Anion Gap Research Articles

Sodium-chloride difference is not strongly correlated with base excess in chronic kidney disease: an anion gap problem.

The prevalence of metabolic acidosis is high in patients with chronic kidney disease (CKD). For the diagnosis, a blood gas analysis is necessary, but not always available. The aim of the study was to evaluate the base excess (BE) of the sodium-chloride difference (BENa-Cl = Na+-Cl--34mmol/l) as a screening parameter for hyperchloremic metabolic acidosis. We retrospectively performed acid-base analyses of 168non-dialysedpatientswith CKDaccording to the physiologic and to the Stewart's approach. We performed linear regression analysis, Bland-Altman plot and receiver operating characteristics (ROC) analysis of BENa-Cland BE to evaluate the accuracy of BENa-Clpredicting the BE. We further investigated possible confounding factors. The corrected R2for the correlation of BENa-Cland BE was 0.60 (p < 0.001). The Bland-Altman plot showed a good overall agreement. The bias was negligible, but the 95%-limits of agreement showed a wide interval (10.4mmol/l). For BE ≤ 2mmol/l, the ROC analysis yielded an AUC of 0.89 and moderate sensitivity (0.75) and specificity (0.86) for the optimal BENa-Clthreshold (≤ 2mmol/l). Subgroup analysis showed similar results. The main factor for the imprecision of BENa-Clpredicting the BE across all stages of CKD is the variability of the serum anion gap (SAG). The BENa-Clis not an adequate parameter for screening of hyperchloremic acidosis because of the high variability of the SAG. Only, if the BENa-Clis ≤ 5mmol/l, a hyperchloremic acidosis should be suspected. Therefore, a complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease.

Fanconi Syndrome Due to Tenofovir Disoproxil Fumarate in a Patient with Chronic Hepatitis B Induced Cirrhosis: A Case Report

We present a 63-year-old woman with chronic hepatitis B. The patient has a history of cirrhosis due to chronic hepatitis B and is under treatment with Tenofovir disoproxil fumarate. The patient presented to our center with nausea, vomiting, and severe metabolic acidosis. After initial evaluation, along with the typical course of events and the exclusion of differential diagnoses of normal anion gap metabolic acidosis, we determined that the cause of illness was related to Tenofovir disoproxil fumarate. All our practical and laboratory data supported a diagnosis of proximal tubular acidosis. After discontinuing the drug for two weeks and providing supportive management, metabolic acidosis and electrolyte imbalance improved. The other isoform of Tenofovir (Tenofovir alafenamide) was initiated for the patient, and after two months of follow- up, there were no signs of acidosis or electrolyte imbalance

Predictors and Predictive Score of In-Hospital Mortality in Diabetic Ketoacidosis: A Retrospective Cohort Study

Background and Objectives: Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus (DM). The primary objective of this study was to identify relevant clinical and biochemical predictors and create a predictive score for in-hospital DKA mortality. Materials and Methods: A 6-year retrospective cohort study of adult patients diagnosed with DKA and admitted to Chiang Mai University Hospital, a tertiary care center in Chiang Mai, Thailand, from 1 January 2015 to 31 December 2021, was conducted. Baseline clinical data and laboratory investigations were collected. The primary outcome was in-hospital mortality. Multivariable logistic regression analysis, clustered by type of diabetes, was performed to identify significant predictors. A predictive risk score was created using significant predictive factors identified by multivariable analysis. The results were presented as odds ratios (ORs) and 95% confidence intervals (CIs), with a significant p-value set at &lt;0.05. Results: Ninety-three patients diagnosed with DKA were included in the study. Ten patients died during admission. Significant predictors for in-hospital mortality of DKA included age &gt; 55 years (OR 7.8, p = 0.007), female gender (OR 3.5, p &lt; 0.001), anion gap &gt; 30 mEq/L (OR 2.6, p = 0.003), hemoglobin levels &lt; 10 g/dL (OR 16.9, p &lt; 0.001), and the presence of cardiovascular disease (OR 1.3, p = 0.046). The predictive risk score ranged from 1 to 14 for low risk, and 14.5–23.5 for high risk of in-hospital mortality. The predictive performance of the scoring system was 0.82 based on the area under the curve, with a sensitivity of 73.8% and specificity of 96.4%. Conclusions: Multiple clinical and biochemical factors, along with a predictive risk score, could assist in predicting in-hospital mortality of DKA and serve as a guide for physicians to identify patients at high risk. Nevertheless, as the predictive score was internally validated with data from a single institution, external validation in diverse healthcare settings with larger datasets or prospective cohorts is crucial to confirm the model’s generalizability and predictive accuracy.

Unveiling the hidden risks: albumin-corrected anion gap as a superior marker for cardiovascular mortality in type 2 diabetes: insights from a nationally prospective cohort study

Unveiling the hidden risks: albumin-corrected anion gap as a superior marker for cardiovascular mortality in type 2 diabetes: insights from a nationally prospective cohort study

TOXIC ALCOHOL POISONING: A CASE REPORT

During the COVID-19 pandemic, toxic alcohol poisoning, notably from methanol, has emerged as a significant concern due to increased consumption of illicit liquor amidst lockdown restrictions. We present a case of a middle-aged man who developed altered consciousness, metabolic acidosis, and shock two days after ingesting hospital spirit. Although initial qualitative tests only detected ethanol, subsequent MRI findings showed classical signs of methanol poisoning, including basal ganglia abnormalities. Prompt management with dialysis, ventilatory support, and adjunctive therapy successfully addressed the acute phase despite the patient remaining delirious for seven days. This case underscores the importance of considering methanol toxicity even in the absence of direct evidence, necessitating comprehensive diagnostic approaches. Awareness and incorporating point-of-care assessments such as arterial blood gas analysis and osmolar gap evaluation in suspected cases are crucial, especially in resource-limited settings. Recognizing unexplained high anion gap metabolic acidosis with a high osmolar gap and characteristic MRI findings can aid in the early diagnosis and management of toxic alcohol poisoning

Biomarkers to Differentiate Acute Chest Syndrome From Vaso-Occlusive Crisis in Children With Sickle Cell Disease.

Acute Chest Syndrome (ACS) is the leading cause of death in children with sickle cell disease (SCD) in the US-about half of the children who develop ACS present initially with pain. Here, we studied biomarkers to differentiate ACS from vaso-occlusive crises (VOC) in children with SCD who presented with pain to the emergency department (ED). We conducted a prospective cohort study of consecutive patients who presented to the ED with pain and were discharged with ACS or VOC between March, 2017 and February, 2020. We identified 7 patients with ACS and 19 patients with VOC. The two groups were comparable in age and sex. All patients with ACS had asthma versus 42% of the VOC group. The ACS group had lower weight and BMI z-scores. Patients with ACS compared to VOC had significantly higher respiratory rates, lower O2 saturation, and longer hospital stays. They also had higher white blood cell count, glucose level (> 99 mg/dL), anion gap (> 9 mEq/L), sPLA2 (> 7 pg/mL), IFN-γ (> 17.8 pg/mL), IL-10 (1.54 pg/mL), and IL-12 (> 0.5 pg/mL) levels. We identified biomarkers associated with ACS development in children with SCD presenting with pain that allow for earlier ACS interventions to reduce mortality and morbidity.

Association between albumin-corrected anion gap and kidney function in individuals with hypertension – NHANES 2009–2016 cycle

Objectives Long-term uncontrolled hypertension increases the risk of kidney decompensation. This study aimed to explore the connection between albumin-corrected anion gap (ACAG) and kidney function in hypertensive patients. Methods This study utilized data from 1988 participants diagnosed with hypertension sourced from the NHANES database. Binary logistic regression analysis and subgroup analysis were utilized to investigate the relationship between ACAG and kidney function. The study employed restricted cubic spline (RCS) to assess the non-linear associations between ACAG and eGFR, as well as ACAG and ACR. Furthermore, mediation and moderation effect analyses were carried out, with blood pressure serving as the mediator and moderator, ACAG as the independent variable, and eGFR and ACR as the dependent variables. Finally, the study developed ACAG-based models for predicting kidney function decline. Results Higher ACAG is identified as an independent risk factor for eGFR < 60 mL/minute/1.73 m2 and ACR ≥ 30 mg/g. Results from RCS indicate a non-linear relationship between ACAG and eGFR, as well as between ACAG and ACR. The mediation effect analysis revealed that DBP mediated the relationship between ACAG and eGFR. Analysis on moderation effect demonstrated that SBP played a significant role in moderating the interaction between ACAG and ACR. Moreover, the models based on ACAG showed strong performance. Conclusions The levels of ACAG are found to be independently associated with both eGFR and ACR. Additionally, ACAG shows promise as a new and dependable biomarker for predicting the decline in kidney function in hypertensive patients.

Metabolic acidosis in patients with diabetes 2 undergoing cardiac surgery: The impact of SGLT2 inhibitor use: a retrospective cohort study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) lower blood sugar and reduce cardiovascular events and kidney failure. However, there have been increasing reports of euglycaemic diabetic ketoacidosis (eDKA) linked to SGLT2-i medicines. Investigating the association between SGLT2-i use and the incidence of metabolic acidosis in patients with type 2 diabetes undergoing cardiac surgery. A retrospective observational cohort study comprising 121 patients, with 38 in the SGLT2-i group and 83 in the control group. A 2-year period at Haukeland University Hospital, a tertiary regional hospital in Western Norway. Patients with type 2 diabetes undergoing cardiac surgery. Collection of clinical and laboratory data, including acid/base balance parameters, surgery details and SGLT2-i use. Base excess and anion gap measurements as indicators of ketosis development. A subgroup analysis in patients without renal failure (glomerular filtration rate > 60 ml min-1 m-2). Lower base excess levels and increased anion gaps were observed in the SGLT2-i group compared with controls at various time points postoperatively, with no significant differences in serum lactate levels.Twelve hours postoperatively, 41% of SGLT2-i patients without renal failure had a base excess -3 mmol l-1 or less after correction for serum lactate (indicating ketosis) compared with only 8% in the control group (P < 0.001). The anion gap was elevated in the SGLT2-i group compared to the control group at 12 h postoperatively (P = 0.018).Multivariable regression analysis identified SGLT2-i use as an independent factor associated with a lower base excess after correction for lactate levels (P < 0.001). Cessation of SGLT2-i medication did not correlate with the degree of acidosis. While taking SGLT2 inhibitors, diabetic patients undergoing heart surgery are at an increased risk of ketosis and possibly metabolic acidosis. This emphasises the importance of careful observation and effective treatment strategies within this group.

Construction of Survival Nomogram for Ventilator-Associated Pneumonia Patients: Based on MIMIC Database.

Objective: To construct and validate a predictive nomogram model for the survival of patients with ventilator-associated pneumonia (VAP) to enhance prediction of 28-day survival rate in critically ill patients with VAP. Methods: A total of 1,438 intensive care unit (ICU) patients with VAP were screened through Medical Information Mart for Intensive Care (MIMIC)-IV. On the basis of multi-variable Cox regression analysis data, nomogram performance in predicting survival status of patients with VAP at ICU admission for 7, 14, and 28 days was evaluated using the C-index and area under the curve (AUC). Calibration and decision curve analysis curves were generated to assess clinical value and effectiveness of model, and risk stratification was performed for patients with VAP. Result: Through stepwise regression screening of uni-variable and multi-variable Cox regression models, independent prognostic factors for predicting nomogram were determined, including age, race, body temperature, Sequential Organ Failure Assessment score, anion gap, bicarbonate concentration, partial pressure of carbon dioxide, mean corpuscular hemoglobin, and liver disease. The model had C-index values of 0.748 and 0.628 in the train and test sets, respectively. The receiver operating characteristic curve showed that nomogram had better performance in predicting 28-day survival status in the train set (AUC = 0.74), whereas it decreased in the test set (AUC = 0.66). Calibration and decision curve analysis curve results suggested that nomogram had favorable predictive performance and clinical efficacy. Kaplan-Meier curves showed significant differences in survival between low, medium, and high-risk groups in the total set and training set (log-rank p < 0.05), further validating the effectiveness of the model. Conclusion: The VAP patient admission ICU 7, 14, and 28-day survival prediction nomogram was constructed, contributing to risk stratification and decision-making for such patients. The model is expected to play a positive role in supporting personalized treatment and management of VAP.

Combined effect of anion gap and red cell distribution width on the risk of acute kidney injury after cardiac surgery

BackgroundThis study was to analyze the roles of red blood cell distribution width (RDW), anion gap (AG) levels and their combined effects on the risk of acute kidney injury (AKI) following cardiac surgery.MethodsThis cohort study extracted the data of 1951 participants aged ≥ 18 years with the assessment of AKI after cardiac surgery during ICU stay from MIMIC-IV database between 2008 and 2019. Receiver operator characteristic (ROC) curve was used to determine the optimal cut-off value AG and RDW. The associations between AG, RDW, and the combined effects of AG and effects were evaluated via univariable and multivariable Logistic models. Odds ratio (OR) with 95% confidence interval (CI) were imputed.ResultsAmong all the participants, 831 participants had AKI, and 1120 did not have AKI. ROC curves revealed that the optimum cut of points of AG and RDW were 12.75 mmol/L, and 13.65%, respectively. Increased risk of AKI was found in patients after cardiac surgery with AG > 12.75 mmol/L (OR = 1.44, 95%CI 1.15–1.80) or RDW > 13.65% group (OR = 1.23, 95%CI 1.01–1.50). In comparison to subjects with AG ≤ 12.75 mmol/L and RDW ≤ 13.65%, AG > 12.75 mmol/L and RDW ≤ 13.65% (OR = 1.42, 95%CI 1.07–1.89), and AG > 12.75 mmol/L and RDW > 13.65% (OR = 1.75, 95%CI 1.24–2.47) were associated with increased odds of AKI in patients after cardiac surgery.ConclusionsAG and RDW had combined effects on risk of AKI in patients after cardiac surgery, which might offer an insight for the management of patients after cardiac surgery.

Association between serum anion gap and 28-day mortality in critically ill patients with infective endocarditis: a retrospective cohort study from MIMIC IV database

BackgroundThe relationship between serum anion gap (AG) and 28-day mortality in critically ill patients with infective endocarditis is currently not well established.ObjectiveThis study aims to investigate the impact of serum AG on 28-day mortality in critically ill patients with infective endocarditis.MethodsA retrospective cohort study was conducted involving 449 participants diagnosed with infective endocarditis and admitted to intensive care units (ICU). Vital signs, laboratory parameters and comorbidity were collected for all participants to analyze the association between anion gap levels and 28-day mortality.ResultsA total of 449 critically ill patients with infective endocarditis (IE) were included in the study. The mean age was 57 years, and 64% were male. The overall 28-day mortality rate was 20%. A greater AG on admission were significantly associated with increased 28-day mortality in unadjusted analysis (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.09–1.18; p < 0.001). After adjusting for all confounders, the association remained significant (adjusted HR 1.07; 95% CI 1.02–1.13; p = 0.003). When AG was converted into categorial variables (quartiles), the risk of 28-day mortality in the greatest Q4 group was significantly higher compared with that in the lowest Q1 group (model 4: HR = 2.62, 95%CI: 1.17–5.83, p = 0.019). Subgroup analysis showed consistent results across different groups.ConclusionA greater AG on admission were independently associated with increased 28-day mortality in critically ill patients with IE. These findings suggest that the AG can serve as a prognostic marker in this population, aiding in risk stratification and guiding clinical management.

The optimal dietary sodium and chloride level for broiler chicks fed a corn-soybean meal diet between 1 and 21 days of age.

The experiment was conducted to estimate the ideal dietary sodium (Na) and chloride (Cl) level for broilers during d 1 to 21 using a corn-soybean meal diet under a dietary Na:Cl ratio of 1:1. A total of 490 one-d-old Arbor Acres male broilers were randomly allotted by bodyweight to 1 of 7 treatments in a completely randomized design. Each treatment consisted of 7 replicate cages with 10 chicks per cage. Broilers were fed a Na and Cl-unsupplemented corn-soybean meal basal diet (control, containing 0.02% Na and 0.08% Cl) and the Na and Cl-supplemented basal diets containing 0.14%, 0.20%, 0.26%, 0.32%, 0.38% and 0.44% Na and Cl levels, respectively for 21 d. The results indicated that average daily gain, average daily feed intake, blood partial pressure of CO2 and concentrations of HCO3-, total CO2, Na+, Cl-, base excess and anion gap, tibial ash and ash Na contents of broilers were affected (P < 0.001) by dietary Na and Cl level, and increased linearly (P < 0.001) and quadratically (P < 0.001) with increasing Na and Cl levels. Feed/gain ratio, mortality, blood K+ concentration, serum osmotic pressure and K+, glucose and uric acid concentrations as well as heart, liver and kidney indices of broilers were affected (P < 0.01) by dietary Na and Cl level, and decreased linearly (P < 0.001) and quadratically (P < 0.001) with increasing Na and Cl levels. The estimates of dietary optimal Na and Cl levels were 0.07%-0.16% according to the best fitted broken-line or asymptotic models (P < 0.001) of the above sensitive indicators. Therefore, the optimal dietary Na and Cl level was suggested to be 0.16% to support all of the above Na and Cl metabolic requirements of broilers fed the corn-soybean meal diet during d 1 to 21, which is lower than the recommendation at 0.20% by the Chinese Feeding Standard of Chicken (2004).

Factors affecting time to recovery from diabetic ketoacidosis in adult diabetic patients in Alexandria Main University Hospital

BackgroundDiabetic ketoacidosis (DKA) is a life-threatening condition as a complication of diabetes and represents a significant healthcare global burden. The current study goal was to determine factors affecting time to recovery from DKA in Alexandria Main University Hospital.Patients and methodsOne hundred fifty patients who had been admitted with DKA were included in this study. All patients were managed with hospitalization for IV fluids, continuous intravenous insulin infusion, electrolyte correction, as well as detection and treatment of the predisposing factor until the full resolution of DKA.ResultsMales contributed to 58.7% of the total patients in this study with a mean age of 32.16 ± 15.06 years. DKA mean time of resolution was 18.76 ± 14.07 h. The majority of patients were with T1DM (86%), while T2DM were 14%. Missed insulin dose was the leading precipitating factor (60.7%) followed by infections (38.7%). There was a statistically significant relationship between DKA resolution time with age, time of presentation, type of diabetes, initial pH, initial serum K+ level, initial HCO3− level, initial anion gap, initial base excess, and initial RBS (p value < 0.001).ConclusionDelayed time of resolution from DKA was associated with initial lower pH, initial lower HCO3− level, initial lower base excess level, initial higher anion gap level, type 2 diabetes mellitus, patients on pre-mixed insulin regimen, old patients, delayed time for seeking medical care, and abnormal serum K+ level.

Association between serum calcium and in-hospital mortality in intensive care unit patients with cerebral infarction: a cohort study.

The relationship between serum calcium levels and the prognosis of cerebral infarction remains controversial. This study aims to investigate the correlation between serum calcium levels and in-hospital mortality in critically ill patients with ischemic stroke admitted to the intensive care unit (ICU). A retrospective cohort study was conducted using data from the MIMIC-IV database. Demographic and clinical data of all participants were collected including gender, age, hypertension, diabetes, myocardial infarction, heart failure, chronic obstructive pulmonary disease, hemoglobin, potassium, sodium, anion gap, platelets, white blood cells, glucose, creatinine, Glasgow coma score (GCS), IV-tPA administration (rt-PA), and mechanical thrombectomy (MT). The outcome measure was in-hospital death. Multivariable-adjusted logistic regression analysis, curve fitting, interaction analysis, and threshold effect analysis were employed to evaluate the relationship between serum calcium levels and in-hospital mortality among ICU patients with cerebral infarction. A total of 2,680 critically ill patients with cerebral infarction were enrolled, with a mean serum calcium level of 8.6 ± 0.8 mg/dL. The overall in-hospital mortality rate was 19.5%, where Group 1 (serum calcium < 8.0 mg/dL) had a mortality rate of 27.7%, Group 2 (serum calcium 8-9 mg/dL) had a rate of 19.8%, and Group 3 (serum calcium ≥ 9 mg/dL) had a rate of 13.9%. There was a non-linear, S-shaped relationship between serum calcium levels and in-hospital mortality. Serum calcium levels within the range of 7.70-9.50 mg/dL were found to be independently associated with increased in-hospital mortality in ICU patients with cerebral infarction. No significant interactions were detected in subgroup analyses, and the results of sensitivity analyses remained stable. Serum calcium levels are independently associated with in-hospital mortality in critically ill patients with cerebral infarction in the ICU setting. Within the range of 7.70-9.50 mg/dL, lower serum calcium levels increase the risk of in-hospital death among these patients, emphasizing the importance of close monitoring by ICU physicians.

The association between anion gap and length of stay in patients undergoing hip fracture surgery: data from the MIMIC-IV database

ObjectiveTo explore the relationship between anion gap (AG) and length of stay (LOS) in patients undergoing hip fracture surgery.MethodsClinical data of patients diagnosed with hip fracture and undergoing surgery were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Logistic regression analysis by adjusting different covariables and threshold effect analysis were used to analyze the relationship between AG and LOS. Subgroup analysis and interaction test were also performed to detect their relationship. Receiver Operating Characteristic (ROC) analysis was performed to identify the prediction performance and cutoff value of AG.Kaplan-Meier (KM) survival analysis was used to explore the influence of AG on overall survival.ResultsA total of 1508 patients were enrolled and the median LOS was 4.9 days. The correlation between AG and LOS > 7 days was observed among 3 regression models when regarding AG as continuous variables (all OR > 1, all P < 0.05). After stratifying samples with AG quartiles, their relationship was only presented in the Q4 group both in model 1 and model 2 (all P < 0.001). The risk of LOS > 7 days gradually increased with increasing AG quartiles (all P for trend < 0.05). Further, threshold effect analysis found that their association was mainly observed when AG ≥ 14 mEq/L (OR = 1.122, P < 0.001). Subgroup analysis showed that their correlation was not influenced by sex, age, BMI, ethnicity, classification of fracture, therapeutic method, CHD, hypertension, osteoporosis, diabetes and admitted to the ICU (all P for interaction > 0.05). ROC analysis identified 14.5 as the cutoff value of AG for predicted LOS > 7 days. Survival analysis found that patients in the AG < 14.5 group had better overall survival.ConclusionIn patients undergoing hip fracture surgery, the AG was positively correlated with LOS, and 14.5 mEq/L AG was the cutoff value for predicting LOS > 7 days. The cutoff value can favorably distinguish the survival difference of patients.

Euglycemic Diabetic Ketoacidosis Presenting as Chest Pain and Vomiting in a Patient taking SGLT-2 inhibitor

Empagliflozin-induced Euglycemic Diabetic Ketoacidosis (EDKA) is a life-threatening metabolic emergency of Diabetes Mellitus. It is characterized by metabolic acidosis (i.e., pH &lt;7.3 and Serum bicarbonate &lt;15mEq/dl) with an increased anion gap, ketonemia and relatively normal serum glucose level. EDKA resembles Diabetic Keto Acidosis (DKA) but does not exhibit the typical high blood sugar levels. In EDKA, blood glucose is usually below 200 mg/dL. This condition is a diagnostic challenge as euglycemia masks the underlying diabetic ketoacidosis. Here we present a case of Empagliflozin-induced Euglycemic Diabetic Ketoacidosis presented with palpitation and several episodes of vomiting. The aim of this article is to create awareness among clinicians to consider this diagnosis in the differential, especially in the patients taking SGLT-2 inhibitors. Bangladesh Crit Care J September 2024; 12 (2): 172-174

Effect of Pre-Analytical Line Settings on Artefactually Elevated Anion Gap Results

Abstract Introduction When the core lab at a large tertiary care hospital introduced an automated laboratory system from a major manufacturer, the automated line aliquoted patient serum into open cups for all chemistry testing. It was subsequently discovered that if sample testing was delayed, electrolyte abnormalities could be introduced from evaporation, resulting in an increased anion gap (presumably due to a loss of bicarbonate with evaporation of carbon dioxide). To address this issue, the core lab changed the sample processing protocol in April 2023 from an open cup system to testing primary tubes on the analyzers. The purpose of this study was to evaluate the impact of switching to a primary tube testing system on artefactually elevated anion gap results. Methods Equivalent ten-week blocks of anion gap, creatinine and sample turnaround time (from receipt on the line to analyzer perform time) results from pre- to post-primary tube conversion were collected from the laboratory information system. Data from weekend testing and from repeat samples from the same patient were excluded. Data was cleaned and analyzed using R. Results Multivariable linear regression showed that when adjusted for the turnaround time and creatinine result, the open cup system was significantly associated (p&amp;lt;0.0001) with a 0.95 [95% CI 0.69-1.21] increase in anion gap. There was a positive relationship between turnaround time and anion gap, with a slope of 0.017 (i.e., a 0.017 increase in anion gap per minute delay; p&amp;lt;0.0001). Overall, the proportion of abnormal results (defined as anion gap &amp;gt;=16) decreased from 26% to 10% after switching to a primary tube testing system. Furthermore, there was an association between the times of day in which the lines were overloaded with specimens, turnaround time, and an increase in abnormal anion gap results. Overall, the mean anion gap decreased by 1 with a turnaround time of one hour and 2 after two hours by switching to the primary tube system. This trend in anion gap was largely driven by a corresponding decrease in bicarbonate. Sodium and chloride levels did not show any relationship with turnaround time. Conclusions Using an open cup system for electrolyte testing can cause spuriously elevated anion gap levels, especially with testing delays. Switching to a primary tube testing system largely resolved the issue; however, the data still showed a weakly positive relationship between turnaround time and anion gap for the primary tube testing system, so additional work is needed to identify potential causes of this relationship.

Mind the Gap: Influence of Monoclonal Immunoglobulin on Anion Gap in Multiple Myeloma

Abstract Background Multiple myeloma (MM) is a plasma cell disorder in which anion gap and sodium measurement are critically influenced by the presence of abnormal protein concentrations. This study investigates the relationship between anion gap, pseudohyponatremia, and monoclonal immunoglobulin levels (IgG, IgA, IgM), particularly the common IgG. Focusing on the clinical implications of these laboratory results. Methods We retrospectively analyzed data from 136 patients diagnosed with MM, focusing on anion gap values, monoclonal immunoglobulin levels, and sodium levels. The patients were categorized based on their anion gap values (&amp;lt;8) into five groups (anion gap=3, 4, 5, 6, and 7). Monoclonal immunoglobulin levels were standardized to the same units as the anion gap for direct comparison. Additionally, we investigated the pseudohyponatremia by examining sodium levels in these patients. Results Among the 136 MM patients, 70 patients’ anion gap were lower than 8. A negative correlation between MM monoclonal immunoglobulins and anion gap values were observed. The anion gap decreased from 7 to 3 as the IgG average levels ranged increasing from 1755 mg/dL to 2655 mg/dL (RI 610-1616 mg/dL). Similarly, the anion gap decreased from 6 to 3 as the IgM average levels ranged increasing from 1170 mg/dL to 2880 mg/dL (RI 35-242 mg/dL). Additionally, a number of low sodium levels (&amp;lt;136 mmol/L) was observed in each group. Conclusion Our study highlights the negative impact of MM monoclonal immunoglobulins, particularly IgG and IgM, on the anion gap. Both laboratory and clinical personnel should be aware of these phenomena, might prevent unnecessary diagnosis, streamlining patient management and avoiding potential mismanagement.

A rare and underestimated cause of anion gap metabolic acidosis in a pediatric patient

Abstract Recognized causes of anion gap metabolic acidosis include methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, iron, lactic acidosis, ethylene glycol, and salicylates, which is taught as the mnemonic, MUDPILES. While this mnemonic can be a useful learning tool, it is important to consider other, atypical causes. Here, we present the case of a 9-year-old male patient with a complex medical history, including trisomy 21 and Lennox-Gastaut syndrome who presented to the emergency department (ED) in hypotensive shock. Upon admission, he was noted to have a distended abdomen, evidence of acute pancreatitis and possible sepsis. Of note, his initial labs revealed an anion gap of 30.1 mmol/L, a whole blood lactate of 4.4 mmol/L, a pH of 7.2, and a normal pCO2, indicting an anion gap metabolic acidosis. Importantly, methanol, ethylene glycol, ketones, and salicylates were not detected, and renal function was normal. However, he did have an extensive medication history, including several antiepileptic drugs (AEDs). Over the coming weeks, he recovered from the acute pancreatitis, but developed fluid overload, electrolyte derangements (hypernatremia and hypokalemia), a worsening metabolic acidosis with an anion gap up to 54.6 mmol/L, and hyperammonemia (plasma NH3 of 232 μmol/L). At this point, the metabolism team was contacted for concerns regarding the rising ammonia levels, which subsequently responded to a combination of lactulose and Rifaximin. An inborn error of metabolism (IEM) was considered, and plasma amino acid analysis was performed (Waters Acquity MassTrak AAA solution) but was not diagnostic. Notably, the patient developed a significantly elevated gamma glutamyl transpeptidase (GGT) up to 4088 U/L, suggesting glutathione depletion, however, transaminases and alkaline phosphatase were normal. The laboratory was contacted by the metabolism providers for other possible causes of metabolic acidosis and it was suggested that the patient undergo urine organic acid testing. Urine specimens were analyzed using gas chromatography/mass spectrometry (GC/MS) (Aligent system). The results were notable for marked excretion of pyroglutamic acid (5-oxoproline), which is typically associated with acetaminophen, however, the patient’s acetaminophen levels were less than 5 μg/mL, indicating another, atypical cause of increased pyroglutamic acid. In this case, vigabatrin, an anticonvulsant known to cause glutathione depletion and secondary pyroglutamic aciduria was suspected, and subsequently withdrawn. The patient was also started on a trial of N-acetylcysteine (NAC) to replenish glutathione, which resolved the pyroglutamic aciduria and anion gap, and corrected the metabolic acidosis. This case highlights the importance of recognizing pyroglutamic acid as a rare cause of anion gap metabolic acidosis, even in the setting of normal acetaminophen levels, and the importance of organic acid testing in the work-up of such patients. Wider use of the mnemonic GOLD MARK, where the “O” stands for oxoproline, may help in the differential diagnosis of anion gap metabolic acidosis.

Urgent-Start Peritoneal Dialysis in Metformin-Associated Lactic Acidosis: A Critical Alternative When Immediate Hemodialysis is Unavailable.

Introduction Intermittent hemodialysis (IHD) is a preferable renal replacement therapy (RRT) option in metformin-associated lactic acidosis (MALA) due to rapid correct metabolic acidosis. However, IHD might not be started immediately. Immediate urgent-start peritoneal dialysis (iUSPD) is used as a life-saving dialysis option and then followed by IHD. The outcomes of iUSPD were compared with other extracorporeal dialysis in MALA. Methods In two tertiary hospitals in Thailand, the outcomes of patients with MALA who had received three different RRT modalities (iUSPD followed by IHD, IHD, and continuous renal replacement therapy [CRRT]) from January 2015 to December 2019 were compared. The primary outcome was 30-day mortality. The secondary outcomes were door-to-dialysis time and 90-day RRT dependence. Results 180 MALA cases that required dialysis were included (20 iUSPD, 120 IHD, and 40 CRRT). Their mean age was 64 years. Most of the patients had severe metabolic acidosis (mean pH 6.91, HCO3 6 mmol/L, and anion gap 40 mmol/L) and were critically ill. The 30-day mortality was 30% in iUSPD, 9.2% in IHD, and 32.5% in CRRT, p = 0.001). The mortality risk in the iUSPD group was not significantly different from those of the IHD and CRRT groups (adjusted HR 2.5, 95% CI 0.65-9.6 and adjusted HR 0.75, 95% CI 0.2-2.78, respectively). All dialysis modalities had comparable 90-day dialysis dependence. iUSPD exhibited the shortest door-to-dialysis time. Conclusion In MALA, iUSPD followed by IHD might be a viable RRT option to save patient lives if no other dialysis option are available.