Unmeasured Anions Research Articles

Acid-Base Balance in Peritoneal Dialysis Patients: A Stewart-Fencl Analysis

Background. Evaluation of acid-base disorders using the Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the total concentration of non-volatile weak acids (Atot). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle, which is a necessary yet insufficient condition to describe the state of the system. The aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles. Methods. A total of 17 patients with chronic renal failure (10 men), aged 60.7 (22–84) years, treated by PD for 25.7 (1–147) months were examined. A control group included 17 healthy volunteers (HV) (8 males), with a mean age of 42.7 (22–77) years and normal renal function. Patients were treated with a solution containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) as buffers; eleven of them used, during the nighttime dwell, a solution with icodextrin buffered by lactate at a concentration of 40 mmol/L. The following equations were employed for calculations of acid-base parameters according to the Stewart-Fencl principle. The first is SID = [Na+] + [K+] + 2[Ca2+] + 2[Mg2+] − [Cl−] − [UA−], where SID is the strong ion difference and [UA−] is the concentration of undetermined anions. For practical calculation of SID, the second equation, SID = [HCO3−] + [Alb−] + [Pi−], was used, where [Alb−] and [Pi−] are the charges carried by albumin and phosphates. The third is Atot, the total concentration of weak non-volatile acids, albumin [Alb] and phosphates [Pi]. Results. The capillary blood pH in PD group was 7.41 (7.27–7.48), [HCO3−] levels 23.7 (17.6–29.5) mmol/L, SID 36.3 (29.5–41.3) mmol/L, sodium-chloride difference 39.0 (31.0–44.0) mmol/L, [Pi] 1.60 (0.83–2.54) mmol/L, and [Alb] 39.7 (28.8–43.4) g/L (median, min-max). Bicarbonate in blood correlated positively with SID (Rho = 0.823; p < 0.001), with the sodium-chloride difference (Rho = 0.649; p < 0.01) and pH (Rho = 0.754; p < 0.001), and negatively with residual renal function (Rho = −0.517; p < 0.05). Moreover, the sodium-chloride difference was also found to correlate with SID (Rho = 0.653; p < 0.01). While the groups of PD and HV patients did not differ in median bicarbonate levels, significantly lower median value of SID were observed in PD patients, 36.3 vs. 39.3 mmol/L (p < 0.01); additionally, PD patients were shown to have significantly lower mean value of serum sodium levels, 138 vs. 141 mmol/L (p < 0.01), and serum chlorides levels, 100 vs. 104 mmol/L (p < 0.001). Despite the higher [UA−] levels in PD patients, 9.1 vs. 5.4 mmol/L (p < 0.001), this parameter was not found to correlate with bicarbonate levels. Conclusions. The results suggest that the decreased bicarbonate in PD patients results from a combination of decreased sodium-chloride difference and mildly increased unmeasured anions.

Differences in acid-base behavior between intensive care unit survivors and nonsurvivors using both a physicochemical and a standard base excess approach: A prospective, observational study

Purpose This study aimed to test the hypothesis that intensive care unit survivors and nonsurvivors differ with regard to type and severity of acid-base disorders. Materials and Methods Prospective, observational, cohort study of 107 consecutive patients admitted in a 7-bed intensive care unit during a 6-month period that stayed at least 4 days. All acid-base variables for the first 3 days and the day of discharge were analyzed. Results Survivors had significant metabolic acidosis upon admission, which was due to hyperlactatemia, an excess of unmeasured anions, and principally, hyperchloremia. A progressive decrease in these anions in the presence of constant hypoalbuminemia led to normal standard base excess at discharge. Nonsurvivors had greater metabolic acidosis upon admission with acidifying variables in similar proportions to that of the survivors. On the day of death, nonsurvivors had a similar degree of metabolic acidosis but a different proportion of the anions (less chloride and more lactate) compared with the day of admission. Unmeasured anions were greater in nonsurvivors both on the day of admission and on the day of death. Conclusions Intensive care unit survivors and nonsurvivors differed in the severity of metabolic acidosis; however, the proportion of the different anions causing the acidosis on admission was similar between these 2 groups.

Diagnosing metabolic acidosis in the critically ill: bridging the anion gap, Stewart, and base excess methods

Metabolic acid-base disorders are common in critically ill patients. Clinicians may have difficulty recognizing their presence when multiple metabolic acid-base derangements are present in a single patient. Clinicians should be able to identify the components of complex metabolic acid-base disorders since metabolic acidoses due to unmeasured anions are associated with increased mortality in critically ill patients. This review presents the derivation of three commonly used methods of acid-base analysis, which include the anion gap, Stewart physiochemical, and modified base excess. Clinical examples are also provided to demonstrate the subtleties of the different methods and to demonstrate their application to real patient data. A comparison of these methods shows that each one is equally adept at identifying a metabolic acidosis due to unmeasured anions; however, the Stewart physiochemical and the modified base excess methods better evaluate complex metabolic acid-base disorders. While all three methods correctly identify metabolic acidosis due to unmeasured anions, which is a predictor of mortality, it remains unclear if further delineation of complex metabolic acid-base disorders using the Stewart physiochemical or the modified base excess methods is clinically beneficial.

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia

BackgroundBase deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples.MethodsWe conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L.ResultsFrom 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 ± 15.7 years. Mean Lac was 2.11 ± 2.6 mmol/L, mean AG was 9.0 ± 5.1, mean ACAG was 14.1 ± 3.8, mean BD was 1.50 ± 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively.ConclusionAG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.

Acid-Base Effects of a Bicarbonate-Balanced Priming Fluid during Cardiopulmonary Bypass: Comparison with Plasma-Lyte 148. A Randomised Single-Blinded Study

Fluid-induced metabolic acidosis can be harmful and can complicate cardiopulmonary bypass. In an attempt to prevent this disturbance, we designed a bicarbonate-based crystalloid circuit prime balanced on physico-chemical principles with a strong ion difference of 24 mEq/l and compared its acid-base effects with those of Plasma-Lyte 148, a multiple electrolyte replacement solution containing acetate plus gluconate totalling 50 mEq/l. Twenty patients with normal acid-base status undergoing elective cardiac surgery were randomised 1:1 to a 2 litre prime of either bicarbonate-balanced fluid or Plasma-Lyte 148. With the trial fluid, metabolic acid-base status was normal following bypass initiation (standard base excess 0.1 (1.3) mEq/l, mean, SD), whereas Plasma-Lyte 148 produced a slight metabolic acidosis (standard base excess -2.2 (2.1) mEq/l). Estimated group difference after baseline adjustment was 3.6 mEq/l (95% confidence interval 2.1 to 5.1 mEq/l, P=0.0001). By late bypass, mean standard base excess in both groups was normal (0.8 (2.2) mEq/l vs. -0.8 (1.3) mEq/l, P=0.5). Strong ion gap values were unaltered with the trial fluid, but with Plasma-Lyte 148 increased significantly on bypass initiation (15.2 (2.5) mEq/l vs. 2.5 (1.5) mEq/l, P < 0.0001), remaining elevated in late bypass (8.4 (3.4) mEq/l vs. 5.8 (2.4) mEq/l, P < 0.05). We conclude that a bicarbonate-based crystalloid with a strong ion difference of 24 mEq/l is balanced for cardiopulmonary bypass in patients with normal acid-base status, whereas Plasma-Lyte 148 triggers a surge of unmeasured anions, persisting throughout bypass. These are likely to be gluconate and/or acetate. Whether surges of exogenous anions during bypass can be harmful requires further study.

Strong ion gap and outcome after cardiac arrest: another nail in the coffin of traditional acid–base quantification

The role of unmeasured anions in critical care patients remains a controversial issue. Recent data demonstrate that circulating anions can be quantified and that this might have prognostic value.

The strong ion gap and outcome after cardiac arrest in patients treated with therapeutic hypothermia: a retrospective study

This study investigates whether the strong ion gap (SIG) is associated with long-term outcome after cardiac arrest in patients treated with therapeutic hypothermia. The hypothesis of the study was that an elevated SIG was associated with unfavourable outcome after cardiac arrest. Retrospective review of records from 1995 to 2007 of patients who received cardiopulmonary resuscitation. Emergency department of a university hospital. Patients who were successfully resuscitated after cardiac arrest (n = 288) and treated with mild therapeutic hypothermia. None. Acid-base variables were calculated according to Stewart's approach, as modified by Figge and Fencl, and were determined immediately on admission and 12 h after the return of spontaneous circulation. Acid-base variables were determined at 37 degrees C and are reported without correction for patient temperature. Differences in SIG were compared between patients with favourable (survival 6 months with cerebral performance category 1 or 2) and unfavourable outcomes. SIG on admission and 12 h after return of spontaneous circulation was higher in patients with unfavourable outcome (n = 151; 52%). SIG 12 h after return of spontaneous circulation was identified as an independent predictor of outcome. A SIG > 8.9 mmol/L was associated with an increased cumulative hazard of death. An elevated SIG 12 h after return of spontaneous circulation may be associated with unfavourable outcome in patients after cardiac arrest treated with mild therapeutic hypothermia. The unmeasured anions hidden behind an elevated SIG may represent markers of tissue damage.

Effects of fluid therapy on total protein and its influence on calculated unmeasured anions in the anesthetized dog

AbstractObjective – To determine the effects of IV lactated Ringer's solution at a rate of 10 mL/kg/h in anesthetized dogs on total protein (TP) measurement and calculation of unmeasured anions (UAs) using 2 quantitative methods of acid‐base status determination, strong ion gap, and modified base deficit.Design – Prospective clinical study.Animals – Forty‐three dogs, anesthetic health status I or II according to the American Society of Anesthesiologists, undergoing surgery under general anesthesia.Interventions – Arterial blood analyses for gas tensions, acid‐base balance, electrolytes, lactate, hemoglobin (Hb), PCV, and TP were performed under general anesthesia immediately after induction and again after administration of approximately 10 mL/kg of lactated Ringer's solution (given over 1 h). UAs were determined using strong ion gap and modified base deficit.Measurements and Main Results – Fluid replacement for 1 hour decreased TP, Hb, and PCV by 8%, 7.8%, and 8.6%, respectively. The degree of decrease in TP did not impact the calculation of UAs by quantitative methods when the prefluid administration TP value was used instead of the postfluid TP value in the calculation. Comparison of the two methods showed a low correlation (r≤0.68) and marked differences in the precision (1.96 SD).Conclusions: The degree of decrease in TP after 1 hour of fluid replacement at approximately 10 mL/kg does not affect determination of UAs when prefluid TP is used within that time period.

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.

Acid-base Balance in Combined Severe Hepatic and Renal Failure: A Quantitative Analysis

Severe hepatic failure (SHF) commonly leads to major changes in acidbase balance status. However, the direct effects of liver failure per se on acid base balance are poorly understood because this condition is usually associated with acute renal failure (ARF). To assess the effect of SHF on acid-base balance. Retrospective laboratory investigation. Thirty-seven critically ill patients with SHF complicated by ARF, and 42 patients with severe ARF without liver failure prior to renal replacement therapy. Retrieval of clinical and laboratory data from prospective unit and laboratory databases. Quantitative acid-base assessment using Stewart-Figge methodology. Comparison of findings between the two groups. Comparison of demographic and clinical features. Patients with combined SHF and ARF were younger and had significantly higher mean bilirubin, ALT and INR levels (p<0.0001). Their mean lactate concentration was higher (6.4 vs. 2.1 mmol/L; p<0.0001) leading to a greater anion gap (25.8 vs. 16.1 mmol/L; p<0.0001). The ionized calcium concentration (1.00 vs. 1.15 mmol/L; p<0.0001) was lower but the strong ion difference apparent (SIDa) was greater (42.0 vs. 38.0 mEq/L; p<0.005) due to hypochloremia. The albumin concentration was low but higher than in control patients (28 vs. 24 g/L; p<0.01) and the calculated strong ion gap (SIG) was greater (12.6 vs. 9.3 mEq/L; p<0.01). The base excess was similar to controls and the pH was preserved in the near normal range by marked hypocapnea. Combined SHF and ARF is a syndrome with unique acid-base changes due mostly to lactic metabolic acidosis and, in smaller part, to the accumulation of unmeasured anions. This acidosis, like that of ARF, is attenuated by hypoalbuminemia, by a unique preservation of the SIDa due to hypochloremia, and by marked hypocapnea.

The early phase of critical illness is a progressive acidic state due to unmeasured anions

Stewart's and Fencl's methods have recently been proposed to interpret acid-base disorders where traditional theory has proven inadequate. Our objectives were to evaluate: (1) the occurrence of acid-base disturbances in critically ill patients and their trend over the first 3 intensive care unit days, (2) whether Stewart's theory offers advantages over the traditional theory in the diagnosis of acid-base metabolic disturbances and (3) whether variables derived from Stewart's and Fencl's methods offer advantages over the traditional method to predict patient mortality. A prospective cohort study in a general intensive care unit. Blood samples were analysed for arterial blood gases, electrolytes and proteins. PaCO2, pH, bicarbonate, base excess, standard base-excess, sodium, potassium, chloride, phosphorous, calcium, magnesium and lactate were measured. Anion gap, Stewart's and Fencl's variables were calculated. When using Stewart's method, metabolic acidosis and metabolic alkalosis were found in 92.9% and 93.4% of samples, respectively. Corresponding figures obtained with the traditional method were 15% and 18.7%. In 245 (64.5%) samples, Stewart's method revealed that metabolic acidosis and alkalosis were simultaneously present, whereas the traditional method revealed a normal acid-base status. Strong ion gap increased significantly over the first 3 intensive care unit days. Strong ion gap and lactate were independent predictors of 28-day mortality. Metabolic acidosis by unmeasured anions is a clinically relevant phenomenon, which is correlated with mortality. Progressive metabolic acidosis may be ongoing in the early phase of critical illness despite the absence of acidaemia.

The nature of unmeasured anions in critically ill patients

We read with interest the commentary of Venkatesh and Morgan in the February issue of Critical Care [1], in which they discuss the continuing need for clarification of the nature of unmeasured anions in critically ill patients. The questions asked in this commentary arise from the study of Bruegger and colleagues in a previous issue of this journal [2]. The main issue discussed is the ongoing uncertainty about the contribution of intermediates of the tricarboxylic acid (TCA) cycle to the strong ion gap (SIG). As Venkatesh and Morgan accurately point out, the extremely high concentrations of acetate and citrate found by Bruegger and colleagues may very well be confounded by the exogenous administration of resuscitation fluids and blood products in the animal model described. In the March issue of Critical Care Medicine, we published our study conducted in critically ill patients with a metabolic acidosis with and without an increased SIG, representing the absence or presence of unmeasured anions [3]. We explored the presence of and contribution to the SIG of a large variety of compounds, largely organic acids and amino acids, by use of several laboratory techniques such as ion-exchange column chromatography and gas chromatography. In addition, proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to quantify intermediates of the TCA cycle. Despite our elaborate attempt, only 7.9% of the difference in SIG between the low and high SIG groups could be explained by the presence of high concentrations of amino acids, uric acid, and organic acids. As a single compound, uric acid was responsible for the largest relative contribution to the SIG, namely 2.2%. Our study excludes many other potent unmeasured anions, such as uremic toxins and pyroglutamic acid, as major contributors to the SIG. As to the presence of TCA cycle intermediates, only succinic acid was significantly elevated in the high SIG group but it accounted for only 0.07% of the increased SIG. Furthermore, concentrations of isocitrate and citrate obtained by gas chromatography were not relevantly elevated in the high SIG group and all intermediates of the TCA cycle quantified with 1H-NMR spectroscopy, including acetic acid, corresponded to the published reference ranges. As outlined in our discussion, these findings are in contradiction to a recent human study [4]. The accumulation of TCA cycle intermediates by the mechanism of accelerated amino acid catabolism would imply distinct patterns of altered amino acid concentrations, which also was not supported by the results of our study. Our research enables us to answer the last question posed in the commentary of Venkatesh and Morgan. Raised concentrations of (iso)citrate and acetate do not clarify the SIG in the critically ill. Thus, a significant contribution of TCA cycle intermediates to the SIG in human acidosis is excluded. However, given the small percentage of the SIG that was represented by the measured anions, a largely unclarified portion of the strong anion gap remains to be explored.

Unmeasured anions: the unknown unknowns

Evidence is emerging that elevated concentrations of the intermediates of the citric acid cycle may contribute to unmeasured anions in critical illness. Both the anion gap and the strong ion gap are used as scanning tools for recognition of these anions. The mechanisms underlying these elevations and their significance require further clarification.

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 R(2) = 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.

Hyperchloremia is the dominant cause of metabolic acidosis in the postresuscitation phase of pediatric meningococcal sepsis*

Metabolic acidosis is common in septic shock, yet few data exist on its etiological temporal profile during resuscitation; this is partly due to limitations in bedside monitoring tools (base excess, anion gap). Accurate identification of the type of acidosis is vital, as many therapies used in resuscitation can themselves produce metabolic acidosis. Retrospective, cohort study. Multidisciplinary pediatric intensive care unit with 20 beds. A total of 81 children with meningococcal septic shock. None. Acid-base data were collected retrospectively on 81 children with meningococcal septic shock (mortality, 7.4%) for the 48 hrs after presentation to the hospital. Base excess was partitioned using abridged Stewart equations, thereby quantifying the three predominant influences on acid-base balance: sodium chloride, albumin, and unmeasured anions (including lactate). Metabolic acidosis was common at presentation (mean base excess, -9.7 mmol/L) and persisted for 48 hrs. However, the pathophysiology changed dramatically from one of unmeasured anions at admission (mean unmeasured anion base excess, -9.2 mmol/L) to predominant hyperchloremia by 8-12 hrs (mean sodium-chloride base excess, -10.0 mmol/L). Development of hyperchloremic acidosis was associated with the amount of chloride received during intravenous fluid resuscitation (r = .44), with the base excess changing, on average, by -0.4 mmol/L for each millimole per kilogram of chloride administered. Hyperchloremic acidosis resolved faster in patients who 1) manifested larger (more negative) sodium chloride-partitioned base excess, 2) maintained a greater urine output, and 3) received furosemide; and slower in those with high blood concentrations of unmeasured anions (all, p < .05). Hyperchloremic acidosis is common and substantial after resuscitation for meningococcal septic shock. Recognition of this entity may prevent unnecessary and potentially harmful prolonged resuscitation.

Acute phase proteins do not account for unmeasured anions in critical illness

The increasingly recognized prognostic impact of the strong ion gap in critical illness is in contrast to its largely unknown chemical nature. Experimental and clinical evidence suggest that acute phase proteins might account for elevation of the strong ion gap. The hypothesis of this investigation was that acute phase proteins account for strong ion gap in critically ill patients. The charges of the two acute phase proteins C-reactive protein and fibrinogen were estimated by a computer model. Additionally, 142 patients admitted to a medical intensive care unit of a university hospital were studied prospectively during a six month period. Serial daily observations were recorded and classified according to the systemic inflammatory state. The acute phase proteins C-reactive protein and fibrinogen were measured and the strong ion gap was calculated from the measured acid-base variables. The approximated mean charges of C-reactive protein and fibrinogen at a pH of 7.4 are -4.0 and -13.6 per molecule, respectively. Therefore, their negative charge is too small to explain the elevated strong ion gap even during a substantial increase of C-reactive protein and fibrinogen due to an acute-phase reaction. Moreover, C-reactive protein did not correlate with the strong ion gap when partialized for creatinine (R = 0.02, P = 0.567). Fibrinogen did not correlate with the strong ion gap. Creatinine correlated with the strong ion gap (R = 0.42, P < 0.001). Neither systemic inflammatory state nor increasing C-reactive protein levels were associated with an increasing strong ion gap. Acute phase proteins do not account for an elevated strong ion gap in critically ill patients.

Acid–base disturbances in critically ill patients with cirrhosis

The equilibrium of offsetting metabolic acid-base disorders in stable cirrhosis might be lost during episodes of hepatic decompensation, haemorrhage or sepsis. The purpose of this study was to determine whether the acid-base state is destabilized in critically ill patients with cirrhosis and whether this is associated with mortality. One-hundred and eighty-one consecutive patients with cirrhosis were investigated in a prospective observational cohort study on admission to a medical intensive care unit (ICU) of a university hospital. Arterial acid-base state was assessed according to the Gilfix methodology. Clinical data, ICU mortality and hospital mortality were recorded. Patients had net metabolic acidosis owing to unmeasured anions and owing to hyperchloraemic, dilutional and lactic acidosis. Lactic acidosis, acidemia and acute renal failure on ICU admission were associated with increased mortality. Lactate and pH discriminated survivors from non-survivors. The presence of lactic acidosis could not always be recognized by customary acid-base parameters. The stable equilibrium of acid-base disorders is lost when patients with cirrhosis become critically ill. Lactic acidosis and acidaemia are associated with increased ICU mortality caused by severe underlying organ dysfunction.

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions

IntroductionMetabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.MethodsEleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions.ResultsDuring induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), α-ketoglutarate (35.3 μEq/L), fumarate (6.2 μEq/L), sulfate (0.1 mEq/L), and urate (55.9 μEq/L) after shock induction.ConclusionLarge amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.

UNMEASURED ANIONS ACCOUNT FOR MOST OF THE METABOLIC ACIDOSIS IN PATIENTS WITH HYPERLACTATEMIA

To characterize the different components of metabolic acidosis in patients with hyperlactatemia in order to determine the degree to which lactate is responsible for the acidosis and the relevance that this might have in the outcome of these patients. Arterial blood gas, arterial lactate, Na+, K+, Ca2+, Mg2+, Cl-, phosphate, albumin, and creatinine were measured on admission to make a diagnosis of the acid-base disturbances present. Intensive Care Unit and in-hospital mortality were also recorded. A total of 58 patients with hyperlactatemia were included. They usually had a mild acidemia (pH 7.31 +/- 0.12) and a significantly high Standard Base Deficit (7.6 +/- 6.7 mEq/L). In addition to lactate (4.3 +/- 2.3 mEq/L), chloride (106.9 +/- 9.5 mEq/L) and unmeasured anions (8.6 +/- 5.0 mEq/L) accounted for the metabolic acidosis. Unmeasured anions were primarily responsible for the acidosis in both Intensive Care Unit survivors and nonsurvivors (44.7% +/- 26.0% and 46.0% +/- 17.5%, respectively, P = 0.871). Lactate contributed in similar percentages to the acidosis in both groups (23.0% +/- 11.8% and 24.2% +/- 9.7% in Intensive Care Unit survivors and nonsurvivors, respectively; P = 0.753). Correlation between Standard Base Deficit and lactate was found only in Intensive Care Unit nonsurvivors (r = 0.662, P < 0.01). Hyperlactatemia is usually accompanied by metabolic acidemia, but lactate is responsible for a minor percentage of the acidosis; unmeasured anions account for most of the acidosis in patients with hyperlactatemia. The percentage of the acidosis due to hyperlactatemia was not relevant in terms of outcome.

Clinical Significance of Strong Ion Gap: between ICU and Hemodialysis Patients with Metabolic Acidosis

Metabolic acidosis is the most frequent acid-base disorder in critically ill patients and dialysis patients. This study is to compare the conventional approach with the physicochemical approach between the intensive care unit (ICU) and hemodialysis (HD) patients. Fifty-seven ICU patients and 33 HD patients were enrolled. All data sets included simultaneous measurements of arterial blood gas with base deficit (BD), serum electrolytes, albumin, lactate, and calculated anion gap observed (AGobs). Physiochemical analysis was used to calculate the albumin and lactate-corrected anion gap (AGcorr), the base deficit corrected for unmeasured anions (BDua), the strong ion difference apparent (SIDa), the strong ion difference effective (SIDe), and the strong ion gap (SIG). The SIDa (37.5±5.3 vs 33.9±9.0, p=0.045) and SIG (12.3±5.3 vs 8.6±8.8, p=0.043) was significantly higher in the HD group than the ICU group. SIG in the ICU group showed the highest correlation coefficient with AGobs, whereas SIG in the HD group with AGcorr. Concerning the contributions of the three main causes of metabolic acidosis, increased SIG was comparable between the ICU and HD group (n=48, 90.6% vs n=30, 93.8%), whereas hyperlactatemia (n=9, 17.0% vs n=0, 0%) and hyperchloremia (n=20, 35.1% vs n=2, 6.1%) was significantly increased in the ICU group compared with the HD group. Multiple underlying mechanisms are present in most of the ICU patients with metabolic acidosis compared with the HD patients. In conclusion, the physicochemical approach can elucidate the detailed mechanisms of metabolic acidosis in ICU and HD patients compared with conventional measures.