Strong ion gap: A methodology for exploring unexplained anions

doi:10.1016/0883-9441(95)90016-0

Journal of Critical Care

Volume 10, Issue 2, June 1995, Pages 51-55

https://doi.org/10.1016/0883-9441(95)90016-0 Get rights and content

Abstract

$Purpose:$ This paper describes the calculation of the strong ion gap (SIG), a physical chemical methodology similar to the anion gap (AG), as a measure of the anion/cation balance exclusive of sodium, potassium, chloride, and bicarbonate. We compared the SIG and AG methodologies in three groups of subjects with and without unexplained anions. These groups were (1) healthy volunteers with hyperlacticemia during exercise; (2) intensive care unit (ICU) patients with sepsis; and (3) ICU patients with severe liver disease.

$Methods:$ The SIG, AG, and corrected AG (AGc) were calculated for each group from data available in the original reports (groups 1 and 2) and by retrospective chart review (group 3).

$Results:$ The SIG correlated poorly with the AG in group 2, whereas no correlation was seen in groups 1 and 3. The AGc correlated with SIG in all three groups (r = .99, .93, and .91 respectively; P < .01 for each group). Although the AG was similar, the SIG differed for each group. Group 1 had levels of SIG near zero, and groups 2 and 3 had mean SIG's of 4.80 ± 4.67 mEq/L and 9.60 ± 6.43 mEq/L respectively. The composition of the anion gap differed markedly among subject types.

$Conclusions:$ The SIG correlates with the AG once corrected for all known anions. The SIG technique can detect unknown anions in a patient population known to have them and does not detect unknown anions in healthy volunteers during exercise. This test detects large amounts of unknown anions in some patients with sepsis or liver disease. Therefore, the test is both sensitive and specific in characterizing metabolic acidosis.

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Clinical Approach to Assessing Acid-Base Status: Physiological vs Stewart
2022, Advances in Chronic Kidney Disease
Citation Excerpt :
Although he conducted theoretical work in a flask, he concluded that his concepts are applicable to whole organisms.46-49,68,80-82 Utilizing SID, his followers described SIG that is proposed to better detect increased unmeasured anions, particularly in critically ill patients.56,57 SIG assesses excess unmeasured anions without requiring the clinician to adjust for albumin as it is the case for AG.
Evaluation of acid-base status depends on accurate measurement of acid-base variables and their appropriate assessment. Currently, 3 approaches are utilized for assessing acid-base variables. The physiological or traditional approach, pioneered by Henderson and Van Slyke in the early 1900s, considers acids as H⁺ donors and bases as H⁺ acceptors. The acid-base status is conceived as resulting from the interaction of net H⁺ balance with body buffers and relies on the H₂CO₃/HCO₃⁻ buffer pair for its assessment. A second approach, developed by Astrup and Siggaard-Andersen in the late 1950s, is known as the base excess approach. Base excess was introduced as a measure of the metabolic component replacing plasma [HCO₃⁻]. In the late 1970s, Stewart proposed a third approach that bears his name and is also referred to as the physicochemical approach. It postulates that the [H⁺] of body fluids reflects changes in the dissociation of water induced by the interplay of 3 independent variables—strong ion difference, total concentration of weak acids, and PCO₂. Here we focus on the physiological approach and Stewart's approach examining their conceptual framework, practical application, as well as attributes and drawbacks. We conclude with our view about the optimal approach to assessing acid-base status.
Acid-base abnormalities and liver dysfunction
2022, Annals of Hepatology
In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.
Effect of sodium–chloride ion difference on pH regulation
2021, Clinical Biochemistry
In the Stewart approach, the difference between the cation and anion concentrations, especially between sodium, accounting for the majority of cations, and chloride, comprising the majority of anions, is an important factor in pH regulation. This study investigated the effect of sodium–chloride ion difference (SCD) on pH regulation comparing with those of PaCO₂ and lactate.
Arterial blood gas samples measured at our pediatric intensive care unit of a tertiary children’s hospital between January and June 2020 were included. Samples that met the following criteria were excluded: samples collected from patients taking potassium bromide and samples with lactate concentration of >25 mmol/L. From the eligible data, pH was chosen as the dependent variable and SCD, lactate, and PaCO₂ as independent variables, and then, a multiple regression analysis was performed.
In total, 5360 samples were included. Of these, five samples were excluded according to the exclusion criteria. Finally, 5355 samples were analyzed. As the variance inflation factors were <2.0 for all three variables, there was no multicollinearity. The following model was derived: pH = 7.384 + [0.97 × SCD (mEq/L) − 0.66 × PaCO₂ (mmHg) − 1.33 × Lac (mmol/L)] × 10⁻² (adjusted R-squared = 0.73; P value < 0.001). Based on the standardized partial regression coefficients (β), pH was affected in the order of PaCO₂ (β_PaCO2 = −0.95), SCD (β_SCD = 0.72), and lactate (β_lactate = −0.33).
The prevention of SCD reduction, together with respiratory and metabolic management, is important for pH regulation.
The effects of severe hemoconcentration on acid-base equilibrium in critically ill patients: the forgotten role of buffers in whole blood
2020, Journal of Critical Care
Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a paroxysmal permeability disorder characterized by abrupt onset of shock and hemoconcentration due to massive shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesize that increased hemoglobin concentration has a pivotal role in the acid-base imbalance during life-threatening crises.
Analysis of the acid-base balance fluctuations during six severe ISCLS flares admitted to ICU of a referral center for ISCLS.
Acid-base equilibrium was assessed for plasma and the whole blood by single and multicompartmental models. The acute phase of ISCLS was characterized by shock, hypoalbuminemia, severe hemoconcentration, and acidosis. The physical-chemical approach for plasma found a remarkable component of unmeasured anions (SIG) during the acute phase. After correction of the physical-chemical model for the whole blood, the SIG variations disappeared because the buffer role of hemoglobin was relevant.
Hemoglobin has a remarkable role in buffering metabolic acidosis during the shock phase of ISCLS. In these circumstances, the assessment of acid-base equilibrium in plasma alone may overestimate unmeasured anions. On the contrary, the physical-chemical model corrected for whole blood better explains the metabolic component of acid-base imbalance when marked shift of hemoglobin concentration occurs.
Changes in the SID<inf>Actual</inf> and SID <inf>Effective</inf> Values in the Course of Respiratory Acidosis in Horses With Symptomatic Severe Equine Asthma—An Experimental Study
2019, Journal of Equine Veterinary Science
Equine asthma syndrome is an allergic, inflammatory airway disease that usually affects older horses. Respiratory acidosis is an acid–base imbalance caused by alveolar hypoventilation. The acid–base balance may be assessed using the Henderson–Hasselbalch equation as well as the Stewart model. The authors hypothesized that systemic respiratory acidosis changes the ionic concentrations affecting water dissociation. The study group included 16 Warmblood, mixed breed horses of both sexes with a history of severe equine asthma, and 10 healthy horses were used as controls. Arterial and venous blood were collected from all the horses. The pH, pO₂, and pCO₂ and HCO₃₋ were assessed in the arterial blood. Na, K, Cl, albumin, and P_inorganic (P_i) were assessed in the venous blood. The obtained results were used to calculate the anion gap (AG), modified AG, actual strong ion difference (SID_a), weak non-volatile acids, and effective strong ion difference (SID_e) values for all the horses. A systemic, compensatory respiratory acidosis was diagnosed in the study group. The concentration of Na in the blood serum in the study group was significantly higher, whereas the concentration of Cl was significantly lower than the values in the control group. The SID_a and SID_e values calculated in the horses from the study group were significantly higher than those in the control group. Significantly higher SID_a and SID_e values confirm the presence of ionic changes that affect water dissociation in the course of respiratory acidosis in horses. The SID_a and SID_e values may be useful in the diagnosis and treatment of respiratory acidosis in horses, which warrant further investigation.
Sodium bicarbonate therapy for critically ill patients with metabolic acidosis: A scoping and a systematic review
2019, Journal of Critical Care
We aimed to assess the biochemical and physiological effects, clinical efficacy, and safety, of intravenous NaHCO3 therapy in critically ill patients with acute metabolic acidosis.
We conducted a scoping review concerning the biochemical and physiological effects of NaHCO3 (PART A), and a systematic review regarding clinical efficacy (PART B). We searched MEDLINE in Part A and MEDLINE, EMBASE, Cochrane, the National Institute of Health Clinical Trials Register, and the WHOICTRP for randomised controlled trials in Part B.
Twelve studies in Part A and two trials in Part B fulfilled the eligibility criteria. Intravenous NaHCO3 increased blood pH, base excess, serum bicarbonate, sodium, and PaCO2 during and after administration and decreased anion gap and potassium value. For clinical efficacy, only one study contributed to the effect estimate. The risk ratio (RR) for all-cause mortality was 0.83 (95% confidence interval, 0.68 to 1.02), and the risk of hypocalcaemia was increased in the bicarbonate group (RR 1.65, 95% confidence interval 1.09 to 2.50). There were inadequate data on hemodynamic indices.
Given the lack of data on the effects of intravenous NaHCO3 therapy to support its clinical use and the frequency of bicarbonate therapy, a program of investigation appears justified.

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Original investigationStrong ion gap: A methodology for exploring unexplained anions

Abstract

J Crit Care

Am J Med

ABC's of interpretive laboratory data

Relationship between spectral shifts and structural changes in uric acids and related compounds

J Am Chem Soc

Acid-base disorders in critical care medicine

Ann Rev Med

The role of serum proteins in acid-base equilibria

J Lab Clin Med

Serum proteins and acid-base equilibria: A follow-up

J Lab Clin Med

Diagnostic importance of an increased serum anion gap

N Engl J Med

Original investigation
Strong ion gap: A methodology for exploring unexplained anions