Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit

Purpose: The aim of this study was to characterize the first 48-hour evolution of metabolic acidosis of adult patients with diabetic ketoacidosis admitted to the intensive care unit. Materials and Methods: We studied 9 patients retrieved from our prospective collected database, using the physicochemical approach to acid-base disturbances. Results: Mean (SD) age was 34 (13) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score was 16 (10); mean (SD) blood glucose level on admission was 480 (144) mg/dL; mean (SD) pH was 7.17 (0.18); and mean (SD) standard base excess was -16.8 (7.7) mEq/L. On admission, a great part of metabolic acidosis was attributed to unmeasured anions (strong ion gap [SIG], 20 +/- 10 mEq/L), with a wide range of strong ion difference (41 +/- 10 mEq/L). During the first 48 hours of treatment, 297 +/- 180 IU of insulin and 9240 +/- 6505 mL of fluids were used. Metabolic improvement was marked by the normalization of pH, partial correction of standard base excess, and a reduction of hyperglycemia. There was a significant improvement of SIG (7.6 +/- 6.2 mEq/L) and a worsening of strong ion difference acidosis (36 +/- 5 mEq/L) in the first 24 hours, with a trend toward recuperation between 24 and 48 hours (38 +/- 6 mEq/L). Conclusion: Initial metabolic acidosis was due to SIG, and the treatment was associated with a significant decrease of SIG with an elevation of serum chloride above the normal range. (C) 2011 Elsevier Inc. All rights reserved.

Characterization of acid-base status in maintenance hemodialysis: physicochemical approach

Acidosis is a common and deleterious aspect of maintenance dialysis. Traditionally, it is considered to be an elevated anion gap acidosis caused by the inability to excrete nonvolatile anions. Stewart`s approach made it possible to identify real determinants of the acid-base status and allowed quantification of the components of these disturbances, especially the unmeasured anions. We performed a cross-sectional study to identify and quantify each component of acidosis in hemodialysis maintenance patients. Sixty-four maintenance hemodialysis patients and 14 controls were enrolled in this study. Gasometrical and biochemical analysis were performed before the midweek dialysis session. Quantitative physicochemical analysis was carried out using the Stewart methodology. Hemodialysis patients were found to have mild acidemia (mean pH: 7.33 +/- 0.06 versus 7.41 +/- 0.05) secondary to metabolic acidosis (serum bicarbonate: 18.8 +/- 0.26 versus 25.2 +/- 0.48 mEq/l). The metabolic acidosis was due to retention of unmeasured anions (6.5 +/- 0.29 versus 3.1 +/- 0.62 mEq/l), hyperchloremia (105.1 +/- 0.5 versus 101.8 +/- 0.7 mEq/l), and hyperphosphatemia (5.90 +/- 0.19 versus 3.66 +/- 0.14 mg/dl). Compared with control values, the unmeasured anions and hyperchloremia had a similar acidifying effect (3.4 and 3.3 mEq/l), corresponding to almost 90% of the metabolic acidosis. Unmeasured anions and hyperchloremia are important components of acidosis in maintenance hemodialysis, in addition to phosphorus. Future studies to determine the etiology and consequences of hyperchloremic acidosis are warranted.

Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients

The aims of this study were to determine whether standard base excess (SBE) is a useful diagnostic tool for metabolic acidosis, whether metabolic acidosis is clinically relevant in daily evaluation of critically ill patients, and to identify the most robust acid-base determinants of SBE. Thirty-one critically ill patients were enrolled. Arterial blood samples were drawn at admission and 24 h later. SBE, as calculated by Van Slyke's (SBE VS) or Wooten's (SBE W) equations, accurately diagnosed metabolic acidosis (AUC = 0.867, 95%CI = 0.690-1.043 and AUC = 0.817, 95%CI = 0.634-0.999, respectively). SBE VS was weakly correlated with total SOFA (r = -0.454, P < 0.001) and was similar to SBE W (r = -0.482, P < 0.001). All acid-base variables were categorized as SBE VS <-2 mEq/L or SBE VS <-5 mEq/L. SBE VS <-2 mEq/L was better able to identify strong ion gap acidosis than SBE VS <-5 mEq/L; there were no significant differences regarding other variables. To demonstrate unmeasured anions, anion gap (AG) corrected for albumin (AG A) was superior to AG corrected for albumin and phosphate (AG A+P) when strong ion gap was used as the standard method. Mathematical modeling showed that albumin level, apparent strong ion difference, AG A, and lactate concentration explained SBE VS variations with an R² = 0.954. SBE VS with a cut-off value of <-2 mEq/L was the best tool to diagnose clinically relevant metabolic acidosis. To analyze the components of SBE VS shifts at the bedside, AG A, apparent strong ion difference, albumin level, and lactate concentration are easily measurable variables that best represent the partitioning of acid-base derangements.

Effect of chloride dialysate concentration on metabolic acidosis in aintenance hemodialysis patients

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Metabolic acidosis in patients with severe sepsis and septic shock: A longitudinal quantitative study

Objective: To describe the composition of metabolic acidosis in patients with severe sepsis and septic shock at intensive care unit admission and throughout the first 5 days of intensive care unit stay. Design: Prospective, observational study. Setting: Twelve-bed intensive care unit. Patients: Sixty patients with either severe sepsis or septic shock. Interventions: None. Measurements and Main Results: Data were collected until 5 days after intensive care unit admission. We studied the contribution of inorganic ion difference, lactate, albumin, phosphate, and strong ion gap to metabolic acidosis. At admission, standard base excess was -6.69 +/- 4.19 mEq/L in survivors vs. -11.63 +/- 4.87 mEq/L in nonsurvivors (p < .05); inorganic ion difference (mainly resulting from hyperchloremia) was responsible for a decrease in standard base excess by 5.64 +/- 4.96 mEq/L in survivors vs. 8.94 +/- 7.06 mEq/L in nonsurvivors (p < .05); strong ion gap was responsible for a decrease in standard base excess by 4.07 +/- 3.57 mEq/L in survivors vs. 4.92 +/- 5.55 mEq/L in nonsurvivors with a nonsignificant probability value; and lactate was responsible for a decrease in standard base excess to 1.34 +/- 2.07 mEq/L in survivors vs. 1.61 +/- 2.25 mEq/L in nonsurvivors with a nonsignificant probability value. Albumin had an important alkalinizing effect in both groups; phosphate had a minimal acid-base effect. Acidosis in survivors was corrected during the study period as a result of a decrease in lactate and strong ion gap levels, whereas nonsurvivors did not correct their metabolic acidosis. In addition to Acute Physiology and Chronic Health Evaluation 11 score and serum creatinine level, inorganic ion difference acidosis magnitude at intensive care unit admission was independently associated with a worse outcome. Conclusions: Patients with severe sepsis and septic shock exhibit a complex metabolic acidosis at intensive care unit admission, caused predominantly by hyperchloremic acidosis, which was more pronounced in nonsurvivors. Acidosis resolution in survivors was attributable to a decrease in strong ion gap and lactate levels. (Crit Care Med 2009; 37:2733-2739)

The acid-base impact of free water removal from, and addition to, plasma

Water, compared with plasma at a pH of 7.4, is a weak acid. The addition of free water to a patient should have an acidifying effect (dilutional acidosis) and the removal of it, an alkalinizing effect (concentrational alkalosis). The specific effects of free water loss or gain in a relatively complex fluid such as plasma has, to the authors' knowledge, not been reported. This information would be useful in the interpretation of the effect of changes in free water in patients. Plasma samples from goats were either evaporated in a tonometer to 80% of baseline volume or hydrated by the addition of distilled water to 120% of baseline volume. The pH and partial pressure of carbon dioxide, sodium, potassium, ionized calcium, chloride, lactate, phosphorous, albumin, and total protein concentrations were measured. Actual base excess (ABE), standard bicarbonate, anion gap, strong ion difference, strong ion gap, unmeasured anions, and the effects of sodium, chloride, phosphate, and albumin changes on ABE were calculated. Most parameters changed 20% in proportion to the magnitude of dehydration or hydration. Bicarbonate concentration, however, increased only 11% in the evaporation trial and decreased only -2% in the dehydration trial. The evaporation trial was associated with a mild, but significant, metabolic alkalotic effect (ABE increased 3.2 mM/L), whereas the hydration trial was associated with a slight, insignificant metabolic acidotic effect (ABE decreased only 0.6 mM/L). The calculated free water ABE effect (change in sodium concentration) was offset by opposite changes in calculated chloride, lactate, phosphate, and albumin ABE effects.

Physicochemical analysis of blood and urine in the course of acute kidney injury in critically ill patients: a prospective, observational study

Abstract Background Sequential physicochemical alterations in blood and urine in the course of acute kidney injury (AKI) development have not been previously described. We aimed to describe these alterations in parallel to traditional renal and acid–base parameters. Methods One hundred and sixty eight consecutive critically ill patients with no previous kidney disease, who had an indwelling urinary catheter at ICU admission and who remained with the catheter for at least two days without dialysis were included. A sample of blood and spot urine were collected simultaneously, once daily, until catheter removal or dialysis requirement. Traditional acid–base and renal parameters were sequentially evaluated in parallel to blood and urinary physicochemical parameters. Patients were classified during this period as having or not AKI and, for patients with AKI, duration (transient or persistent) and severity (creatinine-based AKIN stage) were evaluated. Results One hundred and thirteen patients (67.3%) had AKI: 92 at ICU admission and 21 during the observation period. AKI development was characterized in blood by increased values of phosphate and unmeasured anions (SIG), decreased albumin, and in urine by decreased values of sodium (NaU), chloride (ClU) as well as high urinary strong ion difference (SIDu). These alterations began to occur before AKI diagnosis, and they reverted in transient AKI but remained in persistent AKI. NaU, ClU and albumin decreased, and phosphate, SIG and SIDu increased with AKI severity progression. NaU and ClU values increased again when AKIN stage 3 was reached. Conclusions Simultaneous physicochemical analysis of blood and urine revealed standardized alterations that characterize AKI development in critically ill patients. These alterations paralleled AKI duration and severity. Future studies should consider including sequential evaluation of urine biochemistry as part of the armamentarium for AKI diagnosis and management.

Clinical acid-base pathophysiology: disorders of plasma anion gap.

The plasma anion gap is a frequently used parameter in the clinical diagnosis of a variety of conditions. The commonest application of the anion gap is to classify cases of metabolic acidosis into those that do and those that do not leave unmeasured anions in the plasma. While this algorithm is useful in streamlining the diagnostic process, it should not be used solely in this fashion. The anion gap measures the difference between the unmeasured anions and unmeasured cations and thus conveys much more information to the clinician than just quantifying anions of strong acids. In this chapter, the significance of the anion gap is emphasized and several examples are given to illustrate a more analytic approach to using the clinical anion gap; these include disorders of low anion gap, respiratory alkalosis and pyroglutamic acidosis.

Spin states of C-60(3-) and C120On- (n=2, 3, 4) anions using electron spin transient nutation spectroscopy

Electron spin transient nutation (ESTN) experiments show that the spin multiplicity of the ground state of C-60(3-) in frozen solution is a doublet with S = 1/2. In purified samples, there is no evidence for excited states or other species with higher multiplicity. In the anions Of C120On- (n = 2, 3, 4), where the CW EPR experiments have shown that a mixture of species is present, ESTN experiments confirm that a doublet with S = 1/2 is associated with the 3- anion and triplets with S = 1 are associated with the 2- and 4- anions. A weak nutation peak attributable to m(s) = -1/2 1/2 transitions within a quartet state may arise from association of anions with spins of 1/2 and 1 in solute aggregates.

Generation of Naphthoquinone Radical Anions by Electrospray Ionization: Solution, Gas-Phase, and Computational Chemistry Studies

Radical anions are present in several chemical processes, and understanding the reactivity of these species may be described by their thermodynamic properties. Over the last years, the formation of radical ions in the gas phase has been an important issue concerning electrospray ionization mass spectrometry studies. In this work, we report on the generation of radical anions of quinonoid compounds (Q) by electrospray ionization mass spectrometry. The balance between radical anion formation and the deprotonated molecule is also analyzed by influence of the experimental parameters (gas-phase acidity, electron affinity, and reduction potential) and solvent system employed. The gas-phase parameters for formation of radical species and deprotonated species were achieved on the basis of computational thermochemistry. The solution effects on the formation of radical anion (Q(center dot-)) and dianion (Q(2-)) were evaluated on the basis of cyclic voltammetry analysis and the reduction potentials compared with calculated electron affinities. The occurrence of unexpected ions [Q + 15](-) was described as being a reaction between the solvent system and the radical anion, Q(center dot-).The gas-phase chemistry of the electrosprayed radical anions was obtained by collisional-induced dissociation and compared to the relative energy calculations. These results are important for understanding the formation and reactivity of radical anions and to establish their correlation with the reducing properties by electrospray ionization analyses.

Temperature effect on the sorption of cholate anions on calcined LDH

Layered Double Hydroxides are a class of materials that can be described as positively charged layers of divalent and trivalent cations in the centre of edge-sharing octahedra. Cholesterol derivatives such as cholic acid are substances that play an important role in the digestion of fat components by the organism. This work presents a study on the intercalation of cholate anions in calcined MgAl-CO(3)-HDL. Isotherm experiments were performed at three different temperatures to evaluate the capacity of anion removal by sorption in the calcined LDH. The plateau was reached in all conditions. Increasing temperature results in decreasing cholate sorption. Characteristic peaks of LDH regenerated with OH(-) anions were observed at lower cholate concentrations. A peak in 2 theta equals to 7.5 degrees and peaks between 15 degrees and 20 degrees are observed. Those peaks are the same as the ones observed in the pure sodium cholate PXRD. At higher cholate concentrations the sorbed solids present PXRD related to an additional layered phase, which is related to intercalation of cholate anions with basal spacing equal to 34.3 angstrom. Thus, the cholate anions are also intercalated with a bilayer molecular arrangement at equilibrium concentrations at the isotherms plateau. (C) 2009 Elsevier Ltd. All rights reserved.

Gas-phase dissociation of 1,4-naphthoquinone derivative anions by electrospray ionization tandem mass spectrometry

Gas-phase dissociation pathways of deprotonated 1,4-naphthoquinone (NQ) derivatives have been investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The major decomposition routes have been elucidated on the basis of quantum chemical calculations at the B3LYP/6-31+G(d,p) level. Deprotonation sites have been indicated by analysis of natural charges and gas-phase acidity. NQ anions underwent an interesting reaction under collision-induced dissociation conditions, which resulted in the radical elimination of the lateral chain, in contrast with the even-electron rule. Possible pathways have been suggested, and their mechanisms have been elucidated on the basis of Gibbs energy and enthalpy values for the anions previously described at each pathway. Copyright (C) 2009 John Wiley & Sons, Ltd.

Adsorption of cholate anions on layered double hydroxides: effects of temperature, ionic strength and pH

Layered Double Hydroxides are a class of materials that can be described as positively charged planar layers consisting of divalent and trivalent cations in the center of edge-sharing octahedra. The positive charge in the LDH layers must be compensated by anion intercalation. These materials have applications that include adsorption and/or sorption of anionic species. Cholic acid is one of the main acids produced by the liver. It promotes transport of lipids through aqueous systems. This work reports on the adsorption of Cholic acid anions in MgAl-CO3-LDH taking ionic strength, pH, and temperature effects into account. The adsorbent was characterized by different techniques. Cholate anion adsorption was performed at two different temperatures (298 and 323 K), two different ionic strength conditions (0.0 and 0.1 M of NaCl), and two different pH values (7.0 and 10.0). The results show that the sorption of Cholate anions in calcined LDH can remove a considerable amount of these anions from the medium. Cholate anion adsorption in the LDH with no calcining also occurs, but at a lower amount.

A ferrocene functionalised macrocyclic receptor for cations and anions

The isolation and characterisation of a new macrocyclic hexaamine trans-6,13-bis(ferrocenylmethylamino)-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane (L-2) bearing two ferrocenyl groups appended to its exocyclic amines is reported. The crystal structures of L-2 and its dihydrochloride salt L-2. 2HCl . 2H(2)O have been determined. In the latter case cation-anion hydrogen bonding is observed in the solid state. Substrate binding by the electroactive L-2 in MeCN-CH2Cl2 solution has been examined by cyclic voltammetry and reveals the receptor electrochemically to recognise benzoate and chloride anions. The macrocyclic N-donors may also bind transition metal cations such as Cu-II and Zn-II.

Sensitivity analysis for unmeasured confounders using an electronic spreadsheet

In studies assessing the effects of a given exposure variable and a specific outcome of interest, confusion may arise from the mistaken impression that the exposure variable is producing the outcome of interest, when in fact the observed effect is due to an existing confounder. However, quantitative techniques are rarely used to determine the potential influence of unmeasured confounders. Sensitivity analysis is a statistical technique that allows to quantitatively measuring the impact of an unmeasured confounding variable on the association of interest that is being assessed. The purpose of this study was to make it feasible to apply two sensitivity analysis methods available in the literature, developed by Rosenbaum and Greenland, using an electronic spreadsheet. Thus, it can be easier for researchers to include this quantitative tool in the set of procedures that have been commonly used in the stage of result validation.