Administration Of Bicarbonate Research Articles

Effect of early clinical management on metabolic acidemia in neonates with hypoxic-ischemic encephalopathy.

To determine the safety and effectiveness of sodium bicarbonate administration in the management of metabolic acidemia and short-term outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). Retrospective cohort study of neonates born at ≥35 weeks of gestation and receiving therapeutic hypothermia. Demographics, pH, lactate, base deficit, treatment, MRI findings, seizure incidence, death prior to discharge were collected. There was higher mortality (p = 0.010) and injury on MRI (p = 0.008)-primarily deep gray matter (p < 0.001) and cortical injury (p = 0.003)-in the bicarbonate groupcompared to controls in univariate analysis. The combined outcome of death or abnormal MRI was not significantly associated (OR 1.97, 95% CI 0.80-4.87, p = 0.141) with bicarbonate administration when adjusting for sex, 5-minute Apgar, and initial base deficit. This study demonstrated association between bicarbonate use after HIE and negative short-term outcomes. Future prospective trials could overcome the treatment bias limitation demonstrated in this retrospective study.

Lyophilized rumen fluid as a ruminal fermentation modifier in high grain-fed acidotic goats.

Rumen cud transfaunation re-establishes rumen micro environment and improves fermentation in recipient animals affected with digestive disorders. Preserving rumen cud or fluid will increase its availability for the treatment of rumen fermentation disorders, without having to maintain donor animals. Rumen fluid collected from healthy goats, fed standard ration having roughage 70% and concentrate 30%, was lyophilized (prefreezing -80°C, 48h; lyophilization -45°C, 32h) using 5% glycerol as cryoprotectant. The 16 S metagenome analysis of the lyophilized rumen fluid (LRF) revealed an abundance of Prevotella (33.2%). Selenomonas ruminantium (1.87%) and Megasphaera elsdenii (0.23%) were also present. Twenty-four goats having history of high grain feeding and exhibiting clinical symptoms of rumen fermentation disorders were randomly distributed into either one of the two treatment groups viz., T1 = oral administration of LRF 31g/animal/day and T2 = oral administration of sodium bicarbonate (SB) 15g/animal/day. Post intervention LRF and SB, improved animal body condition, feed intake, fecal consistency, elevated the ruminal pH at 48h, reduced propionate and lactate at 48h, reduced total volatile fatty acids (TVFA) and ammonia nitrogen at 24h. Significant reduction in serum blood urea nitrogen (BUN) and urea levels were observed even from 24h post intervention irrespective of the treatments. LRF significantly improved acetate and decreased propionate production compared to SB. LRF at 7.5% (v/v) can thus be used to counteract ruminal fermentation disorders in goats sequel to high grain ration.

Assessing Cognition in Chronic Kidney Disease Using the NIH Toolbox®.

Chronic kidney disease (CKD) is largely an age-related clinical disorder with accelerated cognitive and cardiovascular aging. Cognitive impairment is a well-documented occurrence in midlife and older adults with CKD and affects multiple domains. We examined cognition function and potential sex differences in cognition in adults with CKD. We included 105 individuals (49.5% women) with CKD stage 3b-4 (eGFR 15-44 mL/min) from the Bicarbonate Administration in CKD Trial (NCT02915601). We measured cognitive function using the National Institutes of Health (NIH) Toolbox® Cognition Battery, which assesses cognitive and motor measures such as executive function, attention, memory, and dexterity. All study measures were collected and analyzed at the study baseline. The mean (SD) age and eGFR were 61 ± 12 years and 34.9 ± 9.8 mL/min/1.73m2. Overall, when compared to the NIH Toolbox reference population, participants scored, on average, below the 50th percentile across all cognitive domain tests and the dexterity test. Total cognition scores were also below the 50th percentile. Participants with stage 4 CKD had significantly lower fluid cognition scores compared to those with CKD stage 3b (β-Estimate -5.4 (95% CI-9.8 to -0.9); p=0.03). Female participants with CKD performed significantly better on the episodic memory tests and dexterity tests (dominant and non-dominant pegboard tests), and had higher crystallized cognition scores, on average, compared to males. Participants with CKD had detectable cognitive deficits in fluid cognition, dexterity, and total cognition. Additionally, sex differences in cognitive measures were found among people with CKD.

Potential of Alkalization Therapy for the Management of Metastatic Pancreatic Cancer: A Retrospective Study.

Current treatments for patients with pancreatic cancer offer limited benefits. In this study, we applied alkalization therapy, which was efficacious for other solid tumors at our clinic, to stage 4 pancreatic cancer patients, and investigated its effect on disease prognosis. Patients with metastatic pancreatic cancer who were treated at Karasuma Wada Clinic in Kyoto, Japan, between January 2011 and April 2022, were included in the study. All patients received alkalization therapy (a combination of an alkaline diet, bicarbonate, and citric acid administration), alongside standard chemotherapy. Urine samples were collected to assess urine pH as a marker of whole-body alkalization. In the 98 patients analyzed, the median overall survival (OS) from the time of diagnosis was 13.2 months. Patients with a mean urine pH of 7.5 or greater had a median OS of 29.9 months, compared with 15.2 months for those with a mean urine pH of 6.5 to 7.5, and 8.0 months for those with a mean urine pH of less than 6.5, which suggests a trend of a longer OS in patients with a higher urine pH (p = 0.0639). Alkalization therapy may offer a viable approach to extending the survival of stage 4 pancreatic cancer patients, who typically have an unfavorable prognosis.

End-tidal carbon dioxide after sodium bicarbonate infusion during mechanical ventilation or ongoing cardiopulmonary resuscitation

PurposeEnd-tidal CO2 is used to monitor the ventilation status or hemodynamic efficacy during mechanical ventilation or cardiopulmonary resuscitation (CPR), and it may be affected by various factors including sodium bicarbonate administration. This study investigated changes in end-tidal CO2 after sodium bicarbonate administration. Materials and methodsThis single-center, prospective observational study included adult patients who received sodium bicarbonate during mechanical ventilation or CPR. End-tidal CO2 elevation was defined as an increase of ≥20% from the baseline end-tidal CO2 value. The time to initial increase (lag time, Tlag), time to peak (Tpeak), and duration of the end-tidal CO2 rise (Tduration) were compared between the patients with spontaneous circulation (SC group) and those with ongoing resuscitation (CPR group). ResultsThirty-three patients, (SC group, n = 25; CPR group, n = 8), were included. Compared with the baseline value, the median values of peak end-tidal CO2 after sodium bicarbonate injection increased by 100% (from 21 to 41 mmHg) in all patients, 89.5% (from 21 to 39 mmHg) in the SC group, and 160.2% (from 15 to 41 mmHg) in the CPR group. The median Tlag was 17 s (IQR: 12–21) and the median Tpeak was 35 s (IQR: 27–52). The median Tduration was 420 s (IQR: 90–639). The median Tlag, Tpeak, and Tduration were not significantly different between the groups. Tduration was associated with the amount of sodium bicarbonate for SC group (correlation coefficient: 0.531, p = 0.006). ConclusionThe administration of sodium bicarbonate may lead to a substantial increase in end-tidal CO2 for several minutes in patients with spontaneous circulation and in patients with ongoing CPR. After intravenous administration of sodium bicarbonate, the use of end-tidal CO2 pressure as a physiological indicator may be limited.

Adverse Impact of Sodium Bicarbonate Administration on Multiple Outcomes in Acute Pancreatitis Patients With Hyperlactatemia.

Hyperlactatemia is likely to occur among patients with acute pancreatitis (AP). Sodium bicarbonate (SB) therapy could be applied to correct potential detrimental acidic disturbances, but the exact impact of SB treatment is unknown. This study aims to investigate the impact of SB on AP patients complicated with hyperlactatemia. The study was conducted based on the database named Medical Information Mart for Intensive Care-IV (MIMIC-IV). Propensity matching (PSM) and inverse probability weighting (IPTW) were used to balance the baseline differences. Multivariate regression and marginal structural Cox models were performed to investigate the association between SB and multiple outcomes. Three hundred fifty-three AP patients with hyperlactatemia (initial serum lactate, >2.0 mmol/L) were extracted from the MIMIC-IV database. We found that SB treatment was significantly associated with worse multi-outcomes of AP patients with hyperlactatemia (in-hospital mortality: hazard ratio, 2.46; 95% confidence interval, 1.38-4.39; P < 0.01). Further analysis through marginal structural Cox models showed that SB had adverse impact on in-hospital prognosis of patients with severe lactic acidosis (pH < 7.15,lactate > 2.0 mmol/L). Sodium bicarbonate might not be an appropriate treatment for AP patients with hyperlactatemia (lactate > 2.0 mmol/L) or with severe lactic acidosis (pH < 7.15, lactate > 2.0 mmol/L).

Abstract 16851: Tricyclic Antidepressant Induced Wide Complex Tachycardia With Brugada Pattern

Case Description: A 52-year-old male with bipolar disorder and depression was brought to the ED after he was found confused following an episode of syncope. He reported taking 5 pills of his new dose of Nortriptyline 75mg instead of 5 pills of his previous dose of Nortriptyline 25mg. ECG from the field showed a wide complex tachycardia (WCT) with a rightward axis and a Brugada pattern in V1 and V2 at a rate of 120-130s. Upon arrival in the ED, he continued to have WCT, and was treated with Amiodarone, Magnesium Sulfate, and Sodium Bicarbonate. Following treatment, his heart rate improved and the QRS duration shortened with a gradual loss of Brugada pattern (Figure 1). Six hours from initial presentation, his QRS completely normalized. Transthoracic echocardiogram (TTE) showed normal LV function. His presentation was consistent with tricyclic antidepressant (TCA) overdose. Discussion: The cardiotoxic effects of TCAs are mediated through their behavior as class IA antiarrhythmic drugs. This results in lengthening of both depolarization and repolarization of the cardiac action potential resulting in a widened QRS complex and QT prolongation. Sodium channel blockade can precipitate a Brugada phenotype which resolves after Sodium Bicarbonate administration. Similar to class IA agents, TCAs also exhibit use dependence and in our patient, the Brugada pattern began to resolve soon after presentation, possibly due to slowing of the tachycardia. Recognition of TCA toxicity is important to allow for timely administration of bicarbonate which facilitates prompt reversal.

Sodium Bicarbonate and Calcium Chloride for the Treatment of Hyperkalemia-Induced Cardiac Arrest: A Randomized, Blinded, Placebo-Controlled Animal Study.

Current international guidelines recommend administrating calcium chloride and sodium bicarbonate to patients with hyperkalemia-induced cardiac arrest, despite limited evidence. The aim of this study was to evaluate the efficacy of calcium chloride and sodium bicarbonate on return of spontaneous circulation (ROSC) in a pig model of hyperkalemia-induced cardiac arrest. A randomized, blinded, placebo-controlled experimental pig study. Hyperkalemia was induced by continuous infusion of potassium chloride over 45 minutes followed by a bolus. After a no flow period of 7 minutes, pigs first received 2 minutes of basic cardiopulmonary resuscitation and subsequently advanced life support. The first intervention dose was administered after the fifth rhythm analysis, followed by a defibrillation attempt at the sixth rhythm analysis. A second dose of the intervention was administered after the seventh rhythm analysis if ROSC was not achieved. In case of successful resuscitation, pigs received intensive care for 1 hour before termination of the study. University hospital laboratory. Fifty-four female Landrace/Yorkshire/Duroc pigs (38-42 kg). The study used a 2 × 2 factorial design, with calcium chloride (0.1 mmol/kg) and sodium bicarbonate (1 mmol/kg) as the interventions. Fifty-two pigs were included in the study. Sodium bicarbonate significantly increased the number of animals achieving ROSC (24/26 [92%] vs. 13/26 [50%]; odds ratio [OR], 12.0; 95% CI, 2.3-61.5; p = 0.003) and reduced time to ROSC (hazard ratio [HR] 3.6; 95% CI, 1.8-7.5; p < 0.001). There was no effect of calcium chloride on the number of animals achieving ROSC (19/26 [73%] vs. 18/26 [69%]; OR, 1.2; 95% CI, 0.4-4.0; p = 0.76) or time to ROSC (HR, 1.5; 95% CI, 0.8-2.9; p = 0.23). Administration of sodium bicarbonate significantly increased the number of animals achieving ROSC and decreased time to ROSC. There was no effect of calcium chloride on the number of animals achieving ROSC or time to ROSC.

Comparison of the Effect of Oral Sodium Bicarbonate and Tolterodine in Women with Symptoms of Overactive Bladder with Acidic Urine- A Single-Blind Randomized Clinical Trial

Background: Urine alkalinization with oral sodium bicarbonate seems to improve urinary symptoms in female patients with overactive bladder with acidic urinary pH. Aim: Therefore, the aim of this study was to compare the effect of oral sodium bicarbonate and tolterodine in women with symptoms of overactive bladder with acidic urinary pH. Methods: In this single-blind randomized clinical trial, 72 female patients with symptoms of overactive bladder syndrome with acidic urinary pH in the age group of 28-60 years were referred to the gynecology clinic of Mahdieh Hospital affiliated with Shahid Beheshti University of Medical Sciences, Tehran, Iran in 2021-2022 were studied. These patients were randomly divided into two groups oral sodium bicarbonate (36 patients) and tolterodine group (36 patients) and received the treatment for one month. Group matching was performed between patients. At the end of the study, the Overactive Bladder- Validated 8-question Awareness tool (OAB-V8), frequency, nocturia, urgency, and urinary incontinence (UI) was measured and compared between patients in the two groups. Results: Patients were matched for age, underlying disease, BMI, acidic urinary pH, and menopause status at the baseline. After 30 days of medication therapy, a significant decrease in OAB-V8 score, frequency, nocturia, urgency, and urinary incontinence (UI) was observed in both groups receiving oral sodium bicarbonate and tolterodine in female patients with symptoms of overactive bladder syndrome with acidic urine. The degree of improvement in outcomes after treatment was similar between both groups. Conclusion: Oral sodium bicarbonate administration in patients with overactive bladder with acidic urinary pH has a significant positive effect on OAB-V8 symptoms, frequency, nocturia, urgency, and urinary incontinence (UI) and these results are similar to tolterodine treatment. Given that the acidic urinary pH may play a role in the etiology of an overactive bladder, it seems that sodium bicarbonate improves the symptoms of an overactive bladder by alkalizing the urine. Clinical Trial Registration Number: The clinical studies were registered in the Iranian clinical trial database at irct.ir (IRCT20131203015634N3).

Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model.

Triple-negative breast cancer (TNBC), as one of the most aggressive forms of breast cancer, is characterized by a poor prognosis and a very low rate of disease-free and overall survival. In recent years, immunotherapeutic approaches targeting T cell checkpoint molecules, such as cytotoxic lymphocyte antigen-4 (CTLA-4), programmed death1 (PD-1) or its ligand, programmed death ligand 1 (PD-L1), have shown great potential and have been used to treat various cancers as single therapies or in combination with other modalities. However, despite this remarkable progress, patients with TNBC have shown a low response rate to this approach, commonly developing resistance to immune checkpoint blockade, leading to treatment failure. Extracellular acidosis within the tumor microenvironment (also known as the Warburg effect) is one of the factors preventing immune cells from mounting effective responses and contributing to immunotherapy treatment failure. Therefore, reducing tumor acidity is important for increasing cancer immunotherapy effectiveness and this has yet to be realized in the TNBC environment. In this study, the oral administration of sodium bicarbonate (NaHCO3) enhanced the antitumor effect of anti-PD-L1 antibody treatment, as demonstrated by generated antitumor immunity, tumor growth inhibition and enhanced survival in 4T1-Luc breast cancer model. Here, we show that NaHCO3 increased extracellular pH (pHe) in tumor tissues in vivo, an effect that was accompanied by an increase in T cell infiltration, T cell activation and IFN-γ, IL2 and IL12p40 mRNA expression in tumor tissues, as well as an increase in T cell activation in tumor-draining lymph nodes. Interestingly, these changes were further enhanced in response to combined NaHCO3 + anti-PD-L1 therapy. In addition, the acidic extracellular conditions caused a significant increase in PD-L1 expression in vitro. Taken together, these results indicate that alkalizing therapy holds potential as a new tumor microenvironment immunomodulator and we hypothesize that NaHCO3 can enhance the antitumor effects of anti-PD-L1 breast cancer therapy. The combination of these treatments may have an exceptional impact on future TNBC immunotherapeutic approaches by providing a powerful personalized medicine paradigm. Therefore, our findings have a great translational potential for improving outcomes in TNBC patients.

The Association of Prehospital End-Tidal Carbon Dioxide with Survival Following Out-of-Hospital Cardiac Arrest

Objective End tidal carbon dioxide (ETCO2) is often used to assess ventilation and perfusion during cardiac arrest resuscitation. However, few data exist evaluating the relationship between ETCO2 values and mortality in the context of contemporary resuscitation practices. We aimed to explore the association between ETCO2 and mortality following out-of-hospital cardiac arrest (OHCA). Methods We used the 2018–2021 ESO annual datasets to query all non-traumatic OHCA patients with attempted resuscitation. Patients with documented DNR/POLST, EMS-witnessed arrest, ROSC after bystander CPR only, or < 2 documented ETCO2 values were excluded. The lowest and highest ETCO2 values recorded during the total prehospital interval, in addition to the pre- and post-ROSC intervals for resuscitated patients, were calculated. Multivariable logistic regression models adjusted for age, sex, initial rhythm, witnessed status, bystander CPR, etiology, OHCA location, sodium bicarbonate administration, number of milligrams of epinephrine administered, and response interval were used to evaluate the association between measures of ETCO2 and mortality. Results Hospital outcome data were available for 14,122 patients, and 2,209 (15.6%) were classified as surviving to discharge. Compared to patients with maximum prehospital ETCO2 values of 30–40 mmHg, odds of mortality were increased for patients with maximum prehospital ETCO2 values of <20 mmHg (aOR: 3.5 [2.1, 5,9]), 20–29 mmHg (aOR: 1.5 [1.1, 2.1]), and >50 mmHg (aOR: 1.5 [1.2, 1.8]). After 20 minutes of ETCO2 monitoring, <12% of patients had ETCO2 values <10 mmHg. This cutpoint was 96.7% specific and 6.9% sensitive for mortality. Conclusion In this dataset, both high and low ETCO2 values were associated with increased mortality. Contemporary resuscitation practices may make low ETCO2 values uncommon, and field termination decision algorithms should not use ETCO2 values in isolation.

Physicians' perspectives on different therapeutic approaches for aluminum phosphide poisoning and their relevant outcomes.

Aluminum phosphide is a highly toxic pesticide that results in high mortality. To date, there is neither a definitive antidote nor a unified protocol for managing acute aluminum phosphide poisoning. This cross-sectional questionnaire-based study aims to explore different management approaches and rely on the expertise of Egyptian medical professionals to enhance the prognosis for acute aluminum phosphide poisoning. A self-administered questionnaire was formulated and electronically distributed according to published literature and experience of senior physicians. Responses were received from 151 physicians from 10 governorates. Management modalities were variable among respondents. Noradrenaline was used by 90.7% of respondents with no fixed-dose regimen. In all, 84.1% of participants utilized oil in gastrointestinal decontamination; paraffin oil was the most used solution. Overall, 92.1, 61.6, 46.4, and 34.4% of participants used sodium bicarbonate, proton pump inhibitors, IV magnesium sulfate, and antioxidants, respectively. Regarding the frequency of acute aluminum phosphide poisoning, 47% of participants managed these cases daily or a few times a week. Participants' responses denoted a poor prognosis of acute aluminum phosphide poisoning, and high percentages attributed the prognosis to exposure factors rather than treatment modalities. Statistical analysis revealed that using oil in gastrointestinal decontamination improved the outcome by 4.62-fold. Clinical toxicologists were more likely to rescue≥30% of the cases about 3-fold (2.97) than other specialties. Clinical toxicologists used oil in gastrointestinal decontamination, magnesium sulfate, and antioxidant therapy and calculated base deficit before administration of sodium bicarbonate by 7.70-, 5.30-, 3.26-, and 2.08-fold than other specialties.

Severe diabetic ketoacidosis complicated with severe dyslipidemia, cerebral edema and acute kidney injury in a pediatric girl with type 1 diabetes mellitus: a case study

Diabetic ketoacidosis (DKA) is a life-threatening acute metabolic complication occurring in patients with type 1 diabetes, due to an insulin deficiency. Moderate hypertriglyceridemia is commonly observed in DKA but severe hypertriglyceridemia with a triglyceride level exceeding 10 g/l is very rarely reported. Acute kidney injury (AKI) is a serious condition which still carries a mortality of around 50%. Cerebral edema is a devastating complication of DKA which is leading cause of diabetes-related death in the pediatric population. Newly diagnosed diabetes, younger age, first episode of DKA, severity of DKA at presentation, and administration of bicarbonate are predictive of cerebral edema in DKA. We present a case of 8-year-old girl who presented with severe DKA, whose clinical course was complicated by renal failure, severe dyslipidemia and cerebral edema.

Sodium bicarbonate treatment for QRS widening in bupropion overdoses

Introduction Bupropion cardiotoxicity widens QRS complexes by inhibiting cardiac gap junctions. Sodium bicarbonate is the standard treatment for QRS widening from sodium channel blockade, but its effect on QRS widening in bupropion cardiotoxicity is not well-studied. Methods This is a retrospective cohort study of bupropion overdoses from 10 hospitals between January 2010 and June 2022. Patients with documented administration of sodium bicarbonate and QRS duration > 100 milliseconds on pre-bicarbonate electrocardiogram were included. Patients with no electrocardiogram within four hours of treatment or with baseline pre-overdose wide QRS and < 10 milliseconds widening from baseline were excluded. The primary outcome was a change in QRS duration between the pre-bicarbonate electrocardiogram and the first electrocardiogram after initial bicarbonate administration. Secondary outcomes included prevalence of post-bicarbonate QRS < 100 milliseconds, change in electrocardiogram intervals after total bicarbonate administration, and change in metabolic parameters and hemodynamics. Wilcoxon signed-rank testing was performed on the primary outcome. Linear regression modeling was performed to test for an association between change in QRS and bicarbonate dosing. Results Thirteen patients were included for final analysis. The median age was 32 years, and 54% were male. Six patients developed seizures; one developed ventricular tachycardia, and four received vasopressors. The median QRS and QTc pre-bicarbonate were 116 and 495 milliseconds, respectively. The median change in QRS duration was −2.0 milliseconds, which was not statistically significant (P = 0.42). The median bicarbonate dose administered before the first post-bicarbonate electrocardiogram was 100 milliequivalents. We did not identify an association between QRS change and bicarbonate dosing (P = 0.9, R-squared = 0.001). No patient had a QRS duration < 100 milliseconds after the initial bicarbonate dose. There was minimal change in QTc, electrolytes, heart rate, or blood pressure; alkalemia post-bicarbonate was achieved in eight patients. Conclusion Sodium bicarbonate did not significantly decrease QRS duration in this small retrospective cohort of bupropion overdoses.

Decompensated metabolic acidosis in the emergency department: Epidemiology, sodium bicarbonate therapy, and clinical outcomes

ObjectiveThis article aims to describe the epidemiology of decompensated metabolic acidosis, the characteristics of sodium bicarbonate (SB) administration and outcomes in emergency department (ED) patients. DesignThis is a retrospective cohort study. SettingED of a tertiary referral hospital in Melbourne, Australia. ParticipantsAdult patients presenting to the ED between 1 July 2011 and 20 September 2020 with decompensated metabolic acidosis diagnosed on arterial blood gas (ABG). Main outcome measuresWe compared characteristics between those treated with or without SB. We studied SB administration characteristics, change in laboratory variables, factors associated with use and dose, and clinical outcomes. ResultsAmong 753,613 ED patients, 314 had decompensated metabolic acidosis on ABG, with 17.8% receiving SB. Patients in the SB group had lower median pH, CO2, bicarbonate, and base excess (BE) levels compared with the No SB group (P < 0.01). The median number of SB doses in the SB group was one treatment. This was given at a median total dose of 100 mmol and at a median of 2.8 h after the diagnostic blood gas results. Only 42% of patients in the SB group had a subsequent blood gas measured. In such patients, there was no significant change in pH, bicarbonate, or BE. SB therapy was not independently associated with mortality. ConclusionsABG-confirmed decompensated metabolic acidosis was rare but associated with a high mortality. SB administration occurred in a minority of patients and in more acidaemic patients. However, SB dose was stereotypical and not tailored to acidosis severity. Assessment of SB effect was infrequent and showed no correction of acidosis. Systematic studies of titrated SB therapy are required to inform current practice.

A Review of Bicarbonate Use in Common Clinical Scenarios

BackgroundThe use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. ObjectiveIn this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate. DiscussionSodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation. ConclusionsEmpiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.

Maternal and umbilical cord blood lactate for predicting perinatal death: a secondary analysis of data from a randomized controlled trial

BackgroundIn high resource settings, lactate and pH levels measured from fetal scalp and umbilical cord blood are widely used as predictors of perinatal mortality. However, the same is not true in low resource settings, where much of perinatal mortality occurs. The scalability of this practice has been hindered by difficulty in collecting fetal scalp and umbilical blood sample. Little is known about the use of alternatives such as maternal blood, which is easier and safer to obtain. Therefore, we aimed to compare maternal and umbilical cord blood lactate levels for predicting perinatal deaths.MethodsThis was secondary analysis of data from a randomized controlled trial assessing the effect of sodium bicarbonate on maternal and perinatal outcomes among women with obstructed labour at Mbale regional referral hospital in Eastern Uganda. Lactate concentration in maternal capillary, myometrial, umbilical venous and arterial blood was measured at the bedside using a lactate Pro 2 device (Akray, Japan Shiga) upon diagnosis of obstructed labour. We constructed Receiver Operating Characteristic curves to compare the predictive ability of maternal and umbilical cord lactate and the optimal cutoffs calculated basing on the maximal Youden and Liu indices.ResultsPerinatal mortality risk was: 102.2 deaths per 1,000 live births: 95% CI (78.1–130.6). The areas under the ROC curves were 0.86 for umbilical arterial lactate, 0.71 for umbilical venous lactate, and 0.65 for myometrial lactate, 0.59 for maternal lactate baseline, and 0.65 at1hr after administration of bicarbonate. The optimal cutoffs for predicting perinatal death were 15 0.85 mmol/L for umbilical arterial lactate, 10.15mmol/L for umbilical venous lactate, 8.75mmol/L for myometrial lactate, and 3.95mmol/L for maternal lactate at recruitment and 7.35mmol/L after 1 h.ConclusionMaternal lactate was a poor predictor of perinatal death, but umbilical artery lactate has a high predictive value. There is need for future studies on the utility of amniotic fluid in predicting intrapartum perinatal deaths.

Prevention of Contrast-Induced Nephropathy After Emergency Percutaneous Coronary Intervention With a Single Bolus Administration of High-Concentrate Sodium Bicarbonate - Rationale and Design of a Single-Arm Study Compared With Historical Controls.

Background: Contrast-induced nephropathy (CIN) is clinically important because of its poor prognosis. The incidence of CIN is higher in emergency than elective percutaneous coronary intervention (PCI) because there is no established method to prevent CIN. The aim of this study is to evaluate whether bolus administration of a concentrated solution of sodium bicarbonate can prevent CIN in patients undergoing emergency PCI. Methods and Results: This multicenter prospective single-arm trial with historical controls will include patients who are aged ≥20 years and will undergo cardiac catheterization for suspected acute myocardial infarction (AMI). Patients will receive an intravenous bolus administration of concentrated sodium bicarbonate solution (7% or 8.4%, 20 mEq) and will be observed for 72±12 h. Data for the control group, comprising all patients who underwent PCI for AMI between January 1, 2020 and December 31, 2020 across participating hospitals, will be extracted. The primary endpoint is the incidence of CIN, defined as an increase in serum creatinine of >0.5 mg/dL or >25% from baseline within 48±12 h. We will evaluate the endpoints in the prospective group and compare them with those in the historical control group. Conclusions: This study will evaluate whether a single bolus administration of concentrated sodium bicarbonate can prevent CIN after emergency PCI.

Acidity-mediated induction of FoxP3+ regulatory T cells.

Glucose limitation and increased lactic acid levels are consequences of the elevated glycolytic activity of tumor cells, and constitute a metabolic barrier for the function of tumor infiltrating effector immune cells. The immune-suppressive functions of regulatory T cells (Tregs) are unobstructed in lactic-acid rich environments. However, the impact of lactic acid on the induction of Tregs remains unknown. We observed increased TGFβ-mediated induction of Forkhead box P3+ (FoxP3+ ) cells in the presence of extracellular lactic acid, in a glycolysis-independent, acidity-dependent manner. These CD4+ FoxP3+ cells expressed Treg-associated markers, including increased expression of CD39, and were capable of exerting suppressive functions. Corroborating these results in vivo, we observed that neutralizing the tumor pH by systemic administration of sodium bicarbonate (NaBi) decreased Treg abundance. We conclude that acidity augments Treg induction and propose that therapeutic targeting of acidity in the tumor microenvironment (TME) might reduce Treg-mediated immune suppression within tumors.

Early sodium bicarbonate therapy for critically ill patients with septic shock and acute moderate metabolic acidosis

To the editor: In recent decades, septic shock has continued to be a life-threatening health problem around the world.[1] Meanwhile, metabolic acidosis (MA) is also well known in critically ill patients, and even moderate metabolic acidosis (MMA) is associated with higher mortality than sepsis.[2] Although the administration of sodium bicarbonate (SB) is widely used in sepsis shock with MA in the intensive care unit (ICU), its clinical efficacy is not well established. In the 2021 update of the Surviving Sepsis Campaign guidelines, Evans et al. recommend the administration of SB in adults with septic shock, severe metabolic acidemia (pH ≤7.2), and acute kidney injury (AKI, AKIN score 2 or 3).[3,4] However, clinical evidence for the efficacy of the administration of SB in critically ill patients with septic shock and acute MMA is still limited. We retrospectively investigated a large ICU database (MIMIC-IV, https://www.physionet.org/) from 2008 to 2019 in 6 ICUs at a single-center hospital (Beth Israel Deaconess Medical Centre; Boston, MA). All adults with septic shock and acute MMA (7.2 < pH < 7.3, bicarbonate concentration <20 mmol/L, and PaCO2 <50 mmHg) within the first 48 hours after ICU admission were included in this study. Propensity score analysis[5] (PSA) was performed to account for differences in the probability of receiving or not receiving SB. For the PSA, we matched patients 1 to 1. The marginal structural Cox model[5] (MSCM) was developed to adjust for both baseline and time-varying confounding variables. The primary outcome was ICU and in-hospital mortality. Variables, including sex, age, body mass index, comorbidities on ICU admission, mechanical ventilation, vasopressors, and renal replacement therapy, were extracted from the MIMIC-IV database for the first 24 hours of ICU admission. Serum creatinine within the first 48 hours of an ICU stay was used to identify AKI stages. Administration of lactate solution for the first 24 hours was also included in the study. To account for the possible influence of clinical practice in previous years, the year of admission was used as a random factor in a mixed-effects model. Laboratory variables (PaO2, PaCO2, pH, and bicarbonate concentration) were recorded throughout the ICU period. For patients who underwent multiple tests, the highest values of lactate and PaCO2 and the lowest values of PaO2, bicarbonate concentration, and pH on each day were used for analysis. The above variables included in the PSA and MSCM are listed in Supplemental Table 1 (https://links.lww.com/ECCM/A58). A total of 577 patients with septic shock and MMA were identified, of whom 194 were included in the SB and 383 in the non-SB groups (Supplemental Table 2, https://links.lww.com/ECCM/A58). In the PSA group, early SB infusion was associated with both lower ICU mortality (hazards ratio [HR]: 0.61; 95% confidence interval [CI]: 0.40–0.93; P < 0.05) and lower in-hospital mortality (HR: 0.69; 95% CI: 0.50–0.97; P < 0.05; Fig. 1). In MSCM, our study also found a statistically significant positive effect of early SB infusion on ICU mortality (HR: 0.31; 95% CI: 0.13–0.72; P < 0.01) and hospital mortality (HR: 0.55; 95% CI: 0.31–0.97; P < 0.05) in patients with septic shock and MMA (Supplementary Figure 1, https://links.lww.com/ECCM/A59).Figure 1: Forest plot showing the effect of early sodium bicarbonate infusion on ICU and hospital mortality in the PSA for critically ill patients with septic shock and acute moderate metabolic acidosis. The hazard ratios were estimated using the PSA. After propensity score matching, 194 patients from the non-SB group were matched to SB group (n = 194) to balance the baseline differences in the probability to receive SB or not. The x-axis tick marks follow a logarithmic scale. ICU, intensive care unit; PSA, propensity score analysis; SB, sodium bicarbonate.Our observational study suggests that early infusion of SB in critically ill adult patients with septic shock and MMA within the first 48 hours after ICU admission has a significant beneficial effect on both ICU and hospital mortality. Further large, randomized, controlled clinical trials are needed to provide high-quality evidence to improve the Surviving Sepsis Campaign guidelines.