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Research Notes: Electrolytes, Acid-base and Anion GapSee also - Lactic acidosis Sodium Hyponatremia is low sodium and hypernatremia is high sodium.
Anion gap Anion gap = (Na+ + K+) - (HCO3- + Cl-) or (Na+) - (HCO3- + Cl-) Calculated using the results of an electrolyte panel to help distinguish between anion-gap and non-anion-gap metabolic acidosis. Specifically, the anion gap evaluates the difference between measured and unmeasured electrical particles (ions or electrolytes). Positive ions (cations) and negative ions (anions) should be equal, but not all ions are routinely measured. The calculated AG result represents the unmeasured ions and primarily consists of anions, hence the name "anion gap." The anion gap is non-specific. It is increased when the number of unmeasured anions increases, indicating a state of anion-gap metabolic acidosis, but does not indicate what is causing the imbalance. Causes can include uncontrolled diabetes, starvation, kidney damage, and ingestion of potentially toxic substances such as antifreeze, excessive amounts of aspirin, or methanol. A low anion gap can also occur, most commonly seen when albumin (an anion as well as a protein) is low, while immunoglobulins (cations as well as proteins) are increased. Resources:
Emerg Med J. 2006 Aug. BACKGROUND: An elevated lactate level reflects impaired tissue oxygenation and is a predictor of mortality. Studies have shown that the anion gap is inadequate as a screen for hyperlactataemia, particularly in critically ill and trauma patients. A proposed explanation for the anion gap's poor sensitivity and specificity in detecting hyperlactataemia is that the serum albumin is frequently low. This study therefore, sought to compare the predictive values of the anion gap and the anion gap corrected for albumin (cAG) as an indicator of hyperlactataemia as defined by a lactate > or =2.5 mmol/l. METHODS: A retrospective review of 639 sets of laboratory values from a tertiary care hospital. Patients' laboratory results were included in the study if serum chemistries and lactate were drawn consecutively. The sensitivity, specificity, and predictive values were obtained. A receiver operator characteristics curve (ROC) was drawn and the area under the curve (AUC) was calculated. RESULTS: An anion gap > or =12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 79%, and 58%, respectively, and a cAG > or =12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 59%, 66%, and 69%, respectively. The ROC curves between anion gap and cAG as a predictor of hyperlactataemia were almost identical. The AUC was 0.757 and 0.750, respectively. CONCLUSIONS: The sensitivities, specificities, and predictive values of the anion gap and cAG were inadequate in predicting the presence of hyperlactataemia. The cAG provides no additional advantage over the anion gap in the detection of hyperlactataemia. Arch Dis Child. 2003 May. AIMS: Hypoalbuminaemia has significance in adult critical illness as an independent predictor of mortality. In addition, the anion gap is predominantly due to the negative charge of albumin, thus hypoalbuminaemia may lead to its underestimation. We examine this phenomenon in critically ill children, documenting the incidence, early evolution, and prognosis of hypoalbuminaemia (<33 g/l), and quantify its influence on the anion gap. METHODS: Prospective descriptive study of 134 critically ill children in the paediatric intensive care unit (ICU). Paired arterial blood samples were taken at ICU admission and 24 hours later, from which blood gases, electrolytes, and albumin were measured. The anion gap (including potassium) was calculated and then corrected for albumin using Figge's formula. RESULTS: The incidence of admission hypoalbuminaemia was 57%, increasing to 76% at 24 hours. Neither admission hypoalbuminaemia, nor extreme hypoalbuminaemia (<20 g/l) predicted mortality; however, there was an association with increased median ICU stay (4.9 v 3.6 days). After correction for albumin the incidence of a raised anion gap (>18 mEq/l) increased from 28% to 44% in all samples (n = 263); this discrepancy was more pronounced in the 103 samples with metabolic acidosis (38% v 73%). Correction produced an average increase in the anion gap of 2.7 mEq/l (mean bias), with limits of agreement of +/-3.7 mEq/l. CONCLUSION: Admission hypoalbuminaemia is common in critical illness, but is not an independent predictor of mortality. However, failure to correct the anion gap for albumin may underestimate the true anion gap, producing error in the interpretation of acid-base abnormalities. This may have treatment implications. Arch Dis Child. 2002 Dec. BACKGROUND: It is believed that hypoalbuminaemia confounds interpretation of the anion gap (AG) unless corrected for serum albumin in critically ill children with shock. Aim: To compare the ability of the AG and the albumin corrected anion gap (CAG) to detect the presence of occult tissue anions. METHODS: Prospective observational study in children with shock in a 22 bed multidisciplinary paediatric intensive care unit of a university childrenr's hospital. Blood was sampled at admission and at 24 hours, for acid-base parameters, serum albumin, and electrolytes. Occult tissue anions (lactate + truly "unmeasured" anions) were calculated from the strong ion gap. The anion gap ((Na + K) - (Cl + bicarbonate)) was corrected for serum albumin using the equation of Figge: AG + (0.25 x (44 - albumin)). Occult tissue anions (TA) predicted by the anion gap were calculated by (anion gap - 15 mEq/l). Optimal cut off values of anion gap were compared by means of receiver operating characteristic (ROC) curves. Ninety three sets of data from 55 children (median age 7 months, median weight 4.9 kg) were analysed. Data are expressed as mean (SD), and mean bias (limits of agreement). RESULTS: The incidence of hypoalbuminaemia was 76% (n = 42/55). Mean serum albumin was 25 g/l (SD 8). Mean AG was 15.0 mEq/l (SD 6.1), compared to the CAG of 19.9 mEq/l (SD 6.6). Mean TA was 10.2 mmol/l (SD 6.3). The AG underestimated TA with mean bias 10.2 mmol/l (4.1-16.1), compared to the CAG, mean bias 5.3 mmol/l (0.4-10.2). A clinically significant increase of TA >5 mmol/l was present in 83% (n = 77/93) of samples, of which the AG detected 48% (n = 36/77), and the CAG 87% (n = 67/77). Post hoc ROC analysis revealed optimal cut off values for detection of TA >5 mmol/l to be AG >10 mEq/l, and CAG >15.5 mEq/l. CONCLUSION: Hypoalbuminaemia is common in critically ill children with shock, and is associated with a low observed anion gap that may fail to detect clinically significant amounts of lactate and other occult tissue anions. We suggest that the albumin corrected anion gap should be calculated to screen for occult tissue anions in these children. J Pediatr. 1999 Dec. OBJECTIVES: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum anion gap can be used to distinguish newborns with lactic acidosis from those with hyperchloremic metabolic acidosis. STUDY DESIGN: Umbilical arterial blood gases and serum electrolyte and lactate concentrations were measured simultaneously in 210 samples from 63 infants over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na(+)] - [C1(-)] - [TCO (2)]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. RESULTS: In 89 blood samples with BD <4 mmol/L, serum lactate concentration decreased with postnatal age (r = 0.51). The upper limit of serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 and 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The mean serum anion gap +/- 2 SD in 174 samples without lactic acidosis was 8 +/- 4 mmol/L; in 36 samples with lactic acidosis it was 16 +/- 9 mmol/L (P <.0001). Serum anion gap and lactate concentration were poorly correlated for samples without lactic acidosis (r = 0.04) but highly correlated in those with lactic acidosis (r = 0.81, P <.0001). None of the 85 samples with metabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L; only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. However, 25 of 36 samples with lactic acidosis had serum anion gaps of 8 to 16 mmol/L. CONCLUSION: In the presence of metabolic acidosis, a serum anion gap >16 mmol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highly predictive of the absence of lactic acidosis; an anion gap = 8 - 16 mmol/L has no use in the differential diagnosis of metabolic acidosis in the critically ill newborn. Intensive Care Med. 1997 Apr. OBJECTIVE: To evaluate the sensitivity, specificity, and predictive values of an elevated anion gap as an indicator of hyperlactatemia and to assess the contribution of blood lactate to the serum anion gap in critically ill patients. DESIGN: Prospective study. SETTING: General intensive care unit of a university hospital. PATIENTS: 498 patients, none with ketonuria, severe renal failure or aspirin, glycol, or methanol intoxication. MEASUREMENTS AND RESULTS: The anion gap was calculated as [Na+]-[Cl-]-[TCO2]. Hyperlactatemia was defined as a blood lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was 3.7 +/- 3.2 mmol/l and the mean serum anion gap was 14.3 +/- 4.2 mEq/l. The sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44% [95% confidence interval (CI) 38 to 50], whereas specificity was 91% (CI 87 to 94 and the positive predictive value was 86% (CI 79 to 90). As expected, the poor sensitivity of the anion gap increased with the lactate threshold value, whereas the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity = 67% (CI 58 to 75) and specificity = 83% (CI 79 to 87)]. The correlation between the serum anion gap and blood lactate was broad (r2 = 0.41, p < 0.001) and the slope of this relationship (0.48 +/- 0.026) was less than 1 (p < 0.001). The serum chloride concentration in patients with a normal anion gap (99.1 +/- 6.9 mmol/l) was comparable to that in patients with an elevated anion gap (98.8 +/- 7.1 mmol/l). CONCLUSIONS: An elevated anion gap is not a sensitive indicator of moderate hyperlactatemia, but it is quite specific, provided the other main causes of the elevated anion gap have been eliminated. Changes in blood lactate only account for about half of the changes in anion gap, and serum chloride does not seem to be an important factor in the determination of the serum anion gap. Clin Intensive Care. 1994. OBJECTIVE: The normal reference range for the anion gap (AG) has recently been questioned by several authors. Lowering the upper limit of normal of the AG has been found to be more sensitive in predicting elevated lactate in critically ill adults. The objectives of this study are i) to define a new upper limit of normal of the AG in a study population of healthy adult volunteers, ii) to determine the sensitivity, specificity, the positive predictive value and the negative predictive value of the new upper limit for AG in detecting elevated lactate in critically ill children and to compare these results to the old upper limit of normal of AG (16 mmol/l), iii) to construct a receiver-operating-characteristic (ROC) curve for anion gap as a predictor of elevated lactate, iv) to determine the relationship between anion gap and serum lactate levels in critically ill patients. DESIGN: A prospective, cohort study. SETTING: Paediatric Intensive Care Unit of a University Hospital. SUBJECTS: Part I: Convenience sample of healthy adult volunteers to provide a reference range for anion gap calculation. Part II: Consecutive children admitted to the Paediatric Intensive Care Unit who had lactate levels measured for clinical reasons. MEASUREMENTS: Part I: Electrolytes and blood gases were measured from blood samples drawn from 25 adult volunteers. The reference range for AG was calculated using the equation, AG = Na - (Cl + HCO3). The upper limit of normal was calculated as mean + 2 SD. Part II: Eligible ICU patients were included in this study if they had lactate, electrolytes and blood gases obtained simultaneously. The AG was calculated as above. The new upper limit of normal AG was compared to an AG of 16 for diagnosing an elevated plasma lactate. RESULTS: The mean anion gap in the normal population was 9.4 +/- 1 mmol/l with 11 mmol/l being used as the new upper limit of normal. Thirty-six ICU patients had 189 arterial blood samples from which lactate, electrolytes and blood gas were measured simultaneously. The sensitivity, specificity, positive predictive value and negative predictive value of using an AG of 11 mmol/l as the upper limit of normal were 86%, 40%, 65% and 69% respectively, compared to 49%, 84%, 80% and 55% respectively using the upper limit of normal of AG of 16 mmol/l. The ROC curve supported lowering the upper limit of normal for the anion gap to predict an elevated lactate. There was a linear relationship between anion gap and serum lactate levels. CONCLUSIONS: An AG of 11 mmol/l as the upper limit of normal has a higher sensitivity and higher negative predictive value but lower specificity and lower positive predictive value for detecting elevated lactate in critically ill children. Crit Care Med. 1991 May. OBJECTIVE: To quantitate the contribution of lactate, phosphate, urate, total serum proteins, and unidentified anions to the anion gap in patients with severe sepsis. DESIGN: Thirty critically ill patients with evidence of severe sepsis and systemic hypoperfusion were prospectively studied. MEASUREMENTS: The anion gap was calculated as [Na+] + [K+] - [Cl-] - [HCO3]. A corrected anion gap was calculated as the anion gap minus the anionic contribution of lactate, phosphate, urate, and total serum proteins. The corrected anion gap is a marker of unmeasured anion less unmeasured cation concentration. RESULTS: The mean anion gap was 21.8 +/- 1.4 mmol/L and the corrected anion gap was 3.7 +/- 0.8 mmol/L. The mean arterial blood lactate concentration was 5.9 +/- 0.8 mmol/L. The magnitude of the lactate concentration correlated linearly with the anion gap (r2 = .61, lactate = 0.4 anion gap - 3.9, n = 30, p less than .01). The corrected anion gap was greater than 0 in 24 (80%) of 30 patients. The magnitude of the corrected anion gap correlated linearly with the anion gap (r2 = .66, corrected anion gap = 0.5 anion gap - 6.3, n = 30, p less than .01). Since the slope of the regression line for estimating corrected anion gap from anion gap was 0.5, the contribution of unmeasured anions was as important as lactate in determining the anion gap. CONCLUSION: These data indicate that lactic acidosis does not entirely account for the metabolic acidosis during severe sepsis. Furthermore, the increased corrected anion gap suggests the presence of an unidentified anion (or anions) that is (or are) responsible, in large part, for the development of metabolic acidosis in patients with sepsis. Ann Emerg Med. 1990 Nov. The anion gap (AG) is a helpful, yet underused, clinical tool. Not only does the presence of a high AG suggest a certain differential, but knowledge of the relationship between the rise in AG (delta AG) and the fall in bicarbonate (delta HCO3) is important in understanding mixed acid-based disorders. Simple arithmetic converts this relationship into a numerical value, the delta gap (delta gap). The delta gap = delta AG - delta HCO3. If the delta gap is significantly positive (greater than +6), a metabolic alkalosis is usually present because the rise in AG is more than the fall in HCO3. Conversely, if the delta gap is significantly negative (less than -6), then a hyperchloremic acidosis is usually present because the rise in AG is less than the fall in HCO3. Familarity with the relationship between the changes in AG and HCO3 can be useful in unmasking occult metabolic disorders. Crit Care Med. 1990 Mar. The anion gap is commonly used as a screening test for the presence of lactic acidosis. Analysis of the distribution of anion gaps for 56 adult surgical ICU patients with peak blood lactate levels greater than or equal to 2.5 mmol/L showed the anion gap to be an insensitive screen for elevated lactate in a critically ill, hospitalized population. All patients (11/11) with a peak lactate greater than or equal to 10 mmol/L had an anion gap greater than or equal to 16 mmol/L; however, 50% (6/12) of patients with lactates between 5.0 and 9.9 mmol/L and 79% (26/33) of those with lactates between 2.5 and 4.9 mmol/L had anion gaps less than 16 mmol/L. Hyperlactatemia was associated with considerable mortality at all levels: 100% among patients with lactate levels greater than or equal to 10 mmol/L, 75% between 5.0 and 9.9 mmol/L, and 36.4% between 2.5 and 4.9 mmol/L. Acidosis (pH less than 7.30) did not significantly alter mortality by lactate level. The observation that, for 57% of patients in this study, an elevated lactate level was not accompanied by an elevated anion gap suggests that hyperlactatemia should be included in the differential diagnosis of nonanion gap acidosis. |
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