate levels at birth, neonatal sepsis and early neonatal death upto 7 days postnatal, as well as the side effects of sodium bicarbonate, primary postpartum hemorrhage, maternal sepsis and mortality at 14 days postpartum., Results: The median maternal venous lactate was 6.4 (IQR 3.3-12.3) in the intervention and 7.5 (IQR 4.0-15.8) in the control group, with a statistically non-significant median difference of 1.2 mmol/L; p-value = 0.087. Vargha and Delaney effect size was 0.46 (95% CI 0.40-0.51) implying very little if any effect at all., Conclusion: The 4.2g of preoperative intravenous sodium bicarbonate was safe but made little or no difference on blood lactate levels., Trial Registration: PACTR201805003364421., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Metformin-associated lactic acidosis (MALA) carries a high mortality rate. It is seen in patients with type 2 diabetes on metformin or patients who attempt suicide with metformin overdose. We present the case of a man in his early 20s with type 2 diabetes, hypertension and hypothyroidism who presented with agitation, abdominal pain and vomiting after ingesting 50-60 g of metformin; he developed severe lactic acidosis (blood pH 6.93, bicarbonate 7.8 mEq/L, lactate 28.0 mEq/L). He was managed with intravenous 8.4% bicarbonate infusion and continuous venovenous haemodiafiltration. He also developed acute renal failure (ARF) requiring intermittent haemodialysis and continuous haemodiafiltration. MALA is uncommon and causes changes in different vital organs and even death. The primary goals of therapy are restoration of acid-base status and removal of metformin. Early renal replacement therapy for ARF can result in rapid reversal of the acidosis and good recovery, even with levels of lactate normally considered to be incompatible with survival., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic metabolic acidosis (CMA) is a common complication of chronic kidney disease (CKD). Its treatment in patients with diabetes mellitus and CKD could also improve insulin resistance. We investigated the current therapeutic approaches in diabetes mellitus (DM) with CKD in a survey among diabetologic specialists and general practitioners with additional qualification in diabetology about their approach to CMA and cooperation with nephrologists., Methods: 5863 practitioners were invited to complete a 27 item survey. 97 completed surveys were analysed descriptively., Results: Most participants were internists with additional qualification in diabetology (46 %). They cared for median 50 (10; 112) patients with DM type I and 210 (100; 450) patients with diabetes m, type II per quarter. CMA was observed by 12 % of practitioners during the last 12 months in median 4 (2; 6) patients with DM type I and 10 (3; 30) with type II. CMA was mainly diagnosed via serum bicarbonate (28 %) or base excess (20 %). 39 % received a recommendation from the nephrologic colleagues about treatment of CMA. About one third of diabetologists rated this recommendation as highly relevant (29 %) and feasible (27 %). For treatment of CMA, oral bicarbonate is preferred (39 %). Most participants preferred their nephrological colleagues doing specialist diagnostics (90 %) including blood gas analysis, as well as taking care of the treatment of CMA (62 %) and anemia (53 %). 34 % had not treated CMA in their practice so far. The cooperation between the participants and nephrologists was evaluated good (81 %). Most participants (78 %) would appreciate further education with a focus on CMA., Discussion: Cooperation between diabetologists and nephrologists works well. Nephrologists are mainly responsible for diagnosis and treatment of CMA. However, because CMA may worsen insulin resistance, its relevance for DM treatment appears to be underestimated. Further education may be required in this field., Competing Interests: H.G. ist Mitglied im Beratungsgremium der Fresenius Medical Care Deutschland GmbH. M.K., S.R. und S.B. geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

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 β-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.

The effectiveness of 7% hypertonic saline solution (HSS) and 6% hypertonic bicarbonate solution (HBS) followed by intraruminal water administration for the treatment of acute rumen lactic acidosis (ARLA) has not been evaluated yet. The hypothesis of the study is that treatment with HBS causes a faster correction of imbalances and clinical recovery than treatment with HSS. ARLA was induced in six healthy mature female sheep with sucrose twice. The sheep received both treatment regimens in a cross over design. After 18 h of induction, rumen lavage was performed and IV infusion of 7% HSS (4 mL/kg BW) or 6% HBS (6.7 mL/kg BW) was done over 5 min, followed by intraruminal administration of water (8% BW). The solutions provided 4.8 mmol/kg BW of sodium. Physical and laboratory tests were performed for 168 h. Both treatments increased plasma volume. After HSS treatment, pH and HCO 3 - returned to baseline values at 144 h and BE at 168 h. With HBS treatment, pH returned to baseline at 24 h, and HCO 3 - and BE at 48 h. In both treatments, the ruminal motility and the maximum hay intake were restored at 96 and 120 h, respectively. In conclusion, administration of HSS or HBS followed by intraruminal water corrects dehydration and mild-to-moderate metabolic acidosis in sheep with ARLA. Treatment with HBS promoted a faster correction of metabolic acidosis and could be indicated for the most severe cases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

The aim of this experiment was to measure enteric methane (CH 4 ) emission and its relation with rumen digestion in dairy cows fed diets rich in 1 of the 2 carbohydrate sources, starch or sugar. The rations were based on late first-cut grass-clover silage supplemented with wheat (Wh), NaOH-treated wheat (Wh+NaOH), sugar beet molasses (Mo), or sugar beet molasses with addition of sodium bicarbonate (Mo+Bic). Wheat and molasses made up 35% of dry matter in the 2 diets with molasses and wheat, respectively. Four cows fitted with ruminal, duodenal, and ileal canulae were used in a 4 × 4 Latin square design. Nutrient digestibility was measured using chromium oxide and titanium oxide as flow markers, and emissions of CH 4 and hydrogen were measured via open-circuit indirect calorimetry on 4 consecutive days. Data were analyzed using PROC MIXED of SAS (version 9.4; SAS Institute Inc., Cary, NC) with treatment and period as fixed effects and cow as random effect. Furthermore, orthogonal contrasts were calculated. The cows produced 32.5, 33.6, 36.2, and 35.1 L of CH 4 /kg of dry matter intake (DMI) on diets Wh, Wh+NaOH, Mo, and Mo+Bic, respectively. The emission of CH 4 per day, per kilogram of DMI, and per kilogram of energy-corrected milk as well as daily hydrogen emission were higher on the Mo diet compared with the Wh diet. With the present inclusion of wheat and molasses in the diet, no effects of NaOH treatment of wheat or of sodium bicarbonate supplementation to the Mo diet could be demonstrated on CH 4 emission expressed per kilogram of DMI or per kilogram of energy-corrected milk. The duodenal flow of starch was higher when wheat was treated with NaOH. Under the conditions in the present experiment, ruminal NDF digestibility was not affected by carbohydrate source, NaOH treatment of wheat, or bicarbonate supplementation. Total volatile fatty acid concentration in the rumen and the proportions of acetate and propionate were not affected by carbohydrate source, NaOH treatment of wheat, or bicarbonate supplementation. Likewise, we could not show any influence of diet on microbial protein synthesis or efficiency of microbial protein synthesis expressed as grams of microbial protein synthesis per kilogram of true rumen-digested organic matter. We concluded that CH 4 emission was increased when wheat was replaced by molasses, whereas no effect of manipulating rumen fermentation by NaOH treatment of wheat or addition of bicarbonate to molasses could be found with a level of approximately 25% of dry matter from starch and sugar, respectively., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Ingestion of toxic alcohols (TA) typically presents with a high anion gap (AG) metabolic acidosis, and elevated osmolar gap (OG). Hemodialysis (HD) has not been recommended in early phases of intoxication with high OG and normal AG metabolic acidosis. We describe the case of a 40-year-old male who was brought to our emergency department for reported paint thinner ingestion. He was unable to protect his airway and required intubation. Blood gas showed respiratory acidosis, an initial AG, corrected by albumin of 12.75, lactic acid 5.26 mmol/L, and an OG of 170. Patient was treated with bicarbonate drip, fomepizole and emergent HD, which improved his neurologic status. Days after his admission, alcohol levels came positive for a co-ingestion of ethylene glycol, diethylene glycol, and methanol. Most of the TA are metabolized into their toxic byproducts by the enzyme alcohol dehydrogenase (ADH). The kinetics of these alcohols will be altered when there is co-ingestion of multiple substances. Moreover, early ingestions will translate in a high OG without a high AG. False elevation of lactate can occur with the ingestion of ethylene glycol due to a cross-reaction with L-lactate oxidase in the analyzer. In our case, the administration of fomepizole followed by an early HD given the poor clinical improvement, was followed by a fast recovery of the neurological status and potentially prevented renal failure. A high index of suspicion for TA ingestion should be raised when encountering an individual with lactic acidosis, high OG, and normal AG.

Lignocaine is one of the most commonly-used agents to anaesthetise an area preoperatively. It can, however, cause undesirable effects such as burning on injection, relatively slow onset, and unreliable, or lack of, numbness when injected into infected tissues as a result of the acidic pH of commercial preparations (the pH is between 3.5 and 7.0 compared with the physiological pH, which is between 7.35 and 7.45). The aim of this comparative study was to evaluate the efficacy of buffered local anaesthetic on infected areas by altering the pH with 8.4% sodium bicarbonate, to measure the pain before and after the injection, and to record the time of onset of anaesthesia. All 60 patients were given 2% lignocaine hydrochloride with adrenaline 1:80,000 and 30 patients were randomly allocated to have 10:1 dilution of 8.4% sodium bicarbonate (study group). Pain was assessed on a visual analogue scale and a verbal rating scale. There was a significant difference in the amount of pain between control and study groups (p=0.025). The mean (SD) time (minutes) to onset of local anaesthesia in the study group was 1.06 (0.25) compared with 2.96 (0.81) in the control group (p<0.001). Our results confirm the efficacy of the buffered local anaesthetic solution in reducing pain on injection and resulting in quicker onset of anaesthesia. Increasing the pH of lignocaine solutions with bicarbonate immediately before use, therefore, should be considered when treating various acute infections of the head and neck., (Copyright © 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Methanol is a clear liquid with high toxicity. Methanol intoxication may result from accidental exposure, overconsumption of compounds containing methanol with suicidal intent, or following consumption of distilled and contaminated alcoholic beverages. This report describes a case of transdermal methanol intoxication, which is a rare condition. A 58-year-old woman presented with nausea, vomiting, weakness, diplopia and dizziness. On neurological examination, she only had diplopia. On physical examination, a hyperemic lesion with clear borders was found over the right knee. The patient's recent medical history revealed that four days prior to the onset of symptoms, she had covered her knee with a methanol-soaked bandage in an attempt to alleviate her knee pain. She had a high osmolar gap as well as high anion-gap metabolic acidosis (HAGMA). Methanol intoxication was suspected due to HAGMA and high osmolar gap. Serum methanol levels were subsequently measured and found to be 37.9 mg/ dL. The patient was treated with intravenous (IV) bicarbonate, IV ethyl alcohol and hemodialysis. She was discharged with no central nervous system or ophthalmologic sequelae. Methanol poisoning should be kept in mind in patients with diplopia and unexplained metabolic acidosis. Although most methanol intoxication cases occur after oral ingestion, it should be considered that methanol poisoning may occur transdermally., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses the desired anti-tumor effect of ICPis, can lead to side effects, and is cost-ineffective. We report the first case of the successful treatment of grade 3 ITID with steroids and an amino acid-based oral rehydration solution (AA-ORS), enterade. Research suggests that AA-ORS may be used to reduce diarrhea and adequately hydrate patients, in contrast to glucose-based oral rehydration solutions, which have been implicated as a contributing factor to diarrhea in cancer patients. We hypothesize that an AA-ORS may mitigate ITID via safer and more economically viable means than the current standard of care, but more controlled trials are needed to test this hypothesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Acute gastroenteritis is defined as a diarrheal disease of rapid onset, with or without nausea, vomiting, fever, or abdominal pain. In the United States, acute gastroenteritis accounts for 1.5 million office visits, 200,000 hospitalizations, and 300 deaths in children each year. Evaluation of a child with acute gastroenteritis should include a recent history of fluid intake and output. Significant dehydration is unlikely if parents report no decrease in oral intake or urine output and no vomiting. The physical examination is the best way to evaluate hydration status. The four-item Clinical Dehydration Scale can be used to determine severity of dehydration based on physical examination findings. In children with mild illness, stool microbiological tests are not routinely needed when viral gastroenteritis is the likely diagnosis. Mild gastroenteritis in children can be managed at home. Oral rehydration therapy, such as providing half-strength apple juice followed by the child's preferred liquids, is the mainstay of treatment for mild dehydration and is as effective as intravenous rehydration for preventing hospitalization and return to the emergency department. Oral rehydration solutions are recommended for moderate dehydration. Ondansetron may be prescribed if needed to prevent vomiting and improve tolerance of oral rehydration solutions. Hospitalization and intravenous fluids are recommended for children who do not respond to oral rehydration therapy plus an antiemetic and patients with severe dehydration (i.e., signs of shock or more than 10% dehydration). Handwashing, breastfeeding, and rotavirus vaccination reduce the incidence of acute gastroenteritis in young children.

Ketoacidosis is uncommon in non-diabetic women, but occurs in the postpartum period as a rare complication of continuing to breastfeed during periods of acute illness. We report a case of a lactating woman who presented with severe symptomatic ketoacidosis in the early postpartum period. We also review the pathophysiology and management of lactation ketoacidosis., (© 2019 Royal Australasian College of Physicians.)

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., (© 2019 S. Karger AG, Basel.)

Hydration is one of the most significant issues for combat sports as athletes often use water restriction for quick weight loss before competition. It appears that alkaline water can be an effective alternative to sodium bicarbonate in preventing the effects of exercise-induced metabolic acidosis. Therefore, the main aim of the present study was to investigate, in a double blind, placebo controlled randomized study, the impact of mineral-based highly alkaline water on acid-base balance, hydration status, and anaerobic capacity. Sixteen well trained combat sport athletes (n = 16), were randomly divided into two groups; the experimental group (EG; n = 8), which ingested highly alkaline water for three weeks, and the control group (CG; n = 8), which received regular table water. Anaerobic performance was evaluated by two double 30 s Wingate tests for lower and upper limbs, respectively, with a passive rest interval of 3 minutes between the bouts of exercise. Fingertip capillary blood samples for the assessment of lactate concentration were drawn at rest and during the 3rd min of recovery. In addition, acid-base equilibrium and electrolyte status were evaluated. Urine samples were evaluated for specific gravity and pH. The results indicate that drinking alkalized water enhances hydration, improves acid-base balance and anaerobic exercise performance., Competing Interests: The authors have declared that no competing interests exist.

Anaerobic power and anaerobic capacity significantly influence performance in many sport disciplines. These include prolonged sprints in athletics, swimming, or cycling, and other high intensity intermittent sports, such as soccer or basketball. Considering the association of exercise-induced acidosis and fatigue, the ingestion of potential buffering agents such as sodium bicarbonate, has been suggested to attenuate metabolic acidosis and improve anaerobic performance. Since elite soccer players cover from 200 to 350 m while sprinting, performing 40⁻60 all out sprints during a game, it seems that repeated sprint ability in soccer players is among the key components of success. In our experiment, we evaluated the effectiveness of chronic supplementation with sodium and potassium bicarbonate, fortified with minerals, on speed and speed endurance in elite soccer players. Twenty-six soccer players participated in the study. The subjects were randomly divided into two groups. The experimental group was supplemented with sodium bi-carbonate and potassium di-carbonate fortified with minerals, while the control group received a placebo. The athletes were tested at baseline and after nine days of supplementation. Anaerobic performance was evaluated by the Repeated Anaerobic Sprint Test (RAST) protocol which involved 6 × 30 m max sprints, separated by 10 s of active recovery. Resting, post ingestion and post exercise concentrations of HCO₃ - and blood pH were measured as well as lactate concentration. The current investigation demonstrated a significant increase in RAST performance of elite soccer players supplemented with sodium and potassium bicarbonate along with calcium phosphate, potassium citrate, and magnesium citrate ingested twice a day over a nine-day training period. The improvements in anaerobic performance were caused by increased resting blood pH and bicarbonate levels.

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To compare and report the intra- and postoperative outcomes of phacoemulsification between longitudinal (LPKE) and torsional (TPKE) mode, using active fluidics along with the intrepid balanced tip., Methods: This single center prospective randomized comparative study comprised a total 108 consecutive eyes of 108 patients having senile cataract subdivided into nuclear opalescence (NO) grades II-IV according to the lens opacities classification system III (LOCS III). Cataracts of each grade were randomly assigned to two groups LPKE (n = 54) and TPKE (n = 54) mode, who were operated on by the same surgeon using same machine (Centurion ® Alcon Laboratories, Inc., USA) having features of both active fluidics and intrepid balanced tip. Pre-, intra-, and postoperative evaluations were done independently by a different author, who was masked to the surgical procedures. Patients were evaluated on the postoperative days (PODs) 1, 7, 15, and 28. Intraoperative outcome measures were cumulative dissipated energy (CDE) and ultrasound time (UST). Postoperative outcome measures were endothelial cell loss (ECL), central corneal thickness (CCT), and best-corrected visual acuity (BCVA)., Results: Age, gender, and NO-grade distribution among two modes were comparable (P > 0.05). Difference of CDE and UST between modes were found to be significant (P < 0.001) in favor of TPKE with all NO-grades. TPKE mode performs better than LPKE mode with regard to ECL, CCT-change, and BCVA-change, although the differences were found to be insignificant (P > 0.05)., Conclusion: When using active fluidics along with the intrepid balanced tip, TPKE mode appeared to be a more efficient mode of PKE with reduced mean UST and CDE across all NO-grades, as compared to LPKE mode. However, ECL, CCT-change, and BCVA-change were seemed to be comparable between the two modes., Competing Interests: There are no conflicts of interest

Objectives: As acid-base imbalance is involved in many pathological processes, the capability to image tissue pH alterations in the clinic could offer new ways to detect disease and respond to treatment. In this study, the authors show that tissue pH can be imaged in vivo with 11 C-labeled bicarbonate (H 11 CO 3 - ) buffer and positron emission tomography (PET)., Methods: H 11 CO 3 - was produced by on-column NaOH adsorption. Biodistribution of H 11 CO 3 - in normal mice was determined. In addition, uptake studies and inhibition experiments of H 11 CO 3 - in the S180 fibrosarcoma-bearing mice and the inflammatory mice were investigated with PET imaging. The tumor and inflammatory interstitial pH was measured by a needle pH microelectrode., Results: PET imaging demonstrated the high uptake of H 11 CO 3 - in mice tumor tissues and inflammatory tissues, which showed that the average tumor or inflammatory interstitial pH was significantly lower than the surrounding tissue. Administration of sodium bicarbonate in the drinking water increased the measured tumor pH, while the uptake of H 11 CO 3 - in mice model tissues had no change. Similarly, administration with ammonium chloride (NH 4 Cl) decreased the pH, whereas the unchanged uptake of H 11 CO 3 - in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H 11 CO 3 - in mice model tissues was observed., Conclusions: H 11 CO 3 - solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H 11 CO 3 - PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation.

Background: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration. Because ROTAVAC®, a WHO prequalified vaccine, was derived from the 116E neonatal strain, we evaluated the immunogenicity and safety of ROTAVAC® without buffer and ROTAVAC® with buffer in a phase 4, multicentre, single-blind, randomized clinical trial in healthy infants in India., Methods: 900 infants, approximately 6, 10 and 14 weeks of age, were assigned to 3 groups to receive ROTAVAC® (0.5 mL dose) orally: (i) 2.5 mL of citrate-bicarbonate buffer 5 minutes prior to administration of ROTAVAC® (Group I), (ii) ROTAVAC®, alone, without any buffer (Group II), or (iii) ROTAVAC®, mixed with buffer immediately before administration (Group III). Non-inferiority was compared among the groups for differences in serological responses (detected by serum anti-rotavirus IgA) and safety., Results: Geometric mean titers post vaccination at day 84 (28 days after dose 3) were 19.6 (95%CI: 17.0, 22.7), 20.7 (95%CI: 17.9, 24) and 19.2 (95%CI: 16.8, 22.1) for groups I, II and III respectively. Further, seroconversion rates and distribution of adverse events were similar among groups., Conclusions: Administration of ROTAVAC® at a 0.5 mL dose volume without buffering agent was shown to be well tolerated and immunogenic. Given the homologous nature of the strain, it is plausible that ROTAVAC® replicates well and confers immunity even without buffer administration.

The aim of the study was to compare the effect of fiber- or starch-rich diets based on grass silage, supplemented or not with bicarbonate, on CH 4 emissions and milk fatty acid (FA) profile in dairy cows. The experiment was conducted as a 4 × 4 Latin square design with a 2 × 2 factorial arrangement: carbohydrate type [starch- or fiber-rich diets with dietary starch level of 23.1 and 5.9% on a dry matter basis, respectively], without or with bicarbonate addition [0 and 1% of the dry matter intake, respectively]. Four multiparous lactating Holstein cows were fed 4 diets with 42% grass silage, 8% hay, and 50% concentrate in 4 consecutive 4-wk periods: (1) starch-rich diet, (2) starch-rich diet with bicarbonate, (3) fiber-rich diet, and (4) fiber-rich diet with bicarbonate. Intake and milk production were measured daily and milk composition was measured weekly; CH 4 emission and total-tract digestibility were measured simultaneously (5 d, wk 4) when animals were in open-circuit respiration chambers. Sensors continuously monitored rumen pH (3 d, wk 4), and fermentation parameters were analyzed from rumen fluid samples taken before feeding (1 d, wk 3). Cows fed starch-rich diets had less CH 4 emissions (on average, -18% in g/d; -15% in g/kg of dry matter intake; -19% in g/kg of milk) compared with fiber-rich diets. Carbohydrate type did not affect digestion of nutrients, except starch, which increased with starch-rich diets. The decrease in rumen protozoa number (-36%) and the shift in rumen fermentation toward propionate at the expense of butyrate for cows fed the starch-rich diets may be the main factor in reducing CH 4 emissions. Milk of cows fed starch-rich diets had lower concentrations in trans-11 C18:1, sum of cis-C18, cis-9,trans-11 conjugated linoleic acid (CLA), and sum of CLA, along with greater concentration of some minor isomers of CLA and saturated FA in comparison to the fiber-rich diet. Bicarbonate addition did not influence CH 4 emissions or nutrient digestibility regardless of the carbohydrate type in the diet. Rumen pH increased with bicarbonate addition, whereas other rumen parameters and milk FA composition were almost comparable between diets. Feeding dairy cows a starch-rich diet based on grass silage helps to limit the negative environmental effect of ruminants, but does not lead to greater milk nutritional value because milk saturated FA content is increased., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Long-term exposure of conventional peritoneal dialysis (PD) fluid is associated with structural membrane alterations and technique failure. Previously, it has been shown that infiltrating IL-17-secreting CD4+T cells and pro-fibrotic M2 macrophages play a critical role in the PD-induced pathogenesis. Although more biocompatible PD solutions are recognized to better preserve the peritoneal membrane integrity, the impact of these fluids on the composition of the peritoneal cell infiltrate is unknown., Materials and Methods: In a uremic PD mouse model, we compared the effects of daily instillation of standard lactate (LS) or bicarbonate/lactate-buffered solutions (BLS) and respective controls on peritoneal fibrosis, vascularisation, and inflammation., Results: Daily exposure of LS fluid during a period of 8 weeks resulted in a peritoneal increase of αSMA and collagen accompanied with new vessel formation compared to the BLS group. Effluent from LS-treated mouse showed a higher percentage of CD4 + IL-17 + cell population while BLS exposure resulted in an increased macrophage population. Significantly enhanced inflammatory cytokines such as TGFβ1, TNFα, INFγ, and MIP-1β were detected in the effluent of BLS-exposed mice when compared to other groups. Further, immunohistochemistry of macrophage subset infiltrates in the BLS group confirmed a higher ratio of pro-inflammatory M1 macrophages over the pro-fibrotic M2 subset compared to LS., Conclusion: Development of the peritoneal fibrosis and angiogenesis was prevented in the BLS-exposed mice, which may underlie its improved biocompatibility. Peritoneal recruitment of M1 macrophages and lower number of CD4 + IL-17 + cells might explain the peritoneal integrity preservation observed in BLS-exposed mouse.

Background: A novel pyruvate-based oral rehydration salt (Pyr-ORS) was demonstrated of superiority over bicarbonate- or citrate-based one to preserve organ function and correct lactic acidosis in rehydration of lethal shock in animals. This study further compared these effects between low-osmolar Pyr-ORS and equimolar citrate-based counterpart., Methods: Eighty rats, using a fatal burn shock model, were randomized into four groups (two subgroups per group: n = 10): the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group CR), and no rehydration group. ORS was delivered by manual gavage during 24 h following burns. Oral administration consisted of half of counted volume in the initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral organ surface blood flow, organ function, and metabolic acidosis were determined at 8 h and 24 h after burn. Another set of rats with identical surgical procedures without tests was observed for survival., Results: Survival was markedly improved in the groups PR and CR; the former showed a higher survival rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics, visceral blood flow, and function of heart, liver, and kidney were greatly restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36 versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L; all P < 0.05) at 24 h after injury., Conclusions: Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h., (Copyright © 2018 Elsevier Inc. All rights reserved.)

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day -1 potassium bicarbonate (KHCO₃) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO₃; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day -1 ) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO₃ or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover ( 15 N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmol∙day -1 in KHCO₃ and 43.9 ± 27.8 mmol∙day -1 in PLA ( p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended ( p = 0.09) to be higher in KHCO₃ vs. PLA following energy restriction, and NAE was inversely associated ( r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO₃ supplementation following energy restriction as lower NAE indicated higher urea synthesis.

Objective/background: Up to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI., Methods: A novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO 3 ) immediately before EVAR (1 mL/kg of 8.4% NaHCO 3 ) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output., Results: Fifty-eight patients (84% of those screened; median age 75 years [range 57-89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO 3 . Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO 3 developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up., Conclusion: Bolus high dose NaHCO 3 and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

In the kidney, final urinary acidification is achieved by V-ATPases expressed in type A intercalated cells. The B1 subunit of the V-ATPase is required for maximal urinary acidification, while the role of the homologous B2 subunit is less clear. Here we examined the effect of acute acid/alkali loading in humans on B1 and B2 subunit abundance in urinary exosomes in normal individuals and of acid loading in patients with distal renal tubular acidosis (dRTA). Specificities of B1 and B2 subunit antibodies were verified by yeast heterologously expressing human B1 and B2 subunits, and murine wild-type and B1-deleted kidney lysates. Acute ammonium chloride loading elicited systemic acidemia, a drop in urinary pH, and increased urinary ammonium excretion. Nadir urinary pH was achieved at four to five hours, and exosomal B1 abundance was significantly increased at two through six hours after ammonium chloride loading. After acute equimolar sodium bicarbonate loading, blood and urinary pH rose rapidly, with a concomitant reduction of exosomal B1 abundance within two hours, which remained lower throughout the test. In contrast, no change in exosomal B2 abundance was found following acid or alkali loading. In patients with inherited or acquired distal RTA, the urinary B1 subunit was extremely low or undetectable and did not respond to acid loading in urine, whereas no change in B2 subunit was found. Thus, both B1 and B2 subunits of the V-ATPase are detectable in human urinary exosomes, and acid and alkali loading or distal RTA cause changes in the B1 but not B2 subunit abundance in urinary exosomes., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Diet composition influences acid-base status of the body. This may become more relevant as renal functional capacity declines with aging. We examined the effects of low (LD) versus high dietary acid load (HD) on blood acid-base status and exercise performance. Participants included 22 adolescents, 33 young adults (YA), and 33 elderly (EL), who followed a 7-day LD and HD in a randomized order. At the end of both diet periods the subjects performed a cycle ergometer test (3 × 10 min at 35%, 55%, 75%, and (except EL) until exhaustion at 100% of maximal oxygen uptake). At the beginning of and after the diet periods, blood samples were collected at rest and after all workloads. Oxygen uptake, respiratory exchange ratio (RER), and heart rate (HR) were monitored during cycling. In YA and EL, bicarbonate (HCO 3 - ) and base excess (BE) decreased over the HD period, and HCO 3 - , BE, and pH were lower at rest after HD compared with LD. In YA and EL women, HCO 3 - and BE were lower at submaximal workloads after HD compared with LD. In YA women, the maximal workload was 19% shorter and maximal oxygen uptake, RER, and HR were lower after HD compared with LD. Our data uniquely suggests that better renal function is associated with higher availability of bases, which may diminish exercise-induced acidosis and improve maximal aerobic performance. Differences in glomerular filtration rate between the subject groups likely explains the larger effects of dietary acid load in the elderly compared with younger subjects and in women compared with men.

We examined whether escalating doses of potassium bicarbonate (KHCO 3 ) supplements alter urinary nitrogen excretion expressed as a ratio to same day nitrogen intake (measure of muscle-protein breakdown). The ratio declined significantly from placebo to low to high dose of KHCO 3 supplementation in older adults over 3 months, suggesting muscle-sparing., Introduction: Neutralization of dietary acid load with alkali supplementation (i.e., KHCO 3 ) has been hypothesized to have muscle protein-sparing effects. In controlled feeding studies with fixed nitrogen (N) intake/day, 24-h urinary N excretion is a good marker of muscle breakdown. However, in studies with self-selected diets, changes in 24-h urinary N excretion can be influenced by shifts in N intake., Methods: We evaluated changes in 24-h total urinary N excretion as a ratio of N excretion to concurrent N intake in 233 older men and women who participated in an 84-day KHCO 3 supplementation randomized placebo-controlled trial., Results: After adjustment for relevant cofactors, escalating doses of KHCO 3 (1 mmol/kg/day [low] or 1.5 mmol/kg/day [high]) resulted in a progressive decline in urinary N excretion/N intake compared to placebo (overall P for trend = 0.042). The 84-day change in urinary N excretion/N intake in the high-dose KHCO 3 group was statistically significantly lower compared to placebo (P = 0.012) but not compared to the low-dose KHCO 3 group (P = 0.276). The 84-day change in urinary N excretion/N intake in the low-dose KHCO 3 group did not differ significantly from placebo (P = 0.145)., Conclusions: Urinary N excretion expressed as ratio to same day N intake declined steadily with increasing doses of KHCO 3 supplementation from low 1 mmol/kg/day to high 1.5 mmol/kg/day, suggesting a nitrogen-sparing effect. Compared to urinary N excretion alone, this ratio could be a more reasonable measure of muscle protein metabolism in large-scale long-term human studies., Trial Registration: Clinicaltrials.gov NCT1475214.

Purpose: To optimize the production of hyperpolarized 13 C-bicarbonate from the decarboxylation of hyperpolarized [1- 13 C]pyruvate and use it to image pH in the lungs and heart of rats with acute lung injury., Methods: Two forms of catalysis are compared calorimetrically to maximize the rate of decarboxylation and rapidly produce hyperpolarized bicarbonate from pyruvate while minimizing signal loss. Rats are injured using an acute lung injury model combining ventilator-induced lung injury and acid aspiration. Carbon images are obtained from both healthy (n = 4) and injured (n = 4) rats using a slice-selective chemical shift imaging sequence with low flip angle. pH is calculated from the relative HCO3- and CO 2 signals using the Henderson-Hasselbalch equation., Results: It is demonstrated that base catalysis is more effective than metal-ion catalysis for this decarboxylation reaction. Bicarbonate polarizations up to 17.2% are achieved using the base-catalyzed reaction. A mean pH difference between lung and heart of 0.14 pH units is measured in the acute lung injury model. A significant pH difference between injured and uninjured lungs is also observed., Conclusion: It is demonstrated that hyperpolarized 13 C-bicarbonate can be efficiently produced from the base-catalyzed decarboxylation of pyruvate. This method is used to obtain the first regional pH image of the lungs and heart of an animal. Magn Reson Med 78:1121-1130, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Background: In the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients., Methods: The Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD., Results: Data from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events., Conclusions: A small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate., Trial Registration: This trial was registered on ClinicalTrials.gov on 11 Dec 2014 ( NCT02334267 ).

We aim to present an overview of the possible influence of drinking water in general and mineral water in particular in improving glycemic parameters in persons with or without type 2 diabetes. We performed a literature search that produced 15 randomized controlled trials (RCTs) on this topic with mainly small sample sizes. We also discuss relevant observational and animal studies as well as the effects of important supplements in mineral water such as hydrogencarbonate and magnesium. There is low evidence for the positive effects of water or mineral water in improving glycemic parameters in diabetic and non-diabetic persons, and the results are heterogenous, making it difficult to reach an unequivocal conclusion. Meta-analyses of prospective cohort studies and other observational studies, studies with animal models and interventional studies using hydrogencarbonate and magnesium supplements suggest a probable positive effect of drinking water and mineral water in particular on glycemic parameters, supporting the positive results found in some of the RCTs, especially those substituting diet beverages or caloric beverages with water, or those using bicarbonate and magnesium-rich water. Regarding the high prevalence, the associated suffering and the resulting health expenditures of type 2 diabetes, it is imperative to conduct larger and more rigorous trials to answer the question whether drinking water or mineral water can improve glycemic parameters in diabetic and non-diabetic persons., Competing Interests: Johannes Naumann received support from balneology organisations such as Deutscher Heilbäderverband and Heilbäderverband Baden-Württemberg and is a member of these organisations. Diana Biehler received support from Verband Deutscher Mineralbrunnen. None of the organisations financed this work. The authors declare no conflict of interest.

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.

Objective: To investigate the nociceptive and clinical effects of buffering a lidocaine-epinephrine solution with sodium bicarbonate in caudal epidural block in mares., Study Design: Prospective randomized controlled trial., Animals: Six mixed-breed mares weighing 350-440 kg., Methods: Each animal was administered two caudal epidural injections, 72 hours apart, using different solutions prepared immediately before injection. The control solution was 7 mL 2% lidocaine hydrochloride with epinephrine hemitartrate (1:200,000) added to 3 mL sterile water for injection (pH 2.9). The alkalinized solution was 7 mL of lidocaine-epinephrine solution added to 2.3 mL sterile water for injection and 0.7 mL 8.4% sodium bicarbonate (pH 7.4). Nociception was evaluated by response to skin pinching at 31 sites in the sacral region and around the perimeter of the anogenital area (distances of 10, 15 and 20 cm) before, and 5, 10 and 15 minutes after epidural injection, then every 15 minutes until the return of nociception in all evaluated sites. The onset and duration times, and intensity of ataxia (grades 0 to 3) were recorded. The paired t test was used to compare the onset and duration of anesthesia and ataxia (p<0.05)., Results: Alkalization of the solution resulted in significant decreases in the average time of onset of loss of nociception in the sacral region (40%) and around the perimeter of the anogenital area extending up to 5 cm (36%) and from 5 to 10 cm (32%) from the anus and vulva. Alkalization also decreased the average duration of ataxia (33%), without affecting the duration and extent of anesthesia or the degree of ataxia., Conclusions and Clinical Relevance: Alkalization of lidocaine-epinephrine solution is advantageous in shortening the duration of ataxia and hastening the onset of anesthesia in areas adjacent to the anogenital area, without reducing the duration of epidural anesthesia, in mares., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Pain on injection of lidocaine is often considered a necessary evil, but it can be reduced by simple means.

Background: Severe cholera is a life-threatening illness of hypovolemic shock and metabolic acidosis due to rapid and profuse diarrheal fluid loss. Emergency life-saving therapy is i.v. saline, optionally supplemented with potassium and alkali to correct the fluid deficit, potassium losses and acidosis. After this initial rehydration, for the next 2 days ongoing stool losses are replaced with oral rehydration solution (ORS), which contains sodium chloride, potassium and alkali together with glucose or rice powder as a source of glucose to serve as a carrier for sodium., Results: In actual field trials, antibiotics are given to reduce fluid requirements, but large volumes averaging about 7 liters of i.v. fluid followed by about 14 liters of ORS have been given to adult patients. Disturbing trends during therapy have included overhydration, hyponatremia and polyuria., Conclusions: It is suggested that stool output and fluid requirements could be reduced, if borne out in future research, by avoiding overhydration by restricting ORS intake to match stool output and promoting intestinal reabsorption of luminal fluid by early introduction of glucose without salts into the intestine, more gradual correction of dehydration, giving mineralocorticoid and vasopressin, and infusing glucose or short-chain fatty acids into the proximal colon., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although preoperative fluid intake 2 hours before anesthesia is generally considered safe, there are concerns about delayed gastric emptying in obese subjects. In this study, the gastric fluid volume (GFV) change in morbidly obese subjects was investigated after ingesting an oral rehydration solution (ORS) and then compared with that in nonobese subjects., Methods: GFV change over time after the ingestion of 500 mL of ORS containing 2.5% carbohydrate (OS-1) was measured in 10 morbidly obese subjects (body mass index [BMI], >35) scheduled for bariatric surgery and 10 nonobese (BMI, 19-24) using magnetic resonance imaging. After 9 hours of fasting, magnetic resonance imaging scans were performed at preingestion, 0 min (just after ingestion), and every 30 minutes up to 120 minutes. GFV values were compared between morbidly obese and control groups and also between preingestion and postingestion time points., Results: The morbidly obese group had a significantly higher body weight and BMI than the control group (mean body weight and BMI in morbidly obese, 129.6 kg and 46.3 kg/m, respectively; control, 59.5 kg and 21.6 kg/m, respectively). GFV was significantly higher in the morbidly obese subjects compared with the control group at preingestion (73 ± 30.8 mL vs 31 ± 19.9 mL, P = .001) and at 0 minutes after ingestion (561 ± 30.8 mL vs 486 ± 42.8 mL; P < .001). GFV declined rapidly in both groups and reached fasting baseline levels by 120 minutes (morbidly obese, 50 ± 29.5 mL; control, 30 ± 11.6 mL). A significant correlation was observed between preingestion residual GFV and body weight (r = .66; P = .001)., Conclusions: Morbidly obese subjects have a higher residual gastric volume after 9 hours of fasting compared with subjects with a normal BMI. However, no differences were observed in gastric emptying after ORS ingestion in the 2 populations, and GFVs reached baseline within 2 hours after ORS ingestion. Further studies are required to confirm whether the preoperative fasting and fluid management that are recommended for nonobese patients could also be applied to morbidly obese patients.

We aimed to evaluate the sensitivity and specificity of 8 biochemical scanning tools in signalling the presence of unmeasured anions. We used blood gas and biochemical data from 15 patients during and after cardio-pulmonary bypass. Sampling time-points were pre-bypass (T1), 2 min post equilibration with priming fluid containing acetate and gluconate anions (T2), late bypass (T3) and 4 h after surgery (T4). We calculated the anion gap (AG), albumin-corrected anion gap (AGc), whole blood base excess (BE) gap, plasma BE gap, standard BE gap and the strong ion gap (SIG), plus 2 new indices-the unmeasured ion index (UIX) and unmeasured plasma anions according to the interstitial, plasma and erythrocyte acid-base model (IPEua). Total measured plasma concentrations of acetate and gluconate [XA] were proxies for unmeasured plasma anions. [XA] values (mmol/L) were 1.41 (0.87) at T1, 11.73 (3.28) at T2, 4.80 (1.49) at T3 and 1.36 (0.73) at T4. Corresponding [albumin] values (g/L) were 32.3 (2.0), 19.8 (2.6), 21.3 (2.5) and 29.1 (2.3) respectively. Only the AG failed to increase significantly at T2 in response to a mean [XA] surge of >10 mEq/L. At an [XA] threshold of 6 mEq/L, areas under receiver -operator characteristic curves in rank order were IPEua and UIX (0.88 and 0.87 respectively), SIG (0.81), AGc (0.79), standard BE gap (0.77), plasma BE gap (0.71), BE gap (0.70) and AG (0.59). Similar ranking hierarchies applied to positive and negative predictive values. We conclude that during acute hemodilution UIX and IPEua are superior to the anion gap (with and without albumin correction) and 4 other indices as scanning tools for unmeasured anions.

Objective:: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement., Methods:: A total of 110 patients who underwent single (aortic or mitral) valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients), long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood-based cardioplegia solution) was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters., Results:: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43) and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23) in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65) in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB), Troponin-I levels, lactate level and cardiac functions postoperatively., Conclusion:: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

Dialysate composition is a critical aspect of the hemodialysis prescription. Despite this, trial data are almost entirely lacking to help guide the optimal dialysate composition. Often, the concentrations of key components are chosen intuitively, and dialysate composition may be determined by default based on dialysate manufacturer specifications or hemodialysis facility practices. In this review, we examine the current epidemiological evidence guiding selection of dialysate bicarbonate, calcium, magnesium, and potassium, and identify unresolved issues for which pragmatic clinical trials are needed., (© 2017 Wiley Periodicals, Inc.)