Strong Ion Gap Research Articles

Independent variables of pH: Ten Knights of the Hydrogen Ion Kingdom-Part I. A prospective observational study.

CO2, HCO3, SID, and total weak acids have been defined as pH's independent variables. However, according to Gamble, HCO3 should be equal to the difference between the sum of cations and the sum of anions besides HCO3. Therefore, if this mathematical expression is substituted for HCO3 in the Henderson-Hasselbalch equation, all independent variables of pH can be demonstrated. Our aim is to test this theory in this study. This prospective observational study was conducted between 2019 and 2020. All admitted patients to the intensive care unit who were >18 years old were included. Demographic data, blood gas parameters, albumin, magnesium, and inorganic phosphorus levels, and outcomes were recorded twice (at admission and at the 24th hour). The multivariate linear regression model was used to determine pH's independent variables. In the multivariate linear regression model, pH was significantly increased by each unit increase in Na, K, Ca, and Mg (mmol L-1). In contrast, pH was significantly decreased by each unit increase in CO2, Cl, lactate, albumin (g dL-1), inorganic phosphorus (mg dL-1), and the strong ion gap. Ten independent variables can accurately predict the changes in pH. For this reason, all ten independent variables should be separately evaluated when interpreting the acid-base status. With this understanding, all algorithms regarding acid-base evaluation may become unnecessary.

Physico-chemical characterization of acid base disorders in patients with COVID-19: A cohort study

BACKGROUND Acid-base imbalance has been poorly described in patients with coronavirus disease 2019 (COVID-19). Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques. In a cohort of critically ill COVID-19 patients, we looked for an association between metabolic acidosis surrogates and worse clinical outcomes, such as mortality, renal dialysis, and length of hospital stay. AIM To describe the acid-base disorders of critically ill COVID-19 patients using Stewart’s approach, associating its variables with poor outcomes. METHODS This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan. Laboratory and clinical data were obtained from electronic records. Categorical variables were compared using Fisher’s exact test. Continuous data were presented as median and interquartile range. The Mann-Whitney U test was used for comparisons. RESULTS In total, 211 patients were analyzed. The mortality rate was 13.7%. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pondus hydrogenii. Of those presenting with acidosis, most had a low apparent strong ion difference (SID) (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61.0%) had respiratory origin. The non-survivors were older, had more comorbidities, and had higher Charlson’s and simplified acute physiology score 3. We did not find severe acid-base imbalance in this population. The analyzed Stewart’s variables (effective SID, apparent SID, and strong ion gap and the effect of albumin, lactate, phosphorus, and chloride) were not different between the groups. CONCLUSION Alkalemia is prevalent in COVID-19 patients. Although we did not find an association between acid-base variables and mortality, the use of Stewart’s methodology may provide insights into this severe disease.

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.

Strong ion gap and anion gap corrected for albumin and lactate in patients with sepsis in the intensive care unit.

Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis. The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AGcl]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AGcl], [SIG] and inorganic [SIG] ([SIGi]) on admission. There was a strong correlation linking [AGcl] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AGcl] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AGcl] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIGi] AUC: 0.581, 95% CI [0.457, 0.705], [AGcl] AUC: 0.529, 95% CI [0.401, 0.656]. [AGcl] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.

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.

Evaluation of the Acid-Base Status in Patients Admitted to the ICU Due to Severe COVID-19: Physicochemical versus Traditional Approaches.

Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO3-]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome. This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive [HCO3-], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIGcorr). The acid-base status was evaluated in each patient using the BE, [HCO3-], and physicochemical approaches. We included 185 patients. The physicochemical approach detected more individuals with metabolic acid-base abnormalities than the BE and [HCO3-] approaches (p < 0.001), and at least one acid-base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO3 62/186 (33%) methods. Regarding the derived acid-base status variables, non-survivors had greater AGadj, (p = 0.013) and SIGcorr (p = 0.035) compared to survivors. The identification of hidden acid-base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid-base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.

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.

Prognostic Significance of the Strong Ion Gap in Patients in Medical and Surgical Intensive Care Units.

Background This study aimed to analyze acid-base imbalance by assessing the arterial blood gas (ABG) samples of the medical and surgical intensive care unit (ICU) patients by the Stewart approach and demonstrate the advantages of this method in delineating the acid-base status in cases where Henderson-Hasselbalch, anion gap, and base excess cannot optimally depict the imbalance and create recognition in the clinicians in this regard. Methodology Adult (i.e., age > 18 years) patients admitted to the ICU of our institution during a one-year study period were included in this study. The patients were divided into two groups based on the indication of admission to the ICU as medicalor surgical. The ABG, sodium, potassium, calcium, magnesium, phosphate, chloride, albumin, lactate, hemoglobin, hematocrit, leukocyte, blood urea nitrogen, and creatinine values determined during the first 24-hour period were used for calculating the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE II), strong ion difference apparent (SIDa), and SID effective (SIDe) scores, which were subsequently compared between the groups. Results Overall, 220 (110 medical and 110 surgical) patients were included. The mean patient age was 63.56 ± 18.08 years. The mean APACHE II scores were 21.99 and 19.63 in the medical and surgical groups, respectively. Overall, 110 patients died, while 110 were referred to the regular patient floor. The mean APACHE II score of the patients who died was 28.3, and the latter group had a mean APACHE II score of 13.57. There was a significant difference between the surgical and medical patient groups regarding mean values of APACHE II, SIDa, and SIDe scores. Also, the differences were significant between the patients who died and were discharged. There was a significant difference between the patients who died and were discharged regarding the strong ion gap (SIG); however, the medical and surgical patient groups were not different concerning the SIG values. Conclusions We conclude that SIDa, SIDe, and SIG can be used in medical and surgical ICU patients to predict prognosis.

Comparison of Fluid Replacement with Sterofundin ISO® vs. Deltajonin® in Infants Undergoing Craniofacial Surgery-A Retrospective Study.

The purpose of this study was to compare the effects of Sterofundin ISO® (SF) therapy with the balanced isochloremic solution Deltajonin® (DJ) (106 mmol/L chloride) on the acid-base status in infants undergoing craniofacial surgery. This retrospective, non-blinded study included 100 infants undergoing craniectomy due to isolated nonsyndromic sagittal craniosynostosis. The first 50 infants received Sterofundin ISO®. Due to changes in national guidelines, the infusion was changed to the isoionic Deltajonin® in an additional 50 infants in 2017. Pre- and postoperative values of chloride, pH, base excess, bicarbonate, and albumin and phosphate were determined, and the strong-ion difference, strong-ion gap, anion gap, and weak acids were calculated. Both groups were comparable in terms of their age, sex, underlying disease, preoperative electrolytes (except K at 3.9 ± 0.3 mmol/L (SF) vs. 4.1 ± 0.3 mmol/L (DJ) and lactate 8.7 ± 2.1 (SF) vs. 9.6 ± 2.6 mmol/L (DJ)). In the Sterofundin ISO® group, hyperchloremic metabolic acidosis was observed in 19 patients, whereas only 2 infants in the Deltajonin® group had hyperchloremic metabolic acidosis. The postoperative chloride level was 111 ± 2.7 mmol/L (SF) vs. 108 ± 2.4 mmol/L (DJ). The difference in anion gap was 12.5 ± 3.0 mmol/L (SF) vs. 14.6 ± 2.8 mmol/L (DJ), and the difference in SIDa (apparent strong-ion difference) was 30.9 mmol/L (SF) vs. 33.8 mmol/L (DJ). Hyperchloremic acidosis can be induced by the volume replacement with high-chloride-concentration crystalloids such as Sterofundin ISO®. This can be detected using the Stewart model.

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.

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.

Physicochemical properties of abnormal blood acid-base buffering.

This paper describes two new features 1) development of physicochemically based, two-compartment models describing acid-base-state changes in normal and abnormal blood and 2) use of model results to view and describe physicochemical properties of blood, in terms of Pco2 as the causative independent variable and effected [H+] changes as the dependent variable. Models were derived from an in vitro experimental study, where normal blood was made both hypoproteinemic and hyperalbuminemic and then equilibrated with CO2. Strong-ion gap (SIG) values were selected to match model and experimental pH. The effect of individual physicochemical factors affecting blood acid-base-state were evaluated from their induced changes on buffer curve linearized slope (βH+) and [H+] curve shift at 40 mmHg ([H+]40). Model findings were: 1) in severe hypoproteinemia, hemoglobin enhances buffering (decreases βH+), whereas albumin compromises it, resulting in an almost unchanged βH+; [H+]40 decreases (alkalemia) due to hypoalbuminemia. 2) Severe hyperalbuminemia greatly increases both βH+ and [H+]40, hence, compromising buffering and causing a severe acidemia. 3) Pco2-induced changes in the electrical-charge concentration of hemoglobin are the principal factor responsible for maintaining normal buffering characteristics in hypoproteinemia and hyperalbuminemia. 4) SIG values are a third Pco2-independent characteristic of blood acid-base state and 5) the quantities, βH+, [H+]40, and SIG, derived from a [H+] vs. Pco2 perspective, are a more informative and intuitive way to characterize blood acid-base state.NEW & NOTEWORTHY This study represents the most up-to-date, physicochemical, multi-compartment computer model of the processes involved in determining the acid-base buffering state of blood. Previous models lack this capability, notably by being single compartment and/or lacking electroneutrality and osmotic constraints. Model results, analyzed from a different perspective of dependent [H+] changes resulting from independent Pco2 changes, provide a new set of Pco2-independent parameters, characteristic of blood buffering properties.

Does postprandial lipemia interfere with blood gas analysis and assessment of acid-base status in dogs?

To evaluate the interference of postprandial lipemia on blood gas parameters and to assess the acid-base status by the quantitative approach of the strong ion model blood samples of 15 healthy dogs were collected during fasting (0 h) and at one (1 h), three (3 h) and five (5 h) hours after the induction of lipemia with a hypercaloric diet. Total cholesterol (TC) and triglyceride (TG) levels were used to assess lipemia and these were correlated with the parameters evaluated accordingly. Anion gap decreased at 5 h without correlation with TC and TG, whereas other parameters measured by the blood gasometer did not change. In the evaluation of the acid base state, the apparent strong ion difference (SIDa) and the strong ion gap (SIG) showed a decrease at 5 h without correlation with lipemia. Lipid levels correlated with the effective strong ion difference (SIDe), the concentration of total non-volatile weak acids (Atot), albumin, phosphate, and magnesium. The SIDe increased at 1 h and at 3 h; the Atot at 1 h, 3 h, and 5 h; albumin increased at 1 h and 3 h; phosphate increased at 1 h, 3 h and 5 h; and magnesium decreased at 5 h. Though postprandial lipemia does not interfere with blood gas analysis, it can cause errors in the variables used to assess the acid-base status, which are dependent on biochemical analytes. Therefore, caution is required when interpreting electrolyte disturbances that result from the postprandial state.

A Comparison of the Commonly Used Surrogate Markers for Citrate Accumulation and Toxicity during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

Introduction: Continuous renal replacement therapy using regional citrate anticoagulation is commonly used as a modality of organ support in the critically ill population. Currently, citrate accumulation or toxicity is assessed using surrogate markers, notably the uncorrected total-to-ionized calcium ration. The accuracy and utility of this method have been questioned. Objectives/Aims: The aim of this study was to compare the surrogate markers used for assessing citrate accumulation or toxicity using the measurement of plasma citrate as the gold standard. Methods: Blood was sampled from 20 patients before, during, and after episodes of filtration with citrate concentration measured using spectrophotometry. Demographic and other clinical and biochemical data were also collected. According to protocol, a 15 mmol/L solution of trisodium citrate was used as the prefilter anticoagulant. Results were analyzed using STATA (v16.0) and presented as mean (SD), median (IQR), or simple proportion. Univariate linear regression using citrate concentration as the dependent variable was performed with all surrogate markers. Results: Twenty patients (17 males) were enrolled in the study with a mean (SD) age of 62.7 (9.9) years. The uncorrected calcium ratio had the best fit to the citrate data with an R2 value of 0.39. The albumin-corrected calcium ratio, pH, anion gap (AG), albumin-corrected AG, standard base excess, and strong ion gap all had R2 values less than 0.05. Conclusion(s): In the absence of direct measurement of citrate concentration, uncorrected total-to-ionized calcium ratio is superior to other surrogate markers, though not ideal, in assessing citrate accumulation or toxicity.

Utility of Stewart's Approach to Diagnose Missed Complex Acid-Base Disorders as Compared to Bicarbonate-anion Gap-based Methodology in Critically Ill Patients: An Observational Study.

BackgroundTraditional arterial blood gas (ABG) analysis may miss out on some metabolic acid–base disorders. We prospectively compared Stewart's approach in critically ill patients to traditional bicarbonate-anion gap-based methods (with and without correction for albumin) to diagnose acid–base disorders.Patients and methodsFive hundred ABG samples from medical or surgical patients in the ICU were analyzed with traditional bicarbonate-anion gap-based methodology with and without correction for albumin and Stewart's biochemical approach. The primary outcome identification of additional metabolic disorders diagnosed with Stewart's approach in comparison to bicarbonate system-based approaches. We also looked at the correlation between the strong ion gap (SIG) and the albumin-corrected anion gap (acAnion Gap).ResultsStewart's approach detected missed metabolic disorders in 58 (11.6%) blood gas results reported as “within normal limits” with the bicarbonate-uncorrected anion gap approach. In 50 (10%) of these ABGs, the acAnion Gap approach was able to diagnose the missed metabolic disorders. Thus, the albumin-corrected anion gap method had a similar diagnostic performance to Stewart's approach, as it missed additional disorders in only eight (1.6%) blood gases.ConclusionIn this study, we found that the acAnion Gap approach was similar in diagnostic performance to Stewart's approach. We feel that the corrected anion gap approach can be safely used if a ready calculator for Stewart's approach is not available.How to cite this articlePaliwal R, Pakavakis A, Divatia JV, Kulkarni AP. Utility of Stewart's Approach to Diagnose Missed Complex Acid–Base Disorders as Compared to Bicarbonate-anion Gap-based Methodology in Critically Ill Patients: An Observational Study. Indian J Crit Care Med 2022;26(1):23–32.

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.

Stewart analysis unmasks acidifying and alkalizing effects of ionic shifts during acute severe respiratory alkalosis.

Although both the Henderson-Hasselbalch method and the Stewart approach can be used to analyze acid-base disturbances and metabolic and respiratory compensation mechanisms, the latter may be superior in detecting subtle metabolic changes. We analyzed acid-base disturbances using both approaches in six healthy male volunteers practicing extreme voluntary hyperventilation. Arterial blood gas parameters were obtained during a breathing exercise consisting of approximately 30 cycles of powerful hyperventilation followed by breath retention for approximately 2 min. Hyperventilation increased pH from 7.39 ± 0.01 at baseline to 7.74 ± 0.06, PaCO2 decreased from 34.1 ± 1.1 to 12.6 ± 0.7 mmHg, PaO2 increased from 116 ± 4.6 to 156 ± 4.3 mmHg. Baseline apparent strong ion difference was 42.3 ± 0.5 mEq/L, which decreased to 37.1 ± 0.7 mEq/L following hyperventilation. The strong ion gap significantly decreased following hyperventilation, with baseline levels of 10.0 ± 0.9 dropping to 6.4 ± 1.1 mEq/L. Henderson-Hasselbalch analysis indicated a profound and purely respiratory alkalosis with no metabolic compensation following extreme hyperventilation. The Stewart approach revealed metabolic compensation occurring within minutes. These results challenge the long-held axiom that metabolic compensation of acute respiratory acid-base changes is a slow process.

The hidden secrets of a neutral pH\u2014blood gas analysis of postoperative patients according to the Stewart approach

BackgroundThe superiority of either the traditional or Stewart based approach to acid-base balance has focused primarily on analyzing metabolic acidemia, with little attention given to patients with neutral pH. In this study, we evaluate metabolic disturbances in patients in the immediate postoperative period focusing on patients with neutral pH, while comparing the Stewart and traditional approach.MethodsWe conducted a single center retrospective observational cohort study. Over a 17-month period, data on arterial blood gas analysis, electrolytes, and albumin on the morning after surgery were retrieved from patients admitted to the postsurgical high dependency unit (HDU). Albumin-corrected anion gap (AG), apparent (SIDa) and effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated.ResultsOut of 1207 HDU admissions, 400 cases had a complete set of laboratory-data including albumin of which 281 presented with neutral pH (7.35 ≤ pH ≤ 7.45), 64 with acidemia (pH < 7.35) and 55 with alkalemia (pH > 7.45). In pH neutral patients, the following acidifying disturbances were found: SIDa was lowered in 101 (36%), and SIG was raised in 60 (21%). Base excess (BE) was decreased in 16 (6%) and corrected AG raised in 107 (38%). The alkalizing effect of hypoalbuminemia was present in 137 (49%). Out of 134 cases with normal BE and corrected AG, SIDa was lowered in 58 (43%). Out of 136 cases with normal SIDa and SIG, none had lowered BE and 28 increased AG (21%). Length of stay was significantly longer in patients with hypoalbuminemia, lowered SIDa, and increased corrected AG, but not decreased BE (hypoalbuminemia: 16 days vs. 10 days, P < 0.001; low SIDa: 15 days vs. 12 days, P = 0.015; increased AG: 16 days vs. 11 days, P < 0.001; low BE: 14 days vs. 13 days, P = 0.736).ConclusionsMetabolic disturbances, characterized mainly by the presence of lowered SIDa, increased AG, and hypoalbuminemia, are frequent in our population with apparent neutral acid-base balance based on pH and base excess. These changes on the morning after surgery are associated with increased length of stay.

Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery.

Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. Single-center prospective cohort study. Twenty-two bed surgical/medical PICU. Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. None. We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.

Severe metabolic acidosis in critically Ill patients and its association with the outcome in North Karnataka

Background: Outcomes of metabolic acidosis remain unsure and needs to be explored deeply. This article presents a rational approach to diagnosis and management of metabolic acidosis. The data focusing specifically on severe metabolic acidosis (pH&lt;7.20) is scanty. Methods: It was a prospective observational study. A total of 50 consecutive critically ill patients (APACHE II score of 18 or more) with single severe metabolic acidosis (pH&lt;7.20) admitted to the intensive care units (ICUs) of Shri BM Patil Medical College, Vijayapura. Arterial blood gas analysis along with other relevant investigations was done within first 24 h of ICU admission.Results: Among 50 patients, 32 patients expired compared to 18 patients who were discharged from hospital in stable condition. Out of 29 patients, who had lactic acidosis, 21 (72%) patients died compared to 8 (28%) patients who were discharged in stable condition. Out of 22 patients who have low Strong Ion Difference (SID) 16 patients had expired (76%) remaining 6 (24%) patients are discharged at stable condition. Out of 27 patients who were put on mechanical ventilator on the first day, 22 (80%) patients expired. 18 patients required vasopressor support on admission out of which 16 (90%) patients had lactic acidosis. Conclusions: Lactic acidosis and strong ion gap are found to be associated with higher mortality. Hypotensive patients required vasopressor support on admission. Monitoring of serum pH, HCO3−, lactate levels and strong ion gap may have prognostic and therapeutic implications.