Unmeasured Anions Research Articles

SERIAL CHANGES IN METABOLIC ACID-BASE STATUS IN THREE SPECIES OF ANESTHETIZED CAPTIVE LARGE FELID.

Determination of acid-base status contributes important information about patient health, including for patients under anesthesia. There is a paucity of information about the determinants of acid-base status of large felids managed under anesthesia, and advancement of such knowledge may contribute to patient safety. This study serially monitored the individual metabolic acid-base status of 11 large felids, including lions (Panthera leo), tigers (Panthera tigris), and cheetahs (Acinonyx jubatus), under general anesthesia. We analyzed the contributions of measured strong ions (sodium, chloride, potassium, lactate), weak acids and buffers (albumin, phosphate and bicarbonate), and unmeasured anions to standardized extracellular base excess (SBE). A general linear model assessed for species differences in these parameters, with time since immobilization, SBE, and mean arterial pressure as covariates. By employing a Stewart-based analytical approach, it was possible to separate chloremic and unmeasured anion contributions to metabolic acid base status. This provided a basis for identifying mixed metabolic processes, generating differentials for underlying causes. Using normal acid base parameters for domestic felids, metabolic acidosis was found to be prevalent. Frequent evidence of unmeasured anion accumulation was also found, with unmeasured anions occasionally exceeding 5mmol/L. These findings warrant further inquiry into the drivers and clinical significance of metabolic acidosis and unmeasured anion accumulations in anesthetized large felids, encouraging further anion identity studies to elucidate possible causes. Reference ranges need to be established for acid-base parameters in large felids as a foundation for interpreting more controlled, prospective research into determinants of metabolic acid-base status in these animals under anesthesia.

Biochemical Approach of Acid-Base Disturbances: Diagnosis Algorithm

Context: The biochemical approach to acid-base balance classifies disturbances in two categories based on cellular mechanisms. The first one being cellular respiration (ATP), which presents high anion gap and changes in carbon dioxide levels, and the second one, cellular metabolism (ion transport through membrane channels), which evidences normal anion gap and changes in other cations and anions. Objective: To present a new diagnostic algorithm for acid-base disturbances, based on the biochemical approach. Method: Original research with systematic analysis and data organization, following biochemical processes that affect acid-base balance. Results: A simple, three-step algorithm which classifies information in a diagnostic table that connects blood gas analysis results (pH, anion gap or base excess, bicarbonate, carbon dioxide and unmeasured anions) with the biochemical cause and most probable clinical findings. Conclusions: The biochemical approach is considered the new model to understand, explain and diagnose acid-base balance and disturbances. All high anion gap disturbances occur in cellular respiration, while all normal anion gap disturbances occur in membrane channel function. The diagnosis algorithm simplifies and organizes the information to describe medical conditions with data from a blood gas analysis. This approach is the first model to establish a linear correlation between lab results, biochemical cause, and clinical findings of acid-base disturbances.

The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline?

The ratio of delta anion gap and delta bicarbonate (ΔAG/ΔHCO3) is used to detect co-existing acid-base disorders in patients with high anion gap metabolic acidosis. The ΔAG/ΔHCO3 ratio of 1.6-1.8:1 in lactic acidosis is derived from limited data using mean normal values for AG and serum HCO3. The objective of this study was to be the first to examine the ΔAG/ΔHCO3 using each patient's individual baseline AG and serum HCO3. This was a retrospective cohort study of adult ICU patients with sepsis. Lab data from simultaneously drawn chemistry panel, including anion gap and serum lactate on admission to the ICU was obtained. Baseline AG, HCO3 and albumin measurements were obtained 1-24 months prior to ICU admission. The ΔAG/ΔHCO3 was calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3. 344 patients were included. 128 patients had normal serum lactate levels (≤1.9 mmol/L) and 216 patients had elevated serum lactate levels (>1.9 mmol/L). ΔAG/ΔHCO3 was calculated for the 216 patients who had elevated serum lactate levels (>1.9 mmol/L). The mean ΔAG/ΔHCO3 for all patients with elevated serum lactate levels was 1.20 (SD 1.50). The mean ΔAG/ΔHCO3 calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3 was 1.20. The ΔAG/ΔHCO3 reported in prior literature which used mean normal AG and serum HCO3 was 1.6-1.8, highlighting that use of mean normal values affects the calculation of the ΔAG/ΔHCO3 and subsequent conclusions about underlying pathophysiology. The use of these mean normal values can result in misdiagnosis of complex acid-base disorders and inappropriate treatment. Our analysis indicates that the elevated ΔAG/ΔHCO3 is likely due to unmeasured anions contributing to an elevation in AG.

Prognostic role of unmeasured anions determined by the Stewart approach in septic shock: A prospective cohort study

Background: Unlike standard methods for the analysis of acid-base disturbances, the Stewart approach allows for a precise quantification of unmeasured anions (strong ion gap, SIG). The prognostic value of these unmeasured anions has been reported in various clinical situations in the intensive care unit (ICU), but not specifically in septic shock. The aim of the present study was to assess whether or not the SIG could be a prognostic marker for 28-day mortality in critically ill patients admitted to the ICU for septic shock. Methods: This prospective cohort study was conducted from June 2016 to December 2017 in three ICUs of a French teaching hospital. All patients admitted to the ICU for septic shock and equipped with an arterial blood line were eligible. Oral consent was collected after delivering oral and written information to the patient or his/her family. The SIG was calculated from a complete blood sampling (blood electrolytes and arterial blood gas) collected immediately upon ICU admission. Receiver operating characteristics (ROC) curves were determined to assess the ability of SIG to predict 28-day mortality. Results: A total of 116 patients were analyzed. The 28-day mortality rate was 41.4%. Median (interquartile range [IQR]) SIG at admission was 7.1 (4.6-9.6) mEq/L for the 28-day survivors and 8.0 (6.1-10.3) mEq/L for non-survivors (P = 0.051). The area under ROC of SIG at admission for 28-day mortality prediction was 0.607 (95% confidence interval [CI] 0.504-0.710; P = 0.051). Conclusion: SIG is not a relevant prognostic marker for mortality in septic shock.

Solução intravenosa poliiônica com concentração elevada de lactato (84 mEq/L) é eficaz para o tratamento de bezerros com diarreia

ABSTRACT This study aimed to evaluate the effectiveness of an electrolyte solution with a high lactate concentration (84mEq/L; L84) in correcting imbalances in diarrheal calves. Another solution with similar electrolyte composition, containing 84mEq/L of bicarbonate (B84) was used for comparison. Diarrhea was induced in neonatal calves by rotavirus infection, sucrose ingestion and furosemide administration. When a moderate degree of metabolic acidosis was reached, the calves were treated with intravenous infusion of L84 (n=10) or B84 (n=10) solutions. Venous blood and urine samples were collected before starting the infusion (0 h), in the middle (2.5 h), at the end (5.0 h) and 2.5 hours later. Total plasma protein concentration, blood and urine pH, blood pCO2, HCO3 -, and BE, plasma and urine concentration of L-lactate, and serum and urine concentrations of Na+, K+, and Cl- were measured. Strong ion difference, total concentration of non-volatile weak acids, anion gap, strong ion gap, percentage change in plasma volume, and urinary fractional clearances of Na+, K+, Cl-, and L-lactate were calculated. The calves demonstrated moderate dehydration, hypernatremia, hyperchloremia, metabolic acidosis, and unmeasured anion accumulation. These changes were completely corrected with the L84 solution, and the effects did not differ from those observed with B84 solution. The calves recovered without further therapeutic procedures, demonstrating that the L84 solution was effective for treating diarrheal calves.

Elevated strong ion gap: A predictor of the initiation of continuous renal replacement therapy in acute kidney injury

BackgroundThere is no optimal timing for continuous renal replacement therapy (CRRT) in acute kidney injury (AKI). AKI is a reason for the increased unmeasured anions, which refers to the increased organic acids in the blood, and they can be detected by calculating strong ion gap (SIG). SIG level at the moment of the AKI diagnosis may be a predictor for the initiation of CRRT. MethodsPatients who were diagnosed with AKI in the first week of the intensive care unit (ICU) period were included in this prospective observational study. At the moment of the AKI diagnosis, blood gas samples were recorded, and SIG was calculated. ResultsThe median level of SIG at the moment of the AKI diagnosis of CRRT (+) patients was significantly higher than CRRT (-) patients (7.4 and 3.2 mmol L−1, respectively). In the multivariate Cox regression analysis, the likelihood of the initiation of CRRT was increased 1.16-fold (1.01-1.33) and 4.0-fold (1.9-8.7) by only 1 mmol L−1 increases in SIG and SIG ≥6 mmol L-1 at the moment of AKI diagnosis, respectively (p = 0.035 and p < 0.001). ConclusionsIncreased SIG at the moment of the AKI diagnosis in patients with AKI may be a predictive marker to initiate CRRT.

Application of delta gap equation for the assessment of metabolic acidosis in renal failure patients

Introduction: Metabolic acidosis is commonly encountered in chronic kidney disease (CKD) which contributes to its progression. The metabolic acidosis in chronic kidney disease is presumed to be due to accumulation of unmeasured anions leading to a high anion gap (AG). The aim of the study was to assess the metabolic acidosis in renal failure patients using the calculation of delta gap. Methods: 100 renal failure cases were included. Their abnormal urea and creatinine values were utilized to calculate the BUN/creatinine ratio for all the cases. Based on the dipstick urine testing grading, proteinuric renal diseases were identified. The urine and serum osmolality were calculated in these renal failure patients. Serum osmolality was calculated using the values of serum sodium and urea. Urinary density which is also called urine specific gravity was used for indirect calculation of urine osmolality. Modified delta gap equation was applied for quick evaluation of mixed metabolic acid-base disorders. Results: Out of the 100 cases, 41 were proteinuric renal disease cases and 59 were non-proteinuric renal disease cases. High anion gap metabolic acidosis were seen in 65% of the total 100 cases. In 33% of the total cases, non-anion gap metabolic acidosis was also seen in addition to the high anion gap metabolic acidosis as it is evidenced by the delta gap value of less than -6 mmol/L. Conclusions: Earlier identification of the type and causative mechanism of metabolic acidosis in these patients may help to decrease the morbidity and mortality of these patients. The delta gap that can be easily calculated using this quick and short equation at the bedside may serve as a marker in the management of metabolic acidosis in renal failure patients. Keywords: delta gap; modified quick equation; metabolic acidosis; renal failure

Calcium-Citrate Anticoagulation during Continuous Renal Replacement Therapy in Patients with Metformin Intoxication: A Case Series, Mathematical Estimation of Citrate Accumulation, and Literature Review

Plain Language SummaryMetformin intoxication is a potentially life-threatening condition characterized by severe metabolic acidosis that could require intensive care unit admission and renal replacement therapy (RRT) for metformin removal. According to current guidelines, a citrate solution is commonly administered to generate regional anticoagulation in RRT due to its effect on chelating ionized calcium, an essential element of the coagulation pathway. Citrate metabolism can be impaired during metformin intoxication, and its administration could lead to accumulation worsening the metabolic acidosis. Citrate is not routinely measured, and its accumulation is clinically diagnosed by the ratio between total and ionized plasma calcium concentration (T/I calcium ratio) >2.5 or estimating the presence of unmeasured anions (UA), calculating the strong ion gap (SIG), i.e., the difference between the strong anions and cation, and the concentration of bicarbonate, dissociated albumin, and phosphates. We compared our results obtained from a case series of three patients with a theoretical model of citrate accumulation. Finally, we reviewed the literature to unveil clinical practice in this scenario. Our results support that diluted citrate can be safely used for RRT in patients with metformin toxicity, and the SIG is a valuable tool to estimate the presence of UA and can be used to detect and monitor citrate accumulation in this context.

Prognosis of critically ill patients with extreme acidosis: A retrospective study

ObjectiveThis study aims to assess the impact of different subtypes of extreme acidosis on the mortality of critically ill patients. MethodsThis retrospective cohort study included critically ill patients who were admitted to the intensive care unit (ICU) with a pH level <7. Clinical data and blood gas analyses were collected from electronic medical records. The primary outcome was in-hospital mortality. The use of vasopressors, mechanical ventilation (MV), and renal replacement therapy (RRT), the duration of MV and RRT, and the length of ICU and hospital stay were secondary outcomes. The simplified Stewart approach to acid-base disorders was used to analyze the causes of acidosis. ResultsA total of 231 patients with 371 arterial blood gas analyses with pH < 7 were admitted from January 2012 to December 2021 and 222 were included in the study. Out of the 222 patients analyzed, respiratory acidosis was the primary disorder in 11.3% of patients (n = 25), metabolic acidosis in 33.8% (n = 75), and mixed acidosis in 55% (n = 122). Overall mortality was 42.8% (n = 95). No significant difference was observed in mortality among patients with respiratory, metabolic, or mixed acidosis (28%, 42.7%, and 45.9%, respectively; p = 0.26). The primary disorder affected the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Patients with extreme acidosis due to unmeasured anions with lactate levels of 4 mmol/L or higher had higher mortality compared with patients with lactate levels <4 mmol/L (55.6% and 27.7%, respectively; p = 0.007). ConclusionAmong critically ill patients with extreme acidosis, the primary disorder is not associated with mortality, but it is associated with the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Additionally, hyperlactatemia is a predictor of poor prognosis in patients with extreme acidosis.

Unmeasured Organic Anions as Predictors of Clinical Outcomes in Lactic Acidosis due to Sepsis.

Background and Objectives: In lactic acidosis, lactate can only explain 30% of the variance in the anion gap (AG), and the elevated AG not explained by lactate is due to unmeasured organic anions (UOAs). Some studies using less precise surrogates for UOA have suggested that UOA may predict clinical outcomes better than lactate. The aim of this study was to determine whether UOA predicts clinical outcomes better than lactate levels. Design, Setting, Participants, & Measurements: This was a retrospective cohort study of adult ICU patients with sepsis. Baseline AG and albumin measurements were obtained. An albumin-corrected delta AG was calculated. UOAs were estimated using the formula: Delta AG - serum lactate. A multivariate logistic regression model with its respective ROC curve was constructed to explore the relationship between in-hospital mortality, UOA, and lactate. Results: 526 patients were included. In the combined model examining both lactate and UOA, the odds ratio (OR) [95% CI] for predicting ICU length of stay (LOS) was 1.050 [1.029-1.072] and 1.022 [1.009-1.035], respectively; the OR [95% CI] for predicting in-hospital mortality was 1.224 [1.104-1.358] and 0.997 [0.943-1.054], respectively. The ROC curve for in-hospital mortality demonstrated that the Area Under the Curve (AUC) for lactate, UOA, and combined lactate and UOA was 0.7726, 0.7486, and 0.7732, respectively. The AUC for combined lactate and UOA were not statistically significantly higher than the AUC for lactate alone (P .9193). Conclusions: As expected, serum lactate predicted both ICU LOS and in-hospital mortality. UOA did predict ICU LOS, although the reason for this association is not known. UOA did not predict in-hospital mortality based on the OR and the ROC curve's AUC, contrary to some previous studies. However, our study used a more precise quantitative estimate of UOA, including the use of baseline albumin-corrected AG. Prior studies attempting to identify UOA have identified Krebs cycle intermediates including citrate and isocitrate, suggesting that in our study these anions associated with the Krebs cycle contributed to the UOA.

The elevation of the anion gap in steady state chronic kidney disease may be less prominent than generally accepted.

A presumed cause of metabolic acidosis in chronic kidney disease (CKD) is accumulation of unmeasured anions, leading to a high anion gap (AG). In patients with CKD with a high AG, only minor increases are expected. The aim of this study is to evaluate the magnitude of the AG in documented steady state CKD to examine the effect of CKD on a high-AG metabolic acidosis (HAGMA). In this cross-sectional study the AG, bicarbonate, and chloride were evaluated in 1045 blood and urine samples of 501 patients with steady state CKD in the outpatient clinic. The influence of phosphate, albumin and potassium on the AG were evaluated. The mean AG increased from 8.8mEq/l (±1.57) in CKD stage 1 to 11.2mEq/l (±2.22) in CKD stage 5 (P<0.001). Correction for albumin or phosphate did not influence the magnitude of the AG. Correction for potassium did alter the prevalence of HAGMA, but not the severity. [HCO3-] decreased between CKD stages 1 and 5 by 5.1mEq/l. The [Cl-] increased by 2.6mEq/l between CKD stages 1 and 5. The elevation of the AG in patients with steady state CKD is limited and less pronounced than the decrease in [HCO3-]. Normal AG metabolic acidosis seems to be more important in CKD than HAGMA. The CKD stage and the magnitude of the AG should be taken into account when evaluating a patient with HAGMA. This study suggests that an AG >15mEq/l is rarely due to renal failure alone.

Acid base disturbances in leptospirosis patients: Comparison of conventional and Stewart method

Background: The Henderson-Hasselbalch equation is used in the conventional assessment of acid-base status. In 1983, P. Stewart put up an alternate strategy. The Henderson-Hasselbalch equation uses variations in PCO2 and bicarbonate to explain the acid-base state. On the other hand, the Stewart theory states that albumin, inorganic phosphate, PCO2, Strong Ion Difference (SID), and SID dictate acid-base status. Therefore, these variables have an important role in clinical management. The metabolic acidosis caused by unmeasured anions is accurately identified by the Stewart physiochemical approach, and it is a predictor of mortality in patients with leptospirosis. Aims and Objectives: Comparison of the leptospirosis patient’s S. albumin (requiring ABG analysis) and arterial blood gas (ABG) analysis parameters (pH, PO2, PCO2, HCO3-, BE, SaO2, S.Na+, S.K+, S.Cl, S.PO43-, and anion gap) to compare the conventional and Stewart methods and determine the type of acid-base disturbances present in leptospirosis patients in the intensive care unit. Materials and Methods: Following approval by the ethics committee, ABG and S. Albumin were taken from the clinical notes of fifty patients. The Henderson-Hasselbalch equation, in its conventional form, was unable to identify complex acid-base problems. Thus, we integrated this with the Stewart method. Results: The majority of leptospirosis patients had a mixed disorder characterized by respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. The most prevalent conditions were metabolic acidosis, respiratory alkalosis, and metabolic alkalosis. Stewart’s method can help explain the cause of metabolic disorders. Stewart’s approach also made occult acid-base disorders visible. Conclusion: Stewart’s approach emphasizes the significance of Na+, K+, Cl-, Alb, and PO43- and clarifies their part in the development of metabolic abnormalities, particularly those involving Alb and PO43-. This demonstrates unequivocally that the cause of the metabolic abnormalities can be explained by Stewart’s method, which is highly helpful in planning the management.

Promjena acidobazne ravnoteže krvi u lakon ovaca tijekom različitih stadija laktacije

The aim of the present study was to determine the acid-base balance in the blood of the Lacaune sheep during different lactation stages. Thirty lactating Lacaune sheep were involved in the research, and were monitored in the early (day 60), medium (day 120), and late lactation stages (day 180). The following parameters were determined in the blood plasma: pH, partial pressure of carbon dioxide – pCO2, partial pressure of oxygen – pO2, total pressure of carbon dioxide – tCO2, oxygen saturation – sO2, actual base excess Cbase – B, standard base excess Cbase – Ecf and electrolytes (Na+, K+, Ca2+, Cl- and HCO3- – bicarbonate), while total proteins – TP and albumin ALB were determined in the serum. Also, strong ion difference - SID, z value, anion gap - AG, weak anions, and cations - ATOTtp and ATOTalb, strong ion gap - SIG, unmeasured anions – XA and globulin concentrations were calculated. A significant effect of the lactation stage on most of the acid-base parameters in the blood of the Lacaune sheep was determined, except for pCO2, Cl-, z values and the SID. A significant increase of pO2, sO2, ATOTtp, ATOTalb, AG, SIGalb, SIGtp, XA, Na+, total proteins and albumins, as well as the decreased concentrations of K+ and Ca2+, were determined in the blood of the Lacaune sheep during lactation. During the medium stage of lactation, significant changes were determined in most of the acid-base parameters in the blood of the Lacaune sheep when compared to the other stages. A lactation stage may significantly affect the acid-base balance parameters in the blood of the Lacaune sheep, although the calculations of SIG, base excess (BE), and unmeasured anion (XA) values should also be included for the obtainment of a more comprehensive picture of the acid-base balance.

Unmeasured Organic Anions as Predictors of Clinical Outcomes in Lactic Acidosis due to Sepsis

Unmeasured Organic Anions as Predictors of Clinical Outcomes in Lactic Acidosis due to Sepsis

Calf Diarrhea Is Associated With a Shift From Obligated to Facultative Anaerobes and Expansion of Lactate-Producing Bacteria.

Diarrhea is the leading cause of morbidity, mortality and antimicrobial drug use in calves during the first month of age. Alteration in the bacterial communities of the gastrointestinal tract occurs during diarrhea. Diarrheic calves often develop anion gap (AG) acidosis associated with increased concentrations of unmeasured anions including D- and L-lactate. However, studies investigating the association between gut microbiota alterations and the development of acid-base disorders in diarrheic calves are lacking. We investigated the fecal bacterial alterations of calves with diarrhea and its association with changes in blood pH, and AG. Blood and fecal samples from healthy and diarrheic veal calves were taken 7 days after arrival to the farm. The fecal microbiota of healthy and diarrheic calves was assessed by sequencing of 16S ribosomal RNA gene amplicons. Blood gas analysis was completed using an i-Stat analyzer. In healthy calves, higher richness, evenness, and diversity were observed compared to diarrheic calves. Phocaeicola, Bacteroides, Prevotella, Faecalibacterium, Butyricicoccus, Ruminococcaceae and Lachnospiraceae were enriched in healthy compared with diarrheic calves. Enterococcus, Ligilactobacillus, Lactobacilus, Gallibacterium Streptococcus, and Escherichia/Shigella were enriched in diarrheic calves. In diarrheic calves, an increased abundance of lactate-producing bacteria including Lactobacillus, Streptococcus, Veillonella, Ligilactobacillus and Olsenella was detected. Diarrheic calves had a lower pH and bicarbonate concentration and a higher AG concentration than healthy calves. Together, these results indicate that calf diarrhea is associated with a shift from obligated to facultative anaerobes and expansion of lactate-producing bacteria which are related to acidemia, low bicarbonate and increase AG. Our results highlight the importance of the gastrointestinal microbiota on the clinicopathological changes observed in diarrheic calves.

The Significance of the Strong Ion Gap in Predicting Acute Kidney Injury and In-hospital Mortality in Critically Ill Patients with Acute Poisoning

Purpose: A high anion gap (AG) is known to be a significant risk factor for serious acid-base imbalances and death in acute poisoning cases. The strong ion difference (SID), or strong ion gap (SIG), has recently been used to predict in-hospital mortality or acute kidney injury (AKI) in patients with systemic inflammatory response syndrome. This study presents a comprehensive acid-base analysis in order to identify the predictive value of the SIG for disease severity in severe poisoning. Methods: A cross-sectional observational study was conducted on acute poisoning patients treated in the emergency intensive care unit (ICU) between December 2015 and November 2020. Initial serum electrolytes, base deficit (BD), AG, SIG, and laboratory parameters were concurrently measured upon hospital arrival and were subsequently used along with Stewart's approach to acid-base analysis to predict AKI development and in-hospital death. The area under the receiver operating characteristic curve (AUC) and logistic regression analysis were used as statistical tests. Results: Overall, 343 patients who were treated in the intensive care unit were enrolled. The initial levels of lactate, AG, and BD were significantly higher in the AKI group (n=62). Both effective SID [SIDe] (20.3 vs. 26.4 mEq/L, p&lt;0.001) and SIG (20.2 vs. 16.5 mEq/L, p&lt;0.001) were significantly higher in the AKI group; however, the AUC of serum SIDe was 0.842 (95% confidence interval [CI]=0.799-0.879). Serum SIDe had a higher predictive capacity for AKI than initial creatinine (AUC=0.796, 95% CI=0.749-0.837), BD (AUC=0.761, 95% CI=0.712-0.805), and AG (AUC=0.660, 95% CI=0.607-0.711). Multivariate logistic regression analyses revealed that diabetes, lactic acidosis, high SIG, and low SIDe were significant risk factors for in-hospital mortality. Conclusion: Initial SIDe and SIG were identified as useful predictors of AKI and in-hospital mortality in intoxicated patients who were critically ill. Further research is necessary to evaluate the physiological nature of the toxicant or unmeasured anions in such patients.

Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study.

Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical metabolic acidosis in this population, we examined prospective associations of body mass index (BMI) with elevated anion gap and whether anion gap values in obesity associate with low bicarbonate. Data from adult outpatients (n=94,448) in the Bronx, New York were collected from 2010 to 2018. Mixed effects models and Cox proportional hazards models were used to examine associations of BMI with elevated anion gap and anion gap metabolic acidosis and of baseline anion gap with incident low bicarbonate and anion gap metabolic acidosis. Anion gap was defined using traditional and albumin-corrected calculations. Greater BMI was associated with higher anion gap over time and with progressively greater risk of developing an elevated anion gap (hazard ratio [HR] for body mass index [BMI]≥40 kg/m2 versus 18 to <25 kg/m2, 1.32; 95% confidence interval [95% CI], 1.23 to 1.42 for traditional and HR for BMI≥40 kg/m2 versus 18 to <25 kg/m2, 1.74; 95% CI, 1.63 to 1.85 for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI≥40 kg/m2, 1.53; 95% CI, 1.39 to 1.69). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HR for fourth versus first quartile, 1.29; 95% CI, 1.23 to 1.44 for traditional and HR for fourth versus first quartile, 1.36; 95% CI, 1.26 to 1.48 for corrected) and higher risk of anion gap metabolic acidosis (HR for fourth versus first quartile, 1.78; 95% CI, 1.59 to 1.99). Obesity is characterized by unmeasured anion accumulation and acid retention or overproduction. Modest elevations in anion gap among patients with obesity are associated with previously unrecognized anion gap metabolic acidosis.

The Δ Anion Gap/Δ Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?

The ratio of Δ anion gap and Δ bicarbonate (ΔAG/ΔHCO3) is used to detect coexisting acid-base disorders in patients with high anion gap metabolic acidosis. Classic teaching holds that, in lactic acidosis, the ΔAG/ΔHCO3 is 1:1 within the first few hours of onset and subsequently rises to 1.8:1. However, this classic 1:1 stoichiometry in early lactic acidosis was derived primarily from animal models and only limited human data. The objective of this study was to examine the ΔAG/ΔHCO3 within the first hours of the development of lactic acidosis. Data were obtained prospectively from a convenience sample of adult (age >18 years) trauma-designated patients at a single level-1 trauma center. Venous samples, including a chemistry panel and serum lactate, were drawn before initiation of intravenous fluid resuscitation. A total of 108 patients were included. Of these, 63 patients had normal serum lactate levels (≤2.1 mmol/L) with a mean AG of 7.1 mEq/L, the value used to calculate subsequent ΔAG values. ΔAG/ΔHCO3 was calculated for 45 patients who had elevated serum lactate levels (>2.1 mmol/L). The mean ΔAG/ΔHCO3 for all patients with elevated serum lactate levels was 1.86 (SD, 1.40). The mean ΔAG/ΔHCO3 was 1.86 within the first hours of the development of lactic acidosis due to hypovolemic shock, confirming a small prior human study. This contradicts the traditional belief that, in lactic acidosis, the ΔAG/ΔHCO3 is 1:1 within the first several hours. The classic 1:1 stoichiometry was determined on the basis of animal models in which lactic acid is infused into the extracellular space, facilitating extracellular buffering of protons by bicarbonate. In contrast, our results demonstrate a higher initial ΔAG/ΔHCO3 ratio in early endogenous lactic acidosis in humans. Our analysis indicates this is likely due to unmeasured anions contributing to an elevation in AG.

Pseudo Metabolic Acidosis in the Setting of Hypertriglyceridemia: A Case Report

Low serum bicarbonate, with or without an elevated anion gap, can indicate metabolic acidosis. High anion gap metabolic acidosis is due to the unmeasured anions. Hypertriglyceridemia can also be associated with spuriously low serum bicarbonate levels due to lab interference. We present a 44-year-old woman who presented with anion gap metabolic acidosis in the presence of severe hypertriglyceridemia

Umbilical Cord Unmeasured Anions and Tissue Acid Levels According to Stewart’s Method in Term Newborn Infants and the Impact of Delivery Mode on these parameters

Aim: To determine the reference values of strong ion difference (SID), effective SID (SIDe), unmeasured anions (UMA), tissue acids (TA), lactate and Chloride-Sodium (Cl-Na) ratio of umbilical cord blood, and to evaluate the impact of delivery mode on these parameters.&#x0D; Methods: This prospective study was performed on healthy term newborn infants that had normal progress throughout the first and second stages of labor during normal spontaneous delivery (NSD) and cesarean section (C/S). Immediately after birth, 1ml and 2 ml of umbilical venous cord blood samples were obtained for blood gas analysis and blood chemistry respectively. The Cl-Na ratio, anion gap (AG), albumin corrected AG (AGCorr), SID, SIDe, UMA and TA were calculated in NSD and C/S groups.. &#x0D; Results: A total of 181 healthy newborn infants were included the study. Fifty-one infants were delivered by NSD and 130 infants by C/S. The pH and PCO2 values were similar in both groups. The mode of delivery had a significant impact on the umbilical cord AG, AGCorr, SID, lactate, UMA, and TA levels. All these values were significantly higher in NSD than C/S group. &#x0D; Conclusion: Umbilical cord blood gas analysis is a common practice to evaluate fetal status at delivery. The calculation of blood gas parameters in perinatal problems according to Stewart’s method may lead further understanding how perinatal conditions of the mother influence the fetus and newborn infant.