Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT.

BACKGROUND: Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. OBJECTIVES: The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. DESIGN: A parallel-group, double-blind, placebo-controlled randomised trial. SETTING: The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. PARTICIPANTS: Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of < 22 mmol/l. INTERVENTIONS: Eligible participants were randomised 1 : 1 to oral sodium bicarbonate or matching placebo. Dosing started at 500 mg three times daily, increasing to 1 g three times daily if the serum bicarbonate concentration was < 22 mmol/l at 3 months. MAIN OUTCOME MEASURES: The primary outcome was the between-group difference in the Short Physical Performance Battery score at 12 months, adjusted for baseline. Other outcome measures included generic and disease-specific health-related quality of life, anthropometry, 6-minute walk speed, grip strength, renal function, markers of bone turnover, blood pressure and brain natriuretic peptide. All adverse events were recorded, including commencement of renal replacement therapy. For the health economic analysis, the incremental cost per quality-adjusted life-year was the main outcome. RESULTS: In total, 300 participants were randomised, 152 to bicarbonate and 148 to placebo. The mean age of participants was 74 years and 86 (29%) were female. Adherence to study medication was 73% in both groups. A total of 220 (73%) participants were assessed at the 12-month visit. No significant treatment effect was evident for the primary outcome of the between-group difference in the Short Physical Performance Battery score at 12 months (-0.4 points, 95% confidence interval -0.9 to 0.1 points; p = 0.15). No significant treatment benefit was seen for any of the secondary outcomes. Adverse events were more frequent in the bicarbonate arm (457 vs. 400). Time to commencement of renal replacement therapy was similar in both groups (hazard ratio 1.22, 95% confidence interval 0.74 to 2.02; p = 0.43). Health economic analysis showed higher costs and lower quality of life in the bicarbonate arm at 1 year, with additional costs of £564 (95% confidence interval £88 to £1154) and a quality-adjusted life-year difference of -0.05 (95% confidence interval -0.08 to -0.01); placebo dominated bicarbonate under all sensitivity analyses for incremental cost-effectiveness. LIMITATIONS: The trial population was predominantly white and male, limiting generalisability. The increment in serum bicarbonate concentrations achieved was small and a benefit from larger doses of bicarbonate cannot be excluded. CONCLUSIONS: Oral sodium bicarbonate did not improve a range of health measures in people aged ≥ 60 years with chronic kidney disease category 4 or 5 and mild acidosis, and is unlikely to be cost-effective for use in the NHS in this patient group. Once other current trials of bicarbonate therapy in chronic kidney disease are complete, an individual participant meta-analysis would be helpful to determine which subgroups, if any, are more likely to benefit and which treatment regimens are more beneficial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.

Patients with advanced chronic kidney disease often have excessive levels of acid in their blood (acidosis). Acidosis has been associated with a range of other problems that particularly affect patients with chronic kidney disease, including weaker muscles, weaker bones, worse blood vessel health and kidney disease that worsens more quickly. For decades, acidosis has been treated with sodium bicarbonate tablets (the ingredient found in baking soda) to neutralise the excess acid. However, sodium bicarbonate is awkward to take, may cause side effects and may increase blood pressure. To clarify whether or not sodium bicarbonate caused an overall improvement in health, we carried out a study involving 300 people aged ≥ 60 years with advanced chronic kidney disease and mild acidosis. Half received sodium bicarbonate capsules and half received dummy capsules (placebo), for up to 2 years. The treatments were chosen randomly by a computer and the participants, their doctors and the researchers were not aware of the treatment received until the end of the study. We measured physical function (walking speed, ability to stand from a chair, balance) alongside quality of life, kidney function, bone and blood vessel health, side effects and health service use over 2 years. We found that sodium bicarbonate did not improve physical function or quality of life compared with placebo. Sodium bicarbonate also did not improve kidney function, bone health or blood vessel health compared with placebo. More people in the sodium bicarbonate group than in the placebo group had side effects, although blood pressure was the same in both groups. Health-care costs were higher in the sodium bicarbonate group than in the placebo group. We conclude that oral sodium bicarbonate did not significantly improve health measures compared with placebo for older people (aged ≥ 60 years) with advanced chronic kidney disease associated with mild acidosis.

Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial.

BACKGROUND: Chronic kidney disease with metabolic acidosis is common in older people, but the effectiveness of oral sodium bicarbonate therapy in this group is unclear. We tested whether oral sodium bicarbonate provides net health benefit for older people with advanced chronic kidney disease and serum bicarbonate concentrations < 22 mmol/L. METHODS: Pragmatic multicentre, parallel group, double-blind, placebo-controlled randomised trial. We recruited adults aged ≥ 60 years with estimated glomerular filtration rate of < 30 mL/min/1.73 m2, not receiving dialysis, with serum bicarbonate concentration < 22 mmol/L, from 27 nephrology and geriatric medicine departments in the UK. Participants received oral sodium bicarbonate (up to 3 g/day) or matching placebo given for up to 2 years, randomised in a 1:1 ratio. The primary outcome was between-group difference in the Short Physical Performance Battery (SPPB) at 12 months, adjusted for baseline values, analysed by intention to treat. Secondary outcomes included generic and disease-specific quality of life (EQ-5D and KDQoL tools), anthropometry, renal function, walk distance, blood pressure, bone and vascular health markers, and incremental cost per quality-adjusted life year gained. RESULTS: We randomised 300 participants between May 2013 and February 2017, mean age 74 years, 86 (29%) female. At 12 months, 116/152 (76%) participants allocated to bicarbonate and 104/148 (70%) allocated to placebo were assessed; primary outcome data were available for 187 participants. We found no significant treatment effect for the SPPB: bicarbonate arm 8.3 (SD 2.5) points, placebo arm 8.8 (SD 2.2) and adjusted treatment effect - 0.4 (95% CI - 0.9 to 0.1, p = 0.15). We found no significant treatment effect for glomerular filtration rate (0.6 mL/min/1.73 m2, 95% CI - 0.8 to 2.0, p = 0.39). The bicarbonate arm showed higher costs and lower quality of life as measured by the EQ-5D-3L tool over 1 year (£564 [95% CI £88 to £1154]); placebo dominated bicarbonate under all sensitivity analyses. Adverse events were more frequent in those randomised to bicarbonate (457 versus 400). CONCLUSIONS: Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group. TRIAL REGISTRATION: European Clinical Trials Database (2011-005271-16) and ISRCTN09486651; registered 17 February 2012.

The Prevalence and Management of Metabolic Acidosis of Chronic Kidney Disease

Aim Emerging evidence supports initiating oral sodium bicarbonate (OSB) at a serum bicarbonate (HCO3) level of less than 22mmol/L. We look to identify the prevalence of metabolic acidosis of chronic kidney disease (MA-CKD) and its management with OSB at a regional university hospital. Methods Retrospective data was collected using the national electronic renal database (eMED) to identify chronic kidney disease (CKD) patients with MA-CKD over a one-year period. Results One-hundred and forty-four patients were identified with CKD, of which 131 (89%) were tested for HCO3. MA-CKD was present in 44 patients (34%), all had eGFR< 30ml/min/1.73m2, 7 (16%) were prescribed OSB, 7(16%) OSB was contraindicated, and 37 (84%) patients managed with dietary input only. Mean HCO3 level at initiation in OSB group was 18.3±1mmol/L compared to 19.4±1.4mmol/L in dietary input only group which was statistically significant (p<0.05). Conclusion A high burden of advanced CKD was found in the regional nephrology centre, with one third of patients demonstrating MA-CKD. Majority had dietary input only. Further awareness and consensus need to be established on the benefits of treating MA-CKD with OSB.

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial.

BACKGROUND: Metabolic acidosis is more common with advancing chronic kidney disease, and has been associated with impaired physical function, impaired bone health, accelerated decline in kidney function and increased vascular risk. Although oral sodium bicarbonate is widely used to correct metabolic acidosis, there exist potential risks of therapy including worsening hypertension and fluid overload. Little trial evidence exists to decide whether oral bicarbonate therapy is of net benefit in advanced chronic kidney disease, particularly in older people who are most commonly affected, and in whom physical function, quality of life and vascular health are at least as important outcomes as decline in renal function. METHODS/DESIGN: BiCARB is a multi-centre, double-blind, placebo controlled, randomised trial evaluating the clinical and cost-effectiveness of oral sodium bicarbonate in the management of older people with chronic kidney disease and severely reduced glomerular filtration rate (GFR) who have a mild degree of metabolic acidosis. The trial will recruit 380 patients from renal, Medicine for the Elderly, and primary care services across centres in the United Kingdom. Male and female patients aged 60 years and older with an estimated glomerular filtration rate of <30 mL/min/1.73 m(2), not on dialysis, and with serum bicarbonate concentrations <22 mmol/L will be eligible for participation. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at 12 months. Secondary outcomes include muscle strength, quality of life measured using the EQ-5D score and KDQoL tools, cost effectiveness, renal function, presence of albuminuria and blood pressure. Markers of bone turnover (25-hydroxyvitamin D, 1,25-hydroxyvitamin D, tartrate-resistant acid phosphatase-5b and bone-specific alkaline phosphatase) and vascular health (B-type natriuretic peptide) will be measured. Participants will receive a total of 24 months of either bicarbonate or placebo. The results will provide the first robust test of the overall clinical and cost-effectiveness of this commonly used therapy in older patients with severely reduced kidney function. TRIAL REGISTRATION: www.isrctn.com; ISRCTN09486651, registered 17 February 2012.

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea.

BACKGROUND: The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. RESULTS: After being lifted, many calves were able to stand despite base excess levels below -20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below -5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. CONCLUSIONS: Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250 mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis.

[Assessment of in vitro activity and stability of antifungal suspensions for mouthrinses: to a reappraisal of empiric practices?]. / Étude d'activité in vitro et de stabilité de suspensions antifongiques pour bain de bouche : vers une remise en question de pratiques empiriques ?

Establishment of an effective prophylaxis against oral candidiasis by local treatment is essential for immunocompromised patients. The aim of the study is to assess effectiveness and stability of antifungal suspensions for mouthrinses. The assessed suspensions are compounded by one solvent among sterile water, spring water or sodium bicarbonate associated with amphotericin B (Fungizone®) or nystatine (Mycostatine®). Two others mixes are assessed: Mycostatine®-bicarbonate and Mycostatine®-Hextril®-bicarbonate as well as the two straight antifungal. In vitro activity is tested on five Candida species (C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis) after a five minutes contact between yeasts and the assessed suspension. A galenic study is realized during 3 days. Mixes associating a polyene with sodium bicarbonate have no effectiveness on Candida albicans, others mixes shows intermediate effectiveness (the percentage of yeast growth inhibition lies between 35% and 68%). Effectiveness results of Hextril®-based mixes are not explainable because of alcohol in its composition. Spring water-based mixes must be evicted due to microbiologic contaminations after 48hours. Mycostatine®-Hextril®-bicarbonate mix is not stable during 3 days. All those mouthrinses, poorly effective, excepted on C. glabrata, should be avoided. Straight Mycostatine® shows a good antifungal effectiveness excepted on C. krusei and its use should be recommended.

Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo.

Methods for the simultaneous polarization of multiple 13C-enriched metabolites were developed to probe several enzymatic pathways and other physiologic properties in vivo, using a single intravenous bolus. A new method for polarization of 13C sodium bicarbonate suitable for use in patients was developed, and the co-polarization of 13C sodium bicarbonate and [1-(13)C] pyruvate in the same sample was achieved, resulting in high solution-state polarizations (15.7% and 17.6%, respectively) and long spin-lattice relaxation times (T1) (46.7 s and 47.7 s respectively at 3 T). Consistent with chemical shift anisotropy dominating the T1 relaxation of carbonyls, T1 values for 13C bicarbonate and [1-(13)C] pyruvate were even longer at 3 T (49.7s and 67.3s, respectively). Co-polarized 13C bicarbonate and [1-(13)C] pyruvate were injected into normal mice and a murine prostate tumor model at 3T. Rapid equilibration of injected hyperpolarized 13C sodium bicarbonate with 13C CO2 allowed calculation of pH on a voxel by voxel basis, and simultaneous assessment of pyruvate metabolism with cellular uptake and conversion of [1-(13)C] pyruvate to its metabolic products. Initial studies in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model demonstrated higher levels of hyperpolarized lactate and lower pH within tumor, relative to surrounding benign tissues and to the abdominal viscera of normal controls. There was no significant difference observed in the tumor lactate/pyruvate ratio obtained after the injection of co-polarized 13C bicarbonate and [1-(13)C] pyruvate or polarized [1-(13)C] pyruvate alone. The technique was extended to polarize four 13C labelled substrates potentially providing information on pH, metabolism, necrosis and perfusion, namely [1-(13)C]pyruvic acid, 13C sodium bicarbonate, [1,4-(13)C]fumaric acid, and 13C urea with high levels of solution polarization (17.5%, 10.3%, 15.6% and 11.6%, respectively) and spin-lattice relaxation values similar to those recorded for the individual metabolites. These studies demonstrated the feasibility of simultaneously measuring in vivo pH and tumor metabolism using nontoxic, endogenous species, and the potential to extend the multi-polarization approach to include up to four hyperpolarized probes providing multiple metabolic and physiologic measures in a single MR acquisition.

Evaluation of relationship between arterial and venous blood gas values in the patients with tricyclic antidepressant poisoning.

INTRODUCTION: Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients. METHODS: This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method. RESULTS: Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation. CONCLUSION: In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.

Otic drops used to clear a blocked grommet: an in vitro prospective randomized controlled study with blinded assessment.

Clinicians often prescribe otic drops anecdotally to try and clear grommets blocked with blood. We carried out an in vitro double-blind randomized controlled study comparing the efficacy of sodium bicarbonate, Locorten Vioform and olive oil drops in clearing Shah grommets placed in 'artificial ears' and blocked with blood in a standardized fashion. There were 33 grommets in each group, and drops were inserted three times a day for 7 days. Olive oil drops cleared 17 of 33 (51.51%), Locorten Vioform cleared one of 33 (3%) and sodium bicarbonate cleared zero of 33 (0%) blocked grommets. Statistical comparison between pairs indicates that olive oil was significantly better than both Locorten Vioform (P < 0.001) and sodium bicarbonate drops (P < 0.001) at clearing grommets blocked with blood.

Automated on-line bicarbonate concentrate production: microbiological, chemical and economic benefits.

We all know that "bicarbonate dialysate" became the world wide used fluid for use in haemodialysis and related techniques. To prepare bicarbonate dialysate we actually have to use two separate concentrates: one containing sodium bicarbonate, solely or in combination with other electrolytes other than calcium, and a second concentrate containing mostly all the other electrolytes (sodium, magnesium, potassium, chloride and/or some acetate).

In vitro buffering capacities of proprietary non-particulate antacids available in New Zealand.

Four commercially available non-particulate antacid preparations were titrated against 1M hydrochloric acid to assess buffering capacity as compared to 30 ml 0.3M sodium citrate solution. All antacids were used in the manufacturers "unit dose". All antacids tested demonstrated some in vitro buffering capacity, and "Eno" (Reckitt and Colman) had a buffering capacity similar to that of sodium citrate. The retail cost per unit dose was established for each proprietary antacid and for sodium citrate. It was concluded that while proprietary antacids are cheaper per dose than sodium citrate, preparations differ in their acid-neutralising capacity.