The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.

Endoscopic lithotripsy combined with drug lithotripsy vs. drug lithotripsy for the treatment of phytobezoars: analysis of 165 cases.

AIM: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars. METHODS: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B). RESULTS: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A. CONCLUSION: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Effect of Acute Sodium Bicarbonate and Caffeine Coingestion on Repeated-Sprint Performance in Recreationally Trained Individuals: A Randomized Controlled Trial.

INTRODUCTION: The acute and isolated ingestion of sodium bicarbonate (NaHCO3) and caffeine (CAF) improves performance and delays fatigue in high-intensity tasks. However, it remains to be elucidated if the coingestion of both dietary supplements stimulates a summative ergogenic effect. This study aimed to examine the effect of the acute coingestion of NaHCO3 and CAF on repeated-sprint performance. METHODS: Twenty-five trained participants (age: 23.3 [4.0] y; sex [female/male]: 12/13; body mass: 69.6 [12.5] kg) participated in a randomized, double-blind, placebo (PLA) -controlled, crossover study. Participants were assigned to 4 conditions: (1) NaHCO3 + CAF, (2) NaHCO3, (3) CAF, or (4) PLA. Thus, they ingested 0.3 g/kg of NaHCO3, 3 mg/kg of CAF, or PLA. Then, participants performed 4 Wingate tests (Wt), consisting of a 30-second all-out sprint against an individualized resisted load, interspersed by a 1.5-minute rest period between sprints. RESULTS: Peak (Wpeak) and mean (Wmean) power output revealed a supplement and sprint interaction effect (P = .009 and P = .049, respectively). Compared with PLA, NaHCO3 + CAF and NaHCO3 increased Wpeak performance in Wt 3 (3%, P = .021) and Wt 4 (4.5%, P = .047), while NaHCO3 supplementation increased mean power performance in Wt 3 (4.2%, P = .001). In Wt 1, CAF increased Wpeak (3.2%, P = .054) and reduced time to Wpeak (-8.5%; P = .008). Plasma lactate showed a supplement plus sprint interaction (P < .001) when NaHCO3 was compared with CAF (13%, P = .031) and PLA (23%, P = .021). CONCLUSION: To summarize, although the isolated ingestion of CAF and NaHCO3 improved repeated-sprint performance, the coingestion of both supplements did not stimulate a synergic ergogenic effect.

Oral regimen for high dose methotrexate urine alkalinization: a systematic review and meta-analysis.

OBJECTIVE: Urine alkalinization prevents nephrotoxicity in patients receiving high-dose methotrexate (HDMTX). While the standard approach involves IV sodium bicarbonate, alternative oral bicarbonate regimens are crucial in drug shortages and outpatient settings. This study aims to review the efficacy and safety of such regimens. METHODS: PubMed, WOS, and Scopus were systematically searched using the PRISMA protocol for relevant studies involving human subjects, including randomized clinical trials, retrospective, prospective, cohort, case reports, and case series studies. There were no restrictions on language, time, or age group. Qualified and eligible papers were used to extract data on efficacy and safety indicators, and the final relevant records were assessed for quality using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) assessment tool. RESULTS: 12 studies with 1212 participants were included in the systematic review, with pooled data from 8 studies used for meta-analysis. No significant differences in mean differences (MDs) or odds ratio (OR) were found after the oral bicarbonate regimen, except for when urine pH fell to < 7 (MD: 0.91, 95% CI: 0.32, 1.5, P < 0.05) and the incidence of diarrhea (OR: 2.92, 95% CI: 1.69, 5.05, P < 0.05). CONCLUSION: An oral bicarbonate regimen is a safe and effective way to alkalize HDMTX urine, providing a viable and cost-effective alternative to IV protocols. Further prospective multicenter studies are necessary. Systematic review registration identifier: CRD42023379666.

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

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

Safety and Efficacy of Acute Central Venous Catheters for Hemodialysis with Sodium Bicarbonate versus an Antibiotic Catheter Locking Solution.

This study was conducted to determine the safety and efficacy of acute central venous catheters (CVC) using a sodium bicarbonate catheter locking solution (SBCLS) versus an antibiotic catheter locking solution (ACLS). Our study included patients aged >18 years on hemodialysis initiated through an internal jugular non-tunneled CVC. Safety was assessed by comparing catheter loss resulting from catheter dysfunction (CD) and catheter-related blood stream infections (CRBSI) in two study groups: the SBCLS group (using 7.5% sodium bicarbonate) and the ACLS group (using antibiotic + heparin). Efficacy was assessed by the adequacy of blood flow (>300 mL/min). In total, 160 patients were included: 80 with the SBCLS and 80 with the ACLS. There were no statistically significant differences in clinical demographics between the groups. The average duration of the catheters was 23 days in the ACLS group and 22 days in the SBCLS group. In the ACLS group, four lost catheters to CD, two lost them to CRBSI, and five lost them to other malfunctions. Adequate blood flow was achieved in 71 patients. In the SBCLS group, three lost catheters to CD, three lost them to CRBSI, and four lost them to other malfunctions. Adequate blood flow was achieved in 73 patients. No significant differences between the groups were observed for catheter loss to CRBSI (P = 0.648), CD (P = 0.699), malfunction (P = 0.731), and blood flow (P = 0.598). The safety and efficacy of non-tunneled CVC with sodium bicarbonate as the catheter locking solution were similar to those of the ACLS.

Comparación del efecto de omeprazol como monoterapia y su combinación con bicarbonato de sodio en el tratamiento de la pirosis moderada a severa: ensayo clínico controlado, aleatorizado y doble ciego / Comparison of the effect of omeprazole monotherapy and its combination with sodium bicarbonate in the treatment of moderate to severe heartburn: a double-blind, randomized controlled clinical trial

Heartburn occurs in 75% of patients with digestive discomfort of any origin and is one of the main symptoms of gastroesophageal reflux disease. Treatment focuses on lifestyle modification and symptomatology management with various drugs; when heartburn is moderate to severe, a proton pump inhibitor is more suitable. Omeprazole (OMZ) combined with sodium bicarbonate (BC) has demonstrated significant and sustained suppression of acid secretion. The objective was to compare the effect of sequential OMZ/BC therapy compared to OMZ monotherapy for the improvement of heartburn in Mexican individuals. The study was a double-blind, randomized, controlled, multicenter clinical study including 277 subjects with moderate to severe heartburn. Patients received 7 days of OMZ/BC and 7 days of OMZ (OMZ/BC7) or 14 days of OMZ (OMZ14). The primary endpoint was defined as the change in the number of days a week that the patient has heartburn, it was evaluated at 14 days. Both treatments reduced time (days) with heartburn by less than 4 days (OMZ14 3.9 vs. 4.2 days OMZ/BC7), as well as duration, number of events and intensity of heartburn. The treatments improved the quality of life, and the control of the symptoms. The proportion of adverse events was lower with OMZ/BC. The non-inferiority of OMZ/BC7 with respect to OMZ14 was verified.

La pirosis se presenta en el 75% de los pacientes con molestias digestivas de cualquier origen y es uno de los principales síntomas de la enfermedad por reflujo gastroesofágico. El tratamiento se enfoca en la modificación del estilo de vida y el manejo de la sintomatología con diversos fármacos; cuando la pirosis es moderada a severa, un inhibidor de la bomba de protones es más adecuado. El omeprazol (OMZ) combinado con bicarbonato de sodio (BC) ha demostrado supresión significativa y sostenida de la secreción ácida. El objetivo fue comparar el efecto de la terapia secuencial de OMZ/BC en comparación con el tratamiento continuo de OMZ para la mejoría de la pirosis en individuos mexicanos. Estudio clínico multicéntrico, doble ciego, controlado, aleatorizado que incluyó 277 sujetos con pirosis moderada a severa. Los pacientes recibieron 7 días de OMZ/BC y 7 días de OMZ (OMZ/BC7) o 14 días de OMZ (OMZ14). La variable primaria fue definida como el cambio del número de días a la semana que el paciente presenta pirosis, se evaluó a los 14 días. Ambos tratamientos redujeron los días con pirosis en menos 4 días (OMZ14 3,9 vs. 4,2 días OMZ/BC7), así como la duración, el número de eventos e intensidad de la pirosis. Los tratamientos mejoraron los indicadores de calidad de vida, y el control del padecimiento. La proporción de eventos adversos fue menor con OMZ/BC. Se comprobó la no-inferioridad de OMZ/BC7 respecto OMZ14.

Effects of sodium bicarbonate infusion on mortality in medical–surgical ICU patients with metabolic acidosis—A single-center propensity score matched analysis / Efectos de la infusión de bicarbonato de sodio sobre la mortalidad en pacientes de UCI médico-quirúrgica con acidosis metabólica: un análisis de puntuación de propensión en un solo Centro

Objective Metabolic acidosis is associated with high mortality. Despite theoretical benefits of sodium-bicarbonate (SB), current evidence remains controversial. We investigated SB-related effects on outcomes in ICU patients with metabolic acidosis. Design Retrospective analysis. Setting Academic medical center. Patients or participants 971 ICU patients with metabolic acidosis defined as arterial pH<7.3 and CO2<45mmHg treated between 2012 and 2016. A propensity score (PS) was estimated using logistic regression. Patients were matched in pairs using the PS. Interventions 441 patients were treated with SB 8.4% (SB-group) and n=530 patients were not (control group). Main variables of interest Primary outcome was all-cause mortality at ICU-discharge. Average Treatment Effect (ATE), Average Treatment effect in Treated (ATT), and estimated relative survival effects at 20 days were computed. Results In the full cohort, we observed considerable differences in pH, base excess, additional acidosis-related indices, and ICU mortality (controls 31% vs. SB-group 56%, p<.001) at baseline between the two groups. After PS-matching (n=174 in each group), no significant difference in ICU mortality was observed (controls 32% vs. SB-group 41%; p=.07). Odds ratios (OR) for ATE and ATT showed no association with ICU mortality (OR ATE: 1.08, 95%-CI 0.99–1.17; p=.08; OR ATT 1.09; 95%-CI 0.99–1.2; p=.09). Hazard ratios at 20-days (multivariable HR, matched sample n=348: 1.16, 95%-CI 0.86–1.56, p=.33) showed similar survival in the two study groups. Conclusions We did not observe effects of SB infusion on all-cause mortality in critically ill patients with metabolic acidosis (AU)

Objetivo La acidosis metabólica se asocia con una alta mortalidad. A pesar de los beneficios teóricos del bicarbonato de sodio (BS), la evidencia actual sigue siendo controvertida. Investigamos los efectos relacionados con el BS sobre los resultados en pacientes de la UCI con acidosis metabólica. Diseño Análisis retrospectivo. Ÿmbito Centro médico académico. Pacientes o participante Se incluyeron 971 pacientes de la Unidad de Cuidados Intensivos (UCI) con acidosis metabólica (pH < 7,3, CO2 < 45 mmHg) tratados entre 2012 y 2016. Se calculó una puntuación de propensión (PS) mediante regresión logística. Los pacientes se emparejaron utilizando el PS. Variables de interés principales Intervenciones; 441 pacientes fueron tratados con BS 8,4% (grupo BS) y n = 530 pacientes no (grupo control). Resultados El resultado primario fue la mortalidad por todas las causas al alta de la UCI. Se calcularon el efecto promedio del tratamiento (ATE), el efecto promedio del tratamiento en los tratados (ATT) y los efectos de supervivencia relativa estimados a los 20 días. En la cohorte completa se observaron diferencias considerables en el pH, el exceso de bases y la mortalidad en la UCI (control 31% vs. grupo BS 56%, p < 0,001) al inicio del estudio entre los grupos. Después del emparejamiento de PS (n = 174 en cada grupo), no se observaron diferencias significativas en la mortalidad en la UCI (control 32% vs. grupo BS 41%; p = 0,07). Los odds ratios (OR) para ATE y ATT no mostraron asociación con la mortalidad en la UCI (OR ATE: 1,08, IC 95%; 0,99-1,17; p = 0,08; OR ATT 1,09; IC 95%; 0,99-1,2; p = 0,09). Los cocientes de riesgo a los 20 días (HR multivariable, muestra emparejada n = 348: 1,16, IC 95%; 0,86-1,56, p = 0,33) mostraron una supervivencia comparable. Conclusiones No observamos efectos de la infusión de BS sobre la mortalidad por todas las causas en pacientes con acidosis metabólica (AU)

Bicarbonato de sodio intravenoso ¿Cuándo, cómo y por qué utilizarlo? / Intravenous sodium bicarbonate. When, how and why to use it?

Severe metabolic acidosis is defined by a pH < 7.2 with HCO3− < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.

Aplicación de la técnica WALANT en las cirugías de mano / Use of WALANT Technique in Hand Surgeries

Introducción: En los últimos años la anestesia local sin torniquete y con el paciente despierto, técnica conocida por WALANT (por sus siglas en inglés), ha ganado mucha popularidad en las cirugías de la mano y la muñeca. Objetivo: Reportar nuestra experiencia con el uso de la técnica WALANT, a fin de prescindir del uso del torniquete en las cirugías de la mano. Métodos: En noviembre del 2020 fueron intervenidos 30 pacientes por diversas enfermedades ortopédicas, entre las que figuraron: dedos en resorte, síndrome del túnel carpiano, tenovaginitis estenosante del pulgar, gangliones del carpo y amputación del tercer radio por rigidez en extensión postraumática, entre otras. Para la evaluación de la técnica tuvimos en cuenta: tiempo quirúrgico, magnitud del sangrado, dolor durante la infiltración anestésica, la intervención, y en las primeras 24 horas del postoperatorio, la necesidad de refuerzo anestésico, uso de isquemia, complicaciones y nivel de satisfacción del paciente. Resultados: Los resultados obtenidos con esta técnica anestésica son semejantes a otras, con las ventajas que el sangrado es leve, no hay que utilizar isquemia, el tiempo quirúrgico es menor y el efecto anestésico duró entre 10 y 12 horas en todos los pacientes. En ninguno de los pacientes hubo necesidad de refuerzo anestésico. Conclusiones: Se demuestra la efectividad de la técnica WALANT en las cirugías de mano. Con ella se disminuye el gasto de materiales para el acto quirúrgico, así como de personal, es de fácil aplicación y disminuyen las sensaciones desagradables y los peligros del uso de isquemia en los pacientes(AU)

Introduction: Currently, the use of local anaesthetic with no tourniquet and wide awake patient (Wide Awake Local Anaesthetic No Tourniquet - WALANT) has gained popularity in surgeries of the hand and wrist. Objective: To report our experience in the use of WALANT technique in order to discard the use of tourniquet in hand surgeries. Method: In November 2020, thirty patients underwent surgery due to different orthopaedic conditions, among them trigger fingers, carpal tunnel syndrome, stenosing tenovaginitis of the thumb, carpal ganglion and amputation of the third radius due to post trauma stiffness, among others. In order to assess this technique, we considered surgical time, volume of bleeding, pain during anesthetic infiltration, intervention and the need for additional anesthetic during the first 24 hours after surgery; we considered also ischemia, complications and level patient´s satisfaction. Results: This technique had similar results to others; however, the bleeding is mild, there is no need for ischemia, the surgical time is lesser and the anesthetic effect lasted 10 to 12 hours in all patients. None of them required additional anesthetic. All subjects felt the initial infiltration but none complained of pain during the rest of the anesthetic injection or during the surgical act. There were no complications. Conclusions: The effectiveness of WALANT technique in hand surgeries is shown. The cost of materials for the surgical act is reduced with it, as well as the surgical staff, it is easy to use and unpleasant sensations and dangers of the use of ischemia in patients are reduced(AU)

Determinants of hypokalemia following hypertonic sodium bicarbonate infusion.

The hypokalemic response to alkali infusion has been attributed to the resulting extracellular fluid (ECF) expansion, urinary potassium excretion, and internal potassium shifts, but the dominant mechanism remains uncertain. Hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) to unanesthetized dogs with normal acid-base status or one of the four chronic acid-base disorders decreased plasma potassium concentration ([K+]p) at 30 min in all study groups (Δ[K+]p, - 0.16 to - 0.73 mmol/L), which remained essentially unaltered up to 90-min postinfusion. ECF expansion accounted for only a small fraction of the decrease in ECF potassium content, (K+)e. Urinary potassium losses were large in normals and chronic respiratory acid-base disorders, limited in chronic metabolic alkalosis, and minimal in chronic metabolic acidosis, yet, ongoing kaliuresis did not impact the stability of [K+]p. All five groups experienced a reduction in (K+)e at 30-min postinfusion, Δ(K+)e remaining unchanged thereafter. Intracellular fluid (ICF) potassium content, (K+)i, decreased progressively postinfusion in all groups excluding chronic metabolic acidosis, in which a reduction in (K+)e was accompanied by an increase in (K+)i. We demonstrate that hypokalemia following hypertonic NaHCO3 infusion in intact animals with acidemia, alkalemia, or normal acid-base status and intact or depleted potassium stores is critically dependent on mechanisms of internal potassium balance and not ECF volume expansion or kaliuresis. We envision that the acute NaHCO3 infusion elicits immediate ionic shifts between ECF and ICF leading to hypokalemia. Thereafter, maintenance of a relatively stable, although depressed, [K+]e requires that cells release potassium to counterbalance ongoing urinary potassium losses.

Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans.

PURPOSE: To investigate the suitability of microdosed oral omeprazole for predicting CYP2C19 activity in vivo in combination with simultaneous assessment of CYP3A and CYP2D6 activity using both microdosed midazolam and yohimbine. METHODS: An open, fixed-sequence study was carried out in 20 healthy participants. Single microdosed (100 µg) and therapeutic (20 mg) doses of omeprazole were evaluated without comedication and after administration of established CYP2C19 perpetrators fluconazole (inhibition) and rifampicin (induction). To prevent degradation of the uncoated omeprazole microdose, sodium bicarbonate buffer was administered. The pharmacokinetics of omeprazole and its 5-hydroxy-metabolite were assessed as well as the pharmacokinetics of midazolam and yohimbine to estimate CYP3A4 and CYP2D6 activity. RESULTS: Calculated pharmacokinetic parameters after administration of 100 µg and 20 mg omeprazole in healthy subjects suggest dose proportionality. Omeprazole clearance was significantly decreased by fluconazole from 388 [95% CI: 266-565] to 47.2 [42.8-52.0] mL/min after 20 mg omeprazole and even further after 100 µg omeprazole (29.4 [24.5-35.1] mL/min). Rifampicin increased CYP2C19-mediated omeprazole metabolism. The omeprazole hydroxylation index was significantly related to omeprazole clearance for both doses. Both fluconazole and rifampicin altered CYP3A4 activity whereas no change of CYP2D6 activity was observed at all. CONCLUSIONS: Microdosed oral omeprazole is suitable to determine CYP2C19 activity, also during enzyme inhibition and induction. However, the administration of sodium bicarbonate buffer also had a small influence on all victim drugs used. TRIAL REGISTRATION: EudraCT: 2017-004270-34.

[Intravenous sodium bicarbonate. When, how and why to use it?] / Bicarbonato de sodio intravenoso ¿Cuándo, cómo y por qué utilizarlo?

Severe metabolic acidosis is defined by a pH < 7.2 with HCO3- < 8 mE- q/L in plasma. Its best treatment is to correct the underlying cause. However, acidemia produces multiple complications such as resistance to the action of catecholamines, pulmonary vasoconstriction, impaired cardiovascular function, hyperkalemia, immunological dysregulation, respiratory muscle fatigue, neurological impairment, cellular dysfunction, and finally, it contributes to multisystemic failure. Intravenous NaHCO3 buffers severe acidemia, preventing the associated damage and gains time while the causal disease is corrected. Its indication requires a risk-benefit assessment, considering its complications. These are hypernatremia, hypokalemia, ionic hypocalcemia, rebound alkalosis, and intracellular acidosis. For this reason, therapy must be "adapted" and administered judiciously. The patient will require monitoring with serial evaluation of the internal environment, especially arterial blood gases, plasma electrolytes, and ionized calcium. Isotonic solutions should be preferred instead of hypertonic bicarbonate. The development of hypernatremia must be prevented, calcium must be provided for hypocalcemia to improve cardiovascular function. Furthermore, in mechanically ventilated patients, a respiratory response similar to the one that would develop physiologically, must be established to be able to extract excess CO2 and thus avoid intracellular acidosis. It is possible to estimate the bicarbonate deficit, speed, and volume of its infusion. However, the calculations are only for reference. More important is to start intravenous NaHCO3 when needed, administer it judiciously, manage its side effects, and continue it to a safe goal. In this review we address all the necessary elements to consider in the administration of intravenous NaHCO3, highlighting why it is the best buffer for the management of severe metabolic acidosis.

The impact of stenting prior to oral chemolysis of upper urinary tract uric acid stones.

PURPOSE: To evaluate the impact of ureteral stenting on the success rate of oral chemolysis in the management of suspected uric acid upper urinary tract (UUT) stones. METHODS: Retrospective matched-pair analysis of 172 patients treated with oral chemolysis from 01/2010 to 12/2019. Patients with low density (upon non-contrast enhanced computer tomography [NCCT]), radiolucent (on plain radiography) urinary stones, a low urine pH (< 6) and/or history of uric acid urolithiasis were included. Potassium citrate and/or sodium bicarbonate were used for alkalization (target urine pH: 6.5-7.2). Patient 1:1 matching was performed for the presence of indwelling ureteral stent, stone diameter, stone density, and stone localization. Stone-free status was evaluated after 12 weeks using NCCT. Multivariable logistic regression analysis was used to assess factors affecting the outcome. RESULTS: Mean patient age was 61 years (73% males). Mean stone size was 12 mm. Overall success rates after 12-weeks of chemolysis for stones at any localization in the UUT and ureteral stones were 60.5 and 77.3%, respectively. Smaller stone size (OR = 0.94; CI 0.888-0.992; p = 0.026) and lower pre-treatment urine pH (OR = 0.131; CI 0.023-0.737; p = 0.021) significantly increased the success of oral chemolysis. Ureteral stenting did not have any impact on the efficacy of oral chemolysis. CONCLUSION: Oral chemolysis is an effective treatment modality for patients with UUT stones suspected of uric acid content irrespective of ureteral stenting. Smaller stone diameter and lower urine pH at diagnosis increase its efficacy.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Oral sodium bicarbonate in people on haemodialysis: a randomised controlled trial.

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 .

Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. METHODS: This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. RESULTS: Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. CONCLUSIONS: The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.