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Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real-world Data Results from the AlcalUN Study.
Beaume, J, Figueres, L, Bobot, M, de Laforcade, L, Ayari, H, Dolley-Hitze, T, Gueutin, V, Braconnier, A, Golbin, L, Citarda, S, et al
Clinical pharmacology and therapeutics. 2022;(1):252-262
Abstract
Oral alkalization with sodium bicarbonate (NaHCO3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO3 -containing or no-NaHCO3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO3 is no longer associated with an ECV increase compared to citrate in real-life settings.
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Oral sodium bicarbonate in people on haemodialysis: a randomised controlled trial.
Kourtellidou, SI, Ashby, DR, Johansson, LR
BMC nephrology. 2021;(1):346
Abstract
BACKGROUND Adverse events and mortality tend to cluster around dialysis sessions, potentially due to the impact of the saw-toothed profile of uraemic toxins such as potassium, peaking pre-dialysis and rapidly dropping during dialysis. Acidosis could be contributing to this harm by exacerbating a rise in potassium. The objectives of this study were to investigate the effects of oral bicarbonate treatment on reducing inter-dialytic potassium gain as well as other clinical consequences of preserving muscle mass and function and reducing intradialytic arrhythmia risk in people on haemodialysis. METHODS Open-label randomised controlled trial in a single-centre (London, UK). Forty-three clinically stable adults on haemodialysis were recruited, with a 6 month average pre-dialysis serum bicarbonate level < 22 mmol/l and potassium > 4 mmol/l. Thirty-three participants completed the study. Oral sodium bicarbonate tablets titrated up to a maximum of 3 g bd (6 g total) in intervention group for 12 weeks versus no treatment in the control group. Outcomes compared intervention versus non-intervention phases in the treated group and equivalent time points in the control group: pre- and post-dialysis serum potassium; nutritional assessments: muscle mass and handgrip strength and electrocardiograms (ECGs) pre and post dialysis. RESULTS Participants took an average of 3.7 ± 0.5 g sodium bicarbonate a day. In the intervention group, inter-dialytic potassium gain was reduced from 1.90 ± 0.60 to 1.69 ± 0.49 mmol/l (p = 0.032) and pre-dialysis potassium was reduced from 4.96 ± 0.62 to 4.79 ± 0.49 mmol/l without dietary change. Pre-dialysis bicarbonate increased from 18.15 ± 1.35 to 20.27 ± 1.88 mmol/l, however with an increase in blood pressure. Nutritionally, lean tissue mass was reduced in the controls suggesting less catabolism in the intervention group. There was no change in ECGs. Limitations are small sample size and unblinded study design lacking a placebo, with several participants failing to achieve the target of 22 mmol/l serum bicarbonate levels due mainly to tablet burden. CONCLUSION Oral sodium bicarbonate reduced bicarbonate loss and potassium gain in the inter-dialytic period, and may also preserve lean tissue mass. TRIAL REGISTRATION The study was registered prospectively on 06/08/2015 with EU Clinical Trials Register EudraCT number 2015-001439-20 .
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Comparison of Microplegia Solution and Del Nido Cardioplegia Solution in Coronary Artery Bypass Grafting Surgery: Which One is More Effective?
Urcun, YS, Pala, AA
The heart surgery forum. 2021;(5):E842-E848
Abstract
BACKGROUND The aim of this study is to compare the efficacy of the microplegia solution and Del Nido cardioplegia solution in coronary artery bypass surgery with clinical, biochemical, and echocardiographic data. METHODS Three hundred patients, who underwent coronary artery bypass surgery between January 2017 and January 2020, by the same surgical team were included in the study. Preoperative, operative and postoperative data (cardiac biomarker levels, cross-clamp and CPB times, echocardiographic measurements, etc.) of the patients were compared. RESULTS In the study, cross-clamp time was significantly shorter in the DN cardioplegia group (55.60 ± 13.49 min/75.58 ± 12.43 min, P = 0.024). No significant difference was observed between the two groups in terms of intensive care stay, extubation time, hospital stay, and cardiopulmonary bypass time. In our study, it was shown that both the left and right ventricular ejection fraction was better protected in the Del Nido cardioplegia group (5.34±3.03 vs. 3.40±2.84, P = 0.017 and 3.82±1.19 vs. 2.28±1.87, P = 0.047, respectively), and the need for inotrope support was lower in this group (28% vs. 44%, P < 0.021). There was no significant difference between the groups, in terms of blood transfusion rates, IABP requirement. CONCLUSION In light of short-term results, we can say that Del Nido cardioplegia provides better myocardial protection than microplegia. In addition, Del Nido cardioplegia can be given as a single dose for 90 minutes of cross-clamp time and therefore can be preferred to increase surgical comfort and reduce cross-clamp times.
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Effects of Del Nido and Terminal Warm Blood Cardioplegia on Myocardial Protection and Rhythm in Isolated CABG Patients.
Karaarslan, K, Abud, B
The heart surgery forum. 2021;(5):E808-E813
Abstract
OBJECTIVE To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients. MATERIAL AND METHODS A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared. RESULTS There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation. CONCLUSIONS We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.
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Sodium bicarbonate therapy for acute respiratory acidosis.
Chand, R, Swenson, ER, Goldfarb, DS
Current opinion in nephrology and hypertension. 2021;(2):223-230
Abstract
PURPOSE OF REVIEW Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. RECENT FINDINGS There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. SUMMARY There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it.
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Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy.
Yagi, K, Fujii, T
Critical care (London, England). 2021;(1):314
Abstract
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
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Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events.
Shastry, S, Ellis, J, Loo, G, Vedanthan, R, Richardson, LD, Manini, AF
Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2021;(1):27-36
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Abstract
BACKGROUND Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE. METHODS This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2). RESULTS Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19). CONCLUSION In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.
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Extracellular buffer choice influences acid-base responses and gastrointestinal symptoms.
Peacock, J, Sparks, SA, Middlebrook, I, Hilton, NP, Tinnion, D, Leach, N, Saunders, B, McNaughton, LR
Research in sports medicine (Print). 2021;(6):505-516
Abstract
To compare the bicarbonate kinetics and gastrointestinal (GI) symptom responses between an equal dose of sodium bicarbonate and sodium citrate using delayed-release capsules. Thirteen active males (age 20.5 ± 2.1 y, height 1.8 ± 0.1 m and body mass [BM] 76.5 ± 9.6 kg) consumed either 0.3 g.kg-1 BM sodium bicarbonate, sodium citrate or a placebo, using a double-blind, randomized crossover design. Blood bicarbonate ion (HCO3-) concentration, pH and GI symptoms were measured pre-consumption and every 10 min for 180 min post-consumption. Blood HCO3- concentration (P < 0.001) and pH (P = 0.040) were significantly higher in the sodium bicarbonate condition compared with sodium citrate condition up to 3 h post-consumption. Peak blood HCO3- concentration was significantly higher with the sodium bicarbonate compared with citrate (P < 0.001). Mean GI symptom scores were lower (P = 0.037) for sodium citrate (1.5 ± 1.8 AU) than bicarbonate (2.6 ± 3.1 AU), with considerable inter-individual variability. No GI symptoms were reported following consumption of the placebo. Both substances increase HCO3- values significantly, with sodium bicarbonate causing significantly higher pH and HCO3- values than the same dose of sodium citrate, but results in slightly more severe GI symptoms.
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Effects of Combining Caffeine and Sodium Bicarbonate on Exercise Performance: A Review with Suggestions for Future Research.
Grgic, J
Journal of dietary supplements. 2021;(4):444-460
Abstract
This paper aimed to: (a) critically review studies that explored the isolated and combined effects of caffeine and sodium bicarbonate ingestion on exercise performance; (b) discuss some of the possible reasons for the discrepancy in findings; and, (c) provide suggestions for future studies. Out of the eight studies that examined this topic, only one study found that the combined ingestion of both supplements provided additive effects. In other studies, the following findings were observed: (a) only caffeine was ergogenic; (b) isolated and combined ingestion of both supplements was comparably ergogenic; (c) neither isolated nor combined ingestion of caffeine and sodium bicarbonate provided a performance-enhancing effect; and, (d) caffeine and caffeine plus sodium bicarbonate improved performance compared to sodium bicarbonate (but not as compared to placebo). Even though studies used currently recommended protocols of caffeine supplementation and exercise tasks for which the isolated ergogenic effects of caffeine and sodium bicarbonate are already established, the response to sodium bicarbonate supplementation was very variable, which might largely explain the discrepancies in the findings. The protocols of sodium bicarbonate ingestion generally resulted in high incidence and severity of side-effects, which might have had a negative effect on exercise performance. Future studies that optimize protocols of sodium bicarbonate supplementation are needed to fully explore if combining caffeine and sodium bicarbonate indeed provides any additive effects on exercise performance.
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Exogenous Ketosis Impairs 30-min Time-Trial Performance Independent of Bicarbonate Supplementation.
Poffé, C, Wyns, F, Ramaekers, M, Hespel, P
Medicine and science in sports and exercise. 2021;(5):1068-1078
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PURPOSE We recently demonstrated that coingestion of NaHCO3 to counteract ketoacidosis resulting from oral ketone ester (KE) intake improves mean power output during a 15-min time trial (TT) at the end of a 3-h cycling race by ~5%. This ergogenic effect occurred at a time when blood ketone levels were low, as ketosis was only induced during the initial ~2 h of the race. Therefore, in the current study, we investigated whether performance also increases if blood ketone levels are increased in the absence of ketoacidosis during high-intensity exercise. METHODS In a double-blind crossover design, 14 well-trained male cyclists completed a 30-min TT (TT30') followed by an all-out sprint at 175% of lactate threshold (SPRINT). Subjects were randomized to receive (i) 50 g KE, (ii) 180 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON). RESULTS KE ingestion increased blood d-ß-hydroxybutyrate to ~3-4 mM during the TT30' and SPRINT (P < 0.001 vs CON). In KE, blood pH and bicarbonate concomitantly dropped, causing 0.05 units lower pH and 2.6 mM lower bicarbonate in KE compared with CON during the TT30' and SPRINT (P < 0.001 vs CON). BIC coingestion resulted in 0.9 mM higher blood d-ß-hydroxybutyrate (P < 0.001 vs KE) and completely counteracted ketoacidosis during exercise (P > 0.05 vs CON). Mean power output during TT30' was similar between CON and BIC at 281 W, but was 1.5% lower in the KE conditions (main effect of KE: P = 0.03). Time to exhaustion in the SPRINT was ~64 s in CON and KE and increased by ~8% in the BIC conditions (main effect of BIC: P < 0.01). DISCUSSION Neutralization of acid-base disturbance by BIC coingestion is insufficient to counteract the slightly negative effect of KE intake during high-intensity exercise.