Unmeasured anions in critically ill patients: can they predict mortality?

OBJECTIVE: To determine whether base excess, base excess caused by unmeasured anions, and anion gap can predict lactate in adult critically ill patients, and also to determine whether acid-base variables can predict mortality in these patients. DESIGN: Retrospective study. SETTING: Adult intensive care unit of tertiary hospital. PATIENTS: Three hundred adult critically ill patients admitted to the intensive care unit. INTERVENTIONS: Retrieval of admission biochemical data from computerized records, quantitative biophysical analysis of data with the Stewart-Figge methodology, and statistical analysis. MEASUREMENTS AND MAIN RESULTS: We measured plasma Na+, K+, Mg2+, Cl-, HCO3-, phosphate, ionized Ca2+, albumin, lactate, and arterial pH and Paco2. All three variables (base excess, base excess caused by unmeasured anions, anion gap) were significantly correlated with lactate (r2 =.21, p <.0001; r2 =.30, p <.0001; and r2 =.31. p <.0001, respectively). Logistic regression analysis showed that the area under the receiver operating characteristic (AUROC) curves had moderate to high accuracy for the prediction of a lactate concentration >5 mmol/L: AUROC curves, 0.86 (95% confidence interval [CI], 0.78-0.94), 0.86 (95% CI, 0.78-0.93), and 0.85 (95% CI, 0.77-0.92), respectively.Logistic regression analysis showed that hospital mortality rate correlated significantly with Acute Physiology and Chronic Health Evaluation (APACHE) II score, anion gap corrected (anion gap corrected by albumin), age, lactate, anion gap, chloride, base excess caused by unmeasured anions, strong ion gap, sodium, bicarbonate, strong ion difference effective, and base excess. However, except for APACHE II score, AUROC curves for mortality prediction were relatively small: 0.78 (95% CI, 0.72-0.84) for APACHE II, 0.66 (95% CI, 0.59-0.73) for lactate, 0.64 (95% CI, 0.57-0.71) for base excess caused by unmeasured anions, and 0.63 (95% CI, 0.56-0.70) for strong ion gap. CONCLUSIONS: Base excess, base excess caused by unmeasured anions, and anion gap are good predictors of hyperlactatemia (>5 mmol/L). Acid-base variables and, specifically, "unmeasured anions" (anion gap, anion gap corrected, base excess caused by unmeasured anions, strong ion gap), irrespective of the methods used to calculate them, are not accurate predictors of hospital mortality rate in critically ill patients.     

Reliability of anion gap as an indicator of blood lactate in critically ill patients

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 (r ² = 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. Received: 22 May 1996 Accepted: 13 January 1997     

Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients

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.     

The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU

OBJECTIVE: To examine whether the strong ion gap (SIG) or standard base excess corrected for abnormalities of serum chloride and albumin (BE(UA)) can predict outcome and to compare the prognostic abilities of these variables with standard base excess (SBE), anion gap (AG), pH, and lactate, the more traditional markers of acid-base disturbance. DESIGN: Prospective, observational study. SETTING: University teaching hospital, general adult ICU. PATIENTS: One hundred consecutive patients on admission to the ICU. MEASUREMENTS AND RESULTS: The anion gap (AG) was calculated and corrected for abnormal serum albumin (AG(corrected)). Serum lactate was measured and SBE, BE(UA), SIG, and APACHE II scores calculated for each patient. 28-day survival was recorded. There was a significant difference between the mean APACHE II (P < 0.001), SBE (P < 0.001), lactate (P = 0.008), AG (P = 0.007), pH (P < 0.001), and BE(UA) (P = 0.009) of survivors and non-survivors. There was no significant difference between the mean SIG (P = 0.088), SIDeff (P = 0.025), and SID app (P = 0.254) between survivors and non-survivors. The pH and SBE demonstrated the best ability of the acid-base variables to predict outcome (AUROC curves 0.72 and 0.71, respectively). Neither of these were as good as the APACHE II score (AUROC 0.76) CONCLUSION: Traditional indices of SBE, BE(UA,) lactate, pH, AG, and APACHE II all discriminated well between survivors and non-survivors. In this group of patients the SIG, SIDeff, and SIGapp appear to offer no advantage in prediction of outcome and their use as prognostic markers can therefore not be advocated.     

Lower anion gap increases sensitivity in predicting elevated lactate.

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.     

Correcting the anion gap for hypoalbuminaemia does not improve detection of hyperlactataemia

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 ⩾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 ⩾12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 79%, and 58%, respectively, and a cAG ⩾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.     

Alterations in anion gap following cardiopulmonary bypass.

OBJECTIVES: To evaluate the changes in the anion gap and their relation to hyperlactatemia and alterations in plasma proteins after cardiopulmonary bypass. DESIGN: Prospective study. SETTING: Cardiothoracic intensive therapy unit. PATIENTS: One hundred eleven consecutive patients after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Data were collected before cardiopulmonary bypass and every 6 hrs for 24 hrs after cardiopulmonary bypass. Results were analyzed for the entire cohort and for hyperlactatemic subgroups. The major finding of this study was that the anion gap decreased significantly at all sampling periods relative to precardiopulmonary bypass values, despite the presence of clinically important hyperlactatemia. No correlation between the decrease in plasma protein concentrations and the decrease in anion gap could be demonstrated. CONCLUSIONS: The decrease in anion gap after cardiopulmonary bypass appears to represent a balance between the influences of increased serum chloride and lactate concentrations and reduced plasma protein concentrations. This analysis demonstrates the limitations of the anion gap in the evaluation of a metabolic acidosis after cardiopulmonary bypass.     

Unaccounted for anion in metabolic acidosis during severe sepsis in humans

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.     

Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap

BACKGROUND: Conflicting data exist as to what extent hypoalbuminemia reduces the anion gap; estimates range from 1.5 to 2.5 mM per g/dL decrease in serum albumin. METHODS: We measured serum albumin, total protein, and electrolyte concentrations in 5328 consecutive patients aged 1 month to 102 years. Most patients (3750; 70%) had a normal albumin, but 1158 had hypoalbuminemia (< or =3.4 g/dL); 420 had hyperalbuminemia (> or =4.7 g/dL). Relationships between serum albumin or total protein and the anion gap were analyzed by linear regression. RESULTS: 309 (27%) hypoalbuminemic patients had a decreased anion gap, and 257 hyperalbuminemic patients (61%) had an increased anion gap. Among the entire group of 5328 patients, there were highly significant correlations between either serum albumin or total protein and the anion gap (P < 0.001). The slope of the regression for albumin versus anion gap was 2.3 mM per g/dL. Using this slope, anion gap could be adjusted for abnormal serum albumin levels: anion gap(adjusted) =anion gap + 2.3 (4-albumin). The initial assessment of an anion gap as being increased, normal, or decreased changed in 44% of the patients with hypo- or hyperalbuminemia once anion gap had been adjusted with this formula. CONCLUSIONS: Before considering whether a disorder associated with an increased or decreased anion gap is present, the anion gap should be first adjusted for abnormal serum albumin concentrations. Our data suggest that physicians use 2.3 times the change in serum albumin, whereas those of Figge et al suggest 2.5; either approach gives similar results.     

Update on value of the anion gap in clinical diagnosis and laboratory evaluation

Anion gap (AG) is a calculated value commonly used in clinical practice. It approximates the difference between the concentration of unmeasured anions (UA) and unmeasured cations (UC) in serum. At present, the reference range of anion gap has been lowered from 8-16 to 3-11 mmol/l because of the changes in technique for measuring electrolyte. However, clinicians and textbooks still refer and use the old reference value of 8-16 mmol/l. This may lead to misinterpretation of the value of anion gap. Our study updated the value of anion gap in clinical diagnosis and laboratory evaluation. Criteria for using anion gap were also suggested. We analyzed serum electrolyte using the Beckman Synchron CX5. The anion gap was calculated from the formula: [Na(+)-(Cl(-)+HCO(3)(-))]. We estimated the reference range using the non-parametric percentile estimation method. The reference range of anion gap obtained from 124 healthy volunteers was 5-12 mmol/l, which was low and confirmed the reports from other studies (3-11 mmol/l) using ion-selective electrode. From the retrospective study on the 6868 sets of serum electrolyte among hospitalized patients, we found the incidences of normal, increased, and decreased anion gaps were 59.5%, 37.6%, and 2.9%, respectively. The mean and central 90% range of increased anion gap were 16 and 13-20 mmol/l, which was lower than those reported in previous study (25 and 19-28 mmol/l). Anion gap exceeding 24 mmol/l was rare. The mean and central 90% range of decreased anion gap were 3 and 2-4 mmol/l, which were lower than those reported in previous study (6 and 3-8 mmol/l). The value of less than 2 mmol/l was rare. The most common causes of increased anion gap (hypertensive disease, chronic renal failure, malignant neoplasms, diabetes mellitus and heart diseases) and decreased anion gap (liver cirrhosis and nephrotic syndrome) in this study were similar to those in previous studies. We found two cases of IgG multiple myeloma with anion gap of 2 mmol/l. In conclusion, clinicians and laboratorians can use the anion gap as clue in quality control. They can check the incidences of increased and decreased anion gap. If one finds high incidence of increased anion gap (>24 mmol/l) or decreased anion gap (<2 mmol/l), one should check the quality control of electrolyte and whether the patients were hypoalbuminemia or hyperglobulinemia. An anion gap exceeding 24 mmol/l will suggest the presence of metabolic acidosis. It is very rare to find anion gap with the negative sign.     

Bench-to-bedside review: lactate and the kidney

The native kidney has a major role in lactate metabolism. The renal cortex appears to be the major lactate-consuming organ in the body after the liver. Under conditions of exogenous hyperlactatemia, the kidney is responsible for the removal of 25–30% of all infused lactate. Most of such removal is through lactate metabolism rather than excretion, although under conditions of marked hyperlactatemia such excretion can account for approximately 10–12% of renal lactate disposal. Indeed, nephrectomy results in an approximately 30% decrease in exogenous lactate removal. Importantly and differently from the liver, however, the kidney's ability to remove lactate is increased by acidosis. While acidosis inhibits hepatic lactate metabolism, it increases lactate uptake and utilization via gluconeogenesis by stimulating the activity of phospho-enolpyruvate carboxykinase. The kidney remains an effective lactate-removing organ even during endotoxemic shock. The artificial kidney also has a profound effect on lactate balance. If lactate-buffered fluids are used in patients who require continuous hemofiltration and who have pretreatment hyperlactatemia, the serum lactate levels can significantly increase. In some cases, this increase can result in an exacerbation of metabolic acidosis. If bicarbonate-buffered replacement fluids are used, a significant correction of the acidosis or acidemia can also be achieved. The clinician needs to be aware of these renal effects on lactate levels to understand the pathogenesis of hyperlactatemia in critically ill patients, and to avoid misinterpretations and unnecessary or inappropriate diagnostic or therapeutic activities.     

The riddle of hyperlactatemia

A recent observational study in a large cohort of critically ill patients confirms the association between hyperlactatemia and mortality. The mechanisms regulating the rates of lactate production and clearance in critical illness remain poorly understood. During exercise, hyperlactatemia clearly results from an imbalance between oxygen delivery and energy requirements. In critically ill patients, the genesis of hyperlactatemia is significantly more complex. Possible mechanisms include regional hypoperfusion, an inflammation-induced upregulation of the glycolitic flux, alterations in lactate-clearing mechanisms, and increases in the work of breathing. Understanding how these complex processes interact to produce elevations in lactate continues to be an important area of research.     

Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis

Introduction

Metabolic acidosis is the most frequent acid–base disorder in the intensive care unit. The optimal analysis of the underlying mechanisms is unknown.

Aim

To compare the conventional approach with the physicochemical approach in quantifying complicated metabolic acidosis in patients in the intensive care unit

Patients and methods

We included 50 consecutive patients with a metabolic acidosis (standard base excess ≤ -5). We measured sodium, potassium, calcium, magnesium, chloride, lactate, creatinine, urea, phosphate, albumin, pH, and arterial carbon dioxide and oxygen tensions in every patient. We then calculated HCO₃ ^-, the base excess, the anion gap, the albumin-corrected anion gap, the apparent strong ion difference, the effective strong ion difference and the strong ion gap.

Results

Most patients had multiple underlying mechanisms explaining the metabolic acidosis. Unmeasured strong anions were present in 98%, hyperchloremia was present in 80% and elevated lactate levels were present in 62% of patients. Calculation of the anion gap was not useful for the detection of hyperlactatemia. There was an excellent relation between the strong ion gap and the albumin-corrected and lactate-corrected anion gap (r ² = 0.934), with a bias of 1.86 and a precision of 0.96.

Conclusion

Multiple underlying mechanisms are present in most intensive care unit patients with a metabolic acidosis. These mechanisms are reliably determined by measuring the lactate-corrected and albumin-corrected anion gap. Calculation of the more time-consuming strong ion gap according to Stewart is therefore unnecessary.     

Prognostic value of blood lactate in critically ill patients

Hyperlactatemia is frequently observed in critically ill patients. A correlation of blood lactate concentrations and outcome of patients has been proven in circulatory shock, circulatory arrest, acute myocardial infarction, acute hypnotic drug poisoning and severe pancreatitis. However, the prognostic relevance of hyperlactatemia yields from statistical examinations in larger groups of patients. It should not be misused as a reliable prognostic sign in the individual patient, but is of high value in comparing groups of patients. In individual patients, hyperlactatemia is a useful indicator pointing to the severity of illness and to superimposed complications. Blood lactate is of considerable value for the metabolic monitoring of critically ill patients.     

Acid–base chemistry of plasma: consolidation of the traditional and modern approaches from a mathematical and clinical perspective

Objective  

Debate still exists as to whether the Stewart (modern) or traditional model of acid–base chemistry is best in assessing the acid–base status of critically ill patients. Recent studies have compared various parameters from the modern and traditional approaches, assessing the clinical usefulness of parameters such as base excess, anion gap, corrected anion gap, strong ion difference and strong ion gap. To compare the clinical usefulness of these parameters, and hence the different approaches, requires a clear understanding of their meaning; a task only possible through understanding the mathematical basis of the approaches. The objective of this paper is to provide this understanding, limiting the mathematics to a necessary minimum.     

Unmeasured anions identified by the Fencl-Stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit.

OBJECTIVES: This study was undertaken to compare three methods for the identification of unmeasured anions in pediatric patients with critical illness. We compared the base excess (BE) and anion gap (AG) methods with the less commonly used Fencl-Stewart strong ion method of calculating BE caused by unmeasured anions (BEua). We measured the relationship of unmeasured anions identified by the three methods to serum lactate concentrations and to mortality. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric intensive care unit in an academic pediatric hospital. PATIENTS: The study population included 255 patients in the pediatric intensive care unit who had simultaneous measurements of arterial blood gases, electrolytes, and albumin during the period of July 1995 to December 1996. Sixty-six of the 255 patients had a simultaneous measurement of serum lactate. MEASUREMENTS AND MAIN RESULTS: The BEua was calculated using the Fencl-Stewart method. The AG was defined as (sodium plus potassium) - (chloride plus total carbon dioxide). BE was calculated from the standard bicarbonate, which is derived from the Henderson-Hasselbalch equation and reported on the blood gas analysis. A BE or BEua value of < or =-5 mEq/L or an AG > or =17 mEq/L was defined as a clinically significant presence of unmeasured anions. A lactate level of > or =45 mg/dL was defined as being abnormally elevated for this study. The presence of unmeasured anions identified by significantly abnormal BEua was poorly identified by BE or AG. Of the 255 patients included in the study, 67 (26%) had a different interpretation of acid base balance when the Fencl method was used compared with when BE and AG were used. Plasma lactate concentration correlated better with BEua (r2 = .55; p = .0001) than with AG (r2 = .41; p = .0005) or BE (r2 = .27; p = .025). Mortality was more strongly related to BEua < or =-5 mEq/L (relative risk of death = 10.25; p = .002) than to lactate > or =45 mg/dL (relative risk of death = 2.35; p = .04). In logistic regression analysis, mortality was more strongly associated with BEua (area under the receiver operating characteristic curve = 0.79; p = .0002) than lactate (receiver operating characteristic curve area = 0.63; p = .05), BE (receiver operating characteristic curve area = 0.53; p = .32), or AG (receiver operating characteristic curve area = 0.64; p = .08) in this patient sample. CONCLUSIONS: Critically ill patients with normal BE and normal AG frequently have elevated unmeasured anions detectable by BEua. The Fencl-Stewart method is better than BE and similar to AG in identifying patients with high lactate levels. Elevated unmeasured anions identified by the Fencl-Stewart method were more strongly associated with mortality than with BE, AG, or lactate in this patient sample.     

The impact of lactate-buffered high-volume hemofiltration on acid-base balance

OBJECTIVE: To evaluate the effect of high-volume hemofiltration (HVHF) with lactate-buffered replacement fluids on acid-base balance. DESIGN: Randomized crossover study. SETTING: Intensive Care Unit of Tertiary Medical Center PARTICIPANTS: Ten patients with septic shock and acute renal failure. INTERVENTIONS: Random allocation to 8 h of isovolemic high-volume hemofiltration (ultrafiltration rate: 6 l/h) or 8 h of isovolemic continuous venovenous hemofiltration (ultrafiltration rate: 1 l/h) with lactate-buffered replacement fluid with subsequent crossover. MEASUREMENTS AND RESULTS: We measured blood gases, electrolytes, albumin, and lactate concentrations and completed quantitative biophysical analysis of acid-base balance changes. Before high-volume hemofiltration, patients had a slight metabolic alkalosis [pH: 7.42; base excess (BE) 2.4 mEq/l] despite hyperlactatemia (lactate: 2.51 mmol/l). After 2 h of high-volume hemofiltration, the mean lactate concentration increased to 7.30 mmol/l ( p=0.0001). However, a decrease in chloride, strong ion difference effective, and strong ion gap (SIG) compensated for the effect of iatrogenic hyperlactatemia so that the pH only decreased to 7.39 ( p=0.05) and the BE to -0.15 ( p=0.001). After 6 h, despite persistent hyperlactatemia (7 mmol/l), the pH had returned to 7.42 and the BE to 2.45 mEq/l. These changes remained essentially stable at 8 h. Similar but less intense changes occurred during continuous venovenous hemofiltration. CONCLUSIONS: HVHF with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. However, such hyperlactatemia only has a mild and transient acidifying effect. A decrease in chloride and strong ion difference effective and the removal of unmeasured anions all rapidly compensate for this effect.     

择期腹部大手术后首次动脉乳酸浓度对POSSUM评分预测并发症发生率的影响

目的:观察择期腹部大手术后首次动脉血乳酸浓度与术后并发症发生率的关系,并进一步分析对POSSUM(physiological and operative severity score for the enumeration of mortality and morbidity)评分预测并发症发生率的影响。方法:收集104例择期腹部大手术患者的一般相关资料、POSSUM评分、术后首次动脉血气指标pH、乳酸浓度、碱缺、PaO2/FiO2及术后各种并发症。ROC曲线比较酸碱血气指标预测术后并发症的价值,并确定乳酸最佳预测临界值。根据临界值将患者分为高乳酸组和正常乳酸组,比较两组术后实际与POSSUM评分预测并发症发生率的差异。结果:29例(28%)出现各种术后并发症。除乳酸外(AUC=0.661,95%CI0.562～0.751,P=0.010),其他血气指标pH、碱缺、PaO2/FiO2均无统计学意义的预测价值(均P>0.20)。乳酸预测术后并发症的最佳临界值为1.5mmol/L。两组POSSUM评分无明显差异,高乳酸组(>1.5mmol/L)并发症发生率与POSSUM评分预测率相仿(45%vs33%,P=0.136),正常乳酸组(≤1.5mmol/L)并发症发生率明显低于高乳酸组(14/71vs15/33,P=0.013),亦低于POSSUM评分预测率(20%vs31%,P=0.040)。结论:择期腹部大手术后首次动脉乳酸浓度可预测术后并发症,维持正常乳酸水平(≤1.5mmol/L)能降低术后POSSUM评分预测并发症发生率。     

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

Introduction

Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.

Methods

This observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L^-1 (i.e. relative hyperlactatemia).

Results

We obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P < 0.0001). This significant association was first detectable at lactate concentrations > 0.75 mmol.L^-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L^-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P < 0.001).

Conclusions

In critically ill patients, relative hyperlactataemia is independently associated with increased hospital mortality. Blood lactate concentrations > 0.75 mmol.L^-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed.