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.

A Case of Transient Hyperlactatemia Induced by Intravenous Glycerol Administration in a Patient With Brain Trauma.

Elevated lactate levels are associated with a poor prognosis in patients with sepsis and shock. Intravenous glycerol administration is often used in Japan to treat patients with acute stroke or brain trauma, but such treatment can cause elevated lactate levels. We experienced a case of transient hyperlactatemia induced by intravenous glycerol administration in a patient with brain trauma. A 74-year-old woman underwent decompressive craniotomy because of loss of consciousness and brain edema. Glycerol was administered after the operation for management of the brain edema. Although the patient's hemodynamics remained stable, her lactate level decreased and increased repeatedly. We recognized that the elevation in her lactate level was associated with the administration of intravenous glycerol. This case suggests that intravenous glycerol administration can induce transient hyperlactatemia.

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.

Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors.

INTRODUCTION: Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. METHODS: In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. RESULTS: After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. CONCLUSION: We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

Clinical impact of lactate on postoperative pancreatic fistula after pancreaticoduodenectomy: A single-center retrospective study of 1,043 patients.

BACKGROUND/OBJECTIVES: Several hemodynamic markers have been studied to predict postoperative complication which is a risk factor for poor quality of life and prognosis. The aim of this study was to determine whether postoperative lactate clearance could affect clinical outcome based on complications in one surgical patient group. METHODS: We retrospectively reviewed data from all patients who underwent pancreaticoduodenectomy (PD) at Samsung Medical Center from January 2015 to December 2019. Differences in baseline characteristics of patients, intraoperative outcome, and postoperative outcome were evaluated according to the presence or absence of clinically relevant postoperative pancreatic fistula (CR-POPF). RESULTS: Among a total of 1107 patients, 1043 patients were tested for arterial lactate levels immediately after surgery, and the day after surgery. Immediately postoperative hyperlactatemia (lactate ≥2.0 mmol/L) was not related to CR-POPF (P = 0.269). However, immediately postoperative hyperlactatemia with a negative lactic clearance on postoperative day (POD) 1 was related to CR-POPF (P = 0.003). In multivariate analyses, non-pancreatic cancer (hazard ratio (HR): 2.545, P < 0.001), soft pancreatic texture (HR: 1.884, P < 0.001), and postoperative hyperlactatemia with negative lactate clearance on POD 1 (HR: 1.805, P = 0.008) were independent risk factors for CR-POPF. CONCLUSIONS: Hyperlactatemia with negative lactate clearance after PD, one of the high-risk surgeries requiring postoperative ICU care, is a risk factor for CR-POPF. In case of immediately postoperative hyperlactatemia after PD, lactate clearance with serial lactate level follow-up can be used for achieving the hemodynamic goal to prevent CR-POPF.

Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury.

BACKGROUND: Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. METHODS: A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1-7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models. RESULTS: A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22-2.20) and 4.18 (2.99-5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score). CONCLUSIONS: Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

Hyperlactatemia and altered lactate kinetics are associated with excess mortality in sepsis : A multicenter retrospective observational study.

Severe hyperlactatemia (>10mmol/L) or impaired lactate metabolism are known to correlate with increased mortality. The maximum lactate concentration on day 1 of 10,724 septic patients from the eICU Collaborative Research Database was analyzed and patients were divided into three groups based on maximum lactate in the first 24 h (<5mmol/l; ≥5mmol/l & <10mmol/l; ≥10mmol/l). In addition, delta lactate was calculated using the following formula: (maximum lactate day 1 minus maximum lactate day 2) divided by maximum lactate day 1. A multilevel regression analysis was performed, with hospital mortality serving as the primary study end point. Significant differences in hospital mortality were found in patients with hyperlactatemia (lactate ≥10mmol/l: 79%, ≥5mmol/l & <10mmol/l: 43%, <5mmol/l, 13%; p<0.001). The sensitivity of severe hyperlactatemia (≥10mmol/l) for hospital mortality was 17%, the specificity was 99%. In patients with negative delta lactate in the first 24 h, hospital mortality was excessive (92%). In conclusion, mortality in patients with severe hyperlactatemia is very high, especially if it persists for more than 24 h. Severe hyperlactatemia, together with clinical parameters, could therefore provide a basis for setting treatment limits.

Characteristics and predictors of ICU-mortality in critically ill patients with hyperlactatemia requiring CRRT: A retrospective cohort study.

BACKGROUND: Hyperlactatemia is a common complication in critically ill patients with high morbidity and mortality. Hyperlactatemia patients who require continuous renal replacement therapy (CRRT) constitute a subgroup with increased mortality risk. The clinical significance of serum lactate in these patients was not well understood and clearance of lactate using CRRT shown no survival benefits. The aim of this study is to investigate the incidence and non-lactate risk factors for ICU mortality in hyperlactatemia patients who underwent CRRT. METHOD: Hyperlactatemia patients with a serum lactate level >2 µmol/L who underwent CRRT between January, 2014 and May, 2021 were retrospectively investigated. Demographic characteristics and clinical data were collected from the electronic medical record system. The primary endpoint was predictors for ICU mortality which were identified by using multivariate logistic regression analysis. RESULTS: A total of 178 eligible patients were finally included with a mean age of 56.6 ± 17.9 years and a median APACHE II score of 18 (IQR (14-22)). The multivariate regression results showed that male gender (OR 0.55 (95%CI 0.27-1.12), p = 0.1), mechanical ventilation (OR 2.60 (95%CI 1.27-5.34), p = 0.008), history of hypertension (OR 2.40 (95%CI 1.12-5.14), p = 0.02), SOFA score (OR 1.16 (95%CI 1.05-1.28), p = 0.002), AST (OR 1.0005 (95%CI 0.99-1.001), p = 0.08), and PT (OR 1.08 (95%CI 0.99-1.17), p = 0.06) were independently associated with ICU mortality. After adjusting for age, illness severity (APACHE II score), and serum lactate level, the statistical significances of SOFA score (OR 1.16 (95%CI 1.04-1.29), p = 0.005), hypertension (OR 2.25 (95%CI 1.02-4.95), p = 0.04), and mechanical ventilation (OR 2.54 (95%CI 1.22-5.25), p = 0.01) were not affected. The overall ICU mortality was 58.4% (104/178). CONCLUSION: The hyperlactatemia patients who underwent CRRT were at increased ICU mortality. Gender, AST, PT, SOFA score, history of hypertension, and mechanical ventilation were independent predictors for ICU mortality. Future studies with prospectively design, large sample size, and subgroup analyses are warranted to validate these findings.

Central Neurogenic Hyperventilation and Hyperlactatemia After Resection of a Fourth Ventricle Tumor: A Case Report.

We report a rare case of central neurogenic hyperventilation (CNH) and hyperlactatemia after resection of a fourth ventricle tumor. Our management consisted of close monitoring and exclusion of alternate causes of hyperventilation and hyperlactatemia. We hypothesize that a localized increase in tissue lactate, related to tumor metabolism, may have triggered CNH in our patient through stimulation of the brainstem respiratory centers. CNH should be considered during the differential diagnosis of perioperative hyperventilation with respiratory alkalosis in patients with posterior fossa tumors. Hyperlactatemia can trigger compensatory hyperventilation but will not result in alkalosis.

A case report of mitochondrial myopathy with membranous nephropathy.

BACKGROUND: MtDNA 3243 A > G mutation leads to mitochondrial myopathies with predominant hyperlactatemia. Given the ubiquitous nature of mitochondria, cellular dysfunction can also appear in tissues with high metabolic turnover; thus, there can be cardiac, digestive, ophthalmologic, and kidney complications. MtDNA 3243 A > G mutation has been shown to be with renal involvement in the previous cases of which are FSGS and tubularinterstitial nephritis. CASE PRESENTATION: We report a case of patient who had the mitochondrial myopathy with mitochondrial DNA (mtDNA) 3243 A > G mutation diagnosed membranous nephropathy by kidney biopsy, which was never reported before. Our patient was found to have chest tightness and shortness of breath with hyperlactatemia and was diagnosed mitochondrial myopathy with mtDNA 3243 A > G mutation 11 months ago. Acute kidney injury occurred with hyperuricemia (urid acid 1011umol/L) which may be associated with mtDNA mutation. Since then, persistent proteinuria was also found and the 24-h urine protein quantitative was around 2 g. Kidney biopsy was performed and the result was consistent with membranous nephropathy, with abnormal mitochondria seen in renal tubules by electron microscopy. CONCLUSIONS: Patients with mitochondrial myopathy could also have renal presentation of membranous nephropathy. Patients with mtDNA mutation may have various renal manifestations so that more attention should be paid on their kidneys.

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.

Lessons of the month 1: Shoshin beriberi: A case report of fulminant cardiovascular collapse, intractable hyperlactatemia and deteriorating consciousness.

Shoshin beriberi is a fulminant variant of thiamine deficiency, often presenting with severe lactic acidosis and cardiogenic shock. Due to the sparsity of this condition, delays in diagnosis can lead to fatality. However, rapid reversal of symptoms can be easily achieved through intravenous thiamine replacement.In this case report, we discuss a 57-year-old woman, who was previously fit and well, who presented to the emergency department with a 3-day history of extreme malaise, breathlessness and abdominal pain, with marked hypotension and tachycardia requiring vasopressor support and a severe rising lactic acidosis. Upon further questioning, a history of alcohol excess was noted. Rapid reversal of the marked haemodynamic instability was achieved upon administration of intravenous thiamine and the patient was discharged within 48 hours.

The risk factors of intraoperative hyperlactatemia in patients undergoing laparoscopic colorectal surgery.

AIM: The aim of this study is to determine the incidence of intraoperative hyperlactatemia and its risk factors in patients undergoing laparoscopic colorectal surgery. MATERIAL AND METHODS: We retrospectively enrolled 75 patients who underwent laparoscopic resection for colorectal cancer. Initial lactate levels were determined from blood gas analysis before the incision. The end lactate values were recorded after the termination of the pneumoperitoneum. Hyperlactatemia defined as lactate levels between 2 mmol/L and 5 mmol/L without evidence of acidosis. The patients were divided into two groups as normolactatemia and hyperlactatemia according to lactate values at the end of the surgery. RESULTS: Of the 75 patients, 45 (60.0%) had higher lactate levels than normal at the end of the surgery. The median age of the study population was 62 (24-84) years. Forty (53.3%) of the patients were male. Most of the patients in the study had colon cancer origin [56 cases (74.7%)]. Univariate logistic regression analysis for a possible independent risk factor in terms of hyperlactatemia showed that Charlson comorbidity index (CCI) ≥ 3, body mass index (BMI) ≥ 30 kg/m2, the operative time, and the tumor size were significant (p < 0.05). Multivariate analysis found that only BMI ≥ 30 kg/m2 and the operative time were significant (p = 0.004, and p < 0.001, respectively). CONCLUSION: According to our work, obesity (BMI ≥ 30 kg/m2) and the operative time in laparoscopic colorectal surgery were independent risk factors for intraoperative hyperlactatemia at the end of the operation. Therefore, clinicians should be vigilant about the inevitable consequences of surgery by making appropriate preparation. KEY WORDS: Colorectal cancer, Lactate, Hyperlactatemia, Laparoscopy.

Hyperlactacidemia as a risk factor for intensive care unit-acquired weakness in critically ill adult patients.

INTRODUCTION/AIMS: Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication of critical illness. Serum lactate is a useful biomarker in critically ill patients. The relationship between serum lactate level and ICUAW remains controversial. This study evaluated whether hyperlactacidemia (lactate level >2 mmol/L) was an independent risk factor for ICUAW in critically ill adult patients. METHODS: An observational cohort study was performed in a general multidisciplinary intensive care unit (ICU). Sixty-eight consecutive adult critically ill patients without preexisting neuromuscular disease or a poor pre-ICU functional status whose length of ICU stay was 7 or more days were evaluated. Patients were screened daily for signs of awakening. Muscle strength assessment using the Medical Research Council score was performed on the first day a patient was considered awake. Patients with clinical muscle weakness were considered to have ICUAW. RESULTS: Among the 68 patients who achieved a satisfactory state of consciousness, the diagnosis of ICUAW was made in 30 patients (44.1%). After multivariate analysis, hyperlactacidemia (P = .02), Acute Physiology and Chronic Health Evaluation II score (P = .04), duration of mechanical ventilation (P = .02), and the use of norepinephrine (P = .04) were found to be significantly associated with the development of ICUAW in critically ill patients. DISCUSSION: This study shows a number of risk factors to be significantly associated with the development of ICUAW in critically ill adults. These factors should be considered when building early prediction models or designing prevention strategies for ICUAW in future studies.

Prognostic value of lactate levels and lactate clearance in sepsis and septic shock with initial hyperlactatemia: A retrospective cohort study according to the Sepsis-3 definitions.

ABSTRACT: The 2016 Surviving Sepsis Campaign guidelines suggest guiding resuscitation to normalize lactate levels in patients with sepsis-associated hyperlactatemia as a marker of tissue hypoperfusion. This study evaluated the prognostic value of lactate levels and lactate clearance for 30-day mortality in patients with sepsis and septic shock diagnosed in the emergency department.We performed a retrospective cohort study of sepsis patients with initial lactate levels of ≥2 mmol/L. All patients met the Sepsis-3 definitions. The prognostic value of 6-hour lactate levels, 6-hour lactate clearance, 6-hour lactate metrics (≥2 mmol/L), and lactate clearance metrics (<10%, <20%, and <30%) was evaluated. We compared the sensitivity and specificity between metrics.Of the 363 sepsis and septic shock patients, 148 died (30-day mortality: 40.8%). Nonsurvivors had significantly higher 6-hour lactate levels and lower 6-hour lactate clearance than those of survivors. Six-hour lactate levels and 6-hour lactate clearance were associated with 30-day mortality after adjusting for potential confounders (odds ratio, 1.191 [95% confidence interval (CI), 1.097-1.294] and 0.989 [0.983-0.995], respectively). Six-hour lactate levels had better prognostic value than 6-hour lactate clearance (area under the curve, 0.720 [95% CI, 0.670-0.765] vs 0.656 [0.605-0.705]; P = .02). Six-hour lactate levels of ≥3.5 mmol/L and 6-hour lactate clearance of <24.4% were the optimal cut-off value in predicting the 30-day mortality. The prognostic value of 6-hour lactate metrics and 6-hour lactate clearance metrics did not differ. Six-hour lactate levels (≥2 mmol/L) had the highest sensitivity (89.2%).Six-hour lactate levels proved to be more accurate in predicting 30-day mortality than 6-hour lactate clearance and initial lactate levels.

The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study.

BACKGROUND: Infection with Plasmodium falciparum leads to severe malaria and death in approximately 400 000 children each year in sub-Saharan Africa. Blood transfusion might benefit some patients with malaria but could potentially harm others. The aim of this study was to estimate the association between transfusion and death among children admitted to hospital with P falciparum malaria. METHODS: In this prospective, multicentre observational study, we analysed admissions to six tertiary care hospitals in The Gambia, Malawi, Gabon, Kenya, and Ghana that participated in the Severe Malaria in African Children network. Patients were enrolled if they were younger than 180 months and had a Giemsa-stained thick blood smear that was positive for P falciparum. Blood transfusion (whole blood at a target volume of 20 mL per kg) was administered at the discretion of the responsible physicians who were aware of local and international transfusion guidelines. The primary endpoint was death associated with transfusion, which was estimated using models adjusted for site and disease severity. We also aimed to identify factors associated with the decision to transfuse. The exploratory objective was to estimate optimal haemoglobin transfusion thresholds using generalised additive models. FINDINGS: Between Dec 19, 2000, and March 8, 2005, 26 106 patients were enrolled in the study, 25 893 of whom had their transfusion status recorded and were included in the primary analysis. 8513 (32·8%) patients received a blood transfusion. Patients were followed-up until discharge from hospital for a median of 2 days (IQR 1-4). 405 (4·8%) of 8513 patients who received a transfusion died compared with 689 (4·0%) of 17 380 patients who did not receive a transfusion. Transfusion was associated with decreased odds of death in site-adjusted analysis (odds ratio [OR] 0·82 [95% CI 0·71-0·94]) and after adjusting for the increased disease severity of patients who received a transfusion (0·50 [0·42-0·60]). Severe anaemia, elevated lactate concentration, respiratory distress, and parasite density were associated with greater odds of receiving a transfusion. Among all study participants, transfusion was associated with improved survival when the admission haemoglobin concentration was up to 77 g/L (95% CI 65-110). Among those with impaired consciousness (Blantyre Coma Score ≤4), transfusion was associated with improved survival at haemoglobin concentrations up to 105 g/L (95% CI 71-115). Among those with hyperlactataemia (blood lactate ≥5·0 mmol/L), transfusion was not significantly associated with harm at any haemoglobin concentration-ie, the OR of death comparing transfused versus not transfused was less than 1 at all haemoglobin concentrations (lower bound of the 95% CI for the haemoglobin concentration at which the OR of death equals 1: 90 g/L; no upper bound). INTERPRETATION: Our findings suggest that whole blood transfusion was associated with improved survival among children hospitalised with P falciparum malaria. Among those with impaired consciousness or hyperlactataemia, transfusion was associated with improved survival at haemoglobin concentrations above the currently recommended transfusion threshold. These findings highlight the need to do randomised controlled trials to test higher transfusion thresholds among African children with severe malaria complicated by these factors. FUNDING: US National Institute of Allergy and Infectious Diseases.

Hyperlactatemia: An Update on Postoperative Lactate.

While hyperlactatemia in postoperative cardiac surgery patients was once believed to solely reflect hypoperfusion, either from the accumulated "oxygen debt" during bypass or ongoing inadequate perfusion, our understanding of lactate generation, clearance, and management has evolved. A contemporary understanding of lactate balance is critical to the management of the postoperative patient with hyperlactatemia. In this review, we summarize the current understanding of lactate metabolism in pediatric patients following cardiac surgery and highlight two types of hyperlactatemia: type A, which is secondary to inadequate oxygen delivery and tissue hypoxia, and type B, which in postoperative pediatric cardiac surgery patients largely reflects increased glycolysis driven by the stress response. Both types may coexist; thus, it is imperative that providers first assess the patient for evidence of hypoperfusion. In patients with evidence of adequate perfusion, a type B component is often associated with a concomitant balanced (normal anion gap) metabolic acidosis and hyperglycemia. These patients will benefit from a more nuanced approach to their type B hyperlactatemia, as many will have a benign course and may be managed expectantly.

Acidosis láctica por metformina: ¿debemos ser más cautelosos con la disfunción renal? / Metformin-induced lactic acidosis: should we be more careful with renal dysfunction?

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Perspectives on perfusion monitoring in septic shock after the ANDROMEDA-SHOCK trial / Perspectivas sobre la monitorización de la perfusión en el choque séptico tras el ensayo ANDROMEDA-SHOCK

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Clinical impact of intraoperative hyperlactatemia during craniotomy.

OBJECT: Patients often develop markedly elevated serum lactate levels during craniotomy although the reason for this is not entirely understood. Elevated lactate levels have been associated with poor outcomes in critically ill septic shock patients, as well as patients undergoing abdominal and cardiac surgeries. We investigated whether elevated lactate in craniotomy patients is associated with neurologic complications (new neurological deficits) as well as systemic complications. METHODS: We performed a cohort study of elective craniotomy patients. Demographic and intraoperative data were collected, as well as three timed intraoperative arterial lactate values. Additional lactate, creatinine and troponin values were collected immediately postoperatively as well as 12 and 24 hours postoperatively. Assessment for neurologic deficit was performed at 6 hours and 2 weeks postoperatively. Hospital length-of-stay and 30-day mortality were collected. RESULTS: Interim analysis of 81 patients showed that no patient had postoperative myocardial infarction, renal failure, or mortality within 30 days of surgery. There was no difference in the incidence of new neurologic deficit in patients with or without elevated lactate (10/26, 38.5% vs. 15/55 27.3%, p = 0.31). Median length of stay was significantly longer in patients with elevated lactate (6.5 vs. 3 days, p = 0.003). Study enrollment was terminated early due to futility (futility index 0.16). CONCLUSION: Elevated intraoperative serum lactate was not associated with new postoperative neurologic deficits, other end organ events, or 30 day mortality. Serum lactate was related to longer hospital stay.