Acid-base Interpretation Research Articles

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.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Correcting Acid Base Interpretation for High Altitudes.

Correcting Acid Base Interpretation for High Altitudes.

Identifying hydric, electrolytic and acid-base imbalances through traditional and quantitative approaches in dogs with hemorrhagic gastroenteritis

ABSTRACT Vomiting and diarrhea are two important clinical signs that can cause significant electrolytic and acid-base imbalances. The purposes of this study were to characterize hydric, electrolytic and acid-base disorders presented by puppies with hemorrhagic gastroenteritis and to compare the traditional and quantitative approaches to acid-base status interpretation. Sixty-one animals with a history of vomiting and/or diarrhea were used in this study and the following tests were performed: complete blood count, total plasma protein concentration and hemogasometry. Mean, standard deviation and Kappa values were calculated. The imbalances characterized by both approaches were: 42 (69%) animals without imbalance, 17 (28%) with metabolic alkalosis and 2 (3%) with metabolic acidosis by the traditional approach and 17 (28%) dogs without imbalance, 26 (43%) with metabolic alkalosis and 18 (29%) with metabolic acidosis by the quantitative approach. The agreement calculated between two approaches coincide in 28 cases, with a moderate Kappa value equivalent to 0.459. The most found imbalances were metabolic alkalosis, hypokalemia, and mild dehydration. Most of acid-base disturbances were not identified by the traditional approach, whereas by the quantitative approach, they were easily determined. Thus quantitative approach proved to be superior in identification of possible acid-base imbalances.

Parametric correlation of arterial blood gas status with the duration of stay in hospital in cases of acute severe asthmatic children

Background: Asthma is one of the common causes of chronic illness in early childhood having frequent admitting diagnosis in pediatric ward. It needs proper evaluation for their treatment and management. Determination of arterial blood gas (ABG) analysis plays important role as pulmonary function test; it is important laboratory test for critically ill asthmatic patients where acid-base status interpretation is needed for their hospital admission and proper management. Aims and Objectives: The aims of the study were to assess the severity of disorders with the parameters of ABG report with their hospital stay of severe asthmatics pediatric patients during their acute exacerbations. Materials and Methods: A hospital-based prospective study conducted in forty-three severe acute bronchial asthmatic patients of 1–17 years done using automated ABG analyzer machine (COMBISYS-II), analysis of ABG report done using mean, median, and standard deviation. Results: Their comparison with the dysfunction of ABG report with their hospital stay showed positive correlation. Conclusion: Our study supported the hypothesis of enhanced hospital stay with abnormal and mixed type of ABG report.

Evaluation of the association between strong ion acid-base disturbances and mortality in dogs: a retrospective study.

Acid–base abnormalities are frequently encountered in veterinary emergency and critical care, but information regarding the prognostic value of these findings is limited. Several systems for analysing acid–base disturbances have been reported, but the prognostic abilities of these systems have not been compared in dogs. The objectives of this retrospective study were to determine if the commonly used acid–base interpretation methods (Henderson–Hasselbalch, Stewart and semi‐quantitative) have prognostic value, and to compare the performance of the three methods. Electronic medical records were searched to create a database containing point‐of‐care blood‐gas, electrolyte and serum chemistry values for 1024 dogs assessed at a university teaching hospital. Dogs with contemporaneous blood‐gas analysis, blood lactate and serum biochemistry samples were eligible for study, and only the first recorded analyses for each patient visit were included. Components of the Henderson–Hasselbalch, Stewart and semi‐quantitative methods were calculated. To assess prognostic ability and to compare analysis system performance, receiver‐operating characteristic (ROC) curves for survival to hospital discharge were created. Of the 1024 dogs identified, case fatality rate was 23.8%. Area under the ROC curve did not exceed 0.63 for any calculated variable. Performance of all three analysis systems was similar. While some acid–base abnormalities identified were associated with mortality, no individual abnormality or system output yielded sensitive and specific cut‐off values for mortality prediction, and no interpretation method outperformed the others. This study suggests that initial acid–base abnormalities have limited prognostic utility and that various analysis systems can be used to assess acid–base disturbances in critically ill dogs.

The Influence of Chloride for the Interpretation of Plasma Bicarbonate During the Treatment of Diabetic Ketoacidosis.

Hyperchloremic metabolic acidosis can occur in diabetic ketoacidosis (DKA) and may affect the acid-base interpretation during treatment. This study aims to describe the prevalence of hyperchloremia during the treatment of DKA and its effect on the interpretation of bicarbonate value. A cross-sectional study, including all cases of DKA in patients aged 1 to 18 years old admitted from 2010 to 2015, was performed. Laboratory tests were performed on admission (baseline), 2 and 6 hours after admission, and when resolution of DKA was achieved. Adjusted bicarbonate value was calculated using regression equations. Seventy-nine DKA episodes were included. The average age was 13.3 ± 3.8 years. Baseline levels were as follows: plasma glucose, 479 ± 133 mg/dL; pH 7.1 ± 0.083; bicarbonate, 9.65 ± 2.9; and anion gap, 23.9 ± 7.5. The time to achieve resolution of DKA was 12.2 ± 4.4 hours, and the decrease in capillary glucose was 25.5 (19.7-38.2) mg/dL per hour. After 6 hours of treatment, the proportion of patients presenting hyperchloremia increased from 23% to 77%. By using adjusted bicarbonate, the percentage of patients achieving resolution of DKA after 6 hours of treatment would have been 35.4% (confidence interval 95%, 28-49), in comparison with 24.1% (confidence interval 95%, 18-37) using observed bicarbonate (P = 0.004). The hyperchloremia developed during the treatment of DKA could modify the value of measured plasma bicarbonate concentration and unnecessarily prolong the initial phase of treatment.

Understanding the role of the cerebrospinal fluid in acid-base disorders.

The importance of acid–base interpretation is witnessed by the bulk of literature constantly being published on the topic [1, 2]. However, none of the recently published papers specifically addresses the acid–base equilibrium of the cerebrospinal fluid (CSF), which is an important compartment, since it influences the activity of the central controllers of respiration. Here, we will briefly discuss the characteristics of CSF acid–base equilibrium and their implications on the control of breathing, basing our reasoning on Stewart’s approach [3]. Moreover, we will highlight some clinical implications that, we believe, are usually not fully considered by clinicians.

Base excess, strong ion difference, and expected compensations

The main purpose of this article is to provide some practical insights into acid-base disorders interpretation, comparing the three most widespread diagnostic approaches. After a brief summary of the history of blood gas analysis and the shift from a purely chemical approach to more clinically useful applications, the pros and cons of the different methodologies are compared and discussed. Reviewing the most important publications in the field, the authors attempt to show that each diagnostic strategy is acceptable, although the one based on base-excess calculation perhaps seems too 'rough' to understand the mixed disorders, whereas the Stewart approach is attractive from a chemical point of view, but unsuitable for the emergency physician because of the cumbersome calculations needed. Finally, the anion gap and 'expected compensation' approach seems to be more comprehensive and feasible at the bedside.

Clinical utility of serum biochemical variables for predicting acid-base balance in critically ill horses.

Profiles from serum biochemical analyzers include the concentration of strong electrolytes (including l-lactate), total carbon dioxide (tCO2 ), and total protein. These variables are associated with changes in acid-base balance. Application of physicochemical principles may allow predicting acid-base balance from serum biochemistry without measuring whole blood pH and pCO2 . The purpose of the study was to determine if the acid-base status of critically ill horses could be accurately predicted using variables included in standard serum biochemical profiles. Two jugular venous blood samples were prospectively obtained from critically ill horses and foals. Samples were analyzed using a whole blood gas and pH analyzer (BG) and a serum biochemistry multi analyzer system (AMAS). Linear regression, Deming regression, and Bland-Altman plots were used for method comparison and P<.05 was considered significant. Values from 70 horses and foals for Na, K, Cl, and total protein concentrations, and consequently the calculated variables used for acid base interpretation, were different between the AMAS and BG analyzer. Using physicochemical principles, BG results accurately predicted pH, whereas the AMAS results did not when a fixed value for pCO2 was used. Measurement of pCO2 is required in critically ill horses for accurate prediction of whole blood pH. Differences in the measured values of Na and Cl concentration exist when measured in serum by the AMAS and in whole blood or plasma by BG, indicating that the accurate prediction of whole blood pH is analyzer-dependent. Application of physicochemical principles to plasma or serum provides a practical method to evaluate analyzer accuracy.

Comparative Study between Traditional Approach and Physico-Chemical Approach in Acid Base Disorders Interpretation in Critically Ill Patients

Objective: The traditional approach for acid base interpretation is based on Handerson-Hasselbalch formula and includes Base Excess (BE), bicarbonate (HCO3), albumin corrected anion gap. The Physicochemical approach is centered on the Carbon Dioxide tension (PCO2), the strong ion difference (SID), strong ion gap (SIG) = SID apparent-SID effective and totally weak acids (Atot). The study aims to compare between the traditional approach and the physicochemical approach in acid base disorder interpretation. Design: Prospective observational study in an adult Intensive Care Unit (ICU) recruiting six hundred and sixty one patients. Methods: Arterial blood samples were analyzed to measure pH, PaCO2 sodium, potassium, chloride and lactate. Venous blood samples were analyzed to measure ionized calcium, magnesium, phosphorous and albumin. These samples were interpreted by both techniques. Results: Normal HCO3 and BE were detected by traditional approach in 49 cases of which SIG acidosis was detected in 22 cases (46%) and Hyperchloremic acidosis was detected in 29 cases (60%) by physicochemical method. SIG was elevated in 72 cases (58%) of 124 cases with high anion gap acidosis. SIDeff and BE were strongly correlated, r = 0.8, p 0.0001, while SIG and Albumin corrected Anion Gap (ALAG) were moderately correlated r = 0.56, p Conclusion: Both approaches are important for interpretation of the acid base status. Traditional approach identifies the diagnostic description without many calculations and detects body compensatory response to acid base disorders. Physicochemical approach is essential to identify the exact causation and the severity of the acid base disorders.

Advanced arterial blood gas analysis in septic shock: A Singaporean nursing case review

The admission to the intensive care unit with a diagnosis of sepsis and/or septic shock is not uncommon. The aim of this article is to present a nursing case review of a patient admitted to the intensive care unit with a diagnosis of septic shock and the use of bedside acid-base formulae to inform clinical decision making. We chose to use a case review. This method is useful in reporting unusual or rare cases and is typically seen more in medicine than in nursing. The gentleman in question was a self-presentation with a short history of fever and worsening shortness of breath. His condition worsened where he required admission to the intensive care unit. The use of 'advanced' acid-base interpretation to guide his nursing care provided a platform from which to advance a deeper understanding of the intricacies the critically ill patient often presents. The use of case review is enlightening in understanding the disease process and the decision-making that accompanies this. The lessons learnt are applicable to a wider nursing audience because understanding acid-base physiology is beneficial in supporting and advancing critical care nursing practice.

Acid-Base Disorders in ICU Patients

Metabolic acid-base disorders are comnom clinical problems in ICU patients. Arterial blood gas analysis and anion gap (AG) are important laboratory data in approaching acid-base interpretation. When measuring the AG, several factors such as albumin have influence on unmeasured anions and unmeasured cations. If a patient has hypoalbuminemia, the AG should be adjusted according to the albumin level. High AG metabolic acidoses including lactic acidosis, ketoacidosis, and ingestion of toxic alcohols are common in ICU patients. The treatment target of lactic acidosis and ketoacidosis is not the acidosis, but the underlying condition causing acidosis. Gastric acid loss, diuretics, volume depletion, renal compensation for respiratory acidosis, hypokalemia, and mineralocorticoid excess are common causes of metaboic alkalosis. In chloride responsive metaboic alkalosis, volume and potassium repletion are mandatory.

Invited commentary: Putting standard base excess to the test

The interface between acid-base physiology and blood gas interpretation is historically both stimulating and turbulent [1]. In 2009, most clinicians accept a bimodal categorization of acid-base disorders as either “respiratory” or “metabolic,” with arterial PCO2 (PaCO2) as the primary index of respiratory acid-base status. However, even today, there is no agreed method of defining and quantifying the metabolic component. An important milestone was passed nearly 50 years ago with the advent of “base excess” (BE), introduced by Siggaard-Andersen and Engel [2] after a series of experiments on the blood of Danish volunteers. Base excess was promoted as the ultimate measure of metabolic acid-base status. The subsequent debate was divisive [3], with practitioners separating into 2 “schools,” Boston or Copenhagen. Base excess became the flagship of the Copenhagen school. Base excess is determined from measurements of plasma pH, blood PCO2, and hemoglobin concentration. It can be defined as the concentration of titratable hydrogen ion required to return the pH of in vitro whole blood to 7.4 at 37°C, with PCO2 held at 40 mm Hg. For the first 17 years, BE was calculated empirically from the Danish nomogram. Then, Siggaard-Andersen [4] published a new equation, derived from expressions linking plasma and intraerythrocytic buffering and associated Gibbs-Donnan ionic distributions. He named it the Van Slyke equation, in honor of the American clinical chemist and acid-base pioneer, Donald Dexter Van Slyke. A prerequisite for any stand-alone metabolic acid-base parameter is “CO2 invariance.” By this, we mean that pure respiratory acid-base fluctuations have no distorting effect. Unfortunately, although the Van Slyke equation displays admirable CO2 invariance when applied to blood ex vivo [5], it falls short in the living patient [6]. The problem is that neither the nomogram nor the subsequent Van Slyke

Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization

Objectives Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses. Design and Patients Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study. Results Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant ( P < .0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure. Conclusions Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis < metabolic acidosis < respiratory acidosis < mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.

Comment on “The influence of hyperchloraemia on acid--base interpretation in diabetic ketoacidosis” by Taylor et al.

Sir: I read with great interest the paper “The influence of hyperchloraemia on acid–base interpretation in diabetic ketoacidosis” [1], especially after the introduction, “Diabetic ketoacidosis (DKA) is a common, life-threatening complication of diabetes mellitus in children. . . . The importance of acid–base monitoring during therapy is widely acknowledged, yet many guidelines do not provide detailed instructions on how to interpret and act upon acid–base abnormalities in this setting”. However, in the following seven pages the authors did not say what is life-threatening in DKA. Nor did they give “instructions on how to interpret and act upon acid–base abnormality” with the aim of treating life-threatening situations and preventing them. In DKA, immediately lifethreatening is coma, and according to Alberti et al. [2] the cause of coma is very low blood pH (= very high concentration of hydrogen ions H+). This inhibits the activity of the pH-dependent glycolytic enzyme phosphofructokinase, resulting in impaired utilization of glucose, deleterious especially for brain cells whose main energy-yielding substrate is glucose. Zero lethality in comatose patients with DKA is reported only by authors who have administered to the comatose patients, as soon as possible, infusions of alkalizing solutions to increase the low blood pH (e.g., Wagner et al., reference 18 in the authors’ paper, Umpierrez et al. [3], and Yordam et al. [4]). No doubt, very interesting is the authors’ observation that in DKA the proportion of chloride in the base deficit increases from 2% to 98% during the first 20 h after admission. However, the anions usually measured in DKA – chloride, acetoacetate, β-hydroxybutyrate, bicarbonate – are not life-threatening per se. If an anion is life-threatening, e.g., cyanide CN–, then it is life-threatening as acid HCN and also as alkaline salt KCN or NaCN, regardless of the pH of the solution. In DKA, life-threatening is the high concentration of H+ regardless of the accompanying anion (or anions). References

The influence of hyperchloraemia on acid base interpretation in diabetic ketoacidosis

During the acute treatment of diabetic ketoacidosis we (a) determined the temporal incidence of hyperchloraemia, and (b) quantified the influence of hyperchloraemia on interpretation of common blood gas derived acid base parameters, namely base deficit and bicarbonate. Retrospective chart review in two regional paediatric intensive care units. Stewart's physicochemical theory was used to develop regression equations quantifying the acidifying effect of hyperchloraemia on both base deficit and bicarbonate. These were then applied retrospectively to blood chemistry results from 18 children (median age 12.7 years, weight 43 kg) with diabetic ketoacidosis. Plasma ketonaemia was estimated using the albumin-corrected anion gap. The incidence of hyperchloraemia, as documented by a ratio of plasma chloride to sodium of greater than 0.79, increased from 6% at admission to 94% after 20 h of treatment. Correction for chloride produced a dramatic improvement in the relationship between changes in the anion gap vs. both base deficit (from R(2)=0.55 to R(2)=0.95) and bicarbonate (from R(2)=0.51 to R(2)=0.96) during treatment. After 20 h of treatment the mean base deficit had decreased from 24.7 mmol/l to 10.0 mmol/l however, the proportion that was due to hyperchloraemia increased from 2% to 98%. It is now possible using a simple correction factor to quantify the confounding effect of hyperchloraemia on both base deficit and bicarbonate in diabetic ketoacidosis. This bedside tool may be a useful adjunct to guide therapeutic interventions.

The hyponatramia of multiple myeloma is true and not pseudohyponatramia

The hyponatremia found in multiple myeloma and which is associated with a reduced anion gap (ag) is considered to be pseudohyponatremia due to the displacement of water by the high globulin content in the blood. Serum proteins participate in acid-base balance. Stewart and other authors in their approach to acid-base interpretation acknowledge electrical neutrality as a fundamental characteristic of body fluids. Furthermore, they have shown that both the strong ion difference (SID) and protein, specifically, negatively-charged albumin affect hydrogen ion concentration (H(+)) in the body--i.e., for example an increase in SID leads to a decrease in H(+) and a decrease in albumin leads to a similar effect. The M proteins of multiple myeloma are positively charged. As a result they cause a decrease in sodium levels and the anion gap and thus a true hyponatremia.

Application of simulated annealing fuzzy model tuning to umbilical cord acid-base interpretation

Fuzzy logic and fuzzy set theory provide an important framework for representing and managing imprecision and uncertainty in medical expert systems, but the need remains to optimize such systems to enhance performance. The paper presents a general technique for optimizing fuzzy models in fuzzy expert systems (FESs) by simulated annealing (SA) and N-dimensional hill climbing simplex method. The application of the technique to a FES for the interpretation of the acid-base balance of blood in the umbilical cord of newborn infants is presented. The Spearman rank order correlation statistic was used to assess and to compare the performance of a commercially available crisp expert system, an initial FES, and a tuned FES with experienced clinicians. Results showed that without tuning, the performance of the crisp system was significantly better (correlation of 0.80) than the FES (correlation of 0.67). The performance of the tuned FES was better than the crisp system and effectively indistinguishable from the clinicians (correlation of 0.93) on training data and was the best of the expert systems on validation data. Unlike most applications of fuzzy logic where all fuzzy sets have normalized heights of unity, in this application it was found that a reduction in the height of some fuzzy sets was effective in enhancing performance. This suggests that the height of fuzzy sets may be a generally useful parameter in tuning FESs.