Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Biological significance and clinical utility of lactate in sepsis. / Significado biológico y utilidad clínica del lactato en la sepsis.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

The Warburg effect in patients with brain tumors: a comprehensive analysis of clinical significance.

PURPOSE: The Warburg Effect, referring to an elevation in serum lactate level attributable to increased tumor metabolism, is present in patients with brain tumors. This study comprehensively analyzes the Warburg effect in patients undergoing brain tumor resection. METHODS: We retrospectively analyzed the baseline intraoperative serum lactate levels of 2,053 patients who underwent craniotomies, including 415 with cerebral aneurysms and 1,638 with brain tumors. The brain tumor group was divided into subgroups based on the tumor pathology (extra-axial and intra-axial tumor) and the WHO tumor grade (high-grade and low-grade). RESULTS: Serum lactate level was significantly higher in the tumor group than in the aneurysm group (1.98 ± 0.97 vs. 1.09 ± 0.57 mmol/L, p < 0.001). The hyperlactatemia incidence (serum lactate level > 2.2 mmol/L) was higher in the tumor group (33.5 vs. 3.1%, p < 0.001). Severe hyperlactatemia (serum lactate level > 4.4 mmol/L) was found in 34 patients (2.1%) of only the tumor group. In patients with intra-axial tumors, serum lactate level was greater in high- than low-grade tumors (2.10 ± 1.05 vs. 1.88 ± 0.92 mmol/L, p = 0.006). Factors predictive of hyperlactatemia included supratentorial tumor location (odds ratio[95%CI] 2.926[2.127-4.025], p < 0.001) and a long tumor diameter (1.071[1.007-1.139], p = 0.028). In high-grade intra-axial brain tumor patients, there was a significant difference in overall survival between patients with hyperlactatemia than those without (p = 0.048). CONCLUSION: Our results show that brain tumor patients exhibit the Warburg effect and serum lactate may be a useful diagnostic and prognostic biomarker in patients with high-grade intra-axial brain tumors.

Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial.

BACKGROUND: Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. METHODS: We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. RESULTS: The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). CONCLUSIONS: Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

Elevated lactate levels and impaired lactate clearance during extracorporeal life support (ECLS) are associated with poor outcome in cardiac surgery patients.

The use of extracorporeal life support (ECLS) as part of cardio-circulatory support has increased rapidly in recent years. Severe hyperlactatemia is not uncommon in this group of patients. Lactate peak concentrations and lactate clearance have already been identified as independent marker for mortality in critical ill patients without mechanical device support. The aim of this study was to determine a supposed correlation between the variables lactate peak concentration and clearance in the blood and mortality in the ECLS context. Therefore, a total of 51 cardiac surgery ICU patients with ECLS therapy were included in this retrospective, clinical observational study (survivors n = 23; non-survivors n = 28). Lactate measurement was performed before, during and after ECLS therapy. Further, common ICU scores (SAPSII, SOFA, TISS28), the rates of transfusion and the different vasopressor therapies will be compared. Significant elevated peak lactate levels and poor lactate clearance were associated with higher mortality during ECLS therapy (p < 0.001). Deceased patients had higher SAPSII scores (p < 0.001), received more transfusions (p < 0.001) and presented with higher rates of epinephrine (p < 0.001). In conclusion, hyperlactatemia during ECLS therapy is a time sensitive emergency. Lactate cannot be cleared in all patients. Reversible causes should be explored and treated. In cases where the cause is irreversible, the prognosis of elevated lactate concentrations and reduced clearance is very poor.

Severe hyperlactatemia in unselected surgical patients: retrospective analysis of prognostic outcome factors.

BACKGROUND: Etiology of hyperlactatemia in ICU patients is heterogeneous-septic, cardiogenic or hemorrhagic shock seem to be predominant reasons. Multiple studies show hyperlactatemia as an independent predictor for ICU mortality. Only limited data exists about the etiology of hyperlactatemia and lactate clearance and their influence on mortality. The goal of this single-center retrospective study, was to evaluate the effect of severe hyperlactatemia and reduced lactate clearance rate on the outcome of unselected ICU surgical patients. METHODS: Overall, 239 surgical patients with severe hyperlactatemia (> 10 mmol/L) who were treated in the surgical ICU at the University Medical Center Freiburg between June 2011 and August 2017, were included in this study. The cause of the hyperlactatemia as well as the postoperative course and the patient morbidity and mortality were retrospectively analyzed. Lactate clearance was calculated by comparing lactate level 12 h after first measurement of > 10 mmol/L. RESULTS: The overall mortality rate in our cohort was 82.4%. Severe hyperlactatemia was associated with death in the ICU (p < 0.001). The main etiologic factor was sepsis (51.9%), followed by mesenteric ischemia (15.1%), hemorrhagic shock (13.8%) and liver failure (9.6%). Higher lactate levels at ICU admission were associated with increased mortality (p < 0.001). Lactate clearance after 12 h was found to predict ICU mortality (ANOVA p < 0.001) with an overall clearance of under 50% within 12 h. The median percentage of clearance was 60.3% within 12 h for the survivor and 29.1% for the non-survivor group (p < 0.001). CONCLUSION: Lactate levels appropriately reflect disease severity and are associated with short-term mortality in critically ill patients. The main etiologic factor for surgical patients is sepsis. When elevated lactate levels persist more than 12 h, survival chances are low and the benefit of continued maximum therapy should be evaluated.

Hyperlactatemia and other perioperative metabolic disturbances in neuroanesthesia.

PURPOSE OF REVIEW: The concept of 'brain-body cross-talking' has gained growing interest in the last years. The understanding of the metabolic disturbances (e.g., hypernatraemia/hyponatraemia and hyperlactatemia) in neurosurgical patients has improved during the last years. RECENT FINDINGS: The impact of elevated lactate without acidosis in neurosurgical patients remains controversial. The pathophysiology of inappropriate secretion of antidiuretic hormone (SIADH) has become clearer, whereas the diagnosis of cerebral salt wasting should be used more carefully. SUMMARY: These findings will contribute to a better understanding of the pathophysiology involved and enable better prevention and therapy where possible in clinical practice.

Risk Factors and Consequences of Late-Onset Hyperlactatemia After Cardiac Surgery With Cardiopulmonary Bypass: A Single-Center Retrospective Study.

OBJECTIVE: Mechanisms and consequences of late-onset hyperlactatemia after cardiac surgery remain unclear. The aim of this study was to identify risk factors and outcomes of late hyperlactatemia, defined as a lactate value ≥3 mmol/L developing in the intensive care unit (ICU) after not being elevated on admission after cardiac surgery with cardiopulmonary bypass. DESIGN: A retrospective analysis of prospectively collected data. SETTING: A single-center University Hospital. PARTICIPANTS: Patients who underwent elective cardiac surgery with cardiopulmonary bypass in 2019 and who had normal lactatemia at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided in 2 groups according to their lactatemia on postoperative day 1 (14.0 ± 3.0 hours after ICU admission): normal lactatemia (control group) and late hyperlactatemia (HL group). Risk factors for late hyperlactatemia were identified using a multivariate analysis, and postoperative outcomes were compared using a composite criterion of severe outcomes. Of the 432 included patients, 37 (8.5%) presented with late hyperlactatemia. Risk factors independently associated with hyperlactatemia were afternoon surgery (odds ratio [OR] 4.24, 95% CI 2.00-9.35), a bleeding >300 mL within the 6 hours after surgery (H6) (OR 3.77, 95% CI 1.71-8.30), and H6 fluid loading >250 mL (OR 2.64, 95% CI 1.22-5.55). Patients with hyperlactatemia presented more frequently with major postoperative complications, including acute kidney injury, and received more frequent red-cell transfusion. CONCLUSION: The strongest risk factors associated with late-onset hyperlactatemia in the authors' population were afternoon surgery and H6 bleeding >300 mL. Poor postoperative outcomes were more frequent in patients with late hyperlactatemia, even in the absence of early hyperlactatemia or severe obvious condition.

Hyperlactatemia associated with elective tumor craniotomy: Protocol for an observational study of pathophysiology and clinical implications.

Hyperlactatemia occurs frequently after brain tumor surgery. Existing studies are scarce and predominantly retrospective, reporting inconsistent associations to new neurological deficits and prolonged hospital stay. Here we describe a protocol for a prospective observational study of hyperlactatemia during and after elective tumor craniotomy and the association with postoperative outcome, as well as selected pathophysiological aspects, and possible risk factors. We will include 450 brain tumor patients scheduled for elective craniotomy. Arterial blood samples for lactate and glucose measurement will be withdrawn hourly during surgery and until six hours postoperatively. To further explore the association of hyperlactatemia with perioperative insulin resistance, additional blood sampling measuring markers of insulin resistance will be done in 100 patients. Furthermore, in a subgroup of 20 patients, blood from a jugular bulb catheter will be drawn simultaneously with blood from the radial artery to measure the arterial to jugular venous concentration difference of lactate, in order to study the direction of cerebrovascular lactate flux. Functional clinical outcome will be determined by the modified Rankin Scale, length of stay and mortality at 30 days, 6 months, 1 year and 5 years. Clinical outcome will be compared between patients with and without hyperlactatemia. Multivariate logistic regression will be used to identify risk factors for hyperlactatemia. A statistical analysis plan will be publicized to support transparency and reproducibility. Results will be published in a peer-reviewed journal and presented at international conferences.

Hyperlactatemia as a prognostic indicator for contemporary left ventricular assist device implantation.

BACKGROUND: This study evaluates the impact of early post-operative hyperlactatemia on outcomes after left ventricular assist device (LVAD) implantation. METHODS: Adults undergoing contemporary LVAD implantation between 2009 to 2018 were included. Peak post-operative (within 24-h) lactate level was analyzed. The cohort was stratified into patients with and without post-operative hyperlactatemia, which was defined as peak > 3.5 mMol/L. The primary outcome was survival, and secondary outcomes included post-implant adverse events. Sub-analysis was performed to evaluate the impact of time for lactate normalization, define as lactate < 2 mMol/L. Multivariable cox regression was used for risk-adjustment. RESULTS: A total of 190 patients were included. 49.5% experienced early post-operative hyperlactatemia. Patients with post-operative hyperlactatemia had significantly higher rates of post-implant complications including re-operation, renal failure, and hepatic dysfunction (all, p ≤ 0.05). The post-operative hyperlactatemia group also had significantly higher 90-day and 1-year mortality rates following LVAD implantation (both, p ≤ 0.05). In multivariable analysis, post-operative hyperlactatemia (HR 1.69, 95% CI 1.09-2.60, p = 0.02) was an independent predictor of overall mortality following LVAD implantation. Increased time for normalization of lactate also adversely impacted risk-adjusted overall mortality following implantation as a continuous variable (HR 1.02, 95% CI 1.01-1.03, p < .001). CONCLUSIONS: This study demonstrates early post-operative hyperlactatemia is associated with increased morbidity and mortality following LVAD implantation. Even early post-operative lactate trends within the first 24 post-operative hours appear to have a useful role in predicting longitudinal survival following implantation. Careful monitoring of post-operative lactate with measures to normalize levels should be considered in the early care of LVAD patients.

Hyperlactatemia in children following brain tumor resection: prevalence, associated factors, and clinical significance.

PURPOSE: Hyperlactatemia is associated with worse outcome among critically ill patients. The prevalence of hyperlactatemia in children following craniotomy for intracranial tumor resection is unknown. This study was designed to assess the prevalence, associated factors, and significance of postoperative hyperlactatemia in this context. METHODS: A retrospective study was conducted at an intensive care unit of a tertiary, pediatric medical center. Children younger than 18 years admitted following craniotomy for brain tumor resection between October 2004 and November 2019 were included. RESULTS: Overall, 222 elective craniotomies performed in 178 patients were analyzed. The mean age ± SD was 8.5 ± 5.5 years. All but two patients survived to discharge. All were hemodynamically stable. Early hyperlactatemia, defined as at least one blood lactate level ≥ 2.0 mmol/L during the first 24 h into admission, presented following 74% of the craniotomies; lactate normalized within a mean ± SD of 11 ± 6.1 h. The fluid balance per body weight at 12 h and 24 h into the intensive care unit admission was similar in children with and without hyperlactatemia [7.0 ± 17.6 vs 3.5 ± 16.4 ml/kg, p = 0.23 and 4.0 ± 27.2 vs 4.6 ± 29.4 ml/kg, p = 0.96; respectively]. Hyperlactatemia was associated with higher maximal blood glucose, older age, and a pathological diagnosis of glioma. Intensive care unit length of stay was similar following craniotomies with and without hyperlactatemia (p = 0.57). CONCLUSIONS: Hyperlactatemia was common in children following craniotomy for brain tumor resection. It was not associated with hemodynamic impairment or with a longer length of stay.

Association Between Hyperlactatemia, Perfusional Parameters, and Lymphocyte Mitochondrial Dysfunction in Septic Shock Patients.

INTRODUCTION: In septic shock, mitochondrial dysfunction, and hypoperfusion are the main triggers of multi-organ failure. Little is known about the crosstalk between mitochondrial dysfunction and hemodynamic alterations, especially in the post-resuscitation phase. Here, we assess whether hypoperfusion and lactate levels are associated with oxygen consumption linked to mitochondrial bioenergetic activity in lymphocytes of patients admitted with septic shock. PATIENTS AND METHODS: Prospective cohort study in patients with septic shock defined as the requirement of vasopressors to maintain a mean arterial pressure 65 mm Hg after initial fluid administration. Basal mitochondrial and Complex I respiration was measured to evaluate mitochondrial activity. Both variables and capillary refill time were compared with arterial lactate post-fluid resuscitation. We also compared mitochondrial activity measurements between patients with and without hypoperfusion status. RESULTS: A total of 90 patients were included in analysis. The median arterial lactate at the time of septic shock diagnosis was 2.0 mmol/Dl (IQR 1.3-3.0). Baseline respiration at the time of septic shock diagnosis was correlated with lactate (Spearman -0.388, 95% CI -0.4893 to -0.1021; P = 0.003), as well as Complex I respiration (Spearman -0.403, 95% CI -0.567 to -0.208; P < 0.001). Patients with hypoperfusion status had no difference in basal respiration when compared with patients who did not have hypoperfusion status (P = 0.22) nor in Complex I respiration (P = 0.09). CONCLUSION: Changes in lymphocytic mitochondrial metabolism are associated with post-resuscitation arterial lactate in septic shock; however, they are not associated with the presence of a hypoperfusional status. In this scenario, it is therefore suggested that systemic perfusion and mitochondrial metabolism have different courses.

Hyperlactatemia in diabetic ketoacidosis.

AIMS: The study examined the prevalence and degree of lactate elevation in diabetic ketoacidosis, and explored which biochemical abnormalities predicted L-lactate levels. METHODS: We reviewed episodes of diabetic ketoacidosis from 79 diabetes patients (one episode per patient). Separate univariate linear regression models were specified to predict lactate level from each of nine biochemical variables. Significant predictors from the univariate models were included in a final multivariate linear regression model to predict lactate levels. RESULTS: Mean (SD) lactate level was 3.05 (1.66) mmol/L; about 65% of patients had lactate levels >2 mmol/L. In the final multivariate linear regression model (R2  = 0.45), higher lactate levels were associated with greater hydrogen ion concentration (standardised ß = .60, t = 4.16, p < 0.0001), higher blood glucose (standardised ß = .28, t = 2.67, p = 0.009) and lower glomerular filtration rate estimated from creatinine (standardised ß = -.23, t = 2.29, p = 0.025). Bicarbonate, beta-hydroxybutyrate, body mass index, mean arterial pressure and calculated osmolality were not significant predictors of lactate level. There were three distinct patterns of lactate levels with treatment of diabetic ketoacidosis: group 1 = gradual decline, group 2 = initial increase and then decline and group 3 = initial decline followed by a transient peak and subsequent decline. CONCLUSIONS: Elevated lactate level is the norm in patients with diabetic ketoacidosis. Higher blood glucose levels and higher hydrogen ion concentrations are related to greater lactate. With treatment, there are different patterns of decline in lactate levels.

Electrolyte Derangements, Hyperlactatemia, and Cardiac Abnormalities Secondary to Refeeding in Three Dogs: Case Report.

Three dogs that presented to the emergency service in severely emaciated body conditions were admitted to the hospital for monitoring and refeeding. During their hospitalization, all three dogs developed electrolyte derangements or required supplementation to prevent hypophosphatemia and hypomagnesemia. Additionally, all dogs developed hyperlactatemia, which was suspected to be secondary to thiamine deficiency. Two dogs were reported to have cardiac abnormalities, including cardiac arrhythmias, systolic dysfunction, and spontaneous echogenic contrast. These cases highlight the complexity of refeeding syndrome and its associated complications that extend beyond electrolyte deficiencies.

Risk factors and in-hospital mortality of postoperative hyperlactatemia in patients after acute type A aortic dissection surgery.

BACKGROUND: Hyperlactatemia may be caused by increased production due to tissue hypoxia or non-hypoxia. The aim of this study was first to identify risk factors for postoperative hyperlactatemia (POHL) after Stanford type A acute aortic dissection surgery (AADS) and construct a predictive model, and second to evaluate the impact of POHL on prognosis. METHODS: This retrospective study involved patients undergoing AADS from January 2016 to December 2019 in Wuhan Union Hospital. Multivariate logistic regression analysis was performed to identify independent risk factors for POHL. A nomogram predicting POHL was established based on these factors and was validated in the original dataset. The receiver operating characteristic curve was drawn to assess the ability of postoperative lactate levels to predict the in-hospital mortality. RESULTS: A total of 188 patients developed POHL after AADS (38.6%). Male gender, surgery history, red blood cell transfusion and cardiopulmonary bypass time were identified as independent predictors. The C-index of the prediction model for POHL was 0.72, indicating reasonable discrimination. The model was well calibrated by visual inspection and goodness-of-fit test (Hosmer-Lemeshow χ2 = 10.25, P = 0.25). Decision and clinical impact curves of the model showed good clinical utility. The overall in-hospital mortality rate was 10.1%. Postoperative lactate levels showed a moderate predictive power for postoperative in-hospital mortality (C-index: 0.72). CONCLUSION: We developed and validated a prediction model for POHL in patients undergoing AADS, which may have clinical utility in personal risk evaluation and preventive interventions. The POHL could be a good predictor for in-hospital mortality.

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.

Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit.

BACKGROUND: Children with diabetic ketoacidosis often have elevated lactate. In this study, we investigated the clinical variables associated with hyperlactatemia in children with diabetic ketoacidosis. METHODS: We designed a single-center retrospective descriptive study of children with diabetic ketoacidosis in a pediatric intensive care unit. RESULTS: Of the 107 patients with diabetic ketoacidosis included in the analysis, 61 developed hyperlactatemia. Multivariate logistic regression analysis showed that heart rate (p = 0.003),diastolic blood pressure (p = 0.001) and stage of severity (p = 0.042) were independently associated with the development of hyperlactatemia in diabetic ketoacidosis. We found that lactate level was not significantly associated with length of hospital stay (p = 0.115) or the length of time to diabetic ketoacidosis resolution (p = 0.143). CONCLUSIONS: Children with diabetic ketoacidosis presenting with severer stage, elevated heart rate and higher diastolic blood pressure may be prone to hyperlactatemia. Hyperlactatemia was not associated with length of time to DKA resolution and length of hospital stay.