Elevated lactate in Mauriac syndrome: still a mystery.

BACKGROUND: The Mauriac syndrome was described in 1930 as a peculiar combination of poorly controlled diabetes mellitus type 1, stunted growth and glycogenic hepatopathy. More recently, lactic acidosis was recognized as an additional feature, often induced by insulin treatment. CASE PRESENTATION: A 17-year old girl known for diabetes type 1A and Mauriac syndrome was admitted to the emergency room with hyperglycemia of > 41 mmol/l without ketoacidosis. Under a standard insulin regimen, hyperglycemia was rapidly corrected but marked hyperlactatemia occurred. CONCLUSIONS: The mechanism of impaired glucose utilization and lactate elevation independent of ketoacidosis in Mauriac syndrome is intriguing. The rarity of Mauriac syndrome and its resemblance to glycogen storage diseases suggest the presence of a specific metabolic or genetic predisposition that remains to be identified.

Prognostic value of serum lactate kinetics in critically ill patients with cirrhosis and acute-on-chronic liver failure: a multicenter study.

Lactate clearance (Δ24Lac) was reported to be inversely associated with mortality in critically ill patients. The aim of our study was to assess the value of Δ24Lac for the prognosis of critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF). We analysed 954 cirrhotic patients with hyperlactatemia admitted to intensive care units (ICUs) in the United States and eastern China. The patients were followed up for at least 1 year. In the unadjusted model, we observed a 15% decrease in hospital mortality with each 10% increase in Δ24Lac. In the fully adjusted model, the relationship between the risk of death and Δ24Lac remained statistically significant (hospital mortality: odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.78- 0.90, p < 0.001; 90-day mortality: hazard ratio [HR] 0.94, 95%CI 0.92- 0.97, p < 0.001; for Δ24Lac per 10% increase). Similar results were found in patients with ACLF. We developed a Δ24Lac-adjusted score (LiFe-Δ24Lac), which performed significantly better in the area under the receiver operating characteristic curves (AUROCs) than the original LiFe score for predicting mortality. Lactate clearance is an independent predictor of death, and the LiFe-Δ24Lac score is a practical tool for stratifying the risk of death.

Hyperlactatemia Predicts Citrate Intolerance With Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy.

PURPOSE:: We aim to determine whether hyperlactatemia, which suggests multi-organ dysfunction and impaired organic substrate metabolism, may predict intolerance to regional citrate anticoagulation (RCA) during continuous venovenous hemofiltration (CVVH). METHODS:: We performed a single-center, retrospective observational study in critically ill patients with acute kidney injury or end-stage renal disease and evaluated the association of peak serum lactate levels with citrate intolerance (CI) during the initial 72 hours of RCA-CVVH, defined by serum total-to-ionized calcium >2.5 plus systemic hypocalcemia. RESULTS:: Eighty-eight patients were studied (aged 59 ± 14 years, 66% males, Acute Physiology and Chronic Health Evaluation II: 31 ± 8). Citrate was dosed at median 2.1 mmol/L of blood flow, with citrate load of 30 mmol/h, and CVVH effluent of 43 mL/kg/h. Twenty patients developed CI. Comparing patients with CI versus none, peak lactate levels were 8 (5-11) versus 3 (2-6) mmol/L, calcium replacement was 13 (10-17) versus 11 (8-12) mmol/h, and standard base excess was -4 (-12 to 1) versus 2(-4 to 7) mmol/L, respectively ( P < .05). Citrate intolerance developed in 38%, 44%, and 55%, in patients with peak lactate >4, >6, >7 mmol/L, respectively, versus 7% in those with peak lactate ≤4 mmol/L ( P ≤ .001), despite comparable citrate load and effluent rates across all categories. On multivariate analysis, hyperlactatemia and hyperbilirubinemia predicted CI ( P ≤ .01), which was associated with increasing calcium infusion requirement. Higher peak lactate from >4 to >7 mmol/L predicted CI with graded increase in odds ratio and specificity from 59% to 87%, but the corresponding negative predictive value from 93% to 87%. Area under nonparametric receiver operating characteristic curve for peak lactate and CI was 0.78. CONCLUSION:: Hyperlactatemia predicts CI during RCA-CVVH with reasonable discriminatory performance in critically ill patients. Serum lactate surveillance may help preempt issues with citrate toxicity.

Increase of Perfusion Index During Vascular Occlusion Test is Paradoxically Associated With Higher Mortality in Septic Shock After Fluid Resuscitation: A Prospective Study.

Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (ΔPI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (ΔPI0-60) and metabolic mechanisms (ΔPI60-120). We compared nonsurvivors with survivors and patients with lowest and highest ΔPI peaks, divided by 50th percentile. ΔPI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between ΔPI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The ΔPI peak values were higher in nonsurvivors [79% (47%-169%) vs. 48% (25%-85%); P=0.003] although peaks were reached slower in nonsurvivors. ΔPI0-60 was similar between groups [-12% (-42% to 28%) vs. 01% (-16%-23%); P = 0.211]. However, ΔPI60-120 was higher in nonsurvivors [49% (29%-84%) vs. 31% (12%-65%); P = 0.035]. Additionally, the group with higher ΔPI peaks had higher mortality than those with lower peaks [HR 2.25 (95% CI = 1.32-4.14); P = 0.003]. Mortality was extremely high in the presence of hyperlactatemia. ΔPI peaks were positively correlated with noradrenaline doses and increased after increasing doses.In conclusion, high values of PI during VOT indicate higher mortality in septic shock and are associated with adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.

Base excess is superior to lactate-levels in prediction of ICU mortality after cardiac surgery.

INTRODUCTION: Cardiac surgery with the use of cardiopulmonary bypass is known to induce distinct metabolic changes. Respective changes in acid-base status including increased systemic lactate levels were previously related to clinical outcomes, but data remain controversial. Therefore, we aim to investigate the relevance of lactate and base excess (BE) levels on ICU-mortality in patients admitted to the ICU after cardiac surgery. MATERIALS AND METHODS: Perioperative data of patients treated in a tertiary care academic center admitted to the ICU after on-pump surgery were analyzed in a retrospective fashion. Receiver operation characteristic (ROC) curves were constructed for admission lactate-levels and BE with calculation of optimal cut-off values to predict ICU mortality. Univariate followed by multivariate regression models were constructed to identify potential outcome-relevant indices. RESULTS: Data from 1,058 patients were included in the analysis. Area under the curves for prediction of ICU mortality were 0.79 for lactate levels at ICU admission (sensitivity 61.9%/ specificity 87.5%; optimal cut-off level 3.9mmol/l), and 0.7 for BE (sensitivity 52.4%/ specificity 93.8%, optimal cut-off level -6.7), respectively. Multivariate regression identified BE < -6.7 as the single metabolic predictor of ICU-mortality (HR 4.78, 95%-CI 1.4-16.33, p = 0.01). Explorative subgroup analyses revealed that the combination of lactate ≤3.9mmol/l and BE ≤ -6.7 has stronger impact on mortality than a combination of lactate of >3.9mmol/l and BE > -6.7 (HR 2.56, 95%-CI 0.18-37.17). CONCLUSIONS: At ICU-admission, severely reduced BE appears superior to hyperlactatemia with regard to prediction of ICU-mortality in patients after cardiac surgery.

Hyperlactatemia, Lactate Kinetics and Prediction of Citrate Accumulation in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy With Regional Citrate Anticoagulation.

OBJECTIVES: Citrate accumulation is a major complication of regional citrate anticoagulation during continuous renal replacement therapy. We studied the prediction of citrate accumulation during continuous veno-venous hemodialysis with regional citrate anticoagulation by initial lactate concentrations and lactate kinetics. DESIGN: A retrospective follow-up analysis from a cohort of critically ill patients. SETTING: Mixed medical-surgical ICUs at a university hospital. PATIENTS: All adult patients with acute kidney injury and treated with regional citrate anticoagulation-continuous veno-venous hemodialysis during a 3-year period (n = 1,070) were included in this retrospective study and screened for metabolic signs of citrate accumulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of citrate accumulation during the first 48 hours of therapy was 2.26%. In patients with initial normal lactate (< 2.2 mmol/L), elevated lactate (≥ 2.2 to < 4 mmol/L), or severe hyperlactatemia (≥ 4 mmol/L), the frequency of citrate accumulation was 0.77%, 2.70%, and 6.33%, respectively. Receiver operating characteristics-area under the curve of initial lactate concentration was 0.789 for the prediction of citrate accumulation. Optimal cutoff from receiver operating characteristics (2.39 mmol/L) showed strong negative prediction (99.28%), but weak positive prediction (5.21%). The slope intercept of lactate kinetics over 48 hours was positive and significantly higher in patients with citrate accumulation compared to those without (+0.2 vs -0.006 mmol/L/hr; p < 0.001). In patients with initial severe hyperlactatemia (≥ 4 mmol/L), the median calculated lactate clearance at 6, 12, and 18 hours was 24.0%, 48.1%, and 59.4% in the nonaccumulation group. These clearance rates were significantly higher at each time-point compared to patients with citrate accumulation (-9.8%, -20.5%, and 2.3%, respectively; p < 0.001 for each time-point). The highest receiver operating characteristics-area under the curve for citrate accumulation was observed for 12-hour values of lactate clearance (area under the curve = 0.839; 95% CI, 0.751-0.927) with an optimal cut-off value of 24.3%. CONCLUSIONS: Risk of citrate accumulation during regional citrate anticoagulation in a well-selected cohort of patients is low even in case of initial severe hyperlactatemia. Lactate kinetics rather than initially elevated lactate concentration should be considered in assessing the risk of citrate accumulation.

Persistent hyperlactatemia-high central venous-arterial carbon dioxide to arterial-venous oxygen content ratio is associated with poor outcomes in early resuscitation of septic shock.

OBJECTIVE: Several studies reported Pv-aCO2/Ca-vO2 ratio as a surrogate of VCO2/VO2 to detect global tissue hypoxia. The present study aimed to evaluate the prognostic value of Pv-aCO2/Ca-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock. METHODS: A retrospective study was conducted in 144 septic shock patients in a 30-bed mixed ICU. A Pv-aCO2/Ca-vO2 ratio>1.4 was considered abnormal. Patients were classified into four predefined groups according to lactate levels and Pv-aCO2/Ca-vO2 ratio after the first 6h of resuscitation. Sequential Organ Failure Assessment (SOFA) score at day 3 was assessed. A Kaplan-Meier curve showed the survival probabilities at day 28 using a log-rank test to evaluate the differences between groups. A receiver operating characteristics (ROC) curve evaluated the ability of lactate, Pv-aCO2/Ca-vO2 ratio and Pv-aCO2/Ca-vO2 ratio combined with lactate to predict mortality at day 28. RESULTS: Combination of hyperlactatemia and high Pv-aCO2/Ca-vO2 ratio was associated with poor SOFA scores and low survival rates at day 28 (P<0.001). The Cox multivariate survival analysis demonstrated that Pv-aCO2/Ca-vO2 ratio and lactate at T6 were independent predictors of mortality at day 28. The area under the ROC curve of the Pv-aCO2/Ca-vO2 ratio combined with lactate for predicting mortality at day 28 was highest and superior to that of lactate and Pv-aCO2/Ca-vO2 ratios. CONCLUSION: Combination of Pv-aCO2/Ca-vO2 ratio and lactate at early stages of resuscitation of septic shock can better predict the prognosis of patients. The Pv-aCO2/Ca-vO2 ratio may become a useful parameter supplementary to lactate in the resuscitation of septic shock.

Lactate minimum underestimates the maximal lactate steady-state in swimming mice.

The intensity of lactate minimum (LM) has presented a good estimate of the intensity of maximal lactate steady-state (MLSS); however, this relationship has not yet been verified in the mouse model. We proposed validating the LM protocol for swimming mice by investigating the relationship among intensities of LM and MLSS as well as differences between sexes, in terms of aerobic capacity. Nineteen mice (male: 10, female: 9) were submitted to the evaluation protocols for LM and MLSS. The LM protocol consisted of hyperlactatemia induction (30 s exercise (13% body mass (bm)), 30 s resting pause and exhaustive exercise (13% bm), 9 min resting pause and incremental test). The LM underestimated MLSS (mice: 17.6%; male: 13.5%; female: 21.6%). Pearson's analysis showed a strong correlation among intensities of MLSS and LM (male (r = 0.67, p = 0.033); female (r = 0.86, p = 0.003)), but without agreement between protocols. The Bland-Altman analysis showed that bias was higher for females (1.5 (0.98) % bm; mean (MLSS and LM): 4.4%-6.4% bm) as compared with males (0.84 (1.24) % bm; mean (MLSS and LM): 4.5%-7.5% bm). The error associated with the estimated of intensity for males was lower when compared with the range of means for MLSS and LM. Therefore, the LM test could be used to determine individual aerobic intensity for males (considering the bias) but not females. Furthermore, the females supported higher intensities than the males. The differences in body mass between sexes could not explain the higher intensities supported by the females.

Sepsis-associated hyperlactatemia.

There is overwhelming evidence that sepsis and septic shock are associated with hyperlactatemia (sepsis-associated hyperlactatemia (SAHL)). SAHL is a strong independent predictor of mortality and its presence and progression are widely appreciated by clinicians to define a very high-risk population. Until recently, the dominant paradigm has been that SAHL is a marker of tissue hypoxia. Accordingly, SAHL has been interpreted to indicate the presence of an 'oxygen debt' or 'hypoperfusion', which leads to increased lactate generation via anaerobic glycolysis. In light of such interpretation of the meaning of SAHL, maneuvers to increase oxygen delivery have been proposed as its treatment. Moreover, lactate levels have been proposed as a method to evaluate the adequacy of resuscitation and the nature of the response to the initial treatment for sepsis. However, a large body of evidence has accumulated that strongly challenges such notions. Much evidence now supports the view that SAHL is not due only to tissue hypoxia or anaerobic glycolysis. Experimental and human studies all consistently support the view that SAHL is more logically explained by increased aerobic glycolysis secondary to activation of the stress response (adrenergic stimulation). More importantly, new evidence suggests that SAHL may actually serve to facilitate bioenergetic efficiency through an increase in lactate oxidation. In this sense, the characteristics of lactate production best fit the notion of an adaptive survival response that grows in intensity as disease severity increases. Clinicians need to be aware of these developments in our understanding of SAHL in order to approach patient management according to biological principles and to interpret lactate concentrations during sepsis resuscitation according to current best knowledge.