Electrophoretic Determination of Symmetric and Asymmetric Dimethylarginine in Human Blood Plasma with Whole Capillary Sample Injection.

Asymmetric and symmetric dimethylarginines are toxic non-coded amino acids. They are formed by post-translational modifications and play multifunctional roles in some human diseases. Their determination in human blood plasma is performed using capillary electrophoresis with contactless conductivity detection. The separations are performed in a capillary covered with covalently bonded PAMAPTAC polymer, which generates anionic electroosmotic flow and the separation takes place in the counter-current regime. The background electrolyte is a 750 mM aqueous solution of acetic acid with pH 2.45. The plasma samples for analysis are treated by the addition of acetonitrile and injected into the capillary in a large volume, reaching 94.5% of the total volume of the capillary, and subsequently subjected to electrophoretic stacking. The attained LODs are 16 nm for ADMA and 22 nM for SDMA. The electrophoretic resolution of both isomers has a value of 5.3. The developed method is sufficiently sensitive for the determination of plasmatic levels of ADMA and SDMA. The determination does not require derivatization and the individual steps in the electrophoretic stacking are fully automated. The determined plasmatic levels for healthy individuals vary in the range 0.36-0.62 µM for ADMA and 0.32-0.70 µM for SDMA.

Possible Role of Electrolytes on the Formation of Precipitates during the Infusion of Nafamostat Mesilate in Hemodialysis.

Nafamostat mesilate (NFM) is used as an anticoagulant during hemodialysis in patients who have had complications due to hemorrhages. The formation of precipitates, which could lead to the interruption of hemodialysis has been reported when NFM is infused into blood during hemodialysis. We report herein on an examination of possible factors that could cause this. The effects of electrolytes such as phosphates, citrates or succinates on the formation of precipitates were examined by mixing NFM with aqueous solutions or plasma that contained these electrolytes. The formation of precipitates was observed in all electrolyte solutions when higher concentrations of NFM were mixed at around physiological pH. In the case of plasma, precipitates were observed when solutions containing higher concentrations of NFM were mixed with plasma that contained phosphate and citrate. In addition, the formation of precipitates under dynamic conditions where NFM was infused into flowing electrolyte solutions was also evaluated. The data suggested that such precipitates might be formed and disrupt the blood flow and/or an NFM infusion when NFM is infused into blood flowing in the hemodialysis circuit. The findings presented herein suggest the serum levels of anionic electrolytes (e.g., phosphate), the type of excipients present in pharmaceutical products (e.g., succinic acid or citric acid), the concentration of NFM used for the infusion or the rates of NFM infusion and blood flow are all factors that could affect precipitate formation during NFM infusions for hemodialysis.

The usefulness of measuring the anion gap in diagnosing metformin-associated lactic acidosis: a case series.

BACKGROUND: Metformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain. CASE PRESENTATION: Cases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14. CONCLUSIONS: In patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.

Acid-base variables in acute and chronic form of nontuberculous mycobacterial infection in growing goats experimentally inoculated with Mycobacterium avium subsp. hominissuis or Mycobacterium avium subsp. paratuberculosis.

In current literature, data assessing the acid-base equilibrium in animals and humans during bacterial infection are rare. This study aimed to evaluate acid-base deteriorations in growing goats with experimentally induced NTM (nontuberculous mycobacteria) infections by application of the traditional Henderson-Hasselbalch approach and the strong ion model. NTM-challenged animals were orally inoculated with either Mycobacterium avium subsp. hominissuis (MAH; n = 18) or Mycobacterium avium subsp. paratuberculosis (MAP; n = 48). Twenty-five goats served as non-infected controls. Until 51st week post-inoculation (wpi), blood gas analysis, serum biochemical analysis, and serum electrophoresis were performed on venous blood. Fifty percent (9/18) of goats inoculated with MAH developed acute clinical signs like apathy, fever, and diarrhea. Those animals died or had to be euthanized within 11 weeks post-inoculation. This acute form of NTM-infection was characterized by significantly lower concentrations of sodium, calcium, albumin, and total protein, as well as significantly higher concentrations of gamma globulin, associated with reduced albumin/globulin ratio. Acid-base status indicated alkalosis, but normal base excess and HCO3- concentrations, besides significantly reduced levels of SID (strong ion difference), Atot Alb (total plasma concentration of weak non-volatile acids, based on albumin), Atot TP (Atot based on total protein) and markedly lower SIG (strong ion gap). The remaining fifty percent (9/18) of MAH-infected goats and all goats challenged with MAP survived and presented a more sub-clinical, chronic form of infection mainly characterized by changes in serum protein profiles. With the progression of the disease, concentrations of gamma globulin, and total protein increased while albumin remained lower compared to controls. Consequently, significantly reduced albumin/globulin ratio and lower Atot Alb as well as higher Atot TP were observed. Changes were fully compensated with no effect on blood pH. Only the strong ion variables differentiated alterations in acid-base equilibrium during acute and chronic NTM-infection.

Serum Anion Gap Is Associated with All-Cause Mortality among Critically Ill Patients with Congestive Heart Failure.

BACKGROUND: Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) is associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear. METHODS AND RESULTS: A retrospective analysis of data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4 was conducted in critically ill patients with CHF. The clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were used to determine the relationship between SAG and mortality in patients with CHF, the consistency of which was further verified by subgroup analysis. RESULTS: A total of 7426 subjects met the inclusion criteria. Multivariate analysis showed that after adjusting for age, gender, ethnicity, and other potential confounders, increased SAG was significantly related to an increase in 30- and 90-day all-cause mortalities of critically ill patients with CHF compared with decreased SAG (tertile 3 versus tertile 1: adjusted hazard ratio, 95% confidence interval: 1.74, 1.46-2.08; 1.53, 1.32-1.77). Subgroup analysis indicated that the association between SAG and all-cause mortality presented similarities in most strata. CONCLUSION: SAG at admission could be a promising predictor of all-cause mortality in critically ill patients with CHF.

Effect of a commercial anionic dietary supplement on urinary pH and concentrations of electrolytes and pH in blood of horses.

Aims: To compare urine urinary pH, blood pH and concentration of electrolytes in blood of healthy horses fed an anionic salt supplement to achieve diets with a dietary cation-anion difference (DCAD) of -40 or 0 mEq/kg DM, with horses a fed a diet with a DCAD of 85 mEq/kg DM.Methods: Eight healthy horses received each of three diets in a randomised crossover design. Diets consisted of grass hay and concentrate feed, with a varying amount of an anionic supplement to achieve a DCAD of 85 (control), 0 or -40 mEq/kg DM. They were fed for 14 days each with a washout period of 7 days between. Urine pH was measured daily and blood samples were collected on Days 0, 7 and 14 of each study period for the measurement of pH and concentration of electrolytes.Results: Four horses voluntarily consumed the anionic supplement with their feed, but four horses required oral supplement administration via dose syringe. During the study period mean urine pH was lower in horses fed diets with a DCAD of 0 (6.91; SD 0.04) and -40 (6.83; SD 0.04) mEq/kg DM compared to the control diet (7.30; SD 0.04). Compared with horses fed the control diet, mean urine pH was lower in horses fed the 0 and -40 mEq/kg DM diets on Days 1-12 and 14 (p < 0.05) of the study period. On Day 13 it was only lower in horses fed the -40 mEq/kg DM diet (p < 0.01). Urine pH was similar for horses fed the 0 and -40 mEq/kg DM diets (p = 0.151). The DCAD of the diet had no effect on blood pH, ionised Ca or anion gap. Mean concentrations of bicarbonate in blood were affected by diet (p = 0.049); they were lower when horses were fed the 0 mEq/kg diet relative to the control diet on Day 14.Conclusions and clinical relevance: The anionic supplement reduced urine pH in horses fed diets with a DCAD of 0 or -40 mEq/kg DM compared with 85 mEq/kg DM. However as urinary pH did not fall below pH 6.5, the pH below which calcium carbonate uroliths do not form, this reduction in urine pH is unlikely to be clinically significant. The supplement was variably palatable and showed minimal promise as an effective urinary acidifier at the doses administered in this study.

L-lactic acidosis: pathophysiology, classification, and causes; emphasis on biochemical and metabolic basis.

L-lactic acidosis (L-LA) is the most common cause of metabolic acidosis in the critical care setting, which has been associated with a large increase in mortality. The purpose of this article is to provide clinicians with an overview of the biochemical and metabolic background required to understand the different pathophysiological mechanisms that may lead to the development of L-LA. We propose a classification based on whether the pathophysiology of L-LA is due predominantly to increased production or decreased removal of L-lactic acid. In this article, we provide an overview of the biochemical and metabolic aspects of glucose oxidation, the production and removal of L-lactic acid, and a discussion of the pathophysiology of the various causes of L-LA.

Plasmonic resonance energy transfer from a Au nanosphere to quantum dots at a single particle level and its homogenous immunoassay.

Plasmonic resonance energy transfer (PRET) from a Au nanosphere (AuNS) to a quantum dot (QD) is discovered at the single particle level. A homogenous immunoassay based on this PRET is verified using a prostate specific antigen (PSA) as an example. The limit of detection of the PSA is determined to be 0.2 fM.

Determination of inorganic anions in the whole blood by ion chromatography.

A fast, precise, and accurate method that can simultaneously determine 7 anions in whole blood was established by on line dialysis-double suppression ion chromatography. Performance parameters which could affect the determination of anions were optimized, including the selection of protein precipitant in samples, the amount of filtrate discarded, selection of eluent flow rate, influence of the Ag-Na column on experimental results, influence of ethylenediamines on ClO2-, and investigation of nitrogen drying. Finally, 3.6 mmol/L sodium carbonate was selected as eluent, with a flow rate of 0.8 mL/min, to separate the 7 anions. Blood and alcohol (v/v, 1:4) were used to precipitate the proteins in blood. The 7 anions reached an adequate recovery rate when the first 2 mL of filtrate from the C18 column was discarded. The recovery rate at LLOQ, low, medium, and high concentrations was 80-120%. The correlation coefficients (r2) of the calibration curves of the targeted anions ranged from 0.9975 to 0.9998. The limit of detection (LOD) was 0.309-7.71 µg/L. This method has simple pretreatment, high accuracy, and good reproducibility and selectivity, and is suitable for the separation and determination of anions in blood.

Quantitative relationships among plasma lactate, inorganic phosphorus, albumin, unmeasured anions and the anion gap in lactic acidosis.

BACKGROUND: Quantitative relationships among plasma [Lactate], [Pi], [Albumin], unmeasured anions ([UA]) and the anion gap (AGK) in lactic acidosis (LA) are not well defined. METHODS: A mathematical model featuring compensatory potassium and chloride shifts and respiratory changes in LA demonstrated: (1) AGK=[Lactate]+Zp×[Pi]+2.4×[Albumin]+constant1+e, where Zp is a function of pH, and e reflects unmeasured anions and cations plus pH-related variations. Eq. (1) can be algebraically rearranged to incorporate the albumin-corrected anion gap, cAGK: (2) cAGK=[Lactate]+Zp×[Pi]+constant2+e. Eq. (1) was tested against 948 data sets from critically ill patients with [Lactate] 4.0mEq/L or greater. AGK and cAGK were evaluated against 12,341 data sets for their ability to detect [Lactate]>4.0mEq/L. RESULTS: Analysis of Eq. (1) revealed r2=0.5950, p<0.001. cAGk>15mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3-94.5] in detecting [Lactate]>4.0mEq/L, whereas AGK>15mEq/L exhibited a sensitivity of only 70.4% [67.5-73.2]. Additionally, [Lactate]>4.0mEq/L and cAGK>20mEq/L were each strongly associated with intensive care unit mortality (χ2>200, p<0.0001 for each). CONCLUSIONS: In LA, cAGK is more sensitive than AGK in predicting [Lactate]>4.0mEq/L.

Relationship of at Admission Lactate, Unmeasured Anions, and Chloride to the Outcome of Critically Ill Patients.

OBJECTIVES: To investigate the association between the concentration of the causative anions responsible for the main types of metabolic acidosis and the outcome. DESIGN: Prospective observational study. SETTING: Teaching ICU. PATIENTS: All patients admitted from January 2006 to December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four thousand nine hundred one patients were admitted throughout the study period; 1,609 met criteria for metabolic acidosis and 145 had normal acid-base values. The association between at admission lactate, unmeasured anions, and chloride concentration with outcome was assessed by multivariate analysis in the whole cohort and in patients with metabolic acidosis. We also compared the mortality of patients with lactic, unmeasured anions, and hyperchloremic metabolic acidosis with that of patients without acid-base disorders. In the whole population, increased lactate and unmeasured anions were independently associated with increased mortality, even after adjusting for potential confounders (odds ratio [95% CI], 1.14 (1.08-1.20); p < 0.0001 and 1.04 (1.02-1.06); p < 0.0001, respectively). In patients with metabolic acidosis, the results were similar. Patients with lactic and unmeasured anions acidosis, but not those with hyperchloremic acidosis, had an increased mortality compared to patients without alterations (17.7%, 12.7%, 4.9%, and 5.8%, respectively; p < 0.05). CONCLUSIONS: In this large cohort of critically ill patients, increased concentrations of lactate and unmeasured anions, but not chloride, were associated with increased mortality. In addition, increased unmeasured anions were the leading cause of metabolic acidosis.

Effects of synergistic and non-synergistic anions on the iron binding site from serum transferrin: A molecular dynamic simulation analysis.

The role of the anions in transferrin chemistry highlights the importance of the anion binding site in transferrin family. A synergistic anion as carbonate is an anion that is required for iron binding by transferrin while non-synergistic anions do not act as the synergistic anions to promote iron binding, but affect the iron binding and release. Some questions remain unclear about the difference between synergistic and non-synergistic anion functions. In the present work, molecular dynamic simulation techniques were employed in order to gain access into a molecular level understanding of the iron binding site of the human serum transferrin during the synergistic and non-synergistic anion binding. For this purpose, a comparative analysis was performed to illustrate the observed changes. In addition to the comparison between the synergistic and non-synergistic anions, structural differences between two synergistic anions, Carbonate and Oxalate were studied. Meanwhile,the simulation of the open (Apo), partially closed (Carbonate) and fully closed (Carbonate-Fe) forms of the transferrin structure allows a direct comparison between the iron binding site of these three states.On the basis of results, synergistic anions form high affinity binding site, while non-synergistic anions act like Apo state of the transferrin structure and change the proper conformation of the binding site. In order to act as a synergistic anion and form high affinity binding site, anion stereochemistry and interactions must be able to achieve a Carbonate-like configuration. Carbonate complex showed the highest binding affinity and electrostatic energy is the major favorable contributor to synergistic anion-transferrin interaction. Carbonate and Oxalatecomplexes as synergistic anions have many features in common, without a significant change in the transferrin structure. Only the residues in the vicinity of the binding site showed a little different conformation depending on whether the synergistic anion is Carbonate orOxalate.Finally, the results show thatASP63, GLY65 and HIS249 residues have the maximum displacement during the Carbonate and iron binding. ASP63 and HIS249 are the residues, which are coordinated to the iron and GLY65 is in the second shell residuesof the transferrin structure.

Carrot-derived carbon dots modified with polyethyleneimine and nile blue for ratiometric two-photon fluorescence turn-on sensing of sulfide anion in biological fluids.

In this article, a facile and green synthesis of carbon dots (CDs) was developed by using natural carrot as new carbon source. After direct hydrothermal carbonization for 5h at 180°C, CDs were prepared facilely. Then, CDs were conjugated with polyethyleneimine (PEI) and Nile Blue (NB) chloride to produce CDs/PEI/NB nanocomposites under electrostatic interactions. Upon excitation at 800nm, two-photon fluorescence (TPF) of the nanocomposites was observed, with TPF peaks of CDs at 415nm and NB at 675nm. The addition of Cu2+ could lead to TPF quenching of CDs via inner filter effect, but hardly any impacted on TPF of NB. Afterward, the added S2- combined with Cu2+ to form stable species that caused the separation of Cu2+ from CDs surface and the TPF recovery of CDs, with negligible effects on TPF of NB. Herein, a new CDs-based ratiometric TPF turn-on probe of S2- was developed and showed a good linear relationship (R2 =0.9933) between ratiometric TPF intensity (I415/I675) and S2- concentration (0.1-8.0µM), with a low detection limit of 0.06µM. This probe was highly selective and sensitive toward S2- over potential interferences in real biological fluids, with high detection recoveries.

[Clinical evaluation of acid-base status: Henderson-Hasselbalch, or Stewart-Fencl approach?] / Klinické hodnocení poruch acidobázické rovnováhy: Hendersonuv-Hasselbalchuv, nebo Stewartuv-Fencluv prístup?

Two approaches have been used in clinical evaluation the acid-base status: traditional (bicarbonate-centered) is based on the Henderson-Hasselbalch equation complemented by calculation of the anion gap, and more recent quantitative approach proposed by Stewart and Fencl. The latter method defines the three independent variables, which regulate pH. These include: the difference between the sum of charges carried by strong plasma cations and anions termed the strong ion difference - SID (decrease causes acidosis, and vice versa); the total concentration of the weak non-volatile acids [Atot] (inorganic phosphate and albumin, decrease causes alkalosis and vice versa), and pCO2. According to this approach, pH and bicarbonate are dependent variables. Their concentrations change if and only if one or more independent variables are altered.The main advantage of the Stewart-Fencl approach is the calculation of the concentration of plasma acids, which are not routinely measured. In the traditional approach, their presence is inferred from the anion gap. The correction of the value of anion gap according to the serum albumin level increases the specificity. This correction brings traditional approach closer to the Stewart-Fencl method that precisely calculates unmeasured strong anions by further adjustment of the corrected anion gap according to the serum phosphate, calcium and magnesium levels. The precise calculation of unmeasured anions is important in critically ill patients with the metabolic breakdown, where the traditional approach may overlook the presence of unmeasured anions. Consideration of the sodium-chloride difference draws the attention to acid-base disturbance caused by change of the strong ion difference.

Evaluation of acid-base status in patients admitted to ED-physicochemical vs traditional approaches.

BACKGROUND: The aim of this study is to evaluate the value of physicochemical, base excess (BE), and plasma bicarbonate concentration ([HCO3(-)]) approaches on the assessment of acid-base status in patients presented to the emergency department (ED). METHODS: Upon presentation at ED, patients whose arterial blood was deemed in need of analysis were studied. Arterial blood gases, serum electrolytes, and proteins were measured and used 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 (SIGcor). In each patient the acid-base status was evaluated using the BE, [HCO3(-)], and physicochemical approaches. RESULTS: A total of 365 patients were studied. Compared with BE (n = 202) and [HCO3(-)] (n = 151), physicochemical approach (n = 279) identified significantly more patients with metabolic acid-base disturbances (P < .0001). Significantly fewer patients with unmeasured anions acidosis were identified with AGadj than with SIGcor (164 vs 230; P < .0001). On the basis of BE, 75 patients had normal acid-base balance, and 65 (87%) of them exhibited at least 1 hidden acid-base disturbance, identified by the physicochemical approach. The corresponding values with [HCO3(-)] approach were 108 and 95 (88%) patients. When patients with high AGadj were excluded, 44 patients with BE and 67 with [HCO3(-)] approach had normal acid-base status, and most of them exhibited at least 1 acid-base disturbance with the physicochemical approach, whereas 12 and 21 patients, respectively, had high SIGcor. CONCLUSION: Compared with the BE and [HCO3(-)] methods, the physicochemical approach has a better diagnostic accuracy to identify metabolic acid-base disturbances.

Metabolic acidosis components in advanced chronic kidney disease: association with serum albumin and parathyroid hormone.

OBJECTIVE: To investigate the associations between the 2 main components of metabolic acidosis (unmeasured anions [UA] and hyperchloremia) with serum albumin and intact parathormone (iPTH) in patients with advanced chronic kidney disease. DESIGN AND METHODS: Cross-sectional study with advanced chronic kidney disease patients (estimated glomerular filtration rate <30 mL/minute/1.73 m(2)) not receiving phosphate binders, alkali therapy, or vitamin D analogs. Arterial blood sample was collected for biochemical and blood gas analysis. UA and strong ion difference (SID) were calculated according to quantitative acid-base analysis. Reduced SID was used as a measure of hyperchloremia. MAIN OUTCOME MEASURES: Serum albumin and parathormone (iPTH). RESULTS: A total of 383 patients were included with a mean age of 64.7 ± 16.3 year and a mean estimated glomerular filtration rate of 19.9 ± 12.1 mL/minute/1.73 m(2). Among patients with metabolic acidosis, 45.7% had metabolic acidosis exclusively because of UA and 53.7% had a hyperchloremic component (either mixed metabolic acidosis or pure hyperchloremic metabolic acidosis). Considering the main acid-base status determinants, only UA had a significant correlation with serum albumin (r = -0.278, P < .001). There was no correlation between serum albumin and SID (r = 0.083, P = .156). This is in opposition to serum iPTH, where there was no correlation with UA (r = 0.082, P = .114), but an inverse correlation between iPTH and SID was observed (r = -0.228, P < .001). Multiple linear regressions with all acid-base determinants confirmed these findings. CONCLUSIONS: Our data brings further knowledge on the associations between metabolic acidosis with bone disorders and nutritional status, suggesting that the two main metabolic acidosis components (UA and hyperchloremia) have different effects on serum parathormone and serum albumin.

Electrolyte shifts across the artificial lung in patients on extracorporeal membrane oxygenation: interdependence between partial pressure of carbon dioxide and strong ion difference.

PURPOSE: Partial pressure of carbon dioxide (PCO2), strong ion difference (SID), and total amount of weak acids independently regulate pH. When blood passes through an extracorporeal membrane lung, PCO2 decreases. Furthermore, changes in electrolytes, potentially affecting SID, were reported. We analyzed these phenomena according to Stewart's approach. METHODS: Couples of measurements of blood entering (venous) and leaving (arterial) the extracorporeal membrane lung were analyzed in 20 patients. Changes in SID, PCO2, and pH were computed and pH variations in the absence of measured SID variations calculated. RESULTS: Passing from venous to arterial blood, PCO2 was reduced (46.5 ± 7.7 vs 34.8 ± 7.4 mm Hg, P < .001), and hemoglobin saturation increased (78 ± 8 vs 100% ± 2%, P < .001). Chloride increased, and sodium decreased causing a reduction in SID (38.7 ± 5.0 vs 36.4 ± 5.1 mEq/L, P < .001). Analysis of quartiles of ∆PCO2 revealed progressive increases in chloride (P < .001), reductions in sodium (P < .001), and decreases in SID (P < .001), at constant hemoglobin saturation variation (P = .12). Actual pH variation was lower than pH variations in the absence of measured SID variations (0.09 ± 0.03 vs 0.12 ± 0.04, P < .001). CONCLUSIONS: When PCO2 is reduced and oxygen added, several changes in electrolytes occur. These changes cause a PCO2-dependent SID reduction that, by acidifying plasma, limits pH correction caused by carbon dioxide removal. In this particular setting, PCO2 and SID are interdependent.

Unmeasured anions are associated with short-term mortality in patients with hypoxic hepatitis.

OBJECTIVE: Hypoxic hepatitis is a common cause of hepatic impairment in critically ill patients and is an independent risk factor for mortality. An elevated level of unmeasured anions is another unfavourable prognostic marker in many disease entities. While the biochemical nature of unmeasured anions is unknown, data suggest that they may be released from the liver. Therefore, the purpose of this study was to determine whether the strong ion gap-the gold standard for estimation of unmeasured anions-is elevated and associated with outcome in patients with hypoxic hepatitis. METHODS: One hundred and five consecutive patients with hypoxic hepatitis admitted to the (intensive care unit) ICU of a university hospital were prospectively included in the study and compared with 15 healthy controls. RESULTS: Compared with the controls, patients with hypoxic hepatitis had an elevated strong ion gap (4.0 ± 2.6 vs. 7.8 ± 4.0 mmol/L; p = 0.0002) that contributed to metabolic acidosis. Patients dying within 5 days had a larger strong ion gap upon admission than did patients surviving beyond 5 days. The mean strong ion gap (SIG) over the course of the first 5 days after admission to the ICU was 1.3 mmol/L (0.3-2.3 mmol/L) larger in patients who died compared with patients who survived, p = 0.008. In multivariate Cox-regression, larger strong ion gaps were associated with shorter survival time. The SIG correlated positively with both AST and ALT. CONCLUSIONS: Unmeasured anions are elevated in patients with hypoxic hepatitis, contribute to metabolic acidosis and are associated with mortality. The liver is a possible source of the unmeasured anions, which may represent markers of tissue damage in hypoxic hepatitis.

Comparison of three methods of diagnosis of plasma unmeasured anions in critically ill patients.

BACKGROUND: The measurement of plasma unmeasured anions (PUA) is paramount in assessing metabolic acid base disorders. The aim of this study was to compare the accuracy of three methods in diagnosing abnormal PUA values: standard base excess (SBE), the albumin corrected anion gap (AGc), and the Stewart-Figge approach, based on unidentified anions (XAc-). METHODS: Acid-base variables were prospectively collected in ICU patients admitted January-September 2008. Whatever the method, PUA values measured two standard deviations above or below the mean of those in control subjects were considered as abnormal. RESULTS: Of the 205 consecutives patients included, 179 had an abnormal PUA value. The accuracy of AGc and XAc- in diagnosing abnormal PUA values was comparable (AUC: 0.89±0.03 and 0.89±0.03, P=0.82) but greater than that of SBE (0.67±0.06, P<0.001 and P<0.001, respectively). Of the high PUA values (n=161), 96% were diagnosed by XAc-, 88% by AGc (P<0.01) and 48% by SBE (P<0.001). Hyperlactatemia (n=111) was diagnosed equally by AGc and XAc-, (81% and 86%, P=0.37) but less by SBE (50%, P<0.001 and P<0.001, respectively). High PUA not associated with hyperlactatemia (N.=61) was more frequently diagnosed by XAc- (97%) than by AGc (84%, P=0.03). CONCLUSION: In ICU patients, AGc and the Stewart-Figge approach should be preferred over SBE for diagnosing abnormal PUA values and predicting hyperlactatemia. The Stewart-Figge approach based on unidentified anions, is the most efficient in diagnosing high PUA values not associated with hyperlactatemia.